KR20160015192A - 1h-인돌-1-카복스아마이드 유도체를 포함하는 국소 수성 안과용 조성물 및 안과용 질환의 치료를 위한 이의 용도 - Google Patents
1h-인돌-1-카복스아마이드 유도체를 포함하는 국소 수성 안과용 조성물 및 안과용 질환의 치료를 위한 이의 용도 Download PDFInfo
- Publication number
- KR20160015192A KR20160015192A KR1020157022071A KR20157022071A KR20160015192A KR 20160015192 A KR20160015192 A KR 20160015192A KR 1020157022071 A KR1020157022071 A KR 1020157022071A KR 20157022071 A KR20157022071 A KR 20157022071A KR 20160015192 A KR20160015192 A KR 20160015192A
- Authority
- KR
- South Korea
- Prior art keywords
- indole
- carboxamide
- pyrimidin
- methyl
- yloxy
- 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.)
- Withdrawn
Links
- 239000000203 mixture Substances 0.000 title claims abstract description 265
- CQILOHWHIWNQOE-UHFFFAOYSA-N indole-1-carboxamide Chemical class C1=CC=C2N(C(=O)N)C=CC2=C1 CQILOHWHIWNQOE-UHFFFAOYSA-N 0.000 title claims abstract description 96
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 title abstract description 21
- 201000010099 disease Diseases 0.000 title abstract description 20
- 230000000699 topical effect Effects 0.000 title abstract description 17
- 238000011282 treatment Methods 0.000 title abstract description 13
- -1 (6 - ((methylamino) methyl) pyrimidin-4-yl) oxy Chemical group 0.000 claims abstract description 328
- 239000000725 suspension Substances 0.000 claims abstract description 22
- 150000003839 salts Chemical class 0.000 claims abstract description 19
- 206010064930 age-related macular degeneration Diseases 0.000 claims abstract description 17
- 208000002780 macular degeneration Diseases 0.000 claims abstract description 17
- 150000001875 compounds Chemical class 0.000 claims abstract description 13
- 239000000243 solution Substances 0.000 claims abstract description 11
- 206010057190 Respiratory tract infections Diseases 0.000 claims description 102
- 210000001508 eye Anatomy 0.000 claims description 75
- 239000004354 Hydroxyethyl cellulose Substances 0.000 claims description 41
- 229920000663 Hydroxyethyl cellulose Polymers 0.000 claims description 41
- 235000019447 hydroxyethyl cellulose Nutrition 0.000 claims description 41
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 34
- 229920005862 polyol Polymers 0.000 claims description 33
- 150000003077 polyols Chemical class 0.000 claims description 32
- 229920002678 cellulose Polymers 0.000 claims description 28
- 239000001913 cellulose Substances 0.000 claims description 28
- 125000004289 pyrazol-3-yl group Chemical group [H]N1N=C(*)C([H])=C1[H] 0.000 claims description 28
- 239000000375 suspending agent Substances 0.000 claims description 23
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 22
- 229910052739 hydrogen Inorganic materials 0.000 claims description 21
- 239000001257 hydrogen Substances 0.000 claims description 21
- 239000003002 pH adjusting agent Substances 0.000 claims description 21
- 125000004284 isoxazol-3-yl group Chemical group [H]C1=C([H])C(*)=NO1 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 18
- HFHDHCJBZVLPGP-UHFFFAOYSA-N schardinger α-dextrin Chemical class O1C(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC(C(O)C2O)C(CO)OC2OC(C(C2O)O)C(CO)OC2OC2C(O)C(O)C1OC2CO HFHDHCJBZVLPGP-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 claims description 16
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 16
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 14
- 206010038848 Retinal detachment Diseases 0.000 claims description 14
- 210000001525 retina Anatomy 0.000 claims description 14
- 230000004264 retinal detachment Effects 0.000 claims description 14
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 13
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 13
- 239000003755 preservative agent Substances 0.000 claims description 13
- 229910052799 carbon Inorganic materials 0.000 claims description 12
- 210000004087 cornea Anatomy 0.000 claims description 12
- 125000000623 heterocyclic group Chemical group 0.000 claims description 12
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 12
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 claims description 11
- 206010029113 Neovascularisation Diseases 0.000 claims description 11
- 229960000686 benzalkonium chloride Drugs 0.000 claims description 11
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 claims description 11
- 230000007170 pathology Effects 0.000 claims description 11
- 125000006432 1-methyl cyclopropyl group Chemical group [H]C([H])([H])C1(*)C([H])([H])C1([H])[H] 0.000 claims description 10
- 150000001642 boronic acid derivatives Chemical class 0.000 claims description 10
- 239000003981 vehicle Substances 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 9
- 229910052736 halogen Inorganic materials 0.000 claims description 9
- 150000002367 halogens Chemical class 0.000 claims description 9
- 229910052760 oxygen Inorganic materials 0.000 claims description 9
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 9
- 150000003856 quaternary ammonium compounds Chemical class 0.000 claims description 9
- 229910052717 sulfur Inorganic materials 0.000 claims description 9
- XAGLYPURPUETCX-UHFFFAOYSA-N 2-[(6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)oxy]indole-1-carboxamide Chemical compound CC1CC2=C(N=CN=C2OC=2N(C3=CC=CC=C3C=2)C(=O)N)CN1 XAGLYPURPUETCX-UHFFFAOYSA-N 0.000 claims description 8
- FBPFZTCFMRRESA-FSIIMWSLSA-N D-Glucitol Natural products OC[C@H](O)[C@H](O)[C@@H](O)[C@H](O)CO FBPFZTCFMRRESA-FSIIMWSLSA-N 0.000 claims description 8
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 claims description 8
- 125000005842 heteroatom Chemical group 0.000 claims description 8
- 230000002335 preservative effect Effects 0.000 claims description 8
- BTBUEUYNUDRHOZ-UHFFFAOYSA-N Borate Chemical compound [O-]B([O-])[O-] BTBUEUYNUDRHOZ-UHFFFAOYSA-N 0.000 claims description 7
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 7
- JVFGXECLSQXABC-UHFFFAOYSA-N ac1l3obq Chemical compound O1C(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC(C(O)C2O)C(COCC(O)C)OC2OC(C(C2O)O)C(COCC(C)O)OC2OC2C(O)C(O)C1OC2COCC(C)O JVFGXECLSQXABC-UHFFFAOYSA-N 0.000 claims description 7
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 7
- 125000000171 (C1-C6) haloalkyl group Chemical group 0.000 claims description 6
- FBPFZTCFMRRESA-JGWLITMVSA-N D-glucitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-JGWLITMVSA-N 0.000 claims description 6
- 229930195725 Mannitol Natural products 0.000 claims description 6
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 6
- 239000004310 lactic acid Substances 0.000 claims description 6
- 235000014655 lactic acid Nutrition 0.000 claims description 6
- 235000010355 mannitol Nutrition 0.000 claims description 6
- 239000000594 mannitol Substances 0.000 claims description 6
- 125000001624 naphthyl group Chemical group 0.000 claims description 6
- 235000010356 sorbitol Nutrition 0.000 claims description 6
- 239000000600 sorbitol Substances 0.000 claims description 6
- 230000033115 angiogenesis Effects 0.000 claims description 5
- KGBXLFKZBHKPEV-UHFFFAOYSA-N boric acid Chemical group OB(O)O KGBXLFKZBHKPEV-UHFFFAOYSA-N 0.000 claims description 5
- 239000000872 buffer Substances 0.000 claims description 5
- DFDIROLDLLFVOE-UHFFFAOYSA-N n-methyl-1-pyrimidin-4-ylmethanamine Chemical compound CNCC1=CC=NC=N1 DFDIROLDLLFVOE-UHFFFAOYSA-N 0.000 claims description 5
- 239000004094 surface-active agent Substances 0.000 claims description 5
- 108091008605 VEGF receptors Proteins 0.000 claims description 4
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 claims description 4
- 239000004037 angiogenesis inhibitor Substances 0.000 claims description 4
- 230000015572 biosynthetic process Effects 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000001072 heteroaryl group Chemical group 0.000 claims description 4
- 230000003204 osmotic effect Effects 0.000 claims description 4
- 125000004497 pyrazol-5-yl group Chemical group N1N=CC=C1* 0.000 claims description 4
- FUXJMHXHGDAHPD-UHFFFAOYSA-N pyrimidine-2-carboxamide Chemical compound NC(=O)C1=NC=CC=N1 FUXJMHXHGDAHPD-UHFFFAOYSA-N 0.000 claims description 4
- ODLHGICHYURWBS-LKONHMLTSA-N trappsol cyclo Chemical compound CC(O)COC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](COCC(C)O)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)COCC(O)C)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1COCC(C)O ODLHGICHYURWBS-LKONHMLTSA-N 0.000 claims description 4
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 4
- 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004739 (C1-C6) alkylsulfonyl group Chemical group 0.000 claims description 3
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 3
- 125000003341 7 membered heterocyclic group Chemical group 0.000 claims description 3
- 206010048964 Carotid artery occlusion Diseases 0.000 claims description 3
- 208000003569 Central serous chorioretinopathy Diseases 0.000 claims description 3
- 208000033379 Chorioretinopathy Diseases 0.000 claims description 3
- 206010008790 Choroidal rupture Diseases 0.000 claims description 3
- 208000002691 Choroiditis Diseases 0.000 claims description 3
- 206010058202 Cystoid macular oedema Diseases 0.000 claims description 3
- 206010012688 Diabetic retinal oedema Diseases 0.000 claims description 3
- IAJILQKETJEXLJ-UHFFFAOYSA-N Galacturonsaeure Natural products O=CC(O)C(O)C(O)C(O)C(O)=O IAJILQKETJEXLJ-UHFFFAOYSA-N 0.000 claims description 3
- 201000002563 Histoplasmosis Diseases 0.000 claims description 3
- 206010065630 Iris neovascularisation Diseases 0.000 claims description 3
- 208000001344 Macular Edema Diseases 0.000 claims description 3
- 201000010183 Papilledema Diseases 0.000 claims description 3
- 208000003971 Posterior uveitis Diseases 0.000 claims description 3
- 102000001253 Protein Kinase Human genes 0.000 claims description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 claims description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 claims description 3
- 208000007135 Retinal Neovascularization Diseases 0.000 claims description 3
- 201000007527 Retinal artery occlusion Diseases 0.000 claims description 3
- 206010038886 Retinal oedema Diseases 0.000 claims description 3
- 206010038933 Retinopathy of prematurity Diseases 0.000 claims description 3
- 201000005485 Toxoplasmosis Diseases 0.000 claims description 3
- 206010046851 Uveitis Diseases 0.000 claims description 3
- IAJILQKETJEXLJ-QTBDOELSSA-N aldehydo-D-glucuronic acid Chemical compound O=C[C@H](O)[C@@H](O)[C@H](O)[C@H](O)C(O)=O IAJILQKETJEXLJ-QTBDOELSSA-N 0.000 claims description 3
- 125000004429 atom Chemical group 0.000 claims description 3
- 230000001684 chronic effect Effects 0.000 claims description 3
- 201000010206 cystoid macular edema Diseases 0.000 claims description 3
- 201000011190 diabetic macular edema Diseases 0.000 claims description 3
- 229940097043 glucuronic acid Drugs 0.000 claims description 3
- 125000005843 halogen group Chemical group 0.000 claims description 3
- 150000002431 hydrogen Chemical class 0.000 claims description 3
- 208000015181 infectious disease Diseases 0.000 claims description 3
- 230000002458 infectious effect Effects 0.000 claims description 3
- 230000002757 inflammatory effect Effects 0.000 claims description 3
- 230000001404 mediated effect Effects 0.000 claims description 3
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 3
- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 3
- 239000002997 ophthalmic solution Substances 0.000 claims description 3
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 claims description 3
- 108060006633 protein kinase Proteins 0.000 claims description 3
- 208000008128 pulmonary tuberculosis Diseases 0.000 claims description 3
- 201000011195 retinal edema Diseases 0.000 claims description 3
- 208000004644 retinal vein occlusion Diseases 0.000 claims description 3
- 229920006395 saturated elastomer Polymers 0.000 claims description 3
- SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- UCDDWBVLTFCBJN-UHFFFAOYSA-N 1-(5,7-dihydropyrrolo[3,4-d]pyrimidin-6-yl)ethanone Chemical compound N1=CN=C2CN(C(=O)C)CC2=C1 UCDDWBVLTFCBJN-UHFFFAOYSA-N 0.000 claims description 2
- UWKGCTDATIKZDI-UHFFFAOYSA-N 2-[(7-acetyl-6-methyl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl)oxy]indole-1-carboxamide Chemical compound C(C)(=O)N1CC=2N=CN=C(C=2CC1C)OC=1N(C2=CC=CC=C2C=1)C(=O)N UWKGCTDATIKZDI-UHFFFAOYSA-N 0.000 claims description 2
- LPCQBTAOTIZGAE-UHFFFAOYSA-N 2h-pyrimidine-1-carboxamide Chemical compound NC(=O)N1CN=CC=C1 LPCQBTAOTIZGAE-UHFFFAOYSA-N 0.000 claims description 2
- FGFZUHKYTRVORA-UHFFFAOYSA-N 4-fluoro-5-[6-(hydroxymethyl)pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=NC(CO)=CC(OC=2C(=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)F)=N1 FGFZUHKYTRVORA-UHFFFAOYSA-N 0.000 claims description 2
- PUYPJCVHLPNOON-UHFFFAOYSA-N 5-(1-methylcyclopropyl)-1,2-oxazole Chemical compound C=1C=NOC=1C1(C)CC1 PUYPJCVHLPNOON-UHFFFAOYSA-N 0.000 claims description 2
- RTNBWCYGJNXZBW-UHFFFAOYSA-N 5-(5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yloxy)-n-[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C=1C(NC(=O)N2C3=CC=C(OC=4C=5CCNCC=5N=CN=4)C=C3C=C2)=NOC=1C1(C(F)(F)F)CC1 RTNBWCYGJNXZBW-UHFFFAOYSA-N 0.000 claims description 2
- NLPLUYRSIUXZHN-UHFFFAOYSA-N 5-(6,7-dihydro-5h-pyrrolo[3,4-d]pyrimidin-4-yloxy)-n-[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C=1C(NC(=O)N2C3=CC=C(OC=4C=5CNCC=5N=CN=4)C=C3C=C2)=NOC=1C1(C(F)(F)F)CC1 NLPLUYRSIUXZHN-UHFFFAOYSA-N 0.000 claims description 2
- WGGSXHRZQATNAN-UHFFFAOYSA-N 5-[(6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl)oxy]-n-[5-[1-(trifluoromethyl)cyclopropyl]-1,2-oxazol-3-yl]indole-1-carboxamide Chemical compound C1NC(C)CC2=C1N=CN=C2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1(C(F)(F)F)CC1 WGGSXHRZQATNAN-UHFFFAOYSA-N 0.000 claims description 2
- BIPJNBSRIWQGOI-UHFFFAOYSA-N 5-[2-(methylaminomethyl)pyridin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=C1 BIPJNBSRIWQGOI-UHFFFAOYSA-N 0.000 claims description 2
- ODNIRXCKGWBXDJ-UHFFFAOYSA-N 5-[6-(aminomethyl)pyrimidin-4-yl]oxy-N-(5-cyclopropyl-1-methylpyrazol-3-yl)indole-1-carboxamide Chemical compound Cn1nc(NC(=O)n2ccc3cc(Oc4cc(CN)ncn4)ccc23)cc1C1CC1 ODNIRXCKGWBXDJ-UHFFFAOYSA-N 0.000 claims description 2
- DTINAYGDNIERCY-UHFFFAOYSA-N 5-[6-(ethylaminomethyl)pyrimidin-4-yl]oxy-n-(5-propan-2-yl-1h-pyrazol-3-yl)indole-1-carboxamide Chemical compound C1=NC(CNCC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NNC(=C2)C(C)C)=N1 DTINAYGDNIERCY-UHFFFAOYSA-N 0.000 claims description 2
- KSNTWEXIIUNPMO-UHFFFAOYSA-N 5-[6-(hydroxymethyl)pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=NC(CO)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 KSNTWEXIIUNPMO-UHFFFAOYSA-N 0.000 claims description 2
- CLANWTXQBASPPX-UHFFFAOYSA-N 5-[6-(methoxymethyl)pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=NC(COC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 CLANWTXQBASPPX-UHFFFAOYSA-N 0.000 claims description 2
- JGQCTOQSKJYTIU-UHFFFAOYSA-N 5-[6-(methylaminomethyl)pyrimidin-4-yl]oxy-n-(5-propan-2-yl-1,2-oxazol-3-yl)indole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NOC(=C2)C(C)C)=N1 JGQCTOQSKJYTIU-UHFFFAOYSA-N 0.000 claims description 2
- RTSWFHTZWZRGRG-UHFFFAOYSA-N 5-[6-(methylaminomethyl)pyrimidin-4-yl]oxy-n-(5-propan-2-yl-1h-pyrazol-3-yl)indole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NNC(=C2)C(C)C)=N1 RTSWFHTZWZRGRG-UHFFFAOYSA-N 0.000 claims description 2
- LKIVAEYQGVYZTP-UHFFFAOYSA-N 5-[6-(methylaminomethyl)pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 LKIVAEYQGVYZTP-UHFFFAOYSA-N 0.000 claims description 2
- WRLCZIGPUIJLGX-UHFFFAOYSA-N 5-[6-[(dimethylamino)methyl]pyrimidin-4-yl]oxy-n-[3-(trifluoromethyl)phenyl]indole-1-carboxamide Chemical compound C1=NC(CN(C)C)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C=CC=2)C(F)(F)F)=N1 WRLCZIGPUIJLGX-UHFFFAOYSA-N 0.000 claims description 2
- NECNKMSPAJPETH-INIZCTEOSA-N 5-[[(6S)-7-acetyl-6-methyl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]oxy]-N-(1,5-dicyclopropylpyrazol-3-yl)indole-1-carboxamide Chemical compound C1(CC1)N1N=C(C=C1C1CC1)NC(=O)N1C=CC2=CC(=CC=C12)OC=1C2=C(N=CN1)CN([C@H](C2)C)C(C)=O NECNKMSPAJPETH-INIZCTEOSA-N 0.000 claims description 2
- LWKQWZZNASBIEY-HNNXBMFYSA-N 5-[[(6S)-7-acetyl-6-methyl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]oxy]-N-(1,5-dimethylpyrazol-3-yl)indole-1-carboxamide Chemical compound C[C@H]1Cc2c(CN1C(C)=O)ncnc2Oc1ccc2n(ccc2c1)C(=O)Nc1cc(C)n(C)n1 LWKQWZZNASBIEY-HNNXBMFYSA-N 0.000 claims description 2
- OSFGNCWFGJIGLF-INIZCTEOSA-N 5-[[(6S)-7-acetyl-6-methyl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]oxy]-N-(1-cyclopropyl-5-ethylpyrazol-3-yl)indole-1-carboxamide Chemical compound CCc1cc(NC(=O)n2ccc3cc(Oc4ncnc5CN([C@@H](C)Cc45)C(C)=O)ccc23)nn1C1CC1 OSFGNCWFGJIGLF-INIZCTEOSA-N 0.000 claims description 2
- YLZRJICQHVFCRU-HNNXBMFYSA-N 5-[[(6S)-7-acetyl-6-methyl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]oxy]-N-(1-cyclopropyl-5-methylpyrazol-3-yl)indole-1-carboxamide Chemical compound C1(CC1)N1N=C(C=C1C)NC(=O)N1C=CC2=CC(=CC=C12)OC=1C2=C(N=CN1)CN([C@H](C2)C)C(C)=O YLZRJICQHVFCRU-HNNXBMFYSA-N 0.000 claims description 2
- KFYCOCFXSNDQHO-HNNXBMFYSA-N 5-[[(6S)-7-acetyl-6-methyl-6,8-dihydro-5H-pyrido[3,4-d]pyrimidin-4-yl]oxy]-N-(5-cyclopropyl-1-methylpyrazol-3-yl)indole-1-carboxamide Chemical compound C1(CC1)C1=CC(=NN1C)NC(=O)N1C=CC2=CC(=CC=C12)OC=1C2=C(N=CN1)CN([C@H](C2)C)C(C)=O KFYCOCFXSNDQHO-HNNXBMFYSA-N 0.000 claims description 2
- QFGLCVUCLKAPKT-UHFFFAOYSA-N 5-propan-2-yl-1h-pyrazole-3-carboxamide Chemical compound CC(C)C1=CC(C(N)=O)=NN1 QFGLCVUCLKAPKT-UHFFFAOYSA-N 0.000 claims description 2
- NNQSCTAVJXHCPC-UHFFFAOYSA-N 6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine Chemical compound CC1CC2=C(N=CN=C2)CN1 NNQSCTAVJXHCPC-UHFFFAOYSA-N 0.000 claims description 2
- VZRXGNMWNJILDB-UHFFFAOYSA-N 8H-pyrido[3,4-d]pyrimidine-7-carboxylic acid Chemical compound C1C2=NC=NC=C2C=CN1C(=O)O VZRXGNMWNJILDB-UHFFFAOYSA-N 0.000 claims description 2
- ALKQTQGAXAVBIV-HNNXBMFYSA-N CCOC(=O)N1Cc2ncnc(Oc3ccc4n(ccc4c3)C(=O)Nc3cc(on3)C3(CC3)C(F)(F)F)c2C[C@@H]1C Chemical compound CCOC(=O)N1Cc2ncnc(Oc3ccc4n(ccc4c3)C(=O)Nc3cc(on3)C3(CC3)C(F)(F)F)c2C[C@@H]1C ALKQTQGAXAVBIV-HNNXBMFYSA-N 0.000 claims description 2
- QSSWDCZNDWFBGL-UHFFFAOYSA-N FC(C1(CC1)C1=CC=NO1)(F)F Chemical compound FC(C1(CC1)C1=CC=NO1)(F)F QSSWDCZNDWFBGL-UHFFFAOYSA-N 0.000 claims description 2
- MKOMIOOGIUZRHM-HNNXBMFYSA-N N-(1,5-dicyclopropylpyrazol-3-yl)-5-[[(6S)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C1(CC1)N1N=C(C=C1C1CC1)NC(=O)N1C=CC2=CC(=CC=C12)OC=1C2=C(N=CN1)CN[C@H](C2)C MKOMIOOGIUZRHM-HNNXBMFYSA-N 0.000 claims description 2
- 201000000582 Retinoblastoma Diseases 0.000 claims description 2
- 206010039491 Sarcoma Diseases 0.000 claims description 2
- 208000001445 Uveomeningoencephalitic Syndrome Diseases 0.000 claims description 2
- 208000025749 Vogt-Koyanagi-Harada disease Diseases 0.000 claims description 2
- 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
- ZLCRLQDKXHLOEE-HNNXBMFYSA-N ethyl (6s)-4-[1-[(5-cyclopropyl-1,2-oxazol-3-yl)carbamoyl]indol-5-yl]oxy-6-methyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidine-7-carboxylate Chemical compound CCOC(=O)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 ZLCRLQDKXHLOEE-HNNXBMFYSA-N 0.000 claims description 2
- 238000007429 general method Methods 0.000 claims description 2
- 230000002401 inhibitory effect Effects 0.000 claims description 2
- RUZLIIJDZBWWSA-INIZCTEOSA-N methyl 2-[[(1s)-1-(7-methyl-2-morpholin-4-yl-4-oxopyrido[1,2-a]pyrimidin-9-yl)ethyl]amino]benzoate Chemical group COC(=O)C1=CC=CC=C1N[C@@H](C)C1=CC(C)=CN2C(=O)C=C(N3CCOCC3)N=C12 RUZLIIJDZBWWSA-INIZCTEOSA-N 0.000 claims description 2
- OTLHPXPVTBTRNZ-UHFFFAOYSA-N n-(1-tert-butylpyrazol-3-yl)-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NN(C=C2)C(C)(C)C)=N1 OTLHPXPVTBTRNZ-UHFFFAOYSA-N 0.000 claims description 2
- VWVGYFLGXIFKNY-SFHVURJKSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-(3-methylbutyl)-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CC(C)CCN([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 VWVGYFLGXIFKNY-SFHVURJKSA-N 0.000 claims description 2
- QHVQQSQAJCXBBM-HNNXBMFYSA-N n-(5-cyclopropyl-1,2-oxazol-3-yl)-5-[[(6s)-6-methyl-7-propanoyl-6,8-dihydro-5h-pyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound CCC(=O)N([C@H](CC1=2)C)CC1=NC=NC=2OC(C=C1C=C2)=CC=C1N2C(=O)NC(=NO1)C=C1C1CC1 QHVQQSQAJCXBBM-HNNXBMFYSA-N 0.000 claims description 2
- HCHRZWORJORBKT-UHFFFAOYSA-N n-(5-cyclopropyl-1h-pyrazol-3-yl)-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NNC(=C2)C2CC2)=N1 HCHRZWORJORBKT-UHFFFAOYSA-N 0.000 claims description 2
- JJHZWXPGYFADRV-ZDUSSCGKSA-N n-[1-ethyl-5-(trifluoromethyl)pyrazol-3-yl]-5-[[(6s)-6-methyl-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4-yl]oxy]indole-1-carboxamide Chemical compound C1=C(C(F)(F)F)N(CC)N=C1NC(=O)N1C2=CC=C(OC=3C=4C[C@H](C)NCC=4N=CN=3)C=C2C=C1 JJHZWXPGYFADRV-ZDUSSCGKSA-N 0.000 claims description 2
- PGHNRLMKTNYWMX-UHFFFAOYSA-N n-[2-fluoro-3-(trifluoromethyl)phenyl]-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C(=C(C=CC=2)C(F)(F)F)F)=N1 PGHNRLMKTNYWMX-UHFFFAOYSA-N 0.000 claims description 2
- HJPXIQLHMYRVJE-UHFFFAOYSA-N n-[2-fluoro-3-(trifluoromethyl)phenyl]-5-[6-(methylsulfonylmethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CS(=O)(=O)C)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C(=C(C=CC=2)C(F)(F)F)F)=N1 HJPXIQLHMYRVJE-UHFFFAOYSA-N 0.000 claims description 2
- KGLDIAWBXBMFEB-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethyl)phenyl]-5-[6-(methylsulfonylmethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CS(=O)(=O)C)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 KGLDIAWBXBMFEB-UHFFFAOYSA-N 0.000 claims description 2
- 229940054534 ophthalmic solution Drugs 0.000 claims description 2
- 230000008569 process Effects 0.000 claims description 2
- 201000008979 rubeosis iridis Diseases 0.000 claims description 2
- 229940032330 sulfuric acid Drugs 0.000 claims 4
- KRQUFUKTQHISJB-YYADALCUSA-N 2-[(E)-N-[2-(4-chlorophenoxy)propoxy]-C-propylcarbonimidoyl]-3-hydroxy-5-(thian-3-yl)cyclohex-2-en-1-one Chemical compound CCC\C(=N/OCC(C)OC1=CC=C(Cl)C=C1)C1=C(O)CC(CC1=O)C1CCCSC1 KRQUFUKTQHISJB-YYADALCUSA-N 0.000 claims 2
- 206010015995 Eyelid ptosis Diseases 0.000 claims 2
- 229960000583 acetic acid Drugs 0.000 claims 2
- 239000006172 buffering agent Substances 0.000 claims 2
- 229960000448 lactic acid Drugs 0.000 claims 2
- 229960004838 phosphoric acid Drugs 0.000 claims 2
- 201000003004 ptosis Diseases 0.000 claims 2
- 230000037361 pathway Effects 0.000 claims 1
- 239000000839 emulsion Substances 0.000 abstract description 4
- 239000007762 w/o emulsion Substances 0.000 abstract description 2
- 229940002612 prodrug Drugs 0.000 abstract 1
- 239000000651 prodrug Substances 0.000 abstract 1
- 239000012453 solvate Substances 0.000 abstract 1
- 239000003814 drug Substances 0.000 description 26
- 229940079593 drug Drugs 0.000 description 25
- 229920000858 Cyclodextrin Polymers 0.000 description 17
- 238000009472 formulation Methods 0.000 description 17
- 239000002253 acid Substances 0.000 description 16
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 14
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 14
- 229920000642 polymer Polymers 0.000 description 12
- 239000004615 ingredient Substances 0.000 description 10
- 210000003161 choroid Anatomy 0.000 description 9
- XPIHPLVWOUDMPF-UHFFFAOYSA-N 5-[6-(methylaminomethyl)pyrimidin-4-yl]oxy-n-[1-methyl-5-(trifluoromethyl)pyrazol-3-yl]indole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC2=NN(C)C(=C2)C(F)(F)F)=N1 XPIHPLVWOUDMPF-UHFFFAOYSA-N 0.000 description 8
- 150000007513 acids Chemical class 0.000 description 8
- 230000002776 aggregation Effects 0.000 description 8
- 239000003112 inhibitor Substances 0.000 description 8
- 238000004220 aggregation Methods 0.000 description 7
- 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 description 7
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 6
- 241000700159 Rattus Species 0.000 description 6
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 6
- 229920003123 carboxymethyl cellulose sodium Polymers 0.000 description 6
- 229940063834 carboxymethylcellulose sodium Drugs 0.000 description 6
- 229920002125 Sokalan® Polymers 0.000 description 5
- 239000001768 carboxy methyl cellulose Substances 0.000 description 5
- 235000010948 carboxy methyl cellulose Nutrition 0.000 description 5
- 239000008112 carboxymethyl-cellulose Substances 0.000 description 5
- 229940105329 carboxymethylcellulose Drugs 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000000546 pharmaceutical excipient Substances 0.000 description 5
- 210000001519 tissue Anatomy 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 4
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 4
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 4
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 4
- 239000004327 boric acid Substances 0.000 description 4
- GDSRMADSINPKSL-HSEONFRVSA-N gamma-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO GDSRMADSINPKSL-HSEONFRVSA-N 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 210000003786 sclera Anatomy 0.000 description 4
- 235000000346 sugar Nutrition 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 3
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 3
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 3
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 3
- 102000003923 Protein Kinase C Human genes 0.000 description 3
- 108090000315 Protein Kinase C Proteins 0.000 description 3
- 208000017442 Retinal disease Diseases 0.000 description 3
- 229940027983 antiseptic and disinfectant quaternary ammonium compound Drugs 0.000 description 3
- 239000007864 aqueous solution Substances 0.000 description 3
- 150000003857 carboxamides Chemical class 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 235000011187 glycerol Nutrition 0.000 description 3
- 229960005150 glycerol Drugs 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000002245 particle Substances 0.000 description 3
- 238000004321 preservation Methods 0.000 description 3
- 235000013772 propylene glycol Nutrition 0.000 description 3
- 229960004063 propylene glycol Drugs 0.000 description 3
- 150000005846 sugar alcohols Chemical class 0.000 description 3
- 238000013268 sustained release Methods 0.000 description 3
- 239000012730 sustained-release form Substances 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 2
- 241000228245 Aspergillus niger Species 0.000 description 2
- 229920000896 Ethulose Polymers 0.000 description 2
- 239000001856 Ethyl cellulose Substances 0.000 description 2
- ZZSNKZQZMQGXPY-UHFFFAOYSA-N Ethyl cellulose Chemical compound CCOCC1OC(OC)C(OCC)C(OCC)C1OC1C(O)C(O)C(OC)C(CO)O1 ZZSNKZQZMQGXPY-UHFFFAOYSA-N 0.000 description 2
- 239000001859 Ethyl hydroxyethyl cellulose Substances 0.000 description 2
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 2
- 229920001479 Hydroxyethyl methyl cellulose Polymers 0.000 description 2
- 229920002153 Hydroxypropyl cellulose Polymers 0.000 description 2
- 206010061218 Inflammation Diseases 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- 101150062285 PGF gene Proteins 0.000 description 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 102100035194 Placenta growth factor Human genes 0.000 description 2
- ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
- 206010038923 Retinopathy Diseases 0.000 description 2
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 2
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 2
- TVXBFESIOXBWNM-UHFFFAOYSA-N Xylitol Natural products OCCC(O)C(O)C(O)CCO TVXBFESIOXBWNM-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 230000000844 anti-bacterial effect Effects 0.000 description 2
- 230000000845 anti-microbial effect Effects 0.000 description 2
- 239000007900 aqueous suspension Substances 0.000 description 2
- 125000003118 aryl group Chemical group 0.000 description 2
- WHGYBXFWUBPSRW-FOUAGVGXSA-N beta-cyclodextrin Chemical class OC[C@H]([C@H]([C@@H]([C@H]1O)O)O[C@H]2O[C@@H]([C@@H](O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O[C@H]3O[C@H](CO)[C@H]([C@@H]([C@H]3O)O)O3)[C@H](O)[C@H]2O)CO)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@@H]3O[C@@H]1CO WHGYBXFWUBPSRW-FOUAGVGXSA-N 0.000 description 2
- 125000004432 carbon atom Chemical group C* 0.000 description 2
- 210000000795 conjunctiva Anatomy 0.000 description 2
- 238000001647 drug administration Methods 0.000 description 2
- 235000019325 ethyl cellulose Nutrition 0.000 description 2
- 229920001249 ethyl cellulose Polymers 0.000 description 2
- 235000019326 ethyl hydroxyethyl cellulose Nutrition 0.000 description 2
- 235000010944 ethyl methyl cellulose Nutrition 0.000 description 2
- 238000005189 flocculation Methods 0.000 description 2
- 230000016615 flocculation Effects 0.000 description 2
- 230000002209 hydrophobic effect Effects 0.000 description 2
- 239000001863 hydroxypropyl cellulose Substances 0.000 description 2
- 235000010977 hydroxypropyl cellulose Nutrition 0.000 description 2
- 239000001866 hydroxypropyl methyl cellulose Substances 0.000 description 2
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 2
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 2
- UFVKGYZPFZQRLF-UHFFFAOYSA-N hydroxypropyl methyl cellulose Chemical compound OC1C(O)C(OC)OC(CO)C1OC1C(O)C(O)C(OC2C(C(O)C(OC3C(C(O)C(O)C(CO)O3)O)C(CO)O2)O)C(CO)O1 UFVKGYZPFZQRLF-UHFFFAOYSA-N 0.000 description 2
- 230000004054 inflammatory process Effects 0.000 description 2
- 230000005764 inhibitory process Effects 0.000 description 2
- 230000000302 ischemic effect Effects 0.000 description 2
- 238000005259 measurement Methods 0.000 description 2
- HEBKCHPVOIAQTA-UHFFFAOYSA-N meso ribitol Natural products OCC(O)C(O)C(O)CO HEBKCHPVOIAQTA-UHFFFAOYSA-N 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- 235000010981 methylcellulose Nutrition 0.000 description 2
- 229920003087 methylethyl cellulose Polymers 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 2
- 239000010452 phosphate Substances 0.000 description 2
- 238000006116 polymerization reaction Methods 0.000 description 2
- 210000003583 retinal pigment epithelium Anatomy 0.000 description 2
- 239000011780 sodium chloride Substances 0.000 description 2
- 238000006467 substitution reaction Methods 0.000 description 2
- 150000008163 sugars Chemical class 0.000 description 2
- 208000006379 syphilis Diseases 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 238000012360 testing method Methods 0.000 description 2
- 238000011200 topical administration Methods 0.000 description 2
- 235000010447 xylitol Nutrition 0.000 description 2
- 239000000811 xylitol Substances 0.000 description 2
- HEBKCHPVOIAQTA-SCDXWVJYSA-N xylitol Chemical compound OC[C@H](O)[C@@H](O)[C@H](O)CO HEBKCHPVOIAQTA-SCDXWVJYSA-N 0.000 description 2
- 229960002675 xylitol Drugs 0.000 description 2
- WWUZIQQURGPMPG-UHFFFAOYSA-N (-)-D-erythro-Sphingosine Natural products CCCCCCCCCCCCCC=CC(O)C(N)CO WWUZIQQURGPMPG-UHFFFAOYSA-N 0.000 description 1
- OMDQUFIYNPYJFM-XKDAHURESA-N (2r,3r,4s,5r,6s)-2-(hydroxymethyl)-6-[[(2r,3s,4r,5s,6r)-4,5,6-trihydroxy-3-[(2s,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@H](O)[C@H](O)O1 OMDQUFIYNPYJFM-XKDAHURESA-N 0.000 description 1
- LOGFVTREOLYCPF-KXNHARMFSA-N (2s,3r)-2-[[(2r)-1-[(2s)-2,6-diaminohexanoyl]pyrrolidine-2-carbonyl]amino]-3-hydroxybutanoic acid Chemical compound C[C@@H](O)[C@@H](C(O)=O)NC(=O)[C@H]1CCCN1C(=O)[C@@H](N)CCCCN LOGFVTREOLYCPF-KXNHARMFSA-N 0.000 description 1
- UQLANBZLKVLADA-UHFFFAOYSA-N 1-methyl-5-(trifluoromethyl)pyrazole Chemical compound CN1N=CC=C1C(F)(F)F UQLANBZLKVLADA-UHFFFAOYSA-N 0.000 description 1
- VFHUJFBEFDVZPJ-UHFFFAOYSA-N 1h-indole-2-carboxamide Chemical class C1=CC=C2NC(C(=O)N)=CC2=C1 VFHUJFBEFDVZPJ-UHFFFAOYSA-N 0.000 description 1
- ZILVNHNSYBNLSZ-UHFFFAOYSA-N 2-(diaminomethylideneamino)guanidine Chemical compound NC(N)=NNC(N)=N ZILVNHNSYBNLSZ-UHFFFAOYSA-N 0.000 description 1
- QGBLCIBATKETJC-UHFFFAOYSA-N 3,7-dioxido-2,4,6,8,9-pentaoxa-1,3,5,7-tetraborabicyclo[3.3.1]nonane;manganese(2+) Chemical compound [Mn+2].O1B([O-])OB2OB([O-])OB1O2 QGBLCIBATKETJC-UHFFFAOYSA-N 0.000 description 1
- 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 1
- WLCZTRVUXYALDD-IBGZPJMESA-N 7-[[(2s)-2,6-bis(2-methoxyethoxycarbonylamino)hexanoyl]amino]heptoxy-methylphosphinic acid Chemical compound COCCOC(=O)NCCCC[C@H](NC(=O)OCCOC)C(=O)NCCCCCCCOP(C)(O)=O WLCZTRVUXYALDD-IBGZPJMESA-N 0.000 description 1
- 241001331781 Aspergillus brasiliensis Species 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 102100032957 C5a anaphylatoxin chemotactic receptor 1 Human genes 0.000 description 1
- 101710098483 C5a anaphylatoxin chemotactic receptor 1 Proteins 0.000 description 1
- 101100496968 Caenorhabditis elegans ctc-1 gene Proteins 0.000 description 1
- 241000222122 Candida albicans Species 0.000 description 1
- 208000002177 Cataract Diseases 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- KRKNYBCHXYNGOX-UHFFFAOYSA-K Citrate Chemical compound [O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O KRKNYBCHXYNGOX-UHFFFAOYSA-K 0.000 description 1
- 206010061788 Corneal infection Diseases 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 229930105110 Cyclosporin A Natural products 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 206010013774 Dry eye Diseases 0.000 description 1
- 208000019878 Eales disease Diseases 0.000 description 1
- 241000588724 Escherichia coli Species 0.000 description 1
- OTMSDBZUPAUEDD-UHFFFAOYSA-N Ethane Chemical compound CC OTMSDBZUPAUEDD-UHFFFAOYSA-N 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 1
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 1
- 206010015911 Eye burns Diseases 0.000 description 1
- 239000001116 FEMA 4028 Substances 0.000 description 1
- 229920000926 Galactomannan Polymers 0.000 description 1
- 208000003923 Hereditary Corneal Dystrophies Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 102000003777 Interleukin-1 beta Human genes 0.000 description 1
- 108090000193 Interleukin-1 beta Proteins 0.000 description 1
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 description 1
- 101100221647 Neurospora crassa (strain ATCC 24698 / 74-OR23-1A / CBS 708.71 / DSM 1257 / FGSC 987) cox-1 gene Proteins 0.000 description 1
- 101150062589 PTGS1 gene Proteins 0.000 description 1
- 229920000289 Polyquaternium Polymers 0.000 description 1
- 241000589517 Pseudomonas aeruginosa Species 0.000 description 1
- 108020004459 Small interfering RNA Proteins 0.000 description 1
- 241000191967 Staphylococcus aureus Species 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 description 1
- 206010054094 Tumour necrosis Diseases 0.000 description 1
- 241000700605 Viruses Species 0.000 description 1
- 238000009825 accumulation Methods 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000002411 adverse Effects 0.000 description 1
- 108010081667 aflibercept Proteins 0.000 description 1
- 238000005054 agglomeration Methods 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 150000003868 ammonium compounds Chemical class 0.000 description 1
- 238000000540 analysis of variance Methods 0.000 description 1
- 230000001772 anti-angiogenic effect Effects 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 229940120638 avastin Drugs 0.000 description 1
- 229960004853 betadex Drugs 0.000 description 1
- 208000010217 blepharitis Diseases 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- 238000011685 brown norway rat Methods 0.000 description 1
- 230000003139 buffering effect Effects 0.000 description 1
- 239000001273 butane Substances 0.000 description 1
- 238000001354 calcination Methods 0.000 description 1
- 229940095731 candida albicans Drugs 0.000 description 1
- 238000006243 chemical reaction Methods 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 208000027129 choroid disease Diseases 0.000 description 1
- 229960001265 ciclosporin Drugs 0.000 description 1
- 239000013256 coordination polymer Substances 0.000 description 1
- 208000021921 corneal disease Diseases 0.000 description 1
- 206010011005 corneal dystrophy Diseases 0.000 description 1
- 229940111134 coxibs Drugs 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 229940097362 cyclodextrins Drugs 0.000 description 1
- 239000003260 cyclooxygenase 1 inhibitor Substances 0.000 description 1
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 description 1
- 229930182912 cyclosporin Natural products 0.000 description 1
- 230000003412 degenerative effect Effects 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- 229960001259 diclofenac Drugs 0.000 description 1
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 238000012377 drug delivery Methods 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 208000024519 eye neoplasm Diseases 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 229940051306 eylea Drugs 0.000 description 1
- 238000000799 fluorescence microscopy Methods 0.000 description 1
- 229940080345 gamma-cyclodextrin Drugs 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 230000008595 infiltration Effects 0.000 description 1
- 238000001764 infiltration Methods 0.000 description 1
- 208000014674 injury Diseases 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000011835 investigation Methods 0.000 description 1
- 239000007951 isotonicity adjuster Substances 0.000 description 1
- 238000002356 laser light scattering Methods 0.000 description 1
- 229920001684 low density polyethylene Polymers 0.000 description 1
- 239000004702 low-density polyethylene Substances 0.000 description 1
- 229940076783 lucentis Drugs 0.000 description 1
- 229940092110 macugen Drugs 0.000 description 1
- 230000014759 maintenance of location Effects 0.000 description 1
- 206010025482 malaise Diseases 0.000 description 1
- 229960001855 mannitol Drugs 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 244000005700 microbiome Species 0.000 description 1
- NJTGANWAUPEOAX-UHFFFAOYSA-N molport-023-220-454 Chemical compound OCC(O)CO.OCC(O)CO NJTGANWAUPEOAX-UHFFFAOYSA-N 0.000 description 1
- 230000036651 mood Effects 0.000 description 1
- OQCQXSQLVCYSLF-UHFFFAOYSA-N n-[4-fluoro-3-(trifluoromethyl)phenyl]-5-[6-(methylaminomethyl)pyrimidin-4-yl]oxyindole-1-carboxamide Chemical compound C1=NC(CNC)=CC(OC=2C=C3C=CN(C3=CC=2)C(=O)NC=2C=C(C(F)=CC=2)C(F)(F)F)=N1 OQCQXSQLVCYSLF-UHFFFAOYSA-N 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- 229960002009 naproxen Drugs 0.000 description 1
- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical compound C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
- 201000001119 neuropathy Diseases 0.000 description 1
- 230000007823 neuropathy Effects 0.000 description 1
- 201000008106 ocular cancer Diseases 0.000 description 1
- 201000002575 ocular melanoma Diseases 0.000 description 1
- 229940023490 ophthalmic product Drugs 0.000 description 1
- 229940100654 ophthalmic suspension Drugs 0.000 description 1
- 238000010979 pH adjustment Methods 0.000 description 1
- 244000045947 parasite Species 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 208000033808 peripheral neuropathy Diseases 0.000 description 1
- 238000002428 photodynamic therapy Methods 0.000 description 1
- 239000008389 polyethoxylated castor oil Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920000136 polysorbate Polymers 0.000 description 1
- 229950008882 polysorbate Drugs 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 239000001294 propane Substances 0.000 description 1
- 239000008213 purified water Substances 0.000 description 1
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 1
- 230000009257 reactivity Effects 0.000 description 1
- 108091006082 receptor inhibitors Proteins 0.000 description 1
- 108020003175 receptors Proteins 0.000 description 1
- 102000005962 receptors Human genes 0.000 description 1
- 230000002829 reductive effect Effects 0.000 description 1
- 230000004044 response Effects 0.000 description 1
- 230000002207 retinal effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 201000000306 sarcoidosis Diseases 0.000 description 1
- 238000004062 sedimentation Methods 0.000 description 1
- 229960002930 sirolimus Drugs 0.000 description 1
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- 238000005063 solubilization Methods 0.000 description 1
- 230000007928 solubilization Effects 0.000 description 1
- 230000003381 solubilizing effect Effects 0.000 description 1
- 229960002920 sorbitol Drugs 0.000 description 1
- WWUZIQQURGPMPG-KRWOKUGFSA-N sphingosine Chemical compound CCCCCCCCCCCCC\C=C\[C@@H](O)[C@@H](N)CO WWUZIQQURGPMPG-KRWOKUGFSA-N 0.000 description 1
- 238000013112 stability test Methods 0.000 description 1
- 150000003431 steroids Chemical class 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 125000004964 sulfoalkyl group Chemical group 0.000 description 1
- 229940097346 sulfobutylether-beta-cyclodextrin Drugs 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002195 synergetic effect Effects 0.000 description 1
- 229940124597 therapeutic agent Drugs 0.000 description 1
- 230000001225 therapeutic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 230000008733 trauma Effects 0.000 description 1
- VLCLHFYFMCKBRP-UHFFFAOYSA-N tricalcium;diborate Chemical compound [Ca+2].[Ca+2].[Ca+2].[O-]B([O-])[O-].[O-]B([O-])[O-] VLCLHFYFMCKBRP-UHFFFAOYSA-N 0.000 description 1
- NFMWFGXCDDYTEG-UHFFFAOYSA-N trimagnesium;diborate Chemical compound [Mg+2].[Mg+2].[Mg+2].[O-]B([O-])[O-].[O-]B([O-])[O-] NFMWFGXCDDYTEG-UHFFFAOYSA-N 0.000 description 1
- WUUHFRRPHJEEKV-UHFFFAOYSA-N tripotassium borate Chemical compound [K+].[K+].[K+].[O-]B([O-])[O-] WUUHFRRPHJEEKV-UHFFFAOYSA-N 0.000 description 1
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 description 1
- BSVBQGMMJUBVOD-UHFFFAOYSA-N trisodium borate Chemical compound [Na+].[Na+].[Na+].[O-]B([O-])[O-] BSVBQGMMJUBVOD-UHFFFAOYSA-N 0.000 description 1
- 229960000281 trometamol Drugs 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 239000011345 viscous material Substances 0.000 description 1
- 239000000230 xanthan gum Substances 0.000 description 1
- 229920001285 xanthan gum Polymers 0.000 description 1
- 235000010493 xanthan gum Nutrition 0.000 description 1
- 229940082509 xanthan gum Drugs 0.000 description 1
Images
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings
- C07D403/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- 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
- A61K31/44—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
-
- 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
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and 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
- A61K31/495—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
-
- 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
- A61K31/55—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having seven-membered rings, e.g. azelastine, pentylenetetrazole
-
- 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
- A61K31/70—Carbohydrates; Sugars; Derivatives thereof
- A61K31/715—Polysaccharides, i.e. having more than five saccharide radicals attached to each other by glycosidic linkages; Derivatives thereof, e.g. ethers, esters
- A61K31/716—Glucans
- A61K31/724—Cyclodextrins
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/02—Inorganic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
- A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/16—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing nitrogen, e.g. nitro-, nitroso-, azo-compounds, nitriles, cyanates
- A61K47/18—Amines; Amides; Ureas; Quaternary ammonium compounds; Amino acids; Oligopeptides having up to five amino acids
- A61K47/186—Quaternary ammonium compounds, e.g. benzalkonium chloride or cetrimide
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
- A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/08—Solutions
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/10—Dispersions; Emulsions
-
- 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
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- 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
-
- 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
- A61P9/14—Vasoprotectives; Antihaemorrhoidals; Drugs for varicose therapy; Capillary stabilisers
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/12—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings linked by a chain containing hetero atoms as chain links
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D403/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00
- C07D403/14—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, not provided for by group C07D401/00 containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/14—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing three or more hetero rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- 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
- C07D487/02—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 two hetero rings
- C07D487/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D495/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms
- C07D495/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having sulfur atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
- C07D495/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Inorganic Chemistry (AREA)
- Oil, Petroleum & Natural Gas (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Molecular Biology (AREA)
- Ophthalmology & Optometry (AREA)
- Biochemistry (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Dispersion Chemistry (AREA)
- Vascular Medicine (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicinal Preparation (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361831834P | 2013-06-06 | 2013-06-06 | |
| US61/831,834 | 2013-06-06 | ||
| US14/292,082 US10174006B2 (en) | 2013-06-06 | 2014-05-30 | Topical aqueous ophthalmic compositions containing a 1H-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease |
| US14/292,082 | 2014-05-30 | ||
| PCT/US2014/040892 WO2014197584A1 (en) | 2013-06-06 | 2014-06-04 | Topical aqueous ophthalmic compositions containing a 1h-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| KR20160015192A true KR20160015192A (ko) | 2016-02-12 |
Family
ID=52005966
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| KR1020157022071A Withdrawn KR20160015192A (ko) | 2013-06-06 | 2014-06-04 | 1h-인돌-1-카복스아마이드 유도체를 포함하는 국소 수성 안과용 조성물 및 안과용 질환의 치료를 위한 이의 용도 |
Country Status (15)
| Country | Link |
|---|---|
| US (1) | US10174006B2 (enExample) |
| EP (1) | EP3003270A1 (enExample) |
| JP (1) | JP6522592B2 (enExample) |
| KR (1) | KR20160015192A (enExample) |
| CN (1) | CN105188663A (enExample) |
| AR (1) | AR096473A1 (enExample) |
| AU (1) | AU2014274955B2 (enExample) |
| BR (1) | BR112015019744A8 (enExample) |
| CA (1) | CA2897949A1 (enExample) |
| CL (1) | CL2015003460A1 (enExample) |
| HK (1) | HK1221160A1 (enExample) |
| MX (1) | MX2015014091A (enExample) |
| PH (1) | PH12015501555A1 (enExample) |
| RU (1) | RU2015155604A (enExample) |
| WO (1) | WO2014197584A1 (enExample) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US10174006B2 (en) | 2013-06-06 | 2019-01-08 | Novartis Ag | Topical aqueous ophthalmic compositions containing a 1H-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease |
| GB2561355A (en) * | 2017-04-10 | 2018-10-17 | Eaststone Ltd | Pharmaceutical composition and a method for manufacturing the same |
| KR102125256B1 (ko) * | 2018-12-28 | 2020-07-07 | 현대바이오사이언스 주식회사 | 점안용 담체 복합체, 이를 포함하는 약학 조성물, 및 약학 조성물의 제조방법 |
| AU2019429068B2 (en) | 2019-02-13 | 2025-01-30 | DEBx Medical Holding B.V. | Compositions for removing necrotic or infected tissues from body surface lesions and from oral cavity |
Family Cites Families (20)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3931319A (en) | 1974-10-29 | 1976-01-06 | Millmaster Onyx Corporation | Capped polymers |
| US4027020A (en) | 1974-10-29 | 1977-05-31 | Millmaster Onyx Corporation | Randomly terminated capped polymers |
| US4407791A (en) | 1981-09-28 | 1983-10-04 | Alcon Laboratories, Inc. | Ophthalmic solutions |
| US4525346A (en) | 1981-09-28 | 1985-06-25 | Alcon Laboratories, Inc. | Aqueous antimicrobial ophthalmic solutions |
| US4836986A (en) | 1984-09-28 | 1989-06-06 | Bausch & Lomb Incorporated | Disinfecting and preserving systems and methods of use |
| US5037647A (en) | 1988-09-15 | 1991-08-06 | Alcon Laboratories, Inc. | Aqueous antimicrobial opthalmic solutions comprised of quaternary ammonium compound, citric acid, citrate and sodium chloride |
| US5145643A (en) | 1990-01-05 | 1992-09-08 | Allergan, Inc. | Nonoxidative ophthalmic compositions and methods for preserving and using same |
| US5362758A (en) * | 1992-09-18 | 1994-11-08 | Pfizer Inc. | Ophthalmic piroxicam solution |
| US5300287A (en) | 1992-11-04 | 1994-04-05 | Alcon Laboratories, Inc. | Polymeric antimicrobials and their use in pharmaceutical compositions |
| TW434023B (en) | 1995-09-18 | 2001-05-16 | Novartis Ag | Preserved ophthalmic composition |
| US5800807A (en) * | 1997-01-29 | 1998-09-01 | Bausch & Lomb Incorporated | Ophthalmic compositions including glycerin and propylene glycol |
| GB9714917D0 (en) | 1997-07-17 | 1997-09-17 | Hodgkinson William | Can cleaning and delivery apparatus |
| EP0938896A1 (en) | 1998-01-15 | 1999-09-01 | Novartis AG | Autoclavable pharmaceutical compositions containing a chelating agent |
| US20060141059A1 (en) * | 2004-12-27 | 2006-06-29 | Alcon, Inc. | Self-preserved ophthalmic pharmaceutical compositions containing tobramycin |
| US20100249062A1 (en) * | 2007-09-28 | 2010-09-30 | Yasuko Matsumura | Ophthalmic composition |
| JO3265B1 (ar) * | 2008-12-09 | 2018-09-16 | Novartis Ag | مثبطات بيريديلوكسى اندولات vegf-r2 واستخدامها لعلاج المرض |
| EP2196941A1 (fr) | 2008-12-11 | 2010-06-16 | Gemalto SA | Dispositif de connexion à une carte à puce |
| AU2011322597B2 (en) | 2010-10-27 | 2015-09-10 | Novartis Ag | Dosing regimes for the treatment of ocular vascular disease |
| US20120269862A1 (en) * | 2011-04-22 | 2012-10-25 | Chowhan Masood A | Ophthalmic composition with a viscosity enhancement system having two different viscosity enhancing agents |
| US10174006B2 (en) | 2013-06-06 | 2019-01-08 | Novartis Ag | Topical aqueous ophthalmic compositions containing a 1H-indole-1-carboxamide derivative and use thereof for treatment of ophthalmic disease |
-
2014
- 2014-05-30 US US14/292,082 patent/US10174006B2/en not_active Expired - Fee Related
- 2014-06-04 HK HK16109315.1A patent/HK1221160A1/zh unknown
- 2014-06-04 BR BR112015019744A patent/BR112015019744A8/pt not_active Application Discontinuation
- 2014-06-04 JP JP2016517959A patent/JP6522592B2/ja not_active Expired - Fee Related
- 2014-06-04 RU RU2015155604A patent/RU2015155604A/ru not_active Application Discontinuation
- 2014-06-04 AR ARP140102179A patent/AR096473A1/es unknown
- 2014-06-04 WO PCT/US2014/040892 patent/WO2014197584A1/en not_active Ceased
- 2014-06-04 CA CA2897949A patent/CA2897949A1/en not_active Abandoned
- 2014-06-04 CN CN201480011697.0A patent/CN105188663A/zh active Pending
- 2014-06-04 MX MX2015014091A patent/MX2015014091A/es unknown
- 2014-06-04 AU AU2014274955A patent/AU2014274955B2/en not_active Ceased
- 2014-06-04 EP EP14736523.3A patent/EP3003270A1/en not_active Withdrawn
- 2014-06-04 KR KR1020157022071A patent/KR20160015192A/ko not_active Withdrawn
-
2015
- 2015-07-13 PH PH12015501555A patent/PH12015501555A1/en unknown
- 2015-11-26 CL CL2015003460A patent/CL2015003460A1/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| AU2014274955B2 (en) | 2019-02-21 |
| AR096473A1 (es) | 2015-12-30 |
| EP3003270A1 (en) | 2016-04-13 |
| BR112015019744A2 (pt) | 2017-07-18 |
| CL2015003460A1 (es) | 2016-07-08 |
| JP6522592B2 (ja) | 2019-05-29 |
| CA2897949A1 (en) | 2014-12-11 |
| JP2016521706A (ja) | 2016-07-25 |
| MX2015014091A (es) | 2015-12-15 |
| WO2014197584A1 (en) | 2014-12-11 |
| CN105188663A (zh) | 2015-12-23 |
| HK1221160A1 (zh) | 2017-05-26 |
| BR112015019744A8 (pt) | 2019-11-05 |
| US10174006B2 (en) | 2019-01-08 |
| PH12015501555A1 (en) | 2015-09-21 |
| AU2014274955A1 (en) | 2015-07-16 |
| US20140364392A1 (en) | 2014-12-11 |
| RU2015155604A3 (enExample) | 2018-05-28 |
| RU2015155604A (ru) | 2017-07-17 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US9968603B2 (en) | Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant | |
| JP6965308B2 (ja) | 後眼部へ薬物を送達するための眼用製剤 | |
| JP2021518352A (ja) | チモロールを含む医薬組成物 | |
| AU2008319074A1 (en) | Non-aqueous water-miscible materials as vehicles for drug delivery | |
| AU2004287443B2 (en) | Suspension of loteprednol etabonate and tobramycin for topical ophthalmic use | |
| KR20160015192A (ko) | 1h-인돌-1-카복스아마이드 유도체를 포함하는 국소 수성 안과용 조성물 및 안과용 질환의 치료를 위한 이의 용도 | |
| AU2025203019A1 (en) | Ophthalmic Compositions Containing A Nitric Oxide Releasing Prostamide | |
| TW202342108A (zh) | 多劑量眼用組成物 | |
| JP7470791B2 (ja) | 眼疾患の予防または治療用点眼組成物 | |
| KR102888598B1 (ko) | 약물 전달을 위한 약학적 생분해성 겔 | |
| KR20230018418A (ko) | 비정상적인 혈관형성을 치료하기 위한 국소 안과학적 조성물 및 방법 | |
| CA3088185C (en) | Suspension compositions of multi-target inhibitors | |
| JP2019534269A5 (enExample) | ||
| WO2025127910A1 (es) | Formulación de base lipídica de uso tópico oftálmico para incrementar la biodisponibilidad de los antiinflamatorios no esteroideos en los tejidos intraoculares | |
| JP2024512028A (ja) | N-オキソピリジン化合物の発生を抑制する眼疾患の予防または治療用点眼組成物 | |
| HK40018890B (en) | Ophthalmic compositions containing a nitric oxide releasing prostamide | |
| HK40018890A (en) | Ophthalmic compositions containing a nitric oxide releasing prostamide |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PA0105 | International application |
Patent event date: 20150813 Patent event code: PA01051R01D Comment text: International Patent Application |
|
| PG1501 | Laying open of application | ||
| PC1203 | Withdrawal of no request for examination | ||
| WITN | Application deemed withdrawn, e.g. because no request for examination was filed or no examination fee was paid |