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    • 专利摘要:
    DEVICE FOR APPLYING A MEDICINE AND METHODS TO IMPROVE PAIN. The present invention relates to a device for delivering a drug to a patient in need thereof, which includes: (a) an injector that includes a first end configured to remain outside a patient's nasal passage and a second end configured to enter in the patient's nasal passage, where the injector is mobile between a storage position and a coupling position; and (b) an introducer configured for coupling with a patient's nostril, wherein the introducer includes a passageway configured to receive the injector slide, and the introducer includes a curvature along a portion thereof adjacent to the passageway. Methods to improve pain in a patient include (a) introducing the injector through the patient's nasal passage into a substantially medial and / or posterior and / or inferior region to a patient's sphenopalatine ganglion; and (b) applying a medication from the injector superiorly and / or laterally and / or anteriorly towards the sphenopalatine ganglion.
    公开号:BR112013011591B1
    申请号:R112013011591-2
    申请日:2011-10-28
    公开日:2020-11-24
    发明作者:Tian Xia
    申请人:Tian Xia；
    IPC主号:
    专利说明:

    [0001] [0001] This order is a continuation in part of the previous Order No. 12 / 414,300, filed on March 30, 2009, which in turn is a continuation in part of the previous Order No. 12 / 184,358, filed on August 1, 2009 2008. The entire content of both requests referenced above is hereby incorporated by reference, except that in the case of any inconsistent description or definition of this application, their description or definition shall be considered to prevail. TECHNICAL FIELD
    [0002] [0002] The present invention relates to devices and methods for pain management - specifically, though not exclusively, to the pain management associated with headaches, facial pains, and the like. INTRODUCTION
    [0003] [0003] Conventional methods for treating pain associated with headaches and facial pain are not as safe and effective as desired. As an example, non-steroidal anti-inflammatory drugs (NSAIDs), such as the COX-2 drug brand, should be used sparingly and only for short periods in view of their potential to cause ulcers and heart attacks - a disadvantage that is additionally increased by the ineffectiveness of these medications in a large number of patients. The use of narcotics is also undesirable in view of its potentially addictive properties. In addition, the use of tryptamine-based drugs - which include, but are not limited to sumatriptan (sold under the brand name IMITREX by GlaxoSmithKline) and zolmitriptan (sold under the brand name ZOMIG by AstraZeneca) - is undesirable in view of the high cost and potentially high toxicity of these drugs.
    [0004] [0004] A method that has been employed to control the pain associated with headaches and facial pain is known as an SPG block. In this proposal, an anesthetic is applied to a patient's sphenopalatine ganglion (GSP) by a trained medical professional, who typically inserts a cotton-tipped applicator soaked in the anesthetic into a patient's nostril in order to apply the anesthetic to the GSP. Using the medium turbine as a point of reference, cotton-tipped applicators are pushed upward in what is essentially a blind advance (the success of which depends very heavily on the physician's skill and experience). Clearly, the effectiveness and safety of this procedure leaves much to be desired. Furthermore, the effectiveness and safety of conventional GSP blocks may have been significantly compromised by an erroneous belief among clinicians that the GSP is located posterior to the upper turbine - which it is not.
    [0005] [0005] In summary, there is an urgent need among patients and clinicians for safer and more effective methods and devices to achieve a GSP block - specifically those that can be employed directly by a patient without the assistance or supervision of a medical professional trained. SUMMARY
    [0006] [0006] The scope of the present invention is defined only by the appended claims, and is not affected to any degree by the statements in this summary.
    [0007] [0007] A device for delivering a drug to a patient in need of it includes: (a) an injector that includes a first end configured to remain outside a patient's nasal passage and a second end configured to enter the patient's nasal passage, wherein the injector is movable between a storage position and a coupling position; and (b) an introducer configured for coupling with a patient's nostril, wherein the introducer includes a passageway configured to receive the injector slide, and the introducer includes a curvature along a portion thereof adjacent to the passageway.
    [0008] [0008] A method for improving pain in a patient includes (a) introducing the injector of a device of the type described above through the patient's nasal passage into a substantially medial and / or posterior region and / or less than a sphenopalatine ganglion of the patient; and (b) applying a medication from the injector superiorly and / or laterally and / or anteriorly towards the sphenopalatine ganglion. BRIEF DESCRIPTION OF THE DRAWINGS
    [0009] [0009] FIG. 1 shows a cross-sectional side view of a first device for delivering a drug to a patient in need of it before insertion of the device into a patient's nostril according to the principles described herein.
    [0010] [00010] FIG. 2 shows a top plan view in cross section of the device of FIG. 1 taken along line 2-2.
    [0011] [00011] FIG. 3 shows a side cross-sectional view of the device of FIG. 1 after the introducer has been coupled with a patient's nostril according to the principles described here.
    [0012] [00012] FIG. 4 shows a side cross-sectional view of the device of FIG. 1 after the introducer has been coupled with a patient's nostril and after the injector has been moved from its storage position to a coupling position that positions the second end of the medial injector, posteriorly, and inferior to the sphenopalatine ganglion.
    [0013] [00013] FIG. 5 shows a median cross-sectional view of a human head with the SPG 2 shown in its correct anatomical position after the medium turbine 4.
    [0014] [00014] FIG. 6 shows a side elevation of a second device for delivering a drug to a patient in need of it before inserting the cube into the housing and with the injector in its storage position.
    [0015] [00015] FIG. 7 shows a partial partial cross-sectional side view of the device of FIG. 6 with the injector in its storage position.
    [0016] [00016] FIG. 8 shows a side view in partial cross-section of the device of FIG. 6 with the injector in a coupling position.
    [0017] [00017] FIG. 9 shows an exploded perspective view of the device of FIG. 6. DETAILED DESCRIPTION
    [0018] [00018] The hitherto unknown and highly effective methods for improving pain in a patient - specifically although not exclusively the pain associated with headaches, facial pains, and the like - and user friendly devices that allow easy self-administration of medicines according to these methods have been discovered and are described here. As further explained below, the methods and devices described herein allow the application of a drug superiorly and / or laterally and / or anteriorly towards the sphenopalatine ganglion of a substantially medial and / or posterior and / or inferior region of the sphenopalatine ganglion.
    [0019] [00019] As used herein, the phrase "towards the sphenopalatine ganglion" and such similar phrases used with reference to the application of a drug are intended to include the SPG itself as well as the pterygopalatine fossa which houses the SPG and the sphenopalatine foramen.
    [0020] [00020] As an introduction, FIG. 5 shows a median cross-sectional view of a human head that correctly identifies the location of the SPG 2 as being posterior to the middle turbine 4 - not posterior to the upper turbine 6 or the apex 8 of the nasal cavity in the vicinity of the cribriform plate 9 like several doctors have mistakenly imagined. In addition, the correct location of the SPG 2 is actually displaced laterally from the drawing plane - in other words, the SPG is not on a two-dimensional plane with respect to the presented cross section, as was also mistakenly believed by several doctors.
    [0021] [00021] In United States Patent No. 4,886,493, Jordan Yee describes a process for performing an SPG block in which a tube is inserted through a patient's nostril in an attempt to apply a medication to the pterygopalatine fossa, which it houses the GSP. Unfortunately, as shown in FIG. 3 of US Patent No. 4,886,493, the location of the pterygopalatine fossa 18 was misidentified as being posterior to the upper turbine and in an xy plane accessible by a straight line from the nostril through a tube 11. As a result of this misunderstanding - in addition the expected lack of efficacy that one would expect to apply a drug to the wrong place - the terminal end 13 of Yee's device comes dangerously close to contacting the delicate cribriform plate. As the cribriform plaque as a sieve and in communication with the frontal lobe of the brain, it is extremely dangerous to introduce anesthetics in the vicinity of this plaque since they can easily penetrate through the frontal lobe.
    [0022] [00022] United States Patent Number 6,491,940 B1 to Bruce H. Levin describes an alternative procedure for performing an SPG block. In contrast to the Yee patent described above, U.S. Patent Number 6,491,940 B1 appears to recognize the lateral displacement of the SPG as it describes a curved rather than a straight body (100) for introducing the anesthetic. Unfortunately, similarly to Yee's patent, Levin's patent also fails to recognize that the correct location of the SPG is posterior to the middle turbine - not at the apex of the nasal cavity as shown in FIG. Levin 4A and as described therein (for example, column 72, lines 20-22). Thus, as in the case of Yee's patent, the process described in Levin's patent once again introduces an anesthetic delivery device dangerously close to the cribriform plate with all the accompanying risks and diminished efficacies associated with it.
    [0023] [00023] United States Patent Number 6,332,542 B1, assigned to AstraZeneca, describes a device for delivering drugs into a patient's nasal cavity. Despite the stated objective of this device is to effectively apply a medication to the posterior region of the nasal cavity (column 1, lines 29-32), its configuration (for example, the linearity of the tubular member 35) is poorly adapted to apply a medication to or in the vicinity of the GSP. Instead, the drug will be applied largely to the region 7 shown in FIG. 5 of this application. The application of anesthetics in the vicinity of region 7 is highly undesirable as anesthetics can readily suppress the vomiting reflex, thereby creating a risk of aspiration pneumonia.
    [0024] [00024] Despite neither wishing to be bound by any specific theory, nor intending to affect in any measure the scope of the attached claims or their equivalents, the following historical information is provided regarding the present day understanding of the anatomy of the SPG in order to further elucidate a description of the devices and methods provided below.
    [0025] [00025] The SPG (also known as the pterygopalatine ganglion) is the largest group of neurons outside the cranial cavity and is located within the pterygopalatine fossa, which is approximately 1 cm wide and approximately 2 cm high. The pterygopalatine fossa is previously limited by the posterior wall of the maxillary sinus, posteriorly by the medial plate of the pterygoid process, medially by the perpendicular plate of the palatal bone, and superiorly by the sphenoid sinus. Laterally, the pterygopalatine fossa communicates with the infratemporal fossa.
    [0026] [00026] The SPG inside the fossa is located posterior to the middle turbine of the nose and is a few millimeters (1 mm to 5 mm) deep in the lateral nasal mucosa. The SPG has a complex neural center and multiple connections. The GSP is suspended from the maxillary branch of the trigeminal nerve in the pterygopalatine fossa through the pterygopalatine nerves, and is medial to the maxillary branch when viewed in the sagittal plane. Subsequently, the SPG is connected to the vidian nerve. The SPG itself has efferent ramifications and forms the superior posterior lateral nasal and pharyngeal nerves. Caudally, the ganglion (SPG) is in direct connection with the largest and smallest palatine nerves.
    [0027] [00027] The SPG has sensory, motor and autonomic components. Sensory fibers arise from the maxillary nerve, pass through the GSP, and are distributed to the nasal membranes, the soft palate and some parts of the pharynx. Few motor nerves are also believed to be carried by the sensory trunks.
    [0028] [00028] The GSP's autonomic innervations are more complex. The sympathetic component begins with the pre-ganglionic sympathetic fibers that originate in the upper thoracic spine cord, forming white ramie communicants, running through the sympathetic ganglion, where the pre-ganglionic fibers form a synapse with those post-ganglionic fibers. The post-ganglionic fibers then join with the carotid nerves before branching and moving through the deep periotic and vidian nerves. The post-ganglionic sympathetic nerves continue their path through the GSP on their way to the lacrimal gland and the nasal and palatal mucosa.
    [0029] [00029] The GSP is usually considered parasympathetic in function. The parasympathetic component of the SPG has its pre-ganglionic origin in the superior salivary nucleus, so it travels through a portion of the facial nerve (VII) before forming the larger periotic nerve to form the vidian nerve, which ends in the SPG. Within the ganglion, the pre-ganglionic fibers form a synapse with their post-ganglionic cells and continue forward to the nasal mucosa, and a branch travels with the maxillary nerve to the lacrimal gland.
    [0030] [00030] Despite the above description, and regardless of the currently believed theories regarding the anatomy of GSP, a safe and effective improvement of pain can be achieved as a result of using the devices and methods described below. Although representative devices 10 and 54 are described with reference to Figures 1-4 and Figures 6-9, respectively, it should be understood that these representative devices are merely illustrative and that alternative structures can likewise be used to deliver a drug according to with the principles described here. It should be understood that the elements and characteristics of the various representative devices described below can be combined in different ways to produce new modalities that likewise fall within the scope of the present teachings. The drawings and description below are provided for illustration only and are not intended to limit the scope of the attached claims or their equivalents.
    [0031] [00031] Figures 1-4 show a representative device 10 for delivering a drug to a patient in need of it. Device 10 includes an injector 12 comprising a first end 29 configured to remain outside a patient's nasal passage and a second end 30 configured to enter the patient's nasal passage. The device 10 also includes an introducer 18 configured for coupling with a patient's nostril and comprising a passageway 48 configured to receive the injector sliding 12. The injector 12 is movable between a storage position (best shown in FIG. 1) preceding the coupling the introducer 18 with a patient's nostril, and a coupling position (best shown by FIG. 4) in accordance with the coupling of the introducer 18 with the patient's nostril. However, when initially introducing the introducer 18 with a patient's nostril, the injector 12 is desirably kept - at least for a while - in a storage position (best shown in FIG. 3) until it is deliberately moved to a coupling position (best shown in FIG. 4) under the direction of a user. In some embodiments, the injector 12 coupling position is located medial and / or below the SPG. In other embodiments, the injector 12 coupling position is located medial, lower, and posterior to the SPG, as best shown by FIG. 4.
    [0032] [00032] As used herein, the phrases "storage position" and "coupling position" are each intended to cover multiple positions within a selected range. For example, in some embodiments, the degree to which injector 12 is extended into the nostril of a first patient (e.g., a child) will vary from the degree to which injector 12 is extended into the nostril of a second patient ( for example, an adult man). Despite this, the phrase "coupling position" is intended to cover many variations in the precise position of the injector 12 within the nostril, any of which is properly considered to be medial and / or posterior and / or less than the SPG. In some embodiments, the injector 12 is not slidable within the introducer 18 but instead is fixed in a predetermined position so as to be medial and / or less than the SPG when coupling the introducer 18 with a patient's nostril. In other embodiments, the injector 12 is not slidable inside the introducer 18, but instead is fixed in a predetermined position so that it is medial, posterior, and inferior to the SPG when the introducer 18 is coupled with a patient's nostril.
    [0033] [00033] The injector 12 comprises a tubular section 24 (a so-called snake tube in recognition of the extensibility of the tube) that includes a channel 22 and extends from the first end 29 to the second end 30 and configured to receive a drug. In some embodiments, the tubular section 24 has an external diameter of approximately 5 mm and the channel 22 has an internal diameter of approximately 2 mm. Throughout this description, measurements and distances, as well as diameters only given, should be strictly considered to be merely representative and in no way limiting and / or fixed. Considerable variation in all the measurements and distances provided in this description is possible, as will be readily appreciated by someone skilled in the art.
    [0034] [00034] In some embodiments, the second end 30 of the injector 12 contains a nozzle 28 that has a tip 34 that contains one or a plurality of openings 36 configured to spray a drug superiorly and / or laterally and / or anteriorly in the direction of the GSP . In some embodiments, the nozzle 28 is configured to spray a medicine laterally and / or superiorly in the direction of the SPG, and in other embodiments, the nozzle 28 is configured to spray a medicine laterally, superiorly, and anteriorly in the direction of the SPG.
    [0035] [00035] In some embodiments, the nozzle 28 extends at an upward tilt angle from the second end 30 of the injector 12. In some embodiments, the nozzle 28 extends in a lateral, anterior, and upper direction at an inclination angle that varies from approximately 45 degrees to approximately 60 degrees to accommodate variable patient anatomies in which the GSP resides in a lateral cavity posterior to the middle turbine. In some embodiments, the nozzle 28 has a length ranging from approximately 2 mm to approximately 5 mm. In some embodiments, the injector 12 is designed to exhibit a right-to-left capability so that in some embodiments, the injector 12 is configured to mate with a patient's left nostril, while in other embodiments, the injector 12 is configured to coupling with a patient's right nostril (with the outline of a left injector being generally complementary to the outline of a right injector).
    [0036] [00036] Introducer 18 can be directed into a nostril to provide a horizontal path substantially parallel to the bottom of the nasal cavity or bottom of the nose - so that the introducer 18 is supported on the bottom of the nasal cavity - to a medial position to the lower turbine. This self-seating feature of the introducer 18 facilitates quick and accurate use by a patient without requiring supervision by a medical professional. In some embodiments, the introducer 18 provides an extended path between approximately 1.5 cm and approximately 2 cm into the nostril. Once the introducer 18 is placed firmly against the nose, the tip of the nose will tend to point upwards. The tubular section 24 of the injector 12 can then be pushed partially or completely into the rear of the nostril. In order to accommodate the slightly curved nature of the interior anatomy of the nose, the passageway 48 within which the tubular section 24 rests can be slightly curved into the ipsilateral nostril by approximately 5 to approximately 20 degrees. Once the tubular section 24 is in position, a drug can then be applied to the SPG of the nozzle 28 to exert the desired SPG blocking effect. In some embodiments, device 10 is provided with a safety stopper to limit the extent of displacement into the nostril available to the injector 12.
    [0037] [00037] As best shown in Figures 1, 3 and 4, the introducer 18 contains a first portion 44 and a second portion 38. In some embodiments, a cross-sectional area of the first portion 44 is larger than a cross-sectional area of the second portion 38. In some embodiments, the first portion 44 is generally concave and has a contour 46 configured to be complementary in shape to an interior of the nostril in order to substantially conform to it. In some embodiments, the second narrow portion 38 has a rounded convex portion 39 and a bottom side 40 that has a generally flat surface 42. Passage 48 of the introducer 18 slips the tubular section 24 of the injector 12 and, in some embodiments, has a diameter between approximately 6 mm and approximately 7 mm. In some embodiments, the second portion 38 of the introducer 18 contains a nostril coupling tip that extends from approximately 1 cm to approximately 3 cm. In some embodiments, the first portion 44 of the introducer 18 extends from approximately 2 cm to approximately 3 cm. In some embodiments, introducer 18 is designed to exhibit a right-to-left capability, so that in some embodiments, introducer 18 is configured to mate with a patient's left nostril, while in other embodiments, introducer 18 is configured for coupling with a patient's right nostril (with the outline of a left introducer being generally complementary to the outline of a right introducer).
    [0038] [00038] In some embodiments, the device 10 even includes a container 14 in communication with the first end 29 and the channel 22 of the injector 12, which is configured to contain a medicament 16 (for example, an anesthetic). In some embodiments, as shown in Figures 1, 3, and 4, the container 14 is supported on a rod 26 which has a lower section 31 which, in some embodiments, has an outside diameter substantially the same as that of the tubular section 24 The lower section 31 can extend outward and / or upward and / or at a tilt angle of the first end 29 of the injector 12 and, in some embodiments, connects to an upper section 32 that has an increased diameter configured to receive a outlet 33 of container 14. Similar to the lower section 31, the upper section 32 can extend outward and / or upward and / or at an angle of inclination.
    [0039] [00039] In some embodiments, the container 14 is operatively connected, assembled or otherwise attached to the upper stem section 32 and is fully or partially filled with a medication 16. As the container 14 is in communication with the injector channel 22 12, the medically 16 can be applied along the tubular section 24 and released through one or more openings 36 of the nozzle 28. The container 14 can be formed of plastic, metal or similar, and can be compressible and / or pressurized to facilitate application of the medication within the channel 22. In some embodiments, the container 14 is replaced by an orifice (not shown), so that a medication can be introduced through the orifice into the upper section 32 can be an application device, such as , a syringe.
    [0040] [00040] In some embodiments, the device 10 even includes an optional handle 20 connected to a rear portion of the introducer 18 adjacent to the first portion 44. The handle 20 includes an upwardly facing groove 50 that provides a rail 52 configured to receive and in communication with the passage 48 of the introducer 18 for sliding the tubular section 24 of the injector 12. In some embodiments, the rail 52 has a depth or width between approximately 6 mm and approximately 7 mm. The handle 20 is configured to move towards a patient's face, so that a further movement of the handle 20 moves the introducer 18 in coupling with the patient's nostril.
    [0041] [00041] The injector 12, the introducer 18, and the handle 20 can be formed in any way from materials that include, but are not limited to, flexible, rigid or semi-rigid polymeric materials (for example, plastics, rubbers, etc.) , metals and their alloys, and the like, and their combinations. In some embodiments, the injector 12 is formed of a flexible plastic, the introducer 18 is formed of an elastomeric and / or resilient plastic or rubber, and the handle 20 is formed of plastic. In some embodiments, one or more of the injector 12, the introducer 18, and the handle 20 are designed from a material so as to be disposable and / or biodegradable.
    [0042] [00042] Although the representative device 10 described above can be used to apply a drug superiorly and / or laterally and / or anteriorly towards a patient's sphenopalatine ganglion according to the principles presented here, alternative structures can likewise be employed to similarly execute such an application.
    [0043] [00043] Just as an example, an application tube that has a curved portion at one of its ends configured for insertion into a patient's nostril - analogous to the inclined nozzle 28 provided on the second end 30 of the injector 12 - can be housed inside substantially cylindrical housing (for example, in the form of a pen or cigar). The application tube can be formed of a flexible or semi-rigid material (such as plastic) so that it can be kept in a substantially linear or non-curved arrangement while in its storage position within the housing, but readily restored to its curved configuration when extended from the housing to a coupling position. In such a device, one or more internal surfaces of the outer housing acts to straighten or restrict - completely or at least partially - the inherent curvature of the application tube until such time when the application tube is moved to a coupling position, by means of that the curvature of the tube is restored. In some embodiments, at least a portion of the delivery tube (for example, the end designed to deliver the drug) can be expandable if desired (for example, when air, oxygen and / or other gases, and / or drugs are forced through pressure tube).
    [0044] [00044] By providing one or more optional index markings on the cylindrical housing described above, a user can readily identify the direction of curvature of the application tube stored inside, so that by rotating the housing around a 360 degree arc, the user can select any desired spray direction to apply a drug through the application tube. By simply rotating the housing, the spray direction can be incrementally changed through a continuous arc between 0 degrees and 360 degrees inclusive. In the design, one end of the housing can be equipped with a luer lock configured to couple with a syringe containing the medication. Alternatively, the end of the housing configured to remain outside the nostril may be equipped with a septum or such a similar membrane through which a medicament can be introduced into the delivery tube housed therein.
    [0045] [00045] Numerous other modifications to the application devices described herein, as well as alternative structures, are likewise contemplated for use to the degree that they similarly allow the application of a drug superiorly and / or laterally and / or previously in the direction of a sphenopalatine ganglion of a patient according to the present teaching. As an example, the portion of the device configured for insertion into a patient's nostril (e.g., a portion of injector 12 described above) can be formed of any therapeutically acceptable malleable material (e.g., plastics, metals, metal alloys, and the like) capable of receiving and retaining a desired shape when manipulated by a user (e.g., an increased or decreased curvature of the inclined nozzle 28 provided on the second end 30 of the injector 12). Such a feature may be desirable, for example, when a clinician wants to customize the exact geometry of a device before using it on a patient in a clinical setting.
    [0046] [00046] Figures 6-9 show a representative device 54 for delivering a drug to a patient in need of it. Device 54 includes an injector 56 that comprises a first end 58 configured to remain outside a patient's nasal passage and a second end 60 configured to enter the patient's nasal passage. The device 54 also includes an introducer 62 configured for coupling with a patient's nostril and comprising a passageway 64 configured to receive the injector 56 sliding. The injector 56 is movable between a storage position (best shown by Figures 6 and 7) that precedes the coupling of the introducer 62 with the nostril of a patient, and a coupling position (best shown in FIG. 8) as the coupling of the introducer 52 with the patient's nostril.
    [0047] [00047] As best shown by Figures 6 and 7, the injector 56 is coupled to a hub 66 equipped with a luer locking mechanism configured to couple with the threads of a syringe (not shown) that contains a drug to be applied to a patient. As best shown by Figures 7-9, hub 66 is coupled to a stop bar 68 which is compressible. Before coupling with a syringe, hub 66 is configured to remain outside housing 70 and resist rotation there since the stop bar 68 is positioned within a keyway 72 formed by the two halves of housing 70. According to hub 66 is pressed axially into the housing 70 (for example, by a syringe attached to the luer locking mechanism on the hub 66), the stop bar 68 moves along the keyway 72 until it reaches the lip 74 at which point the stop bar 68 engages the lip 74, thereby preventing the cube 66 from retracting from inside the housing 70, at which point the cube 66 (and the syringe attached to it) becomes rotatable over a fixed strip. The irreversibility of the axial displacement of the cube 66 within the housing 70 provides a useful way for the practitioner to readily distinguish a used device from an unused one - namely, if the cube 66 does not project from the housing 70, the device has previously been used.
    [0048] [00048] As can be understood from a consideration of Figures 8 and 9, the stop bar 68 is additionally configured to act in conjunction with a projection 78 within the housing 70 so that the rotation range of the hub 66 (and the syringe) coupled to it) is limited to predetermined angles (for example, approximately 45 ° clockwise or 45 ° counterclockwise). Rotation beyond predetermined angles (which are determined based on the position of the protrusion 78) is prevented when the stop bar 68 touches the protrusion 78. This feature facilitates the precision of use by a user by limiting the positions from which the medicine can be introduced from injector 56 for those that have the desired trajectory towards a target location.
    [0049] [00049] As best shown by FIG. 8, the injector 56 - which in some embodiments comprises a flexible plastic tube that has shape memory - retains a slight curvature that is conferred on it by the curved introducer 62 during storage. In view of this curvature, and providing one or a plurality of openings along the side of the second end 60, the injector 56 is designed to be used in both a patient's left and right nostrils without regard to right - left capacity.
    [0050] [00050] In some embodiments, the diameter of one or a plurality of openings along the side of the second end 60 of the injector 56 is less than an outside diameter of the flexible plastic tube, so that the liquid expelled through the opening when pressing the syringe plunger is forced out. In some embodiments, depending on the flexibility of the plastic tube, the injector 56 undergoes an additional curvature under the pressure exerted by the depression of the syringe plunger (for example, in a direction away from that of the liquid coming out of the opening). In some embodiments, the diameter of one or a plurality of openings is less than an internal diameter of the flexible plastic tube. In some embodiments, the flexible plastic tube comprises a nylon resin (for example, such as that sold under the brand name PEBAX 72D). In some embodiments, the flexible plastic tube comprises PEBAX 72D, has an outer diameter □ of 0.99 0.025 mm (0.039 0.001), has a wall thickness of 0.12 0.025 mm (0.005 0.001 (that is, five thousandths of a one inch)), and has an opening with a diameter of 0.12 0.025 mm (0.005 0.001). In some embodiments, the opening is oriented at an angle of 50 ° in a direction oriented in the direction of the cube. In some embodiments, the introducer 62, the housing 70, the keyed slot 72, the lip 74, and the projection 78 are integrally formed (in some embodiments, as two complementary molded halves assembled by pressure and / or adhered together, such as, with adhesives, sonic welding or similar) and, in some modalities, these portions comprise polycarbonate. In some embodiments, hub 66 and stop bar 68 likewise comprise polycarbonate.
    [0051] [00051] A method for improving pain in a patient in accordance with the present teachings includes applying a drug superiorly and / or laterally and / or anteriorly towards a patient's sphenopalatine ganglion using a device as described herein. In some modalities, the drug is applied laterally and / or superiorly in the direction of the SPG. In other modalities, the medication is applied laterally, superiorly, and anteriorly in the direction of the SPG.
    [0052] [00052] In some embodiments a method for improving pain in a patient includes (a) introducing an injector 12 through a patient's nasal passage into a substantially medial and / or posterior region and / or less than a patient's GSP; and (b) applying a drug from the injector 12 superiorly and / or laterally and / or anteriorly in the direction of the SPG. In some modalities, the injector 12 is introduced through the patient's nasal passage in a substantially medial and / or inferior region for the GSP, while in other modalities the injector 12 is introduced in a substantially medial, inferior, and posterior region for the SPG. In some modalities, the medicine is applied laterally and / or anteriorly in the direction of the SPG, while in other modalities the medicine is applied laterally, superiorly, and anteriorly in the direction of the SPG. In some embodiments, the injector has a second end 30 that contains one or a plurality of openings 36 through which a drug is sprayed towards the SPG.
    [0053] [00053] In some embodiments, injector 12 is received sliding into an introducer 18, as described above, and the method further includes (c) coupling introducer 18 with a patient's nostril, so that a portion of the nose is raised when coupling with introducer 18; and (d) sliding the injector 12 from a storage position to a coupling position after the introducer 18 is coupled with the nostril. As described above, the coupling position of the injector 12 is located medial and / or posterior and / or inferior to the SPG - medial and / or inferior in some modalities, and medial, inferior, and posterior in other modalities. In some embodiments, the medication is provided in a container 14 connected with and in communication with the injector 12, as described above, and the method further includes (e) compressing the container 14 containing the medication in order to spray the medication in the direction of the GSP.
    [0054] [00054] In some embodiments, the method includes pushing the introducer 18 snugly and comfortably into one nostril to lift the tip of the patient's nose before positioning the nozzle 28 of the injector 12 in the vicinity of the SPG, sliding the tubular section 24 of the injector 12 through the passage 48 in the introducer 18 and / or slide the tubular section 24 of the injector 12 onto a rail 52 of the handle 20.
    [0055] [00055] All modes of medication suitable for introduction into or in the vicinity of the GSP are contemplated for use in accordance with the present teachings. The physical state of the drug includes, but is not limited to, liquids, solids, semi-solids, suspensions, powders, pastes, gels, and the like, and combinations thereof. In some embodiments, the drug is provided in at least partially liquid form. In some modalities, the drug contains an anesthetic. Anesthetics that can be used according to the modalities described herein include, but are not limited to ambucaine, amolanone, aminocaine, benoxinate, betoxicaine, biphenamine, bupivacaine, butacaine, butamben, butanilicicaine, butetamine, butoxycine, carticaine, cocaetylene , cyclomethacin, dibucaine, dimethisoquin, dimetocaine, diperodon, diclonin, ecgonidine, ecgonine, ethyl aminobenzoate, ethyl chloride, ethidocaine, □ -eucaine, euprocine, phenalcomine, fomocaine, hexylcaine, hydroxyprocaine, isohydrate, hydroxymethylacaine , levoxadrol, lidocaine, meperidine, mepivacaine, meprilcaine, metabutoxicain, methyl chloride, mirtecain, naepaine, octacaine, orthocaine, oxetazaine, paretoxicaine, phenacaine, phenol, a pipecoloxylide, piperocaine, propidocaine, pyridocaine, pridocaine, pridocaine, pridocaine, proparacaine, propipocaine, propoxicaine, pseudococaine, pyrrocaine, quinine urea, risocaine, ropivacaine, salicylic alcohol, tetracaine, tolicaine, trimecain, veratridine, zolamine, and the like, and their combinations, as well as all of their optics and / or stereoisomers, and all of their pharmaceutically acceptable salts.
    [0056] [00056] In some modalities, the drug comprises an anesthetic selected from the group consisting of benzocaine, tetracaine, ropivacaine, linodocaine, water, saline, and their combinations. In some embodiments, the drug comprises water and / or saline that has a temperature less than approximately 10 ° C and in other embodiments less than approximately 5 ° C. In some embodiments, the drug comprises water and / or saline that has a temperature of approximately 4 ° C. In some embodiments, the drug comprises water a combination of benzocaine, tetracaine, and ropivacaine. In some embodiments, the drug comprises an anesthetic comprising approximately 14% benzocaine, approximately 2% tetracaine, and approximately 1% ropivacaine by weight based on the total weight of the anesthetic.
    [0057] [00057] In some embodiments, a mixture of benzocaine, tetracaine, and ropivacaine is used to obtain a rapid onset of SPG block as well as to prolong the pain relief effects, thereby reducing the need for repeated applications and minimizing any potential dose-related complications and / or side effects. Benzocaine - which is very effective in topical use and has a toxic dose in addition to approximately 200 mg - has a start time of approximately 30 seconds and lasts between approximately 0.5 and approximately 1 hour. Benzocaine provides an almost immediate onset of pain relief and can increase the absorption of other local anesthetics when mixed with these. Ropivacaine - which has a toxic dose of approximately 175 mg - typically starts slowly but lasts between approximately 2 and approximately 6 hours. Ropivacaine provides an extended nerve block and lasting pain relief. Tetracaine is a very intense local anesthetic that has a rapid onset and lasts between approximately 0.5 and approximately 1 hour. When tetracaine is combined with ropivacaine, the duration of pain relief exceeds 6 hours.
    [0058] [00058] In some embodiments, the medication used according to the present teachings is provided in a container 14 (shown in Figures 1, 3, and 4) as a pressurized or aerosol mixture. The medication optionally contains preservatives, liquid transport, and / or other inert ingredients and additives as will be readily appreciated by those skilled in the art.
    [0059] [00059] The amount of medication applied in accordance with the present teachings can be readily determined by someone skilled in the art and will vary according to factors such as the nature and / or concentration of the medication, the age of the patient, the condition, and / or sensitivity to the drug, and the like. In some modalities, the dosage of anesthetic ranges from approximately 0.1 cm3 to approximately 1.0 cm3. In some modalities, the anesthetic dosage is approximately 0.5 cm3.
    [0060] [00060] The methods and devices described herein are contemplated for use in the treatment of all modes of conditions for which the introduction of a drug superiorly and / or laterally and / or previously in the direction of a patient's GSP is desirable. Representative conditions that can be treated include, but are not limited to, sphenopaladine neuralgia, trigeminal neuralgia including glossopharyngeal neuralgia, migraine with or without aura, tension headaches, cluster headaches including chronic cluster headaches, paroxysmal hemicranias, neuralgia superior laryngeal, atypical facial pain, ophthalmic herpes zoster, vasomotor rhinitis, major depression, fibromyalgia, and the like, and their combinations.
    [0061] [00061] Topical administrations of a drug in human tissue for the systemic application of a pharmaceutically active agent typically includes the use of transdermal and / or transmucosal pastes, creams, liquids, solids, semi-solids and the like. However, the systemic application of pharmaceutically active agents by topical administration is hindered by the difficulty of diffusing an agent through the tissue to which the agent is applied in order to reach the blood vessels, whereby the agent can then be absorbed for application systemic. Thus, to resolve this difficulty, the methods and devices described herein can be invoked to achieve increased permeability of the cerebral blood barrier in the administration of any medication.
    [0062] [00062] Conventional GSP blocking procedures have been used to treat a wide range of patient ailments, and the methods and devices described herein are contemplated for use in treating all of these. Representative ailments include, but are not limited to, the pain and / or discomfort associated with muscle spasm, vasospasm, neuralgia, reflex sympathetic dystrophy, chronic low back pain of multiple aetiology (eg, muscular, discogenic, arthritic, etc.), cricoidinia external, lower jaw tooth pain, glossodynia, ear pain (in the case of Eustachian tube) and middle ear injuries, secondary ear pain from laryngeal cancer, laryngeal tuberculosis pain, spasm of the face and upper respiratory tract, syphilitic headache, malarial headache, cluster headaches, ophthalmic migraine, dysmenorrhea, intercostal pain (neuralgia), gastric pain, nausea and diarrhea, myalgia of the neck muscles, sciatica, maxillary neuralgia, sensory facial neuralgia, toothache upper teeth, pain associated with tooth extraction, foreign body sensation in the throat, persistent itching in the external ear canal, herpes zoster optics, taste disorders, pain atypical facial, painful tic, cervical arthritis, myofascial syndrome, peripheral neuropathy, post-herpetic neuralgia, secondary osteoporosis fracture, lumbosacral tension, extremity arthritis, various other arthritic conditions, and the like, and combinations thereof. Additional indications for which the devices and methods described herein are contemplated include, but are not limited to, anger management, depression improvement, and the like.
    [0063] [00063] As used herein, the term "kit" refers to a set of materials that are used in the execution of a method in accordance with the present teachings. Such kits may include one or a plurality of devices and / or their components, including but not limited to the representative devices described above, and may further include one or more drugs to be used with them, including but not limited to one or a plurality of anesthetics described above.
    [0064] [00064] In some embodiments, a kit includes an injector and / or an introducer, each of which is configured for coupling with the patient's left nostril. In some embodiments, a kit includes an injector and / or an introducer, configured for coupling with a patient's right nostril. In some embodiments, a kit includes an injector and an introducer configured for coupling with a patient's left nostril, as well as an injector and an introducer configured for coupling with a patient's right nostril. Optionally, an interchangeable handle can also be provided for connection on either the right or left introducer. In other embodiments, the wrist itself exhibits a right-to-left capacity, and separate handles can be provided for each of the right introducer and the left introducer.
    [0065] [00065] In some embodiments, the device is provided in a fully assembled state, while in other embodiments the assembly of the device is required. In some embodiments, the device provided in the kit includes an application tube that has a curved portion at one end configured for insertion into a patient's nostril, where the application tube is housed within a substantially cylindrical housing (for example , in the form of a pen or cigar), such as the type described above. In some embodiments, one or a plurality of the components of the device is disposable and, optionally, biodegradable.
    [0066] [00066] The drug provided in a kit can contain a single reagent or a plurality of reagents. Representative drugs for use in accordance with the present teachings include, but are not limited to those described above. The drugs can be supplied in a combination packaged within them or in separate containers, depending on their cross-reactivity and stability, and in liquid or lyophilized form. The quantities and proportions of any reagents provided in the kit can be selected to provide optimal results for a specific application.
    [0067] [00067] The drugs included in the kits can be supplied in all modes of containers so that the activities of the different components are substantially preserved, while the components themselves are not substantially adsorbed or altered by the materials in the container. Suitable containers include, but are not limited to ampoules, bottles, test tubes, small bottles, vials, syringes, bags and envelopes (for example, film-coated), and the like. Containers can be formed from any suitable material including, but not limited to glass, organic polymers (eg, polycarbonate, polystyrene, polyethylene, etc.), ceramic, metal (eg aluminum), metal alloys (eg steel), cork, and the like. In addition, containers can contain one or more sterile access holes (for example, for access through a needle), just as it can be provided by a septum. Preferred materials for septa include rubber and polymers including, but not limited to, for example, polytetrafluoroethylene of the type sold under the brand name TEFLON by DuPont (Wilmington, DE). In addition, containers can contain two or more compartments separated by partitions or membranes that can be removed to allow mixing of components.
    [0068] [00068] Kits according to the present teachings can also be supplied with other items known in the art and / or which may be desirable from a commercial and user point of view, such as empty syringes, tubes, gauze, dressings , disinfectant solution, cleaning solutions, instructions for performing an SPG nerve block and / or for mounting, using, and / or cleaning the device, and the like, and combinations thereof.
    [0069] [00069] In some modalities, the instructions can be affixed to one or more components of the device and / or containers (for example, bottles), or in a larger container in which one or more components of the kit are packed for transport. The instructions can also be provided as a separate insert, called the packaging insert. Instructional materials provided with the kits can be printed (for example, on paper) and / or supplied in a readable electronic medium (for example, floppy disk, CD-ROM, DVD-ROM, zip disk, video tape, audio tape , etc.). Alternatively, instructions can be provided by directing a user to an Internet website (for example, specified by the kit manufacturer or distributor) and / or via electronic mail.
    [0070] [00070] The following examples illustrate the characteristics of the devices and methods described herein and are provided for illustration only. These are not intended to limit the scope of the attached claims and their equivalents. EXAMPLES 1-30
    [0071] [00071] The devices and / or methods described above have been applied in the treatment of 30 patients suffering from chronic headaches, such as migraine headaches and tension headaches. The results of these tests are surprising and unexpected. As an illustration, the methods described above resulted in a reduction of at least 90% in pain and 100% effective SPG block in patients. The onset of pain relief ranged from approximately 30 seconds to approximately 60 seconds with a duration of pain relief ranging from approximately 4 to approximately 24 hours. Each SPG block was performed using only 0.5 cm3 or less of an anesthetic mixture containing benzocaine, tetracaine, ropivacaine in the amounts described above. In at least 10 of the patients, the duration of pain relief achieved in accordance with the present teachings exceeded 24 hours. In total, extremely effective headache control was observed. Patients were able to return to work and avoid toxic pain medications almost 100% of the time.
    [0072] [00072] The devices and methods described here are applicable for most patients over the age of 15 in 95% of the population - regardless of the patient's height, weight, sex or race. Furthermore, although it is presently believed that the devices and methods described herein will be primarily used in the treatment of human patients, these devices and methods can also be applied in the treatment of all types of non-human patients. Any non-human patient who has a nostril (for example, other mammals such as primates, dogs, cats, pigs, horses, cows, and the like, as well as non-mammals) can likewise be treated (for example, by a veterinarian) according to the principles presented here.
    [0073] [00073] In summary, devices and methods for providing safer and more effective pain relief associated with headaches, facial pains, and the like, have been described. The devices and methods are economical and can be readily used on patients by trained medical professionals as well as by the patients themselves without the supervision of a medical specialist to provide a reliable and replicable drug application to a target location. In some embodiments, the devices and methods described herein can be self-employed by patients twice an hour or as needed.
    [0074] [00074] In use, the optional handle 20 of the devices 10 described here can be pushed towards the patient's face until the introducer 18 engages comfortably and comfortably engages and adjusts into the patient's nostril to lift the flat tip of the patient's nose to aim superiorly and slightly later. Thereafter, the injector 12 can be pushed further towards the patient's nose to slide the tubular section 24 and the nozzle 28 back until the nozzle 28 is located medially and / or posteriorly and / or inferiorly to the SPG -medially and / or inferiorly in some modalities, and medially, inferiorly, and later in other modalities. After that, a drug such as an anesthetic can be injected and sprayed through openings 36 of the mouthpiece 28 upwards and / or laterally and / or anteriorly in the direction and around the SPG to improve the pain - laterally and / or upwards in some modalities, and laterally, upwards, and previously in other modalities. When an appropriate anesthetic is sprayed over the GSP, a rapid and prolonged vasoconstriction of the blood vessels in the ipsilateral head or brain can be achieved resulting in effective pain management later.
    [0075] [00075] The above detailed description and accompanying drawings have been provided as an explanation and illustration, and are not intended to limit the scope of the attached claims. Many variations in the presently preferred modalities illustrated herein will be apparent to someone skilled in the art and remain within the scope of the appended claims and their equivalents.
    权利要求:
    Claims (10)
    [0001]
    Device (54) for delivering a drug to a patient in need of it comprising: an injector (56) comprising a first end (58) configured to remain outside a patient's nasal passage and a second end (60) configured to enter the patient's nasal passage; and a curved introducer (62) configured for coupling with a patient's nostril, wherein the introducer comprises a passageway (64) configured to receive the injector slidingly, and wherein the curved introducer (62) comprises a curvature along an adjacent and surrounding portion thereof, corresponding to, and providing curvature of, a distal length of the passage, where the injector is movable, relative to the introducer, between a position storage and a hitch position; characterized by a housing (70) of the introducer, in which a first end of the housing is configured to remain outside a nasal passage of the patient and in which a second end of the housing comprises the curvature portion of the introducer, and the passage slidingly receiving a syringe into the introducer.
    [0002]
    Device (54), as defined in claim 1, characterized by the fact that the injector comprises a flexible tube configured to adopt at least a portion of the passage curvature.
    [0003]
    Device (54) according to claim 2, characterized in that the injector comprises one or a plurality of openings along one side of the flexible tube adjacent to the second end.
    [0004]
    Device (54) according to claim 1, characterized in that the hub is configured to remain outside the housing prior to connection to the syringe and is configured to enter the housing substantially, irreversibly, when pushed in an axial direction in the direction introducer.
    [0005]
    Device (54) according to claim 1, characterized by the fact that the hub comprises a luer lock.
    [0006]
    Device (54) according to claim 1, characterized in that the hub comprises a stop bar (68) and the housing comprises a keyed slot (72) configured to receive the stop bar.
    [0007]
    Device (54) according to claim 6, characterized in that the housing still comprises a lip (74) configured to prevent the cube from retracting from an interior of the housing.
    [0008]
    Device (54) according to claim 4, characterized in that the hub is configured to rotate between a predetermined range of angles when positioned substantially inside the housing but is substantially prevented from rotating when positioned substantially outside the housing.
    [0009]
    Device (54) according to claim 8, characterized in that the predetermined range of angles over which the cube is configured to rotate, comprises approximately a 45 degree clockwise rotation and approximately a counterclockwise rotation 45 degrees.
    [0010]
    Device (54) according to claim 8, characterized in that the hub comprises a stop bar and in which the housing comprises a projection configured to bump against the stop bar on the first and second opposite sides thereof.
    类似技术:
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    同族专利:
    公开号 | 公开日
    PL2640450T3|2016-04-29|
    US8905980B2|2014-12-09|
    AU2011329425B2|2016-04-28|
    TW201219075A|2012-05-16|
    US9597486B2|2017-03-21|
    JP5813125B2|2015-11-17|
    CA2815513C|2015-06-30|
    MY165993A|2018-05-21|
    US20110152838A1|2011-06-23|
    JP2013543772A|2013-12-09|
    TWI478741B|2015-04-01|
    BR112013011591A2|2017-08-01|
    EP2640450A4|2014-08-20|
    KR20130127455A|2013-11-22|
    KR101755070B1|2017-07-06|
    CR20130201A|2013-06-13|
    RU2589645C2|2016-07-10|
    MX2013005399A|2013-08-01|
    EP2640450B1|2015-12-09|
    EP2640450A1|2013-09-25|
    CN103298511A|2013-09-11|
    CA2815513A1|2012-05-24|
    US20150045775A1|2015-02-12|
    AU2011329425A1|2013-05-23|
    NZ609747A|2014-11-28|
    HK1189522A1|2014-06-13|
    SG190283A1|2013-06-28|
    RU2013127129A|2014-12-27|
    WO2012067787A1|2012-05-24|
    CN103298511B|2016-01-27|
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    法律状态:
    2018-12-18| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|
    2019-09-03| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|
    2020-05-12| B06A| Notification to applicant to reply to the report for non-patentability or inadequacy of the application [chapter 6.1 patent gazette]|
    2020-09-15| B09A| Decision: intention to grant [chapter 9.1 patent gazette]|
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    US12/946,576|US8905980B2|2008-08-01|2010-11-15|Devices for delivering a medicament and methods for ameliorating pain|
    US12/946,576|2010-11-15|
    PCT/US2011/058238|WO2012067787A1|2010-11-15|2011-10-28|Devices for delivering a medicament and methods for ameliorating pain|
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