CN111297858B - Application of PARP-1 inhibitor and pharmaceutical composition thereof in preparation of drugs for treating eye diseases - Google Patents
Application of PARP-1 inhibitor and pharmaceutical composition thereof in preparation of drugs for treating eye diseases Download PDFInfo
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- 239000003112 inhibitor Substances 0.000 title claims abstract description 34
- 239000003814 drug Substances 0.000 title claims abstract description 12
- 208000030533 eye disease Diseases 0.000 title claims abstract description 6
- 239000008194 pharmaceutical composition Substances 0.000 title claims abstract description 6
- 108010064218 Poly (ADP-Ribose) Polymerase-1 Proteins 0.000 title claims abstract 10
- 102100023712 Poly [ADP-ribose] polymerase 1 Human genes 0.000 title claims abstract 10
- 229940079593 drug Drugs 0.000 title description 8
- HWGQMRYQVZSGDQ-HZPDHXFCSA-N chembl3137320 Chemical compound CN1N=CN=C1[C@H]([C@H](N1)C=2C=CC(F)=CC=2)C2=NNC(=O)C3=C2C1=CC(F)=C3 HWGQMRYQVZSGDQ-HZPDHXFCSA-N 0.000 claims abstract description 9
- 206010030043 Ocular hypertension Diseases 0.000 claims abstract description 7
- RURAZZMDMNRXMI-UHFFFAOYSA-N PJ34 hydrochloride Chemical compound Cl.C1=CC=C2C3=CC(NC(=O)CN(C)C)=CC=C3NC(=O)C2=C1 RURAZZMDMNRXMI-UHFFFAOYSA-N 0.000 claims abstract description 5
- 241000699670 Mus sp. Species 0.000 claims description 23
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 16
- 206010030348 Open-Angle Glaucoma Diseases 0.000 claims description 8
- 208000007950 Ocular Hypotension Diseases 0.000 claims description 4
- 238000011282 treatment Methods 0.000 claims description 4
- 239000002904 solvent Substances 0.000 claims description 3
- 201000002862 Angle-Closure Glaucoma Diseases 0.000 claims description 2
- 206010067013 Normal tension glaucoma Diseases 0.000 claims description 2
- 208000022873 Ocular disease Diseases 0.000 claims description 2
- 201000001326 acute closed-angle glaucoma Diseases 0.000 claims description 2
- 201000002978 low tension glaucoma Diseases 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 239000008363 phosphate buffer Substances 0.000 claims 1
- 238000000034 method Methods 0.000 abstract description 3
- RVOUDNBEIXGHJY-UHFFFAOYSA-N 5-(4-piperidin-1-ylbutoxy)-3,4-dihydro-2h-isoquinolin-1-one Chemical compound C1=CC=C2C(=O)NCCC2=C1OCCCCN1CCCCC1 RVOUDNBEIXGHJY-UHFFFAOYSA-N 0.000 abstract description 2
- 230000004410 intraocular pressure Effects 0.000 description 15
- 210000001742 aqueous humor Anatomy 0.000 description 13
- 210000005252 bulbus oculi Anatomy 0.000 description 10
- 241000699666 Mus <mouse, genus> Species 0.000 description 8
- 230000000694 effects Effects 0.000 description 6
- 208000010412 Glaucoma Diseases 0.000 description 5
- UYJZZVDLGDDTCL-UHFFFAOYSA-N PJ34 Chemical compound C1=CC=C2C3=CC(NC(=O)CN(C)C)=CC=C3NC(=O)C2=C1 UYJZZVDLGDDTCL-UHFFFAOYSA-N 0.000 description 4
- 210000001508 eye Anatomy 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 210000001328 optic nerve Anatomy 0.000 description 3
- 230000010412 perfusion Effects 0.000 description 3
- 239000002953 phosphate buffered saline Substances 0.000 description 3
- 210000001585 trabecular meshwork Anatomy 0.000 description 3
- GIANIJCPTPUNBA-QMMMGPOBSA-N (2s)-3-(4-hydroxyphenyl)-2-nitramidopropanoic acid Chemical compound [O-][N+](=O)N[C@H](C(=O)O)CC1=CC=C(O)C=C1 GIANIJCPTPUNBA-QMMMGPOBSA-N 0.000 description 2
- -1 2, 4-thiazol-5-yl Chemical group 0.000 description 2
- NCGICGYLBXGBGN-UHFFFAOYSA-N 3-morpholin-4-yl-1-oxa-3-azonia-2-azanidacyclopent-3-en-5-imine;hydrochloride Chemical compound Cl.[N-]1OC(=N)C=[N+]1N1CCOCC1 NCGICGYLBXGBGN-UHFFFAOYSA-N 0.000 description 2
- 102000012338 Poly(ADP-ribose) Polymerases Human genes 0.000 description 2
- 108010061844 Poly(ADP-ribose) Polymerases Proteins 0.000 description 2
- 229920000776 Poly(Adenosine diphosphate-ribose) polymerase Polymers 0.000 description 2
- 210000002159 anterior chamber Anatomy 0.000 description 2
- 230000001384 anti-glaucoma Effects 0.000 description 2
- 230000036772 blood pressure Effects 0.000 description 2
- 210000004240 ciliary body Anatomy 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 230000004406 elevated intraocular pressure Effects 0.000 description 2
- 239000013642 negative control Substances 0.000 description 2
- 230000008506 pathogenesis Effects 0.000 description 2
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 2
- 201000006366 primary open angle glaucoma Diseases 0.000 description 2
- 210000001747 pupil Anatomy 0.000 description 2
- 230000001603 reducing effect Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 210000001519 tissue Anatomy 0.000 description 2
- QMYGFTJCQFEDST-UHFFFAOYSA-N 3-methoxybutyl acetate Chemical group COC(C)CCOC(C)=O QMYGFTJCQFEDST-UHFFFAOYSA-N 0.000 description 1
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 1
- 206010067484 Adverse reaction Diseases 0.000 description 1
- 206010003694 Atrophy Diseases 0.000 description 1
- 229940122072 Carbonic anhydrase inhibitor Drugs 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010056677 Nerve degeneration Diseases 0.000 description 1
- 206010047555 Visual field defect Diseases 0.000 description 1
- 230000006838 adverse reaction Effects 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 230000004509 aqueous humor production Effects 0.000 description 1
- 230000001746 atrial effect Effects 0.000 description 1
- 230000037444 atrophy Effects 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- 229940097320 beta blocking agent Drugs 0.000 description 1
- 125000004106 butoxy group Chemical group [*]OC([H])([H])C([H])([H])C(C([H])([H])[H])([H])[H] 0.000 description 1
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- 210000004027 cell Anatomy 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 201000010099 disease Diseases 0.000 description 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000001077 hypotensive effect Effects 0.000 description 1
- 238000001802 infusion Methods 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 210000004126 nerve fiber Anatomy 0.000 description 1
- 239000002840 nitric oxide donor Substances 0.000 description 1
- 208000001749 optic atrophy Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000037361 pathway Effects 0.000 description 1
- 230000000750 progressive effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 210000003994 retinal ganglion cell Anatomy 0.000 description 1
- 239000003590 rho kinase inhibitor Substances 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
Classifications
-
- 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/472—Non-condensed isoquinolines, e.g. papaverine
- A61K31/4725—Non-condensed isoquinolines, e.g. papaverine containing further heterocyclic 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
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/473—Quinolines; Isoquinolines ortho- or peri-condensed with carbocyclic ring systems, e.g. acridines, phenanthridines
-
- 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
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/50—Pyridazines; Hydrogenated pyridazines
- A61K31/5025—Pyridazines; Hydrogenated pyridazines ortho- or peri-condensed with heterocyclic ring systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P25/00—Drugs for disorders of the nervous system
-
- 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
- A61P27/06—Antiglaucoma agents or miotics
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- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
An application of PARP-1 inhibitor in preparing medicament for treating eye diseases is provided, wherein the PARP-1 inhibitor is selected from any one of DPQ, BMN673 and PJ34 HCl. The invention also includes methods of practicing the use, as well as pharmaceutical compositions for treating ocular hypertension.
Description
Technical Field
The invention belongs to the field of PARP-1 inhibitors, and particularly relates to an application of a PARP-1 inhibitor and a pharmaceutical composition thereof in preparing medicines for treating eye diseases.
Background
Glaucoma is the first irreversible blinding eye disease worldwide and is characterized by optic disc dishing atrophy, retinal ganglion cell apoptosis, thinning of nerve fiber layers and visual field defects, with pathological elevated intraocular pressure being a major risk factor. Primary open angle glaucoma (primary open angle glaucoma, POAG) has the highest incidence but its exact pathogenesis is not yet defined. The aqueous humor outflow channel of the POAG patient has normal structure, and the pathogenesis of the POAG patient is not clear, and the POAG patient can be related to genetics and the like. It is characterized by elevated intraocular pressure and always open atrial angle, i.e. outflow of aqueous humor is blocked by trabecular meshwork-Schlemm's system. If untreated, sustained intraocular pressure (Intraocular pressure, IOP) is too high, eventually damaging the optic nerve and even blinding. The treatment methods of glaucoma are mainly classified into ocular hypotension, optic nerve protection, laser and surgical treatment. According to the progressive therapeutic principle recommended by the European glaucomatous society, ocular hypotension should be the first drug therapy and then laser or surgical therapy should be considered.
Drug ocular hypotension strategies mainly include both decreased aqueous humor production and increased aqueous humor outflow. Aqueous humor (aqueou) circulation is produced by the ciliary body (ciliary body), through the posterior chamber (posterior chamber), through the pupil (pupil) to the anterior chamber (antrior chamber), and out through the trabecular meshwork adjacent to the Schlemm's canal. About 90% of the aqueous humor flows out through the passage, and 75% of the outflow resistance is located between the trabecular meshwork and the Schlemm tube wall. The ocular surface administration of different PARP-1 (poly ADP-ribose polymerase, poly ADP ribose polymerase) inhibitors to ocular hypertension CAV1ko mice is verified, the PARP-1 inhibitor can rapidly reduce intraocular pressure, and the perfusion experiment further proves that the PARP-1 inhibitor can promote aqueous humor outflow.
To date, no anti-blue light drug directly aiming at etiology treatment exists, and a plurality of drugs are often combined and repeatedly used for controlling the intraocular pressure of a patient within a target intraocular pressure range, so that the blood pressure reducing effect is limited and a plurality of adverse reactions exist. Therefore, the search and research of the anti-glaucoma drug with good etiology, good curative effect and low side effect has important significance.
Disclosure of Invention
The invention aims to solve the technical problems that: provides an anti-glaucoma drug with good curative effect and low side effect,
in order to solve the technical problems, the invention adopts the following technical scheme: the use of PARP-1 inhibitors reduces intraocular pressure in an organism.
The invention uses three PARP-1 inhibitors DPQ [ 3,4-Dihydro-5- [4- (1-piperidinyl) butoxyl ] -1 (2H) -isoquinolone, 3,4-Dihydro-5- [4- (1-piperidinyl) butoxy ] -1 (2H) -isoquinolone ], BMN673 [ 5-fluoro-8- (4-fluorophenyl) -2,7,8,9-tetrahydro-9- (1-methyl-1H-1, 2, 4-thiazol-5-yl) -3H-pyrido [4,3,2-de ] naphthyridine-3-one, (tazoledrine) ] and PJ34 HCl [ N- (5, 6-Dihydro-6-oxo-2-phenanthridinyl) -2- (dimethylamino) acetamide ] to achieve the aim of reducing blood pressure in a short time by increasing the aqueous flow rate, thereby becoming a novel medicine for treating glaucoma.
Cav1KO is a model mouse for ocular hypertension glaucoma, and PARP-1 expression in aqueous outflow tissue is increased compared to wild type C57/B6 mice (WT mice). PARP-1 inhibitors can decrease ocular pressure and increase aqueous outflow in classical pathway in Cav1KO mice. Linsitagliptin (3-morpholino-Sideimine, SIN-1) sustained drug-infusion induced elevated PARP-1 expression in ocular hypertension mice, the use of PARP-1 inhibitors may decrease ocular tension and reduce PARP-1 expression, SIN-1 may increase transmembrane resistance (Transmembrane Resistance, TEER) of porcine AAP cells, and PARP-1 inhibitors such as PJ-34 may decrease TEER.
Use of a PARP-1 inhibitor in the manufacture of a medicament for the treatment of an ocular disorder, the PARP-1 inhibitor being selected from any one of DPQ, BMN673, pj34 HCl, i.e. any one of the following structures:
the application is realized, and the method comprises the following steps:
s1, dissolving the PARP-1 inhibitor in a solvent;
s2, administration of PARP-1 inhibitor in S1 to the ocular surface of CAV1ko mice.
PARP-1 inhibitors may be 2ul 500um DPQ in dimethyl sulfoxide (DMSO), or 2ul 5mm BMN673 in dimethyl sulfoxide (DMSO), or 2ul 100um PJ34 HCl in Phosphate Buffered Saline (PBS).
The disease is selected from open angle glaucoma, closed angle glaucoma, acute closed angle glaucoma, normal tension glaucoma, headache, optic atrophy and optic nerve degeneration caused by ocular hypertension.
A pharmaceutical composition comprising a PARP-1 inhibitor and further comprising one or more of a carbonic anhydrase inhibitor, a prostaglandin derivative, a cholinergic agent, a NO donor, a Rho kinase inhibitor, a beta blocker, an alpha receptor agonist.
Advantageous effects
1. The invention can reduce the pressure of the aqueous humor which is the source for causing the rise of the intraocular pressure.
2. The PARP-1 inhibitor has high depressurization speed.
3. The PARP-1 inhibitor has small side effect and can improve the compliance of patients.
Drawings
FIG. 1 (a) graph of change in intraocular pressure of the eyeball of CAV1ko mouse after administration of 500uM DPQ to the ocular surface
FIG. 1 (b) graph of change in intraocular pressure of WT mouse eyeball after administration of 500uM DPQ to ocular surface
FIG. 2 (a) graph of changes in intraocular pressure of the eyeballs of CAV1ko mice after administration of 5mM BMN673 to the ocular surface
FIG. 2 (b) graph of change in intraocular pressure of WT mouse eyeball after administration of 5mM BMN673 to ocular surface
FIG. 3 (a) graph of change in intraocular pressure of the eyeball of CAV1ko mouse after administration of 100uM PJ34 to the ocular surface
FIG. 3 (b) graph of change in intraocular pressure of WT mouse eyeball after administration of 100uM PJ34 to ocular surface
FIG. 4 graph of outflow rate of CAV1ko mice under different pressure after 200uM DPQ was perfused in vitro
FIG. 5 outflow Rate graph of CAV1ko mice after ex vivo eyeball perfusion with 200uM DPQ
FIG. 6 tonometric comparison of CAV1ko mice and WT mice
Detailed Description
The invention is described below with reference to specific examples. It will be appreciated by those skilled in the art that these examples are for illustration of the invention only and are not intended to limit the scope of the invention in any way.
Experimental method
CAV1ko mice and wild type C57 mice were given ocular surface administration with different PARP-1 inhibitors, DPQ, BMN673, PJ34 HCl, respectively, and Negative Controls (NC) were given to the lateral eyes. Intraocular pressure was measured 3 hours after administration using a tonometer. After confirming that the PARP-1 inhibitor can reduce intraocular pressure, the eyeballs of the mice are completely taken out, and the aqueous humor outflow rate is measured through an in-vitro eyeball perfusion model.
As shown in fig. 1 (a), 2 (a) and 3 (a), CAV1ko mice were given 500uM DPQ, 5mM BMN and 100uM pj34 2ul x 3 times on the ocular surface, respectively, and corresponding equal concentrations and volumes of solvent DMSO, DMSO and PBS were administered to the contralateral eyes, respectively; after 3 hours, the measurement results show that the ocular tension of the mice after ocular surface administration is significantly reduced compared with that of the eyes on the opposite sides, and p is less than 0.05. As shown in fig. 1 (b), fig. 2 (b) and fig. 3 (b), since PARP-1 is significantly increased over WT mice on CAV1ko mouse trabecular meshwork, PARP-1 inhibitors have no significant ocular hypotensive effect on WT mice.
After 200uM DPQ was perfused into the in vitro eyeball of CAV1ko mice, the anterior chamber was punctured using a 33G needle and maintained at constant pressure (8 mmHg) for 30 minutes, and then the aqueous humor flow rate was measured twice under different pressure conditions (6, 8, 11, 15 mmHg) respectively as follows:
the above experiment was repeated using a blank control group. As shown in fig. 4, the aqueous humor flow rate increases linearly with pressure, and the specific linear equation is: y=0.01737 x-0.04370, r 2 ＝0.963。
As shown in fig. 5, CAV1ko mice were perfused with 200um DPQ in vitro, measured after 30min, the aqueous humor outflow rate of experimental group was 0.01737, the aqueous humor outflow rate of blank group was 0.00436, in μl/(min·mmhg), p < 0.05), and the aqueous humor outflow rate was seen to increase after perfusing inhibitor DPQ.
As shown in FIG. 6, CAV1ko is a model mouse of ocular hypertension glaucoma, and PARP-1 expression in aqueous outflow tissue is increased compared to WT mice, and Nitrotyrosine (NT) in the eye of CAV1ko mice is increased and decreased by PARP-1 inhibitors.
Claims (5)
1. Use of a PARP-1 inhibitor or a pharmaceutical composition thereof for the manufacture of a medicament for the treatment of an ocular disorder by ocular hypotension, characterized in that the PARP-1 inhibitor is selected from any one of DPQ, BMN673, pj34 HCl, i.e. any one of the following structures:
the eye disease is selected from open angle glaucoma, closed angle glaucoma, acute closed angle glaucoma, and normal tension glaucoma caused by ocular hypertension.
2. The use according to claim 1, characterized by the steps of:
s1, dissolving the PARP-1 inhibitor in a solvent;
s2, administration of PARP-1 inhibitor in S1 to the ocular surface of CAV1ko mice.
3. The use according to claim 2, characterized in that the PARP-1 inhibitor is 2ul 500um DPQ in dimethyl sulfoxide.
4. The use according to claim 2, characterized in that the PARP-1 inhibitor is 2ul 5mm BMN673 dissolved in dimethyl sulfoxide.
5. Use according to claim 2, characterized in that the PARP-1 inhibitor is PJ34 HCl in 2ul 100um in phosphate buffer.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911177571.1A CN111297858B (en) | 2019-11-26 | 2019-11-26 | Application of PARP-1 inhibitor and pharmaceutical composition thereof in preparation of drugs for treating eye diseases |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN201911177571.1A CN111297858B (en) | 2019-11-26 | 2019-11-26 | Application of PARP-1 inhibitor and pharmaceutical composition thereof in preparation of drugs for treating eye diseases |
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| CN111297858A CN111297858A (en) | 2020-06-19 |
| CN111297858B true CN111297858B (en) | 2023-11-21 |
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Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017199042A1 (en) * | 2016-05-20 | 2017-11-23 | The University Of Birmingham | Treatment of neurological pathologies with inhibitors of dna damage repair |
Family Cites Families (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US20050282902A1 (en) * | 2004-06-22 | 2005-12-22 | Allergan, Inc. | Abnormal cannabidiols as agents for lowering intraocular pressure |
| EP2844268A4 (en) * | 2012-04-20 | 2015-11-25 | Univ Howard | Method of treating an ocular disease and compositions effective for treating an ocular disease |
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Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2017199042A1 (en) * | 2016-05-20 | 2017-11-23 | The University Of Birmingham | Treatment of neurological pathologies with inhibitors of dna damage repair |
Non-Patent Citations (4)
| Title |
|---|
| Andrew A. Pieper等.Poly (ADP-ribose) polymerase, nitric oxide and cell death.《Trends in Pharmacological Sciences》.1999,第20卷(第4期),171-181. * |
| François Paquet-Durand等.Excessive Activation of Poly(ADP-Ribose) Polymerase Contributes to Inherited Photoreceptor Degeneration in the Retinal Degeneration 1 Mouse.《The Journal of Neuroscience》.2007,第27卷(第38期),10311-10319. * |
| N N Osborne等.Neuroprotection in relation to retinal ischemia and relevance to glaucoma.《Survey of Ophthalmology》.1999,第43卷S102-S128. * |
| Yasuhiro Ikeda等.oxidative DNA damage plays a key role in the process of photoreceptor death in inherited retinal degeneration.《ARVO Annual Meeting Abstract》.2011,第52卷摘要. * |
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