CN100534428C - Application of haematopophyrin in treating ophthalmic disease - Google Patents
Application of haematopophyrin in treating ophthalmic disease Download PDFInfo
- Publication number
- CN100534428C CN100534428C CNB031505538A CN03150553A CN100534428C CN 100534428 C CN100534428 C CN 100534428C CN B031505538 A CNB031505538 A CN B031505538A CN 03150553 A CN03150553 A CN 03150553A CN 100534428 C CN100534428 C CN 100534428C
- Authority
- CN
- China
- Prior art keywords
- monomethyl ether
- ethyl
- hematoporphyrin monomethyl
- new vessels
- choroid
- 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.)
- Expired - Lifetime
Links
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/22—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains four or more hetero rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/40—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with one nitrogen as the only ring hetero atom, e.g. sulpiride, succinimide, tolmetin, buflomedil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/10—Ophthalmic agents for accommodation disorders, e.g. myopia
Abstract
An application of hematopropyrin monomethylether as a photosensitizer in treating ophthalmopathy by photodynamic therapy is disclosed. Said diseases may be yellow spot degeneration, eye histoplasmosis, myopia, etc.
Description
Technical field
The present invention relates to field of medicaments, relate more specifically to utilize hematoporphyrin monomethyl ether, treat the application of ophthalmic diseases by eye being applied optical dynamic therapy (PDT).
Background technology
Visual loss is the FAQs that accompanies with old and feeble and various oculopathy.Old and feeble and other causes of disease often cause the generation of deleterious neovascularization on cornea, iris, retina or the choroid, cause visual deterioration and even visual loss.In a lot of known oculopathy, comprise that the choroid neovascularization causes hemorrhage and fibrosis in degeneration of macula, ocular histoplasmosis syndrome, myopia and the diseases associated with inflammation, finally with visual loss.
The degeneration of macula relevant with the age (AMD) is the main cause of old people's visual deterioration, and wherein 10% patient AMD follows the choroid neovascularization, causes rapid visual loss.According to statistics, AMD causes old people's 80% in newly blind to be caused by the choroid neovascularization.
The choroid neovascularization that AMD is caused at present mainly adopts laser light (solid) method of coagulating to treat, and this method can be sealed new vessels, delays visual loss.But also destroyed the normal tela chorioidea around the new vessels and the retinal tissue of internal layer when laser light is coagulated, caused visual deterioration, the patient often leaves atrophic cicatrix and vision blind spot.Another problem of laser Photocoagulation is a most patients to be not suitable for coagulating the method treatment with laser light because of new vessels disperse, obscure boundary, or unsatisfactory curative effect, the relapse rate height.
Photodynamic therapy is to impose Photoactive compounds to the patient, and photosensitizer again with low-intensity laser irradiation, excites photosensitizer to make it to produce photochemical reaction in the enrichment of new vessels position, optionally seals new vessels.This method selectivity is stronger, and laser intensity is low, and is little to the normal surrounding tissue damage, is expected to become the effective means of treatment AMD.
The photosensitizer that is used for optical dynamic therapy has hematoporphyrin derivative (HPD), benzoporphyrin derivative (BPD), chlorin e 6 monoammonium aspartate amide (Npe6), sulfonic acid aluminum phthalocyanine (CASPc), intermediary four (hydroxy phenyl)-chlorin (mTIIPC), stannum ethyl just C.I. Natural Red 8 (SnEt2), 5-amino-laevulic acid (ALA) etc., is used for tumor, dermopathic optical dynamic therapy.Yet these photosensitizer that are used for tumor, dermopathic optical dynamic therapy extremely are not suitable for treating ophthalmic diseases.
United States Patent (USP) 5798349 and corresponding Chinese patent 97192957 disclose the application of green porphyrin (greenporphyrins) in optical dynamic therapy AMD and other choroid neovascularization.Yet its therapeutic effect is still unsatisfactory.
Therefore, this area presses for exploitation new therapeutic agent and Therapeutic Method, so that effectively treatment is because of being harmful to the various ophthalmic diseasess that vascularization causes.
Summary of the invention
Purpose of the present invention just provides a kind of new therapeutic agent and Therapeutic Method, and they can effectively treat the various ophthalmic diseasess that cause because of harmful vascularization.
In a first aspect of the present invention, a kind of purposes of hematoporphyrin monomethyl ether is provided, it is used to prepare the medicine for the treatment of ophthalmic diseases.
In another preference, described ophthalmic diseases is to form the disease that causes because of deleterious new vessels.
In another preference, described new vessels forms and occurs in cornea, iris, retina or choroid.More preferably, described new vessels forms and occurs on the choroid.
In another preference, described ophthalmic diseases is selected from down group: degeneration of macula, ocular histoplasmosis syndrome, myopia or diseases associated with inflammation.
In another preference, described hematoporphyrin monomethyl ether is the chemical compound of following structural formula
In the formula, R1 is 1-hydroxyl-ethyl, 1-methoxyl group-ethyl; R2 is 1-hydroxyl-ethyl, 1-methoxyl group-ethyl.
In another preference, the dosage of described medicine is the 0.1-100mg/kg body weight, presses hematoporphyrin monomethyl ether and calculates.
In another preference, described treatment is an optical dynamic therapy.
In another preference, described optical dynamic therapy condition is that the luminous flux of irradiation is 50-200 joule/cm
2, illuminance is 50-800mW/cm
2, wavelength is 630 ± 20nm.
In a second aspect of the present invention, the purposes of hematoporphyrin monomethyl ether is provided, it is used as the photosensitizer of optical dynamic therapy ophthalmic diseases.
Description of drawings
Fig. 1 has shown the structural formula of hematoporphyrin monomethyl ether.
Fig. 2 A and 2B have shown the effect of hematoporphyrin monomethyl ether on chick chorioallantoic membrane (CAM) model.
Fig. 3 has shown chick chorioallantoic membrane (CAM) model experiment group, matched group one-level blood vessel, secondary vascular counts.
Fig. 4 has shown choroidal neovascularization (CNV) model fluoroscopic visualization.
Fig. 5 has shown choroidal neovascularization (CNV) model tissue slice.
Fig. 6 A and 6B have shown the effect of hematoporphyrin monomethyl ether on choroidal neovascularization (CNV) model.Wherein Fig. 6 A is the matched group tissue slice, and the arrow indication is a choroidal neovascularization.Fig. 6 B is the experimental group tissue slice, and the arrow indication is a choroidal neovascularization, and internal blood vessel has formed thrombosis.
The specific embodiment
Extensive studies has been screened a large amount of chemical compounds to the inventor through going deep into, and finds that the chemical compound hematoporphyrin monomethyl ether is particularly suitable for treating ophthalmic diseases.The optimum absorb wavelength 630nm of hematoporphyrin monomethyl ether, checkout time is short, and photosensitivity can disappear in 24 hours, therefore was suitable as the photosensitizer of photodynamic therapy treatment ophthalmic diseases.Finished the present invention on this basis.
Photoactive compounds
Being suitable for chemical compound of the present invention is hematoporphyrin monomethyl ether.Xu Deyu, Chen Wenhui etc. " Chinese laser medical journal " (1993,2:3-7) and application number be physicochemical property, preparation method and the application in the treatment tumor thereof that discloses hematoporphyrin monomethyl ether in 01131939 the Chinese patent; Chen Wenhui, Xu Deyu etc. are at " The 2nd Army Medical College journal " (1990,11:118-122) delivered hematoporphyrin monomethyl ether in the intravital distribution of tumor-bearing mice: Gu Ying, Liu Guangfan etc. are at " Chinese laser medical journal " (2000, Vol9,1 phase) delivered hematoporphyrin monomethyl ether in the absorption of arterial tissue and distribution character, vascular smooth muscle absorption characteristic to blood quinoline methyl ether, at " Chinese laser medical journal " (2000, Vol9,3 phases) delivered the application of hematoporphyrin monomethyl ether treatment nevus flammeus.All open as a reference at this.
Particularly, be suitable for Photoactive compounds of the present invention and have following structural formula:
Wherein R1 is 1-hydroxyl-ethyl, 1-methoxyl group-ethyl; R2 is 1-hydroxyl-ethyl, 1-methoxyl group-ethyl.Preferably, when R1 was 1-hydroxyl-ethyl, R2 was 1-methoxyl group-ethyl; When R1 was 1-methoxyl group-ethyl, R2 was 1-hydroxyl-ethyl.
Hematoporphyrin monomethyl ether also can be united use with other Photoactive compounds; But the effectiveness of treatment depends on light and is absorbed by Photoactive compounds, therefore, if use mixture, then uses to good with the compound with similar maximum absorption band.
Treatment mechanism
The present invention relates to use the optical dynamic therapy ophthalmic diseases.The photodynamic therapy scheme causes deleterious neovascularization (particularly choroidal neovascularization) reduction, thereby therapeutical effect is played in relevant ophthalmic diseases, improves patient's vision.
In the method for the invention, giving needs the patient of treatment to take suitable Photoactive compounds, presents in an amount at least sufficient to make the Photoactive compounds of patient's ophthalmic to reach valid density.Take after after a while, make the chemical compound of valid density accumulate in the ophthalmic desired zone after, use the rayed that is absorbed by this Photoactive compounds should the zone.Photoactive compounds is produced active oxygen and free radical by optical excitation, causes lesion region cell photochemical damage, the new vessels of sealing diseased region, thus treatment finally improves patient's vision because of the various ophthalmic diseasess that harmful vascularization causes.
Administration and dosage
Photoactive compounds can various administrations, as oral, parenterai administration or rectally, maybe chemical compound directly can be put as in pleasing to the eye.Be advisable with parenterai administration, as intravenous, intramuscular or subcutaneous injection.With intravenous injection is best.
The dosage of Photoactive compounds can be according to administering mode, preparation type, whether coupling targeting part has very big variation.It is generally acknowledged, relevant between preparation, administering mode and the dosage level of optical active matter.Usually, the typical doses scope of hematoporphyrin monomethyl ether is 0.1-100mg/kg, and preferable dosage range is 0.5-50mg/kg, and better dosage range is 1-10mg/kg.Those skilled in the art also can be determined by experiment proper dosage.
Being used for various parameters effective, the selective light photodynamic therapy in the present invention is to be mutually related.Therefore, can adjust dosage with respect to other parameters (for example in the photodynamic therapy interval between employed luminous flux, illuminance, persistent period and dosage, administration and the rayed etc.).The obvious damage of using these parameters all should adjust to significantly improve vision and not producing normal ocular tissue is advisable.Those skilled in the art can be determined by experiment suitable parameters.
In other words, when the dosage of Photoactive compounds reduced, the luminous flux of sealing choroidal neovascular tissue had the trend of increase; Otherwise need to reduce luminous flux, then need to increase the dosage of Photoactive compounds or increase the enrichment degree that the targeting promotion increases the diseased region Photoactive compounds.
The light Therapeutic Method
Some term of light treatment relating to parameters is different in different authors and publication.Such as luminous flux, also claim light dosage, optical energy density; Illuminance also claims power level, power density.These terms are that those skilled in the art uses and understands, and are illustrated at this.
After the Photoactive compounds administration, the target tissue of eye is shone under selecteed drug absorption wavelength.For hematoporphyrin monomethyl ether, selected wave-length coverage about 630 ± 20nm, more preferably is that the penetration power of this range of wavelength in body tissue is relatively good about 630 ± 10nm generally.
The result of irradiation causes Photoactive compounds to be in excited state, and interacts with other chemical compounds, forms singlet oxygen (Singlet Oxygen) and other free radicals, causes the structural deterioration of blood vessel epithelial cell.Singlet oxygen and other free radical main damage membrane structures comprise cell membrane, mitochondrial membrane, lysosome membrane and nuclear membrane.The damage of blood vessel epithelial cell causes follow-up platelet aggregation, takes off granule and thrombosis, causes the obstruction and the sealing of blood vessel.
According to the type, the target tissue degree of depth of tissue and the amount of fluid or blood on it, the luminous flux of irradiation can have very cataclysm.But that preferable is 50-200 joule/cm
2
Illuminance generally changes in 50-800mW/cm
2, with about 100-600mW/cm
2For good.Yet, select to use higher illuminance, can shorten treatment time and reach same effect.
After the Photoactive compounds administration to the most in good time interbody spacer between the light treatment also according to administering mode, form of medication and preparation type and different.Interval after the photosensitizer administration was from 1 minute to 2 hours, and preferable is 5-30 minute, and better is 10-25 minute.
Medicable ophthalmic diseases
The invention provides a kind of method of optical dynamic therapy ophthalmic diseases, comprising that patient to this treatment of needs takes is enough to make the Photoactive compounds preparation of being treated enrichment q.s photosensitizer in patient's eye; Allow time enough that the Photoactive compounds of effective dose is enriched in patient's eye; With the rayed eyes that are fit to sensitiser absorption.
Because in Therapeutic Method of the present invention, utilize hematoporphyrin monomethyl ether, reduce or eliminate deleterious neovascularization on cornea, iris, retina or the choroid effectively by photodynamic therapy, so the inventive method can be used for treating the various ophthalmic diseasess that cause because of harmful vascularization.Representative ophthalmic diseases comprises (but being not limited to): degeneration of macula (degeneration of macula relevant with the age and other degeneration of macula), ocular histoplasmosis syndrome, myopia and diseases associated with inflammation.
The evaluation of treatment
The damage of the effect of optical dynamic therapy available histology's sections observation endotheliocyte on animal model and the encapsulation situations of choroidal neovascularization.Typically, the destruction of new vessels shows as in the vascular endothelial cell endochylema and cavity occurs, and the nucleus shrinkage is unusual, the formation of visible platelet aggregation and blood clot in the lumen of vessels.
Another kind method is the time specific after treatment to observe neovascularity with the angiography technology to reduce.
Below in conjunction with specific embodiment, further set forth the present invention.Should be understood that these embodiment only to be used to the present invention is described and be not used in and limit the scope of the invention.The experimental technique of unreceipted actual conditions in the following example is usually according to the normal condition or the condition of advising according to manufacturer.
Embodiment 1: the preparation of hematoporphyrin monomethyl ether and therapeutic agent
A. the preparation of hematoporphyrin monomethyl ether
Press the method described in the Chinese patent application of CN 01131939, with 20 grams 3, the methanol mixed liquor stirring reaction of 8-two (1-bromoethyl) deuteroporphyrin IX hydrobromate and 3000 milliliters 2 hours, reactant liquor is regulated pH to 13 with the sodium hydroxide of 10mol/L, stirred 4 hours, with the pH to 4-5 of glacial acetic acid conditioned reaction liquid, separate out precipitation again.The precipitation that buchner funnel filter collection is separated out, washing, drying gets 19.5 gram crude products.Get 3.9 gram hematoporphyrin monomethyl ethers (Fig. 1) through silica gel column chromatography separating purification.
Repeat above-mentioned steps, obtain about 20 gram hematoporphyrin monomethyl ethers.
B. the preparation of therapeutic agent
Take by weighing 10 gram hematoporphyrin monomethyl ether crude drug,, use 0.2mol/L hydrochloric acid conditioning solution pH to 7-8 then, add an amount of mannitol, be settled to 400 milliliters with water for injection again with the abundant stirring and dissolving of an amount of 0.2mol/L sodium hydrate aqueous solution; Aseptic filtration is distributed into every bottle and contains 100 milligrams, puts lyophilization in the freezer dryer, jumps a queue and seals, and labels.Redissolve to the desired concn administration with normal saline during use.
Embodiment 2:CAM model is used for measuring in the optical dynamic therapy effect body
Following method is adopted in the foundation of CAM model: 37 ℃ of incubators, air chamber upwards, rotate every day 3～4 times, to incubation the 9th day, the sterilization hatching egg is made a call to 1～2mm aperture on the air chamber top behind the surface, the rectangular region of chorion projection part mark 1.0cm X1.5cm before the distance fetal head between 1cm, two anterior vitelline veins, mill is cut chorion, scratches the aperture of the about 1mm of diameter on membrana putaminis gently.Dripping a little sterile purified water and separate the membrana putaminis of little bore edges, is the minimum place of blood vessel that the microporous filter membrane carrier of 6mm is placed on CAM with aseptic diameter.
Respectively add the hematoporphyrin monomethyl ether that 10ul concentration is 1mg/ml embodiment 1 preparation in carrier central authorities then, matched group adds the 10ul normal saline.Carried out irradiation, spot diameter 2000 μ m, power density 100mW/cm with golden vapor laser in 15 minutes after the dosing
2, irradiation time 200s, energy density 20J/cm
2After the dosing, with aseptic transparent glue seal window, the incubator of putting into 37.8 ℃ behind the labelling was again hatched 3 days.After the optical processing 3 days, every egg injects 1: 1 methanol, acetone mixed in equal amounts fixative 2.5ml.Fix 20 minutes under the room temperature, treat that CAM goes up endovascular blood coagulation after, throw off the hyaline membrane of envelope window, wiping out the above eggshell of CAM level, is that CAM is cut at the center with the filter membrane carrier, puts in the plate that fills low amounts of water and be covered with filter paper and launches, dry in the shade, preserve together with filter paper, shown in Fig. 2 A and 2B.
Count blood vessel with identical amplification under the anatomic microscope, interior with experiment edge, position (being the microporous filter membrane carrier edge) 1mm scope is the one-level blood vessel, 5mm place, edge, position is the secondary blood vessel with experiment, the blood vessel of all genus tropism growths, promptly be that send at the center, all give counting less than 45 degree persons with the angle of filter membrane radius with the carrier; The blood vessel of walking, detouring is then not very interior.The I and II blood vessel is observed counting respectively.Matched group one-level, secondary blood vessel number are respectively 34.7 and 45.2, and experimental group is respectively 21 and 32.5, and experimental group significantly is less than matched group.The result as shown in Figure 3.
The foundation of embodiment 3:CNV mouse model
The CNV model is set up by the following method: 20 bull C57BL-6J of picked at random mice, body weight is 25g-26g.Intraperitoneal injection 0.3% pentobarbital sodium 200 μ L anesthetized mices, 2% Tropicamide and 10% neophryn mydriasis.Through slit lamp and corneal contact lens, laser (wavelength 810nm, diameter 75 μ m, irradiation time 0.1s, power 140mW) is imported mice in the eyes.After laser irradiation, carry out fundus fluorescein angiography (fundus fluorescence angiography 1 week, FFA), choose the light condensation point and do not have fluorescence leakage, be creamy white 9 of the animals of (as Fig. 4) of light condensation point carry out tissue slice and observe conclusive evidence and make the film situation or further carry out the optical dynamic therapy test.
Get 1 of above-mentioned animal, put to death, win eyeball with excessive pentobarbital sodium, fixing in 2% glutaraldehyde and 4% paraformaldehyde respectively, dissect eyeball, distinguish laser point, will organize stick to fix with 1% Osmic acid. by anatomical lens, the dehydration of ethanol gradient, the oxirane displacement, epoxy resin embedding, serial section, Toluidine blue staining, om observation.
Visible retina forms the new vessels of huge tube chamber down under the light microscopic, and pigment epithelium cell is abnormality proliferation (Fig. 5) also.Show and successfully set up the CNV mouse model.
Embodiment 4: the effect of hematoporphyrin monomethyl ether on the CNV mouse model
Test method
The result judges
After one week, put to death mice, win eyeball with excessive pentobarbital sodium, fixing in 2% glutaraldehyde and 4% paraformaldehyde respectively, dissect eyeball, distinguish laser point, will organize stick to fix with 1% Osmic acid. by anatomical lens, the dehydration of ethanol gradient, the oxirane displacement, epoxy resin embedding, serial section, Toluidine blue staining, om observation.
The result:
The visible a large amount of choroid neovascularity of matched group generate, and pigment epithelium cell begins to hold new vessels (as Fig. 6 A).
The visible choriocapillary thrombosis of experimental group, layer of retina,pigment epithelium is arranged and is lost normal continuity, acromere arrangement disorder, vacuolation, the pyknosis of external granular layer cell, retinochrome is normal (as Fig. 6 B) still.
All quote in this application as a reference at all documents that the present invention mentions, just quoted as a reference separately as each piece document.Should be understood that in addition those skilled in the art can make various changes or modifications the present invention after having read above-mentioned teachings of the present invention, these equivalent form of values fall within the application's appended claims institute restricted portion equally.
Claims (4)
1. the purposes of hematoporphyrin monomethyl ether, wherein said hematoporphyrin monomethyl ether is the chemical compound of following structural formula
In the formula, R1 is 1-hydroxyl-ethyl, 1-methoxyl group-ethyl; R2 is 1-hydroxyl-ethyl, 1-methoxyl group-ethyl,
It is characterized in that be used to prepare the medicine with photodynamic therapy treatment ophthalmic diseases, wherein said medicine is used as photosensitizer in described therapy, and described ophthalmic diseases is to form the disease that causes because of deleterious new vessels.
2. purposes as claimed in claim 1 is characterized in that, described new vessels forms and occurs in cornea, iris, retina or choroid.
3. purposes as claimed in claim 2 is characterized in that, described new vessels forms and occurs on the choroid.
4. purposes as claimed in claim 1 is characterized in that, described ophthalmic diseases is selected from down group: degeneration of macula, ocular histoplasmosis syndrome, myopia or diseases associated with inflammation.
Priority Applications (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031505538A CN100534428C (en) | 2003-08-25 | 2003-08-25 | Application of haematopophyrin in treating ophthalmic disease |
| PCT/CN2004/000970 WO2005018634A1 (en) | 2003-08-25 | 2004-08-20 | The use of the hernatoporphyrin monomethyl ether for the treatment of the eye disorders |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031505538A CN100534428C (en) | 2003-08-25 | 2003-08-25 | Application of haematopophyrin in treating ophthalmic disease |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1589791A CN1589791A (en) | 2005-03-09 |
| CN100534428C true CN100534428C (en) | 2009-09-02 |
Family
ID=34201010
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031505538A Expired - Lifetime CN100534428C (en) | 2003-08-25 | 2003-08-25 | Application of haematopophyrin in treating ophthalmic disease |
Country Status (2)
| Country | Link |
|---|---|
| CN (1) | CN100534428C (en) |
| WO (1) | WO2005018634A1 (en) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105435225A (en) * | 2015-12-27 | 2016-03-30 | 海宁市绿升医药科技有限公司 | Chlorin e6 monoester freeze-dried preparation for injection and preparation method of chlorin e6 monoester freeze-dried preparation |
| CN109091685A (en) * | 2018-08-10 | 2018-12-28 | 北京市眼科研究所 | A kind of pair of keratitis extracts the ablation method of bacterial pathogens |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5756541A (en) * | 1996-03-11 | 1998-05-26 | Qlt Phototherapeutics Inc | Vision through photodynamic therapy of the eye |
| CN1255408C (en) * | 2001-10-17 | 2006-05-10 | 上海复旦张江生物医药股份有限公司 | Method for synthesizing 3 (or8)-(1-methoxyethyl)-8-(or3)-(1-hydroxyethyl)-deuteroporphyrin IX |
-
2003
- 2003-08-25 CN CNB031505538A patent/CN100534428C/en not_active Expired - Lifetime
-
2004
- 2004-08-20 WO PCT/CN2004/000970 patent/WO2005018634A1/en active Application Filing
Non-Patent Citations (8)
| Title |
|---|
| 光动力学疗法在眼科的应用. 张泳等.国外医学.眼科学分册，第23卷第4期. 1999 |
| 光动力学疗法在眼科的应用. 张泳等.国外医学.眼科学分册，第23卷第4期. 1999 * |
| 新型肿瘤光化学诊治剂血卟啉单甲醚的眼组织光毒作用. 彭亚军等.第二军医大学学报，第14卷第3期. 1999 |
| 新型肿瘤光化学诊治剂血卟啉单甲醚的眼组织光毒作用. 彭亚军等.第二军医大学学报，第14卷第3期. 1999 * |
| 激光——血卟啉实验性治疗眼视网膜母细胞瘤. 郑邦和等.应用激光，第5期. 1984 |
| 激光——血卟啉实验性治疗眼视网膜母细胞瘤. 郑邦和等.应用激光，第5期. 1984 * |
| 黄斑中心凹下脉络膜新生血管的光动力学治疗. 张青蔚.国外医学.眼科学分册，第26卷第3期. 2002 |
| 黄斑中心凹下脉络膜新生血管的光动力学治疗. 张青蔚.国外医学.眼科学分册，第26卷第3期. 2002 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1589791A (en) | 2005-03-09 |
| WO2005018634A1 (en) | 2005-03-03 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US5576013A (en) | Treating vascular and neoplastic tissues | |
| EP1353692B1 (en) | Methods and compositions for treatment of ocular neovascularization and neural injury | |
| US5633275A (en) | Photochemotherapeutical obstruction of newly-formed blood vessels | |
| TWI260327B (en) | Pharmaceutical compositions for treating ocular neovascular diseases | |
| CN1104908C (en) | Improved vision through photodynamic therapy of eye | |
| AU2002230567A1 (en) | Compositions for treatment of ocular neovascularization and neural injury | |
| Gomer et al. | The effect of localized porphyrin photodynamic therapy on the induction of tumour metastasis | |
| KR20000057510A (en) | Use of green porphyrins for the manufacture of a medicament for the treatment of secondary cataracts | |
| US6524330B1 (en) | Method of ocular treatment | |
| Kim et al. | Photodynamic therapy of pigmented choroidal melanomas of greater than 3-mm thickness | |
| Schuitmaker et al. | Bacteriochlorin a, a new photosensitizer in photodynamic therapy. In vivo results. | |
| Kaye et al. | Photoradiation therapy causing selective tumor kill in a rat glioma model | |
| Li et al. | Liposomal hypocrellin B as a potential photosensitizer for age-related macular degeneration: pharmacokinetics, photodynamic efficacy, and skin phototoxicity in vivo | |
| KR20140110757A (en) | Use of Photosensitizer In Preparation of Virus-Inactivating Medicaments For Treating Diseases | |
| ES2224355T3 (en) | COMPOSITIONS AND ARTICLES TO REDUCE THE EFFECTS OF INFLAMMATION. | |
| CN100534428C (en) | Application of haematopophyrin in treating ophthalmic disease | |
| US6495585B2 (en) | Method for treating hyperproliferative tissue in a mammal | |
| CN101612149A (en) | Hematoporphyrin monomethyl ether is in the new purposes of field of medicaments | |
| CN1527704B (en) | Compositions and method of administering tubulin binding agents for the treatment of ocular diseases | |
| RU2290150C2 (en) | Photodynamic therapy method for treating intraocular neoplasm cases | |
| RU2146159C1 (en) | Method for applying photodynamic therapy of malignant neoplasms | |
| Barishak et al. | Histology of the iris in geese and ducks photosensitized by ingestion of Ammi majus seeds | |
| ES2312788T3 (en) | PHOTODYNAMIC DIAGNOSTIC PROCEDURE FOR VASCULAR DISEASES. | |
| RU2290973C1 (en) | Method of curing subretinal neovascular membrane | |
| RU2364431C1 (en) | Method of systemic endovenous photodynamic therapy of alveolar disease of liver |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20091120 Address after: Shanghai city Pudong New Area Cailun Road No. 308 zip code: 201203 Co-patentee after: TAIZHOU FUDAN ZHANGJIANG PHARMACEUTICAL Co.,Ltd. Patentee after: SHANGHAI FUDAN-ZHANGJIANG BIO-PHARMACEUTICAL Co.,Ltd. Address before: Shanghai city Pudong New Area Cailun Road No. 308 zip code: 201203 Patentee before: SHANGHAI FUDAN-ZHANGJIANG BIO-PHARMACEUTICAL Co.,Ltd. |
|
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20090902 |