photodiagnostic device for detecting differences between healthy and abnormal cervical tissue, photo

专利摘要:
photodiagnostic device for detecting differences between healthy and abnormal cervical tissue, photodynamic treatment device and photodiagnostic, method for detecting autofluorescence of abnormal cervical tissue, and method for diagnosing and treating cervical tissue are provided apparatus, method, computing devices, and programs for computer-related photodiagnosis and photodynamic therapy, methods of using them, and a method for detecting abnormal tissue.
公开号:BR112015002459A2
申请号:R112015002459
申请日:2013-08-02
公开日:2019-12-17
发明作者:De Moraes Mendonça Fernando；Roberto Trujillo Jose
申请人:Cerca Solutions Llc；Mm Optics Ltda；
IPC主号:

专利说明:

BACKGROUND OF THE INVENTION
Field of the Invention [001] The present invention relates to photodiagnosis and photodynamic treatment.
Fundamentals of the Technique [002] Genital human papillomavirus (HPV) is the most common sexually transmitted infection (HPVI) in the United States. More than 40 types of HPV can infect the genital areas of men and women, including the skin of the penis, vulva (external area of the vagina), and anus, and the linings of the vagina, cervix and rectum. These types can also infect the lining of the mouth and throat. HPV types are often referred to as low risk '(wart causing) or high risk' (causing cancer), based on whether they put a person at risk for cancer. The International Agency for Research on Cancer noted that 13 types of HPV can cause cancer of the cervix; one of these types can cause cancers of the vulva, vagina, penis, anus and certain cancers of the head and neck. The types of HPV that can cause genital warts are not the same as the types that can cause cancer. Centers for Disease Control, http://www.cdc.gov/cancer/hpv/basic_info.
[003] Certain types of HPV are highly associated with cervical dysplasia and cervical cancer and are considered to be causative. Walboomers et ah, J, Pathology 189: 12-19 (1999). Annually, hundreds of thousands of women around the world die from cervical cancer, a condition that
2/48 affects millions of women, especially those who are economically disadvantaged. The diagnosis and treatment of cervical HPVI and cervical dysplasia in its early stages will decrease the incidence of cervical cancer, thereby reducing its associated morbidity and mortality.
[004] The current standard for diagnosis is the pathological examination of cervical tissue samples, for example, the Pap smear or Pap smear and biopsy with the help of colonoscopy. However, these diagnostic methods require a delay between the time when a tissue sample is taken and the time when the test results are known. They also require at least one return visit for treatment. In addition, in disadvantaged populations, these diagnostic methods are simply not available. When and where they are available, biopsies can present patient complications including local inflammation, pain, infection and / or bleeding. Furthermore, the accuracy of the pathological examination is dependent on the training and experience of the pathologist and doctor. Furthermore, HPVI and cervical dysplasia can affect multiple sites in the exocervix and endocervix. Thus, a common problem in the diagnosis and treatment of cervical dysplasia and cancer is the failure to detect and treat all existing injuries.
[005] There are several modalities for the treatment of cervical dysplasia and cancer, most of which involve varying degrees of surgical interventions such as Co2 laser vaporization, cryotherapy, electrocauterization, or local excision. Surgical removal of visible lesions is the most common modality and can result in patient complications. In addition, an inability to identify all existing lesions allows HPVI and / or undetected dysplasia to progress to terminal cervical cancer. If cervical dysplasia progresses to cervical cancer, more prolonged surgical procedures are used, typically a hysterectomy and removal of lymph nodes. The entire diseased organ must be removed to ensure that
3/48 all microscopic disease is treated. Since the percentage of these injuries that will progress to a frankly malignant state is unknown and may be a minority of cases, indiscriminate destruction or surgical removal of the entire organ is, in fact, radical and excessive treatment. For survivors of cervical cancer, persistent local injuries, anatomical deformities secondary to surgical interventions, emotional and mental scarring, and other treatment sequelae increase public health costs. This burden is especially heavy in emerging economies.
[006] A device is needed for an accurate, non-invasive, fast and low-cost method to diagnose and treat HPVI, cervical dysplasia, cervical pre-cancer and cervical cancer.
BRIEF SUMMARY OF THE INVENTION [007] Devices are provided here that generally include a photodiagnostic component, and / or a photodynamic treatment component and / or a control component. Such devices achieve numerous goals. For example, these devices allow identification and / or treatment of abnormal tissue in the cervix.
[008] In view of this, a photodiagnostic device is described here that is generally designed to include a laser light source, a heat dissipation system, a lens to collimate light from the light source, an optics with a path of light, a light filter attached to the light path to direct light from the lens to one end of the light path towards the cervical tissue, and a light filter attached to the light path adapted to separate a spectral region of light from a fluorescence of light reflected by the cervical tissue.
[009] In another embodiment, a photodynamic treatment device is described here that is generally designed to include a light source, a heat dissipation system, a light guide attached to the device cover and adapted for vaginal insertion for direct light to the fabric
4/48 cervical, and a light shield that is attached to a distal end of the light guide adapted to wrap the cervical tissue.
[0010] In another embodiment, a therapeutic photodiagnostic and photodynamic device is described here that is generally designed to include a photodiagnostic component including a laser light source, a lens, and a light filter, a photodynamic treatment component including a second light source and a light guide, and a control component attached to the photodiagnosis component and the photodynamic treatment component, and providing power to these, and controlling activation of the laser light source and the second light source.
[0011] In another exemplary embodiment, a method of detecting abnormal cervical tissue autofluorescence is described here, which generally includes generating excitation light from a laser light source, directing the excitation light to the cervical tissue, receiving excitation light reflected and fluorescent light from the cervical tissue and pass the reflected light and the fluorescent light through a light filter to separate the reflected light from the fluorescent light, and see the fluorescent light from abnormal cervical tissue.
[0012] In another exemplary embodiment, a method of treating cervical tissue with a photosensitizing compound disposed in it is described here, which in general includes selecting an appropriate dose of light energy, generating an emission of light by the light source, and directing the emission of light through a light guide to the cervical tissue for a selected period of time to distribute the selected dose of light energy.
[0013] In another exemplary embodiment, a method of diagnosing and treating abnormal cervical tissue is described here, which generally includes: analyzing cervical tissue generating a laser light emission, directing the light emission to the cervical tissue, passing the emission of light through a light filter, and see the fluorescence of the cervical tissue to detect the presence of abnormal cervical tissue; and treat abnormal cervical tissue with a
5/48 photosensitizing compound disposed in it generating a second light emission and directing the second light emission through the cervical tissue to distribute a selected dose of light energy to destroy the abnormal cervical tissue.
BRIEF DESCRIPTION OF THE DRAWINGS / FIGURES [0014] FIG. 1 is a perspective view of a therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0015] FIG. 2 is a top view of a therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0016] FIG. 3 is a perspective view of a photodiagnostic component of the therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0017] FIG. 4 is a sectional view of a photodiagnostic component of the therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0018] FIG. 5 is a perspective view of one of a photodiagnostic component of the therapeutic photodiagnostic and photodynamic device, according to an alternative aspect of the description.
[0019] FIG. 6 is a perspective view of a photodynamic treatment component of the photodynamic and photodynamic therapeutic device, according to an exemplary aspect of the invention.
[0020] FIG. 7 is a sectional view of a portion of a photodynamic treatment component of the therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0021] FIG. 8 is a perspective view of a portion of a photodynamic treatment component of the therapeutic
6/48 photodiagnosis and photodynamics, according to an exemplary aspect of the invention.
[0022] FIG. 9 is a sectional view of a portion of a photodynamic treatment component of the photodynamic and photodynamic therapeutic device, according to an exemplary aspect of the invention.
[0023] FIG. 10 is a perspective view of a photodiagnostic and photodynamic therapeutic device, according to an exemplary aspect of the invention.
[0024] FIG. 11 is a perspective view of a therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0025] FIG. 12 is a front view of a support for a photodynamic treatment component of a therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0026] FIG. 13 is an image representing tissue autofluorescence shown by a photodynamic treatment component of the therapeutic photodiagnostic and photodynamic device, in accordance with an exemplary aspect of the invention.
[0027] FIG. 14 is an image depicting tissue fluorescence shown by a photodynamic treatment component of the therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0028] FIG. 15 is an image representing tissue fluorescence shown by a photodynamic treatment component of the therapeutic photodiagnostic and photodynamic device, in accordance with an exemplary aspect of the invention.
[0029] FIG. 16 represents a user interface, according to
7/48 an exemplary aspect of the invention.
[0030] FIG. 17 represents a user interface, according to an exemplary aspect of the invention.
[0031] FIG. 18 represents a user interface, according to an exemplary aspect of the invention.
[0032] FIG. 19 represents a user interface, according to an exemplary aspect of the invention.
[0033] FIG. 20 represents a user interface, according to an exemplary aspect of the invention.
[0034] FIG. 21 represents a user interface, according to an exemplary aspect of the invention.
[0035] FIG. 22 represents a user interface, according to an exemplary aspect of the invention.
[0036] FIG. 23 represents a user interface, according to an exemplary aspect of the invention.
[0037] FIG. 24 represents a user interface, according to an exemplary aspect of the invention.
[0038] FIG. 25 represents a user interface, according to an exemplary aspect of the invention.
[0039] FIG. 26 represents a user interface, according to an exemplary aspect of the invention.
[0040] FIG. 27 represents an exemplary computer system in which embodiments of the present invention can be implemented.
[0041] FIG. 28 is a front view of a therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0042] FIG. 29 is a top view of a therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
8/48 [0043] FIG. 30 is a rear view of a control component of the therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0044] FIG. 31 is a side view of a therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0045] FIG. 32 is a side view of a photodynamic treatment component of the photodynamic and photodynamic therapeutic device, according to an exemplary aspect of the invention.
[0046] FIG. 33 is a side sectional view of a photodynamic treatment component of the photodynamic and photodynamic therapeutic device, according to an exemplary aspect of the invention.
[0047] FIG. 34 is a sectional front view of a portion of a photodynamic treatment component of the therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0048] FIG. 35 is a bottom view of a portion of a photodynamic treatment component of the therapeutic photodiagnostic and photodynamic device, according to an exemplary aspect of the invention.
[0049] List of Parts:
10-therapeutic photodiagnostic and photodynamic device 200-diagnostic component 202-power button
204-optics
204a-end of the optics 204b-end of the optics 210-optical support 212-anti-reflective filter
214-dichroic filter
9/48
216-notch filter
218-high pass filter
220-ring
222-finishing ring
230-collimating lens
232-laser diode
234-focus adjustment ring
236-heat dissipation system
240-circuit board
242-circuit board
250-shell diagnostic component
252-wire connecting the diagnostic component
260-photo camera
262-ring adapter
300-treatment component
304-light component
306-wire connecting the treatment component
310-guide sleeve nozzle
320-core metal plate
322 high-intensity LEDs
324-spacing ring
326-insulating ring
330-protective screen
334-ring heat sink
336-heatsink
350-shell treatment component
352-end cap
370-guide sleeve
372-light protector
10/48
372a-light protector
372b-light protector
374-glass screen
376-rubber rings
378-protective glove
380-light guide
400-component control
402-power output
404-switch on and off
406-security key mechanism
408-control panel
410-display screen
412-button operation
414-button operation
416a-operation button
416b-operation button
420-diagnostic component support
430-treatment component support
450-hull control component
500-adjustable bracket
510-coupling
520-folding leg
530-flexible rod
540-telescopic tube
540a-adjustment lock
542-telescopic tube
542a-adjustment lock
544-telescopic tube
600-computer system
11/48
602-display interface
604-processor
606-communication infrastructure
608-main memory
610-secondary memory
612-hard drive
614-removable storage unit
618-removable storage unit
620-interface
622-removable storage unit
624-network interface
626-communications path
628-signs
1010-photodiagnostic and photodynamic therapy
1200-component diagnostics
1252-wire connecting the diagnostic component
1300-treatment component
1304-light component
1306-treatment component power connection wire
1310-guide sleeve nozzle
1320-sheet metal core
1322-high intensity LEDs
1324-spacing ring
1326-insulating ring
1330-protective screen
1334-ring heat sink
1336-heatsink
1350-shell treatment component
1352-end cap
12/48
1400-control component
1402-power output
1404-on and off switch
1408-control panel
1410-display screen
1412-button operation
1414-button operation
1416a-operation button
1416b-operation button
1418-cable holder
1420-diagnostic component support
1422-locking
1430-treatment component support
1450-shell control component
1460a-two-way connector
1460b-four-way connector
1500-adjustable bracket
1502a-cable holder
1502b- cable holder
1504a-control component support
1504b-control component support
1510-coupling
1520a-adjustment lock
1530-flexible rod
1542-telescopic element
1542a-adjustment lock
1600-mobile base
1602-wheels
1620-feet
13/48
DETAILED DESCRIPTION OF THE INVENTION [0050] The present invention relates to the detection, diagnosis and treatment of abnormal tissue of the cervix. In one aspect, this invention uses non-invasive photodynamic methods to differentiate healthy tissue from abnormal tissue using photodiagnosis. In one aspect, this invention uses a similar photodynamic method to provide photodynamic treatment (PDT) for the abnormal tissue. In some aspects, the invention is a device that includes a diagnostic component. The diagnostic component is specially adapted to detect abnormal tissue in the cervix. In some aspects, the invention is a device that includes a treatment component. The treatment component is specially adapted for treating abnormal cervical tissue. In some respects, the invention is a device that includes both a diagnostic component and a treatment component. In some aspects, a device of the invention includes a control component including a control panel for operating the diagnostic component and / or the treatment component. In some respects, the invention is methods of diagnosis and / or treatment using a device described herein. In some respects, the invention is a method of providing photodiagnosis of cervical tissue by detecting tissue autofluorescence, tissue fluorescence after application of a photosensitizing compound and / or tissue fluorescence after photodynamic treatment. In some respects, the invention is a method of providing photodiagnosis of cervical tissue before and after the photodynamic treatment of cervical tissue. In some respects, the invention is a method of treating abnormal tissue in the cervix.
[0051] Based on preliminary clinical evaluations, the present diagnostic component allows, for the first time, the identification and diagnosis of abnormal tissue without the use of a photosensitizer (PS). In addition, the treatment component has been successfully used to treat
14/48 twenty-three patients with pre-cancer or cervical cancer. In addition, based on preliminary assessments, it is expected that the treatment component can treat abnormal tissue such as pre-cancer and cancer up to 1 cm deep, and possibly deeper, in and near the cervix. See also Example 4.
[0052] As discussed here, abnormal tissue should refer to tissue with abnormal cell growth or other detectable abnormalities resulting, for example, from infections with microorganisms such as HPV, or from a precancerous state, a cancerous state, or other hyperproliferative states. Abnormal tissue includes cervical intraepithelial neoplasia (CIN), cervical intraepithelial lysis (s) (SIL), cervical cancer (cervical squamous cell carcinoma and cervical adenocarcinoma) and other hyperproliferative tissue.
[0053] The present invention relates to a diagnostic component to illuminate the cervix with a light source to detect differences between healthy and abnormal tissue. The diagnostic component detects fluorescence indicating abnormal tissue, for example, with abnormal cell growth. The structure and biochemical composition of tissue affects its interaction with light, in such a way that healthy tissue has distinctive optical characteristics from those seen in abnormal tissue. Conditions such as infection, cervical dysplasia and cancer change the composition of the affected cells, which, in turn, change their interaction with light. Optical methods for diagnosing tissue abnormalities have a substantial advantage of being non-invasive and as minimal, if any, side effects. Furthermore, the present invention allows for immediate diagnosis, unlike currently available diagnostic methods using such as the Pap smear.
[0054] The diagnostic component is specially adapted for the cervix and includes a light source, such as a low laser diode
15/48 intensity. In some aspects of the invention, the light source generates light at a defined wavelength and defined intensity. As discussed here, the low intensity laser diode is capable of producing a light intensity ranging from approximately 0 mW / cm ² to approximately 100 mW / cm ² . In addition, the low-intensity laser diode is capable of producing a light intensity ranging from approximately 15 mW / cm ² to approximately 24 mW / cm ² . In some aspects of the invention, the diagnostic component includes a heat dissipation system for regulating the temperature of the light source.
[0055] In some aspects, the diagnostic component may include an optic with a light path, and one or more lenses and / or one or more filters and / or one or more mirrors attached to the light path. In some respects, the diagnostic component may include a collimating lens to collect and collimate the generated light. In some ways, the diagnostic component may include a dichroic filter or mirror to direct light into the cervical tissue. In some respects, the diagnostic component may include a second filter to separate a spectral region of light from fluorescence from light reflected by the cervical tissue to better analyze the light returning from the cervical tissue. The diagnostic component can generate a beam of light approximately 20 mm in diameter.
[0056] In some respects, the present invention is a component for treating abnormal tissue in or near the cervix. The treatment component illuminates an area for treating abnormal tissue using photodynamic therapy. In photodynamic therapy, photosensitizers (PS) are used in combination with light irradiation at specific wavelengths to induce oxidative damage in abnormal, for example, hyperproliferative tissues. These abnormal tissues, for example, hyperproliferative, are considered to selectively retain PS and that subsequently induced oxidative damage is located in the areas of PS accumulation.
16/48 [0057] Numerous types of PS have been evaluated and shown to be at least partially effective for photodynamic therapy. Known PS photodynamic therapy includes psoralens, porphyrins, chlorins, bacterioclorins, feoforbide, bacteriofeoforbide and phthalocyanins, as well as precursors to protoporphyrin IX (PpIX) such as 5-aminolevulinic acid (ALA), methyl aminolevulinic acid (MAL), and hexyl aminolinic acid (MAL) HAL), which are converted intracellularly to PpIX. PS compounds are generally administered in a vehicle such as a cream or gel. PS compounds and their vehicles are further described below.
[0058] The treatment component is specially adapted for the cervix and includes a light source, such as a high intensity light-emitting diode (LED) light source, and a light guide for transmitting light to the area defined. In one aspect of the invention, the defined area is approximately 20 mm in diameter. In addition, the treatment component may include a protective glove surrounding the light guide to allow vaginal insertion, and a ring between the light guide and a protective glove to center the protective glove on the light guide and provide a biological barrier between the cervical tissue and the light source.
[0059] As used here, the high intensity LED is an LED array that is capable of producing a light intensity ranging from approximately 0 mW / cm ² to approximately 250 mW / cm ² . In addition, the high intensity LED is capable of producing a light intensity ranging from approximately 40 mW / cm ² to approximately 120 mW / cm ² . In one aspect of the invention, this range of light intensity is established to adapt the energy to the protocols of the specific doctor. In one aspect of the invention, the treatment component includes a heat dissipation system attached to the light source to regulate the temperature of the light source.
[0060] Before treatment, a PS compound is applied to the tissue
17/48 abnormal so that, through illumination by the treatment component, the abnormal cells and tissue are destroyed. As is well known in the art, different PS compounds require light of different wavelengths for photodynamic therapy. After application to the patient's affected area, the photosensitizer naturally penetrates the affected area for a period of approximately 8 to approximately 30 minutes. As is well known in the art, different PS and vehicles will require different values of time to penetrate, and the ideal penetration time can be easily determined. For example, the PS compound can also naturally penetrate the affected area for a period of approximately 60 to approximately 180 minutes. In an alternative aspect of the invention, the PS compound can naturally penetrate the affected area for a period of approximately 8 to approximately 180 minutes.
[0061] In some aspects of the invention, the treatment component includes a light source for generating light at a defined wavelength and a defined intensity for treating abnormal cervical tissue containing a PS. In some aspects of the invention, the treatment component may include a light guide to direct light to the abnormal cervical tissue and a light shield to envelop the cervical tissue and protect anatomical structures close to the generated light. In some aspects of the invention, the light shield can also conform to anatomical variations of the cervix in different patients.
[0062] In some aspects of the invention, after treatment, the diagnostic component can be used to verify the effectiveness of the treatment. In some aspects of the invention, the PS compound can also be reapplied to verify that all abnormal tissues have been destroyed. In some aspects of the invention, residual abnormal tissue can be portrayed with additional photodynamic treatments, for example, for a total of 2, 3, 4, 5, 6, 7, 8, 9 or 10 treatments.
In some aspects of the invention, the diagnostic component and / or treatment component can be portable. In some ways, the diagnostic component is self-contained. In some ways, the diagnostic component is part of a larger device. In some ways, the treatment component is self-contained. In some ways, the treatment component is part of a larger device. In some respects, a device including both a diagnostic component and a treatment component also includes a control component. In some aspects of the invention, a device includes both a diagnostic component and a treatment component. In some respects, a device that includes both a diagnostic component and a treatment component also includes a control component. In some aspects, a device including a diagnostic component and / or a treatment component can be portable.
[0064] In some respects, the present invention is a device that includes a diagnostic component and / or a treatment component. In some ways, the device also includes a control component. In some aspects, the control component provides power to the diagnostic component and / or the treatment component. In some respects, the control component includes a control panel that operates the diagnostic component and / or the treatment component. In some respects, the control panel may include a display screen and input buttons that control the activation of the diagnostic component and / or the treatment component. In some respects, the control panel may also allow the selection of a particular light intensity and duration of light intensity for the diagnostic component and / or the treatment component. In some aspects of the invention, the control panel may allow selection of a particular wavelength of light for the diagnostic component and / or the treatment component.
19/48 [0065] It is well known in the art that each photosensitizer is activated by a specific wavelength of light. See, for example, US 6,645,230 B2. Therefore, the use of different photosensitizers may require the use of different LEDs in the treatment component to produce the desired wavelength. The photosensitizer is mixed in a suitable vehicle, such as cream or gel, for application to the abnormal tissue in the cervical area. The vehicle can include DMSO and EDTA to improve effectiveness. Several PS creams and gels are commercially available. An example that contains MAL is METVIX (Galderma). The percentage or dose of sensitizing compound is easily determined based on knowledge in the art. For example, ALA and MAL are commonly used at a concentration of 20%. Photosensitizers can be used alone or in combination, for example, a mixture of ALA and MAL in a range of ratios from approximately 0% ALA and approximately 100% MAL to approximately 100% ALA and 0% MAL.
[0066] Metatetra (hydroxyphenyl) chlorine (m-THPC) is a proven photosensitizer effective in cancer PDT, especially for squamous cell carcinoma of the head and advanced cervix. Some other porphyrins commonly used for photodynamic therapy are hematoporphyrin IX (HpIX) and hematoporphyrin derivative (HpD). US 4,992,257 and US 5,162,519 describe the use of selected di-idroporphyrins and tetrahydroporphyrins, including m-THPC, to induce necrosis (tissue death) in tumors. US 5,399,583 describes a limited group of hydromonobenzo porphyrins, or green porphyrins, which are photoactive at relatively long wavelengths considered to penetrate deeply into body tissues that may allow the use of lower doses of green porphyrins in PDT. Additional photosensitizers are also known. For example, US 5,458,595, US 5,773,609, US 6,645,230, US 7,351,242 and Allison, et ah, Fotensensitizers in clinical PDT, Fotodiagn. Fotodyn. The R. 1: 27-42 (2004).
20/48 [0067] Pictures of current clinically applied sensitizers are provided in Table 2 by Agostinis, et al., Photodynamic Therapy of Cancer: An Update, CA Cancer J Clin, 61: 250-281 (2011). Sensitizer photo information and corresponding wavelength from Table 2 is provided below.
Photosensitizer Wavelength, nm Porfimer sodium (Photofrine) (HPD) 630 ALLAH 635 ALA esters 635 Temoporfin (Foscan) (MTHPC) 652 Veteporfin 690 HPPH 665 SnEt2 (Purlitine) 660 Talaporfin (I, S11, MAGE, NPe6) 660 Ce6-PVP (Fotolon), Ce6 derivatives (Radachlorine, Photoditazine) 660 Silicon phthalocyanine (Pc4) 675 Padoporfma (TOOKAD) 762 Lutexium Motexafina (Lutex) 732
[0068] As previously mentioned, those skilled in the art know how to match the wavelength of light with each different PS compound. For example, the ideal wavelength range for PpIX, ALA, MAL and HAL is 615 nm at 635 nm and the ideal range for hydromonobenzoporphyrins described in 5,399,583 is 670 nm at 780 nm. Di-idroporphyrins and tetrahydro porphyrins described in US 4,992,257 and US 5,162,519 require a wavelength from 652 nm to 653 nm.
[0069] In some aspects of the invention, a patient is treated for cervical dysplasia and / or potential cervical cancer by first analyzing the cervical tissue with a photodiagnostic device. If abnormal tissue is detected, a PS is applied to the cervical tissue. The PS naturally penetrates the cervical tissue for 60-180 minutes before applying the photodynamic treatment. Optionally, a photodiagnostic device can be used to verify that the PS is selectively used by the abnormal tissue and to confirm the readiness of the cervical tissue for treatment. A selected dose of light energy is then administered to the cervical tissue to destroy the abnormal tissue. The selected dose of light energy can be
21/48 specified range of light intensities and treatment times, from approximately 0 mW / cm ² to approximately 250 mW / cm ² , and approximately one minute to approximately 90 minutes. Alternatively, a fixed dose of light energy can be selected from several pre-programmed options that provide varying combinations of light intensity and treatment time. After the photodynamic treatment, the photodiagnostic device can be used again to verify the effectiveness of the photodynamic treatment in destroying the abnormal tissue.
[0070] The following detailed description of a photodiagnostic and photodynamic therapeutic device refers to the attached figures that illustrate exemplary modalities. Other modalities are possible. Modifications can be made in the modalities described herein without departing from the spirit and scope of the present invention. Therefore, the following detailed description should not be limiting.
[0071] Referring now to FIGS. 1-2, therapeutic photodiagnostic and photodynamic device 10 is an exemplary aspect of the present invention. Device 10 includes a diagnostic component 200 for optical injury detection, a treatment component 300 for injury treatment, and a control component 400 for controlling diagnostic component 200 and treatment component 300.
[0072] As shown in FIGS. 3-5, the diagnostic component 200 includes a series of lenses and filters to allow a medical professional to detect abnormal cells and lesions. The diagnostic component 200 is capable of detecting autofluorescence of lesions and abnormal tissue. As a result, the diagnostic component 200 can be used for detecting and diagnosing abnormal tissue without first having to apply a photosensitive or photosensitizing compound. Diagnostic component 200 is contained in shell 250 and power is supplied to the system via power connection wire 252. Diagnostic component 200 generates an emission
22/48 of light and uses an optical filter system that allows the separation of a spectral region of interest from the fluorescence of the analyzed tissues.
[0073] The lenses and filters are contained in optics 204 and shell 250 of diagnostic component 200. Optics 204 is designed to allow the medical professional to look through the finishing ring 222 at the end of the optics 204a while still returning the end of the optics 204b towards the patient's affected area. Optical support 210 is a cylindrical cavity and provides a support base for attaching an anti-reflective filter 212, a dichroic filter 214, a notch filter 216 and a high-pass filter 218. Optics 204 also includes a ring 220 to provide a base for finishing ring 222 or adapter ring 262. Ring 220 can be attached to finishing ring 222 or adapter ring 262 by means of a threaded fitting, an interference fitting, or other suitable attachment. Finishing ring 222 provides a window for a medical professional through which he sees tissue fluorescence with the naked eye. Alternatively, camera 260 can be used to view and record tissue fluorescence. Camera 260 is attached to the diagnostic component 200 using adapter ring 262. Camera 260 is attached to adapter ring 262 by means of a threaded fitting, an interference fit, or other suitable attachment.
[0074] The light for detecting and diagnosing abnormal tissue is generated by laser diode 232. Laser diode 232 provides a parallel beam of sufficient excitation light to access a patient's cervical tissue through the vagina. In addition, laser-induced tissue fluorescence is cleaner than other light sources, allowing the diagnostic component 200 to detect tissue autofluorescence without having to first apply a photosensitizer to the tissue. The laser diode 232 provides a single wavelength, which allows for better selectivity when viewing abnormal tissue fluorescence and when viewing porphyrin formation.
23/48
In one aspect of the invention, diagnostic component 200 uses a single laser diode 232 that emits light over a single wavelength. In an alternative aspect of the invention, the diagnostic component 200 may include additional laser diodes to generate and provide additional light wavelengths.
[0075] The collimating lens 230 collects the light generated by the laser diode 232 and collimates the light beam, generating uniformity and defining the dimension of the illumination. In one aspect of the invention, the collimating lens 230 is a single lens. In an alternative aspect of the invention, the collimating lens 230 includes a system of two telescopic lenses to collect the light generated by the laser diode 232. In an alternative aspect of the invention, the collimating lens 230 can include additional lenses to define a dimension and size of appropriate lighting.
[0076] The focus adjustment ring 234 can be low intensity and allows an emission of light at a wavelength ranging from approximately 400 nm to approximately 450 nm. In alternative aspects of the invention, the photodiagnostic component 200 can provide light emission at a wavelength ranging from approximately 400 nm to approximately 420 nm; approximately 400 nm to approximately 415 nm; approximately 405 nm to approximately 415 nm; for example, 405 nm, 410 nm, 415 nm, 420 nm, 425 nm, 430 nm, 435 nm, 440 nm, 445 nm, or 450 nm. In an alternative aspect of the invention, the photodiagnostic component 200 can provide a light emission at a wavelength of approximately 418 nm. As previously discussed, one or more additional laser diodes can be provided to generate one or more additional light emitting wavelengths. In one aspect of the invention, the diagnostic component 200 generates a fixed light intensity. In an alternative aspect of the invention, the diagnostic component 200 can generate a continuous variation of
24/48 light intensities ranging from approximately 0 mW / cm ² to approximately 100 mW / cm ² , based on the operating range of the laser diode 232. In an alternative aspect of the invention, the diagnostic component 200 generates a continuous variation of intensities of light ranging from approximately 15 mW / cm ² to approximately 24 mW / cm ² . Particular light intensities for diagnostic component 200 can also be pre-programmed in control panel 408. For example, a user can select a light intensity from approximately 10 mW / cm ² to approximately 30 mW / cm ² , for example, approximately 15 mW / cm ² , approximately 20 mW / cm ² , approximately 25 mW / cm ² , or approximately 30 mW / cm ² . Variation in light intensity of diagnostic component 200 allows the medical professional to see the details of the analyzed tissue better. The ability to vary the light intensity also allows the medical professional to take into account the varying shades of the cervix that exist between different patients and effectively allows the medical professional to control the contrast of the tissue fluorescence image seen through the diagnostic component 200 .
[0077] The 236 heat dissipation system surrounds the laser diode 232 and prevents the laser diode 232 from overheating. The 236 heat dissipation system is designed to increase the surface area in contact with the air around the laser diode 232, thereby cooling the system. In one aspect of the invention, the heat dissipation system 236 is made of metal, for example, aluminum, or other material suitable for the transfer of thermal energy. [0078] The excitation light that leaves the collimating lens 230 reflects on the dichroic filter 214 towards the patient and the tissue to be analyzed. The dichroic filter 214 also protects the optical system from dust and dirt and reduces losses in the transmission of ultraviolet light. The notch filter 216 reflects the excitation light reflected by the analyzed tissue and allows light transmission
Fluorescent 25/48. The high-pass filter 218 allows transmission of the fluorescence signal (red and green) and blocks yellow illumination. Holder 210 also blocks ultraviolet light and allows transmission of fluorescence. This filter system allows the separation of a spectral region of interest from the fluorescence of the analyzed tissues so that a medical professional can see and analyze the tissue fluorescence.
[0079] The power button 202 is located on the shell of the diagnostic component 250 and is connected to a circuit board 242 that controls the activation of laser diode 232. Laser diode 232 is also connected to a circuit board 240 which, in turn, it is connected to circuit board 242. Power is supplied to the diagnostic component 200 via the power connection wire 252.
[0080] Referring now to FIGS. 6-9, treatment component 300 uses high intensity DSEs to treat a patient's affected area. Treatment component 300 includes light component 304 and guide sleeve 370. When not in use, end cap 352 is attached to the shell of light component 350 and covers the distal end of light component 304. In one aspect of end cap 352 contains internal threads for a threaded fit on shell 350. In an alternative aspect of the invention, end cap 352 can also be attached to shell 350 by an interference fit or other suitable attachment.
[0081] 322 high-intensity EEDs are located on the metal plate of the core 320 at the distal end of the light component 304. The metal plate of the core 320 allows the high-intensity LEDs 322 to be distributed circularly in the light component 304 and have a emission of a specified wavelength or range of wavelengths corresponding to the absorption spectrum of one or more photosensitizers in a range from approximately 400 nm to approximately 820 nm, for example approximately 410 nm;
26/48 approximately 440 nm; approximately 447 nm; approximately 456 nm; approximately 480 nm; approximately 505 nm; approximately 525 nm; approximately 540 nm; approximately 580 nm; approximately 625 nm; approximately 630 nm; approximately 635 nm; approximately 650 nm; approximately 652 nm; approximately 653 nm; approximately 660 nm; approximately 664 nm; approximately 665 nm; approximately 670 nm; approximately 675 nm; approximately 685 nm; approximately 690 nm; about
732 nm; approximately 735nm; approximately 762 nm; in approximately 615 nm to approximately 635 nm; in approximately 660 nm to approximately 665 nm; in approximately 660 nm to approximately 700 nm; in approximately 660 nm to approximately 710 nm; in approximately 670 nm to approximately 720 nm; in approximately 670 nm to approximately 780 nm nm; in approximately 780 nm to approximately 810 nm; and in
approximately 780 nm to approximately 820 nm. In an alternative aspect of the invention, the metal sheet of the core 320 may contain multiple LEDs that emit light at different wavelengths. In this regard, the medical professional can select the appropriate wavelength for a particular photosensitizer selectively by activating the appropriate LEDs.
[0082] Furthermore, the treatment component 300 can generate a continuous variation of light intensities ranging from approximately 0 mW / cm ² to approximately 250 mW / cm ² , based on the operational range of 322 high-intensity LEDs. an alternative aspect of the invention, treatment component 300 generates a continuous variation in light intensities ranging from approximately 40 mW / cm ² to approximately 120 mW / cm ² . Particular combinations of light intensity and duration
27/48 treatment for treatment component 300 can also be preprogrammed in control panel 408. For example, a user can select approximately 120 mW / cm ² for 21 minutes, approximately 80 mW / cm ² for 32 minutes, or approximately 40 mW / cm ² for 63 minutes.
[0083] The protective frame 330 is located distal from the metal plate of the core 320 and high intensity LEDs 322 to protect LEDs 322 from dust and dirt and other contaminants. 322 high-intensity LEDs generate a large amount of heat. Therefore, light component 304 includes heatsink 336. The heatsink 336 is designed to increase the surface area in contact with the air around LEDs 322, thereby cooling the system. In one aspect of the invention, heatsink 336 is made of metal, for example, aluminum, or other material suitable for the transfer of thermal energy. The 336 heat sink can also provide electrical contact between the power connection wire 306 and the metal sheet of the core 320.
[0084] The distal end of the heat sink 336 rests on the metal plate of the core 320 in order to dissipate the heat generated by the high-intensity LEDs 322. Ring 334 and insulation ring 336 tighten and hold heat sink 336 in shell 350. Power is supplied in the light component 304 through the power connection wire 306.
[0085] When in use, the end cap 352 is removed and the guide sleeve 370 is attached to the light component 304 at the tip of the guide sleeve 310. The guide sleeve 370 is composed of light guide 380, protective sleeve 378 and light shield 372. To attach the guide sleeve 370 to the light component 304, the light guide 380 is first inserted into the tip of the guide sleeve 310 and attached to the shell 350. Then, the protective sleeve 378 is provided over the light guide 380 and is attached to the tip of the guide sleeve 310. The light shield 372 is then attached to the distal end of the protective sleeve 378.
28/48 [0086] The guide sleeve 370 directs the light from the high intensity LEDs 322 to the affected area of the patient. The light shield 372 is attached to the distal end of the guide sleeve 370 to allow light to spread into the affected area of the patient. In one aspect of the invention, guide sleeve 370 is inserted into the patient's vagina and light shield 372 wraps around the patient's cervix to allow treatment component 300 to illuminate the patient's cervix. In order to conform to anatomical variations of the patient's cervix, light protector 372 can have different sizes ranging from approximately 20 mm to approximately 40 mm in diameter. In one aspect of the invention, the light shield 372a is approximately 27 mm in diameter. In an alternative aspect of the invention, the 372b light shield is approximately 33 mm in diameter. The 372 light shield can make contact with the patient's cervix.
[0087] The guide sleeve 370 also includes a glass screen 374 to protect the device from biological contaminants and to allow uniformity of illumination generated by the high intensity LEDs 322. In one aspect of the invention, the glass screen 374 is attached at the end distant from the guide sleeve 370. In one aspect of the invention, all parts of the guide sleeve 370 are reusable and can be sterilized, for example, in an autoclave. In another aspect of the invention, the guide glove 370 is used with a biological barrier to protect the treatment component 300, particularly the guide glove 370, from biological contaminants and maintain a sterile environment. The biological barrier remains in the guide sleeve 370 during insertion and treatment and can be discarded after treatment. Biological barrier can be a sterile disposable film or cap that adapts to the shape of the 370 guide sleeve. The biological barrier can be plastic and can be cylindrical in shape with a closed end and an open end. The biological barrier can also be clear to allow the light emission to pass unobstructed.
29/48 [0088] The protective sleeve 378 is the outermost surface of the guide sleeve 370 and can be made of metal. In one aspect of the invention, the protective sleeve 378 is stainless steel (Inox) or aluminum. Protective sleeve 378 surrounds light guide 380. Light guide 380 can be made of glass or acrylic material. The light guide 380 channels and directs light generated by the 322 high intensity LEDs to the target location or area. Rubber rings 376 are provided between the light guide 380 and the protective glove 378. Rubber rings 376 center the protective glove 378 on the light guide 380 and provide a biological barrier between the patient and the light component 304.
[0089] In alternative aspects of the invention, the structure and design of the 370 guide sleeve can be modified to allow illumination of areas of varying sizes. The guide sleeve 370 can be provided with an internal diameter of 27 mm or 30 mm to adapt to different cervical areas. In one aspect of the invention, the length of both guide sleeves is approximately 108 mm. The illumination area provided by the guide sleeve is 20 mm in diameter.
[0090] In one aspect of the invention, the target area illuminated by the treatment component 300 is approximately 20 mm in diameter. This lighting area is generally sufficient to illuminate the patient's cervix. Treatment component 300 is able to focus the treatment light beam on a well-circumscribed target area, thereby protecting adjacent normal anatomical structures.
[0091] Referring now to FIGS. 10-11, control component 400 includes control component shell 450, power output 402 and master on-off switch 404. Control component 400 supplies power to diagnostic component 200 and / or treatment component 300 via power connection wires 252 and 306, respectively. Control component 400 also includes support for treatment component 430 and / or support for diagnostic component
30/48
420 that retain the respective components when not in use. Control component 400 includes safety switch mechanism 406 that prevents unauthorized use of the therapeutic photodiagnostic and photodynamic device 10. The safety switch mechanism 406 is a lockable electrical switch that prevents activation of device 10 when the safety key it is not in place and is facing the on position.
[0092] Control component 400 also includes control panel 408. Control panel 408 includes display screen 410 and operation button 412, 414, 416a, and 416b. Control panel 408 controls the operation of diagnostic component 200 and / or treatment component 300. Control panel 408 allows the medical professional to select the use of either diagnostic component 200 or treatment component 300.
[0093] The 408 control panel also controls the activation and light intensity of the diagnostic component 200 and provides indication to the medical professional when light is being emitted by the diagnostic component 200. In one aspect of the invention, the control panel 408 allows that the medical professional manually select the light intensity of a diagnostic component 200 ranging from approximately 0 mW / cm ² to approximately 100 mW / cm ² . In an alternative aspect of the invention, the control panel 408 allows the medical professional to manually select the light intensity of a diagnostic component 200 ranging from approximately 15 mW / cm ² to approximately 24 mW / cm ² . In an alternative aspect of the invention, control panel 408 can be programmed to allow the medical professional to manually select the light intensity of a diagnostic component 200 within a specified range of the operational light intensity range of the 232 laser diode. an alternative aspect of the invention, the control panel 408 provides diagnostic component 200 with options
31/48 fixed light intensity selection including, for example, approximately 15 mW / cm ² , approximately 20 mW / cm ² , approximately 25 mW / cm ² , and approximately 30 mW / cm ² .
[0094] The control panel 408 also allows the medical professional to select the desired dose of light energy to be distributed by the treatment component 300. The treatment component 300 has two operational modes: manual and protocol. Manual mode allows the medical professional to select the light intensity level up to a maximum of approximately 250 mW / cm ² . Therefore, the 408 control panel allows the medical professional to manually select the light intensity of a treatment component 300 ranging from approximately 0 mW / cm ² to approximately 250 mW / cm ² , the 322 high intensity LED operating range of the treatment component 300. In an alternative aspect of the invention, the control panel 408 allows the medical professional to manually select the light intensity of a treatment component 300 ranging from approximately 40 mW / cm ² to approximately 120 mW / cm ² . In an alternative aspect of the invention, the control panel 408 can be programmed to allow the medical professional to manually select the light intensity of a treatment component 300 within a specified range of the light intensity operating range of the high intensity LEDs 322.
[0095] Manual mode also allows a medical professional to select an appropriate treatment duration for a selected light intensity. Thus, the manual mode provides greater flexibility and customization of clinical treatment. Protocol mode provides predefined options for frequently used light intensity and treatment duration combinations that are pre-programmed in the 408 control panel. For example, approximately 120 mW / cm ² for 21 minutes, approximately 80 mW / cm ² for 32 minutes, or approximately 40
32/48 mW / cm ² for 63 minutes. In protocol mode, each treatment combination results in the same dose of light energy, approximately 150 J / cm ² , in the patient. However, other doses may be appropriate which, skilled in the art, can easily determine.
[0096] Referring now to FIG. 12, the adjustable support 500 allows positioning of the treatment component 300 to allow precisely positioning the light in the cervical area during treatment. Support 500 includes a coupling 510 to attach to treatment component 300. Support 500 includes folding legs 520, telescopic tubes 540, 542 and 544, and adjustment locks 540a and 542a to adjust the height and position of treatment component 300. The holder 500 also includes flexible stem 530 for fine adjustments in the positioning of the treatment component 300. In one aspect of the invention, the holder 500 allows a variable height ranging from approximately 80 cm to approximately 140 cm.
[0097] The operation of the diagnostic component 200 will now be described. FIGS. 16-19 represent information displayed on the display screen 410 during operation of the diagnostic component 200. In one aspect of the invention, the control component 400 controls the diagnostic component 200. In another aspect of the invention, the control component 400 controls the treatment component 300. In an alternative aspect of the invention, the control component 400 controls the diagnostic component 200 and / or treatment component 300. In this aspect, shown in FIGS. 16 and 20, the medical professional can select the evidence or detection or diagnosis option to operate the diagnostic component 200 or the treatment option to operate the treatment component 300. The selection is made using one or more of the operation buttons 412, 414 , 416a and 416b.
[0098] If evidence is selected, screen 410 indicates that a selection like this has been made, as shown in FIG. 17. The medical professional
33/48 then presses the operation button 414 on the control component 400 which leaves the display screen 410 ready to show that this diagnostic component 200 is ready for light emission, as shown in FIG. 18. Then, to start the light emission, the medical professional presses the power button 202 on the diagnostic component 200. The display screen 410 then indicates that the light emission has started, as shown in FIG. 19. In one aspect of the invention, the light intensity in the diagnostic component 200 is fixed. In an alternative aspect of the invention, the control panel 408 allows the medical professional to select a light intensity of the diagnostic component 200 within the operating range of the laser diode 232 ranging from approximately 0 to approximately 100 mW / cm ² . In an alternative aspect of the invention, the control panel 408 allows the medical professional to select the light intensity of a diagnostic component 200 ranging from approximately 15 mW / cm ² to approximately 24 mW / cm ² . In a further aspect of the invention, the control panel 408 provides options for selecting the light intensity of the diagnostic component 200 including, for example, approximately 15 mW / cm ² , approximately 20 mW / cm ² , approximately 25 mW / cm ² , and approximately 30 mW / cm ² , In a further aspect of the invention where the diagnostic component 200 includes multiple laser diodes, the control panel 408 can provide options for selecting the light emission wavelength.
[0099] The diagnostic component 200 allows a medical professional to non-invasively detect differences between healthy tissue and abnormal tissue. Diagnostic component 200 can detect abnormal tissue autofluorescence, abnormal tissue fluorescence after the photosensitizer is applied, or abnormal tissue fluorescence after treatment with treatment component 300. An example of Grade Π cervical dysplasia autofluorescence tissue (Ο II) detected
34/48 by the diagnostic component 200 is provided in FIG. 13. An example of Grade I tissue cervical dysplasia (C1N I) fluorescence after the use of a photosensitizer detected by diagnostic component 200 is provided in FIG. 14. An example of Grade I tissue cervical dysplasia (CIN I) fluorescence after treatment with treatment component 300 detected by diagnostic component 200 is provided in FIG. 15.
[00100] The operation of the treatment component 300 will now be described. FIGS. 20-26 represent information displayed on the display screen 410 during treatment component treatment 300. As shown in FIGS. 16 and 20, the medical professional first selects the evidence option to operate the diagnostic component 200 or the treatment option to operate the treatment component 300. After treatment is selected, the medical professional has to choose between one of two operating modes: protocol mode or manual mode, as shown in FIGS. 21 and 24. Protocol mode provides predefined options for frequently used treatment combinations for a fixed dose of approximately 150 J / cm ² . Manual mode allows a medical professional to select an appropriate dose of light energy including an appropriate treatment duration for a particular selected light intensity. Thus, the manual mode provides greater flexibility and customization of clinical treatment.
[00101] In one aspect of the invention, the protocol mode is programmed to provide the medical professional with three predetermined options: PI approximately 120 mW / cm ² for 21 minutes; P2 - approximately 80 mW / cm ² for 32 minutes; or P3 - approximately 40 mW / cm ² for 63 minutes. Each option provides the same dose of light energy, approximately 150 J / cm ² . The medical professional selects the appropriate option and presses the operation button 414 on the control component 400 to activate the high intensity LEDs 322 on the treatment component
35/48
300. After activation, display screen 410 displays the duration of treatment in a countdown format, shown in FIG. 23.
[00102] In an alternative aspect of the invention, the treatment component 300 may include a power button placed on the shell 350. After the medical professional selects the appropriate option and presses the operation button 414, the control panel 408 shows that treatment component 300 is ready for light emission. Then, to start the light emission, the medical professional presses the power button on the treatment component 300. The display screen 410 then indicates that the light emission has started.
[00103] In one aspect of the invention, the manual mode is programmed to provide the medical professional with a selection of 5 intensity levels: approximately 40 mW / cm ² , approximately 60 mW / cra2, approximately 80 mW / cm ² , approximately 100 mW / cm ² , and approximately 120 mW / cm ² . In an alternative aspect of the invention, the medical professional is able to continuously vary the light intensity from approximately 0 mW / cm ² to approximately 250 mW / cm ² in the appropriate manner, within the operational range of 322 high-intensity LEDs. The doctor may also vary the duration of treatment from approximately 1 to approximately 90 minutes at intervals of approximately 1 minute to allow a dose of light energy selected by the medical professional. The intensity and time selections are shown on the display screen 410, as shown in FIG. 25. The medical professional uses arrow buttons 416a and 416b and selection button 414 to make selections of treatment intensity and duration.
[00104] Various aspects of the 408 control panel can be implemented by software, firmware, hardware, or a combination of these. FIG. 27 illustrates an exemplary computer system 600 in which the present invention, or portions thereof, can be implemented as human-readable code.
36/48 computer. Various embodiments of the invention are described in terms of this exemplary computer system 600.
[00105] The computer system 600 includes one or more processors, such as the 604 processor. The 604 processor may be a general purpose or special use processor. The processor 604 is connected to a communication infrastructure 606 (for example, a bus or network).
[00106] Computer system 600 also includes main memory 608, preferably random access memory (RAM), and may also include secondary memory 610. Secondary memory 610 may include, for example, a hard drive 612, a removable storage unit 614 and / or a memory stick. Removable storage unit 614 may comprise a floppy disk drive, a magnetic tape drive, an optical disk drive, a flash memory, or the like. Removable storage unit 614 reads and / or writes to removable storage unit 618 in a well-known manner. The removable storage unit 618 may comprise a floppy disk, magnetic tape, optical disk, etc. which is read and written by the removable storage unit 614. As skilled in the relevant art, the removable storage unit 618 includes computer-usable storage media with computer software and / or data stored therein.
[00107] In alternative implementations, secondary memory 610 may include other similar devices to allow computer programs or other instructions to be loaded onto the computer system 600. Such devices may include, for example, a removable storage unit 622 and an interface 620 Examples of such means may include a program cartridge and cartridge interface (as found in video game devices), a memory chip
37/48 removable (such as an EPROM, or PROM) and associated socket, and other removable storage units 622 and interfaces 620 that allow software and data to be transferred from removable storage unit 622 to computer system 600.
[00108] The computer system 600 may also include a network interface 624. The network interface 624 allows software and data to be transferred between the computer system 600 and external devices. In one aspect of the invention, an external device is an electronic patient database that records and maintains patient records. The network interface 624 can include a modem, a network interface (such as an Ethernet card), a communications port, a dock and PCMCIA card, or the like. Software and data transferred via the 624 network interface are in the form of 628 signals that can be electronic, electromagnetic, optical, or other signals capable of being received by the 624 network interface. These 628 signals are provided on the 624 network interface by middle of a communications path 626. Communications path 626 carries signals 628 and can be implemented using wire or cable, optical fibers, a telephone line, a cellular telephone connection, an RF connection or other communications channels.
[00109] In this document, the terms computer program media and computer usable media are used to refer in general to media such as removable storage unit 618, removable storage unit 622, and a hard disk installed in the hard disk drive 612. Signals carried by the 626 communications path can also incorporate the logic described here. Computer program media and computer-usable media can also refer to memories, such as main memory 608 and secondary memory 610, which can be memory semiconductors (e.g., DRAMs, etc.). These computer program products are devices for providing software on the
38/48 computer system 600.
[00110] Computer programs (also called computer control logic) are stored in main memory 608 and / or secondary memory 610. Computer programs can also be received via the network interface 624. Such computer programs, when executed , allow computer system 600 to implement the present invention as discussed herein. In particular, computer programs, when executed, allow processor 604 to implement the processes of the present invention, as discussed herein. In this way, such computer programs represent controllers of the computer system 600. Where the invention is implemented using software, the software can be stored in a computer program product and loaded onto the computer system 600 using the removable storage unit 614, interface 620, hard disk 612 or network interface 624.
[00111] The invention is also directed to computer program products comprising software stored on any media usable by computer. Such software, when run on one or more data processing devices, causes the data processing device (s) to operate in the manner described herein. Modalities of the invention employ any usable or computer-readable media, known now or in the future. Examples of computer-readable media include, but are not limited to, primary storage devices (for example, any type of random access memory), secondary storage devices (for example, hard drives, floppy disks, CD ROMs, ZIP disks, tapes , magnetic storage devices, optical storage devices, MEMS, nanotechnology storage device, etc.), and media (e.g., wired and wireless communications networks, local area networks, wide area networks, intranets, etc.).
39/48 [00112] The preparation of the patient for diagnosis and photodynamic treatment will now be described. Before diagnosis or treatment, the patient is asked to lie on the operating table with his legs in stirrup with the necessary clothing removed.
[00113] In order to assess the fluorescence of cells in the patient's cervix, the medical professional positions the diagnostic component 200 in front of the patient's vagina and uses a speculum to allow access to the patient's cervix. The medical professional then begins to emit light and illuminates the patient's cervix with diagnostic component 200. The medical professional looks through optics 204 with the naked eye or uses camera 260 to see tissue fluorescence in the patient's affected area. If the medical professional determines which abnormal tissue is present, the medical professional can then use the treatment component 300 to destroy the abnormal tissue.
[00114] The medical professional assesses the fluorescence of cells in the affected area before and after photodynamic treatment using the diagnostic component 200. For example, the diagnostic component 200 can detect abnormal tissue autofluorescence. In addition to detecting abnormal tissue, the medical professional can use the diagnostic component 200 to measure the appropriate production of PpIX before treatment and verify that the photosensitizer has been used completely after treatment. Thus, diagnostic component 200 can be used to assess the efficiency and progress of photodynamic therapy.
[00115] Before using treatment component 300, a photosensitizer is applied to the affected area of the patient including abnormal tissue. In one aspect of the invention, the photosensitizer is MAL. In an alternative aspect of the invention, the photosensitizer is 5-ALA. In an alternative aspect of the invention, the photosensitizer is a combination of ALA and MAL. In an alternative aspect of the invention, the photosensitizer is
40/48 one or a mixture of the photosensitizers discussed here. Each photosensitizer is activated by a specific wavelength of light. Therefore, the use of a different photosensitizer requires the use of different LEDs on the treatment component 300 in order to produce the desired wavelength. The photosensitizer is mixed into a cream for application to the patient's affected area.
[00116] After application in the affected area of the patient, the photosensitizer naturally penetrates the affected area for a period of time as discussed here. After the photosensitizer penetrates, light component 304 is attached to guide sleeve 370 and treatment component 300 is attached to support 500. Treatment component 300 is placed in position for treatment in such a way that the light shield 372 in the guide sleeve 370 is adjacent to the affected area of the patient. In one aspect of the invention, the affected area of the patient can be located in the patient's cervix. To reach the cervix and the affected area, the guide glove 370 passes through the patient's vagina so that the light shield 372 surrounds the cervix. The light component 304 remains external to the patient's body during photodynamic treatment.
[00117] After placing the treatment component 300, the medical professional selects the appropriate dose of light energy to treat the affected area of the patient. The treatment component 300 then delivers the appropriate dose to the patient's affected area to destroy the abnormal cells. After treatment, the medical professional again uses the diagnostic component 200 to assess the fluorescence of cells in the affected area to verify that the photosensitizer has been fully used and to verify the effectiveness of photodynamic therapy.
[00118] The patient can undergo additional diagnosis and treatment with a diagnostic and therapeutic device 10 until the abnormal cells in the affected area of the patient are destroyed.
41/48 [00119] In an alternative aspect of the invention, FIGS. 28-35 represent the therapeutic photodiagnostic and photodynamic device 1010. Device 1010 includes a diagnostic component 1200 for optical injury detection, a treatment component 1300 for injury treatment, a control component 1400 for controlling the diagnostic component 1200 and treatment component 1300, and an adjustable support 1500 on the mobile base 1600. Diagnostic component 1200 includes all features of diagnostic component 200, for example, as previously discussed in paragraphs [0073] to [0080] and [0098 ] to [0100]. Treatment component 1300 includes all treatment component features 300, for example, as previously discussed in paragraphs [0081] to [0091] and [0101] to [0104]. Control component 1400 includes all features of control component 400, for example, as previously discussed in paragraphs [0092] to [0096].
[00120] The adjustable support 1500 allows the positioning of the diagnostic component 1200 or treatment component 1300 to allow precise positioning of the light in the cervical area during diagnosis or treatment. Support 1500 includes a 1510 coupling to attach to diagnostic component 1200 or treatment component 1300. Support 1500 includes adjustment latches 1520a and 1542a and telescopic element 1542 to adjust the height and position of coupling 1510 for positioning diagnostic component 1200 or treatment component 1300. Support 1500 also includes flexible rod 1530 for fine adjustments in the positioning of diagnostic component 1200 or treatment component 1300. In one aspect of the invention, support 1500 allows a variable height ranging from approximately 80 cm to approximately 140 cm. Support 1500 also includes cable supports 1502a and 1502b for retaining a power connection wire for the 1010 photo diagnostic and photodynamic therapeutic device. Support 1500 also
42/48 includes control component supports 1504a and 1504b to retain control component 1400 in support 1500. Support 1500 is attached to the mobile base 1600. The mobile base 1600 includes wheels 1602 and feet 1620. The mobile base 1600 allows the 1010 photodiagnostic and photodynamic therapeutic device is easily maneuvered in place for use.
[00121] Control component 1400 includes control component shell 1450, power output 1402, and master on and off switch 1404. Control component 1400 includes cable support 1418. Control component 1400 also includes locking 1422 to prevent unauthorized access to the control component 1400. The control component 1400 supplies power to the diagnostic component 1200 and / or treatment component 1300 through the power connection wires 1252 and 1306, respectively. Control component 1400 includes two-way connector 1460a to connect to power link wire 1306. Control component 1400 also includes four-way connector 1460b to connect to power link wire 1252. Control component 1400 additionally includes treatment component support 1430 and / or diagnostic component support 1420 that retain the respective components when not in use. Control component 1400 also includes control panel 1408 which includes the same features as the 408 control panel discussed above. For example, control panel 1408 includes display screen 1410 and operating buttons 1412, 1414, 1416a and 1416b. Control panel 1408 controls the operation of diagnostic component 1200 and / or treatment component 1300. Control panel 1408 allows the medical professional to select the use of either diagnostic component 1200 or treatment component 1300.
[00122] Treatment component 1300 uses high intensity LEDs to treat an affected patient area. Treatment component 1300 includes light component 1304 and guide sleeve 370. In this
43/48 aspect of the invention, the guide sleeve 370 is positioned approximately 90 degrees with respect to the light component 1304. In alternative aspects of the invention, the guide sleeve 370 can be positioned at several different angles with respect to the light component 1304 For example, the guide sleeve 370 can be positioned from approximately 0 degrees to approximately 140 degrees with respect to the light component 1304. When the treatment component 1300 is not in use, the guide sleeve 370 can be removed and replaced with the end cap 1352. The end cap 1352 can be attached to the shell of the light component 1350 and can cover the light emitting end of the light component 1304. In one aspect of the invention, the end cap 1352 contains inner threads for a threaded fit on the 1350 shell. In an alternative aspect of the invention, the end cap 1352 can also be attached to the 1350 shell by an interference fit or other proper attachment.
[00123] High intensity LEDs 1322 are located on the metal plate of the core 1320 near the bottom portion of the light component 1304. The metal plate of the core 1320 allows the high intensity LEDs 1322 to be distributed circularly in the light component 1304 and have an emission of a specified wavelength or wavelength range corresponding to the absorption spectrum of one or more sensitizing photos in a range of approximately 400 nm to approximately 820 nm, similar to the 322. high-intensity LEDs discussed above. In an alternative aspect of the invention, the 1320 core metal plate may contain multiple LEDs that emit light at different wavelengths. In this regard, the medical professional can select the appropriate wavelength for a particular photosensitizer by selectively activating the appropriate LEDs.
[00124] Furthermore, the treatment component 1300 can generate a continuous variation of light intensities, similar to the component of
44/48 treatment 300, ranging from approximately 0 mW / cm ² to approximately 250 mW / cm ² , based on the operational range of high intensity LEDs 1322. In an alternative aspect of the invention, treatment component 1300 can generate a variation light intensities ranging from approximately 40 mW / cm ² to approximately 120 mW / cm ² .
[00125] The protective screen 1330 is positioned adjacent to the high intensity LEDs 1322 to protect the LEDs 1322 from dust and dirt and other contaminants. The 1322 high-intensity LEDs generate a large amount of heat. Therefore, the light component 1304 includes a heatsink 1336 positioned adjacent to the metal sheet of the core 1320. The heatsink 1336 is designed to increase the surface area in contact with the air around the LEDs 1322, thereby cooling the system. In one aspect of the invention, the 1336 heatsink is made of metal, for example, aluminum, or other material suitable for the transfer of thermal energy. The heat sink 1336 can also provide electrical contact between the power connecting wire 1306 and the metal sheet of the core 1320. The heat sink ring 1334 is provided and can attach the heat sink 1336 to the shell 1350. The insulation ring 1326 is provided between the heat sink 1336 and the heat sink ring 1334.
[00126] The heat sink 1336 rests on the metal plate of the core 1320 in order to dissipate the heat generated by the high intensity LEDs 1322. Ring 1334 tightens and maintains heat sink 1336 in the shell 1350. Power is supplied in the component light 1304 through the power connection wire 1306.
[00127] When in use, the end cap 1352 is removed and the guide sleeve 370 is attached to the light component 1304 at the tip of the guide sleeve 1310. As previously discussed, the guide sleeve 370 is made up of the light guide 380, protective glove 378 and light protector 372 and directs light from
45/48
1322 high intensity LEDs for the affected patient area.
[00128] It should be noted that the Detailed Description section, not the Summary sections, should be used to interpret the claims. The Summary and Summary sections may have one or more exemplary embodiments of the present invention, but not all, contemplated by the inventor (s), and thus are not intended to limit the present invention and the attached claims in any way. The scope and scope of the present invention should not be limited by any of the exemplary modalities described, but should be defined only in accordance with the following claims and their equivalents.
Examples [00129] The following Examples are provided to illustrate, and not limit, aspects of the present invention.
Example 1
A photosensitizing compound and vehicle.
[00130] The photosensitizer can be mixed in a cream for application in an affected area of the patient. The cream may contain MAL (methyl aminolevulinic acid) 20% (w / w) homogenized with POLAWAX 19.5%; CETIOL V (decyl oleate) 4%; NIPASOL (propyl paraben) 0.2%; dimethyl sulfoxide (DMSO) 5%; NIP AGIN (sodium methyl paraben) 0.15%; propylene glycol 5% '; ethylenediamine tetraacetic acid (EDTA) 0.15%; butylated hydroxytoluene (BHT) 0.05%; GERMAL (imidazolinol urea) 0.2% and deionized water, enough to homogenize the constituents.
[00131] To prepare the cream, the oil phase containing POLAWAX, CETIOL V and NIPASOL and the aqueous phase containing NIP AGIN, propylene glycol, EDTA, BHT, and GERMAL are weighed and heated to approximately 65 to approximately 70 degrees centigrade. Then, the aqueous phase is poured into the oil phase with constant agitation, also incorporating DMSO. Then, the mixture is stirred to form the cream.
46/48
The MAL (20 g) is mixed with 80 g of the cream.
[00132] In this mixture, POLAWAX is an emulsifying wax; DMSO is an organic compound that assists in the penetration of MAL into the tissue; NIPASOL (propyl paraben), NIP AGIN (sodium methyl paraben), and GERMAL (imidazolinol urea) are antifungal and antimicrobial agents; propylene glycol and decyl oleate are emollient agents; EDTA is an iron chelating agent; and BHT is an antioxidant compound.
Example 2
FIGO Cervical Cancer Staging [00133] The diagnostic and therapeutic device 10 can treat cervical dysplasia (cervical intraepithelial neoplasia (CIN); precancerous changes of the cervix, including HPV lesions), stage I cervical cancer including stages IA (IA1, and IA2) , defined by the International Federation of Gynecology and Obstetrics (FIGO). According to the staging FIGO, cervical cancer in stage I, the cancer has grown (invaded) to the cervix, but it is not growing outside the uterus. The cancer did not spread to nearby lymph nodes (NO) or distant sites (MO). In stage IA, there is a very small amount of cancer, and it can be seen only under a microscope. In stage IA1, the cancer is less than 3 mm deep and less than 7 mm wide. In stage IA2, the cancer is between 3 mm and 5 mm deep and less than 7 mm wide.
Example 3
Diagnosis and Detection [00134] The diagnostic component 200 allows a medical professional to non-invasively detect differences between healthy tissue and abnormal tissue. Diagnostic component 200 can detect abnormal tissue autofluorescence, abnormal tissue fluorescence after the photosensitizer is applied, or abnormal tissue fluorescence after treatment with treatment component 300. An example of
47/48 Grade II cervical dysplasia tissue autofluorescence detected by diagnostic component 200 is provided in FIG. 13. An example of Grade I cervical dysplasia tissue fluorescence after the use of a photosensitizer detected by the diagnostic component 200 is provided in FIG. 14. An example of Grade I cervical dysplasia tissue fluorescence after treatment with treatment component 300 detected by diagnostic component 200 is provided in FIG. 15.
Example 4
Treatment [00135] To date, twenty-three patients have been diagnosed with cervical pre-cancer (cervical intraepithelial carcinoma) and successfully treated using a device that includes the diagnostic component and the treatment component. Figure 15 (Fluorescence after treatment) shows the successful treatment. Figure 14 shows an area of fluorescence in the upper portion that is no longer visible after the treatment in Figure 15. Based on these data, the device will soon enter clinical experiments.
[00136] A recent observation shows that a discrete population of squamocolumnar junction cells is implicated in the pathogenesis of cervical cancer. See Herfs et al., A discrete population of squamocolumnar junction cells implicated in the pathogenesis of cervical cancer, PNAS 109: 10516-10521 (2012). This observation shows that these squamocolumnar junction cells are found at the ectoendocervical junction and can be a source for cervical cancer. An observation like this explains the effectiveness of the treatment using the present invention by virtue of the therapeutic photodiagnostic and photodynamic device described here detecting and treating these precancerous cells at the ectoendocervical junction. The photosensitizer penetrates the junction and the treatment component destroys abnormal cells in that area (junction).
48/48 [00137] Each patent and publication cited is incorporated herein by reference in its entirety for all purposes.

权利要求:
Claims (20)
[1]
1. Photodiagnostic device to detect differences between healthy and abnormal cervical tissue, characterized by the fact that it comprises:
a laser light source adapted to illuminate the cervical tissue;
a heat dissipation system to regulate the temperature of the light source;
a lens to collimate light from the light source;
an optician having a passage of light;
a light filter attached to the light passage to direct the light from the lens to one end of the light passage towards the cervical tissue; and a light filter attached to the passage of light adapted to separate a spectral region of light from a fluorescence of light reflected by the cervical tissue.
[2]
2. Photodiagnostic device according to claim 1, characterized by the fact that the photodiagnostic device is portable.
[3]
3. Photodiagnostic device according to claim 1, characterized by the fact that the light filter is a high-pass filter.
[4]
4. Photodiagnostic device according to claim 1, characterized by the fact that the lens for collimating light includes a first lens and a second lens adapted to generate a beam of light approximately 20 mm in diameter.
[5]
5. Photodynamic treatment device, characterized by the fact that it comprises:
a light source;
a heat dissipation system to regulate the temperature of the light source;
2/5 a light guide adapted for vaginal insertion and to direct light generated by the light source to the cervical tissue; and a light shield affixed to a distal end of the light guide adapted to surround the cervical tissue.
[6]
6. Photodynamic treatment device according to claim 5, characterized in that the device produces an illumination area of approximately 20 mm in diameter.
[7]
7. Photodynamic treatment device according to claim 5, characterized by the fact that it additionally comprises:
a protective glove surrounding the light guide, the protective glove adapted for vaginal insertion; and a ring provided between the light guide and the protective glove, adapted to center the protective glove on the light guide and to provide a biological barrier between the cervical tissue and the light source.
[8]
8. Photodynamic and photodiagnostic treatment device, characterized by the fact that it comprises:
a photodiagnostic component, including a laser light source, a lens, and a light filter, adapted to generate and direct a first wavelength of light towards the cervical tissue and to separate a spectral region of light from a light fluorescence reflected by the cervical tissue;
a photodynamic treatment component, including a second light source and a light guide, adapted to generate light at a second wavelength and to direct the second wavelength of light to the cervical tissue; and a control component attached to the photodiagnostic component and the photodynamic treatment component providing power to the photodiagnostic component and the photodynamic treatment component and controlling activation of the laser light source and the second source
3/5 light.
[9]
9. Photodynamic treatment and photodiagnostic device according to claim 8, characterized by the fact that the photodiagnostic component is portable.
[10]
10. Photodynamic treatment and photodiagnostic device according to claim 8, characterized by the fact that the light filter is a high-pass filter.
[11]
11. Photodynamic treatment and photodiagnostic device according to claim 8, characterized by the fact that the laser light source generates a light beam approximately 20 mm in diameter.
[12]
12. Photodynamic treatment and photodiagnostic device according to claim 8, characterized by the fact that the second light source generates a light beam approximately 20 mm in diameter.
[13]
13. Photodynamic treatment and photodiagnostic device according to claim 8, characterized by the fact that the light guide is adapted for vaginal insertion.
[14]
14. Method to detect autofluorescence of abnormal cervical tissue, characterized by the fact that it comprises:
generate excitation light from a laser light source;
direct the excitation light towards the cervical tissue;
receiving reflected excitation light and fluorescent light from the cervical tissue and passing the reflected light and fluorescent light through a light filter to separate the reflected light from the fluorescent light; and see the fluorescent light from the abnormal cervical tissue.
[15]
15. Method according to claim 14, characterized by the fact that the light source and the light filter are incorporated in a portable photodiagnostic device.
[16]
16. Method for treating cervical tissue using the device as defined in claim 5, the cervical tissue having a compound
4/5 photosensitizer placed on it, the method characterized by the fact that it comprises:
select an appropriate dose of light power;
generate a light emission with the light source; and directing the light emission through a light guide to the cervical tissue for a selected period of time to distribute the selected dose of light power.
[17]
17. Method according to claim 16, characterized in that an area illuminated by the emission of light is approximately 20 mm in diameter.
[18]
18. Method for diagnosing and treating abnormal cervical tissue, characterized by the fact that it comprises:
analyze cervical tissue generating a laser light emission, direct the light emission towards the cervical tissue, pass the light emission through a light filter, and see the cervical tissue fluorescence to detect the presence of abnormal cervical tissue;
treating abnormal cervical tissue having a photosensitizing compound disposed on it generating a second light emission and directing the second light emission towards the cervical tissue to distribute a selected dose of light power to destroy the abnormal cervical tissue.
[19]
19. Method according to claim 18, characterized in that it additionally comprises:
after treating abnormal cervical tissue, analyze the cervical tissue by generating a second laser light emission, direct the light emission towards the cervical tissue, pass the light emission through a light filter, and see the cervical tissue fluorescence to detect the presence or absence of abnormal cervical tissue.
[20]
20. Method for diagnosing abnormal cervical tissue,
5/5 characterized by the fact that it comprises:
generate a laser light emission;
direct the emission of light towards the cervical tissue with a photosensitizing compound disposed on it;
pass the light emission through a light filter; and see the fluorescence of the cervical tissue.

类似技术:

---

公开号 | 公开日 | 专利标题

---

JP6670892B2|2020-03-25|Diagnostic devices, therapeutic devices and their use

---

Zimmermann et al.2001|mTHPC‐mediated Photodynamic Diagnosis of Malignant Brain Tumors¶

---

US6846311B2|2005-01-25|Method and apparatus for in VIVO treatment of mammary ducts by light induced fluorescence

---

Chen et al.2004|Successful treatment of oral verrucous hyperplasia with topical 5-aminolevulinic acid-mediated photodynamic therapy

---

AU2010239272B2|2015-09-17|Light-emitting dye for intraoperative imaging or sentinel lymph node biopsy

---

ES2454974T3|2014-04-14|Apparatus for optical inhibition of photodynamic therapy

---

JP2016518904A|2016-06-30|Irradiation device

---

Ladner et al.2001|Photodynamic diagnosis of breast tumours after oral application of aminolevulinic acid

---

US20100305436A1|2010-12-02|Systems, devices, and methods for photoactive assisted resection

---

Rühm et al.2014|5-ALA based photodynamic management of glioblastoma

---

Morshed et al.2018|Wavelength-specific lighted suction instrument for 5-aminolevulinic acid fluorescence-guided resection of deep-seated malignant glioma

---

Vansevičiūtė et al.2014|5-Aminolevulinic acid-based fluorescence diagnostics of cervical preinvasive changes

---

Utsuki et al.2008|Auditory Alert System for Fluorescence-Guided Resection of Gliomas—Technical Note—

---

Gossner et al.2000|Photodynamic therapy of gastric cancer

---

Prosst et al.2004|Kinetics of intraoperative fluorescence diagnosis of parathyroid glands

---

Smith2002|Fluorescence emission‐based detection and diagnosis of malignancy

---

Dayton et al.2010|Light-guided lumpectomy: device and case report

---

Lu et al.2008|Study on characteristic intrinsic fluorescence spectra of urine from ovarian cancer patients

---

US20200406052A1|2020-12-31|Digestive Tract Capsule Endoscopy Integrated With Photodynamic Diagnosis And Therapy

---

Pfefer et al.2001|Long‐term Effects of Photodynamic Therapy on Fluorescence Spectroscopy in the Human Esophagus¶

---

Momchilov et al.2007|Development of low-cost photodynamic therapy device

---

RU2395124C2|2010-07-20|Method of study of photosensitisers biological distribution

---

Ren et al.2014|Multi-channel LED light source for fluorescent agent aided minimally invasive surgery

---

BR102016021204A2|2018-04-03|SYSTEM FOR STUDIES AND ANALYSIS IN BIOPHOTONICS, PHOTOBIOLOGY AND PHOTOMEDICINE

---

Baumgartner et al.1991|First clinical experiences with photodynamic fluorescence diagnosis in urology

同族专利:

---

公开号 | 公开日

---

CN104736044A|2015-06-24|

---

US20140039322A1|2014-02-06|

---

CN104736044B|2017-11-14|

---

TW201424696A|2014-07-01|

---

JP2018143843A|2018-09-20|

---

MX348914B|2017-07-03|

---

IN2015KN00550A|2015-07-17|

---

CA2887770A1|2014-02-06|

---

MX2013008957A|2014-02-21|

---

JP6670892B2|2020-03-25|

---

US20170100073A1|2017-04-13|

---

JP2015531619A|2015-11-05|

---

US9550072B2|2017-01-24|

---

JP6364006B2|2018-07-25|

---

TWI657801B|2019-05-01|

---

EP2879567A1|2015-06-10|

---

CN108236449A|2018-07-03|

---

WO2014022792A1|2014-02-06|

引用文献:

---

公开号 | 申请日 | 公开日 | 申请人 | 专利标题

---

---

US3994288A|1975-06-11|1976-11-30|Frigitronics Of Conn., Inc.|Colposcope|

---

JPS6262322B2|1982-01-20|1987-12-25|Fuji Photo Optical Co Ltd|

---

US5283255A|1987-01-20|1994-02-01|The University Of British Columbia|Wavelength-specific cytotoxic agents|

---

US4807594A|1988-01-15|1989-02-28|Medical Concepts, Incorporated|Adapter assembly for endoscopic video camera|

---

US5162519A|1988-03-11|1992-11-10|Efamol Holdings Plc|Porphyrins and cancer treatment|

---

GB8805849D0|1988-03-11|1988-04-13|Efamol Holdings|Porphyrins & cancer treatment|

---

US4862199A|1988-09-08|1989-08-29|Innovision Optics, Inc.|Adjustable adapter for borescope and film/video camera|

---

US4905670A|1988-12-28|1990-03-06|Adair Edwin Lloyd|Apparatus for cervical videoscopy|

---

US4973848A|1989-07-28|1990-11-27|J. Mccaughan|Laser apparatus for concurrent analysis and treatment|

---

US5421339A|1993-05-12|1995-06-06|Board Of Regents, The University Of Texas System|Diagnosis of dysplasia using laser induced fluoroescence|

---

US5458595A|1993-12-16|1995-10-17|The Regents Of The University Of California|Vaginal speculum for photodynamic therapy and method of using the same|

---

US5522868A|1994-08-23|1996-06-04|Sisters Of Providence In Oregon|Method and apparatus for determination of psoralen concentrations in biological tissues|

---

US20050171408A1|1997-07-02|2005-08-04|Parker Jeffery R.|Light delivery systems and applications thereof|

---

US6008211A|1995-07-27|1999-12-28|Pdt Pharmaceuticals, Inc.|Photoactivatable compounds comprising benzochlorin and furocoumarin|

---

US6081740A|1997-04-23|2000-06-27|Accumed International, Inc.|Method and apparatus for imaging and sampling diseased tissue|

---

US20040147843A1|1999-11-05|2004-07-29|Shabbir Bambot|System and method for determining tissue characteristics|

---

JP2000189527A|1998-12-28|2000-07-11|Ishikawajima Harima Heavy Ind Co Ltd|Laser diagnosic and treatment method and apparatus therefor|

---

GB2370992B|2000-03-23|2002-11-20|Photo Therapeutics Ltd|Therapeutic light source and method|

---

AT429850T|2000-03-28|2009-05-15|Univ Texas|METHOD AND DEVICE FOR THE DIGITAL DIAGNOSTIC MULTISPECTRAL FORMATION|

---

US7351242B1|2000-07-06|2008-04-01|Ceramoptec Industries, Inc.|Active endoscopic photodynamic therapy devices; systems and method|

---

EP1420644B1|2001-08-23|2006-05-31|Bayer CropScience S.A.|Substituted propargylamines|

---

US7153015B2|2001-12-31|2006-12-26|Innovations In Optics, Inc.|Led white light optical system|

---

EP1664854B1|2003-08-19|2015-07-22|Cornell Research Foundation, Inc.|Optical fiber delivery and collection system for biological applications|

---

US20080071331A1|2004-02-13|2008-03-20|Qlt Inc.|Photodynamic Therapy For The Treatment Of Prostatic Conditions|

---

US20050234526A1|2004-04-14|2005-10-20|Gilhuly Terence J|Systems and methods for detection of disease including oral scopes and ambient light management systems |

---

JP4709576B2|2005-04-15|2011-06-22|オリンパスメディカルシステムズ株式会社|Endoscope device|

---

US20070031777A1|2005-08-03|2007-02-08|Bwt Property, Inc.|Multifunctional Dental Apparatus|

---

US7355155B2|2005-10-21|2008-04-08|Bwt Property, Inc.|Light emitting apparatus for medical applications|

---

KR100798486B1|2006-03-29|2008-01-28|한국전기연구원|Light source for Fluorescence Diagnosis and Photodynamic Therapy|

---

WO2007115406A1|2006-04-10|2007-10-18|Led Medical Diagnostics, Inc.|Multipurpose diseased tissue detection devices, systems and methods|

---

US7562755B2|2006-07-07|2009-07-21|Dt Swiss, Inc.|Rear wheel hub, in particular for bicycles|

---

US8292935B2|2006-09-12|2012-10-23|Bistitec Pharma Marketing Ltd|Photonic device and method for treating cervical dysplasia|

---

US20090099460A1|2007-10-16|2009-04-16|Remicalm Llc|Method and device for the optical spectroscopic identification of cervical cancer|

---

US20090062662A1|2007-08-27|2009-03-05|Remicalm, Llc|Optical spectroscopic device for the identification of cervical cancer|

---

JP2009056248A|2007-09-03|2009-03-19|Fujifilm Corp|Light source unit, drive control method of light source unit and endoscope|

---

US8219180B2|2007-10-11|2012-07-10|Tufts University|System and method employing fiber optic shape tracking|

---

WO2009072856A1|2007-12-04|2009-06-11|Diaz Sanchez Joel Gerardo|Vaginal speculum including a system and a specific method for diagnosing lesions caused by the human papillomavirus in the female genital tract|

---

US20100036260A1|2008-08-07|2010-02-11|Remicalm Llc|Oral cancer screening device|

---

GB0900461D0|2009-01-12|2009-02-11|Photocure Asa|Photodynamic therapy device|

---

JP4750192B2|2009-02-18|2011-08-17|オリンパス株式会社|Pattern projection apparatus and endoscope apparatus|

---

US8936630B2|2009-11-25|2015-01-20|Medtronic, Inc.|Optical stimulation therapy|

---

WO2011066149A1|2009-11-30|2011-06-03|Laura Weller-Brophy|Method and apparatus for cervical cancer screening|

---

CN102665559B|2009-12-21|2015-06-24|泰尔茂株式会社|Excitation, detection, and projection system for visualizing target cancer tissue|

---

JP5489157B2|2010-02-17|2014-05-14|ジーイー・メディカル・システムズ・グローバル・テクノロジー・カンパニー・エルエルシー|Ultrasonic diagnostic equipment|

---

KR20130008538A|2010-02-26|2013-01-22|베링거 인겔하임 인터내셔날 게엠베하|4-[cycloalkyloxy arylamino] thieno [2,3-d] pyrimidines having mnk1/mnk2 inhibiting activity for pharmaceutical compositions|

---

JP2011196873A|2010-03-19|2011-10-06|Olympus Corp|Fluorescence detection method and fluorescence detection device|

---

WO2012037355A2|2010-09-16|2012-03-22|Case Western Reserve University|Photodynamic therapy system, device and associated method of treatment|

---

JP5345597B2|2010-09-27|2013-11-20|富士フイルム株式会社|Temperature control device, temperature control method, light source device, and endoscope diagnosis device|

---

CN202069569U|2010-12-09|2011-12-14|深圳大学|Fluorescent spectrum endoscope system|USD903887S1|2012-09-05|2020-12-01|Johnson & Johnson Consumer Inc.|Handheld acne treatment wand|

---

MX2017016776A|2015-06-23|2018-09-21|Johnson & Johnson Consumer Inc|Light therapy spot applicator.|

---

US10092770B2|2011-09-08|2018-10-09|Johnson & Johnson Consumer Inc.|Light therapy spot applicator|

---

WO2015005908A1|2013-07-09|2015-01-15|Brandes Bonnie|Therapeutic signal generator|

---

US10588564B2|2014-09-30|2020-03-17|Moein Health, LLC|Method and kit for diagnosing and treating neoplastic tissue|

---

CN105561306A|2015-01-16|2016-05-11|南京大学|Composition containing singlet oxygen protective agent and preparation method thereof|

---

TWI561219B|2015-02-03|2016-12-11|Hsien-Chang Shih|Medical diagnosis device and medical system thereof|

---

CA2984963A1|2015-05-12|2016-11-17|Klox Technologies Inc.|Devices and methods for phototherapy|

---

JP2016214373A|2015-05-15|2016-12-22|アンリツ株式会社|Light irradiator system, uterine cervix photodynamic therapy device, and irradiation method|

---

RU2596869C1|2015-05-26|2016-09-10|Федеральное государственное бюджетное учреждение науки Институт прикладной физики Российской академии наук|Device for fluorescent diagnosis and monitoring of photodynamic therapy|

---

JP6609220B2|2015-06-01|2019-11-20|マハジャン ニティン|Multi-modality medical flexible video endoscope|

---

ES2604304B1|2015-09-03|2018-02-22|Universidad De Málaga|LED-based lighting device with automated dose control for photodiagnosis of skin diseases related to light exposure, related applications and methods|

---

CN105854189B|2016-05-27|2018-06-29|上海皓欣医疗科技股份有限公司|A kind of laser gun rifle core|

---

JP2020521531A|2017-05-16|2020-07-27|リサーチ ディベロップメント ファウンデーション|Device and method for endometrial tissue identification|

---

CN108714275A|2018-05-31|2018-10-30|合肥大族科瑞达激光设备有限公司|A kind of Bladder stone and semiconductor laser integrate tumor-treating machine|

---

CN109549616B|2018-11-16|2020-07-10|禚元华|Multi-functional intelligent cervical endoscope system|

---

TWI719365B|2018-12-03|2021-02-21|財團法人金屬工業研究發展中心|Medical image modeling system and medical image modeling method|

---

US10909773B2|2018-12-03|2021-02-02|Metal Industries Research & Development Centre|Medical image modeling system and medical image modeling method|

---

JPWO2021044627A1|2019-09-06|2021-03-11|

---

CN110897593A|2019-10-24|2020-03-24|南京航空航天大学|Cervical cancer pre-lesion diagnosis method based on spectral characteristic parameters|

法律状态:
2019-10-01| B08F| Application dismissed because of non-payment of annual fees [chapter 8.6 patent gazette]|

---

2019-10-22| B08H| Application fees: decision cancelled [chapter 8.8 patent gazette]|Free format text: ANULADA A PUBLICACAO CODIGO 8.6 NA RPI NO 2543 DE 01/10/2019 POR TER SIDO INDEVIDA. |

---

2019-12-31| B06F| Objections, documents and/or translations needed after an examination request according [chapter 6.6 patent gazette]|

---

2020-08-11| B06U| Preliminary requirement: requests with searches performed by other patent offices: procedure suspended [chapter 6.21 patent gazette]|

---

2020-12-01| B11B| Dismissal acc. art. 36, par 1 of ipl - no reply within 90 days to fullfil the necessary requirements|

---

2021-10-13| B350| Update of information on the portal [chapter 15.35 patent gazette]|

优先权:

---

申请号 | 申请日 | 专利标题

---

US201261679444P| true| 2012-08-03|2012-08-03|

---

US13/829,686|US9550072B2|2012-08-03|2013-03-14|Diagnostic device, therapeutic device, and uses thereof|

---

PCT/US2013/053459|WO2014022792A1|2012-08-03|2013-08-02|Diagnostic device, therapeutic device, and uses thereof|

---