RU2016106641A - Терапевтические средства, направленные на ecm эндотелия роговицы - Google Patents
Терапевтические средства, направленные на ecm эндотелия роговицы Download PDFInfo
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- RU2016106641A RU2016106641A RU2016106641A RU2016106641A RU2016106641A RU 2016106641 A RU2016106641 A RU 2016106641A RU 2016106641 A RU2016106641 A RU 2016106641A RU 2016106641 A RU2016106641 A RU 2016106641A RU 2016106641 A RU2016106641 A RU 2016106641A
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- tgf
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- 230000001225 therapeutic effect Effects 0.000 title 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 claims 11
- 108090001012 Transforming Growth Factor beta Proteins 0.000 claims 11
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 11
- 239000003814 drug Substances 0.000 claims 11
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical group C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 claims 11
- 230000002265 prevention Effects 0.000 claims 9
- 208000035475 disorder Diseases 0.000 claims 7
- 210000000871 endothelium corneal Anatomy 0.000 claims 7
- 102000010834 Extracellular Matrix Proteins Human genes 0.000 claims 6
- 108010037362 Extracellular Matrix Proteins Proteins 0.000 claims 6
- 229940079593 drug Drugs 0.000 claims 6
- 210000002744 extracellular matrix Anatomy 0.000 claims 6
- 239000003795 chemical substances by application Substances 0.000 claims 4
- 201000010099 disease Diseases 0.000 claims 4
- 230000002401 inhibitory effect Effects 0.000 claims 4
- 108091005735 TGF-beta receptors Proteins 0.000 claims 3
- 102000016715 Transforming Growth Factor beta Receptors Human genes 0.000 claims 3
- 230000005856 abnormality Effects 0.000 claims 3
- 150000003839 salts Chemical class 0.000 claims 3
- 108091023037 Aptamer Proteins 0.000 claims 2
- 206010010996 Corneal degeneration Diseases 0.000 claims 2
- 208000002193 Pain Diseases 0.000 claims 2
- FHYUGAJXYORMHI-UHFFFAOYSA-N SB 431542 Chemical compound C1=CC(C(=O)N)=CC=C1C1=NC(C=2C=C3OCOC3=CC=2)=C(C=2N=CC=CC=2)N1 FHYUGAJXYORMHI-UHFFFAOYSA-N 0.000 claims 2
- 108020004459 Small interfering RNA Proteins 0.000 claims 2
- 241000282485 Vulpes vulpes Species 0.000 claims 2
- 201000004781 bullous keratopathy Diseases 0.000 claims 2
- 210000004087 cornea Anatomy 0.000 claims 2
- 230000003511 endothelial effect Effects 0.000 claims 2
- 238000000034 method Methods 0.000 claims 2
- 230000036407 pain Effects 0.000 claims 2
- 239000012453 solvate Substances 0.000 claims 2
- MHCVCKDNQYMGEX-UHFFFAOYSA-N 1,1'-biphenyl;phenoxybenzene Chemical group C1=CC=CC=C1C1=CC=CC=C1.C=1C=CC=CC=1OC1=CC=CC=C1 MHCVCKDNQYMGEX-UHFFFAOYSA-N 0.000 claims 1
- LBPKYPYHDKKRFS-UHFFFAOYSA-N 1,5-naphthyridine, 2-[3-(6-methyl-2-pyridinyl)-1h-pyrazol-4-yl]- Chemical compound CC1=CC=CC(C2=C(C=NN2)C=2N=C3C=CC=NC3=CC=2)=N1 LBPKYPYHDKKRFS-UHFFFAOYSA-N 0.000 claims 1
- -1 1-methyl-2-phenyl-1H -pyrrolo [2,3-b] pyridin-3-yl-prop-2-enoyl Chemical group 0.000 claims 1
- BERLXWPRSBJFHO-UHFFFAOYSA-N 2-(5-chloro-2-fluorophenyl)-n-pyridin-4-ylpteridin-4-amine Chemical compound FC1=CC=C(Cl)C=C1C1=NC(NC=2C=CN=CC=2)=C(N=CC=N2)C2=N1 BERLXWPRSBJFHO-UHFFFAOYSA-N 0.000 claims 1
- 108010049870 Bone Morphogenetic Protein 7 Proteins 0.000 claims 1
- 102100022544 Bone morphogenetic protein 7 Human genes 0.000 claims 1
- 206010020565 Hyperaemia Diseases 0.000 claims 1
- IBCXZJCWDGCXQT-UHFFFAOYSA-N LY 364947 Chemical compound C=1C=NC2=CC=CC=C2C=1C1=CNN=C1C1=CC=CC=N1 IBCXZJCWDGCXQT-UHFFFAOYSA-N 0.000 claims 1
- 206010023644 Lacrimation increased Diseases 0.000 claims 1
- 206010030113 Oedema Diseases 0.000 claims 1
- 108091034117 Oligonucleotide Proteins 0.000 claims 1
- 206010034960 Photophobia Diseases 0.000 claims 1
- 241000288906 Primates Species 0.000 claims 1
- 206010047513 Vision blurred Diseases 0.000 claims 1
- 206010047571 Visual impairment Diseases 0.000 claims 1
- 239000000074 antisense oligonucleotide Substances 0.000 claims 1
- 238000012230 antisense oligonucleotides Methods 0.000 claims 1
- 210000003683 corneal stroma Anatomy 0.000 claims 1
- 230000003247 decreasing effect Effects 0.000 claims 1
- 239000003889 eye drop Substances 0.000 claims 1
- 230000004313 glare Effects 0.000 claims 1
- 230000004317 lacrimation Effects 0.000 claims 1
- 239000000126 substance Substances 0.000 claims 1
- 208000029257 vision disease Diseases 0.000 claims 1
- 230000004393 visual impairment Effects 0.000 claims 1
Classifications
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- A—HUMAN NECESSITIES
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4427—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems
- A61K31/4439—Non condensed pyridines; Hydrogenated derivatives thereof containing further heterocyclic ring systems containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole
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- A—HUMAN NECESSITIES
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- 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
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/4402—Non condensed pyridines; Hydrogenated derivatives thereof only substituted in position 2, e.g. pheniramine, bisacodyl
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- 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
- A61K31/4709—Non-condensed quinolines and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
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- 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
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- A—HUMAN NECESSITIES
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- 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
- A61K31/4738—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems
- A61K31/4745—Quinolines; Isoquinolines ortho- or peri-condensed with heterocyclic ring systems condensed with ring systems having nitrogen as a ring hetero atom, e.g. phenantrolines
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
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- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/519—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with heterocyclic rings
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- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- C12N15/00—Mutation or genetic engineering; DNA or RNA concerning genetic engineering, vectors, e.g. plasmids, or their isolation, preparation or purification; Use of hosts therefor
- C12N15/09—Recombinant DNA-technology
- C12N15/11—DNA or RNA fragments; Modified forms thereof; Non-coding nucleic acids having a biological activity
- C12N15/113—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing
- C12N15/1136—Non-coding nucleic acids modulating the expression of genes, e.g. antisense oligonucleotides; Antisense DNA or RNA; Triplex- forming oligonucleotides; Catalytic nucleic acids, e.g. ribozymes; Nucleic acids used in co-suppression or gene silencing against growth factors, growth regulators, cytokines, lymphokines or hormones
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Claims (11)
1. Лекарственное средство для лечения или предупреждения заболевания, нарушения или состояния, обусловленного аномалией внеклеточного матрикса (ECM) в эндотелии роговицы, где лекарственное средство содержит средство, ингибирующее сигнал TGF-бета.
2. Лекарственное средство для лечения или предупреждения по п.1, где заболевание, нарушение или состояние представляет собой нарушение, обусловленное эндотелиальной дистрофией роговицы Фукса.
3. Лекарственное средство для лечения или предупреждения по п.1 или 2, где заболевание, нарушение или состояние включает, по меньшей мере, одно заболевание, нарушение или состояние, выбранное из группы, состоящей из фотофобии, неясного зрения, нарушения зрения, боли в глазу, слезоотделения, гиперемии, боли, буллезной кератопатии, неприятных ощущений в глазу, снижения контрастности, бликов, отека стромы роговицы, буллезной кератопатии и помутнения роговицы при эндотелиальной дистрофии роговицы Фукса.
4. Лекарственное средство для лечения или предупреждения п.1, где средство, ингибирующее сигнал TGF-бета, включает по меньшей мере одно из 4-[4-(1,3-бензодиоксол-5-ил)-5-(2-пиридинил)-1H-имидазол-2-ил]бензамида, BMP-7, антитела против TGF-бета, антитела против рецептора TGF-бета, миРНК к TGF-бета, миРНК к рецептору TGF-бета, кшРНК к TGF-бета, кшРНК к рецептору TGF-бета, аптамера к TGF-бета, аптамера к рецептору TGF-бета и антисмыслового олигонуклеотида к TGF-бета, 6,7-диметокси-2-((2E)-3-(1-метил-2-фенил-1H-пирроло[2,3-b]пиридин-3-ил-проп-2-еноил))-1,2,3,4-тетрагидроизохинолона, 3-(6-метил-2-пиридинил)-N-фенил-4-(4-хинолинил)-1H-пиразол-1-карботиоамида, 2-(3-(6-метилпиридин-2-ил)-1H-пиразол-4-ил)-1,5-нафтиридина, 6-(4-(пиперидин-1-ил)этокси)фенил)-3-(пиридин-4-ил)пиразолo[1,5-a]пиримидина, 2-(5-хлор-2-фторфенил)-4-[(4-пиридинил)амино]птеридина, 4-[3-(2-пиридинил)-1H-пиразол-4-ил]хинолина, их фармацевтически приемлемых солей или сольватов, или сольватов фармацевтически приемлемых солей.
5. Лекарственное средство для лечения или предупреждения по п.1, где средство, ингибирующее сигнал TGF-бета, включает 4-[4-(1,3-бензодиоксол-5-ил)-5-(2-пиридинил)-1H-имидазол-2-ил]бензамид или его фармацевтически приемлемую соль.
6. Лекарственное средство для лечения или предупреждения по п.1, где эндотелий роговицы представляет собой эндотелий роговицы примата.
7. Лекарственное средство для лечения или предупреждения по п.1, где эндотелий роговицы представляет собой эндотелий роговицы человека.
8. Лекарственное средство для лечения или предупреждения по п.1, содержащее дополнительный лекарственный компонент.
9. Лекарственное средство для лечения или предупреждения по п.1, представляющее собой глазные капли.
10. Вещество, ингибирующее сигнал TGF-бета, для лечения или предупреждения нарушения, обусловленного аномалией внеклеточного матрикса (ECM) в эндотелии роговицы.
11. Способ лечения или предупреждения нарушения, обусловленного аномалией внеклеточного матрикса (ECM) в эндотелии роговицы у индивидуума, где способ включает стадию введения эффективного количества средства, ингибирующего сигнал TGF-бета, индивидууму.
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| PCT/JP2013/071095 WO2015015654A1 (ja) | 2013-07-30 | 2013-07-30 | 角膜内皮ｅｃｍ治療薬 |
Related Child Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2019107381A Division RU2800931C2 (ru) | 2019-03-15 | Терапевтические средства, направленные на ecm эндотелия роговицы |
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| Publication Number | Publication Date |
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| RU2016106641A true RU2016106641A (ru) | 2017-09-01 |
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| Application Number | Title | Priority Date | Filing Date |
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| RU2016106641A RU2016106641A (ru) | 2013-07-30 | 2013-07-30 | Терапевтические средства, направленные на ecm эндотелия роговицы |
Country Status (7)
| Country | Link |
|---|---|
| US (2) | US11730722B2 (ru) |
| JP (1) | JP6403217B2 (ru) |
| BR (1) | BR112016002015A2 (ru) |
| CA (1) | CA2919316C (ru) |
| MX (1) | MX386503B (ru) |
| RU (1) | RU2016106641A (ru) |
| WO (1) | WO2015015654A1 (ru) |
Families Citing this family (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2015015654A1 (ja) | 2013-07-30 | 2015-02-05 | 京都府公立大学法人 | 角膜内皮ｅｃｍ治療薬 |
| ES2847755T3 (es) * | 2013-10-31 | 2021-08-03 | Kyoto Prefectural Public Univ Corp | Fármaco terapéutico que comprende un inhibidor de la señal de TGF-beta para enfermedades relacionadas con la muerte celular del retículo endoplásmico en el endotelio corneal |
| CA3067332A1 (en) * | 2017-06-16 | 2018-12-20 | The Doshisha | Mtor-inhibitor-containing medicine for treating or preventing ophthalmic symptoms, disorders, or diseases, and application thereof |
| JPWO2018230712A1 (ja) * | 2017-06-16 | 2020-04-16 | 学校法人同志社 | ＴＧＦ−β阻害剤の新規スクリーニング法 |
| JP7398729B2 (ja) * | 2017-12-13 | 2023-12-15 | 学校法人同志社 | （ｔ）ｅｗ－７１９７を含む角膜内皮疾患を治療または予防するための組成物または方法 |
| WO2020009248A1 (ja) * | 2018-07-04 | 2020-01-09 | 京都府公立大学法人 | 眼組織の線維化抑制用組成物 |
| WO2021173712A1 (en) * | 2020-02-24 | 2021-09-02 | The Board Of Regents Of The University Of Texas System | Molecular biomarkers and targets for fuchs' endothelial corneal dystrophy and glaucoma |
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| US5703047A (en) * | 1992-09-21 | 1997-12-30 | Board Of Regents, The University Of Texas System | Methods and treatments for corneal healing with growth factors |
| WO1998024466A1 (en) * | 1996-12-05 | 1998-06-11 | Alcon Laboratories, Inc. | THE USE OF INHIBITORS OF TGF-β'S FUNCTIONS TO AMELIORATE OCULAR PATHOLOGY |
| ES2146552B1 (es) | 1998-11-24 | 2001-04-16 | Inst Cientifico Tecnol Navarra | Peptidos inhibidores de tgf/31 |
| PT1223966E (pt) | 1999-10-29 | 2003-09-30 | Biopharm Ges Biotechn Entwickl | Utilizacao do gdnf para tratamento de defeitos na cornea |
| US20030191137A1 (en) * | 2000-04-07 | 2003-10-09 | Sang-Geon Kim | Prophylactic and therapeutic use of oltipraz as an antifibrotic and anticirrhotic agent in the liver and pharmaceutical composition containing oltipraz |
| WO2003097615A1 (en) | 2002-05-17 | 2003-11-27 | Scios, Inc. | TREATMENT OF FIBROPROLIFERATIVE DISORDERS USING TGF-β INHIBITORS |
| WO2004018430A1 (ja) | 2002-08-23 | 2004-03-04 | Kirin Beer Kabushiki Kaisha | ＴＧＦβ阻害活性を有する化合物およびそれを含んでなる医薬組成物 |
| US8158589B2 (en) | 2003-08-22 | 2012-04-17 | Proyecto Biomedicine Cima, S.L. | Peptides with the capacity to bind to transforming growth factor β1 (TGF-β1) |
| CN101056656A (zh) | 2004-09-15 | 2007-10-17 | 哈佛大学校长及研究员协会 | 在治疗肥胖症和糖尿病中降低er应力 |
| JP2008530100A (ja) | 2005-02-10 | 2008-08-07 | リージェンツ オブ ザ ユニバーシティ オブ ミネソタ | 視覚障害の治療方法 |
| WO2006096011A1 (en) | 2005-03-08 | 2006-09-14 | Medigenes Co., Ltd. | PHARMACEUTICAL COMPOSITION FOR TREATING AVELLINO CORNEA DYSTROPHY COMPRISING AN ANTIBODY AGAINST TGF-β |
| BRPI0619966A2 (pt) | 2005-12-16 | 2011-10-25 | Alcon Inc | controle de pressão intra-ocular usando agentes de modulação de alk5 |
| CA2699454C (en) | 2007-08-27 | 2012-07-24 | Auxagen, Inc. | Methods for inhibiting tgf-.beta. |
| US20100087486A1 (en) | 2008-05-30 | 2010-04-08 | Hiroshi Nakamura | Methods for using tgf-b receptor inhibitors or activin-like kinase (alk) 5 inhibitors a-83-01 and sb-431542 to treat eye disease and wound healing conditions |
| US20100267731A1 (en) * | 2009-04-17 | 2010-10-21 | Summa Health Systems, LLC | Use of transforming growth factor-b receptor inhibitors to suppress ocular scarring |
| US20130288985A1 (en) * | 2010-07-15 | 2013-10-31 | The Schepens Eye Research Institute Inc. | Compositions and methods of treatment of corneal endothelium disorders |
| KR101258166B1 (ko) | 2010-09-01 | 2013-04-25 | 연세대학교 산학협력단 | Ｔｇｆｂｉ 유전자 변이 각막 이상증의 예방 또는 치료용 약제학적 조성물 및 그의 스크리닝 방법 |
| EP2646543A4 (en) | 2010-12-02 | 2014-09-03 | Technion Res & Dev Foundation | METHOD OF GENERATING CORNEAL CELLS AND CELL POPULATIONS THEREWITH |
| HRP20190460T1 (hr) | 2011-12-06 | 2019-04-19 | Astellas Institute For Regenerative Medicine | Postupak proizvodnje endotelnih stanica rožnice usmjerenom diferencijacijom |
| JP6218229B2 (ja) | 2011-12-28 | 2017-10-25 | 京都府公立大学法人 | 角膜内皮細胞の培養正常化 |
| WO2015015654A1 (ja) | 2013-07-30 | 2015-02-05 | 京都府公立大学法人 | 角膜内皮ｅｃｍ治療薬 |
| ES2847755T3 (es) | 2013-10-31 | 2021-08-03 | Kyoto Prefectural Public Univ Corp | Fármaco terapéutico que comprende un inhibidor de la señal de TGF-beta para enfermedades relacionadas con la muerte celular del retículo endoplásmico en el endotelio corneal |
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