CN1371290A - Rhodamine diagnostic agent and diagnostic method for detection of epithelial cancer - Google Patents
Rhodamine diagnostic agent and diagnostic method for detection of epithelial cancer Download PDFInfo
- Publication number
- CN1371290A CN1371290A CN00812220.2A CN00812220A CN1371290A CN 1371290 A CN1371290 A CN 1371290A CN 00812220 A CN00812220 A CN 00812220A CN 1371290 A CN1371290 A CN 1371290A
- Authority
- CN
- China
- Prior art keywords
- rhodamine
- tissue
- stain
- epithelium
- carcinous
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- PYWVYCXTNDRMGF-UHFFFAOYSA-N rhodamine B Chemical compound [Cl-].C=12C=CC(=[N+](CC)CC)C=C2OC2=CC(N(CC)CC)=CC=C2C=1C1=CC=CC=C1C(O)=O PYWVYCXTNDRMGF-UHFFFAOYSA-N 0.000 title claims description 20
- 238000002405 diagnostic procedure Methods 0.000 title claims description 3
- 238000001514 detection method Methods 0.000 title claims 2
- 229940039227 diagnostic agent Drugs 0.000 title description 3
- 239000000032 diagnostic agent Substances 0.000 title description 3
- 201000009030 Carcinoma Diseases 0.000 title 1
- 239000000203 mixture Substances 0.000 claims abstract description 32
- 210000000981 epithelium Anatomy 0.000 claims abstract description 14
- 238000000034 method Methods 0.000 claims abstract description 4
- 210000001519 tissue Anatomy 0.000 claims description 12
- HNONEKILPDHFOL-UHFFFAOYSA-M tolonium chloride Chemical compound [Cl-].C1=C(C)C(N)=CC2=[S+]C3=CC(N(C)C)=CC=C3N=C21 HNONEKILPDHFOL-UHFFFAOYSA-M 0.000 claims description 11
- 238000004140 cleaning Methods 0.000 claims description 6
- 206010028980 Neoplasm Diseases 0.000 claims description 4
- 230000006378 damage Effects 0.000 claims description 4
- 201000011510 cancer Diseases 0.000 claims description 3
- 239000003125 aqueous solvent Substances 0.000 claims description 2
- 210000004087 cornea Anatomy 0.000 claims description 2
- 239000007800 oxidant agent Substances 0.000 claims description 2
- 230000001590 oxidative effect Effects 0.000 claims description 2
- 239000003550 marker Substances 0.000 claims 1
- 230000000717 retained effect Effects 0.000 claims 1
- 239000001022 rhodamine dye Substances 0.000 abstract 1
- 238000003745 diagnosis Methods 0.000 description 8
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 210000000214 mouth Anatomy 0.000 description 6
- 238000002360 preparation method Methods 0.000 description 5
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- 238000004043 dyeing Methods 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 description 3
- 229960000583 acetic acid Drugs 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 231100000915 pathological change Toxicity 0.000 description 3
- 230000036285 pathological change Effects 0.000 description 3
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 208000003445 Mouth Neoplasms Diseases 0.000 description 2
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 2
- 239000012362 glacial acetic acid Substances 0.000 description 2
- 238000007689 inspection Methods 0.000 description 2
- 208000012987 lip and oral cavity carcinoma Diseases 0.000 description 2
- 210000003470 mitochondria Anatomy 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- -1 rhodamine ester Chemical class 0.000 description 2
- 238000012216 screening Methods 0.000 description 2
- 210000004881 tumor cell Anatomy 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- BDKLKNJTMLIAFE-UHFFFAOYSA-N 2-(3-fluorophenyl)-1,3-oxazole-4-carbaldehyde Chemical compound FC1=CC=CC(C=2OC=C(C=O)N=2)=C1 BDKLKNJTMLIAFE-UHFFFAOYSA-N 0.000 description 1
- BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 1
- AGIJRRREJXSQJR-UHFFFAOYSA-N 2h-thiazine Chemical compound N1SC=CC=C1 AGIJRRREJXSQJR-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- 101100309716 Arabidopsis thaliana SD18 gene Proteins 0.000 description 1
- 208000017897 Carcinoma of esophagus Diseases 0.000 description 1
- 206010011968 Decreased immune responsiveness Diseases 0.000 description 1
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 description 1
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- 206010030155 Oesophageal carcinoma Diseases 0.000 description 1
- BPQQTUXANYXVAA-UHFFFAOYSA-N Orthosilicate Chemical compound [O-][Si]([O-])([O-])[O-] BPQQTUXANYXVAA-UHFFFAOYSA-N 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 230000001093 anti-cancer Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000000872 buffer Substances 0.000 description 1
- 239000007853 buffer solution Substances 0.000 description 1
- 150000001768 cations Chemical class 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 201000005619 esophageal carcinoma Diseases 0.000 description 1
- 210000002744 extracellular matrix Anatomy 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 210000001035 gastrointestinal tract Anatomy 0.000 description 1
- 238000010562 histological examination Methods 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 230000003902 lesion Effects 0.000 description 1
- ZDGGJQMSELMHLK-UHFFFAOYSA-N m-Trifluoromethylhippuric acid Chemical compound OC(=O)CNC(=O)C1=CC=CC(C(F)(F)F)=C1 ZDGGJQMSELMHLK-UHFFFAOYSA-N 0.000 description 1
- 229920002521 macromolecule Polymers 0.000 description 1
- 230000003458 metachromatic effect Effects 0.000 description 1
- QPJVMBTYPHYUOC-UHFFFAOYSA-N methyl benzoate Chemical compound COC(=O)C1=CC=CC=C1 QPJVMBTYPHYUOC-UHFFFAOYSA-N 0.000 description 1
- 210000002200 mouth mucosa Anatomy 0.000 description 1
- 210000004400 mucous membrane Anatomy 0.000 description 1
- 150000007523 nucleic acids Chemical class 0.000 description 1
- 102000039446 nucleic acids Human genes 0.000 description 1
- 108020004707 nucleic acids Proteins 0.000 description 1
- 235000019629 palatability Nutrition 0.000 description 1
- 230000007170 pathology Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 230000008447 perception Effects 0.000 description 1
- 150000003222 pyridines Chemical class 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- 239000007974 sodium acetate buffer Substances 0.000 description 1
- 229940087562 sodium acetate trihydrate Drugs 0.000 description 1
- BHZOKUMUHVTPBX-UHFFFAOYSA-M sodium acetic acid acetate Chemical compound [Na+].CC(O)=O.CC([O-])=O BHZOKUMUHVTPBX-UHFFFAOYSA-M 0.000 description 1
- WXMKPNITSTVMEF-UHFFFAOYSA-M sodium benzoate Chemical compound [Na+].[O-]C(=O)C1=CC=CC=C1 WXMKPNITSTVMEF-UHFFFAOYSA-M 0.000 description 1
- 239000004299 sodium benzoate Substances 0.000 description 1
- 235000010234 sodium benzoate Nutrition 0.000 description 1
- 238000010186 staining Methods 0.000 description 1
- 210000004895 subcellular structure Anatomy 0.000 description 1
- 238000012360 testing method Methods 0.000 description 1
- 229950003937 tolonium Drugs 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- AURFVNDXGLQSNN-UHFFFAOYSA-K trisodium 2-hydroxypropane-1,2,3-tricarboxylic acid phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O.OC(=O)CC(O)(C(O)=O)CC(O)=O AURFVNDXGLQSNN-UHFFFAOYSA-K 0.000 description 1
- XPFJYKARVSSRHE-UHFFFAOYSA-K trisodium;2-hydroxypropane-1,2,3-tricarboxylate;2-hydroxypropane-1,2,3-tricarboxylic acid Chemical compound [Na+].[Na+].[Na+].OC(=O)CC(O)(C(O)=O)CC(O)=O.[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O XPFJYKARVSSRHE-UHFFFAOYSA-K 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
- A61K49/006—Biological staining of tissues in vivo, e.g. methylene blue or toluidine blue O administered in the buccal area to detect epithelial cancer cells, dyes used for delineating tissues during surgery
-
- 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
- A61K49/0041—Xanthene dyes, used in vivo, e.g. administered to a mice, e.g. rhodamines, rose Bengal
-
- 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
- A61K49/0063—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres
- A61K49/0069—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form
- A61K49/0071—Preparation for luminescence or biological staining characterised by a special physical or galenical form, e.g. emulsions, microspheres the agent being in a particular physical galenical form solution, solute
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Biomedical Technology (AREA)
- Epidemiology (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Biodiversity & Conservation Biology (AREA)
- Optics & Photonics (AREA)
- Oncology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Physics & Mathematics (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
Rhodamine dye compositions and methods for detecting and/or delineating cancerous and precancerous epithelial tissue.
Description
The present invention relates to novel diagnostic agent, be used to detect carcinous and epithelial tissue precancer.
According to a further aspect, the present invention relates to novel method, its be used for detecting and/or describe carcinous and/or precancer epithelial tissue.
The present invention relates to such diagnotor and agents useful for same thereof on the other hand, they especially can be used for the possible oral cancer patient of screening in the body, as the routine inspection of dentist or doctor physician or the part of program, for example regular dentistry or internal medicine inspection, tooth cleaning etc.
The present invention is relating in one aspect to such program and composition therefor thereof in addition, and they use than easier acquisition of the used stain of prior art program and/or synthetic more cheap Yu simpler and/or purer stain.
The present invention is in the body internal program and the compositions that relate in one aspect to a kind of like this stain of employing in addition, although prior art has opposite instruction, but this stain is enough nontoxic, so that by cleaning whole oral cavity and/or gargling and can be used.
Be used to detect the in-vivo diagnostic program that worsens anterior epithelium cornea damage, for example oral injury and oral cancer and adopt such stain compositions, the selected property ground of organizing that they are taken place because of abnormal development, hypertrophy, tumor and other active surface damages are unusual keeps, and these programs are known in the art.For example, adopt the program of fluorescein or fluorescein derivative to be disclosed among Chenz " Chinese stomatology magazine " (27:44-47 (1992)) and the Filurin (" stomatology " (Russia) 72:44-47 (1993)).These programs relate to and being coated with stain, under uviol lamp, with the naked eye check then, with detect selectivity fluorescigenic carcinous/precancer tissue.
Another kind of prior art program relates in the body cleans with blutene, is normal macroscopy then, to detect the tissue of all selectively stainings.Such program for example is disclosed in the United States Patent (USP) 4,321,251 of the United States Patent (USP) 5,372,801 of Tucci etc. and Mashberg.Toluidine blue has used many decades as vitro tissue pathology stain.It has become known metachromatic stain by this purposes, and is extremely pink the nuclear purple that is rich in DNA and RNA.When stain combined with nucleic acid or other acid cellular macromolecules, the inherent navy blue of blutene became purple or pink.Certainly, such dyeing depends on that stain enters inner subcellular structure, for example nuclear.Only with formaldehyde or other ruptured cell films but the reagent that does not destroy the general structure of cell " fix " tissue samples and can be easy to realize this entering.
Opposite with the mechanism that relates to external purposes, the dyeing oral cavity tissue is because it can the penetration cell wall and depends on mitochondrion in the blutene body, and it is longer that mitochondrion keeps the time ratio extracellular matrix components of stain.
The program of Mashberg relates to gargling with blutene solution cleans whole oral cavity, and water and acetic acid clean to remove not by stain carcinous or tissue reservation precancer then.After 10-14 days, directly, carry out tentative diagnosis then by the Mashberg program to suspecting that the position is coated with the blutene compositions.Tucci's ' 801 patent disclosure according to the employed improvement blutene of the general program compositions of Mashberg instruction.
Papazian " clinical and biology of gastroenterology " 9:16-22 (1985) has proposed a kind of body internal program, relates to the purposes of Lv Geer solution (Lugol ' s solution) (iodine) and blutene, is used for detecting simultaneously the esophageal carcinoma and last air flue digestive tract cancer.
Recently, the United States Patent (USP) 5,882,627 of Pomerantz discloses a class formation Ming Que De oxazine and a thiazine stain, and they generally can be used for the Mashberg diagnosis scheme.
Bemal etc. " cancer research " 43,716-720 (1983) disclose external optionally anticancer growth of rhodamine stain and kill cancer cell.The United States Patent (USP) 5 of Gaboury etc., 773,460 disclose rhodamine is preferentially kept by a lot of tumor cells, has proposed some rhodamine ester and can be used for the external smooth power inhibition of some tumor cell line, but pointed out that also general toxicity may limit its serviceability in chemotherapy.
Rhodamine is 2-(6-amino-3-imino group-3H-xanthene-9-yl) essence of Niobe and ion salt thereof, for example hydrochlorate, is pyridines lipophilic cation stain.General according to Mashberg's the disclosed scheme of ' 251 patent, be applied to epithelium by the part, then by normal macroscopy, it effectively selectivity differentiate and/or describe carcinous and precancer epithelial tissue.
The stain that is fit to be applied to epithelial tissue is preparation like this with the rhodamine compositions, with this stain and the pharmaceutically acceptable solvent that is fit to.Preferably, with the pH of the pharmaceutically acceptable buffer system adjusting rhodamine solution that is fit to, so that final solution is isoosmotic basically, the pH scope is approximately 2.5 to 7, is preferably 4.0-5.0.This can realize with acetic acid-sodium acetate buffer system.Other buffer systems that are fit to comprise citric acid-sodium citrate, or blended silicate system, for example citric acid-sodium phosphate etc.
Being used to the solvent of liquid rhodamine stain compositions of the present invention is provided is a kind of aqueous solvent.According to the present preferred embodiment of the present invention, that solvent comprises is pharmaceutically acceptable, just nontoxic, anergy is pure, ethanol for example.But such solvent can not disturb dyeing mechanism in perception ground, itself can not help stain to be reduced to the procrypsis form from the colour developing form yet.
If use, can add the stable correctives of other components of stain compositions, to improve the palatability of compositions as oral cavity " washing liquid ".
Preferably regulate rhodamine stain measuring to concentration in fluid composition and account for 1% of final composition weight greatly, but also can adopt higher concentration, lower concentration also be at least part effectively.Now, my preferential the employing contains the 0.5 stain compositions to about 3.5 weight % rhodamine components of having an appointment.
The compositions that is used for the inventive method is also contained in the present invention, and wherein by ' the 801 disclosed mode of patent comprises pharmaceutically acceptable oxidant to be similar to Tucci's, any procrypsis form that is present in the stain in the compositions is oxidized to the colour developing form.
Embodiment
The purpose that the following example is provided is to set forth working of an invention to those skilled in the art, but does not limit its scope, and invention scope only is defined by the claims.
Embodiment 1
The preparation of diagnosis composition
In each component shown in following ratio (weight %) mixing, the preparation diagnosis composition:
Pure water U.S.P. 83.85
Glacial acetic acid U.S.P. 4.61
Sodium acetate trihydrate U.S.P. 2.45
SD18 ethanol 7.48
30% hydrogen peroxide, U.S.P. 0.41
IFF Fructus Rubi IC563457 0.20
Rhodamine 1.00
Embodiment 2
The preparation of cleaning solution
In shown in ratio (weight %) mix following component, the preparation cleaning solution:
Pure water U.S.P. 98.70
Glacial acetic acid U.S.P. 1.00
Sodium benzoate U.S.P. 0.10
IFF Fructus Rubi IC563457 0.20
Embodiment 3
Clinical effectiveness
The disclosed diagnosis scheme of ' 251 patent that utilizes Mashberg's, the clinical effectiveness of comparing embodiment 1 and 2 compositionss and the prepared blutene diagnosis reference composition (diagnostic control composition) of ' 801 patent according to Tucci's.
At first adopt TBO reference composition screening pathological change of oral cavity patient.After differentiating potential carcinous or precancerous lesion, water and embodiment 2 acetic acid washing liquids are cleaned repeatedly and are suspected the position, remove all TBO vestiges.
Use the testee of the patient of performance pathological change of oral cavity then as embodiment 1 rhodamine diagnosis composition.2-3cc rhodamine compositions is applied to the pathological changes mucous membrane surface, cleans with washed mixture and water then, to remove excessive rhodamine compositions.
The histological examination of embodiment 1 rhodamine diagnosis composition dyeing part tissue confirms, the rhodamine compositions at least differentiate with describe carcinous and precancer epithelial tissue on the same effective with blutene.
Embodiment 4
Repeat the program of embodiment 3, but gargle, be applied to oral mucosa, rather than directly be applied to suspection part, position by cleaning with test and reference composition.Obtain identical result.
My invention is open to the degree that makes those skilled in the art understand and to implement, and discloses preferred embodiment at present.
Claims (3)
1, be used to differentiate and describe the diagnostic method of carcinous epithelial tissue, comprise:
(a) rhodamine is applied to epithelium, with the selected marker cancerous tissue; With
(b) carcinous tissue site is differentiated and described to be suspect to be to the described epithelium of macroscopy by the color at position more under a cloud and the color of adjacent tissue.
2, worsen the interior detection method of body of anterior epithelium cornea damage and cancer, comprise following consecutive steps:
With being cleaned epithelium with the stain compositions that precancer, tissue selectivity kept by carcinous, wherein this stain compositions form by blutene basically and
Clean epithelium with cleaning combination, removing the stain compositions that is not retained,
The improvement of this method is that wherein this stain compositions comprises rhodamine.
3, be used for detecting in the body biological stain compositions carcinous and tissue precancer, comprise
(a) rhodamine,
(b) pharmaceutically acceptable aqueous solvent and
(c) be used for the pharmaceutically acceptable oxidant of procrypsis rhodamine.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/US2000/018126 WO2002002149A1 (en) | 2000-06-30 | 2000-06-30 | Rhodamine diagnostic agent and diagnostic methods for detection of epithelial cancer |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN1371290A true CN1371290A (en) | 2002-09-25 |
Family
ID=21741551
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN00812220.2A Pending CN1371290A (en) | 2000-06-30 | 2000-06-30 | Rhodamine diagnostic agent and diagnostic method for detection of epithelial cancer |
Country Status (11)
| Country | Link |
|---|---|
| EP (1) | EP1294408A4 (en) |
| JP (1) | JP2004501982A (en) |
| CN (1) | CN1371290A (en) |
| AU (1) | AU784558B2 (en) |
| BR (1) | BR0013636A (en) |
| CA (1) | CA2383697A1 (en) |
| IL (1) | IL148341A0 (en) |
| MX (1) | MXPA02002184A (en) |
| NO (1) | NO20020958L (en) |
| NZ (1) | NZ517445A (en) |
| WO (1) | WO2002002149A1 (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109768151A (en) * | 2019-01-04 | 2019-05-17 | 浙江大学 | It is a kind of to illuminate and show with multi-colored led and preparation method thereof |
Family Cites Families (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69229471T2 (en) * | 1991-10-31 | 1999-11-25 | Zila Inc | BIOLOGICAL DYE COMPOSITION, PROCESS FOR ITS PRODUCTION AND USE FOR MARKING THE OUTLINE OF EPITHELIC CARSINOMAS |
| US5618831A (en) * | 1992-11-17 | 1997-04-08 | Fuji Photo Film Co., Ltd. | Composition and method for treating cancer |
| CA2214829C (en) * | 1996-01-16 | 2002-05-14 | Edwin Pomerantz | Methods and compositions for in-vivo detection of oral cancers and precancerous conditions |
| WO2001064110A1 (en) * | 2000-02-28 | 2001-09-07 | Zila, Inc. | Method for detecting and killing epithelial cancer cells |
-
2000
- 2000-06-30 BR BR0013636-0A patent/BR0013636A/en not_active Application Discontinuation
- 2000-06-30 EP EP00946949A patent/EP1294408A4/en not_active Withdrawn
- 2000-06-30 JP JP2002506770A patent/JP2004501982A/en active Pending
- 2000-06-30 AU AU16752/02A patent/AU784558B2/en not_active Ceased
- 2000-06-30 CA CA002383697A patent/CA2383697A1/en not_active Abandoned
- 2000-06-30 MX MXPA02002184A patent/MXPA02002184A/en not_active Application Discontinuation
- 2000-06-30 IL IL14834100A patent/IL148341A0/en unknown
- 2000-06-30 CN CN00812220.2A patent/CN1371290A/en active Pending
- 2000-06-30 WO PCT/US2000/018126 patent/WO2002002149A1/en active IP Right Grant
- 2000-06-30 NZ NZ517445A patent/NZ517445A/en unknown
-
2002
- 2002-02-27 NO NO20020958A patent/NO20020958L/en not_active Application Discontinuation
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN109768151A (en) * | 2019-01-04 | 2019-05-17 | 浙江大学 | It is a kind of to illuminate and show with multi-colored led and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| EP1294408A1 (en) | 2003-03-26 |
| NO20020958D0 (en) | 2002-02-27 |
| IL148341A0 (en) | 2002-09-12 |
| NO20020958L (en) | 2002-04-24 |
| JP2004501982A (en) | 2004-01-22 |
| AU784558B2 (en) | 2006-05-04 |
| MXPA02002184A (en) | 2002-09-30 |
| AU1675202A (en) | 2002-01-14 |
| NZ517445A (en) | 2004-03-26 |
| BR0013636A (en) | 2005-01-11 |
| EP1294408A4 (en) | 2005-01-05 |
| WO2002002149A1 (en) | 2002-01-10 |
| CA2383697A1 (en) | 2002-01-10 |
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