WO2002010119A1 - Preparation of sterile crystals of 5-aminolevulinic acid utilized for medical diagnostic and therapeutic purposes, and a device for facilitating this diagnostic process - Google Patents
Preparation of sterile crystals of 5-aminolevulinic acid utilized for medical diagnostic and therapeutic purposes, and a device for facilitating this diagnostic process Download PDFInfo
- Publication number
- WO2002010119A1 WO2002010119A1 PCT/CZ2001/000041 CZ0100041W WO0210119A1 WO 2002010119 A1 WO2002010119 A1 WO 2002010119A1 CZ 0100041 W CZ0100041 W CZ 0100041W WO 0210119 A1 WO0210119 A1 WO 0210119A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- crystals
- aminolevulinic acid
- diagnostic
- diagnostic process
- preparation
- Prior art date
Links
- 239000013078 crystal Substances 0.000 title claims abstract description 33
- ZGXJTSGNIOSYLO-UHFFFAOYSA-N 88755TAZ87 Chemical compound NCC(=O)CCC(O)=O ZGXJTSGNIOSYLO-UHFFFAOYSA-N 0.000 title claims abstract description 30
- 229960002749 aminolevulinic acid Drugs 0.000 title claims abstract description 30
- 238000002405 diagnostic procedure Methods 0.000 title claims abstract description 16
- 238000002360 preparation method Methods 0.000 title claims abstract description 8
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 8
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000000126 substance Substances 0.000 claims abstract description 7
- 230000000694 effects Effects 0.000 claims abstract description 5
- 238000004519 manufacturing process Methods 0.000 claims abstract description 4
- 230000003287 optical effect Effects 0.000 claims description 3
- 238000000034 method Methods 0.000 abstract description 5
- 230000001613 neoplastic effect Effects 0.000 abstract 1
- 238000002560 therapeutic procedure Methods 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 description 3
- 206010028980 Neoplasm Diseases 0.000 description 2
- 239000002253 acid Substances 0.000 description 2
- 230000008033 biological extinction Effects 0.000 description 2
- 239000003086 colorant Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- RKTYLMNFRDHKIL-UHFFFAOYSA-N copper;5,10,15,20-tetraphenylporphyrin-22,24-diide Chemical compound [Cu+2].C1=CC(C(=C2C=CC([N-]2)=C(C=2C=CC=CC=2)C=2C=CC(N=2)=C(C=2C=CC=CC=2)C2=CC=C3[N-]2)C=2C=CC=CC=2)=NC1=C3C1=CC=CC=C1 RKTYLMNFRDHKIL-UHFFFAOYSA-N 0.000 description 2
- 125000004122 cyclic group Chemical group 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N d-alpha-tocopherol Natural products OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- 229960001295 tocopherol Drugs 0.000 description 2
- 229930003799 tocopherol Natural products 0.000 description 2
- 235000010384 tocopherol Nutrition 0.000 description 2
- 239000011732 tocopherol Substances 0.000 description 2
- 231100000419 toxicity Toxicity 0.000 description 2
- 230000001988 toxicity Effects 0.000 description 2
- GVJHHUAWPYXKBD-IEOSBIPESA-N α-tocopherol Chemical compound OC1=C(C)C(C)=C2O[C@@](CCC[C@H](C)CCC[C@H](C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-IEOSBIPESA-N 0.000 description 2
- 208000005452 Acute intermittent porphyria Diseases 0.000 description 1
- 102000018832 Cytochromes Human genes 0.000 description 1
- 108010052832 Cytochromes Proteins 0.000 description 1
- 102000001554 Hemoglobins Human genes 0.000 description 1
- 108010054147 Hemoglobins Proteins 0.000 description 1
- 206010036182 Porphyria acute Diseases 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 230000003749 cleanliness Effects 0.000 description 1
- 238000002574 cystoscopy Methods 0.000 description 1
- 238000003745 diagnosis Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000013399 early diagnosis Methods 0.000 description 1
- 238000001839 endoscopy Methods 0.000 description 1
- 238000005286 illumination Methods 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 238000011534 incubation Methods 0.000 description 1
- 208000008127 lead poisoning Diseases 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 210000004877 mucosa Anatomy 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 238000003860 storage Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/001—Preparation for luminescence or biological staining
- A61K49/0013—Luminescence
- A61K49/0017—Fluorescence in vivo
- A61K49/0019—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules
- A61K49/0021—Fluorescence in vivo characterised by the fluorescent group, e.g. oligomeric, polymeric or dendritic molecules the fluorescent group being a small organic molecule
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
- A61K41/0057—Photodynamic therapy with a photosensitizer, i.e. agent able to produce reactive oxygen species upon exposure to light or radiation, e.g. UV or visible light; photocleavage of nucleic acids with an agent
- A61K41/0061—5-aminolevulinic acid-based PDT: 5-ALA-PDT involving porphyrins or precursors of protoporphyrins generated in vivo from 5-ALA
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C227/00—Preparation of compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C227/38—Separation; Purification; Stabilisation; Use of additives
- C07C227/40—Separation; Purification
- C07C227/42—Crystallisation
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61B—DIAGNOSIS; SURGERY; IDENTIFICATION
- A61B5/00—Measuring for diagnostic purposes; Identification of persons
- A61B5/0059—Measuring for diagnostic purposes; Identification of persons using light, e.g. diagnosis by transillumination, diascopy, fluorescence
Definitions
- the present invention relates to preparation of sterile crystals of 5-aminolevulinic acid and its derivatives, consgrubie for medical diagnostic and therapeutic purposes and a device for facilitation of this diagnostic process.
- Appligation of the sterile crystals of 5-aminolevulinic acid, and its mixtures or compounds with substances suppressing influence of singlet oxygen, represents particularly suitable diagnostic and therapeutical means for diagnostics and treatment of tumors, in particular in urology, gynecology and dermatology.
- a device for facilitation of this process enables acquirement and storing of more accurate and reliable results.
- 5-Aminolevulinic acid is a physiological keystone of synthesis of porphyrines - precursors of formation of hemoglobin and cytochromes. Human organism produces approximately 0.5 g per 24 hrs of this acid, which is immediately transformed to other products. Only at pathological conditions, when the synthesis of porhyrines is impaired due to, e.g., lead intoxication or acute intermittent porphyria, ALA remains unused and is secreted out from the body. ALA can be routinely prepared in an industrial scale. Lately, high importance of ALA has been shown as a diagnostic and therapeutical means for photodynamic treatment and fluorescent endoscopy.
- a solution of ALA is applied on the bladder mucosa and after a certain time of incubation, cystoscopy is performed in blue light. This light induces red fluorescence caused by protoporphyrine IX in spots of tumor growth.
- the process enables early diagnosis of tumors detectable by other methods with difficulties. It is very important, for by this way it is possible to prevent patients from a complicated surgery.
- a sterile solution of ALA should be used because ALA is very unstable and under neutral or alkalic pH forms quickly yellow cyclic substances. Toxictty of these compounds is so far not examined and unfavorable effects on patient's health cannot be excluded.
- Preparation and sterilization of ALA and its use for diagnostic and therapeutical purposes is described in many patents, e.g., in published German patent applications DE-OS 197 44 811 or DE-OS 42 28 106, an American patent US 5 856 566 and the latest document WO 99/11 604 Dusa Pharmaceutical, Inc. (CA), where problems of ALA and its use in medical diagnostics are monitored.
- CA Dusa Pharmaceutical, Inc.
- Apparatuses used for diagnostics and treatment usually consist in a source of light and a filter, selecting wavelength. Filtered light illuminates a diagnosed spot, which is scanned, e.g., with a CCD camera, an endoscope or another apparatus, e.g. with optical cables, and resulting data are transmitted in the form of analog signal to a TV monitor.
- Disadvantages of such an equipment lies in limited resolution of TV monitors, which influences in particular realistic conversion and conservation of true colors, and also in limited possibilities of acquisition of necessary accurate values, required for objective analysis of information from this diagnostic process.
- the aim of the invention consists in preparation of sterilized crystals of ALA with warranted purity and negligible toxicity, with dimensions suitable for diagnostics, which are anisotropic with parallel extinction in a polarized light.
- the crystals should show long-term stability during storage, so that they might be applicable immediately in any time for the desirable purpose. Acquisition of very accurate diagnostic results - main followed quantities and values, and reliable color of illuminated diagnosed spots, which is one of the basic identification signs for successful assessment of medical diagnosis - is the second aim of the invention.
- the spot is then scanned with a CCD camera, an endoscope or an optical cable, and the signal is transmitted to a TV monitor.
- An output of the monitor is through an analog- to-digital converter connected to a computer with a graphic display, and to a controlling interface represented by a positioning device of the computer.
- Sterile crystals of 5-aminolevulinic acid were prepared by gamma-rays irradiation at the total dose of 25 kGy during 16 hours.
- the crystals with size 0.1 - 0.8 mm were maintained at deep-cooled state at temperature between -25 °C and - 30 °C.
- the crystals of ALA were clean and transparent, with the same shape as before the irradiation, belonging to hexagonal, tetragonal, orthorhombic or monoc ⁇ nic crystal systems. They showed anisotropic properties, with uniform extinction in a polarized light.
- tocopherol was chosen as a substance decreasing effects of singlet oxygen and free radicals.
- Crystals of ALA were irradiated by gamma irradiation at the total dose of 15 kGy during 13 hours; the crystals were undercooled to temperature -25 °C shortly before irradiation. Resulting characteristics of sterilized crystals shown a little worse cleanliness and transparency, A diagnostic process was not markedly limited, but brought worse general evaluation.
- FIG. 1 On the attached figure, a block diagram of a device for facilitation of a diagnostic process is shown.
- the device is assembled from a usually used part consisting in a CCD camera 1 and a TV monitor 2, to analog input 3 of which an analog-to-digital converter 4 is connected.
- the converter is connected to a computer 5 with a graphic monitor 6 and a controlling interface 7, represented by a positioning device.
- Diagnostic results in particular color scan of a diagnosed spot, can be realistically and reliable transferred to the graphic monitor 6 by means of this device.
- Measured values, coefficients and other parameters of the diagnosed spot are displayed at the same time.
- These data can be in digital and/or text formats, both in real time and in the form for recording in a databank or suitable forteletransmission through, e.g., the Internet.
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Pharmacology & Pharmacy (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Biochemistry (AREA)
- Molecular Biology (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Crystallography & Structural Chemistry (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Abstract
A method of preparation of sterile crystals of 5-aminolevulinic acid and its derivatives for medical diagnostic and therapeutic purposes and a device for the same. The crystals of 5-aminolevulinic acid with the size O.X - 0.8 mm, obtained by a standard industrial method, are cooled before and after irradiation to temperature between -25 and -30°C and irradiated by gamma rays at the total dose of 15 -30 kGy during 13-19 hours. To the crystals used in diagnostic process substances are added, eliminating effects of singlet oxygen and free radicals. The device facilitates a diagnostic process and enables more accurate and reliable analysis of data obtained from diagnostics and therapy of neoplastic illnesses. The data can be saved in a databank or transmitted to a distant equipment.
Description
Preparation of sterile crystals of 5-aminoIevuiinic acid utilized for medical diagnostic and therapeutic purposes, and a device for facilitating this diagnostic process.
BACKGROUND OF THE INVENTION
1. Field of the invention: The present invention relates to preparation of sterile crystals of 5-aminolevulinic acid and its derivatives, utilizabie for medical diagnostic and therapeutic purposes and a device for facilitation of this diagnostic process. Appligation of the sterile crystals of 5-aminolevulinic acid, and its mixtures or compounds with substances suppressing influence of singlet oxygen, represents particularly suitable diagnostic and therapeutical means for diagnostics and treatment of tumors, in particular in urology, gynecology and dermatology. A device for facilitation of this process enables acquirement and storing of more accurate and reliable results.
2. Description of Related Art
5-Aminolevulinic acid (ALA) is a physiological keystone of synthesis of porphyrines - precursors of formation of hemoglobin and cytochromes. Human organism produces approximately 0.5 g per 24 hrs of this acid, which is immediately transformed to other products. Only at pathological conditions, when the synthesis of porhyrines is impaired due to, e.g., lead intoxication or acute intermittent porphyria, ALA remains unused and is secreted out from the body. ALA can be routinely prepared in an industrial scale. Lately, high importance of ALA has been shown as a diagnostic and therapeutical means for photodynamic treatment and fluorescent endoscopy. For diagnostic purposes, e.g., in urology, a solution of ALA is applied on the bladder mucosa and after a certain time of incubation, cystoscopy is performed in blue light. This light induces red fluorescence caused by protoporphyrine IX in spots of tumor growth. The process enables early diagnosis of tumors detectable by other methods with difficulties. It is very important, for by this way it is possible to prevent patients from a complicated surgery.
For instillation, a sterile solution of ALA should be used because ALA is very unstable and under neutral or alkalic pH forms quickly yellow cyclic substances. Toxictty of these compounds is so far not examined and unfavorable effects on patient's health cannot be excluded.
Preparation and sterilization of ALA and its use for diagnostic and therapeutical purposes is described in many patents, e.g., in published German patent applications DE-OS 197 44 811 or DE-OS 42 28 106, an American patent US 5 856 566 and the latest document WO 99/11 604 Dusa Pharmaceutical, Inc. (CA), where problems of ALA and its use in medical diagnostics are monitored. In these documents, however, reasons of yellow or other colors of ALA crystals are not described, and possibility of presence of cyclic derivatives is not foreclosed for a certainty. Toxicity of these derivatives is not exactly known, what from medical point of view does not represent credibility for safe application, especially the internal one. Apparatuses used for diagnostics and treatment usually consist in a source of light and a filter, selecting wavelength. Filtered light illuminates a diagnosed spot, which is scanned, e.g., with a CCD camera, an endoscope or another apparatus, e.g. with optical cables, and resulting data are transmitted in the form of analog signal to a TV monitor.
Disadvantages of such an equipment lies in limited resolution of TV monitors, which influences in particular realistic conversion and conservation of true colors, and also in limited possibilities of acquisition of necessary accurate values, required for objective analysis of information from this diagnostic process.
The aim of the invention consists in preparation of sterilized crystals of ALA with warranted purity and negligible toxicity, with dimensions suitable for diagnostics, which are anisotropic with parallel extinction in a polarized light. The crystals should show long-term stability during storage, so that they might be applicable immediately in any time for the desirable purpose. Acquisition of very accurate diagnostic results - main followed quantities and values, and reliable color of illuminated diagnosed spots, which is one of the basic identification signs for successful assessment of medical diagnosis - is the second aim of the invention.
SUMMARY OF THE INVENTION
Above mentioned disadvantages concerning existing methods of production of sterilized crystals of ALA are eliminated by the present invention. -That is one object of the present invention to provide sterile crystals of 5-aminolevulinic acid, obtained by a standard industrial method, by irradiation with gamma rays. The crystals with size Q.X- 0.8 mm are irradiated by gamma rays at the total dose of 15 - 30 kGy during 13 - 19 hours. Before and after irradiation the crystals are maintained at deep-cooled state at temperatures between -25 °C and - 30 °C, and at a diagnostic process, substances decreasing effects of singlet oxygen and free radicals are added.
It is a further object of the present invention to provide a device facilitating a diagnostic process, consisting in a light source and a filter, by means of which a diagnosed place is illuminated. The spot is then scanned with a CCD camera, an endoscope or an optical cable, and the signal is transmitted to a TV monitor. An output of the monitor is through an analog- to-digital converter connected to a computer with a graphic display, and to a controlling
interface represented by a positioning device of the computer.
EXAMPLES OF REALIZATION OF THE INVENTION Example 1
Sterile crystals of 5-aminolevulinic acid were prepared by gamma-rays irradiation at the total dose of 25 kGy during 16 hours. The crystals with size 0.1 - 0.8 mm were maintained at deep-cooled state at temperature between -25 °C and - 30 °C. After irradiation, the crystals of ALA were clean and transparent, with the same shape as before the irradiation, belonging to hexagonal, tetragonal, orthorhombic or monocϋnic crystal systems. They showed anisotropic properties, with uniform extinction in a polarized light. For the proper diagnostic process, tocopherol was chosen as a substance decreasing effects of singlet oxygen and free radicals.
Example 2
In the second example irradiation of the same crystals of ALA were irradiated at the total dose of 25 kGy during 19 hours at temperature of crystal -30 °C. Prior to irradiation, the crystals were maintained at this temperature for very long time. It was found that the crystals of ALA showed identical properties, they were clear and transparent, with a needle-like or tetragonal shape. During the diagnostic process under illumination, a distinct red color was apparent in a diagnosed spot zone with very pronounced demarcation. Addition of tocopherol, suppressing effects of singlet oxygen, evidently facilitated the diagnostic process.
Example 3
Crystals of ALA were irradiated by gamma irradiation at the total dose of 15 kGy during 13 hours; the crystals were undercooled to temperature -25 °C shortly before irradiation. Resulting characteristics of sterilized crystals shown a little worse cleanliness and transparency, A diagnostic process was not markedly limited, but brought worse general evaluation.
Example 4
On the attached figure, a block diagram of a device for facilitation of a diagnostic process is shown. The device is assembled from a usually used part consisting in a CCD camera 1 and a TV monitor 2, to analog input 3 of which an analog-to-digital converter 4 is connected. The converter is connected to a computer 5 with a graphic monitor 6 and a controlling interface 7, represented by a positioning device.
Diagnostic results, in particular color scan of a diagnosed spot, can be realistically and reliable transferred to the graphic monitor 6 by means of this device. Followed values, coefficients and other parameters of the diagnosed spot are displayed at the same time. These data can be in digital and/or text formats, both in real time and in the form for recording in a databank or suitable forteletransmission through, e.g., the Internet.
From the above mentioned examples of preparation of the sterile crystals of ALA as well as from the example of realization of the device facilitating a diagnostic process by means of these crystals, two necessary conditions of reliable diagnostics, including patient's protection, follow: application of ALA crystals of high purity combined with substances suppressing effects of singlet oxygen, and use of a reliable device for evaluation of diagnostic results.
Accomplishment of both these conditions is provided by the submitted invention. It has appeared that the basic means for accurate diagnostics is maintaining the crystals of ALA in deep-cooled state before and after irradiation, as well as during it.
Claims
1. Preparation of sterile crystals of 5-aminolevulinic acid and its derivatives, utilizable for medical diagnostic and therapeutic purposes, wherein the crystals of 5-aminolevulinic acid obtained by a standard industrial method are irradiated by gamma rays, c h a r a ct e r i z e d i n t h a t the crystals of 5-aminolevulinic acid with size 0.X - 0.8 mm are irradiated at the total dose of 15 - 30 kGy of during 13 - 19 hours, wherein said crystals are maintained at deep- cooled state at temperatures between -25 °C and -30 °C, and wherein at a diagnostic process substances are added, which decrease effects of singlet oxygen and free radicals.
2. A device for facilitation of a diagnostic process, comprising a source of light and a filter, by which a diagnosed spot is illuminated and the illuminated place is scanned with a CCD camera, an endoscope or an optical cable, c h a r a c t e r i z e d i n th at an output (3) of an analog television signal is connected to an analog-to-digital converter (4), which is then linked to a computer (5) with a graphic monitor (6) and a controlling interface (7) represented by a positioning device of the computer (5).
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CZ20002783A CZ295986B6 (en) | 2000-07-28 | 2000-07-28 | Process for preparing sterile crystals of 5-aminolevulinic acid and derivatives thereof employable for medical diagnostic and therapeutic purposes |
| CZPV2000-2783 | 2000-07-28 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| WO2002010119A1 true WO2002010119A1 (en) | 2002-02-07 |
Family
ID=5471469
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PCT/CZ2001/000041 WO2002010119A1 (en) | 2000-07-28 | 2001-07-27 | Preparation of sterile crystals of 5-aminolevulinic acid utilized for medical diagnostic and therapeutic purposes, and a device for facilitating this diagnostic process |
Country Status (2)
| Country | Link |
|---|---|
| CZ (1) | CZ295986B6 (en) |
| WO (1) | WO2002010119A1 (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ301399B6 (en) * | 2004-09-03 | 2010-02-17 | Stabilizing dispersive base for photodynamic diagnostics and therapy |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999011604A1 (en) * | 1997-09-02 | 1999-03-11 | Dusa Pharmaceuticals, Inc. | Sterilized 5-aminolevulinic acid |
| US5954703A (en) * | 1997-10-31 | 1999-09-21 | Dusa Pharmaceuticals, Inc. | Method and apparatus for applying 5-aminolevulinic acid |
-
2000
- 2000-07-28 CZ CZ20002783A patent/CZ295986B6/en not_active IP Right Cessation
-
2001
- 2001-07-27 WO PCT/CZ2001/000041 patent/WO2002010119A1/en active Application Filing
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1999011604A1 (en) * | 1997-09-02 | 1999-03-11 | Dusa Pharmaceuticals, Inc. | Sterilized 5-aminolevulinic acid |
| US5954703A (en) * | 1997-10-31 | 1999-09-21 | Dusa Pharmaceuticals, Inc. | Method and apparatus for applying 5-aminolevulinic acid |
Non-Patent Citations (2)
| Title |
|---|
| BRIAN D REID: "Gamma processing technology: An alternative technology for terminal sterilization of Parenterals", PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY, BETHESDA, MD, US, vol. 49, no. 2, 1995, pages 83 - 89, XP002087677, ISSN: 1079-7440 * |
| KALKA K ET AL: "Photodynamic therapy in dermatology", JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, C.V. MOSBY, ST. LOUIS, MO, US, vol. 42, no. 3, March 2000 (2000-03-01), pages 389 - 413, XP000982056, ISSN: 0190-9622 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CZ20002783A3 (en) | 2002-03-13 |
| CZ295986B6 (en) | 2005-12-14 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| JP7522118B2 (en) | Modular endoscopy system for disease visualization | |
| US6863650B1 (en) | Endoscopic instrument for performing endoscopic procedures or examinations | |
| US6419626B1 (en) | Surgical instrument endoscope with CMOS image sensor and physical parameter sensor | |
| US6196226B1 (en) | Methods and apparatus for optically imaging neuronal tissue and activity | |
| US20230277220A1 (en) | Detachable motor | |
| KR101784063B1 (en) | Pen-type medical fluorescence image device and system which registers multiple fluorescent images using the same | |
| CN113766869A (en) | System and method for medical imaging using rolling shutter imagers | |
| Crosetti et al. | 3D exoscopic surgery (3Des) for transoral oropharyngectomy | |
| EP1427336A2 (en) | Intracorporeal probe for analysis or diagnosis and/or therapy in hollow organs and body cavities in the human or animal body | |
| US20090234236A1 (en) | Nerve blood flow modulation for imaging nerves | |
| CN117043871A (en) | Preoperative and surgical processing for surgical data scenarios | |
| Moghissi et al. | Fluorescence photodiagnosis in clinical practice | |
| RU2661029C1 (en) | Fluorescent navigation device for neurosurgery | |
| WO2002010119A1 (en) | Preparation of sterile crystals of 5-aminolevulinic acid utilized for medical diagnostic and therapeutic purposes, and a device for facilitating this diagnostic process | |
| US20180317774A1 (en) | Infection detection devices and methods | |
| DE102005019143A1 (en) | Malignant tissue diagnosing and therapy providing system, has projection system comprising control units and provided for projecting signal in correct position to object in operation area, where signal is generated by processing system | |
| Idoraşi et al. | Morphological aspects in remineralizing potential of Silver Diamine Fluoride | |
| CN113645889A (en) | System and method for connecting a medical imaging device to a medical imaging controller | |
| RU2369319C1 (en) | Method of projection representation of small parasagittal brain meningioms | |
| CN109645945A (en) | A kind of department of general surgery's clinic check device | |
| CA2500027A1 (en) | Portable, reusable visualization system | |
| US20230165658A1 (en) | Systems and methods for connecting a medical imaging device to a medical imaging controller | |
| CN221980702U (en) | Medical photodynamic multispectral electronic endoscope | |
| Naik | Characterization of a novel, in vivo, laparoscopic hyperspectral imaging system for minimally invasive surgery | |
| Bülbül et al. | A Different Use of Ultrasonography in Emergency Service; A Rare Sore Throat: Tongue Abscess |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| AK | Designated states |
Kind code of ref document: A1 Designated state(s): BR CA HU ID IL JP LV MX PL SI SK US |
|
| AL | Designated countries for regional patents |
Kind code of ref document: A1 Designated state(s): AT BE CH CY DE DK ES FI FR GB GR IE IT LU MC NL PT SE TR |
|
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| 121 | Ep: the epo has been informed by wipo that ep was designated in this application | ||
| 122 | Ep: pct application non-entry in european phase | ||
| NENP | Non-entry into the national phase |
Ref country code: JP |