contrast medium generation and distribution device, sonographic visualization method, and method of

专利摘要:
CONTRAST MEDIA GENERATION AND DISTRIBUTION DEVICE AND METHODS OF SONOGRAPHIC VISUALIZATION OF A BODY STRUCTURE AND DIAGNOSTICATION OF THE PATENT OF A FALLOON HORSE The present invention comprises methods and devices for generating and providing contrast medium for structure sonography , such as ducts and cavities. The invention provides for the creation of a contrast medium comprising detectable acoustic variations between two phases, for example, a gas and a liquid. Sonography is the primary means of image visualization, but other conventional means of detection can also be employed with the present invention.
公开号:BR112013011434B1
申请号:R112013011434-7
申请日:2011-11-09
公开日:2020-12-22
发明作者:Kathy Lee-Sepsick；Max S. Azevedo
申请人:Femasys Inc；
IPC主号:

专利说明:

RELATED REQUESTS
[0001] This application claims the priority of US Patent Application 13 / 219,667, filed on August 27, 2011, and Provisional Patent Application US 61 / 411,856, filed on November 9, 2010, each of which is incorporated this document in its entirety. TECHNICAL FIELD
[0002] The present invention relates to methods and devices for visualizing sonographic image of cavities and conduits, such as organs, ducts and other cavities. In particular, the methods and devices of the present invention use detectable acoustic variations of alternating patterns of a gas phase and a liquid phase that traverse a passage. BACKGROUND OF THE INVENTION
[0003] Non-surgical diagnostic procedures for examining ducts and body cavities, in particular the uterus and fallopian tubes, are well known. One procedure, known as hysterosalpingography, employs contrast agents and diagnostic techniques by viewing fluoroscopic images to view the uterus and fallopian tubes. A safer, cheaper and easier method is hysterosonalpingography or HSG sleep, in which ultrasound is used as the image visualization modality. The ultrasound image visualization also allows the evaluation of the uterine cavity with the use of saline as a preferred method, without the evaluation of the fallopian tube patency. Tubal patency and tubal obstruction can only be assessed under ideal sonographic conditions, limiting their clinical usefulness.
[0004] Currently, no contrast agent indicated for increased contrast during ultrasound assessment of the uterine cavity and fallopian tubes is available in the United States. Other ultrasound contrast agents are available for general use, but are limited to use in cardiac and vascular applications. Most of the vascular contrast agents currently available are stabilized against dissolution and coalescence by the presence of additional materials, such as a solid elastic shell that increases stability, or a surfactant or a combination of two or more surfactants.
[0005] Contrast agents can improve the image quality of sonography both by decreasing the reflectivity of unwanted interfaces and by increasing the backscattered echoes of the desired regions. In the previous approach, contrast agents are taken orally, and for that purpose, the agent is introduced vascularly. To pass through the pulmonary capillaries and enter the systemic circulation, microbubbles within a vascular contrast agent must be less than 10 microns in diameter (2 to 5 microns on average for most newer agents). Stability and permanence become major problems for such small microbubbles and air bubbles in this size range remain in the solution only for a short period of time. Consequently, gas bubbles need to be stabilized in order for the agent to remain long enough and resist pressure changes in the heart for systemic vascular use. Therefore, the availability of contrast agents, the procedural challenges, particularly during the preparation of the patient and the contrast materials, and the cost are disadvantages associated with the known contrast media used sonographically.
[0006] Although conventional contrast agents work properly, the disadvantages inherent in conventional agents create a need for better contrast agents. A disadvantage compared to the contrast agents currently used is that they are very expensive and difficult to obtain for some doctors. Another disadvantage is that conventional contrast agents need to be agitated before injection, both to mix the components and to generate bubbles, thus making the whole diagnostic procedure complicated and eventually a little subjective. A third disadvantage is that the contrast agent composition has a very short life due to its unstable nature since it is prepared for use in a patient.
[0007] Microbubbles in liquids have already been used as a means of contrast. Microbubbles can be generated by such methods as syringe movements back and forth in combinations of air and dispersants, or ultrasonic cavitation means. Such microbubbles are known to be stable only for a short period of time. Preformed microparticles that use temporary or permanent polymeric films were used to solve the short duration of stability. Pressurized systems were used to create microbubbles in solutions. The technique involves a means of generating a concentrated gas jet in order to aerate the fluids with microbubbles. Such microbubbles can coalesce if there is a latency period between generation and application to the structure to be visualized, therefore, these methods used a high-speed liquid flow. Thus, the limitations with this method are that microbubbles introduced into a fluid can coalesce in a reduced number of large bubbles or in a large air pocket, the microbubbles formed must be stable long enough for visualization to occur, and due to the instability of the microbubbles, it is difficult to create reproducible conditions for comparative views.
[0008] Consequently, devices and methods are needed to create contrast agents that solve the problems currently encountered. In particular, methods and devices are necessary for visualizing the structure and function of organs, such as visualization of the uterus and fallopian tubes. SUMMARY
[0009] The present invention comprises methods and devices for producing and using contrast agents. The methods of the present invention comprise the use of a device to generate a contrast agent that is used to sonographically observe bodily organs or structures, for example, the uterus and fallopian tubes. The contrast agent device may comprise a container assembly and, optionally, a catheter assembly fluidly coupled to the container assembly. A container assembly may comprise a first container to provide a solution of a liquid, such as saline, and a second container to supply a gas, such as air, and elements to create an alternating pattern of gas and fluid, which is distributed directly to the organ or structure by the catheter assembly. A container set can comprise one or more containers. A container assembly may comprise elements for delivering the substance contained in a container to the catheter.
[0010] The methods of the present invention comprise sonographically observing a location on a body, such as the uterus and its associated fallopian tubes, using the devices disclosed in this document. One method comprises positioning a catheter delivery end in close proximity to the structure to be observed, and delivering the fluid / gas mixture to the structure. For example, in a method of visualizing a fallopian tube, a delivery device comprising at least one catheter is positioned inside the uterus, and at least one catheter is delivered through the delivery device and is extended to the horns of the uterus and the delivery end of the catheter are held in place, for example, by a final structure such as a balloon. Once the catheter (s) is (are) in place, the liquid / gas mixture, the contrast medium, is supplied from the contrast agent device to the catheter and the tube (s) ( s) fallopian tube. The sonographic visualization is initiated, and one or both fallopian tubes are (are) examined (s). Depending on the delivery device used to deliver the contrast agent, the fallopian tubes can be examined simultaneously or sequentially. If visualization of the entire uterus is desired, for example, after viewing the fallopian tubes, the catheter (s) is (are) extracted from the horns, and retracted (s) until the final structure single catheter is in place at the entrance to the uterus. The final structure, like a balloon, is expanded to provide a liquid seal from the uterus and the liquid / gaseous contrast agent is introduced into the uterus. Sonographic visualization is started and can be continued until a sufficient amount of the liquid / gas contrast agent is inside the uterus.
[0011] One method comprises providing a contrast medium to the uterus and fallopian tubes by supplying a catheter delivery end into the uterus and delivering a contrast medium to the uterus. For example, in a method for evaluating the uterus and at least one fallopian tube, a contrast agent device comprises a catheter, in which the catheter delivery end is positioned inside the uterus. The catheter may optionally comprise an element to prevent retrograde flow, or flow out of the uterus through the cervix, of the fluid supplied to the uterus through the catheter. For example, an expandable balloon is an element to prevent retrograde flow from the uterus to the vagina. Once the catheter (s) is (are) in place, the contrast agent, like a liquid / gas mixture, is delivered from the contrast agent device, through the catheter, to the uterus. Sonographic visualization is initiated, and optionally, the uterus is visualized, and one or both fallopian tubes are (are) visualized (s). The fallopian tubes can be examined simultaneously or sequentially. The contrast agent device can be filled and refilled one or more times to deliver an effective amount of the contrast agent to the uterus and fallopian tubes, or to provide one or more views of the uterus and / or a first or one second fallopian tube. Body structures of humans or animals, or inanimate objects, can be easily observed with the contrast agents of the present invention. The delivery of the contrast agent directly to the structure to be observed with a catheter set helps to maintain the structure of the gas and liquid segments of the liquid / gas mixture. The methods of the present invention assist in the reproducibility of the visualization methods and their comparative results. DESCRIPTION OF THE FIGURES
[0012] Figure 1 is an example of the present invention.
[0013] Figure 2 is an example of the present invention.
[0014] Figure 3 is an example of the present invention.
[0015] Figure 4 is an example of the present invention.
[0016] Figure 5 is a schematic of a pattern of a contrast material in a fallopian tube.
[0017] Figure 6 is a schematic of a contrast medium pattern visualized within the uterus and fallopian tubes provided by an exemplary device of the present invention.
[0018] Figure 7 is a drawing of the interior components, container assembly, of an exemplary device of the present invention.
[0019] Figure 8 is a drawing of an exemplary device of the present invention.
[0020] Figure 9 is a drawing of an exemplary device of the present invention.
[0021] Figure 10 is a drawing of an exemplary device of the present invention.
[0022] Figure 11 is a graph of the pressure readings of experiments with an exemplary device that comprises a pressure relief mechanism. DETAILED DESCRIPTION
[0023] The present invention comprises methods and devices for producing and using contrast agents for sonographic or ultrasound visualization of structures. Such structures may be present in the bodies of humans or animals, or they may be inanimate structures. As discussed in this document, methods and devices are used for ultrasound visualization of a uterus and one or more fallopian tubes of a mammal. It must be understood that the methods and devices are not limited to this application, and can be used in the visualization of ducts or structures, whether in living beings or inanimate structures.
[0024] The present invention comprises devices for producing a contrast medium composition. As used herein, "contrast agent" and "contrast medium" represent a composition that is visible or viewable by methods known to those skilled in the art, including, without limitation, ultrasound, fluorography, radiography, or other methods detection, and the terms can be used interchangeably. One method of the present invention comprises the use of a contrast medium device to generate and distribute a contrast agent that is useful for sonographically observing bodily organs or structures, for example, the uterus and fallopian tubes. One method of the present invention comprises the use of a contrast medium device to generate a contrast agent that is useful for sonographically observing bodily organs or structures, for example, at least one fallopian tube.
[0025] A contrast medium device comprises a container assembly, and optionally, a catheter assembly fluidly coupled to the container assembly. Exemplary embodiments of a container set of the present invention are illustrated in Figures 1 to 4 and Figures 7 to 10. A container set can be provided with a compartment (not shown in the Figures) to enclose at least a portion of the container set . For example, a compartment can enclose the components of a container assembly, and optionally, an outlet opening, an actuator and / or both plunger ends can be located outside the compartment.
[0026] A contrast medium device comprises a container assembly, and optionally, a catheter assembly fluidly coupled to the container assembly, and optionally, pressure control elements. A container assembly can comprise at least one container for a fluid. A fluid can be a liquid or a gas. A container assembly may comprise a first container for a liquid, such as saline, and a second container for a gas, such as air, and elements for creating an alternating pattern of gas and fluid. A container assembly may comprise connecting elements, such as tubes or fluid conduits, to deliver the fluid contained in a container to a contrast pattern generation chamber and the catheter assembly, or from outside the container assembly to a chamber generation of contrast pattern and to a container. The connecting elements can be used to supply fluids from the outside of the device to the containers. A container can comprise one or more outlets through which the fluid, such as gas or liquid, leaves the container, or the outlet can be used to supply a fluid, both liquid and gaseous, to the container. A container assembly may comprise a component for generating force on the fluid contained in the container in order to move it to or from the container. For example, a container can be a cylinder or syringe barrel, and the force-generating component on the fluid is a syringe plunger. A container assembly may comprise an activation component of the power generation component. For example, the container may be a cylinder or syringe barrel, the force generating component on the fluid contained is a syringe plunger, and the plunger activating component may be a pump, or an operator's hand. One aspect of the invention comprises an embodiment in which the contrast medium device comprises two containers, such as two syringe bodies, and the syringe plungers are moved together since the two plunger ends are held together by a component, such as an actuator, so that the syringe plungers move through the syringe cylinder at the same rate, speed and distance. Syringe plungers move at the same rate, speed and distance since the proximal ends of each plunger are connected by an element, such as an actuator.
[0027] The container set can further comprise fluid connections, which are elements of fluid connection between elements that are in fluid connection with each other, such as the one or more containers and a contrast pattern generation chamber. Such fluid connections include, without limitation, conduits, tubes or needles. The container assembly may comprise a contrast pattern generation chamber in which a gas phase and a liquid phase are mixed by addition, and the composition exiting the contrast pattern generation chamber, the contrast medium composition, is characterized by the alternating gas and liquid phases that form the pattern of the contrast medium composition. The container assembly may comprise fluid connections that provide the contrast medium composition to a catheter assembly or directly to a structure to be visualized.
[0028] In one embodiment, a contrast medium device may comprise a container that can function as a contrast pattern generation chamber, in which the contrast medium is produced within the container, without a contrast pattern generation chamber. , and the contrast medium composition, for example, comprising the gas and liquid phases, is provided outside the contrast medium device.
[0029] The container set can be in fluid connection with a catheter set. The catheter assembly may comprise a single or double lumen catheter. The catheter may comprise final structures, such as a balloon at the delivery end of the catheter, where the delivery end is distal to the contrast medium device and the fixation end is proximal to the contrast medium device. The opposite end of the catheter, the fixation end, may have fixing elements for attaching the catheter, for example, to the contrast medium device. Fixation elements, such as a luer lock, can be used to fix the catheter to a contrast medium device, and fixation elements are known. The catheter can comprise other components such as a wire, sensors, cutting elements, recovery elements such as clamps or clamps. Such catheters are known in the art and a person skilled in the art can select a catheter appropriate for the desired procedure.
[0030] The present invention comprises devices for delivering a contrast medium to a structure. It is contemplated in one embodiment of the present invention that the contrast medium is provided by the catheter assembly substantially directly to a structure to be visualized. In one aspect of the invention, for example, in direct distribution to a fallopian tube, the amount of contrast medium used for each fallopian tube evaluation can be small, such as less than 20 mL, less than 15 mL, less than 10 ml, less than 8 ml, less than 5 ml, less than 4 ml, less than 3 ml, less than 2 ml, less than 1 ml, less than 0.5 ml. The amount of contrast fluid used can be any amount that is sufficient to provide an accurate view of the structure. The contrast fluid can substantially fill the visualized structure, or it can be present only in particular places within the structure.
[0031] The present invention comprises contrast medium devices for distributing a contrast medium to one or more structures, such as multiple cavities, organs or conduits that are fluidly connected to each other. It is contemplated in one embodiment of the present invention that the contrast medium is provided by a catheter assembly to at least one structure to be visualized, and optionally, when supplying the contrast medium to a structure, the contrast medium can also flow for a second, third or other structure to be viewed. In one aspect of the invention, for example, visualizing a fallopian tube may first involve supplying a sufficient amount of contrast medium to the uterus so that the fluid fills the uterus to a certain extent, and then the fluid is moved for one or more fallopian tubes in fluid connection with the uterus. The fluid can also move to and through the fallopian tubes to enter the abdominal cavity. The amount of contrast medium used in a procedure to view the uterus and at least one fallopian tube can be from about 5 ml to about 100 ml, from about 10 ml to about 100 ml, from about 15 ml to about 90 ml, from about 10 ml to about 80 ml, from about 20 ml to about 70 ml, from about 30 ml to about 60 ml. The amount of contrast medium generated and distributed to the patient can be about 5 ml, about 10 ml, about 20 ml, about 30 ml, about 40 ml, about 50 ml, about 60 ml, about 70 ml, about 80 ml, about 90 ml, or about 100 ml, or more than 100 ml, if necessary for visualization of the uterus and a fallopian tube, or for multiple views. For example, a large cavity, or a cavity connected to multiple conduits, may require more than 100 mL to view the entire cavity and / or conduits. The amount of contrast fluid used can be any amount that is sufficient to provide an accurate view of the structure to be examined. The contrast fluid can substantially fill the visualized structure, or it can be present only in particular places within the structure.
[0032] For example, a contrast medium device has the capacity to generate a contrast medium composition of about 20 ml, using two containers, syringe bodies, of 10 ml each, and transfer part or all the contrast medium for a catheter system in which the delivery tip is positioned inside the uterus. The contrast medium can enter the uterus and flow directly into the fallopian tubes, in which the contrast medium is visualized, for example, by sonography. Five to ten mL of contrast medium can be used to view both fallopian tubes. The flow of contrast medium can be paused or stopped at that time. If a second visualization is desired, the flow of contrast medium can be resumed, and the visualization of body structures by the presence of the contrast medium can be performed.
[0033] An advantage of the present invention is that the flow of contrast medium is controlled so that part or all of the contrast medium composition can be supplied to a body structure. The flow of the contrast medium out of the device and / or out of a catheter, and to a body structure, can be controlled so that the delivery of the contrast medium can take place in a continuous or intermittent flow, such as delivery of part of the contrast medium, flow interruption, supply of the contrast medium, flow interruption, and so on. The container (s) of a contrast medium device can be refilled one or more times during a procedure. The flow of contrast medium to the structure can be controlled automatically or by an operator. The rate of distribution of contrast medium can be controlled. The rate of distribution can be in a range from fast to slow, and is mainly controlled by the rate of force applied to the component (s) generating force on the fluid contained within the container (s). In an embodiment in which the contrast medium device comprises two containers, such as two syringe bodies, and the component for generating force on the fluid contained within each container is a plunger, the rate of force applied to the fluid in each container it is identical when the pistons are activated simultaneously with the same applied force, to provide the same contrast medium distribution rate as the device.
[0034] One embodiment of the present invention comprises visualizing at least one fallopian tube using a catheter positioned at or near the fallopian tube orifice. Any device that supplies a fallopian tube catheter can be used. A catheter can be connected to the contrast medium device which comprises a container set described in this document. A particular device for delivering a catheter to a body structure, such as a fallopian tube, and which may be useful in methods of visualizing a fallopian tube, is the device taught in US Patent Application 11 / 065,886, in the Application for US Patent 12 / 240,738, and in US Patent Application 12 / 240,791, now US Patents, and each of which is incorporated herein in its entirety. In general, these requests reveal a device that comprises a housing and an introducer stem that is used to be introduced and through the uterus until the tip of the stem approaches or touches the bottom of the uterus. Once the tip of the introducer rod is at the bottom of the uterus, the device can be stabilized. One or more catheters, like two, are fed, through the introducer rod, to the uterine cavity. The placement of the introducer rod allows the three-dimensional alignment of the catheter (s) with the horns of the uterus. The catheter (s) is (are) propelled (s) until the delivery end (s) of the catheter (s) are (are) in place within the horns. A final structure, such as a balloon, is inflated or attached to stabilize the catheter (s) in place, and the final structure can prevent or minimize the backflow of materials exiting the catheter delivery end. Once the final structure is attached, the catheter (s) is (are) ready for distribution of materials or other activities.
[0035] In a method of the present invention, the catheter positioned by the introducer rod comprises a catheter assembly. The end of the catheter opposite the delivery end, referred to herein as the proximal end or fixation end, is attached to a contrast medium device of the present invention. The contrast medium is generated by the actions of the container set, and the contrast medium is supplied, inside and through the catheter (s), to the horns of the uterus and to one or both fallopian tubes. Visualization techniques are initiated as the contrast medium enters the fallopian tube (s) and, if possible, flows through the tube (s) into the peritoneal cavity. If a horn is blocked, the medium will not flow in it, but it may flow to a second horn, the contralateral horn, if it is not blocked. The pressure accumulated by the block may or may not be removed from a final structure in the catheter, such as a balloon, in an attempt to release the pressure, but if the final structure of the catheter is moved, the flow can then be directed to the uterus or the tube not blocked.
[0036] If the device that supplies the catheter uses only one catheter, then the visualization of a fallopian tube occurs, followed by the readjustment of the device, such as the rotation of the introducer stem, as taught in the aforementioned patent applications, and the steps are repeated to provide a contrast medium to the other fallopian tube. The contrast medium provided can be any currently known contrast medium that can be delivered through a catheter to a site.
[0037] One embodiment of the present invention comprises the use of a contrast medium device and catheter to provide a contrast medium to the uterus for viewing at least one fallopian tube, or for viewing at least a portion of the uterus and at least one fallopian tube. When the structure to be visualized is at least a fallopian tube, or a uterus and / or at least one fallopian tube, a contrast media device of the present invention, in combination with a catheter, can be used. A catheter that has elements to prevent retrograde flow of fluid from the uterus can be connected to a contrast medium device that comprises a container assembly as described herein. Catheters with element (s) that prevent retrograde flow are known in the art, and this is known to those skilled in the technique of selecting a catheter to be attached to a contrast media device of the present invention for use in the methods taught in the present document.
[0038] In a method of the present invention, a catheter, such as a balloon catheter, is a catheter assembly. In the method, the delivery end of a catheter is positioned in the uterus, and optionally, the structure to prevent retrograde flow to the cervix is employed, for example, the balloon of a balloon catheter is expanded. The end of the catheter opposite the delivery end, referred to herein as the proximal end or fixation end, is attached to a contrast medium device of the present invention. The contrast medium is generated by the actions of the device and the contrast medium is supplied, inside and through the catheter (s), to the uterus. The desired amount of contrast medium is provided and visualization techniques are started, and can be used to visualize the movement of the contrast medium to the uterus, to visualize at least a portion of the structure of the uterus, for example, by providing the contrast medium, and / or to view the entrance, transit and / or exit of the contrast medium in at least one fallopian tube. If a fallopian tube is blocked, the contrast medium will not flow beyond the block, but it can flow to the contralateral tube if it is not blocked. The pressure accumulated by the blockage may or may not be detected by an element of the contrast medium device that is designed to detect the fluid back pressure created by the absence of continuous flow of the fluid through the structure and / or ducts. If the desired pressure is reached, the flow of contrast medium may be stopped, as by a healthcare professional who, during the supply of contrast medium, may stop applying pressure to the contrast medium device and terminate the fluid supply, through the catheter, to the uterus. The contrast medium provided can be any currently known contrast medium that can be delivered through a catheter to a location, or it can be the liquid / air contrast medium disclosed herein.
[0039] A contrast medium device of the present invention may be provided with containers filled with fluid (s) or it may be provided with empty containers that must first be filled with fluid (s) before generation and distribution of the contrast medium. If all of the fluid in the contrast medium device is used in a procedure and a greater amount of contrast medium is desired, the contrast medium device of the present invention can be refilled once the device containers are filled with the respective fluid (s). By using pre-filled containers, the original containers can be removed and new containers inserted into the device. When using reusable containers, these can be refilled without removing the dispensing tip from the patient's catheter. The contrast medium device can be detached from the proximal end of the catheter and the containers refilled with a greater amount of the same type of fluid, or a different fluid, if desired, as used in the first distribution of contrast medium.
[0040] When using a contrast medium device of the present invention, once an amount of contrast medium is provided and the containers are without contrast medium, the containers can be refilled once or multiple times in order to provide a effective amount of contrast medium to the structure and / or conduits of the body. For example, in one embodiment the contrast medium comprises segments of saline and air in a pattern, which can be produced by a contrast medium device of the present invention that has two containers, one container providing saline and a second container providing air. For example, the containers can be 10 ml syringes, where a first container contains 10 ml of saline and a second container contains 10 ml of air or a gas. The contrast medium is generated or produced by the simultaneous movement of saline and air from each container, such as by applying pressure to a plunger in each container, or by a pump or other means to move a fluid from a syringe or container. similar. The air and saline are moved to a contrast pattern generation chamber. The contrast pattern generation chamber can comprise a static mixer or similar structure to mix air and liquid fluids, creating segments of saline and interspersed air segments, thus generating a contrast medium comprising saline with air bubbles or segments of air. air contained in it. The static mixer may comprise elements, such as helical elements, that simultaneously produce flow-dividing patterns and radial mixing of air and saline fluids. Static mixers are known in the art and generally comprise mixing elements contained in a tube or housing, for example, a cylindrical tube. The static mixing elements can comprise a series of deflectors that are made of metal or a variety of plastics. The static mixer works by continuously mixing two fluids as the fluid streams move through it. Other mixing elements can be used in the present invention, and such elements are known to those skilled in the art. Alternatively, a contrast medium generation chamber may comprise only one conduit into which a gas conduit of the gas container and a liquid conduit of the liquid container enter, and does not comprise a static mixer or other mixing element. As gas and liquid are supplied simultaneously to the conduit of the contrast medium generation chamber, segments of gas are created in the fluid to generate a contrast medium composition.
[0041] When the containers of the contrast medium device are empty, for example, prior to the initiation of a procedure, or when there is substantially no more fluid in the containers, such as during a procedure, in an embodiment of the present invention, the containers can be filled or refilled simultaneously, without disassembling the contrast medium device or removing the containers from the device housing. For example, when a contrast medium device comprises two containers, where a first container contains saline and a second container contains air, the first and second containers can be filled or refilled with saline and air, respectively, without disassembly. the contrast medium device or removing the containers. If a catheter is attached to the outlet opening of the contrast medium device, it can be optionally removed while filling the containers, and left in place on the patient's body. The outlet opening end of the contrast medium device, previously attached to the catheter or before being attached to the catheter, can be immersed in a saline solution. If plungers are present in the containers, such as syringe plungers or similarly movable seals inside the container body, they will be pulled into the syringe cylinder in a proximal and opposite direction to the outlet opening, creating reduced pressure within the container. syringe cylinder, which causes saline and air to enter the respective containers (syringes). Typically, the plungers are controlled simultaneously so that both are pulled from the inside of the syringe cylinder at the same rate so that both syringes are refilled simultaneously with air in the air cylinder and saline in the saline cylinder. The air cylinder is in fluid connection with at least one in-line check valve attached to the air syringe cylinder, and optionally with an in-line air filter, which allows for the unidirectional filling of the air syringe cylinder.
[0042] The trajectory of air or gas when filling a container positioned inside a contrast medium device is as follows. As the cylinder of the air syringe is pulled from the inside of the syringe in a proximal and opposite direction to the outlet opening, while the outlet opening of the device is immersed in a saline solution, air flows through the optional air filter, through fluid connections, to at least one unidirectional check valve, through at least one check valve, by means of connectors that connect to at least one check valve and the syringe (container) outlet, and to the air syringe cylinder. When the plunger reaches the proximal end of the syringe cylinder and / or is pulled to the desired point, for example, the full length of the syringe cylinder, the syringe is filled, for example, with 10 ml of air.
[0043] At the same time and rate at which the air syringe plunger is pulled through the air syringe, the fluid syringe plunger is pulled at the same rate and distance through the fluid syringe cylinder. As the outlet opening of the contrast medium device is immersed in saline, the movement of the plunger of the fluid syringe in a proximal direction, opposite the outlet opening, causes saline to enter the outlet opening of the device and move through the fluid connections to the fluid syringe container. When the plunger reaches the proximal end of the fluid syringe cylinder and / or is pulled to the desired point, for example, the full length of the syringe cylinder, the syringe is filled with, for example, 10 mL of fluid, for example , saline. When the plungers stop moving, for example, when each plunger is at the desired location within the syringe cylinder, the air container and the fluid container contain substantially the same amount of air and saline in the respective containers. The contrast medium device is then filled or refilled. Continuing the visualization procedure, the catheter can be re-attached to the device (s) fixing the outlet opening of the device and, with the opposite action by the plungers, by moving the syringe cylinder down towards the opening of the device. outlet, fluid (saline) and air are forced out of the respective fluid and air containers. The contrast medium is generated in the contrast medium generation chamber, for example, by the fluid / air streams flowing through a mixer, such as a static mixer, or by the mixing fluids in a mixing chamber without a mixing element. , and the contrast medium composition comprising segments of air and liquid leaves the contrast medium device, for example, through the attached catheter. The contrast medium can enter the cavity, such as the uterus, and at least one fallopian tube, in which the visualization of the contrast medium within the structure is conducted, as by sonographic methods, and the body structures are examined.
[0044] The disclosure of this document refers to fluids, such as air or saline, however it is contemplated that the present invention is not limited to air and / or saline, and a person skilled in the art may substitute air and / or saline by other appropriate fluids, such as other liquids, other gases or known contrast medium compositions. The methods of the present invention comprise producing or generating a contrast medium, and distributing a contrast medium to a body structure. A contrast medium device of the present invention is used to produce a contrast medium. For example, one embodiment of a contrast medium device comprising a fluid container may comprise a container comprising a flexible porous material contained therein. An example in which the container is a syringe body is described, as shown in Figure 4. The present invention is not limited to this project, and contemplates other containers that would work in a similar way. The syringe is substantially filled with a flexible, porous material. The flexible porous material includes, without limitation, strips or pieces of woven or non-woven material, an open cell material, such as a sponge, or fragments of a sponge, or any material that contains a gas and releases it under influence, such as compressive forces. For example, the flexible porous material is an open cell sponge. The sponge is positioned in the container and a liquid is added, but the liquid does not move all the air in the sponge. The syringe plunger is applied to the large open end of the syringe and the other end of the syringe is in fluid connection with the catheter assembly. As the plunger is pressed into the syringe, the sponge is compressed and air is forced into the liquid, creating bubbles or air segments. The bubbles and fluid, the air and fluid segments, enter the catheter and travel through it to the structure. The visualization of the structure is then possible. See Figure 5 for an illustration of the visualization of a fallopian tube.
[0045] The present invention comprises contrast media devices that comprise more than one container. For example, the contrast medium device may comprise two containers, as shown in Figure 1 and Figures 7 to 10, an example in which the containers comprise a syringe body, also referred to herein as a syringe cylinder or container. syringe. Optionally, the inside of the syringe cylinder can be traversed by a plunger element. The plunger element can be moved, as by an operator, through the inside of the syringe container, from a proximal location on the cylinder, where "proximal" refers to the end of the device closest to the operator and opposite the outlet opening of the device, to a distal location, where "distal" refers to the end of the device closest to the patient and closest to the outlet opening, and from a distal location on the cylinder to a proximal location on the cylinder. A plunger element can consist of a piston and a fluid seal with two surfaces, where the piston is attached to one surface of the fluid seal, the proximal surface, and the other surface, the distal surface, faces and is in contact with the distributable fluid. A standard syringe plunger is a plunger element. The fluid seal, which has two surfaces, forms a fluid seal within the container, so that a distributable fluid is maintained or contained on the distal surface of the plunger surface (a first surface) and there is no distributable fluid on the proximal surface ( a second surface). A distributable fluid is the fluid contained in the container that is intended to be supplied to the structure to be viewed and / or examined. As a plunger, which comprises a piston and a fluid seal, is moved through a syringe, there may be air or a slight vacuum created on the proximal side of the plunger, but there is no intention to supply air on the proximal side of the seal therefore, this air is not a distributable fluid. The present invention is not limited to this project, and contemplates other containers that would work in a similar way. One of the containers, which can be a pre-filled syringe, contains a liquid. The liquid can be any of those disclosed in this document, such as saline or water, or known contrast agents. A second container, which can be a pre-filled syringe, contains a gas. The gas can be any of those disclosed in this document, such as air, carbon dioxide, oxygen, nitrogen or halogenated compound gases, other gases, or known contrast agent gases. The plungers of the two syringes are pressed simultaneously, manually or mechanically, and the mixture of gas and liquid forms an alternating pattern of gas phase and liquid phase, which is a contrast medium composition. The contrast medium composition then penetrates and runs through a catheter attached to the structure, such as the fallopian tube. The visualization of the structure is possible through ultrasound techniques.
[0046] Alternatively, a device of the present invention may comprise two containers, such as two syringes, which are not provided with fluid. When using such a device, each plunger is pressed to a position at the distal end of each container, such as a syringe, and the outlet opening of the device is positioned in the saline. As each plunger is simultaneously moved to a desired proximal location within the container, air is drawn into a first container and fluid is drawn into a second container. The substantially simultaneous filling of a two-container device is disclosed in this document. Once the containers are filled, the plungers can be pressed, moving the surface of the fluid seal to a more distal location and dispensing the fluids from the containers. The fluids are mixed, gas and liquid are mixed by addition to form a contrast medium composition comprising segments of air and liquid, and the contrast medium composition flows into the outlet opening of the device, and optionally to a catheter positioned within the structure to be examined. One embodiment of the present invention can comprise the movement of a plunger, and the supply of a fluid to a container or the supply of a fluid from a container.
[0047] The compositions of the present invention comprise a contrast medium produced using the methods taught in this document. A contrast medium of the present invention comprises a gas phase in a liquid carrier. The gas phase can be a bubble or an area filled with gas and without liquid adjacent to an area of liquid phase, and the alternation between the area filled with gas and the liquid area can be repeated several times. The sizes of areas filled with gas or areas filled with liquid can be uniform or not. The present invention contemplates an aspect in which the supply of a reduced volume contrast medium is used, in comparison with the quantities currently used, which can be 20 ml or more, as well as the supply of the contrast medium substantially within or well near the structure to be visualized (ie, a fallopian tube).
[0048] The present invention contemplates providing an amount of contrast medium that is effective for visualizing a structure. For example, an effective amount of a contrast medium can comprise 5 ml to 200 ml, depending on the volume of the structure and the number of structures to be examined. For example, if a device of the present invention is used to provide contrast medium to the uterus and fallopian tubes, an effective amount of contrast medium to be supplied to those structures may be greater than the amount used to provide a contrast medium directly. to the fallopian tubes. The present invention controls the amount of gas and liquid used in combination to form the mixed gas / liquid composition that enters the structure. The pattern of the contrast medium composition can vary from predominantly a gas phase (air or other gas) to predominantly a liquid phase (saline or other liquid) and can be supplied in a regular pattern or an irregular pattern. The ratios of the gas to the liquid can be determined by the size of the respective syringe. The larger the air syringe, the larger the air segment in the composition pattern. The use of a porous structure can create a more random or irregular pattern. The amount of contrast medium delivered can be controlled by the amount of displacement of the syringe plunger or by refilling the containers one or more times.
[0049] A contrast medium device of the present invention generates and distributes an alternating pattern of reproducible and safe air and fluid that is visible by means of detection methods such as sonography. The air / liquid pattern produced by a composition generated by a device of the present invention is reproducible in that an alternating pattern of substantially regular repetition of air and liquid generated as a contrast medium composition by the device is supplied to a structure and, for example, is visible in a fallopian tube. The pattern is produced consistently by a device, such as a device of the present invention, which generates a contrast medium composition, in which the distance between the air / saline interfaces is short enough, and is repeated sufficiently regularly so that the movement of the composition through a structure is visible, as by sonography. The consistent pattern can be visualized in the uterus and in the open, unblocked fallopian tubes through detection methods, such as sonography. It is contemplated by the present invention that the distance between the interfaces of a contrast medium of the present invention is not necessarily identical for each pair of interfaces, but the distances are sufficiently similar in size to form the perception of a repetition pattern of white and black by means of detection, such as sonography, and the structure of a body structure, such as a fallopian tube, can be visualized by the movement of the regular black and white pattern produced by the interfaces submitted to the means of detection, such as sonography.
[0050] For example, to assess the fallopian tubes for patency, in order to determine whether the tube is open and free from obstructions or blockages, it is desired that the composition of saline and distributed air have air / saline interfaces that are in an alternating, frequent and regular pattern of variable intervals. Isolated saline appears black when viewed by sonography as it reflects less sound echoes to the probe, so long saline intervals can present a problem for the user when viewing a body structure, such as a fallopian tube. The air appears white, like bones, since the air reflects more sound echoes to the probe, so long intervals of air can be misinterpreted and easily confused with other body tissues, causing uncertainty about the diagnosis of patency of fallopian tube. The movement of the saline and air interfaces in a repetition pattern, as described by the present invention, which is frequent, regular and alternating, allows an effect called reverberation that is caused by the sound that interacts with two structures of sufficiently different reflective properties. The described invention also allows for a comet tail effect, a type of reverberation caused by a series of small highly reflective interfaces, like air bubbles in a fluid. If the pattern is very unstable, as seen in the literature of historical and previously used methods, a safe and accurate diagnosis of the structure or patency of a fallopian tube cannot be assessed, and it is certainly neither easy nor safe. With an unstable and irregular pattern, the complexity of the hysterosonography procedure increases dramatically, making the safety of the procedure questionable, and the learning curve for a health professional to learn and perform the procedure, very steep. Specifically, unstable patterns that consist of small pattern frequencies that create a long segment of air or saline can cause misinterpretation since there is no apparent movement of the contrast medium, and it is the perception of the movement of the contrast medium within and through a structure that is necessary for the health professional to carry out an assessment of the fallopian tubes.
[0051] Additionally, in sonographic procedures that examine the uterus and fallopian tubes, it can be challenging to obtain the ideal position / location of the ultrasound probe in the correct plane due to the different anatomical positions of the patients in relation to the uterus and fallopian tubes. Therefore, the consistent movement of an alternating, frequent and regular pattern of the contrast medium, such as that generated by a device of the present invention, will increase the likelihood that the body structure (s) will be visualized. (s) by the doctor (health professional) to carry out the intended evaluation. During the procedure, the doctor may have difficulty visualizing one of the fallopian tubes, such as where the flow is easily visualized in one fallopian tube and the other tube is blocked, difficult to locate or experiencing tubal spasm. In such and similar situations, the user may need to distribute more saline and air to the patient in order to discard or confirm the block in the unseen tube, therefore, the aspect of the invention that allows a quick and easy refilling of the device with fluids, such as air and saline, are advantageous for the ease and convenience of the procedure. The patient's discomfort or a decision to delay the procedure for a few minutes to allow the tubes to relax in defiance of a difficult tubal evaluation may also require a delay in the distribution of saline and air, prolonging the total time of the procedure. Thus, the provision of a contrast medium composition that provides a regular repetition pattern of the interfaces of the air segments and liquid segments, such as after a pause in the procedure or after a new filling of the device containers, is an advantage of the present invention in view of the previous devices.
[0052] A composition of the present invention can comprise a liquid and a gas, and optionally, surfactants, emulsifiers, or other stabilizing agents. The liquid, which can be seen as a carrier of the gas phase, can be any liquid that is substantially free of solids and flows at normal or body temperatures. For example, the liquid can be water or physiologically acceptable aqueous solutions, including, without limitation, physiological electrolyte solutions, physiological saline solutions, Ringer's solution or aqueous solutions of sodium chloride, calcium chloride, sodium bicarbonate, sodium citrate, sodium acetate, or sodium tartrate, glucose solutions, or mono or polyhydric alcohol solutions, for example, ethanol, n-butanol, ethylene glycol, polyvinylpyrrolidone, or mixtures or combinations thereof. In addition, the liquid carrier may comprise physiologically acceptable non-aqueous solutions, including, without limitation, anhydrous or substantially anhydrous carrier liquids, alcohols, glycols, polyglycols, synthetic perfluorinated hydrocarbons, or in mixtures or combinations with other non-aqueous or aqueous liquids.
[0053] The contrast medium compositions of the present invention may comprise surfactants or compounds that stabilize the gas-liquid interface. Surfactants can be supplied in the liquid phase of the contrast medium. For example, if a contrast medium composition comprises air and a liquid, such as saline, one or more surfactants can be added to the saline. Surfactant compositions can be useful when the contrast medium is supplied to a structure that is larger than the size of the catheter used to transmit the contrast medium. Surfactants include surfactants, such as lecithins; esters and ethers of fatty acids and fatty alcohols with polyoxyethylene and polyoxyethylated polyols such as sorbitol, glycols and glycerol, cholesterol; and polyoxyethylene and polyoxypropylene polymers, compounds that increase viscosity and stabilizers, mono- and polysaccharides (glucose, lactose, sucrose, dextran, sorbitol); polyols, for example, glycerol, polyglycols; and polypeptides such as proteins, gelatin, oxipoligelatin, plasma protein, amphipathic compounds capable of forming stable films in the presence of water and gases, such as lecithins (phosphatidylcholine) and other phospholipids, among others, phosphatidic acid (PA), phosphatidylinositol, phosphatidylethanolamine (PE), phosphatidylserine (PS), phosphatidylglycerol (PG), cardiolipin (CL), sphingomyelin, plasmogens, cerebrosides, natural lecithins, such as egg lecithin or soy lecithin, or synthetic lecithins, such as synthetic lecithins, such as saturated lecithins example, dimyristoylphosphatidylcholine, dipalmitoylphosphatidylcholine or distearoylphosphatidylcholine or unsaturated synthetic lecithins, such as dioleylphosphatidylcholine or dilinoleylphosphatidylcholine, free fatty acids, fatty acid esters with polyoxygenyloglycyloxy compounds; ethers of fatty alcohols with polyoxyalkylene glycols; fatty acid esters with polyoxyalkylated sorbitan; soaps; glycerol-polyalkylene stearate; glycerol-polyoxyethylene ricinoleate; homo and polyalkylene glycols copolymers; polyethoxylated castor oil and soybean oil, as well as hydrogenated derivatives; ethers and esters of sucrose or other carbohydrates with fatty acids, fatty alcohols, which are optionally polyoxyalkylated; mono-, di- and triglycerides of saturated or unsaturated fatty acids; soybean oil and sucrose glycerides, block copolymers of polyoxypropylene and polyoxyethylene (poloxamers) of polyoxyethylene sorbitans, sorbitol, glycerol-polyalkylene stearate, glycerol-polyoxyethylene ricinoleate, homo and copolymers of polyalkylene glycols, as well as hydrochloride and glycogen derivatives, as well as hydrochloride and glycol derivatives. sucrose ethers and esters or other carbohydrates with fatty acids, fatty alcohols, soy oil glycerides, dextran, sucrose and carbohydrates. Surfactants can be film-forming and non-film-forming and can include polymerizable amphiphilic compounds of the type linoleyl-lecithins or polyethylene dodecanoate, phosphatidic acid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylserine, phosphatidylglycerol, phosphatidyl and phosphatidylsol ability to form stable films in the presence of an aqueous phase and a gas, phospholipids, including phosphatidylcholine (PC) with saturated and unsaturated lipids; including phosphatidylcholine, such as dioleylphosphatidylcholine; dimyristoylphosphatidylcholine (DMPC), dipentadecanoylphosphatidylcholine, dilauroylphosphatidylcholine (DLPC), dipalmitoylphosphatidylcholine (DPPC); disteraoylphosphatidylcholine (DSPC); and diaraquidonylphosphatidylcholine (DAPC); phosphatidylethanolamines (PE), such as dioleylphosphatidylethanolamine, dipaimitoylphosphatidylethanolamine (DPPE) and distearoylphosphatidylethanolamine (DSPE); phosphatidylserine (PS), such as dipalmitoylphosphatidylserine (DPPS), disteraoylphosphatidylserine (DSPS); phosphatidylglycerols (PG), such as dipalmitoylphosphatidylglycerol (DPPG), distearoylphosphatidylglycerol (DSPG); and phosphatidylinositol. Surfactants, emulsifiers, or other stabilizing agents can be sprayed into the gas phase.
[0054] Contrast medium compositions can comprise gases, and any physiologically acceptable gas can be present in the compositions of the present invention. The term “gas”, as used in this document, includes any substances (including mixtures) substantially in gaseous form at normal human body temperature (37oC). Approximately 200 different gases have been identified as potentially useful for producing ultrasound contrast agents, and include oxygen, air, nitrogen, carbon dioxide or mixtures thereof, helium, argon, xenon, krypton, CHClF2 or nitrous oxide, sulfur hexafluoride, tetrafluoromethane, chlorotrifluoromethane, dichlorodifluoromethane, bromotrifluormetano, bromochlorodifluoro, dibromodifluormetano, dichlorotetrafluoroethane, chloropentafluoroethane, Hexafluoroethane, hexafluoropropylene, octafluorpropano, hexafluorbutadieno, octafluoro-2-butene, octafluorciclobutano, decafluorbutano, perfluorciclopentano, dodecafluorpentano, fluorinated gases, including materials containing at least one atom fluorine, such as SF6, frees (organic compounds that contain one or more carbon atoms and fluorine, that is, CF4, C2F6, C3F8, C4F8, C4F10, CBrF3, CCl2F2, C2ClF5 and CBrClF2 and perfluorocarbons. The term perfluorocarbon refers to compounds that contain only carbon and fluorine atoms and include i saturated, unsaturated and cyclic perfluorocarbons, such as perfluoralkanes, such as perfluoromethane, perfluorethane, perfluorpropanes, perfluorbutans (for example, perfluor-n-butane, optionally in admixture with other isomers, such as perfluor-isobutane), perfluorpentans, perfluorhex ; perfluoralkenes, such as perfluorpropene, perfluorbutenes (for example, perfluorbut-2-ene) and perfluorbutadiene; perfluoralcines, such as perfluorbut-2-ino, and perfluorocycloalcans, such as perfluorocyclobutane, perfluoromethylcyclobutane, perfluordimethylcyclobutanes, perfluortrimethylcyclobutanes, perfluorcyclopentane, perfluormethylcyclohexane, perfluormethylcyclohexane, perfluorethylcyclohexane, Saturated perfluorocarbons, which are generally preferred, have the formula CnFn + 2, where n is between 1 and 12, preferably between 2 and 10, more preferably between 3 and 8, and most preferably between 3 and 6. Suitable perfluorocarbons include, for example, CF4, C2F6, C3F8, C4F8, C4F10, C5F12, C6F12, C7F14, C8F18 and C9F20.
[0055] The present invention comprises modalities of contrast medium systems and devices. A system of the present invention can comprise separable components; a contrast medium device comprising a container assembly, and a catheter assembly that provides the contrast medium composition, the fluid outlet from the device, into, near or into the target cavity or duct. Alternatively, a system of the present invention can be a simple one-piece construction with a contrast medium device comprising a container assembly attached to a catheter assembly. A contrast medium device can comprise a container assembly that provides a contrast medium comprising a gas phase and a liquid phase. A contrast medium device may comprise a container assembly comprising a conventional modified multi-syringe pump, a hand-held mechanical or manual device capable of accepting syringes of various sizes. The syringe outlets are directed to a conduit or mixing chamber in which the appropriately created gas (i.e., air) and liquid (i.e., saline) sequence is then conducted to the entrance of a catheter assembly. For example, the targeted distribution of the contrast medium in or near the duct (ie, a fallopian tube) will allow sonography of the structure. A contrast medium composition can be supplied directly to the fallopian tube, which means that the contrast medium composition is distributed only to the fallopian tube, or only to the fallopian tube in the first place, and not the filling of the uterus with a fluid and its leakage into the fallopian tubes. A contrast medium composition can be supplied directly to the uterus, which can allow visualization of the uterus, and by providing a sufficient amount of contrast medium, it can flow into one or more fallopian tubes. The contrast medium may or may not enter and flow through the fallopian tube, depending on the patency of the fallopian tube. Providing a composition directly to a structure in this document means that the composition is supplied at or near a hole in the structure to be evaluated, so that the composition enters the structure and does not flow into the structure from a remote distribution location of a composition.
[0056] One aspect of the invention comprises the use of a device of the present invention with known hysterosalpingography procedures. For example, such procedures can be performed before or after using a device of the present invention. A procedure may comprise supplying saline only to the uterine cavity to at least partially fill or distend the uterus. The uterus can be visualized using detection methods, such as sonography. The saline is then released from the uterus, such as by releasing a balloon used to seal the closed uterus from the cervix, or by extracting the catheter that supplied the saline to the uterus. Alternatively, saline can flow out of the fallopian tubes. After this pre-treatment procedure, a contrast medium device of the present invention can be used by attaching the device to a catheter that has its distribution end within the uterus, generating a contrast medium composition and the supply of the contrast medium composition to the uterus and at least one fallopian tube. Post-treatments can also be delivered to the uterus or fallopian tubes after supplying the contrast medium composition. For example, a therapeutic composition or an embryonic composition can then be delivered to the uterus or fallopian tube.
[0057] Although there is no link with any particular theory, it is theorized that the provision of a contrast medium composition of the present invention, with the use of a device of the present invention, aids the fertility of a patient who has undergone methods described in this document. It is believed that there is a higher incidence of pregnancies found in women who have undergone a procedure that comprises the use of a contrast medium device and air / saline contrast medium composition of the present invention. The present invention comprises a method for increasing the possibility of pregnancy in a woman, assisting or obtaining a condition of pregnancy in a woman, or increasing the fertility of a woman, which comprises providing a contrast medium generation and distribution device comprising a container assembly comprising at least one container for containing a fluid, a component for moving a fluid from the container, and connections for fluidly connecting at least one container to a contrast medium generation chamber, such as a device disclosed in this document, to fill at least one container with a fluid; moving the fluid from at least one container to a contrast medium generation container in order to generate a contrast medium composition; and distribute the contrast medium composition to a woman's body structure. Visualization using detection methods such as sonography may or may not be performed.
[0058] In the methods of the present invention, one or both fallopian tubes can (s) be viewed simultaneously, sequentially or in separate procedures. In some cases, it may not be possible to view both fallopian tubes in the same sonographic image viewing plane. One or both fallopian tubes can be filled simultaneously, for example, if a spasm contracts the orifice or a portion of a fallopian tube.
[0059] One aspect of the present invention comprises a contrast medium device comprising a container assembly comprising a contrast pattern generation chamber that has a diameter in a ratio range of 0.3 to 1.8 for the diameter of the structure to be visualized. The diameter of the contrast pattern generation chamber can be in a ratio of 0.1 to 100 for the diameter of the structure to be visualized. The contrast pattern generation chamber can have a diameter ratio of 0.5 to 1 for the structure to be visualized, a diameter ratio of 1 to 1 for the structure to be visualized, a diameter ratio of 1 to 1 , 5 for the structure to be visualized, a diameter ratio of 1 to 2 for the structure to be visualized. One aspect of a contrast medium device comprises a container assembly comprising a contrast pattern generation chamber that has a diameter substantially equal to the diameter of the structure to be viewed, where the ratio of diameters is 1.
[0060] One aspect of the present invention comprises a contrast medium device comprising a container assembly comprising a contrast pattern generation chamber comprising a static mixer used to mix two or more fluids supplied from the (s) container (s). As two or more fluids enter the static mixer, positioned in line and in fluid connection with two or more containers and before the outlet opening, the static mixer mixes the two or more fluids. For example, in one embodiment of a contrast medium device of the present invention, the fluid in one container is saline and the fluid in a second container is air. As the saline and air are moved from the respective containers to the static mixer, air bubbles in the saline or segments of air and saline are created by the static mixer. After leaving the static mixer and exiting the contrast medium device through the outlet opening, optionally for a catheter, the mixture of air and saline, visualized essentially as air bubbles in the saline in an open space such as the uterus or a standardized sequence of air and saline segments when inside a horn, it is a contrast medium that can be used to visualize a structure.
[0061] The interfaces of the alternating gas and liquid phases need to be present in a sufficient number if a duct, tube or structure needs to be visualized by this contrast medium, and both phases must be present in the visualization region during the viewing period. It is the presence of both phases that cross the visualization region that provides the visualization contrast. For example, if only one phase (both liquid and gaseous) is visible in the viewing region at any given time, the evaluation will become difficult or impossible. The creation of multiple interfaces between the two phases in the contrast medium makes it possible to observe the structure because the flow of the contrast medium comprises the interfaces of the phases.
[0062] One aspect of the present invention comprises contrast media devices that comprise contrast pattern generation chambers that have diameters similar to the structure to be observed. For example, if the gas phase created is smaller than the diameter of the structure to be observed, the gas will rise to the upper portion of the duct and coalesce with another gas phase, filling the diameter of the structure. One aspect of the present invention comprises contrast media devices that comprise contrast pattern generation chambers that have diameters that are larger or smaller than the structure to be observed. For example, if very small gas phases are created in the contrast pattern generation chamber, the small gas phases can be maintained in a larger diameter structure using dispersing agents, surfactants, or other similar active components in the liquid phase or gaseous. These small gaseous phases can be achieved by vibrating manipulation of the container assembly. The greater the frequency of oscillations, the smaller the gas phase bubbles released.
[0063] One aspect of the present invention comprises contrast media devices that comprise contrast pattern generation chambers that comprise structures that can mix two or more fluids. For example, a contrast pattern generation chamber may comprise a static mixer. Static mixers and similar elements that can mix two or more fluids are known to those skilled in the art, and the present invention is not limited to the illustrations used in this document. The term "mix" means that two or more fluids are mixed, but the interfaces between the two or more fluids are maintained in the mixed composition. It is the interfaces between the fluids that provide the contrast for the visualization of the structure. The interfaces can be maintained by the use of dispersing agents, surfactants, or other similar active agents in the liquid or gaseous phase. A contrast medium of the present invention comprises interfaces between air and a fluid, such as saline, where interfaces are provided by air bubbles in saline or segments of air and saline, and interfaces are maintained long enough to determine physical aspects of structures like the uterus and / or at least one fallopian tube, or two fallopian tubes. For example, physical aspects may include the shape of a cavity, polyps within a cavity, the patency of ducts and / or the blockage of ducts. The cavities in this document can comprise any cavity in the body, for example, the uterus. The conduits in this document can comprise any conduit in the body, for example, a fallopian tube.
[0064] A manual means of creating a contrast medium can be achieved by using a contrast medium device comprising a container assembly comprising a single syringe and a porous substance, such as open cell foams, sponges, or woven or non-woven fabrics or fibers or combinations thereof. The syringe is loaded with one or more of these substances in a loosely attached manner and the plunger is then replaced in the fully retracted position. The contrast medium is then injected or otherwise fed or extracted into the syringe chamber containing the porous substance (s). By pressing the syringe plunger in a controlled manner, the fluid and air or other gas are expelled in a manner similar to the two syringe system described above. The catheter set distributes the contrast medium for the structure to be evaluated.
[0065] One use of the devices disclosed in this document is to distribute contrast medium compositions to a structure to be visualized. Diagnostic or therapeutic treatments can be provided to humans or animals by distributing compositions, such as contrast medium compositions or compositions comprising therapeutic agents, to a structure using the contrast medium device and a catheter set, as described in this document. For example, therapeutic agents can be supplied to a fallopian tube in combination with alternating phase interfaces provided by introducing a gas into a composition comprising therapeutic agents, and for the treatment of the fallopian tube, these agents include, without limitation , methotrexate, hormones, compounds that improve fertility, compounds that interfere with fertility, compounds that improve motility, compounds that interfere with motility, compounds that affect the eyelash / deciliation cycle, compounds that improve or interfere with eyelash growth, compounds treatment of ovarian follicles, antibacterial, antimicrobial, antifungal, antiviral, antimycoplasmic or antiparasitic compounds, compounds that reduce inflammation or scar tissue formation, compositions comprising one or more antibiotics, antimycoplasmic agents, or antiviral compounds; compositions comprising mucoproteins, electrolytes or enzymes to improve or inhibit fertility, progesterone, estrogen, adrenergic active compounds, noradrenergic active compounds, non-steroidal anti-inflammatory drugs, prostaglandins, other compounds that can treat or prevent fallopian tube diseases, uterus, ovaries, or other organs or linings affected by a composition that flows from the horns or ostia of a fallopian tube, or combinations thereof. Therapeutic compositions comprise fertility hormones, fertility enhancing compounds, gametes, sperm, eggs, combinations of sperm and eggs, one or more zygotes, or one or more embryos, or combinations thereof. In the methods in which the distribution of such compositions of diagnostic or therapeutic agents is offered through the direct delivery of these compositions to structures, the compositions may further comprise the intercalation of a gas between the compositions comprising diagnostic or therapeutic agents, and the distribution of the compositions can be monitored by techniques such as ultrasound. A composition comprising therapeutic agents combined with the interfaces created by combining a gas with the therapeutic composition using a contrast medium device of the present invention can provide both the treatment and the diagnosis of the disease of a structure in one step distribution of the composition. Alternatively, a composition of therapeutic agents combined with gaseous / liquid phase interfaces can be used to limit or locate the drug in the desired structure with the support of sonographic image visualization, allowing the diagnosis and treatment to occur simultaneously or in sequence.
[0066] Figure 1 presents a schematic diagram of a modality of the contrast medium device 100 comprising the container assembly 101, and shows a portion of a catheter assembly 102 in fluid connection with the container assembly 101, to create alternating and repetitive interfaces of gas and liquid phases. The container assembly 100 can be coupled to a catheter assembly comprising a catheter 1. The dimensions of a contrast pattern generation chamber 3 and / or a catheter can include diameters to keep the gas / liquid phases distinct and thus minimize the coalescence of similar phases. In some embodiments, the diameters of the contrast generation chamber and the catheter can vary between about 0.5 mm and about 5.0 mm. A pressure relief valve 2 can minimize the buildup of undue pressure in a structure, such as a fallopian tube, if the structure is blocked, that is, if a fallopian tube is not patent. Such valves can be used in line at other locations on the device (not shown) or the modes may not have valves. These can also act as a secondary relief for a final structure in a catheter, such as a balloon, when it is positioned at the entrance to the fallopian tube, the horns, and the final structure acts to keep the catheter in place.
[0067] The contrast pattern generation chamber 3 creates the phases with interfaces between the liquid phase (for example, saline) 14 and the gas phase (for example, air) 13. The formation of interfaces between the gas and liquid phases occurs as the two media enter the contrast pattern generation chamber after being propelled by the double syringe pump 7. A rubber septum 4 allows a needle 9 to be inserted into the contrast pattern generation chamber 3 with airtight seal . A liquid phase is introduced into the contrast pattern generation chamber 3 via a connection 10, which can be a pipe. Gas or liquid can be supplied from any container. Valves can be added in line, as to prevent possible flow along the path of least resistance, and a one-way check valve 12 can be positioned posterior to needle 9. An in-line aseptic filtration device is located prior to the check valve 5 of about 0.2 microns of porosity, and such filters can be used in-line for one or both media. The embodiments of the present invention can comprise devices that do not include such valves or filters. Syringe 11a, as well as syringe 11b, can be preloaded with their respective medium, both liquid and gas, and positioned and locked on the two syringe pump 7. The syringe pump drive block 8 extracts the respective plungers from the gas and liquid syringes 6a and 6b simultaneously. A junction 15 is formed between the contrast generation chamber and a catheter. A vibrator 16 is an optional element that is used to create vibrations through needle 9 in order to create smaller phases, such as bubbles, from the phase 9 exit needle, both gaseous and liquid.
[0068] An alternative embodiment comprises a double pump in which the actuation block comprises two separate actuators for the two individual syringes. This allows modification of the interface pattern, or of the gas / liquid phases, to provide a phase in smaller or larger segments in relation to each other. This can be accomplished by a slower (or faster) rate of distribution by one plunger in relation to the other.
[0069] The diameter of needle 9 may be relatively smaller or slightly smaller than the diameter of the contrast pattern generation chamber to allow the phase distributed through needle 9 to be affected by the other phase in the contrast pattern generation chamber 3 , so that the phase distributed by the needle 9 is dispersed in discrete quantities. For example, the surface tension of a liquid, distributed through needle 9, can cause a defined amount of liquid to be drawn from the tip of the needle and form a liquid phase in the gas in the contrast pattern generation chamber. For example, the needle gauge can vary between about 10 and 30.
[0070] Figure 2 is similar to Figure 1, except that the contrast medium device 200 has a contrast pattern generation chamber that has a larger diameter than a delivery catheter. Figure 2 is numbered similarly to Figure 1, which shows the container assembly 201 in fluid connection with the catheter assembly 202.
[0071] Figure 3 is similar to Figure 1, except that the contrast medium device 300 has a contrast pattern generation chamber that has a larger diameter than a delivery catheter, and there is no needle 9. Figure 3 is numbered similarly to Figure 1, which shows the container set 301 in fluid connection with the catheter set 302.
[0072] Figure 4 is a schematic diagram of an embodiment of a container assembly 200 used to create and distribute an alternating gas / liquid contrast medium to a catheter assembly or similar device. Syringe 10 is packaged with a porous substance 20. Porous substance 20 is partially saturated with liquid 30. This can be achieved by extracting the plunger 40, immersing the syringe in a liquid, and injecting the liquid through the injection port. syringe 50 or other suitable means of positioning the liquid in the interstices of the porous substance 20. For example, the porous substance can be supplied in a moist state, with the liquid already associated with the porous substance, before positioning in the container. The syringe orifice 50 is suitably coupled, with or without an aseptic filtration component, to a catheter assembly or similar delivery component to transfer the contrast medium to the desired location. The plunger 40 is gradually pulled out so that the liquid and gas phases alternatively exit the syringe orifice 50 into the catheter assembly and are distributed to the intended location to be visualized.
[0073] Figure 5 is a schematic diagram of a fallopian tube visualization using a contrast medium composition of the present invention and a dispensing device, as defined in US Patent Applications 12 / 240,738 and 12 / 240,791 . The introducer rod 60 is shown positioned in the uterus 120. The catheter assembly 70 extends from the introducer rod 60 and the delivery end of the catheter 80 is in place in the horns of the uterus. The contrast medium 130 is present in the fallopian tube 90 and comprises the contrast medium 130 with a fluid phase 100 and a gas phase 110.
[0074] Figure 6 illustrates the distribution of an air / saline contrast medium composition produced by a device of the present invention in which the air / saline composition is delivered directly to the uterus of a female mammal. The delivery end of a catheter 1 with a balloon element to block retrograde flow is positioned within the uterus 2 of a mammal. A gas / liquid contrast medium 3 is generated and distributed, via catheter 1, to the uterus. The contrast medium flows through the uterus to the fallopian tubes 4 which are visible due to the alternating pattern created by the gas / liquid segments of the contrast medium.
[0075] Figure 7 illustrates the container assembly of a contrast medium device 20 comprising a two container embodiment of the present invention. In the figures there is not shown a compartment that can enclose the components shown in the figures, but, optionally, it may not enclose the air outlet opening 6 and / or the ends of the plunger. From the proximal end of the figure, the elements of the device are described. Plunger ends 7a and 7b are attached to syringe plungers (not shown) maintained within syringe bodies 4a and 4b. An element is not shown which connects the two piston ends so that the piston ends 7a and 7b can be actuated simultaneously. Refer to Figure 8 for actuator 35, as an example of an element that connects the two plunger ends. Also, the full length of each plunger is not shown, where each plunger end can be connected to a piston and a displaced fluid seal inside the syringe body. The syringe body (container) 4b is hollow and can contain a liquid, such as saline, and is in fluid connection with a fluid conduit, port 3b. The connection 3b connects to the contrast medium generation chamber 8, which comprises a duct in fluid connection, respectively, with each container (connections 11a and 11b) and a mixing chamber 1, and the static mixer 12. The body of syringe (container) 4a is hollow and can contain a gas, and is in line and in gas connection with a check valve 2a which is in line with port 10 in the air path of the air opening port 5. The port 10 is in line and in fluid connection with an air filter 9 which is in line and in fluid connection with an air opening orifice 5. To fill the container 4a, air can be drawn in through the air opening orifice air 5, and through the filter 9, through the connection 10, through the check valve 2a, through the connection 3a, through the outlet opening of the container 14a, to the container 4a. To supply air to the contrast medium generation chamber 8, air is moved from the container 4a, through the outlet opening of the container 14a, to the connection 3a by applying pressure to the piston end 7a, which moves the piston and sealing fluid through the inner body of the container 4a. The check valve 2b is in fluid (gas) communication with the contrast generation chamber 8 so that the gas in the container 4a is moved from the container 4a, through the outlet opening of the container 14a, through the connection 3a, through from the check valve 2b, to the proximal end of the contrast medium generation chamber 8 at connection 11a, within the contrast generation chamber 8, to the mixing chamber 1, which may comprise a static mixer 12. The generation of contrast medium 8 is fluidly connected to outlet opening 6. One connector, connector 7, is shown, and can be used to connect a catheter to a contrast medium device, as shown. Connecting elements, such as connector 22, luer lock locks or other conduit or pipe connectors, can be used to secure separate elements of the device.
[0076] When supplying saline or any other fluid to the contrast medium generation chamber 8, the saline (or other fluid) is moved from container 4b, through the outlet opening of container 14b, to connection 3b through application pressure to the plunger end 7b, which moves the piston and fluid seal through the inner body of the container 4b. At connection 3b, the saline enters the proximal end of the contrast medium generation chamber 8, which comprises connection 11b, which is in line and fluidly connected to the mixing chamber 1. The distal end of the medium generation chamber of contrast 8 is in fluid connection with the static mixer 12 and the outlet opening 6.
[0077] When filling the device of Figure 7 with a liquid, such as saline, the outlet opening 6 is immersed in the fluid, such as saline, which is found in a container such as a basin or other fluid container. The piston and fluid seal ends of the plunger 7b are located in a more distal position within the container 4b, and a force is applied to move the plunger end, and the piston and fluid seal, in the opposite direction to the opening of the exit 6 and towards the proximal end of container 4b. As the fluid seal moves through the container in a proximal direction, saline is extracted into and through outlet opening 6, through the contrast medium generation chamber 8 and connections 11a and 11b, where the saline cannot flow beyond connection 11a through check valve 2b (a one-way valve), and saline continues to flow through connection 3b and the outlet of container 14b, to container 4b.
[0078] Figure 8 illustrates an alternative mode of a contrast medium device in which the static mixer 12 (shown in Figure 7) is shortened or not present, and the outlet opening 6 is connected to the mixing chamber 1 of the contrast medium generation chamber 8. The other elements are similar to Figure 7.
[0079] Figure 9 is an illustration of the internal components (container set) of a contrast medium device of the present invention with pressure management elements. The structures are numbered as in Figure 7. The distal end of connector 7 is in line and fluidly connected to a channel 21a of the pressure relief mechanism, which comprises at least elements 21a, 21b, 22, 16 and 17. The channel 21a of the pressure relief mechanism is in fluid connection with connection 19 and optionally comprises a tap valve, which can be in an open or closed position by the user of the tap handle 15, and in line and in fluid connection with the connector 18 and outlet opening 20. The relief valve 21b of the pressure relief mechanism is in a closed position and is opened when the fluid pressure in the valve exceeds the allowable pressure. When the permissible pressure is exceeded, the relief valve 21b opens, and fluid flows from channel 21a (or from connection 19 to channel 21a), through relief valve 21b, to and through connector 16, which is connected to the relief valve 21b via pipe connection 22. Connector 16 is a fastener for connecting a container, bag or collection device (not shown) to the fluid flowing through outlet opening 17. If the relief valve relief 21b opens, the tap 15 can be turned to close the connection 19 so that the fluid stops flowing to the relief valve 21b.
[0080] Figure 10 is an illustration of the internal elements of a device of the present invention, and shows the actuator 35, which, when moved in the direction or in the opposite direction of the outlet opening 20, moves both plunger ends 7a and 7b (partially hidden in the drawing by actuator 35), simultaneously. The actuator can be external to a compartment that encloses the internal elements of the device.
[0081] The methods of the present invention comprise the use of a contrast medium to observe structures by means of ultrasound techniques. The present invention comprises producing a contrast medium comprising liquid and gas phases in a pattern using a contrast medium device, as described herein. The contrast medium is distributed directly to or within the structure to be visualized by sonography. For example, if the fallopian tubes need to be examined, the contrast medium can be delivered to the uterine horns or into the fallopian tube orifice through a catheter. Alternatively, a sufficient amount of contrast medium can be supplied to the uterus and fallopian tubes so that the entire organ system, uterus and fallopian tubes, can be assessed by visualization techniques. Complete division of the uterine cavity may not be necessary to assess one or both fallopian tubes. In contrast, other known systems require filling the entire uterus with a liquid, such as saline, and then adding the mixed gas / liquid composition to the saline-filled uterus and waiting until the gas / liquid mixture reaches the Fallopian tubes. There are procedural limitations in relation to such a method in that it requires the uterus to be loaded with sufficient saline for distention before the introduction of air and saline in order to visualize the uterine tubes, with the air present in the uterus or the tubes it can create air pockets that alter fluid flow, and the patient may need to be moved to unusual positions for the gas to flow in a useful direction. The physician needs to perform multiple stages of exchange of a complex nature. The present invention can comprise a single step process using a simple automated contrast medium device or a portable contrast medium device.
[0082] A method of the present invention comprises providing a contrast medium device comprising a first and a second container, for example, each capable of holding 10 ml of fluid and each equipped with a plunger, wherein the containers they are fluidly connected to an outlet opening and the second container is connected via at least one check valve to an air opening; fill both containers simultaneously by positioning the outlet opening inside a saline container and extracting the two plungers through the two containers and in the opposite direction to the outlet opening. One container is filled with saline, while the second container is filled with air. When the plungers are pulled to a specific location, the first container contains saline and the second container contains air. When pressing the plungers simultaneously, so that each plunger moves through its container towards the outlet opening, the saline and air are moved from the respective container to and through separate fluid connections to a media generation chamber. contrast comprising a mixing chamber comprising a static mixer, or alternatively to a contrast medium generation chamber comprising a mixing chamber that is fluidly connected with the two separate connections of each container, and functions as a space container, a conduit, in which the two separate connections of the containers are joined (a mixing chamber with conduit), and there is no static mixer. A contrast medium composition is generated and moves from the contrast medium generation chamber to enter a catheter and a body structure. In a static mixer, air and saline are mixed to form a contrast medium composition that comprises air / saline interfaces. Alternatively, in a modality in which the contrast medium generation chamber does not comprise a static mixer, but comprises a mixing chamber with a duct, the air and saline leave their respective channels and intercalate and mix to form air segments. (bubbles) in the fluid by mixing by adding the fluid streams, carried by the separate connections inside the mixing chamber. Such air / saline interfaces can be the result of air bubbles surrounded by / inside the saline or air and saline segments. The contrast medium composition that leaves the static mixer or mixing chamber with duct optionally flows through an outlet duct to an outlet opening. A catheter can be connected to the conduit and the contrast medium composition flows into the catheter. After dispersing the fluids from the containers, they can be refilled one or more times so that a sufficient amount of contrast medium is produced and distributed. Alternatively, containers can be supplied, previously filled with fluids, such as air and saline, to initially provide contrast medium, and the first pre-filled containers are replaced with new, pre-filled containers containing fluids, such as air and saline, or, now empty, can be refilled using the steps described above.
[0083] With the present invention, the distribution of the contrast medium comprising a gas / liquid interface pattern of the contrast medium device to the fallopian tubes can confirm the patency of the tubes by unobstructed flow during visualization and can does not result in an unnecessary accumulation of material on the dead end. The volume of distribution can be limited to the potential volume of the fallopian tube, approximately 2 milliliters, for a single evaluation and can comprise a larger amount to confirm the initial observations. The image visualization of a fallopian tube may comprise the use of a composition with fluid / gas phase combination of about 0.5 ml to about 20 ml, from about 1 ml to about 15 ml, from about 1 ml about 5 ml, about 1 ml about 10 ml, about 10 ml about 20 ml, about 1 ml about 3 ml, about 15 ml about 20 ml. Viewing an image of a uterus and at least one fallopian tube may comprise the use of a contrast medium composition with a fluid / gas phase combination of about 10 mL to about 150 mL, from about 10 mL to about 100 ml, from about 10 ml to about 50 ml, from about 20 ml to about 100 ml, from about 10 ml to about 80 ml, from about 10 ml to about 90 ml, from about 20 ml to about 90 ml. Tubal obstruction may be evident from the absence of contrast medium mobility along the fallopian tube to the peritoneal cavity. The resulting pressure relief can be provided by a relief valve on the device or by the movement of a final structure in the delivery catheter from its position in the horns. A device of the present invention can be automated, since the syringes are inserted into a pumping system, or activated by manual delivery, once the syringes are inserted or attached to a portable device.
[0084] One embodiment of the present invention contemplates a contrast medium delivery device that does not require complementary systems, such as a liquid reservoir (s) or valve control of the fluid flow of such liquid reservoir (s). attached to the device. Simplified devices and methods, such as those of the present invention that comprise reusable containers, offer a greater likelihood of a successful outcome and procedure. In addition, the present device is capable of maintaining the pattern of alternating phases for periods of time that are useful for sonography. This gives the user the freedom to properly locate structures and reposition the patient or structure, or the catheter during the procedure. In general, there is no coalescence of individual phases. The pattern of gaseous / liquid phases or interfaces created by the contrast medium device is visually observed at the beginning and each media segment and distribution rate can be controlled to satisfy the user's needs.
[0085] The mixture of fluids (air and saline) produces the consistency of the alternating pattern of the air / liquid interfaces, and we want to ideally visualize the path of the image visualization agent in the fallopian tubes. Due to the size of the tubes, the consistency of the alternating pattern is necessary to allow visualization of the flow by ultrasound. Other devices that tried to distribute saline and air did so inconsistently and the procedure was considered very difficult when performing an evaluation of the fallopian tubes and / or the uterus by the medical team. With previous devices, the procedures required a lot of practice and skill development to use them and obtain a visualization that was sufficient for the diagnosis, whereas with the consistent alternating pattern generated by the present invention, many doctors can become proficient in the device. and acquire a sufficient amount of satisfactory data regularly, after just a few uses and patients. An example of a contrast generation chamber can be purchased commercially from Micromedics (part: mixing connector with static mixers) and is an example of a component that can mix liquid and gas consistently to create an alternating pattern that easily viewed. The Micromedics part has a static mixer produced from Keptal F30 which is in a configuration that causes liquid and gas to turbulence. Other materials, such as foam or any porous material, would serve a similar purpose to create turbulence and mix liquid and gas. Alternatively, when the contrast medium generation chamber comprises a mixing chamber without a static mixer, such as one in which the mixing chamber is a space contained in the junction of two individual connections (a mixing vessel with a conduit), the standard alternating may or may not be as consistent as that of a contrast medium generation chamber with a static mixer. The diameter of the separate connections, the contrast medium generation chamber, the mixing chamber and the outlet opening leading to a catheter influences the range of saline and air created and can be optimized to ensure a consistent alternating pattern. The liquid appears black when viewed by ultrasound, while the gas appears white. The alternating black and white pattern, which moves through the cavity or ducts, allows the evaluation of a small diameter tube, such as the fallopian tube or a duct. In some structure passages where volumes and diameters are larger, the two fluid phases can be maintained by additives or surfactants, such as those disclosed in this document. The contrast medium device may comprise containers larger than the syringes shown in this document. For example, a container can be used, and the container can contain a liquid that is foamed. The foam can be created by vibration, by the addition of foaming agents, by sonication or agitation. The foam can be transferred to the cavity to be visualized by transporting it, from the container set, through a catheter set, to the structure to be evaluated. It is evident that other methods of creating the dispersion are possible and may include mechanized means for this. The phase created by these methods allows a person to regulate the sizes of the resulting foam by controlling vibration or agitation, as well as the types and concentrations of dispersants.
[0086] The methods of the present invention allow the evaluation of passages, such as the fallopian tubes and the uterine cavity, by ultrasound, and provide a simple, safe and inexpensive outpatient method. The methods of the present invention comprise sonographically observing a location on the body, such as the uterus and its associated fallopian tubes, using the devices and compositions disclosed in this document.
[0087] In general, the present invention comprises methods and devices for visualizing structures, by providing compositions of contrast medium to the structure and visualization techniques, such as ultrasound. The visualization of the contrast medium in or around the structure provides information to the observer, and such methods and devices can be used to diagnose and treat conditions related to the visualized structure. The methods and devices of the present invention are useful for diagnosing and treating conditions related to the uterus and / or fallopian tubes of humans and animals.
A contrast medium device of the present invention comprises a container assembly comprising at least one container for containing a fluid, a component for moving a fluid from the container, components for connecting the at least one container to the assembly of container, and optionally comprises a catheter assembly in fluid connection with the container assembly. In the embodiments of the invention, the container is a syringe and the component for moving a fluid from the container is a syringe plunger. The embodiments may further comprise a syringe plunger activating component, and the component is a mechanical or manually operated pump. The devices can also comprise connection elements for fluidly connecting device parts, valves, needles, filters, vibrators, pumps and other components.
[0089] The modalities comprise devices in which at least one container further comprises a porous substance and a gas. A porous substance can be any substance that can contain gas and liquid and release the gas and liquid easily through compression or physical force on the porous substance. For example, a porous substance can be a sponge, such as an open cell polyurethane sponge, which can be compressible. For example, a porous substance can be a rigid material that contains a gas and a liquid, but that shrinks by compression, to release the gas and liquid. A porous substance can be supplied to a container in a dry state, where the porous substance contains gas, and a liquid can be added to the container so that the porous substance contains both a gas and a liquid. Alternatively, the porous substance can be wet, and contain both liquid and gas, and thus be supplied to a container. A larger amount of liquid may or may not be added to the container after the insertion of the moistened porous substance. It is theorized that the porous substance comprises a gas in its pores and a liquid associated with them. The liquid and gas can be found in the pores or associated with the porous material in an easily releasable manner, such as by surface tension, hydrogen bonds or other weakly bonded associations.
[0090] The liquids supplied to the containers or the porous substances may further comprise a surfactant, emulsifier, other stabilizing agents, or other dispersing agents. The liquids supplied to the containers or the porous substances may also comprise liquids that are foamed. Liquids can be foamed by methods known in the art.
[0091] The embodiments of the present invention comprise contrast medium devices comprising a container assembly comprising two containers and a contrast pattern generation chamber in fluid connection with the containers. For example, the containers can be syringes, each comprising a component for moving a fluid from the container which is a syringe plunger. Such modalities may also comprise a syringe piston activation component and the component is a mechanical or manually operated pump. In two-vessel devices, one vessel contains a gas and the other vessel contains a liquid. For example, when the containers are syringes, one contains a gas and the other contains a liquid. In the present invention, when two or more containers are used in a device, the containers may or may not have the same size, volume, diameter, length, or they may or may not be made from the same materials.
[0092] A method of the present invention comprises visualizing structures with the use of ultrasound techniques known to those skilled in the art. A method of sonographic visualization of a structure comprises creating a contrast medium comprising alternating phases of a gas and a liquid in a contrast medium device comprising at least one container; providing the contrast medium to a catheter assembly, wherein the catheter assembly comprises a catheter delivery end positioned at or near the structure to be viewed; distribute the contrast medium directly to the structure to be visualized; and visualize the contrast medium in the structure by ultrasound. A method of sonographic visualization of a structure comprises looking at a structure that has a contrast medium of the present invention contained therein or that flows through it. The methods of the present invention comprise producing a contrast medium which comprises mixing by adding a gas and a liquid in a contrast medium device so that the alternating phases of gas and liquid, with visible interfaces between the phases forming a visible pattern by ultrasound, are created to form a contrast medium composition.
[0093] The present invention comprises ultrasound to visualize the contrast medium within a structure. Ultrasound procedures generally use a transvaginal probe in which it can be positioned closer to the fallopian tubes. The positioning of the probe to obtain a sagittal view allows the visualization of the sonographic image visualization agent in the uterine cavity with the catheter in place, verifying that the direct flow to the uterine cavity does not present retrograde flow back to the vagina. Positioning the probe to obtain a cross-sectional view allows the visualization of the sonographic image visualization agent from the uterine cavity to the fallopian tubes, which can result in the visualization of both tubes or each tube in a certain plane.
[0094] Any structure that can be visualized with the use of ultrasound can be visualized using the contrast medium compositions of the present invention, and the contrast medium compositions produced by the contrast medium devices taught in this document. For example, a structure to be visualized is at least a human or animal's fallopian tube.
[0095] The contrast medium compositions of the present invention can be produced with a liquid that is dispersible and forms a discrete liquid phase when in contact with a gas. The liquid contrast medium may or may not comprise visualizable liquids. The contrast medium composition may further comprise a therapeutic composition. Therapeutic compositions comprise therapeutic agents, including, without limitation, methotrexate, hormones, compounds that improve fertility, compounds that interfere with fertility, compounds that improve motility, compounds that interfere with motility, compounds that affect the eyelash / deciliation cycle, compounds that improve or interfere with the growth of cilia, compounds for the treatment of ovarian follicles, antibacterial, antimicrobial, antifungal, antiviral, antimycoplasmic or antiparasitic compounds, compounds that reduce inflammation or scar tissue formation, compositions that comprise one or more antibiotics, antimycoplasmic agents , or antiviral compounds; compositions comprising mucoproteins, electrolytes or enzymes to improve or inhibit fertility, progesterone, estrogen, adrenergic active compounds, noradrenergic active compounds, non-steroidal anti-inflammatory drugs, prostaglandins, other compounds that can treat or prevent fallopian tube diseases, uterus, ovaries, or other organs or linings affected by a composition that flows from the horns or ostia of a fallopian tube, or combinations thereof. The treatment compositions comprise fertility hormones, compounds that improve fertility, gametes, sperm, eggs, combinations of sperm and eggs, one or more zygotes, or one or more embryos, or combinations thereof.
[0096] Methods of visualizing structures may comprise the use of compositions produced by a contrast medium device of the present invention. In the embodiments, the contrast medium device comprises a container containing a porous substance and a fluid. The porous substance further comprises a gas, and the liquid may comprise a surfactant, emulsifier, other stabilizing agents, or other dispersing agents. The liquid can be foamed.
[0097] The methods of the present invention comprise delivering a contrast medium composition of the present invention directly to the structure. For example, a contrast medium composition can be delivered directly to a fallopian tube. The composition can be delivered through a catheter and the catheter can be delivered to the site by devices known in the art and by those taught herein. For example, the catheter can be provided so that the delivery end of the catheter is positioned at the horns of a uterus. The contrast medium composition is supplied through the catheter to the fallopian tube orifice, and the composition flows through the fallopian tube, if possible. The composition of contrast medium is visible by ultrasound and the affection of the fallopian tube can be determined by visualization, diagnoses can be provided or treatment of the fallopian tube or other structures can be provided. For example, the patency or occlusion of at least one fallopian tube is determined by viewing at least one fallopian tube by ultrasound. The methods of the present invention comprise the use of small amounts of contrast medium composition to evaluate or treat structures, such as a fallopian tube, and the amount of contrast medium to be supplied to the structure is less than 20 mL for a single evaluation .
A contrast medium generation and distribution device of the present invention comprises a container assembly comprising at least one container for containing a fluid, a component for moving a fluid from the container, and connections for the fluidic connection of at least one container to a contrast medium generation chamber. A contrast medium generation and distribution device of the present invention can comprise two containers, each with a component for moving a fluid from a container. In one aspect, each container is a syringe and the component for moving a fluid from the container is a syringe plunger. A contrast medium generation and distribution device of the present invention may further comprise a component for driving both syringe plungers simultaneously, referred to in the present document as an actuator. An actuator joins the ends of the syringe plungers so that the actuator moves the plungers simultaneously in the same direction, rate and distance. A contrast medium generation and distribution device of the present invention may comprise a contrast medium generation chamber that comprises a static mixer. A contrast medium generation and distribution device of the present invention may comprise a contrast medium generation chamber that comprises a duct mixing chamber. A contrast medium generation and distribution device of the present invention may comprise a fluidically connected container with an air vent to the atmosphere or another source of gas. A contrast medium generation and distribution device of the present invention can comprise at least one check valve that is in fluid connection with the container in fluid connection with the air opening. A contrast medium generation and distribution device of the present invention can comprise at least two check valves that are in fluid connection with the container in fluid connection with the air opening. A contrast medium generation and distribution device of the present invention can comprise a pressure relief mechanism. A pressure relief mechanism may comprise a pressure release valve. A contrast medium generation and distribution device of the present invention can comprise a contrast medium generation chamber that comprises a mixing chamber and does not include a static mixer. A contrast medium generation and distribution device of the present invention may comprise an outlet opening in fluid connection with the contrast medium generation chamber. A contrast medium generation and distribution device of the present invention may comprise a catheter attached to the outlet opening.
[0099] A method of the present invention comprises a method of sonographic visualization of a body structure, which comprises providing a contrast medium generation and distribution device comprising a container assembly comprising at least one container for containing a fluid, a component for moving a fluid from the container, and connections for fluidly connecting at least one container to a contrast medium generation chamber; fill at least one container with a fluid; moving the fluid from at least one container to a contrast medium generation container in order to generate a contrast medium composition; providing the composition of contrast medium to a body structure through a catheter comprising a catheter delivery end positioned on the same or a different body structure; visualize the composition of contrast medium in one or more body structures by ultrasound. A method of the present invention can comprise at least one container previously filled with fluid. A method of the present invention may comprise a contrast medium device comprising two containers, in which a first container is filled with air and a second container is filled with saline. A method of the present invention may comprise supplying saline and air to a contrast medium generation chamber in which the saline and air are mixed to form a contrast medium composition comprising segments of air and segments of saline in a regular frequency pattern. A method of the present invention may comprise providing a contrast medium composition to the uterus and fallopian tubes, which can be visualized with the use of sonography.
[00100] A method of the present invention comprises diagnosing the patency of a fallopian tube, which comprises providing a contrast medium generation and distribution device comprising a container assembly comprising at least one container for containing a fluid, a component for moving a fluid from the container, and connections for fluidly connecting at least one container to a contrast medium generation chamber; fill at least one container with a fluid; moving the fluid from at least one container to a contrast medium generation container in order to generate a contrast medium composition; providing the contrast medium composition to a body structure through a catheter comprising a catheter delivery end positioned on the same or a different body structure; and visualizing the composition of contrast medium in one or more body structures by ultrasound. A method of the present invention may comprise the contrast medium generation and distribution device comprising two containers, in which the containers are combined to effect simultaneous action, with a first container being filled with air and a second container being filled with saline. , and supplying saline and air to a contrast medium generation chamber in which the saline and air are mixed to form a contrast medium composition comprising segments of air and segments of saline in a regular frequency pattern. A method of the present invention may comprise providing a contrast medium composition to the uterus and at least one fallopian tube, wherein the uterus and / or at least one fallopian tube is visualized with the use of sonography.
[00101] It should be noted that, as used in this specification and in the appended claims, the singular forms "one", "one", "o" and "a" include plural referents, unless the context clearly indicates otherwise .
[00102] All patents, patent applications and references included in this document are specifically incorporated by reference in their entirety.
[00103] It should be understood, of course, that the above refers only to the preferred modalities of the present invention and that numerous modifications or alterations can be made to this document without deviating from the spirit and scope of the invention, as established in this revelation.
[00104] The present invention is illustrated in greater detail by the following examples, which should not be interpreted in any way as imposing limitations on the scope of the same. On the contrary, it must be clearly understood that it may be necessary to resort to various other modalities, modifications and equivalents of the same, which, after reading the description in this document, may appear naturally to those versed in the technique without deviating from the spirit. of the present invention and / or the scope of the appended claims. EXAMPLES EXAMPLE 1 Preparation of contrast medium with two-syringe pump
[00105] A container set comprising a double pump was produced, as represented in a generic way in Figure 1, with two syringes, one 6 cm3 and the other 20 cm3 in volume. The 6 cm3 syringe was completely filled with saline and the 20 cm3 syringe was filled with air. Sterile 0.2 μm filters (Sartorius Minisart or Whatman Syrfil-MF) were attached to the syringes, since the sterilization technique was desired. A 27 gauge spinal needle with a length of 88.9 mm (3.5 in) was used to inject a gas phase into a fluid phase in the contrast pattern generation chamber to create the air and liquid phase interfaces alternating. A T-opening extension for the PICC-Nate catheter and two lengths of extension tubes were used in the installation.
[00106] Variations of syringe bore configurations, pump volume, pumping rate and pumping delay were evaluated and produced an acceptable contrast medium, as visualized on a catheter set in front of the container set. The contrast medium was distributed in transparent PVC tubes that simulated the dimensions of a fallopian tube. The user could change the pattern created with the gas and liquid phases, allowing larger volumes of gas or liquid, and the speed at which the contrast medium was distributed by adjusting the settings on the pump. A reasonably regular pattern of gas / liquid phase interfaces was created by the contrast medium device. EXAMPLE 2 Preparation of contrast medium with two portable syringes
[00107] The set of Example 1 observed with the use of a housing to support the two syringes. A block was positioned behind the plunger of the 6 cm3 syringe that contained saline to be aligned with the distance from the plunger of the 20 cm3 syringe that contained air. The creation of the contrast medium and its distribution to a catheter were controlled and manipulated by means of manual force on the plungers of the two syringes, as necessary, to distribute the contrast medium to the catheter. When the two syringe plungers were propelled simultaneously, the pattern of the contrast medium was uniform, with substantially equal amounts of air and saline phases, alternating in the catheter. When a plunger was driven, followed by the plunger of the other syringe, the pattern was sometimes regular, sometimes irregular, depending on the activation of the individual plungers. Although the sizes of the individual segments of the air and saline phases were not uniform, the liquid / air phases were repeated sufficiently for easy visualization. The contrast medium was distributed to transparent PVC tubes that simulated the dimensions of the fallopian tube. EXAMPLE 3
[00108] Preparation of contrast medium with syringe containing porous substance
[00109] A sterile Optipore asepsis sponge was cut in two longitudinal directions. The plunger of a 60 cm3 syringe was removed and the sponge halves were inserted, one behind the other. The plunger was reinserted into the syringe and pressed to the 15 cm3 mark. The tip of the syringe was submerged in a sterile saline container and the plunger was pulled up to the 30 cm3 mark. The container set was then assembled and loaded. The container set was attached to a catheter set and the plunger was pressed to create a composition of air and saline, a composition of contrast medium, for sonographic visualization. The contrast medium was distributed to transparent PVC tubes that simulated the dimensions of the fallopian tube. An irregular pattern or random pattern was visualized as the user controlled the distribution of the contrast medium. Although the sizes of the individual segments of the air and saline phases were not uniform, the liquid / air phases were repeated sufficiently for easy visualization. EXAMPLE 4
[00110] Study of contrast medium created by a two-syringe pump in a simulated model
[00111] A contrast medium device of Figure 1 and Example 1 was used to distribute the contrast medium created by the device, made with saline as the liquid phase and air as the gas phase, to a channel sized to simulate the tubes human fallopian tubes in a simulated ultrasound model (purchased from Blue Phantom, a division of Advanced Medical Technologies, LLC, Kirkland, Washington, USA). The delivery end of a catheter set was positioned in the simulated fallopian tube. The contrast medium device's pump was activated, creating the contrast medium, and the contrast medium was distributed to the Fallopian tube model and resembled the pattern shown in Figure 5. An ultrasound machine (manufactured by GE Medical Systems, model: Voluson 730Pro) was used to visualize the contrast medium created, which traversed the simulated fallopian tube or tube in real time, and the gas / liquid phase contrast was visualized with the ultrasound probe. EXAMPLE 5
[00112] Study of contrast medium created by a two-syringe pump in human female individuals
[00113] A contrast medium device of Figure 1 and Example 1 was used to distribute the contrast medium to the fallopian tubes of human female individuals. The contrast medium composition was created by the device with the use of saline as the liquid phase and air as the gas phase, each passing through an aseptic filter of approximately 0.2 microns in size to ensure sterility. The catheter set was provided to human patients using a delivery system, described in US Patent Application 11 / 065,886, positioned on the horns of each individual. The contrast medium was distributed through the delivery system catheter and was visualized using an ultrasound instrument (manufacturer: GE Medical Systems, model: Logic 500). Tubal patency was evidenced by the crossing of the contrast medium through the fallopian tubes and its exit to the peritoneal cavity. This assessment was conducted in real time with the estimated flow of contrast medium evident through the appropriate positioning of the distribution system. EXAMPLE 6
[00114] Study of contrast medium created by syringe containing porous substance in a simulated model
[00115] A contrast medium device, as shown in Figure 4 and Example 3, was used to distribute the contrast medium created by the device, where saline was the liquid phase and air was the gas phase, for a channel sized to simulate human fallopian tubes in a simulated ultrasound model (purchased from Blue Phantom, a division of Advanced Medical Technologies, LLC, Kirkland, Washington, USA). The porous substance used was a high-porosity, open cell polyurethane foam designed for protective packaging materials. A delivery end of a catheter set was positioned in the simulated fallopian tube and the contrast medium device was manually activated, creating a contrast medium that had a more irregular pattern than that shown in Figure 5. An ultrasound machine (manufactured by GE Medical Systems, model: Voluson 730Pro) was used to visualize the created contrast medium, which ran in real time through the simulated fallopian tube or fallopian tube, and the composition of the gas / liquid phase contrast medium was visualized with the ultrasound probe. EXAMPLE 7
[00116] Study of contrast medium created by syringe containing porous substance in human female individuals
[00117] A contrast medium device, as shown in Figure 4 and Example 3, was used to distribute the contrast medium created by the device, where saline was the liquid phase and air was the gas phase, for the Fallopian tubes of human female individuals through a catheter assembly incorporated into a delivery system, as described in US Patent Application 11 / 065,886. The delivery device was positioned in the uterus of a human female and the delivery end of one or both catheters was in place in the horns of the uterus. A 60 cm3 sterile syringe was packaged with a 76.2X50.8 mm (3X2 inch) Optipore sterile wound asepsis sponge (manufactured by ConvaTec, division of E.R. Squibb & Sons, LLC, Princeton, NJ, USA). The sponge was made of polyurethane and was highly porous in nature. The saline was pulled into the syringe to fill it, but without removing the air trapped in the sponge. The syringe was attached to the fixation end of one or both catheters of the delivery device. When the plunger of the syringe was pressed, the contrast medium was formed and distributed, through the catheter set, to the fallopian tube (s). The contrast medium was visible by ultrasound (manufacturer: Philips, model: HD3). This assessment was conducted in real time with the estimated flow of contrast medium evident through the appropriate positioning of the distribution system. EXAMPLE 8
[00118] Study of contrast medium created by four channel configurations in bench model
[00119] A contrast medium device, as shown in Figure 7, has been changed to produce the following four configurations in order to assess the contrast medium ranges: a) Contrast medium device, as shown in Figure 7, (with static mixer), with each fluid channel having an internal diameter of 0.559mm (0.022 in) which changes to the internal diameter of 2.54mm (0.100 in) in the static mixer. b) Contrast medium device, as shown in Figure 8, (without static mixer), with each fluid channel having an internal diameter of 0.559mm (0.022 in). c) Contrast medium device, as shown in Figure 8, with each fluid channel having an internal diameter of 1.143 mm (0.045 in). d) Contrast medium device, as shown in Figure 8, with each fluid channel having an internal diameter of 0.432mm (0.017 in).
[00120] All contrast medium devices were connected to a 2.2 mm tube, which simulated the diameter of the fallopian tube to assess the fluid range created. It was found that with these fluid channel internal diameters and with or without a static mixer, the length of the saline gap versus the length of the air gap created were substantially identical, with an average length of about 5 mm. EXAMPLE 9
[00121] Saline and air analyzed for differences in pattern frequency and segment length with various distribution rates
[00122] A system for simulating the female reproductive system, including the cervix, uterine cavity and fallopian tubes, was created to allow the analysis of various distribution rates of the device described in Figure 7 and the possible effects of frequency the air and saline pattern and the lengths of the respective segments. The length of the air segments and the distribution rate of several experiments are shown in Table 1.
[00123] The test device consisted of a transparent soft elastomer material sandwiched between two transparent acrylic plates. The bottom plate had a depression of similar size that represented the uterine cavity on which the elastomer was positioned. The acrylic plates were screwed together, creating a waterproof seal. The top plate consisted of the following: a) an entrance equipped with an elastomer tubing with a 2 mm hole and of reduced length to simulate the inside of the cervix so that it was sufficient to accommodate a standard intrauterine balloon catheter and b) two outlets equipped with two elastomer pipes with a 2 mm hole to simulate the internal diameter of each fallopian tube. The length of each horn was approximately 400 mm to allow multiple data readings. The tester was attached to a standard table tensile testing machine (Instron). A support was manufactured to hold the device to the Instron machine, but allowed removal, as needed, for filling saline and air. The device was connected to the test device that contained the standard intrauterine catheter. The crosshead of the Instron machine was positioned against the plunger of the completely filled device and advanced at a defined rate, simulating the distribution. TABLE 1
EXAMPLE 10
[00124] Saline and air distributed by a device that incorporates a pressure relief mechanism
[00125] The device described in Figure 9 included a 3.0 PSI (155 mmHg) pressure relief valve. A test device consisting of the device connected to a disposable pressure transducer (Utah Medical P / N DPT-100), which was then connected to a pressure monitor (PendoTech PressureMat 3Plus), which was then connected to a standard digital computer, was used to measure the pressure reached when distributing saline and air. A fluid containment bag was attached to the relief opening of the pressure relief valve to capture the excess fluid expelled by the pressure relief valve when activated.
[00126] The device in this example was designed to limit the pressure of the injection of saline and air instilled in a closed system to a value less than or equal to 200 mmHg. When the line pressure reached or exceeded the nominal pressure of 3.0 PSI (155 mmHg), the valve opened, and the fluid was expelled from the relief opening of the pressure relief valve.
[00127] The device's fluid injection pressure measurements were captured in a simulated closed system, which was achieved by positioning a cover over the opening at the opposite end of the transducer. The transducer was prepared with saline, and it was visually verified that there were no air bubbles close to the detection portion of the transducer before obtaining pressure measurements, to ensure accurate fluid pressure readings. The test was repeated 6 times, and the results are represented in the graph shown in Figure 11.

权利要求:
Claims (15)
[0001]
1. Contrast medium generation and distribution device, characterized by the fact that it comprises a first and second syringe, the first syringe configured to contain liquid and the second syringe, configured to contain air or gas, in fluid connection with an opening of air; a contrast medium generating chamber; a first connection for fluid connection between the first syringe and the contrast medium generating chamber; and a second connection for connecting fluid between the second syringe and the contrast medium generating chamber via at least one one-way check valve; an air gap positioned between the second syringe and the contrast medium generating chamber that are in fluid connection with each other through the unidirectional check valve; and a third connection for fluid connection between the contrast medium generating chamber and an outlet opening which is provided distal to the contrast medium generating chamber; first and second syringe plungers, arranged respectively within the first and second syringes and configured to simultaneously move liquid and air or gas into the respective syringes, where the fluid connections to the first syringe for liquid are configured so that the liquid enters in the first syringe by transverse movement of the plungers; and the fluid connections of the second syringe for air or gas are configured so that air or gas enters through the air opening in the second syringe and to simultaneously move the liquid and the air or gas contained in the respective syringe into the air-generating chamber contrast medium to form a contrast medium that exits through the outlet opening.
[0002]
2. Device according to claim 1, characterized in that it further comprises a contrast medium generation chamber comprising a static mixer.
[0003]
3. Device according to claim 1, characterized by the fact that at least one check valve is in fluid connection with the container in fluid connection with the air opening.
[0004]
4. Device according to claim 1, characterized by the fact that at least two check valves are in fluid connection with the container in fluid connection with the air opening.
[0005]
5. Device, according to claim 1, characterized by the fact that the pressure release valve is in fluid connection and located between the contrast medium generating chamber and the outlet opening.
[0006]
6. Device according to claim 1, characterized by the fact that it also comprises a catheter optionally attached to the outlet opening.
[0007]
7. Device according to claim 1, characterized by the fact that it also comprises a tap positioned between the contrast medium generating chamber and the outlet opening.
[0008]
8. Device according to claim 7, characterized by the fact that it also comprises a catheter, optionally connected to the outlet opening.
[0009]
Device according to any one of claims 1 to 8, characterized in that the liquid comprises operational agents.
[0010]
10. Sonographic visualization method of a uterus or at least one fallopian tube, or both, a uterus and at least one fallopian tube, characterized by the fact that it comprises: a) simultaneously filling a first and second syringe of a generation and distribution of contrast medium, comprising a set of containers comprising a first and a second syringe, in which the first syringe is configured to contain liquid and the second syringe is configured to contain air or gas and is in fluid connection with an opening of air; a contrast medium generating chamber; a first connection for fluid connection between the first syringe and the contrast medium generating chamber; and a second connection for connecting fluid between the second syringe and the contrast medium generating chamber via at least one one-way check valve; an air gap positioned between the second syringe and the contrast medium generating chamber that are in fluid connection with each other through the unidirectional check valve; and a third connection for fluid connection between the contrast medium generating chamber and an outlet opening which is provided distal to the contrast medium generating chamber; first and second syringe plungers, arranged respectively within the first and second syringes and configured to simultaneously move liquid and air or gas into the respective syringes, where the fluid connections to the first syringe for liquid are configured so that the liquid enters in the first syringe by transverse movement of the plungers; and the fluid connections for the second syringe for air or gas are configured so that air or gas enters through the air opening in the second syringe, b) simultaneously, in a reverse motion to a), move the first and second plungers from the syringe to move the liquid and air or gas contained from the respective syringe to the chamber generating the contrast medium to form a contrast medium; c) providing the composition of the contrast medium to a uterus or at least one fallopian tube, or both, a uterus and at least one fallopian tube through a catheter; and d) visualize the composition of the contrast medium in a uterus or at least one fallopian tube, or both, a uterus and at least one fallopian tube by ultrasound.
[0011]
11. Method according to claim 10, characterized by the fact that the liquid comprises operational agents.
[0012]
12. Method of diagnosing the patency of at least one fallopian tube, characterized by the fact that it comprises: a) simultaneously filling a first and second syringe of a contrast medium generation and distribution device, comprising a set of containers comprising a first and second syringe in which the first syringe is configured to contain liquid and the second syringe is configured to contain air or gas, and is in fluid connection with an air opening; a contrast medium generating chamber; a first connection for fluid connection between the first syringe and the contrast medium generating chamber; and a second connection for connecting fluid between the second syringe and the contrast medium generating chamber via at least one one-way check valve; an air gap positioned between the second syringe and the contrast medium generating chamber that are in fluid connection with each other through the unidirectional check valve; and a third connection for fluid connection between the contrast medium generating chamber and an outlet opening which is provided distal to the contrast medium generating chamber; first and second syringe plungers, arranged respectively within the first and second syringes and configured to simultaneously move liquid and air or gas into the respective syringes, where the fluid connections to the first syringe for liquid are configured so that the liquid enters in the first syringe by transverse movement of the plungers; and the fluid connections for the second syringe for air or gas are configured so that air or gas enters through the air opening in the second syringe, b) simultaneously, in a reverse motion to a), move the first and second plungers from the syringe to move the liquid and air or gas contained from the respective syringe to the chamber generating the contrast medium to form a contrast medium; c) supplying the composition of the contrast medium to a uterus or at least one fallopian tube or a uterus and at least one fallopian tube through a catheter; and d) visualize the composition of the contrast medium in a uterus or at least one fallopian tube, or both, uterus and at least one fallopian tube, by ultrasound and determine the patency of at least one fallopian tube.
[0013]
13. Method according to claim 12, characterized by the fact that the liquid comprises operational agents.
[0014]
14. Device according to any one of claims 1 to 9, characterized in that it is for use in the sonographic visualization of a body structure.
[0015]
Device according to any one of claims 1 to 9, characterized in that it is for use in diagnosing the patency of at least one fallopian tube.

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引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US315762A|1885-04-14|Reversing-gear |

---

US1892803A|1930-12-10|1933-01-03|Becton Dickinson Co|Injection device|

---

US3042030A|1958-11-25|1962-07-03|Read Thane|Spherical type insert plug for body passageway and tool therefor|

---

US3182662A|1962-07-25|1965-05-11|Vithal N Shirodkar|Plastic prosthesis useful in gynaecological surgery|

---

US3422813A|1965-06-21|1969-01-21|Dow Corning|Method for sterilization of males|

---

US3404682A|1965-11-17|1968-10-08|Tassette Inc|Vaginal cup and means for inserting same|

---

US3405711A|1966-07-22|1968-10-15|Maurice I. Bakunin|Intrauterine contraceptive device|

---

US3467090A|1967-05-03|1969-09-16|Phillip B Zollett|Self-retaining occlusive stem pessary|

---

US3463141A|1967-05-15|1969-08-26|Casimir Mozolf|Male contraceptive|

---

US3803308A|1968-09-18|1974-04-09|Searle & Co|Method of contraception with a soluble non-toxic copper or zinc compound|

---

US3598115A|1969-04-08|1971-08-10|Herbert W Horne Jr|Intra-uterine contraceptive device|

---

CH508391A|1969-04-08|1971-06-15|Charis Aka Charilaos George Ma|Gynecological device intended to be introduced into the uterus|

---

US3680542A|1970-05-11|1972-08-01|Hugo S Cimber|Device for occlusion of an oviduct|

---

US3675642A|1970-07-23|1972-07-11|Peter Herent Lord|Rectal cone for use in postoperative treatment|

---

US3687129A|1970-10-02|1972-08-29|Abcor Inc|Contraceptive device and method of employing same|

---

FR2110697A5|1970-10-27|1972-06-02|Rhone Poulenc Sa|

---

US3858586A|1971-03-11|1975-01-07|Martin Lessen|Surgical method and electrode therefor|

---

US3768102A|1972-02-03|1973-10-30|Univ Utah|Implantable artificial urethral valve|

---

US3856016A|1972-11-03|1974-12-24|H Davis|Method for mechanically applying an occlusion clip to an anatomical tubular structure|

---

US3954108A|1972-11-03|1976-05-04|Davis Hugh J|Occlusion clip and instrument for applying same|

---

US3805767A|1973-02-26|1974-04-23|Erb Rene|Method and apparatus for non-surgical, reversible sterilization of females|

---

USRE29345E|1973-02-26|1977-08-09|The Franklin Institute|Method and apparatus for non-surgical, reversible sterilization of females|

---

US3855996A|1973-03-01|1974-12-24|Medtronic Inc|Contraceptive apparatus and procedure|

---

CH569488A5|1973-03-09|1975-11-28|Population Res Inc|

---

US3948259A|1973-03-09|1976-04-06|Population Research Incorporated|Dispensing instrument|

---

US3972331A|1973-03-09|1976-08-03|Population Research Incorporated|Dispensing catheter|

---

US4126134A|1973-06-13|1978-11-21|Population Research Incorporated|Dispensing instrument|

---

US3822702A|1973-06-25|1974-07-09|Population Res Inc|Dispensing method and apparatus|

---

USRE29207E|1973-06-25|1977-05-10|Population Research Incorporated|Dispensing method and apparatus|

---

US3858571A|1973-07-02|1975-01-07|Arthur I Rudolph|Cornual plug|

---

GB1465684A|1973-07-27|1977-02-23|Emmett L|Contraceptive device|

---

US4374523A|1974-10-29|1983-02-22|Yoon In B|Occlusion ring applicator|

---

US3967625A|1973-07-30|1976-07-06|In Bae Yoon|Device for sterilizing the human female or male by ligation|

---

US3882854A|1973-08-23|1975-05-13|Research Corp|Surgical clip and applicator|

---

US3871374A|1973-09-06|1975-03-18|Population Res Inc|Dispensing instrument|

---

US3918431A|1974-01-11|1975-11-11|Manfred Sinnreich|Fallopian tube obturating device|

---

US3875939A|1974-01-31|1975-04-08|Population Res Inc|Single stroke dispensing method|

---

US4135495A|1975-05-21|1979-01-23|Borgen Jennings O|Method and means for reversible sterilization|

---

US4136695A|1975-07-09|1979-01-30|Gynetech-Denver, Inc.|Transvaginal sterilization instrument|

---

US4416660A|1975-07-09|1983-11-22|Dafoe Charles A|Method of transvaginal sterilization|

---

DE2537620A1|1975-08-23|1977-02-24|Lothar Dr Med Popp|Balloon pessary for blocking fallopian tubes - is inflatable double balloon containing X:ray opaque thread in wall|

---

US4185618A|1976-01-05|1980-01-29|Population Research, Inc.|Promotion of fibrous tissue growth in fallopian tubes for female sterilization|

---

US4109654A|1976-08-10|1978-08-29|Population Research, Inc.|Single stroke dispensing apparatus|

---

US4119098A|1977-01-10|1978-10-10|Population Research Incorporated|Material dispensing apparatus|

---

US4181725A|1977-05-02|1980-01-01|The Regents Of The University Of Michigan|Method for alleviating psoriasis|

---

US4160446A|1977-08-12|1979-07-10|Abcor, Inc.|Apparatus for and method of sterilization by the delivery of tubal-occluding polymer|

---

US4182328A|1977-11-23|1980-01-08|Population Research Incorporated|Dispensing instrument and method|

---

US4509504A|1978-01-18|1985-04-09|Medline Ab|Occlusion of body channels|

---

FR2414925B1|1978-01-24|1983-09-09|Medline Ab|

---

US4226239A|1978-01-31|1980-10-07|Kli, Inc.|Surgical ligating instrument and method|

---

US4245623A|1978-06-06|1981-01-20|Erb Robert A|Method and apparatus for the hysteroscopic non-surgical sterilization of females|

---

US4158050A|1978-06-15|1979-06-12|International Fertility Research Programme|Method for effecting female sterilization without surgery|

---

US4230116A|1978-10-02|1980-10-28|Kli, Inc.|Tubal ligation instrument with anesthesia means|

---

US4207891A|1978-10-10|1980-06-17|Population Research Incorporated|Dispensing instrument with supported balloon|

---

SE419597B|1979-05-04|1981-08-17|Medline Ab|DEVICE FOR TEMPORARY OR PERMANENT CONNECTION OF BODY CHANNELS OR SPACES OF HUMAN AND ANIMALS|

---

US4485814A|1979-09-05|1984-12-04|Yoon In B|One-piece compound elastic occluding member|

---

AU6338680A|1979-09-12|1981-07-06|Population Research Inc.|

---

US4267839A|1979-09-12|1981-05-19|Repromed, Inc.|Surgical instrument for use in reversible sterilization or permanent occlusion procedures|

---

US4359454A|1980-12-16|1982-11-16|World Health Organization|Method and composition containing MCA for female sterilization|

---

US4713235A|1981-05-26|1987-12-15|Crx Medical, Inc.|Radiopaque cyanoacrylates|

---

US4380238A|1981-08-21|1983-04-19|Institute Straunann|Disposable applicator for mini-laparotomy using a clip method|

---

DE3141641A1|1981-10-16|1983-04-28|Schering Ag, 1000 Berlin Und 4619 Bergkamen|ULTRASONIC CONTRAST AGENTS AND THEIR PRODUCTION|

---

US4489725A|1982-02-11|1984-12-25|Simon Population Trust|Sexual sterilization devices|

---

FR2522959B1|1982-03-15|1984-04-20|Hamou Jacques|

---

US4548201A|1982-04-20|1985-10-22|Inbae Yoon|Elastic ligating ring clip|

---

US4537186A|1982-05-17|1985-08-27|Verschoof Karel J H|Contraceptive device|

---

JPS5946500A|1982-09-09|1984-03-15|Mitsubishi Electric Corp|Propulsion system of guided missile|

---

US4523590A|1982-10-25|1985-06-18|Wilfred Roth|Method and device for reversible sterilization in mammals|

---

DE3324754A1|1983-07-06|1985-01-17|Schering AG, 1000 Berlin und 4709 Bergkamen|ULTRASONIC CONTRASTING AGENTS AND THEIR PRODUCTION|

---

JPS5946500U|1983-08-22|1984-03-28|

---

US4631188A|1983-08-31|1986-12-23|S.K.Y. Polymers, Ltd. |Injectable physiologically-acceptable polymeric composition|

---

US4547188A|1983-11-14|1985-10-15|Bionexus, Inc.|Material dispensing apparatus|

---

US4637818A|1983-11-25|1987-01-20|Johnson Richard K|Apparatus for producing sterility in female animals|

---

US4611602A|1984-07-19|1986-09-16|Bionexus, Inc.|Instrument and method of tubal insufflation|

---

US4601698A|1984-09-17|1986-07-22|Moulding Jr Thomas S|Method of and instrument for injecting a fluid into a uterine cavity and for dispersing the fluid into the fallopian tubes|

---

US4606336A|1984-11-23|1986-08-19|Zeluff James W|Method and apparatus for non-surgically sterilizing female reproductive organs|

---

US4679558A|1985-08-12|1987-07-14|Intravascular Surgical Instruments, Inc.|Catheter based surgical methods and apparatus therefor|

---

US4664112A|1985-08-12|1987-05-12|Intravascular Surgical Instruments, Inc.|Catheter based surgical methods and apparatus therefor|

---

US4681106A|1985-08-12|1987-07-21|Intravascular Surgical Instruments, Inc.|Catheter based surgical methods and apparatus therefor|

---

US4700705A|1985-08-12|1987-10-20|Intravascular Surgical Instruments, Inc.|Catheter based surgical methods and apparatus therefor|

---

DE3529195A1|1985-08-14|1987-02-26|Max Planck Gesellschaft|CONTRAST AGENTS FOR ULTRASONIC EXAMINATIONS AND METHOD FOR THE PRODUCTION THEREOF|

---

US4700701A|1985-10-23|1987-10-20|Montaldi David H|Sterilization method and apparatus|

---

IN166447B|1985-11-27|1990-05-12|Ethicon Inc|

---

CS255758B1|1985-12-11|1988-03-15|Frantisek Rypacek|Preparat for the diagnostic of transportion function of oviduct and process for preparing thereof|

---

US4731052A|1987-01-14|1988-03-15|Seitz Jr H Michael|Method for removing tissue and living organisms|

---

US4824434A|1987-01-14|1989-04-25|Seitz Jr H Michael|Apparatus used in a method for removing tissue and living organisms from human body cavities|

---

US4847065A|1987-02-10|1989-07-11|Akimova Alla Y|Composition for occlusion of ducts and cavities of human body|

---

US4834091A|1987-04-10|1989-05-30|Ott Douglas E|Intrauterine fallopian tube ostial plug and surgical process|

---

US4795438A|1987-05-13|1989-01-03|Intravascular Surgical Instruments, Inc.|Method and apparatus for forming a restriction in a vessel, duct or lumen|

---

US4869268A|1987-05-14|1989-09-26|Inbae Yoon|Multi-functional instruments and stretchable ligating and occluding devices|

---

US4788966A|1987-05-14|1988-12-06|Inbae Yoon|Plug for use in a reversible sterilization procedure|

---

HU200554B|1987-06-01|1990-07-28|Kalman Patai|Intra-uterine contraceptive device|

---

US4804691A|1987-08-28|1989-02-14|Richards Medical Company|Method for making a biodegradable adhesive for soft living tissue|

---

AU4191989A|1988-08-24|1990-03-23|Marvin J. Slepian|Biodegradable polymeric endoluminal sealing|

---

US5702716A|1988-10-03|1997-12-30|Atrix Laboratories, Inc.|Polymeric compositions useful as controlled release implants|

---

US5632727A|1988-10-03|1997-05-27|Atrix Laboratories, Inc.|Biodegradable film dressing and method for its formation|

---

USRE37950E1|1990-04-24|2002-12-31|Atrix Laboratories|Biogradable in-situ forming implants and methods of producing the same|

---

US4938763B1|1988-10-03|1995-07-04|Atrix Lab Inc|Biodegradable in-situ forming implants and method of producing the same|

---

US5306226A|1989-02-09|1994-04-26|Salama Fouad A|Urinary control with inflatable seal and method of using same|

---

US4932422A|1989-06-12|1990-06-12|Ragheb Gamal A|Contraceptive device|

---

US5324519A|1989-07-24|1994-06-28|Atrix Laboratories, Inc.|Biodegradable polymer composition|

---

US5487897A|1989-07-24|1996-01-30|Atrix Laboratories, Inc.|Biodegradable implant precursor|

---

US5217030A|1989-12-05|1993-06-08|Inbae Yoon|Multi-functional instruments and stretchable ligating and occluding devices|

---

US5226908A|1989-12-05|1993-07-13|Inbae Yoon|Multi-functional instruments and stretchable ligating and occluding devices|

---

US5217473A|1989-12-05|1993-06-08|Inbae Yoon|Multi-functional instruments and stretchable ligating and occluding devices|

---

US5026379A|1989-12-05|1991-06-25|Inbae Yoon|Multi-functional instruments and stretchable ligating and occluding devices|

---

US5065751A|1990-01-03|1991-11-19|Wolf Gerald L|Method and apparatus for reversibly occluding a biological tube|

---

US4983177A|1990-01-03|1991-01-08|Wolf Gerald L|Method and apparatus for reversibly occluding a biological tube|

---

US5095917A|1990-01-19|1992-03-17|Vancaillie Thierry G|Transuterine sterilization apparatus and method|

---

US5147353A|1990-03-23|1992-09-15|Myriadlase, Inc.|Medical method for applying high energy light and heat for gynecological sterilization procedures|

---

US20080063603A1|1990-04-02|2008-03-13|Bracco International B.V.|Ultrasound contrast agents and methods of making and using them|

---

GB9010696D0|1990-05-12|1990-07-04|Femcare Ltd|Sterilisation devices|

---

US5562099A|1990-10-05|1996-10-08|Massachusetts Institute Of Technology|Polymeric microparticles containing agents for imaging|

---

US5487390A|1990-10-05|1996-01-30|Massachusetts Institute Of Technology|Gas-filled polymeric microbubbles for ultrasound imaging|

---

US5573934A|1992-04-20|1996-11-12|Board Of Regents, The University Of Texas System|Gels for encapsulation of biological materials|

---

US5211627A|1991-02-12|1993-05-18|C. R. Bard, Inc.|Catheter and method for infusion of aerated liquid|

---

US6342491B1|1991-05-21|2002-01-29|American Home Products Corporation|Method of treating estrogen receptor positive carcinoma with 17 α-dihydroequilin|

---

US5474089A|1991-06-26|1995-12-12|The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services|Method and device for reversible sterilization|

---

US5766151A|1991-07-16|1998-06-16|Heartport, Inc.|Endovascular system for arresting the heart|

---

AU661240B2|1991-10-18|1995-07-13|Imagyn Medical, Inc.|Apparatus and method for independent movement of an instrument within a linear eversion catheter|

---

US5364345A|1991-10-18|1994-11-15|Imagyn Medical, Inc.|Method of tubal recanalization and catheter system therefor|

---

US5259954A|1991-12-16|1993-11-09|Sepratech, Inc.|Portable intravenous solution preparation apparatus and method|

---

AU3611793A|1992-02-04|1993-09-01|Colorado State University Research Foundation|Composition and method to prevent conception or to cause sterility in animals|

---

EP0560014A1|1992-03-12|1993-09-15|Atrix Laboratories, Inc.|Biodegradable film dressing and method for its formation|

---

US5273527A|1992-05-12|1993-12-28|Ovamed Corporation|Delivery catheter|

---

US5469867A|1992-09-02|1995-11-28|Landec Corporation|Cast-in place thermoplastic channel occluder|

---

US5389089A|1992-10-13|1995-02-14|Imagyn Medical, Inc.|Catheter with angled ball tip for fallopian tube access and method|

---

AU5457394A|1992-11-02|1994-05-24|Drexel University|Surfactant-stabilized microbubble mixtures, process for preparing and methods of using the same|

---

US5632753A|1992-12-31|1997-05-27|Loeser; Edward A.|Surgical procedures|

---

US5328687A|1993-03-31|1994-07-12|Tri-Point Medical L.P.|Biocompatible monomer and polymer compositions|

---

WO1994024944A1|1993-04-23|1994-11-10|Bohdan Babinec|Method, device and apparatus for reversible contraceptive sterilization|

---

US5701899A|1993-05-12|1997-12-30|The Board Of Regents Of The University Of Nebraska|Perfluorobutane ultrasound contrast agent and methods for its manufacture and use|

---

CA2098246C|1993-06-11|1999-05-04|Alexander George Halliburton|Catheter and method of use thereof|

---

AU7115294A|1993-06-24|1995-01-24|Conceptus, Inc.|Guidewire-type device axially moveable by torque or axial force and methods for use thereof|

---

US5391146A|1993-06-24|1995-02-21|Conceptus, Inc.|Mechanism for manipulating the distal end of a biomedical device|

---

US5372584A|1993-06-24|1994-12-13|Ovamed Corporation|Hysterosalpingography and selective salpingography|

---

GB9315473D0|1993-07-27|1993-09-08|Chemring Ltd|Treatment apparatus|

---

US5350798A|1993-08-17|1994-09-27|The United States Of America As Represented By The Secretary Of The Army|Absorbable tissue adhesives|

---

GB9318288D0|1993-09-03|1993-10-20|Nycomed Imaging As|Improvements in or relating to contrast agents|

---

US5681873A|1993-10-14|1997-10-28|Atrix Laboratories, Inc.|Biodegradable polymeric composition|

---

EP0650739B1|1993-10-28|2003-02-26|Medrad, Inc.|Total system for contrast delivery|

---

GB9400739D0|1994-01-15|1994-03-16|Femcare Ltd|Medical clip|

---

US5795331A|1994-01-24|1998-08-18|Micro Therapeutics, Inc.|Balloon catheter for occluding aneurysms of branch vessels|

---

US5439022A|1994-02-14|1995-08-08|Summers; Daniel A.|Lavage valve|

---

NL9400436A|1994-03-18|1995-11-01|Benedict Marie Doorschodt|Fallopian tube blocking device and blocking assembly.|

---

US5464395A|1994-04-05|1995-11-07|Faxon; David P.|Catheter for delivering therapeutic and/or diagnostic agents to the tissue surrounding a bodily passageway|

---

JP4259610B2|1994-04-08|2009-04-30|キューエルティー・ユーエスエイ・インコーポレーテッド|Liquid delivery composition|

---

US5478837A|1994-06-07|1995-12-26|University Of Southern California|Use of quinacrine in preventing adhesion formation|

---

US6743248B2|1996-12-18|2004-06-01|Neomend, Inc.|Pretreatment method for enhancing tissue adhesion|

---

EP0767819A4|1994-06-28|1997-09-24|Tri Point Medical Corp|pH-MODIFIED BIOCOMPATIBLE MONOMER AND POLYMER COMPOSITIONS|

---

US5846255A|1996-01-31|1998-12-08|Casey Medical Products Limited|Surgical clip|

---

US5612052A|1995-04-13|1997-03-18|Poly-Med, Inc.|Hydrogel-forming, self-solvating absorbable polyester copolymers, and methods for use thereof|

---

US6413539B1|1996-10-31|2002-07-02|Poly-Med, Inc.|Hydrogel-forming, self-solvating absorbable polyester copolymers, and methods for use thereof|

---

US5747058A|1995-06-07|1998-05-05|Southern Biosystems, Inc.|High viscosity liquid controlled delivery system|

---

US6413536B1|1995-06-07|2002-07-02|Southern Biosystems, Inc.|High viscosity liquid controlled delivery system and medical or surgical device|

---

US6176240B1|1995-06-07|2001-01-23|Conceptus, Inc.|Contraceptive transcervical fallopian tube occlusion devices and their delivery|

---

US5968542A|1995-06-07|1999-10-19|Southern Biosystems, Inc.|High viscosity liquid controlled delivery system as a device|

---

US6705323B1|1995-06-07|2004-03-16|Conceptus, Inc.|Contraceptive transcervical fallopian tube occlusion devices and methods|

---

CA2224164C|1995-06-07|2007-12-11|Robert S. Neuwirth|Intrauterine chemical necrosing method and composition|

---

US6187346B1|1995-06-07|2001-02-13|Ablation Products, Inc.|Intrauterine chemical cauterizing method and composition|

---

US6019757A|1995-07-07|2000-02-01|Target Therapeutics, Inc.|Endoluminal electro-occlusion detection apparatus and method|

---

US5888546A|1995-08-28|1999-03-30|The Regents Of The University Of California|Embolic material for endovascular occlusion of abnormal vasculature and method for using the same|

---

US5601600A|1995-09-08|1997-02-11|Conceptus, Inc.|Endoluminal coil delivery system having a mechanical release mechanism|

---

US5728201A|1995-09-14|1998-03-17|Canon Kabushiki Kaisha|Ink, and ink-jet recording method and instruments using the same|

---

US5947958A|1995-09-14|1999-09-07|Conceptus, Inc.|Radiation-transmitting sheath and methods for its use|

---

GB9519982D0|1995-09-30|1995-12-06|Magos Adam L|Device|

---

US5716321A|1995-10-10|1998-02-10|Conceptus, Inc.|Method for maintaining separation between a falloposcope and a tubal wall|

---

US5704899A|1995-10-10|1998-01-06|Conceptus, Inc.|Protective sheath for a fiberoptic image guide within an articulated endoscope|

---

US5702717A|1995-10-25|1997-12-30|Macromed, Inc.|Thermosensitive biodegradable polymers based on polyblock copolymers|

---

US5736152A|1995-10-27|1998-04-07|Atrix Laboratories, Inc.|Non-polymeric sustained release delivery system|

---

US6090063A|1995-12-01|2000-07-18|C. R. Bard, Inc.|Device, system and method for implantation of filaments and particles in the body|

---

US5752974A|1995-12-18|1998-05-19|Collagen Corporation|Injectable or implantable biomaterials for filling or blocking lumens and voids of the body|

---

AU1354497A|1995-12-21|1997-07-14|Drexel University|Hollow polymer microcapsules and method of producing|

---

WO1997037668A1|1996-04-05|1997-10-16|Family Health International|Use of macrolide antibiotics for nonsurgical female sterilization and endometrial ablation|

---

IL118235D0|1996-05-13|1996-09-12|Univ Ben Gurion|Composition and method for forming biodegradable implants in situ and uses of these implants|

---

US6066139A|1996-05-14|2000-05-23|Sherwood Services Ag|Apparatus and method for sterilization and embolization|

---

US5807239A|1996-05-17|1998-09-15|Conceptus, Inc.|Transcervical ostium access device and method|

---

US5830228A|1996-05-29|1998-11-03|Urosurge, Inc.|Methods and systems for deployment of a detachable balloon at a target site in vivo|

---

US6103254A|1996-05-31|2000-08-15|Micro Therapeutics, Inc.|Methods for sterilizing male mammals|

---

WO1997049345A1|1996-06-27|1997-12-31|Chen Hank H|Transcervical electroocclusive sterilization device|

---

US5866554A|1996-07-19|1999-02-02|Shalaby; Shalaby W.|Compositions for prevention of inflammation and adhesion formation and uses thereof|

---

US6037331A|1996-07-19|2000-03-14|Poly-Med, Inc.|Compositions for prevention of inflammation and adhesion formation uses thereof|

---

US5795288A|1996-08-08|1998-08-18|Cohen; Kenneth L.|Apparatus with valve for treating incontinence|

---

US6315762B1|1996-11-14|2001-11-13|Angiodynamics, Inc.|Contrast medium delivery system and associated method|

---

US6010714A|1996-11-22|2000-01-04|Closure Medical Corporation|Non-thermogenic heat dissipating biomedical adhesive compositions|

---

US5989580A|1996-12-11|1999-11-23|Micro Therapeutics, Inc.|Methods for sterilizing female mammals|

---

US20010041900A1|1999-12-21|2001-11-15|Ovion, Inc.|Occluding device and method of use|

---

US7073504B2|1996-12-18|2006-07-11|Ams Research Corporation|Contraceptive system and method of use|

---

CA2275587C|1996-12-20|2006-10-24|Alza Corporation|Injectable depot gel composition and method of preparing the composition|

---

US5935098A|1996-12-23|1999-08-10|Conceptus, Inc.|Apparatus and method for accessing and manipulating the uterus|

---

US6080129A|1996-12-23|2000-06-27|Conceptus, Inc.|Method and apparatus for performing hysterosalpingography|

---

US5788716A|1997-01-13|1998-08-04|Kobren; Myles S.|Surgical instrument and method for fallopian tube ligation and biopsy|

---

AU5926798A|1997-01-21|1998-08-07|Penn State Research Foundation, The|Transcervical contraceptive platinum microcoil|

---

US5986065A|1997-03-10|1999-11-16|Sunol Molecular Corporation|Antibodies for inhibiting blood coagulation and methods of use thereof|

---

US5891457A|1997-05-12|1999-04-06|Neuwirth; Robert S.|Intrauterine chemical necrosing method, composition, and apparatus|

---

US5891192A|1997-05-22|1999-04-06|The Regents Of The University Of California|Ion-implanted protein-coated intralumenal implants|

---

DE69829569T2|1997-06-05|2006-03-23|Adiana, Inc., Redwood City|DEVICE FOR CLOSING THE ELEMENTS|

---

US6071283A|1997-06-06|2000-06-06|Medical Scientific, Inc.|Selectively coated electrosurgical instrument|

---

US6042590A|1997-06-16|2000-03-28|Novomedics, Llc|Apparatus and methods for fallopian tube occlusion|

---

US5962006A|1997-06-17|1999-10-05|Atrix Laboratories, Inc.|Polymer formulation for prevention of surgical adhesions|

---

US6059747A|1997-07-16|2000-05-09|Medex, Inc.|Syringe pump infusion control set|

---

US5935137A|1997-07-18|1999-08-10|Gynecare, Inc.|Tubular fallopian sterilization device|

---

US6290672B1|1997-07-30|2001-09-18|Mick Abae|Exploratory tubular sonogenic catheter|

---

US6485486B1|1997-08-05|2002-11-26|Trustees Of Dartmouth College|System and methods for fallopian tube occlusion|

---

US6179832B1|1997-09-11|2001-01-30|Vnus Medical Technologies, Inc.|Expandable catheter having two sets of electrodes|

---

US6538026B1|1997-09-11|2003-03-25|Provasis Therapeutics, Inc.|Compositions useful for remodeling body spaces|

---

US6258084B1|1997-09-11|2001-07-10|Vnus Medical Technologies, Inc.|Method for applying energy to biological tissue including the use of tumescent tissue compression|

---

US6476070B2|1997-09-11|2002-11-05|Provasis Therapeutics Inc.|Compositions useful for remodeling body spaces|

---

US6476069B2|1997-09-11|2002-11-05|Provasis Therapeutics Inc.|Compositions for creating embolic agents and uses thereof|

---

US6401719B1|1997-09-11|2002-06-11|Vnus Medical Technologies, Inc.|Method of ligating hollow anatomical structures|

---

AU739610B2|1997-11-07|2001-10-18|Salviac Limited|Implantable occluder devices for medical use|

---

US6174919B1|1998-02-18|2001-01-16|Closure Medical Corporation|Cyanoacrylate compositions with vinyl terminated ester groups|

---

CA2324265C|1998-03-19|2008-08-05|Merck & Co., Inc.|Liquid polymeric compositions for controlled release of bioactive substances|

---

US6455064B1|1998-04-30|2002-09-24|Closure Medical Corporation|Method of applying an adhesive composition over a bioactive polymerization initiator or accelerator|

---

US6113614A|1998-05-05|2000-09-05|Ensurg, Inc.|Medical device for dissolution of tissue within the human body|

---

GB9809536D0|1998-05-06|1998-07-01|Microsulis Plc|Sensor positioning|

---

US6635055B1|1998-05-06|2003-10-21|Microsulis Plc|Microwave applicator for endometrial ablation|

---

US6327505B1|1998-05-07|2001-12-04|Medtronic, Inc.|Method and apparatus for rf intraluminal reduction and occlusion|

---

US6493589B1|1998-05-07|2002-12-10|Medtronic, Inc.|Methods and apparatus for treatment of pulmonary conditions|

---

US5972002A|1998-06-02|1999-10-26|Cabot Technology Corporation|Apparatus and method for surgical ligation|

---

US6080152A|1998-06-05|2000-06-27|Medical Scientific, Inc.|Electrosurgical instrument|

---

US6096052A|1998-07-08|2000-08-01|Ovion, Inc.|Occluding device and method of use|

---

JP3858462B2|1998-07-30|2006-12-13|株式会社日立製作所|Manufacturing method of semiconductor device|

---

US6605294B2|1998-08-14|2003-08-12|Incept Llc|Methods of using in situ hydration of hydrogel articles for sealing or augmentation of tissue or vessels|

---

US6514534B1|1998-08-14|2003-02-04|Incept Llc|Methods for forming regional tissue adherent barriers and drug delivery systems|

---

US6152943A|1998-08-14|2000-11-28|Incept Llc|Methods and apparatus for intraluminal deposition of hydrogels|

---

CA2344280C|1998-10-01|2008-05-06|Baxter International Inc.|Improved component mixing catheter|

---

US5979446A|1998-10-22|1999-11-09|Synergyn Technologies, Inc.|Removable fallopian tube plug and associated methods|

---

US6143314A|1998-10-28|2000-11-07|Atrix Laboratories, Inc.|Controlled release liquid delivery compositions with low initial drug burst|

---

US6211296B1|1998-11-05|2001-04-03|The B. F. Goodrich Company|Hydrogels containing substances|

---

US6112747A|1998-11-06|2000-09-05|Jones; Jesse M.|Method of sterilizing females|

---

US6371975B2|1998-11-06|2002-04-16|Neomend, Inc.|Compositions, systems, and methods for creating in situ, chemically cross-linked, mechanical barriers|

---

US6458147B1|1998-11-06|2002-10-01|Neomend, Inc.|Compositions, systems, and methods for arresting or controlling bleeding or fluid leakage in body tissue|

---

US6299631B1|1998-11-12|2001-10-09|Poly-Med, Inc.|Polyester/cyanoacrylate tissue adhesive formulations|

---

US6309384B1|1999-02-01|2001-10-30|Adiana, Inc.|Method and apparatus for tubal occlusion|

---

CA2367414C|1999-03-17|2007-06-26|Sujoy Kumar Guha|An improved reversible contraceptive for male and female|

---

US6297337B1|1999-05-19|2001-10-02|Pmd Holdings Corp.|Bioadhesive polymer compositions|

---

US6514535B2|1999-05-21|2003-02-04|Noveon Ip Holdings Corp.|Bioadhesive hydrogels with functionalized degradable crosslinks|

---

US6663607B2|1999-07-12|2003-12-16|Scimed Life Systems, Inc.|Bioactive aneurysm closure device assembly and kit|

---

US6310166B1|1999-08-12|2001-10-30|Closure Medical Corporation|Sterilized cyanoacrylate solutions containing thickeners|

---

US6709667B1|1999-08-23|2004-03-23|Conceptus, Inc.|Deployment actuation system for intrafallopian contraception|

---

WO2001013835A1|1999-08-23|2001-03-01|Conceptus Inc|Insertion/deployment catheter system for intrafallopian contraception|

---

AU2002344223B2|2001-05-29|2006-07-06|Microvention, Inc.|Method of manufacturing expansile filamentous embolization devices|

---

US6579469B1|1999-10-29|2003-06-17|Closure Medical Corporation|Cyanoacrylate solutions containing preservatives|

---

US6286510B1|1999-11-05|2001-09-11|Terry L. Ray|Apparatus and method for preventing fluid transfer between an oviduct and a uterine cavity|

---

US6461631B1|1999-11-16|2002-10-08|Atrix Laboratories, Inc.|Biodegradable polymer composition|

---

WO2001068720A1|2000-03-13|2001-09-20|Biocure, Inc.|Embolic compositions|

---

GB0011764D0|2000-05-17|2000-07-05|Femcare Cyprus Ltd|Medical clips|

---

WO2001089584A2|2000-05-23|2001-11-29|Amersham Health As|Contrast agents|

---

US6450963B1|2000-06-30|2002-09-17|Ackrad Laboratories, Inc.|Apparatus and method for ultrasonic imaging of the uterus and fallopian tubes using air and saline|

---

US6620846B1|2000-08-02|2003-09-16|Closure Medical Corporation|Absorbable adhesive compositions|

---

US6605667B1|2000-09-08|2003-08-12|Closure Medical Corporation|Antioxidant enriched adhesive compositions and storage containers therefor|

---

US6607631B1|2000-09-08|2003-08-19|Closure Medical Corporation|Adhesive compositions with reduced coefficient of friction|

---

US6610033B1|2000-10-13|2003-08-26|Incept, Llc|Dual component medicinal polymer delivery system and methods of use|

---

US6896682B1|2000-11-14|2005-05-24|Biomedical Engineering Solutions, Inc.|Method and system for internal ligation of tubular structures|

---

WO2002047744A2|2000-12-13|2002-06-20|Flow Focusing, Inc.|Method and catheter for aerating fluids for medical uses|

---

JP4707227B2|2000-12-27|2011-06-22|グンゼ株式会社|Biological duct stent|

---

US6550480B2|2001-01-31|2003-04-22|Numed/Tech Llc|Lumen occluders made from thermodynamic materials|

---

US20020176893A1|2001-02-02|2002-11-28|Wironen John F.|Compositions, implants, methods, and kits for closure of lumen openings, repair of ruptured tissue, and for bulking of tissue|

---

US6703047B2|2001-02-02|2004-03-09|Incept Llc|Dehydrated hydrogel precursor-based, tissue adherent compositions and methods of use|

---

US6685626B2|2001-02-02|2004-02-03|Regeneration Technologies, Inc.|Compositions, devices, methods, and kits for induction of adhesions|

---

US20020177846A1|2001-03-06|2002-11-28|Mulier Peter M.J.|Vaporous delivery of thermal energy to tissue sites|

---

US20020133140A1|2001-03-14|2002-09-19|Harry Moulis|Liquid cautery catheter|

---

US7897141B2|2002-04-01|2011-03-01|Drexel University|Echogenic polymer microcapsules and nanocapsules and methods for production and use thereof|

---

US6599299B2|2001-06-26|2003-07-29|Leonard S. Schultz|Device and method for body lumen occlusion|

---

DE60204021T2|2001-07-26|2006-01-12|Oregon Health Sciences University, Portland|CLOSING DEVICE FOR A VESSEL AND APPLICATION DEVICE|

---

SE0102922D0|2001-08-31|2001-08-31|Astrazeneca Ab|Method and apparatus for sample preparation|

---

US6758831B2|2001-09-24|2004-07-06|Ethicon, Inc.|Device and method for aligning with the tubal ostium|

---

US20030066533A1|2001-10-05|2003-04-10|Loy Randall A.|Removable fallopian tube plug and associated methods|

---

EP1441823B1|2001-11-09|2013-08-21|KBI Biopharma, Inc.|Methods and compositions for chromatography|

---

AU2002359410A1|2001-11-16|2003-06-10|Biocure, Inc.|Methods for initiating in situ formation of hydrogels|

---

US6699940B2|2001-12-04|2004-03-02|Poly Med, Inc.|Cyanoacrylate-capped heterochain polymers and tissue adhesives and sealants therefrom|

---

US20030108586A1|2001-12-11|2003-06-12|Jacques Ramey|Method of long-term reversible contraception for animals|

---

US6736822B2|2002-02-20|2004-05-18|Mcclellan Scott B.|Device and method for internal ligation of tubular structures|

---

US7094369B2|2002-03-29|2006-08-22|Scimed Life Systems, Inc.|Processes for manufacturing polymeric microspheres|

---

US7341716B2|2002-04-12|2008-03-11|Boston Scientific Scimed, Inc.|Occlusive composition|

---

US6780182B2|2002-05-23|2004-08-24|Adiana, Inc.|Catheter placement detection system and operator interface|

---

US6936033B2|2002-06-14|2005-08-30|Medtronic, Inc.|Multiple ratio fluid dispenser|

---

US20040002680A1|2002-07-01|2004-01-01|Ackrad Laboratories, Inc.|Single lumen balloon catheter apparatus|

---

US7267667B2|2002-07-11|2007-09-11|Boston Scientific Scimed, Inc.|Fluid management system for coronary intervention|

---

US20060148897A1|2002-09-13|2006-07-06|Brent Vernon|Method for sterilization using in situ gelling materials|

---

NO20024883D0|2002-10-09|2002-10-09|Amersham Health As|Snake|

---

US20040197302A1|2002-10-15|2004-10-07|Porter Christopher H.|Prepolymeric materials for site specific delivery to the body|

---

DE20218493U1|2002-11-28|2004-04-08|Chemische Fabrik Kreussler & Co. Gmbh|Device for producing medical foam|

---

US20040116955A1|2002-12-12|2004-06-17|Jonathan Foltz|Cervical canal dilator|

---

US20040258761A1|2003-03-20|2004-12-23|Wheatley Margaret A.|Polymer-based microcapsules and nanocapsules for diagnostic imaging and drug delivery and methods for their production|

---

EP1635842A4|2003-06-20|2007-04-04|Alcon Inc|Treatment of amd with combination of ingredients|

---

DE10333165A1|2003-07-22|2005-02-24|Daimlerchrysler Ag|Production of press-quenched components, especially chassis parts, made from a semi-finished product made from sheet steel comprises molding a component blank, cutting, heating, press-quenching, and coating with a corrosion-protection layer|

---

EP1708763A4|2004-01-07|2011-03-23|Trivascular Inc|Methods, compositions, and devices for embolizing body lumens|

---

US8052669B2|2004-02-25|2011-11-08|Femasys Inc.|Methods and devices for delivery of compositions to conduits|

---

US8048086B2|2004-02-25|2011-11-01|Femasys Inc.|Methods and devices for conduit occlusion|

---

US8048101B2|2004-02-25|2011-11-01|Femasys Inc.|Methods and devices for conduit occlusion|

---

US7611503B2|2004-04-16|2009-11-03|Medrad, Inc.|Fluid delivery system, fluid path set, sterile connector and improved drip chamber and pressure isolation mechanism|

---

US20080154214A1|2006-12-22|2008-06-26|Medrad, Inc.|Flow Based Pressure Isolation and Fluid Delivery System Including Flow Based Pressure Isolation|

---

US20050240211A1|2004-04-21|2005-10-27|Stefan Sporri|Apparatus and method for selectably treating a fallopian tube|

---

US7470253B2|2004-05-26|2008-12-30|Bioquiddity, Inc.|Fluid delivery apparatus with adjustable flow rate control|

---

US8123693B2|2005-06-20|2012-02-28|Conceptus, Inc.|Methods and devices for determining lumen occlusion|

---

EP1893279A4|2005-06-21|2010-12-29|Medrad Inc|Medical fluid injection and inflation system|

---

JP2008168168A|2007-01-06|2008-07-24|Konica Minolta Medical & Graphic Inc|Continuous mixing reactor|

---

US8226619B2|2007-06-15|2012-07-24|Kyphon Sarl|Systems and methods for needle access to an intervertebral disc|

---

AU2008275158A1|2007-07-09|2009-01-15|Velomedix, Inc|Hypothermia devices and methods|

---

JP4238922B2|2007-07-09|2009-03-18|三菱電機株式会社|Patch antenna|

---

US20090217932A1|2008-03-03|2009-09-03|Ethicon Endo-Surgery, Inc.|Intraluminal tissue markers|

---

US10070888B2|2008-10-03|2018-09-11|Femasys, Inc.|Methods and devices for sonographic imaging|

---

US9554826B2|2008-10-03|2017-01-31|Femasys, Inc.|Contrast agent injection system for sonographic imaging|

---

US20120029428A1|2009-04-08|2012-02-02|Neer Charles S|Vacuum Asisst Syringe Filling|

---

CN102834102B|2009-12-08|2015-01-14|范德比尔特大学|Improved methods and compositions for vein harvest and autografting|

---

JP5604180B2|2010-05-28|2014-10-08|株式会社ニューギン|Movable direction device for gaming machine|US8048086B2|2004-02-25|2011-11-01|Femasys Inc.|Methods and devices for conduit occlusion|

---

US9554826B2|2008-10-03|2017-01-31|Femasys, Inc.|Contrast agent injection system for sonographic imaging|

---

US10070888B2|2008-10-03|2018-09-11|Femasys, Inc.|Methods and devices for sonographic imaging|

---

US8876833B2|2010-04-30|2014-11-04|Kyphon Sarl|Multi-port delivery system|

---

WO2012064884A1|2010-11-09|2012-05-18|Femasys Inc.|Methods and devices for managing fluid pressure|

---

EP2897673B1|2012-09-24|2020-01-22|Medline Industries, Inc.|Power injector device and method of use|

---

US20140208251A1|2013-01-21|2014-07-24|Angiodynamics, Inc.|Power injector device and method of use|

---

US20140155745A1|2012-12-04|2014-06-05|Cook Medical Technologies, LLC|Venturi Effect Mixing Catheter Apparatus and Methods of Using the Same|

---

US10888639B2|2013-08-30|2021-01-12|Arsenal Medical, Inc.|Delivery catheters for in situ forming foams|

---

US10034986B2|2013-11-11|2018-07-31|Crossbay Medical, Inc.|Method and apparatus of tubal patency catheter and delivery systems|

---

US10245074B2|2013-11-11|2019-04-02|Crossbay Medical, Inc.|Apparatus and methods for accessing and sealing bodily vessels and cavities|

---

US9101391B2|2013-11-11|2015-08-11|Cross Bay Medical, Inc.|Apparatus and methods for accessing and sealing bodily vessels and cavities|

---

WO2016085995A1|2014-11-26|2016-06-02|Simnext, Llc|Device and method for a medical simulator with anatomically accurate inflatable features|

---

KR101525955B1|2014-12-26|2015-06-09|제이씨하이텍|Micro-bubble creating device for sonographic vibration tests|

---

CN105147333A|2015-10-14|2015-12-16|苏州斯科特医学影像科技有限公司|Three-dimensional hystero-salpingography imaging instrument|

---

WO2017143343A1|2016-02-19|2017-08-24|Aegea Medical Inc.|Methods and apparatus for determining the integrity of a bodily cavity|

---

CN110612096A|2017-03-27|2019-12-24|苏州医本生命科技有限公司|Chain medicine structure and preparation facilities and storage device thereof|

---

RU2697370C1|2018-03-13|2019-08-13|Федеральное государственное бюджетное учреждение "Национальный медицинский исследовательский центр акушерства, гинекологии и перинатологии имени академика В.И. Кулакова" Министерства здравоохранения Российской Федерации|Method of echohysterosalpingography with sonovue ultrasound contrast agent|

---

US20200246603A1|2019-01-31|2020-08-06|Becton, Dickinson And Company|Catheter flush device, system, and methods|

---

KR102012824B1|2019-04-11|2019-08-21|김태균|Test kit for fallopian tube ultrasonography|

---

CN109999266A|2019-04-30|2019-07-12|广州医科大学附属第三医院（广州重症孕产妇救治中心、广州柔济医院）|Injection device|

---

CN110279432B|2019-07-26|2021-09-07|河南科技大学第一附属医院|Preparation of microbubble contrast medium and injection device for TCD inspection|

---

WO2021072261A1|2019-10-09|2021-04-15|Crossbay Medical, Inc.|Apparatus and method for everting catheter for iud delivery and placement in the uterine cavity|

法律状态:
2018-12-18| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

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2019-10-29| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

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2020-10-20| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|

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2020-12-22| B16A| Patent or certificate of addition of invention granted [chapter 16.1 patent gazette]|Free format text: PRAZO DE VALIDADE: 20 (VINTE) ANOS CONTADOS A PARTIR DE 09/11/2011, OBSERVADAS AS CONDICOES LEGAIS. |

优先权:

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申请号 | 申请日 | 专利标题

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US41185610P| true| 2010-11-09|2010-11-09|

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US61/411856|2010-11-09|

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US13/219667|2011-08-27|

---

US13/219,667|US9554826B2|2008-10-03|2011-08-27|Contrast agent injection system for sonographic imaging|

---

PCT/US2011/060013|WO2012064866A1|2010-11-09|2011-11-09|Methods and devices for sonographic imaging|

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