IL126836A - Beta-inhibitor of protein kinase C beta-use for use as a drug for the treatment of eye diseases - Google Patents
Beta-inhibitor of protein kinase C beta-use for use as a drug for the treatment of eye diseasesInfo
- Publication number
- IL126836A IL126836A IL12683697A IL12683697A IL126836A IL 126836 A IL126836 A IL 126836A IL 12683697 A IL12683697 A IL 12683697A IL 12683697 A IL12683697 A IL 12683697A IL 126836 A IL126836 A IL 126836A
- Authority
- IL
- Israel
- Prior art keywords
- inhibitor
- macular edema
- protein kinase
- related macular
- isozyme
- Prior art date
Links
- 239000003112 inhibitor Substances 0.000 title claims abstract description 51
- 102000003923 Protein Kinase C Human genes 0.000 title claims abstract description 49
- 108090000315 Protein Kinase C Proteins 0.000 title claims abstract description 49
- 239000003814 drug Substances 0.000 title claims abstract description 17
- 208000022873 Ocular disease Diseases 0.000 title 1
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 claims abstract description 50
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 claims abstract description 50
- 208000001344 Macular Edema Diseases 0.000 claims abstract description 32
- 206010025415 Macular oedema Diseases 0.000 claims abstract description 30
- 201000010230 macular retinal edema Diseases 0.000 claims abstract description 30
- 238000011282 treatment Methods 0.000 claims abstract description 13
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 10
- 208000014245 Ocular vascular disease Diseases 0.000 claims abstract description 8
- 241000124008 Mammalia Species 0.000 claims abstract description 7
- 210000001957 retinal vein Anatomy 0.000 claims abstract description 5
- 238000001356 surgical procedure Methods 0.000 claims abstract description 5
- 206010020772 Hypertension Diseases 0.000 claims abstract description 4
- DQYBRTASHMYDJG-UHFFFAOYSA-N Bisindolylmaleimide Chemical group C1=CC=C2C(C=3C(=O)NC(C=3C=3C4=CC=CC=C4NC=3)=O)=CNC2=C1 DQYBRTASHMYDJG-UHFFFAOYSA-N 0.000 claims abstract 12
- 208000014882 Carotid artery disease Diseases 0.000 claims abstract 3
- 208000004644 retinal vein occlusion Diseases 0.000 claims abstract 3
- 208000007056 sickle cell anemia Diseases 0.000 claims abstract 3
- 208000007014 Retinitis pigmentosa Diseases 0.000 claims abstract 2
- 229940002612 prodrug Drugs 0.000 claims description 16
- 239000000651 prodrug Substances 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 16
- 125000000217 alkyl group Chemical group 0.000 claims description 14
- 108010044467 Isoenzymes Proteins 0.000 claims description 11
- 229910052739 hydrogen Inorganic materials 0.000 claims description 11
- 150000002148 esters Chemical class 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- 229940123924 Protein kinase C inhibitor Drugs 0.000 claims description 7
- 239000003881 protein kinase C inhibitor Substances 0.000 claims description 7
- 101710175516 14 kDa zinc-binding protein Proteins 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000002253 acid Substances 0.000 claims description 4
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 4
- 229910052757 nitrogen Inorganic materials 0.000 claims description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
- IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 3
- QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- 229910052799 carbon Inorganic materials 0.000 claims description 2
- 125000001424 substituent group Chemical group 0.000 claims description 2
- 125000002947 alkylene group Chemical group 0.000 claims 5
- 150000002431 hydrogen Chemical group 0.000 claims 3
- 206010064930 age-related macular degeneration Diseases 0.000 claims 1
- 125000003545 alkoxy group Chemical group 0.000 claims 1
- 125000000539 amino acid group Chemical group 0.000 claims 1
- 125000003118 aryl group Chemical group 0.000 claims 1
- 125000002619 bicyclic group Chemical group 0.000 claims 1
- 239000001273 butane Substances 0.000 claims 1
- 125000001188 haloalkyl group Chemical group 0.000 claims 1
- 125000001475 halogen functional group Chemical group 0.000 claims 1
- 125000004674 methylcarbonyl group Chemical group CC(=O)* 0.000 claims 1
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims 1
- 150000001875 compounds Chemical class 0.000 description 47
- 230000002207 retinal effect Effects 0.000 description 31
- 210000002889 endothelial cell Anatomy 0.000 description 30
- 230000010261 cell growth Effects 0.000 description 20
- 238000000034 method Methods 0.000 description 18
- 230000012010 growth Effects 0.000 description 17
- 230000002792 vascular Effects 0.000 description 16
- 210000004027 cell Anatomy 0.000 description 14
- 230000000694 effects Effects 0.000 description 13
- 230000004856 capillary permeability Effects 0.000 description 12
- 239000000203 mixture Substances 0.000 description 12
- 230000000638 stimulation Effects 0.000 description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 10
- 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 10
- 230000002401 inhibitory effect Effects 0.000 description 10
- 230000035699 permeability Effects 0.000 description 10
- 241000283690 Bos taurus Species 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 206010021143 Hypoxia Diseases 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 239000003102 growth factor Substances 0.000 description 8
- 230000001146 hypoxic effect Effects 0.000 description 8
- 239000002904 solvent Substances 0.000 description 8
- 238000002474 experimental method Methods 0.000 description 7
- 230000001965 increasing effect Effects 0.000 description 7
- 238000002347 injection Methods 0.000 description 7
- 239000007924 injection Substances 0.000 description 7
- 239000002609 medium Substances 0.000 description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 6
- 239000004480 active ingredient Substances 0.000 description 6
- 206010012601 diabetes mellitus Diseases 0.000 description 6
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 6
- 230000003511 endothelial effect Effects 0.000 description 6
- 210000003668 pericyte Anatomy 0.000 description 6
- 108020004414 DNA Proteins 0.000 description 5
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 5
- 201000010099 disease Diseases 0.000 description 5
- 239000000975 dye Substances 0.000 description 5
- 238000009472 formulation Methods 0.000 description 5
- 102000058223 human VEGFA Human genes 0.000 description 5
- 230000004044 response Effects 0.000 description 5
- DBMJMQXJHONAFJ-UHFFFAOYSA-M Sodium laurylsulphate Chemical compound [Na+].CCCCCCCCCCCCOS([O-])(=O)=O DBMJMQXJHONAFJ-UHFFFAOYSA-M 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000037396 body weight Effects 0.000 description 4
- 239000003636 conditioned culture medium Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000011534 incubation Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 230000001225 therapeutic effect Effects 0.000 description 4
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 3
- 206010029113 Neovascularisation Diseases 0.000 description 3
- 229940123866 Protein kinase C beta inhibitor Drugs 0.000 description 3
- 241000700159 Rattus Species 0.000 description 3
- 208000017442 Retinal disease Diseases 0.000 description 3
- 229920002472 Starch Polymers 0.000 description 3
- 244000309466 calf Species 0.000 description 3
- 238000004113 cell culture Methods 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- -1 ester amide Chemical class 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000001727 in vivo Methods 0.000 description 3
- 229910052500 inorganic mineral Inorganic materials 0.000 description 3
- 230000000302 ischemic effect Effects 0.000 description 3
- 229940098779 methanesulfonic acid Drugs 0.000 description 3
- 239000011707 mineral Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 108090000623 proteins and genes Proteins 0.000 description 3
- 230000002829 reductive effect Effects 0.000 description 3
- 210000002966 serum Anatomy 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 235000019698 starch Nutrition 0.000 description 3
- 238000003786 synthesis reaction Methods 0.000 description 3
- 239000012049 topical pharmaceutical composition Substances 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 230000004393 visual impairment Effects 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- 206010002329 Aneurysm Diseases 0.000 description 2
- 201000004569 Blindness Diseases 0.000 description 2
- 206010058202 Cystoid macular oedema Diseases 0.000 description 2
- 206010012689 Diabetic retinopathy Diseases 0.000 description 2
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 2
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
- 208000009857 Microaneurysm Diseases 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- 102000001253 Protein Kinase Human genes 0.000 description 2
- 101710201186 Protein kinase C-like 1 Proteins 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 230000002159 abnormal effect Effects 0.000 description 2
- 230000009471 action Effects 0.000 description 2
- 230000004913 activation Effects 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000001143 conditioned effect Effects 0.000 description 2
- 239000006071 cream Substances 0.000 description 2
- 201000010206 cystoid macular edema Diseases 0.000 description 2
- 230000006378 damage Effects 0.000 description 2
- 230000001419 dependent effect Effects 0.000 description 2
- 231100000673 dose–response relationship Toxicity 0.000 description 2
- 238000002651 drug therapy Methods 0.000 description 2
- 230000001804 emulsifying effect Effects 0.000 description 2
- 229940093499 ethyl acetate Drugs 0.000 description 2
- 235000019439 ethyl acetate Nutrition 0.000 description 2
- 210000000416 exudates and transudate Anatomy 0.000 description 2
- 230000001605 fetal effect Effects 0.000 description 2
- 239000007903 gelatin capsule Substances 0.000 description 2
- 239000003349 gelling agent Substances 0.000 description 2
- 239000008187 granular material Substances 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 238000001990 intravenous administration Methods 0.000 description 2
- 238000002647 laser therapy Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 210000004379 membrane Anatomy 0.000 description 2
- 239000012528 membrane Substances 0.000 description 2
- QIQXTHQIDYTFRH-UHFFFAOYSA-N octadecanoic acid Chemical compound CCCCCCCCCCCCCCCCCC(O)=O QIQXTHQIDYTFRH-UHFFFAOYSA-N 0.000 description 2
- 230000007170 pathology Effects 0.000 description 2
- 239000012071 phase Substances 0.000 description 2
- BQJRUJTZSGYBEZ-YVQNUNKESA-N phorbol 12,13-dibutanoate Chemical compound C([C@]1(O)C(=O)C(C)=C[C@H]1[C@@]1(O)[C@H](C)[C@H]2OC(=O)CCC)C(CO)=C[C@H]1[C@H]1[C@]2(OC(=O)CCC)C1(C)C BQJRUJTZSGYBEZ-YVQNUNKESA-N 0.000 description 2
- 102000020233 phosphotransferase Human genes 0.000 description 2
- INAAIJLSXJJHOZ-UHFFFAOYSA-N pibenzimol Chemical compound C1CN(C)CCN1C1=CC=C(N=C(N2)C=3C=C4NC(=NC4=CC=3)C=3C=CC(O)=CC=3)C2=C1 INAAIJLSXJJHOZ-UHFFFAOYSA-N 0.000 description 2
- 239000001267 polyvinylpyrrolidone Substances 0.000 description 2
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 2
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 2
- 239000000843 powder Substances 0.000 description 2
- 108060006633 protein kinase Proteins 0.000 description 2
- 238000000746 purification Methods 0.000 description 2
- 239000011541 reaction mixture Substances 0.000 description 2
- 239000000790 retinal pigment Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- 239000007787 solid Substances 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 229940124597 therapeutic agent Drugs 0.000 description 2
- 230000000699 topical effect Effects 0.000 description 2
- 238000005303 weighing Methods 0.000 description 2
- UEJJHQNACJXSKW-UHFFFAOYSA-N 2-(2,6-dioxopiperidin-3-yl)-1H-isoindole-1,3(2H)-dione Chemical compound O=C1C2=CC=CC=C2C(=O)N1C1CCC(=O)NC1=O UEJJHQNACJXSKW-UHFFFAOYSA-N 0.000 description 1
- MTJGVAJYTOXFJH-UHFFFAOYSA-N 3-aminonaphthalene-1,5-disulfonic acid Chemical compound C1=CC=C(S(O)(=O)=O)C2=CC(N)=CC(S(O)(=O)=O)=C21 MTJGVAJYTOXFJH-UHFFFAOYSA-N 0.000 description 1
- KIWODJBCHRADND-UHFFFAOYSA-N 3-anilino-4-[1-[3-(1-imidazolyl)propyl]-3-indolyl]pyrrole-2,5-dione Chemical compound O=C1NC(=O)C(C=2C3=CC=CC=C3N(CCCN3C=NC=C3)C=2)=C1NC1=CC=CC=C1 KIWODJBCHRADND-UHFFFAOYSA-N 0.000 description 1
- XPOKDUGZEKOMRB-UHFFFAOYSA-N 5-hydroxy-2-methylidenepentanoic acid Chemical compound OCCCC(=C)C(O)=O XPOKDUGZEKOMRB-UHFFFAOYSA-N 0.000 description 1
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 1
- 241000220479 Acacia Species 0.000 description 1
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 1
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 1
- 208000002249 Diabetes Complications Diseases 0.000 description 1
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 1
- 239000006144 Dulbecco’s modified Eagle's medium Substances 0.000 description 1
- 102000003951 Erythropoietin Human genes 0.000 description 1
- 108090000394 Erythropoietin Proteins 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- 108090000386 Fibroblast Growth Factor 1 Proteins 0.000 description 1
- 102100031706 Fibroblast growth factor 1 Human genes 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 102000014150 Interferons Human genes 0.000 description 1
- 108010050904 Interferons Proteins 0.000 description 1
- 206010065630 Iris neovascularisation Diseases 0.000 description 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- 229920000168 Microcrystalline cellulose Polymers 0.000 description 1
- 102000013566 Plasminogen Human genes 0.000 description 1
- 108010051456 Plasminogen Proteins 0.000 description 1
- 102000015766 Protein Kinase C beta Human genes 0.000 description 1
- 108010024526 Protein Kinase C beta Proteins 0.000 description 1
- 208000007135 Retinal Neovascularization Diseases 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- XUIMIQQOPSSXEZ-UHFFFAOYSA-N Silicon Chemical compound [Si] XUIMIQQOPSSXEZ-UHFFFAOYSA-N 0.000 description 1
- 235000021355 Stearic acid Nutrition 0.000 description 1
- 229930006000 Sucrose Natural products 0.000 description 1
- CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 description 1
- 108010000499 Thromboplastin Proteins 0.000 description 1
- 102100030859 Tissue factor Human genes 0.000 description 1
- GLNADSQYFUSGOU-GPTZEZBUSA-J Trypan blue Chemical compound [Na+].[Na+].[Na+].[Na+].C1=C(S([O-])(=O)=O)C=C2C=C(S([O-])(=O)=O)C(/N=N/C3=CC=C(C=C3C)C=3C=C(C(=CC=3)\N=N\C=3C(=CC4=CC(=CC(N)=C4C=3O)S([O-])(=O)=O)S([O-])(=O)=O)C)=C(O)C2=C1N GLNADSQYFUSGOU-GPTZEZBUSA-J 0.000 description 1
- 206010047513 Vision blurred Diseases 0.000 description 1
- 206010047531 Visual acuity reduced Diseases 0.000 description 1
- 206010047571 Visual impairment Diseases 0.000 description 1
- CPGKMLVTFNUAHL-UHFFFAOYSA-N [Ca].[Ca] Chemical compound [Ca].[Ca] CPGKMLVTFNUAHL-UHFFFAOYSA-N 0.000 description 1
- 230000002745 absorbent Effects 0.000 description 1
- 239000002250 absorbent Substances 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 239000011149 active material Substances 0.000 description 1
- 239000000443 aerosol Substances 0.000 description 1
- 230000032683 aging Effects 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 239000008346 aqueous phase Substances 0.000 description 1
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 210000004369 blood Anatomy 0.000 description 1
- 239000008280 blood Substances 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 210000004204 blood vessel Anatomy 0.000 description 1
- 239000001045 blue dye Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 210000001715 carotid artery Anatomy 0.000 description 1
- 108091092356 cellular DNA Proteins 0.000 description 1
- 239000001913 cellulose Substances 0.000 description 1
- 235000010980 cellulose Nutrition 0.000 description 1
- 229920002678 cellulose Polymers 0.000 description 1
- 238000012512 characterization method Methods 0.000 description 1
- 238000007385 chemical modification Methods 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 238000007796 conventional method Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 230000003247 decreasing effect Effects 0.000 description 1
- 230000007850 degeneration Effects 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000008021 deposition Effects 0.000 description 1
- 238000013461 design Methods 0.000 description 1
- 238000011161 development Methods 0.000 description 1
- 230000018109 developmental process Effects 0.000 description 1
- 201000011190 diabetic macular edema Diseases 0.000 description 1
- 239000003085 diluting agent Substances 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- 210000005081 epithelial layer Anatomy 0.000 description 1
- 210000000981 epithelium Anatomy 0.000 description 1
- 229940105423 erythropoietin Drugs 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 238000013534 fluorescein angiography Methods 0.000 description 1
- 235000003599 food sweetener Nutrition 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 238000000265 homogenisation Methods 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 229940079322 interferon Drugs 0.000 description 1
- 239000000543 intermediate Substances 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 230000002427 irreversible effect Effects 0.000 description 1
- 208000028867 ischemia Diseases 0.000 description 1
- 210000003734 kidney Anatomy 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 208000018769 loss of vision Diseases 0.000 description 1
- 231100000864 loss of vision Toxicity 0.000 description 1
- 230000001050 lubricating effect Effects 0.000 description 1
- IWYDHOAUDWTVEP-UHFFFAOYSA-M mandelate Chemical compound [O-]C(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-M 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 235000019813 microcrystalline cellulose Nutrition 0.000 description 1
- 239000008108 microcrystalline cellulose Substances 0.000 description 1
- 229940016286 microcrystalline cellulose Drugs 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 230000004660 morphological change Effects 0.000 description 1
- 239000000346 nonvolatile oil Substances 0.000 description 1
- OQCDKBAXFALNLD-UHFFFAOYSA-N octadecanoic acid Natural products CCCCCCCC(C)CCCCCCCCC(O)=O OQCDKBAXFALNLD-UHFFFAOYSA-N 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002674 ointment Substances 0.000 description 1
- 238000011369 optimal treatment Methods 0.000 description 1
- 210000003463 organelle Anatomy 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 239000001301 oxygen Substances 0.000 description 1
- 229910052760 oxygen Inorganic materials 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 230000008807 pathological lesion Effects 0.000 description 1
- 230000010412 perfusion Effects 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 239000008194 pharmaceutical composition Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 235000011007 phosphoric acid Nutrition 0.000 description 1
- 150000003016 phosphoric acids Chemical class 0.000 description 1
- 108091008695 photoreceptors Proteins 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 210000004694 pigment cell Anatomy 0.000 description 1
- OXCMYAYHXIHQOA-UHFFFAOYSA-N potassium;[2-butyl-5-chloro-3-[[4-[2-(1,2,4-triaza-3-azanidacyclopenta-1,4-dien-5-yl)phenyl]phenyl]methyl]imidazol-4-yl]methanol Chemical compound [K+].CCCCC1=NC(Cl)=C(CO)N1CC1=CC=C(C=2C(=CC=CC=2)C2=N[N-]N=N2)C=C1 OXCMYAYHXIHQOA-UHFFFAOYSA-N 0.000 description 1
- 230000003389 potentiating effect Effects 0.000 description 1
- 230000002028 premature Effects 0.000 description 1
- 230000008569 process Effects 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000004393 prognosis Methods 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 102000004169 proteins and genes Human genes 0.000 description 1
- 230000005180 public health Effects 0.000 description 1
- 230000008521 reorganization Effects 0.000 description 1
- 210000001525 retina Anatomy 0.000 description 1
- 230000004250 retinal swelling Effects 0.000 description 1
- 230000028327 secretion Effects 0.000 description 1
- 229910052710 silicon Inorganic materials 0.000 description 1
- 239000010703 silicon Substances 0.000 description 1
- 239000008117 stearic acid Substances 0.000 description 1
- 239000012058 sterile packaged powder Substances 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000005720 sucrose Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000011580 syndromic disease Diseases 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 229960003433 thalidomide Drugs 0.000 description 1
- 238000002560 therapeutic procedure Methods 0.000 description 1
- 230000001131 transforming effect Effects 0.000 description 1
- 150000004684 trihydrates Chemical group 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
- 208000029257 vision disease Diseases 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 239000003871 white petrolatum Substances 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
- A61K31/40—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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K41/00—Medicinal preparations obtained by treating materials with wave energy or particle radiation ; Therapies using these preparations
-
- 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
-
- 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
- A61K31/407—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 condensed with other heterocyclic ring systems, e.g. ketorolac, physostigmine
-
- 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
-
- 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
- A61P27/12—Ophthalmic agents for cataracts
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P7/00—Drugs for disorders of the blood or the extracellular fluid
- A61P7/10—Antioedematous agents; Diuretics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US1665896P | 1996-05-01 | 1996-05-01 | |
| US08/841,739 US6114320A (en) | 1996-05-01 | 1997-04-30 | Therapeutic treatment for VEGF related ocular diseases |
| PCT/US1997/007800 WO1997040831A1 (en) | 1996-05-01 | 1997-05-01 | Therapeutic treatment for vegf related occular diseases |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| IL126836A0 IL126836A0 (en) | 1999-09-22 |
| IL126836A true IL126836A (en) | 2004-05-12 |
Family
ID=26688915
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL12683697A IL126836A (en) | 1996-05-01 | 1997-05-01 | Beta-inhibitor of protein kinase C beta-use for use as a drug for the treatment of eye diseases |
Country Status (22)
| Country | Link |
|---|---|
| US (1) | US6114320A (ja) |
| EP (1) | EP0918519B1 (ja) |
| JP (1) | JP4122060B2 (ja) |
| KR (1) | KR100364487B1 (ja) |
| CN (1) | CN1158073C (ja) |
| AT (1) | ATE270548T1 (ja) |
| AU (1) | AU724923B2 (ja) |
| BR (1) | BR9710705A (ja) |
| CA (1) | CA2253613C (ja) |
| CZ (1) | CZ296711B6 (ja) |
| DE (1) | DE69729798T2 (ja) |
| EA (1) | EA001752B1 (ja) |
| ES (1) | ES2224249T3 (ja) |
| HK (1) | HK1020017A1 (ja) |
| HU (1) | HU226378B1 (ja) |
| IL (1) | IL126836A (ja) |
| NO (1) | NO322209B1 (ja) |
| NZ (2) | NZ538109A (ja) |
| PL (1) | PL189020B1 (ja) |
| PT (1) | PT918519E (ja) |
| UA (1) | UA54427C2 (ja) |
| WO (1) | WO1997040831A1 (ja) |
Families Citing this family (23)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5723456A (en) * | 1993-12-07 | 1998-03-03 | Eli Lilly & Company | Therapeutic treatment for cardiovascular diseases |
| US6093740A (en) * | 1997-04-30 | 2000-07-25 | Eli Lilly And Company | Therapeutic treatment for skin disorders |
| EP1105136B1 (en) * | 1998-08-13 | 2007-08-29 | Novartis AG | Method for treating ocular neovascular diseases |
| US6214819B1 (en) | 1998-11-23 | 2001-04-10 | Novartis Ag | Method for treating ocular neovascular diseases |
| ES2211197T3 (es) * | 1998-11-23 | 2004-07-01 | Novartis Ag | Uso de derivados de estaurosporina para tratar enfermedades neovasculares oculares. |
| DE69926536T3 (de) | 1998-12-22 | 2013-09-12 | Genentech, Inc. | Antagonisten von vaskular-endothelialen zellwachstumsfaktoren und ihre anwendung |
| US6271233B1 (en) | 1999-08-10 | 2001-08-07 | Ciba Vision Corporation | Method for treating ocular neovascular diseases |
| US6921763B2 (en) | 1999-09-17 | 2005-07-26 | Abbott Laboratories | Pyrazolopyrimidines as therapeutic agents |
| IL151045A0 (en) | 2000-02-07 | 2003-04-10 | Abbott Gmbh & Co Kg | 2-benzothiazolyl urea derivatives and their use as protein kinase inhibitors |
| MXPA03008560A (es) | 2001-03-22 | 2004-06-30 | Abbot Gmbh & Co Kg | Pirazolopirimidinas como agentes terapeuticos. |
| US20020165158A1 (en) * | 2001-03-27 | 2002-11-07 | King George L. | Methods of modulating angiogenesis |
| US20030119812A1 (en) * | 2001-11-08 | 2003-06-26 | Brazzell Romulus Kimbro | Method for decreasing capillary permeability in the retina |
| US20030236246A1 (en) * | 2002-04-30 | 2003-12-25 | Brazzell Romulus Kimbro | Method for decreasing capillary permeability in the retina |
| EP2319493A3 (en) * | 2002-07-23 | 2011-07-27 | Novartis AG | Ophthalmic ointment composition comprising a drug, an ointment base and a solubilizing/dispersing agent |
| US20070059381A1 (en) * | 2003-06-20 | 2007-03-15 | Barker Ronnie C | Treatment of amd with combination of ingredients |
| JP2007529434A (ja) * | 2004-03-17 | 2007-10-25 | ラース マイケル ラーセン， | 視覚サイクルの阻害による網膜症の予防 |
| BRPI0509576A (pt) | 2004-04-02 | 2007-05-29 | Osi Pharm Inc | composto, método de tratamento de um paciente tendo uma condição que é mediada pela atividade de proteìna quinase, e, composição farmacêutica |
| TW200613306A (en) | 2004-07-20 | 2006-05-01 | Osi Pharm Inc | Imidazotriazines as protein kinase inhibitors |
| AR057960A1 (es) | 2005-12-02 | 2007-12-26 | Osi Pharm Inc | Inhibidores de proteina quinasa biciclicos |
| US7455447B2 (en) * | 2006-05-19 | 2008-11-25 | Mediatek Inc. | Method and apparatus for a portable device |
| AU2007286817A1 (en) * | 2006-08-23 | 2008-02-28 | Novartis Ag | Use of PKC inhibitors in particular indolylmaleimide derivatives in ocular diseases |
| EP2089016A4 (en) * | 2006-10-03 | 2014-10-08 | Univ Pennsylvania | METHOD FOR TREATING MACULAR AGENCY |
| US10360673B2 (en) | 2015-03-26 | 2019-07-23 | Eyekor, Llc | Image analysis |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CZ280738B6 (cs) * | 1988-02-10 | 1996-04-17 | F. Hoffmann - La Roche And Co., Aktiengesellschaft | Substituované pyrroly, jejich použití pro výrobu léčiv a léčiva na jejich bázi |
| IL111851A (en) * | 1993-12-07 | 1998-09-24 | Lilly Co Eli | Improved synthesis of bisindolylsimilides and process for its preparation |
| US5624949A (en) * | 1993-12-07 | 1997-04-29 | Eli Lilly And Company | Protein kinase C inhibitors |
| CN1050844C (zh) * | 1993-12-07 | 2000-03-29 | 伊莱利利公司 | 蛋白激酶ｃ抑制剂 |
| US5545636A (en) * | 1993-12-23 | 1996-08-13 | Eli Lilly And Company | Protein kinase C inhibitors |
| US5481003A (en) * | 1994-06-22 | 1996-01-02 | Eli Lilly And Company | Protein kinase C inhibitors |
| US5491242A (en) * | 1994-06-22 | 1996-02-13 | Eli Lilly And Company | Protein kinase C inhibitors |
-
1997
- 1997-01-05 UA UA98116304A patent/UA54427C2/uk unknown
- 1997-04-30 US US08/841,739 patent/US6114320A/en not_active Expired - Lifetime
- 1997-05-01 PL PL97330463A patent/PL189020B1/pl not_active IP Right Cessation
- 1997-05-01 NZ NZ538109A patent/NZ538109A/en not_active IP Right Cessation
- 1997-05-01 PT PT97923594T patent/PT918519E/pt unknown
- 1997-05-01 CA CA002253613A patent/CA2253613C/en not_active Expired - Fee Related
- 1997-05-01 NZ NZ332833A patent/NZ332833A/en unknown
- 1997-05-01 EA EA199800970A patent/EA001752B1/ru not_active IP Right Cessation
- 1997-05-01 WO PCT/US1997/007800 patent/WO1997040831A1/en active IP Right Grant
- 1997-05-01 AU AU29361/97A patent/AU724923B2/en not_active Ceased
- 1997-05-01 BR BR9710705A patent/BR9710705A/pt not_active Application Discontinuation
- 1997-05-01 CZ CZ0349998A patent/CZ296711B6/cs not_active IP Right Cessation
- 1997-05-01 CN CNB971956995A patent/CN1158073C/zh not_active Expired - Fee Related
- 1997-05-01 ES ES97923594T patent/ES2224249T3/es not_active Expired - Lifetime
- 1997-05-01 IL IL12683697A patent/IL126836A/en not_active IP Right Cessation
- 1997-05-01 JP JP53929897A patent/JP4122060B2/ja not_active Expired - Fee Related
- 1997-05-01 DE DE69729798T patent/DE69729798T2/de not_active Expired - Lifetime
- 1997-05-01 KR KR10-1998-0708799A patent/KR100364487B1/ko not_active IP Right Cessation
- 1997-05-01 EP EP97923594A patent/EP0918519B1/en not_active Expired - Lifetime
- 1997-05-01 HU HU9902805A patent/HU226378B1/hu not_active IP Right Cessation
- 1997-05-01 AT AT97923594T patent/ATE270548T1/de active
-
1998
- 1998-10-30 NO NO19985067A patent/NO322209B1/no not_active IP Right Cessation
-
1999
- 1999-11-19 HK HK99105357A patent/HK1020017A1/xx not_active IP Right Cessation
Also Published As
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| IL126836A (en) | Beta-inhibitor of protein kinase C beta-use for use as a drug for the treatment of eye diseases | |
| WO1997040831A9 (en) | Therapeutic treatment for vegf related occular diseases | |
| AU2017326791B2 (en) | Medicinal composition | |
| JP2018521120A (ja) | 翼状片を治療するための組成物及び方法 | |
| KR20090010161A (ko) | 시클로리그난의 제2형 당뇨병의 치료를 위한, 그리고 피임약으로서의 용도 | |
| EP2156833A1 (en) | Prophylactic or therapeutic agent for posterior ocular disease comprising non-ergot selective d2 receptor agonist as active ingredient | |
| JP5363123B2 (ja) | 網膜神経又は視神経の保護剤 | |
| CN115768419A (zh) | 用于色满卡林前药治疗的改进方法和组合物 | |
| JP5875585B2 (ja) | 緑内障および高眼圧症の処置のためのアデノシンａ１アゴニスト | |
| KR20070040326A (ko) | 백내장, 황반 변성 및 다른 안과 질환의 개선 | |
| US20220324890A1 (en) | Controlled-delivery cromakalim prodrugs | |
| JP2012006918A (ja) | イソキノリンスルホニル誘導体を有効成分として含有する網脈絡膜変性疾患の予防または治療剤 | |
| AU2004255199A1 (en) | Coumarin derivatives for the treatment of ophthalmic disorders | |
| WO2010056710A1 (en) | Compositions and methods for treating eye diseases | |
| MXPA98009160A (en) | Therapeutic treatment of ocular diseases related to the vascular endothelial growth factor (ve | |
| JP2004528310A (ja) | 眼内圧を制御するためのプロペントフィリンの使用 | |
| AU2002250168A1 (en) | Use of propentofylline to control intraocular pressure | |
| ZA200604402B (en) | Amelioration of cataracts, macular degeneration and other ophthalmic diseases |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| FF | Patent granted | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| KB | Patent renewed | ||
| MM9K | Patent not in force due to non-payment of renewal fees |