JP5552102B2 - 長時間放出特性を有する生分解性眼インプラント - Google Patents
長時間放出特性を有する生分解性眼インプラント Download PDFInfo
- Publication number
- JP5552102B2 JP5552102B2 JP2011216499A JP2011216499A JP5552102B2 JP 5552102 B2 JP5552102 B2 JP 5552102B2 JP 2011216499 A JP2011216499 A JP 2011216499A JP 2011216499 A JP2011216499 A JP 2011216499A JP 5552102 B2 JP5552102 B2 JP 5552102B2
- Authority
- JP
- Japan
- Prior art keywords
- implant
- dexamethasone
- release
- polymer
- implants
- 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.)
- Active
Links
- 239000007943 implant Substances 0.000 title claims description 378
- 238000013265 extended release Methods 0.000 title description 18
- 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 claims description 202
- 229960003957 dexamethasone Drugs 0.000 claims description 193
- 239000003814 drug Substances 0.000 claims description 64
- 230000001225 therapeutic effect Effects 0.000 claims description 49
- 208000030533 eye disease Diseases 0.000 claims description 43
- 239000000203 mixture Substances 0.000 claims description 32
- 238000012377 drug delivery Methods 0.000 claims description 23
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims description 16
- RKDVKSZUMVYZHH-UHFFFAOYSA-N 1,4-dioxane-2,5-dione Chemical compound O=C1COC(=O)CO1 RKDVKSZUMVYZHH-UHFFFAOYSA-N 0.000 claims description 11
- 229920001244 Poly(D,L-lactide) Polymers 0.000 claims description 8
- 238000003780 insertion Methods 0.000 claims description 5
- 230000037431 insertion Effects 0.000 claims description 5
- 229940124597 therapeutic agent Drugs 0.000 claims 1
- 239000013543 active substance Substances 0.000 description 141
- 229920000642 polymer Polymers 0.000 description 122
- 238000000034 method Methods 0.000 description 69
- 210000001508 eye Anatomy 0.000 description 68
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 62
- 229940079593 drug Drugs 0.000 description 59
- 201000010099 disease Diseases 0.000 description 50
- 208000002780 macular degeneration Diseases 0.000 description 49
- 229920013641 bioerodible polymer Polymers 0.000 description 40
- 206010046851 Uveitis Diseases 0.000 description 33
- 206010012689 Diabetic retinopathy Diseases 0.000 description 31
- 208000022873 Ocular disease Diseases 0.000 description 31
- 239000002245 particle Substances 0.000 description 31
- 238000011282 treatment Methods 0.000 description 31
- 208000001344 Macular Edema Diseases 0.000 description 28
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 28
- 208000017442 Retinal disease Diseases 0.000 description 27
- 230000032683 aging Effects 0.000 description 26
- 208000010412 Glaucoma Diseases 0.000 description 23
- 238000001727 in vivo Methods 0.000 description 23
- 238000002513 implantation Methods 0.000 description 22
- 238000000338 in vitro Methods 0.000 description 22
- 208000024891 symptom Diseases 0.000 description 22
- -1 antiangiogenic Substances 0.000 description 20
- 238000004519 manufacturing process Methods 0.000 description 20
- 229940124599 anti-inflammatory drug Drugs 0.000 description 19
- 230000000694 effects Effects 0.000 description 19
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 18
- 102100039037 Vascular endothelial growth factor A Human genes 0.000 description 18
- 229920002988 biodegradable polymer Polymers 0.000 description 18
- 239000011159 matrix material Substances 0.000 description 18
- 230000002207 retinal effect Effects 0.000 description 18
- 206010025415 Macular oedema Diseases 0.000 description 17
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 17
- 239000004621 biodegradable polymer Substances 0.000 description 17
- 230000001186 cumulative effect Effects 0.000 description 17
- 201000010230 macular retinal edema Diseases 0.000 description 17
- 238000001125 extrusion Methods 0.000 description 16
- 230000003637 steroidlike Effects 0.000 description 16
- 239000002260 anti-inflammatory agent Substances 0.000 description 15
- 108091008598 receptor tyrosine kinases Proteins 0.000 description 15
- 102000027426 receptor tyrosine kinases Human genes 0.000 description 15
- 102000005962 receptors Human genes 0.000 description 15
- 108020003175 receptors Proteins 0.000 description 15
- 206010038848 Retinal detachment Diseases 0.000 description 14
- 230000004264 retinal detachment Effects 0.000 description 14
- 206010061218 Inflammation Diseases 0.000 description 13
- 239000003795 chemical substances by application Substances 0.000 description 13
- 230000004054 inflammatory process Effects 0.000 description 13
- 229920002959 polymer blend Polymers 0.000 description 13
- 206010012688 Diabetic retinal oedema Diseases 0.000 description 12
- 208000010038 Ischemic Optic Neuropathy Diseases 0.000 description 12
- 206010030924 Optic ischaemic neuropathy Diseases 0.000 description 12
- 230000001154 acute effect Effects 0.000 description 12
- 201000007058 anterior ischemic optic neuropathy Diseases 0.000 description 12
- AQOKCDNYWBIDND-FTOWTWDKSA-N bimatoprost Chemical compound CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-FTOWTWDKSA-N 0.000 description 12
- 201000011190 diabetic macular edema Diseases 0.000 description 12
- JYGXADMDTFJGBT-VWUMJDOOSA-N hydrocortisone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 JYGXADMDTFJGBT-VWUMJDOOSA-N 0.000 description 12
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 11
- 208000009137 Behcet syndrome Diseases 0.000 description 11
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 11
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 11
- 206010058202 Cystoid macular oedema Diseases 0.000 description 11
- 201000007527 Retinal artery occlusion Diseases 0.000 description 11
- 208000007014 Retinitis pigmentosa Diseases 0.000 description 11
- 206010038923 Retinopathy Diseases 0.000 description 11
- 201000010206 cystoid macular edema Diseases 0.000 description 11
- 230000007774 longterm Effects 0.000 description 11
- 238000002156 mixing Methods 0.000 description 11
- 230000004283 retinal dysfunction Effects 0.000 description 11
- 210000001957 retinal vein Anatomy 0.000 description 11
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 11
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 11
- 210000003462 vein Anatomy 0.000 description 11
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 10
- 239000012530 fluid Substances 0.000 description 10
- 208000027866 inflammatory disease Diseases 0.000 description 10
- 230000004410 intraocular pressure Effects 0.000 description 10
- LDDHMLJTFXJGPI-UHFFFAOYSA-N memantine hydrochloride Chemical compound Cl.C1C(C2)CC3(C)CC1(C)CC2(N)C3 LDDHMLJTFXJGPI-UHFFFAOYSA-N 0.000 description 10
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 10
- 210000001525 retina Anatomy 0.000 description 10
- 208000002158 Proliferative Vitreoretinopathy Diseases 0.000 description 9
- 206010038934 Retinopathy proliferative Diseases 0.000 description 9
- 229960004640 memantine Drugs 0.000 description 9
- 208000021971 neovascular inflammatory vitreoretinopathy Diseases 0.000 description 9
- 230000006785 proliferative vitreoretinopathy Effects 0.000 description 9
- 210000003786 sclera Anatomy 0.000 description 9
- TWBNMYSKRDRHAT-RCWTXCDDSA-N (S)-timolol hemihydrate Chemical compound O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 TWBNMYSKRDRHAT-RCWTXCDDSA-N 0.000 description 8
- CQOQDQWUFQDJMK-SSTWWWIQSA-N 2-methoxy-17beta-estradiol Chemical compound C([C@@H]12)C[C@]3(C)[C@@H](O)CC[C@H]3[C@@H]1CCC1=C2C=C(OC)C(O)=C1 CQOQDQWUFQDJMK-SSTWWWIQSA-N 0.000 description 8
- 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 8
- 206010022557 Intermediate uveitis Diseases 0.000 description 8
- 210000005252 bulbus oculi Anatomy 0.000 description 8
- 238000009472 formulation Methods 0.000 description 8
- 230000002209 hydrophobic effect Effects 0.000 description 8
- 229960004716 idoxuridine Drugs 0.000 description 8
- 150000003431 steroids Chemical class 0.000 description 8
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 8
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 7
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 7
- OGQICQVSFDPSEI-UHFFFAOYSA-N Zorac Chemical compound N1=CC(C(=O)OCC)=CC=C1C#CC1=CC=C(SCCC2(C)C)C2=C1 OGQICQVSFDPSEI-UHFFFAOYSA-N 0.000 description 7
- 210000004204 blood vessel Anatomy 0.000 description 7
- 230000015556 catabolic process Effects 0.000 description 7
- 239000003246 corticosteroid Substances 0.000 description 7
- 229960001334 corticosteroids Drugs 0.000 description 7
- 238000006731 degradation reaction Methods 0.000 description 7
- 238000009792 diffusion process Methods 0.000 description 7
- 230000004438 eyesight Effects 0.000 description 7
- 239000011521 glass Substances 0.000 description 7
- 239000003862 glucocorticoid Substances 0.000 description 7
- 239000003446 ligand Substances 0.000 description 7
- 229920000747 poly(lactic acid) Polymers 0.000 description 7
- 239000000126 substance Substances 0.000 description 7
- 230000009885 systemic effect Effects 0.000 description 7
- 229960000565 tazarotene Drugs 0.000 description 7
- 238000012360 testing method Methods 0.000 description 7
- 229960004605 timolol Drugs 0.000 description 7
- 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 6
- 208000002177 Cataract Diseases 0.000 description 6
- 108010053099 Vascular Endothelial Growth Factor Receptor-2 Proteins 0.000 description 6
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 6
- 229940003677 alphagan Drugs 0.000 description 6
- 230000001772 anti-angiogenic effect Effects 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000001413 cellular effect Effects 0.000 description 6
- 150000001875 compounds Chemical class 0.000 description 6
- 229920001577 copolymer Polymers 0.000 description 6
- 230000003628 erosive effect Effects 0.000 description 6
- 229960000890 hydrocortisone Drugs 0.000 description 6
- 229940112534 lumigan Drugs 0.000 description 6
- 230000001404 mediated effect Effects 0.000 description 6
- 210000003205 muscle Anatomy 0.000 description 6
- 229960003876 ranibizumab Drugs 0.000 description 6
- 239000000758 substrate Substances 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- 230000000699 topical effect Effects 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 6
- WLRMANUAADYWEA-NWASOUNVSA-N (S)-timolol maleate Chemical compound OC(=O)\C=C/C(O)=O.CC(C)(C)NC[C@H](O)COC1=NSN=C1N1CCOCC1 WLRMANUAADYWEA-NWASOUNVSA-N 0.000 description 5
- 241000283973 Oryctolagus cuniculus Species 0.000 description 5
- 230000003110 anti-inflammatory effect Effects 0.000 description 5
- 229960002470 bimatoprost Drugs 0.000 description 5
- 229960003679 brimonidine Drugs 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 210000003161 choroid Anatomy 0.000 description 5
- 230000000052 comparative effect Effects 0.000 description 5
- 239000006196 drop Substances 0.000 description 5
- 230000014509 gene expression Effects 0.000 description 5
- 230000001965 increasing effect Effects 0.000 description 5
- 238000002347 injection Methods 0.000 description 5
- 239000007924 injection Substances 0.000 description 5
- 239000000463 material Substances 0.000 description 5
- 108091008046 non-receptor tyrosine kinases Proteins 0.000 description 5
- 102000037979 non-receptor tyrosine kinases Human genes 0.000 description 5
- 210000001328 optic nerve Anatomy 0.000 description 5
- 230000026731 phosphorylation Effects 0.000 description 5
- 238000006366 phosphorylation reaction Methods 0.000 description 5
- 108090000623 proteins and genes Proteins 0.000 description 5
- 102000004169 proteins and genes Human genes 0.000 description 5
- 230000011664 signaling Effects 0.000 description 5
- 238000001356 surgical procedure Methods 0.000 description 5
- 230000008961 swelling Effects 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- 201000004569 Blindness Diseases 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- 230000002159 abnormal effect Effects 0.000 description 4
- 239000002253 acid Substances 0.000 description 4
- 239000012190 activator Substances 0.000 description 4
- 206010064930 age-related macular degeneration Diseases 0.000 description 4
- 230000033115 angiogenesis Effects 0.000 description 4
- 239000002876 beta blocker Substances 0.000 description 4
- 206010012601 diabetes mellitus Diseases 0.000 description 4
- 238000004090 dissolution Methods 0.000 description 4
- 208000027993 eye symptom Diseases 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 230000007062 hydrolysis Effects 0.000 description 4
- 238000006460 hydrolysis reaction Methods 0.000 description 4
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 4
- 230000002401 inhibitory effect Effects 0.000 description 4
- 208000014674 injury Diseases 0.000 description 4
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
- 238000005259 measurement Methods 0.000 description 4
- 230000035755 proliferation Effects 0.000 description 4
- 238000005070 sampling Methods 0.000 description 4
- 239000011343 solid material Substances 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- 229960005221 timolol maleate Drugs 0.000 description 4
- 229960005294 triamcinolone Drugs 0.000 description 4
- GFNANZIMVAIWHM-OBYCQNJPSA-N triamcinolone Chemical compound O=C1C=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@]([C@H](O)C4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 GFNANZIMVAIWHM-OBYCQNJPSA-N 0.000 description 4
- 230000004393 visual impairment Effects 0.000 description 4
- 210000004127 vitreous body Anatomy 0.000 description 4
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical class CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 3
- 229930182837 (R)-adrenaline Natural products 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- 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 3
- 101000595923 Homo sapiens Placenta growth factor Proteins 0.000 description 3
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 description 3
- 206010030348 Open-Angle Glaucoma Diseases 0.000 description 3
- 102100035194 Placenta growth factor Human genes 0.000 description 3
- 229920000954 Polyglycolide Polymers 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 108010053096 Vascular Endothelial Growth Factor Receptor-1 Proteins 0.000 description 3
- 102100033178 Vascular endothelial growth factor receptor 1 Human genes 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 230000000259 anti-tumor effect Effects 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 3
- 229940097320 beta blocking agent Drugs 0.000 description 3
- 239000000872 buffer Substances 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 230000010261 cell growth Effects 0.000 description 3
- 238000006243 chemical reaction Methods 0.000 description 3
- 210000000795 conjunctiva Anatomy 0.000 description 3
- 238000013270 controlled release Methods 0.000 description 3
- 238000000315 cryotherapy Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 230000018109 developmental process Effects 0.000 description 3
- 239000006185 dispersion Substances 0.000 description 3
- 229960005139 epinephrine Drugs 0.000 description 3
- 208000024519 eye neoplasm Diseases 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- 239000003112 inhibitor Substances 0.000 description 3
- 239000003999 initiator Substances 0.000 description 3
- 238000001746 injection moulding Methods 0.000 description 3
- 230000003834 intracellular effect Effects 0.000 description 3
- 238000011068 loading method Methods 0.000 description 3
- 239000003094 microcapsule Substances 0.000 description 3
- 239000000178 monomer Substances 0.000 description 3
- 239000003703 n methyl dextro aspartic acid receptor blocking agent Substances 0.000 description 3
- 210000005036 nerve Anatomy 0.000 description 3
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 3
- 239000001301 oxygen Substances 0.000 description 3
- 229910052760 oxygen Inorganic materials 0.000 description 3
- 230000037361 pathway Effects 0.000 description 3
- 229940005014 pegaptanib sodium Drugs 0.000 description 3
- 230000035699 permeability Effects 0.000 description 3
- 239000004633 polyglycolic acid Substances 0.000 description 3
- 229960005205 prednisolone Drugs 0.000 description 3
- OIGNJSKKLXVSLS-VWUMJDOOSA-N prednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OIGNJSKKLXVSLS-VWUMJDOOSA-N 0.000 description 3
- 230000008569 process Effects 0.000 description 3
- 230000004044 response Effects 0.000 description 3
- 230000019491 signal transduction Effects 0.000 description 3
- 230000004083 survival effect Effects 0.000 description 3
- 229940126585 therapeutic drug Drugs 0.000 description 3
- 230000008733 trauma Effects 0.000 description 3
- IAKHMKGGTNLKSZ-INIZCTEOSA-N (S)-colchicine Chemical compound C1([C@@H](NC(C)=O)CC2)=CC(=O)C(OC)=CC=C1C1=C2C=C(OC)C(OC)=C1OC IAKHMKGGTNLKSZ-INIZCTEOSA-N 0.000 description 2
- UUUHXMGGBIUAPW-UHFFFAOYSA-N 1-[1-[2-[[5-amino-2-[[1-[5-(diaminomethylideneamino)-2-[[1-[3-(1h-indol-3-yl)-2-[(5-oxopyrrolidine-2-carbonyl)amino]propanoyl]pyrrolidine-2-carbonyl]amino]pentanoyl]pyrrolidine-2-carbonyl]amino]-5-oxopentanoyl]amino]-3-methylpentanoyl]pyrrolidine-2-carbon Chemical compound C1CCC(C(=O)N2C(CCC2)C(O)=O)N1C(=O)C(C(C)CC)NC(=O)C(CCC(N)=O)NC(=O)C1CCCN1C(=O)C(CCCN=C(N)N)NC(=O)C1CCCN1C(=O)C(CC=1C2=CC=CC=C2NC=1)NC(=O)C1CCC(=O)N1 UUUHXMGGBIUAPW-UHFFFAOYSA-N 0.000 description 2
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 2
- WRMNZCZEMHIOCP-UHFFFAOYSA-N 2-phenylethanol Chemical compound OCCC1=CC=CC=C1 WRMNZCZEMHIOCP-UHFFFAOYSA-N 0.000 description 2
- HVBSAKJJOYLTQU-UHFFFAOYSA-N 4-aminobenzenesulfonic acid Chemical compound NC1=CC=C(S(O)(=O)=O)C=C1 HVBSAKJJOYLTQU-UHFFFAOYSA-N 0.000 description 2
- AQOKCDNYWBIDND-ABRBVVEGSA-N 5-trans-17-phenyl trinor Prostaglandin F2alpha ethyl amide Chemical compound CCNC(=O)CCC\C=C\C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-ABRBVVEGSA-N 0.000 description 2
- KUVIULQEHSCUHY-XYWKZLDCSA-N Beclometasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(Cl)[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)COC(=O)CC)(OC(=O)CC)[C@@]1(C)C[C@@H]2O KUVIULQEHSCUHY-XYWKZLDCSA-N 0.000 description 2
- 101100381481 Caenorhabditis elegans baz-2 gene Proteins 0.000 description 2
- 208000005623 Carcinogenesis Diseases 0.000 description 2
- 208000024304 Choroidal Effusions Diseases 0.000 description 2
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 2
- 108010036949 Cyclosporine Proteins 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- AOJJSUZBOXZQNB-TZSSRYMLSA-N Doxorubicin Chemical compound O([C@H]1C[C@@](O)(CC=2C(O)=C3C(=O)C=4C=CC=C(C=4C(=O)C3=C(O)C=21)OC)C(=O)CO)[C@H]1C[C@H](N)[C@H](O)[C@H](C)O1 AOJJSUZBOXZQNB-TZSSRYMLSA-N 0.000 description 2
- 102000004190 Enzymes Human genes 0.000 description 2
- 108090000790 Enzymes Proteins 0.000 description 2
- 208000001351 Epiretinal Membrane Diseases 0.000 description 2
- XBLVHTDFJBKJLG-UHFFFAOYSA-N Ethyl nicotinate Chemical compound CCOC(=O)C1=CC=CN=C1 XBLVHTDFJBKJLG-UHFFFAOYSA-N 0.000 description 2
- 206010015943 Eye inflammation Diseases 0.000 description 2
- 206010017533 Fungal infection Diseases 0.000 description 2
- 201000002563 Histoplasmosis Diseases 0.000 description 2
- 101001001487 Homo sapiens Phosphatidylinositol-glycan biosynthesis class F protein Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 208000031471 Macular fibrosis Diseases 0.000 description 2
- 206010025421 Macule Diseases 0.000 description 2
- FQISKWAFAHGMGT-SGJOWKDISA-M Methylprednisolone sodium succinate Chemical compound [Na+].C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2[C@@H](O)C[C@]2(C)[C@@](O)(C(=O)COC(=O)CCC([O-])=O)CC[C@H]21 FQISKWAFAHGMGT-SGJOWKDISA-M 0.000 description 2
- 208000010164 Multifocal Choroiditis Diseases 0.000 description 2
- 208000031888 Mycoses Diseases 0.000 description 2
- HOKKHZGPKSLGJE-GSVOUGTGSA-N N-Methyl-D-aspartic acid Chemical compound CN[C@@H](C(O)=O)CC(O)=O HOKKHZGPKSLGJE-GSVOUGTGSA-N 0.000 description 2
- 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 2
- 229910019142 PO4 Inorganic materials 0.000 description 2
- 229930182555 Penicillin Natural products 0.000 description 2
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 2
- 102000004270 Peptidyl-Dipeptidase A Human genes 0.000 description 2
- 108090000882 Peptidyl-Dipeptidase A Proteins 0.000 description 2
- 108091000080 Phosphotransferase Proteins 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 101100372762 Rattus norvegicus Flt1 gene Proteins 0.000 description 2
- 206010048955 Retinal toxicity Diseases 0.000 description 2
- 206010038903 Retinal vascular occlusion Diseases 0.000 description 2
- 102000014400 SH2 domains Human genes 0.000 description 2
- 108050003452 SH2 domains Proteins 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 206010042742 Sympathetic ophthalmia Diseases 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- OIRDTQYFTABQOQ-UHTZMRCNSA-N Vidarabine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@@H]1O OIRDTQYFTABQOQ-UHTZMRCNSA-N 0.000 description 2
- 208000036142 Viral infection Diseases 0.000 description 2
- 229960004150 aciclovir Drugs 0.000 description 2
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 2
- RJURFGZVJUQBHK-UHFFFAOYSA-N actinomycin D Natural products CC1OC(=O)C(C(C)C)N(C)C(=O)CN(C)C(=O)C2CCCN2C(=O)C(C(C)C)NC(=O)C1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)NC4C(=O)NC(C(N5CCCC5C(=O)N(C)CC(=O)N(C)C(C(C)C)C(=O)OC4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-UHFFFAOYSA-N 0.000 description 2
- 239000000048 adrenergic agonist Substances 0.000 description 2
- 239000003288 aldose reductase inhibitor Substances 0.000 description 2
- 229940090865 aldose reductase inhibitors used in diabetes Drugs 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 229940035676 analgesics Drugs 0.000 description 2
- 229940035674 anesthetics Drugs 0.000 description 2
- 239000000730 antalgic agent Substances 0.000 description 2
- 210000002159 anterior chamber Anatomy 0.000 description 2
- 230000000843 anti-fungal effect Effects 0.000 description 2
- 230000000340 anti-metabolite Effects 0.000 description 2
- 239000000043 antiallergic agent Substances 0.000 description 2
- 229940121375 antifungal agent Drugs 0.000 description 2
- 229940100197 antimetabolite Drugs 0.000 description 2
- 239000002256 antimetabolite Substances 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- 229940092705 beclomethasone Drugs 0.000 description 2
- 102000012740 beta Adrenergic Receptors Human genes 0.000 description 2
- 108010079452 beta Adrenergic Receptors Proteins 0.000 description 2
- 230000033228 biological regulation Effects 0.000 description 2
- 239000008280 blood Substances 0.000 description 2
- 210000004369 blood Anatomy 0.000 description 2
- 210000001124 body fluid Anatomy 0.000 description 2
- 239000010839 body fluid Substances 0.000 description 2
- 230000036952 cancer formation Effects 0.000 description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 2
- 231100000504 carcinogenesis Toxicity 0.000 description 2
- 230000008859 change Effects 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 229960001265 ciclosporin Drugs 0.000 description 2
- 230000001886 ciliary effect Effects 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000009833 condensation Methods 0.000 description 2
- 230000005494 condensation Effects 0.000 description 2
- 229960004544 cortisone Drugs 0.000 description 2
- 229930182912 cyclosporin Natural products 0.000 description 2
- 230000001086 cytosolic effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 230000004069 differentiation Effects 0.000 description 2
- 210000002889 endothelial cell Anatomy 0.000 description 2
- 239000003623 enhancer Substances 0.000 description 2
- 229940088598 enzyme Drugs 0.000 description 2
- WHWZLSFABNNENI-UHFFFAOYSA-N epinastine Chemical compound C1C2=CC=CC=C2C2CN=C(N)N2C2=CC=CC=C21 WHWZLSFABNNENI-UHFFFAOYSA-N 0.000 description 2
- 238000011156 evaluation Methods 0.000 description 2
- 229960000676 flunisolide Drugs 0.000 description 2
- 230000002538 fungal effect Effects 0.000 description 2
- 229960002963 ganciclovir Drugs 0.000 description 2
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 2
- 239000003193 general anesthetic agent Substances 0.000 description 2
- 230000012010 growth Effects 0.000 description 2
- 229920001519 homopolymer Polymers 0.000 description 2
- 239000000017 hydrogel Substances 0.000 description 2
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229960004752 ketorolac Drugs 0.000 description 2
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 2
- 239000004310 lactic acid Substances 0.000 description 2
- 235000014655 lactic acid Nutrition 0.000 description 2
- 229940092110 macugen Drugs 0.000 description 2
- 238000012423 maintenance Methods 0.000 description 2
- 238000007726 management method Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 230000007246 mechanism Effects 0.000 description 2
- 229920000609 methyl cellulose Polymers 0.000 description 2
- 239000001923 methylcellulose Substances 0.000 description 2
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 2
- 229960004584 methylprednisolone Drugs 0.000 description 2
- 239000003607 modifier Substances 0.000 description 2
- BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 description 2
- 229960002009 naproxen Drugs 0.000 description 2
- 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 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 description 2
- 229940049954 penicillin Drugs 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
- 102000020233 phosphotransferase Human genes 0.000 description 2
- 238000002428 photodynamic therapy Methods 0.000 description 2
- 230000036470 plasma concentration Effects 0.000 description 2
- 230000010287 polarization Effects 0.000 description 2
- 239000004626 polylactic acid Substances 0.000 description 2
- 239000002861 polymer material Substances 0.000 description 2
- 229960004618 prednisone Drugs 0.000 description 2
- XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- MIXMJCQRHVAJIO-TZHJZOAOSA-N qk4dys664x Chemical compound O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O.C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O MIXMJCQRHVAJIO-TZHJZOAOSA-N 0.000 description 2
- 231100000385 retinal toxicity Toxicity 0.000 description 2
- 150000004492 retinoid derivatives Chemical class 0.000 description 2
- 230000009049 secondary transport Effects 0.000 description 2
- 150000003384 small molecules Chemical class 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- 230000000638 stimulation Effects 0.000 description 2
- 230000002459 sustained effect Effects 0.000 description 2
- 208000011580 syndromic disease Diseases 0.000 description 2
- 229940037128 systemic glucocorticoids Drugs 0.000 description 2
- 230000004614 tumor growth Effects 0.000 description 2
- VBEQCZHXXJYVRD-GACYYNSASA-N uroanthelone Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)NCC(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(C)C)[C@@H](C)O)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCSC)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)CNC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CS)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](CS)NC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC(N)=O)C(C)C)[C@@H](C)CC)C1=CC=C(O)C=C1 VBEQCZHXXJYVRD-GACYYNSASA-N 0.000 description 2
- 230000002792 vascular Effects 0.000 description 2
- 229960003636 vidarabine Drugs 0.000 description 2
- 230000009385 viral infection Effects 0.000 description 2
- 208000026726 vitreous disease Diseases 0.000 description 2
- 229960002555 zidovudine Drugs 0.000 description 2
- HBOMLICNUCNMMY-XLPZGREQSA-N zidovudine Chemical compound O=C1NC(=O)C(C)=CN1[C@@H]1O[C@H](CO)[C@@H](N=[N+]=[N-])C1 HBOMLICNUCNMMY-XLPZGREQSA-N 0.000 description 2
- MDKGKXOCJGEUJW-VIFPVBQESA-N (2s)-2-[4-(thiophene-2-carbonyl)phenyl]propanoic acid Chemical compound C1=CC([C@@H](C(O)=O)C)=CC=C1C(=O)C1=CC=CS1 MDKGKXOCJGEUJW-VIFPVBQESA-N 0.000 description 1
- VEEGZPWAAPPXRB-BJMVGYQFSA-N (3e)-3-(1h-imidazol-5-ylmethylidene)-1h-indol-2-one Chemical compound O=C1NC2=CC=CC=C2\C1=C/C1=CN=CN1 VEEGZPWAAPPXRB-BJMVGYQFSA-N 0.000 description 1
- MYZDPUZXMFCPMU-LRIWMWCYSA-N (6r,8s,9r,10s,11s,13s,14s,17r)-2-bromo-6,9-difluoro-11,17-dihydroxy-17-(2-hydroxyacetyl)-10,13-dimethyl-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-3-one Chemical compound O=C1C(Br)=C[C@]2(C)[C@@]3(F)[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@@H](F)C2=C1 MYZDPUZXMFCPMU-LRIWMWCYSA-N 0.000 description 1
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
- XUBOMFCQGDBHNK-JTQLQIEISA-N (S)-gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCN[C@@H](C)C1 XUBOMFCQGDBHNK-JTQLQIEISA-N 0.000 description 1
- 229920003178 (lactide-co-glycolide) polymer Polymers 0.000 description 1
- JCIIKRHCWVHVFF-UHFFFAOYSA-N 1,2,4-thiadiazol-5-amine;hydrochloride Chemical compound Cl.NC1=NC=NS1 JCIIKRHCWVHVFF-UHFFFAOYSA-N 0.000 description 1
- BJHCYTJNPVGSBZ-YXSASFKJSA-N 1-[4-[6-amino-5-[(Z)-methoxyiminomethyl]pyrimidin-4-yl]oxy-2-chlorophenyl]-3-ethylurea Chemical compound CCNC(=O)Nc1ccc(Oc2ncnc(N)c2\C=N/OC)cc1Cl BJHCYTJNPVGSBZ-YXSASFKJSA-N 0.000 description 1
- MPDGHEJMBKOTSU-YKLVYJNSSA-N 18beta-glycyrrhetic acid Chemical compound C([C@H]1C2=CC(=O)[C@H]34)[C@@](C)(C(O)=O)CC[C@]1(C)CC[C@@]2(C)[C@]4(C)CC[C@@H]1[C@]3(C)CC[C@H](O)C1(C)C MPDGHEJMBKOTSU-YKLVYJNSSA-N 0.000 description 1
- LKBFFDOJUKLQNY-UHFFFAOYSA-N 2-[3-[(4-bromo-2-fluorophenyl)methyl]-4-oxo-1-phthalazinyl]acetic acid Chemical compound O=C1C2=CC=CC=C2C(CC(=O)O)=NN1CC1=CC=C(Br)C=C1F LKBFFDOJUKLQNY-UHFFFAOYSA-N 0.000 description 1
- AZSNMRSAGSSBNP-UHFFFAOYSA-N 22,23-dihydroavermectin B1a Natural products C1CC(C)C(C(C)CC)OC21OC(CC=C(C)C(OC1OC(C)C(OC3OC(C)C(O)C(OC)C3)C(OC)C1)C(C)C=CC=C1C3(C(C(=O)O4)C=C(C)C(O)C3OC1)O)CC4C2 AZSNMRSAGSSBNP-UHFFFAOYSA-N 0.000 description 1
- YKGYIDJEEQRWQH-UHFFFAOYSA-N 4-[6-(diaminomethylideneamino)-1-oxohexoxy]benzoic acid ethyl ester Chemical compound CCOC(=O)C1=CC=C(OC(=O)CCCCCN=C(N)N)C=C1 YKGYIDJEEQRWQH-UHFFFAOYSA-N 0.000 description 1
- FHIDNBAQOFJWCA-UAKXSSHOSA-N 5-fluorouridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(F)=C1 FHIDNBAQOFJWCA-UAKXSSHOSA-N 0.000 description 1
- MYYIMZRZXIQBGI-HVIRSNARSA-N 6alpha-Fluoroprednisolone Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@H](F)C2=C1 MYYIMZRZXIQBGI-HVIRSNARSA-N 0.000 description 1
- SPBDXSGPUHCETR-JFUDTMANSA-N 8883yp2r6d Chemical compound O1[C@@H](C)[C@H](O)[C@@H](OC)C[C@@H]1O[C@@H]1[C@@H](OC)C[C@H](O[C@@H]2C(=C/C[C@@H]3C[C@@H](C[C@@]4(O[C@@H]([C@@H](C)CC4)C(C)C)O3)OC(=O)[C@@H]3C=C(C)[C@@H](O)[C@H]4OC\C([C@@]34O)=C/C=C/[C@@H]2C)/C)O[C@H]1C.C1C[C@H](C)[C@@H]([C@@H](C)CC)O[C@@]21O[C@H](C\C=C(C)\[C@@H](O[C@@H]1O[C@@H](C)[C@H](O[C@@H]3O[C@@H](C)[C@H](O)[C@@H](OC)C3)[C@@H](OC)C1)[C@@H](C)\C=C\C=C/1[C@]3([C@H](C(=O)O4)C=C(C)[C@@H](O)[C@H]3OC\1)O)C[C@H]4C2 SPBDXSGPUHCETR-JFUDTMANSA-N 0.000 description 1
- GSDSWSVVBLHKDQ-UHFFFAOYSA-N 9-fluoro-3-methyl-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-[1,4]oxazino[2,3,4-ij]quinoline-6-carboxylic acid Chemical compound FC1=CC(C(C(C(O)=O)=C2)=O)=C3N2C(C)COC3=C1N1CCN(C)CC1 GSDSWSVVBLHKDQ-UHFFFAOYSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- 102100038778 Amphiregulin Human genes 0.000 description 1
- 108010033760 Amphiregulin Proteins 0.000 description 1
- 229930183010 Amphotericin Natural products 0.000 description 1
- QGGFZZLFKABGNL-UHFFFAOYSA-N Amphotericin A Natural products OC1C(N)C(O)C(C)OC1OC1C=CC=CC=CC=CCCC=CC=CC(C)C(O)C(C)C(C)OC(=O)CC(O)CC(O)CCC(O)C(O)CC(O)CC(O)(CC(O)C2C(O)=O)OC2C1 QGGFZZLFKABGNL-UHFFFAOYSA-N 0.000 description 1
- 201000002862 Angle-Closure Glaucoma Diseases 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 108091023037 Aptamer Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 102400001242 Betacellulin Human genes 0.000 description 1
- 101800001382 Betacellulin Proteins 0.000 description 1
- 108010006654 Bleomycin Proteins 0.000 description 1
- 101800004538 Bradykinin Proteins 0.000 description 1
- VOVIALXJUBGFJZ-KWVAZRHASA-N Budesonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(CCC)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O VOVIALXJUBGFJZ-KWVAZRHASA-N 0.000 description 1
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZEOWTGPWHLSLOG-UHFFFAOYSA-N Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F Chemical compound Cc1ccc(cc1-c1ccc2c(n[nH]c2c1)-c1cnn(c1)C1CC1)C(=O)Nc1cccc(c1)C(F)(F)F ZEOWTGPWHLSLOG-UHFFFAOYSA-N 0.000 description 1
- 208000003569 Central serous chorioretinopathy Diseases 0.000 description 1
- 229930186147 Cephalosporin Natural products 0.000 description 1
- 239000004099 Chlortetracycline Substances 0.000 description 1
- 208000002691 Choroiditis Diseases 0.000 description 1
- FBRAWBYQGRLCEK-AVVSTMBFSA-N Clobetasone butyrate 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)CCl)(OC(=O)CCC)[C@@]1(C)CC2=O FBRAWBYQGRLCEK-AVVSTMBFSA-N 0.000 description 1
- GJSURZIOUXUGAL-UHFFFAOYSA-N Clonidine Chemical compound ClC1=CC=CC(Cl)=C1NC1=NCCN1 GJSURZIOUXUGAL-UHFFFAOYSA-N 0.000 description 1
- 102000004626 Colony-Stimulating Factor Receptors Human genes 0.000 description 1
- 108010003384 Colony-Stimulating Factor Receptors Proteins 0.000 description 1
- 206010018325 Congenital glaucomas Diseases 0.000 description 1
- 208000016134 Conjunctival disease Diseases 0.000 description 1
- 206010010741 Conjunctivitis Diseases 0.000 description 1
- OMFXVFTZEKFJBZ-UHFFFAOYSA-N Corticosterone Natural products O=C1CCC2(C)C3C(O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 OMFXVFTZEKFJBZ-UHFFFAOYSA-N 0.000 description 1
- UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 229930182843 D-Lactic acid Natural products 0.000 description 1
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 description 1
- 206010053990 Dacryostenosis acquired Diseases 0.000 description 1
- 108010092160 Dactinomycin Proteins 0.000 description 1
- 206010012565 Developmental glaucoma Diseases 0.000 description 1
- 206010012692 Diabetic uveitis Diseases 0.000 description 1
- BXZVVICBKDXVGW-NKWVEPMBSA-N Didanosine Chemical compound O1[C@H](CO)CC[C@@H]1N1C(NC=NC2=O)=C2N=C1 BXZVVICBKDXVGW-NKWVEPMBSA-N 0.000 description 1
- 102100022258 Disks large homolog 5 Human genes 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 1
- 108091008794 FGF receptors Proteins 0.000 description 1
- 102000003974 Fibroblast growth factor 2 Human genes 0.000 description 1
- 108090000379 Fibroblast growth factor 2 Proteins 0.000 description 1
- 102100023593 Fibroblast growth factor receptor 1 Human genes 0.000 description 1
- 101710182386 Fibroblast growth factor receptor 1 Proteins 0.000 description 1
- 102100023600 Fibroblast growth factor receptor 2 Human genes 0.000 description 1
- 101710182389 Fibroblast growth factor receptor 2 Proteins 0.000 description 1
- 102100027842 Fibroblast growth factor receptor 3 Human genes 0.000 description 1
- 101710182396 Fibroblast growth factor receptor 3 Proteins 0.000 description 1
- 102100027844 Fibroblast growth factor receptor 4 Human genes 0.000 description 1
- WJOHZNCJWYWUJD-IUGZLZTKSA-N Fluocinonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)COC(=O)C)[C@@]2(C)C[C@@H]1O WJOHZNCJWYWUJD-IUGZLZTKSA-N 0.000 description 1
- 229930182566 Gentamicin Natural products 0.000 description 1
- CEAZRRDELHUEMR-URQXQFDESA-N Gentamicin Chemical compound O1[C@H](C(C)NC)CC[C@@H](N)[C@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](NC)[C@@](C)(O)CO2)O)[C@H](N)C[C@@H]1N CEAZRRDELHUEMR-URQXQFDESA-N 0.000 description 1
- MPDGHEJMBKOTSU-UHFFFAOYSA-N Glycyrrhetinsaeure Natural products C12C(=O)C=C3C4CC(C)(C(O)=O)CCC4(C)CCC3(C)C1(C)CCC1C2(C)CCC(O)C1(C)C MPDGHEJMBKOTSU-UHFFFAOYSA-N 0.000 description 1
- 102000009465 Growth Factor Receptors Human genes 0.000 description 1
- 108010009202 Growth Factor Receptors Proteins 0.000 description 1
- QXZGBUJJYSLZLT-UHFFFAOYSA-N H-Arg-Pro-Pro-Gly-Phe-Ser-Pro-Phe-Arg-OH Natural products NC(N)=NCCCC(N)C(=O)N1CCCC1C(=O)N1C(C(=O)NCC(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CO)C(=O)N2C(CCC2)C(=O)NC(CC=2C=CC=CC=2)C(=O)NC(CCCN=C(N)N)C(O)=O)CCC1 QXZGBUJJYSLZLT-UHFFFAOYSA-N 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 101800001649 Heparin-binding EGF-like growth factor Proteins 0.000 description 1
- 102400001369 Heparin-binding EGF-like growth factor Human genes 0.000 description 1
- 101000725401 Homo sapiens Cytochrome c oxidase subunit 2 Proteins 0.000 description 1
- 101100063489 Homo sapiens DLG5 gene Proteins 0.000 description 1
- 101000917134 Homo sapiens Fibroblast growth factor receptor 4 Proteins 0.000 description 1
- 101001005128 Homo sapiens LIM domain kinase 1 Proteins 0.000 description 1
- 101000605127 Homo sapiens Prostaglandin G/H synthase 2 Proteins 0.000 description 1
- 101001012157 Homo sapiens Receptor tyrosine-protein kinase erbB-2 Proteins 0.000 description 1
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-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
- 102000004877 Insulin Human genes 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 206010022941 Iridocyclitis Diseases 0.000 description 1
- 102100035792 Kininogen-1 Human genes 0.000 description 1
- WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 1
- FBOZXECLQNJBKD-ZDUSSCGKSA-N L-methotrexate Chemical compound C=1N=C2N=C(N)N=C(N)C2=NC=1CN(C)C1=CC=C(C(=O)N[C@@H](CCC(O)=O)C(O)=O)C=C1 FBOZXECLQNJBKD-ZDUSSCGKSA-N 0.000 description 1
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 1
- 102100026023 LIM domain kinase 1 Human genes 0.000 description 1
- 208000011671 Lacrimal disease Diseases 0.000 description 1
- NNJVILVZKWQKPM-UHFFFAOYSA-N Lidocaine Chemical compound CCN(CC)CC(=O)NC1=C(C)C=CC=C1C NNJVILVZKWQKPM-UHFFFAOYSA-N 0.000 description 1
- OJMMVQQUTAEWLP-UHFFFAOYSA-N Lincomycin Natural products CN1CC(CCC)CC1C(=O)NC(C(C)O)C1C(O)C(O)C(O)C(SC)O1 OJMMVQQUTAEWLP-UHFFFAOYSA-N 0.000 description 1
- 206010063341 Metamorphopsia Diseases 0.000 description 1
- 206010027476 Metastases Diseases 0.000 description 1
- RJQXTJLFIWVMTO-TYNCELHUSA-N Methicillin Chemical compound COC1=CC=CC(OC)=C1C(=O)N[C@@H]1C(=O)N2[C@@H](C(O)=O)C(C)(C)S[C@@H]21 RJQXTJLFIWVMTO-TYNCELHUSA-N 0.000 description 1
- 229930192392 Mitomycin Natural products 0.000 description 1
- HZQDCMWJEBCWBR-UUOKFMHZSA-N Mizoribine Chemical compound OC1=C(C(=O)N)N=CN1[C@H]1[C@H](O)[C@H](O)[C@@H](CO)O1 HZQDCMWJEBCWBR-UUOKFMHZSA-N 0.000 description 1
- 101100268066 Mus musculus Zap70 gene Proteins 0.000 description 1
- NWIBSHFKIJFRCO-WUDYKRTCSA-N Mytomycin Chemical compound C1N2C(C(C(C)=C(N)C3=O)=O)=C3[C@@H](COC(N)=O)[C@@]2(OC)[C@@H]2[C@H]1N2 NWIBSHFKIJFRCO-WUDYKRTCSA-N 0.000 description 1
- 102000004868 N-Methyl-D-Aspartate Receptors Human genes 0.000 description 1
- 108090001041 N-Methyl-D-Aspartate Receptors Proteins 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 108010025020 Nerve Growth Factor Proteins 0.000 description 1
- 102000015336 Nerve Growth Factor Human genes 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 102400000058 Neuregulin-1 Human genes 0.000 description 1
- 108090000556 Neuregulin-1 Proteins 0.000 description 1
- 102100028762 Neuropilin-1 Human genes 0.000 description 1
- 108090000772 Neuropilin-1 Proteins 0.000 description 1
- 206010030113 Oedema Diseases 0.000 description 1
- 208000008469 Peptic Ulcer Diseases 0.000 description 1
- 206010034960 Photophobia Diseases 0.000 description 1
- 102000001393 Platelet-Derived Growth Factor alpha Receptor Human genes 0.000 description 1
- 108010068588 Platelet-Derived Growth Factor alpha Receptor Proteins 0.000 description 1
- 239000002202 Polyethylene glycol Substances 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 239000004372 Polyvinyl alcohol Substances 0.000 description 1
- 208000003971 Posterior uveitis Diseases 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 102100038280 Prostaglandin G/H synthase 2 Human genes 0.000 description 1
- 102000016971 Proto-Oncogene Proteins c-kit Human genes 0.000 description 1
- 108010014608 Proto-Oncogene Proteins c-kit Proteins 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 208000028017 Psychotic disease Diseases 0.000 description 1
- 206010064714 Radiation retinopathy Diseases 0.000 description 1
- 102100030086 Receptor tyrosine-protein kinase erbB-2 Human genes 0.000 description 1
- 101710100969 Receptor tyrosine-protein kinase erbB-3 Proteins 0.000 description 1
- 102100029986 Receptor tyrosine-protein kinase erbB-3 Human genes 0.000 description 1
- 102100029981 Receptor tyrosine-protein kinase erbB-4 Human genes 0.000 description 1
- 101710100963 Receptor tyrosine-protein kinase erbB-4 Proteins 0.000 description 1
- 206010038899 Retinal telangiectasia Diseases 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- 208000004350 Strabismus Diseases 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 101800004564 Transforming growth factor alpha Proteins 0.000 description 1
- 102400001320 Transforming growth factor alpha Human genes 0.000 description 1
- 206010064996 Ulcerative keratitis Diseases 0.000 description 1
- 108010059993 Vancomycin Proteins 0.000 description 1
- 108010073925 Vascular Endothelial Growth Factor B Proteins 0.000 description 1
- 108010073923 Vascular Endothelial Growth Factor C Proteins 0.000 description 1
- 108010073919 Vascular Endothelial Growth Factor D Proteins 0.000 description 1
- 102000016549 Vascular Endothelial Growth Factor Receptor-2 Human genes 0.000 description 1
- 108010053100 Vascular Endothelial Growth Factor Receptor-3 Proteins 0.000 description 1
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 1
- 102100038217 Vascular endothelial growth factor B Human genes 0.000 description 1
- 102100038232 Vascular endothelial growth factor C Human genes 0.000 description 1
- 102100038234 Vascular endothelial growth factor D Human genes 0.000 description 1
- 102100033179 Vascular endothelial growth factor receptor 3 Human genes 0.000 description 1
- 206010053648 Vascular occlusion Diseases 0.000 description 1
- JXLYSJRDGCGARV-WWYNWVTFSA-N Vinblastine Natural products O=C(O[C@H]1[C@](O)(C(=O)OC)[C@@H]2N(C)c3c(cc(c(OC)c3)[C@]3(C(=O)OC)c4[nH]c5c(c4CCN4C[C@](O)(CC)C[C@H](C3)C4)cccc5)[C@@]32[C@H]2[C@@]1(CC)C=CCN2CC3)C JXLYSJRDGCGARV-WWYNWVTFSA-N 0.000 description 1
- 235000009754 Vitis X bourquina Nutrition 0.000 description 1
- 235000012333 Vitis X labruscana Nutrition 0.000 description 1
- 240000006365 Vitis vinifera Species 0.000 description 1
- 235000014787 Vitis vinifera Nutrition 0.000 description 1
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- 229940022663 acetate Drugs 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- RJURFGZVJUQBHK-IIXSONLDSA-N actinomycin D Chemical compound C[C@H]1OC(=O)[C@H](C(C)C)N(C)C(=O)CN(C)C(=O)[C@@H]2CCCN2C(=O)[C@@H](C(C)C)NC(=O)[C@H]1NC(=O)C1=C(N)C(=O)C(C)=C2OC(C(C)=CC=C3C(=O)N[C@@H]4C(=O)N[C@@H](C(N5CCC[C@H]5C(=O)N(C)CC(=O)N(C)[C@@H](C(C)C)C(=O)O[C@@H]4C)=O)C(C)C)=C3N=C21 RJURFGZVJUQBHK-IIXSONLDSA-N 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 230000000996 additive effect Effects 0.000 description 1
- 230000001800 adrenalinergic effect Effects 0.000 description 1
- 239000000674 adrenergic antagonist Substances 0.000 description 1
- 239000000808 adrenergic beta-agonist Substances 0.000 description 1
- 229940126157 adrenergic receptor agonist Drugs 0.000 description 1
- 229940009456 adriamycin Drugs 0.000 description 1
- CXDWHYOBSJTRJU-SRWWVFQWSA-N algestone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@@H](O)[C@@](C(=O)C)(O)[C@@]1(C)CC2 CXDWHYOBSJTRJU-SRWWVFQWSA-N 0.000 description 1
- 229960001900 algestone Drugs 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 102000030484 alpha-2 Adrenergic Receptor Human genes 0.000 description 1
- 108020004101 alpha-2 Adrenergic Receptor Proteins 0.000 description 1
- 125000000539 amino acid group Chemical group 0.000 description 1
- 150000001413 amino acids Chemical group 0.000 description 1
- 229940126575 aminoglycoside Drugs 0.000 description 1
- 229940009444 amphotericin Drugs 0.000 description 1
- APKFDSVGJQXUKY-INPOYWNPSA-N amphotericin B Chemical compound O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1/C=C/C=C/C=C/C=C/C=C/C=C/C=C/[C@H](C)[C@@H](O)[C@@H](C)[C@H](C)OC(=O)C[C@H](O)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 APKFDSVGJQXUKY-INPOYWNPSA-N 0.000 description 1
- 229960000723 ampicillin Drugs 0.000 description 1
- AVKUERGKIZMTKX-NJBDSQKTSA-N ampicillin Chemical compound C1([C@@H](N)C(=O)N[C@H]2[C@H]3SC([C@@H](N3C2=O)C(O)=O)(C)C)=CC=CC=C1 AVKUERGKIZMTKX-NJBDSQKTSA-N 0.000 description 1
- LGEQQWMQCRIYKG-DOFZRALJSA-N anandamide Chemical compound CCCCC\C=C/C\C=C/C\C=C/C\C=C/CCCC(=O)NCCO LGEQQWMQCRIYKG-DOFZRALJSA-N 0.000 description 1
- 239000003098 androgen Substances 0.000 description 1
- 239000004037 angiogenesis inhibitor Substances 0.000 description 1
- 229940121369 angiogenesis inhibitor Drugs 0.000 description 1
- 230000002491 angiogenic effect Effects 0.000 description 1
- 230000000964 angiostatic effect Effects 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 201000004612 anterior uveitis Diseases 0.000 description 1
- 230000000507 anthelmentic effect Effects 0.000 description 1
- 230000001466 anti-adreneric effect Effects 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000001078 anti-cholinergic effect Effects 0.000 description 1
- 230000001384 anti-glaucoma Effects 0.000 description 1
- 230000003276 anti-hypertensive effect Effects 0.000 description 1
- 230000002924 anti-infective effect Effects 0.000 description 1
- 230000000842 anti-protozoal effect Effects 0.000 description 1
- 230000000840 anti-viral effect Effects 0.000 description 1
- 238000011319 anticancer therapy Methods 0.000 description 1
- 229940045687 antimetabolites folic acid analogs Drugs 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003904 antiprotozoal agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 229960002610 apraclonidine Drugs 0.000 description 1
- IEJXVRYNEISIKR-UHFFFAOYSA-N apraclonidine Chemical compound ClC1=CC(N)=CC(Cl)=C1NC1=NCCN1 IEJXVRYNEISIKR-UHFFFAOYSA-N 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 210000001742 aqueous humor Anatomy 0.000 description 1
- LGEQQWMQCRIYKG-UHFFFAOYSA-N arachidonic acid ethanolamide Natural products CCCCCC=CCC=CCC=CCC=CCCCC(=O)NCCO LGEQQWMQCRIYKG-UHFFFAOYSA-N 0.000 description 1
- MDJRZSNPHZEMJH-MTMZYOSNSA-N artisone acetate Chemical compound C1C=C2C[C@@H](O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)COC(=O)C)[C@@]1(C)CC2 MDJRZSNPHZEMJH-MTMZYOSNSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 201000009310 astigmatism Diseases 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- 229960002170 azathioprine Drugs 0.000 description 1
- LMEKQMALGUDUQG-UHFFFAOYSA-N azathioprine Chemical compound CN1C=NC([N+]([O-])=O)=C1SC1=NC=NC2=C1NC=N2 LMEKQMALGUDUQG-UHFFFAOYSA-N 0.000 description 1
- 229960003071 bacitracin Drugs 0.000 description 1
- 229930184125 bacitracin Natural products 0.000 description 1
- CLKOFPXJLQSYAH-ABRJDSQDSA-N bacitracin A Chemical compound C1SC([C@@H](N)[C@@H](C)CC)=N[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H]1C(=O)N[C@H](CCCN)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CC=2N=CNC=2)C(=O)N[C@H](CC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)NCCCC1 CLKOFPXJLQSYAH-ABRJDSQDSA-N 0.000 description 1
- 210000002469 basement membrane Anatomy 0.000 description 1
- 229960000686 benzalkonium chloride Drugs 0.000 description 1
- CADWTSSKOVRVJC-UHFFFAOYSA-N benzyl(dimethyl)azanium;chloride Chemical compound [Cl-].C[NH+](C)CC1=CC=CC=C1 CADWTSSKOVRVJC-UHFFFAOYSA-N 0.000 description 1
- 229960002537 betamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-DVTGEIKXSA-N betamethasone 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-DVTGEIKXSA-N 0.000 description 1
- 229960004324 betaxolol Drugs 0.000 description 1
- NWIUTZDMDHAVTP-UHFFFAOYSA-N betaxolol Chemical compound C1=CC(OCC(O)CNC(C)C)=CC=C1CCOCC1CC1 NWIUTZDMDHAVTP-UHFFFAOYSA-N 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- 230000004071 biological effect Effects 0.000 description 1
- 239000012620 biological material Substances 0.000 description 1
- 230000031018 biological processes and functions Effects 0.000 description 1
- 238000001815 biotherapy Methods 0.000 description 1
- 229960001561 bleomycin Drugs 0.000 description 1
- OYVAGSVQBOHSSS-UAPAGMARSA-O bleomycin A2 Chemical compound N([C@H](C(=O)N[C@H](C)[C@@H](O)[C@H](C)C(=O)N[C@@H]([C@H](O)C)C(=O)NCCC=1SC=C(N=1)C=1SC=C(N=1)C(=O)NCCC[S+](C)C)[C@@H](O[C@H]1[C@H]([C@@H](O)[C@H](O)[C@H](CO)O1)O[C@@H]1[C@H]([C@@H](OC(N)=O)[C@H](O)[C@@H](CO)O1)O)C=1N=CNC=1)C(=O)C1=NC([C@H](CC(N)=O)NC[C@H](N)C(N)=O)=NC(N)=C1C OYVAGSVQBOHSSS-UAPAGMARSA-O 0.000 description 1
- 230000000744 blepharospasm Effects 0.000 description 1
- 206010005159 blepharospasm Diseases 0.000 description 1
- 230000015624 blood vessel development Effects 0.000 description 1
- 229910021538 borax Inorganic materials 0.000 description 1
- QXZGBUJJYSLZLT-FDISYFBBSA-N bradykinin Chemical compound NC(=N)NCCC[C@H](N)C(=O)N1CCC[C@H]1C(=O)N1[C@H](C(=O)NCC(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CO)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)CCC1 QXZGBUJJYSLZLT-FDISYFBBSA-N 0.000 description 1
- 229960004436 budesonide Drugs 0.000 description 1
- 239000006172 buffering agent Substances 0.000 description 1
- XASIMHXSUQUHLV-UHFFFAOYSA-N camostat Chemical compound C1=CC(CC(=O)OCC(=O)N(C)C)=CC=C1OC(=O)C1=CC=C(N=C(N)N)C=C1 XASIMHXSUQUHLV-UHFFFAOYSA-N 0.000 description 1
- 229960000772 camostat Drugs 0.000 description 1
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 1
- 229960004484 carbachol Drugs 0.000 description 1
- 229960003669 carbenicillin Drugs 0.000 description 1
- FPPNZSSZRUTDAP-UWFZAAFLSA-N carbenicillin Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)C(C(O)=O)C1=CC=CC=C1 FPPNZSSZRUTDAP-UWFZAAFLSA-N 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 150000001733 carboxylic acid esters Chemical class 0.000 description 1
- LWAFSWPYPHEXKX-UHFFFAOYSA-N carteolol Chemical compound N1C(=O)CCC2=C1C=CC=C2OCC(O)CNC(C)(C)C LWAFSWPYPHEXKX-UHFFFAOYSA-N 0.000 description 1
- 229960001222 carteolol Drugs 0.000 description 1
- 108020001778 catalytic domains Proteins 0.000 description 1
- 229960001139 cefazolin Drugs 0.000 description 1
- MLYYVTUWGNIJIB-BXKDBHETSA-N cefazolin Chemical compound S1C(C)=NN=C1SCC1=C(C(O)=O)N2C(=O)[C@@H](NC(=O)CN3N=NN=C3)[C@H]2SC1 MLYYVTUWGNIJIB-BXKDBHETSA-N 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 230000036755 cellular response Effects 0.000 description 1
- 230000005754 cellular signaling Effects 0.000 description 1
- 229940124587 cephalosporin Drugs 0.000 description 1
- 238000002512 chemotherapy Methods 0.000 description 1
- VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 229950006229 chloroprednisone Drugs 0.000 description 1
- NPSLCOWKFFNQKK-ZPSUVKRCSA-N chloroprednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3C[C@H](Cl)C2=C1 NPSLCOWKFFNQKK-ZPSUVKRCSA-N 0.000 description 1
- 229960003677 chloroquine Drugs 0.000 description 1
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 1
- 229960004475 chlortetracycline Drugs 0.000 description 1
- CYDMQBQPVICBEU-XRNKAMNCSA-N chlortetracycline Chemical compound C1=CC(Cl)=C2[C@](O)(C)[C@H]3C[C@H]4[C@H](N(C)C)C(O)=C(C(N)=O)C(=O)[C@@]4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-XRNKAMNCSA-N 0.000 description 1
- 235000019365 chlortetracycline Nutrition 0.000 description 1
- 230000001713 cholinergic effect Effects 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- 229960002842 clobetasol Drugs 0.000 description 1
- CBGUOGMQLZIXBE-XGQKBEPLSA-N clobetasol propionate 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)CCl)(OC(=O)CC)[C@@]1(C)C[C@@H]2O CBGUOGMQLZIXBE-XGQKBEPLSA-N 0.000 description 1
- 229960001146 clobetasone Drugs 0.000 description 1
- 229960002896 clonidine Drugs 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 229960001338 colchicine Drugs 0.000 description 1
- 239000002131 composite material Substances 0.000 description 1
- 239000000599 controlled substance Substances 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 210000004087 cornea Anatomy 0.000 description 1
- 208000021921 corneal disease Diseases 0.000 description 1
- 201000007717 corneal ulcer Diseases 0.000 description 1
- OMFXVFTZEKFJBZ-HJTSIMOOSA-N corticosterone Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@H](CC4)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 OMFXVFTZEKFJBZ-HJTSIMOOSA-N 0.000 description 1
- 229960000265 cromoglicic acid Drugs 0.000 description 1
- IMZMKUWMOSJXDT-UHFFFAOYSA-N cromoglycic acid Chemical compound O1C(C(O)=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C(O)=O)O2 IMZMKUWMOSJXDT-UHFFFAOYSA-N 0.000 description 1
- 238000011461 current therapy Methods 0.000 description 1
- 125000004093 cyano group Chemical group *C#N 0.000 description 1
- 229940022769 d- lactic acid Drugs 0.000 description 1
- 229960000640 dactinomycin Drugs 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000007857 degradation product Substances 0.000 description 1
- 230000000881 depressing effect Effects 0.000 description 1
- 229960003662 desonide Drugs 0.000 description 1
- WBGKWQHBNHJJPZ-LECWWXJVSA-N desonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O WBGKWQHBNHJJPZ-LECWWXJVSA-N 0.000 description 1
- 229940084954 dexamethasone 1 mg 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
- 229960002656 didanosine Drugs 0.000 description 1
- 238000006471 dimerization reaction Methods 0.000 description 1
- 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 description 1
- 238000007907 direct compression Methods 0.000 description 1
- 208000037765 diseases and disorders Diseases 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 230000007783 downstream signaling Effects 0.000 description 1
- 238000001647 drug administration Methods 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000009509 drug development Methods 0.000 description 1
- 239000013583 drug formulation Substances 0.000 description 1
- 229940068204 drug implant Drugs 0.000 description 1
- 239000003844 drug implant Substances 0.000 description 1
- 208000011325 dry age related macular degeneration Diseases 0.000 description 1
- 239000003792 electrolyte Substances 0.000 description 1
- 229940112573 elestat Drugs 0.000 description 1
- 230000003028 elevating effect Effects 0.000 description 1
- 239000008393 encapsulating agent Substances 0.000 description 1
- 206010014801 endophthalmitis Diseases 0.000 description 1
- 229960003720 enoxolone Drugs 0.000 description 1
- 230000002255 enzymatic effect Effects 0.000 description 1
- CHNUOJQWGUIOLD-NFZZJPOKSA-N epalrestat Chemical compound C=1C=CC=CC=1\C=C(/C)\C=C1/SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-NFZZJPOKSA-N 0.000 description 1
- 229950010170 epalrestat Drugs 0.000 description 1
- CHNUOJQWGUIOLD-UHFFFAOYSA-N epalrestate Natural products C=1C=CC=CC=1C=C(C)C=C1SC(=S)N(CC(O)=O)C1=O CHNUOJQWGUIOLD-UHFFFAOYSA-N 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 229960003449 epinastine Drugs 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 229950009769 etabonate Drugs 0.000 description 1
- 150000002170 ethers Chemical class 0.000 description 1
- 229940064982 ethylnicotinate Drugs 0.000 description 1
- 239000003889 eye drop Substances 0.000 description 1
- 229940012356 eye drops Drugs 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 230000001605 fetal effect Effects 0.000 description 1
- 239000000835 fiber Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229940043075 fluocinolone Drugs 0.000 description 1
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
- 229960000785 fluocinonide Drugs 0.000 description 1
- XWTIDFOGTCVGQB-FHIVUSPVSA-N fluocortin butyl Chemical group C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@@H]1[C@@H]2[C@@H]2C[C@@H](C)[C@H](C(=O)C(=O)OCCCC)[C@@]2(C)C[C@@H]1O XWTIDFOGTCVGQB-FHIVUSPVSA-N 0.000 description 1
- 229950008509 fluocortin butyl Drugs 0.000 description 1
- 229960001048 fluorometholone Drugs 0.000 description 1
- FAOZLTXFLGPHNG-KNAQIMQKSA-N fluorometholone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FAOZLTXFLGPHNG-KNAQIMQKSA-N 0.000 description 1
- 229960003590 fluperolone Drugs 0.000 description 1
- HHPZZKDXAFJLOH-QZIXMDIESA-N fluperolone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC[C@@](C(=O)[C@@H](OC(C)=O)C)(O)[C@@]1(C)C[C@@H]2O HHPZZKDXAFJLOH-QZIXMDIESA-N 0.000 description 1
- 229960002650 fluprednidene acetate Drugs 0.000 description 1
- DEFOZIFYUBUHHU-IYQKUMFPSA-N fluprednidene acetate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1CC(=C)[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O DEFOZIFYUBUHHU-IYQKUMFPSA-N 0.000 description 1
- 229960000618 fluprednisolone Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- WMWTYOKRWGGJOA-CENSZEJFSA-N fluticasone propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)SCF)(OC(=O)CC)[C@@]2(C)C[C@@H]1O WMWTYOKRWGGJOA-CENSZEJFSA-N 0.000 description 1
- 229960000289 fluticasone propionate Drugs 0.000 description 1
- 150000002224 folic acids Chemical class 0.000 description 1
- 229950000501 gabexate Drugs 0.000 description 1
- XUBOMFCQGDBHNK-UHFFFAOYSA-N gatifloxacin Chemical compound FC1=CC(C(C(C(O)=O)=CN2C3CC3)=O)=C2C(OC)=C1N1CCNC(C)C1 XUBOMFCQGDBHNK-UHFFFAOYSA-N 0.000 description 1
- 229960003923 gatifloxacin Drugs 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 229930195712 glutamate Natural products 0.000 description 1
- 150000004676 glycans Chemical class 0.000 description 1
- 229960002475 halometasone Drugs 0.000 description 1
- GGXMRPUKBWXVHE-MIHLVHIWSA-N halometasone Chemical compound C1([C@@H](F)C2)=CC(=O)C(Cl)=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]2(C)C[C@@H]1O GGXMRPUKBWXVHE-MIHLVHIWSA-N 0.000 description 1
- 230000013632 homeostatic process Effects 0.000 description 1
- 239000007970 homogeneous dispersion Substances 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- FWFVLWGEFDIZMJ-FOMYWIRZSA-N hydrocortamate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)CN(CC)CC)(O)[C@@]1(C)C[C@@H]2O FWFVLWGEFDIZMJ-FOMYWIRZSA-N 0.000 description 1
- 229950000208 hydrocortamate Drugs 0.000 description 1
- VWQWXZAWFPZJDA-CGVGKPPMSA-N hydrocortisone succinate Chemical compound O=C1CC[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COC(=O)CCC(O)=O)[C@@H]4[C@@H]3CCC2=C1 VWQWXZAWFPZJDA-CGVGKPPMSA-N 0.000 description 1
- 229950006240 hydrocortisone succinate Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 125000004435 hydrogen atom Chemical class [H]* 0.000 description 1
- 229920003088 hydroxypropyl methyl cellulose Polymers 0.000 description 1
- 235000010979 hydroxypropyl methyl cellulose Nutrition 0.000 description 1
- 201000001421 hyperglycemia Diseases 0.000 description 1
- 230000000521 hyperimmunizing effect Effects 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 230000001506 immunosuppresive effect Effects 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 229940124589 immunosuppressive drug Drugs 0.000 description 1
- 208000015181 infectious disease Diseases 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 230000028709 inflammatory response Effects 0.000 description 1
- 230000005764 inhibitory process Effects 0.000 description 1
- ZPNFWUPYTFPOJU-LPYSRVMUSA-N iniprol Chemical compound C([C@H]1C(=O)NCC(=O)NCC(=O)N[C@H]2CSSC[C@H]3C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC=4C=CC=CC=4)C(=O)N[C@@H](CC=4C=CC(O)=CC=4)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CC=4C=CC=CC=4)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCCN)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC2=O)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](CC=2C=CC=CC=2)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H]2N(CCC2)C(=O)[C@@H](N)CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N2[C@@H](CCC2)C(=O)N2[C@@H](CCC2)C(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N2[C@@H](CCC2)C(=O)N3)C(=O)NCC(=O)NCC(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CC=2C=CC=CC=2)C(=O)N[C@H](C(=O)N1)C(C)C)[C@@H](C)O)[C@@H](C)CC)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZPNFWUPYTFPOJU-LPYSRVMUSA-N 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- 230000004068 intracellular signaling Effects 0.000 description 1
- 210000000554 iris Anatomy 0.000 description 1
- 229960002418 ivermectin Drugs 0.000 description 1
- 229960000318 kanamycin Drugs 0.000 description 1
- 229930027917 kanamycin Natural products 0.000 description 1
- SBUJHOSQTJFQJX-NOAMYHISSA-N kanamycin Chemical compound O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CN)O[C@@H]1O[C@H]1[C@H](O)[C@@H](O[C@@H]2[C@@H]([C@@H](N)[C@H](O)[C@@H](CO)O2)O)[C@H](N)C[C@@H]1N SBUJHOSQTJFQJX-NOAMYHISSA-N 0.000 description 1
- 229930182823 kanamycin A Natural products 0.000 description 1
- 208000000617 lacrimal duct obstruction Diseases 0.000 description 1
- 238000013532 laser treatment Methods 0.000 description 1
- 229960004194 lidocaine Drugs 0.000 description 1
- 208000013469 light sensitivity Diseases 0.000 description 1
- OJMMVQQUTAEWLP-KIDUDLJLSA-N lincomycin Chemical compound CN1C[C@H](CCC)C[C@H]1C(=O)N[C@H]([C@@H](C)O)[C@@H]1[C@H](O)[C@H](O)[C@@H](O)[C@@H](SC)O1 OJMMVQQUTAEWLP-KIDUDLJLSA-N 0.000 description 1
- 229960005287 lincomycin Drugs 0.000 description 1
- 229940041028 lincosamides Drugs 0.000 description 1
- 239000007788 liquid Substances 0.000 description 1
- 238000004811 liquid chromatography Methods 0.000 description 1
- 210000004185 liver Anatomy 0.000 description 1
- DMKSVUSAATWOCU-HROMYWEYSA-N loteprednol etabonate Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)OCCl)(OC(=O)OCC)[C@@]1(C)C[C@@H]2O DMKSVUSAATWOCU-HROMYWEYSA-N 0.000 description 1
- 229960003744 loteprednol etabonate Drugs 0.000 description 1
- 230000035168 lymphangiogenesis Effects 0.000 description 1
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
- 239000011976 maleic acid Substances 0.000 description 1
- 102000006240 membrane receptors Human genes 0.000 description 1
- 108020004084 membrane receptors Proteins 0.000 description 1
- 229960001810 meprednisone Drugs 0.000 description 1
- PIDANAQULIKBQS-RNUIGHNZSA-N meprednisone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@@H]2[C@@H]1[C@@H]1C[C@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)CC2=O PIDANAQULIKBQS-RNUIGHNZSA-N 0.000 description 1
- 230000002503 metabolic effect Effects 0.000 description 1
- 230000009401 metastasis Effects 0.000 description 1
- 229960000485 methotrexate Drugs 0.000 description 1
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 1
- 239000004292 methyl p-hydroxybenzoate Substances 0.000 description 1
- 229960002216 methylparaben Drugs 0.000 description 1
- 229960003085 meticillin Drugs 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 230000005012 migration Effects 0.000 description 1
- 238000013508 migration Methods 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 239000003604 miotic agent Substances 0.000 description 1
- 229960004857 mitomycin Drugs 0.000 description 1
- 229950000844 mizoribine Drugs 0.000 description 1
- 229960002744 mometasone furoate Drugs 0.000 description 1
- WOFMFGQZHJDGCX-ZULDAHANSA-N mometasone furoate Chemical compound O([C@]1([C@@]2(C)C[C@H](O)[C@]3(Cl)[C@@]4(C)C=CC(=O)C=C4CC[C@H]3[C@@H]2C[C@H]1C)C(=O)CCl)C(=O)C1=CC=CO1 WOFMFGQZHJDGCX-ZULDAHANSA-N 0.000 description 1
- 229960005181 morphine Drugs 0.000 description 1
- 230000000877 morphologic effect Effects 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 239000002637 mydriatic agent Substances 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- 208000001491 myopia Diseases 0.000 description 1
- 230000004379 myopia Effects 0.000 description 1
- YOHYSYJDKVYCJI-UHFFFAOYSA-N n-[3-[[6-[3-(trifluoromethyl)anilino]pyrimidin-4-yl]amino]phenyl]cyclopropanecarboxamide Chemical compound FC(F)(F)C1=CC=CC(NC=2N=CN=C(NC=3C=C(NC(=O)C4CC4)C=CC=3)C=2)=C1 YOHYSYJDKVYCJI-UHFFFAOYSA-N 0.000 description 1
- 239000005445 natural material Substances 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 210000001640 nerve ending Anatomy 0.000 description 1
- 229940053128 nerve growth factor Drugs 0.000 description 1
- 230000004112 neuroprotection Effects 0.000 description 1
- 239000002547 new drug Substances 0.000 description 1
- 229960001699 ofloxacin Drugs 0.000 description 1
- 239000002997 ophthalmic solution Substances 0.000 description 1
- 229940054534 ophthalmic solution Drugs 0.000 description 1
- 229940126701 oral medication Drugs 0.000 description 1
- 150000002895 organic esters Chemical class 0.000 description 1
- 150000002905 orthoesters Chemical class 0.000 description 1
- 230000036961 partial effect Effects 0.000 description 1
- 230000001717 pathogenic effect Effects 0.000 description 1
- 229960003407 pegaptanib Drugs 0.000 description 1
- 239000000137 peptide hydrolase inhibitor Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 238000005191 phase separation Methods 0.000 description 1
- 229940067107 phenylethyl alcohol Drugs 0.000 description 1
- 229940096826 phenylmercuric acetate Drugs 0.000 description 1
- PDTFCHSETJBPTR-UHFFFAOYSA-N phenylmercuric nitrate Chemical compound [O-][N+](=O)O[Hg]C1=CC=CC=C1 PDTFCHSETJBPTR-UHFFFAOYSA-N 0.000 description 1
- DCWXELXMIBXGTH-QMMMGPOBSA-N phosphonotyrosine Chemical group OC(=O)[C@@H](N)CC1=CC=C(OP(O)(O)=O)C=C1 DCWXELXMIBXGTH-QMMMGPOBSA-N 0.000 description 1
- 230000000649 photocoagulation Effects 0.000 description 1
- 230000019612 pigmentation Effects 0.000 description 1
- 229940065514 poly(lactide) Drugs 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920001223 polyethylene glycol Polymers 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 239000003910 polypeptide antibiotic agent Substances 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002451 polyvinyl alcohol Polymers 0.000 description 1
- 229940068984 polyvinyl alcohol Drugs 0.000 description 1
- 229950010884 ponalrestat Drugs 0.000 description 1
- 238000010837 poor prognosis Methods 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- JDOZJEUDSLGTLU-VWUMJDOOSA-N prednisolone phosphate Chemical compound O=C1C=C[C@]2(C)[C@H]3[C@@H](O)C[C@](C)([C@@](CC4)(O)C(=O)COP(O)(O)=O)[C@@H]4[C@@H]3CCC2=C1 JDOZJEUDSLGTLU-VWUMJDOOSA-N 0.000 description 1
- 229960002943 prednisolone sodium phosphate Drugs 0.000 description 1
- 230000001292 preischemic effect Effects 0.000 description 1
- 201000010041 presbyopia Diseases 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 230000002035 prolonged effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 208000022749 pupil disease Diseases 0.000 description 1
- 150000003212 purines Chemical class 0.000 description 1
- 150000003230 pyrimidines Chemical class 0.000 description 1
- 230000002285 radioactive effect Effects 0.000 description 1
- 238000001959 radiotherapy Methods 0.000 description 1
- 208000014733 refractive error Diseases 0.000 description 1
- 230000009703 regulation of cell differentiation Effects 0.000 description 1
- 230000025053 regulation of cell proliferation Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000011160 research Methods 0.000 description 1
- 229940053174 restasis Drugs 0.000 description 1
- 230000000717 retained effect Effects 0.000 description 1
- 210000001210 retinal vessel Anatomy 0.000 description 1
- 229930002330 retinoic acid Natural products 0.000 description 1
- SHGAZHPCJJPHSC-YCNIQYBTSA-N retinoic acid group Chemical group C\C(=C/C(=O)O)\C=C\C=C(\C=C\C1=C(CCCC1(C)C)C)/C SHGAZHPCJJPHSC-YCNIQYBTSA-N 0.000 description 1
- 238000012552 review Methods 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- STECJAGHUSJQJN-FWXGHANASA-N scopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-FWXGHANASA-N 0.000 description 1
- 229960002646 scopolamine Drugs 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- WBHQBSYUUJJSRZ-UHFFFAOYSA-M sodium bisulfate Chemical compound [Na+].OS([O-])(=O)=O WBHQBSYUUJJSRZ-UHFFFAOYSA-M 0.000 description 1
- 229910000342 sodium bisulfate Inorganic materials 0.000 description 1
- 229940100996 sodium bisulfate Drugs 0.000 description 1
- 229940001607 sodium bisulfite Drugs 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000001488 sodium phosphate Substances 0.000 description 1
- 229910000162 sodium phosphate Inorganic materials 0.000 description 1
- 235000011008 sodium phosphates Nutrition 0.000 description 1
- 235000010339 sodium tetraborate Nutrition 0.000 description 1
- AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
- 229940001474 sodium thiosulfate Drugs 0.000 description 1
- 235000019345 sodium thiosulphate Nutrition 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 230000000087 stabilizing effect Effects 0.000 description 1
- 229910001220 stainless steel Inorganic materials 0.000 description 1
- 239000010935 stainless steel Substances 0.000 description 1
- WNIFXKPDILJURQ-UHFFFAOYSA-N stearyl glycyrrhizinate Natural products C1CC(O)C(C)(C)C2CCC3(C)C4(C)CCC5(C)CCC(C(=O)OCCCCCCCCCCCCCCCCCC)(C)CC5C4=CC(=O)C3C21C WNIFXKPDILJURQ-UHFFFAOYSA-N 0.000 description 1
- 229950000244 sulfanilic acid Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 239000013589 supplement Substances 0.000 description 1
- 229960004492 suprofen Drugs 0.000 description 1
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical compound OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 229960000621 suramin sodium Drugs 0.000 description 1
- 238000013268 sustained release Methods 0.000 description 1
- 239000012730 sustained-release form Substances 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- 229960002180 tetracycline Drugs 0.000 description 1
- 229930101283 tetracycline Natural products 0.000 description 1
- 235000019364 tetracycline Nutrition 0.000 description 1
- 229940072172 tetracycline antibiotic Drugs 0.000 description 1
- RTKIYNMVFMVABJ-UHFFFAOYSA-L thimerosal Chemical compound [Na+].CC[Hg]SC1=CC=CC=C1C([O-])=O RTKIYNMVFMVABJ-UHFFFAOYSA-L 0.000 description 1
- 229940033663 thimerosal Drugs 0.000 description 1
- 229960000454 timolol hemihydrate Drugs 0.000 description 1
- 229940034744 timoptic Drugs 0.000 description 1
- 230000000451 tissue damage Effects 0.000 description 1
- 231100000827 tissue damage Toxicity 0.000 description 1
- 229960000187 tissue plasminogen activator Drugs 0.000 description 1
- LUBHDINQXIHVLS-UHFFFAOYSA-N tolrestat Chemical compound OC(=O)CN(C)C(=S)C1=CC=CC2=C(C(F)(F)F)C(OC)=CC=C21 LUBHDINQXIHVLS-UHFFFAOYSA-N 0.000 description 1
- 229960003069 tolrestat Drugs 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- 102000027257 transmembrane receptors Human genes 0.000 description 1
- 108091008578 transmembrane receptors Proteins 0.000 description 1
- 238000002054 transplantation Methods 0.000 description 1
- 229960001727 tretinoin Drugs 0.000 description 1
- 229960002117 triamcinolone acetonide Drugs 0.000 description 1
- YNDXUCZADRHECN-JNQJZLCISA-N triamcinolone acetonide Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]1(C)C[C@@H]2O YNDXUCZADRHECN-JNQJZLCISA-N 0.000 description 1
- 229950006782 triamcinolone benetonide Drugs 0.000 description 1
- GUYPYYARYIIWJZ-CYEPYHPTSA-N triamcinolone benetonide Chemical compound O=C([C@]12[C@H](OC(C)(C)O1)C[C@@H]1[C@@]2(C[C@H](O)[C@]2(F)[C@@]3(C)C=CC(=O)C=C3CC[C@H]21)C)COC(=O)C(C)CNC(=O)C1=CC=CC=C1 GUYPYYARYIIWJZ-CYEPYHPTSA-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
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 125000001493 tyrosinyl group Chemical group [H]OC1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])(N([H])[H])C(*)=O 0.000 description 1
- BDSYKGHYMJNPAB-LICBFIPMSA-N ulobetasol propionate Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H](C)[C@@](C(=O)CCl)(OC(=O)CC)[C@@]2(C)C[C@@H]1O BDSYKGHYMJNPAB-LICBFIPMSA-N 0.000 description 1
- 229950008396 ulobetasol propionate Drugs 0.000 description 1
- 238000009827 uniform distribution Methods 0.000 description 1
- MYPYJXKWCTUITO-LYRMYLQWSA-N vancomycin Chemical compound O([C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@H]1OC1=C2C=C3C=C1OC1=CC=C(C=C1Cl)[C@@H](O)[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@H]3C(=O)N[C@H]1C(=O)N[C@H](C(N[C@@H](C3=CC(O)=CC(O)=C3C=3C(O)=CC=C1C=3)C(O)=O)=O)[C@H](O)C1=CC=C(C(=C1)Cl)O2)=O)NC(=O)[C@@H](CC(C)C)NC)[C@H]1C[C@](C)(N)[C@H](O)[C@H](C)O1 MYPYJXKWCTUITO-LYRMYLQWSA-N 0.000 description 1
- 229960003165 vancomycin Drugs 0.000 description 1
- MYPYJXKWCTUITO-UHFFFAOYSA-N vancomycin Natural products O1C(C(=C2)Cl)=CC=C2C(O)C(C(NC(C2=CC(O)=CC(O)=C2C=2C(O)=CC=C3C=2)C(O)=O)=O)NC(=O)C3NC(=O)C2NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(CC(C)C)NC)C(O)C(C=C3Cl)=CC=C3OC3=CC2=CC1=C3OC1OC(CO)C(O)C(O)C1OC1CC(C)(N)C(O)C(C)O1 MYPYJXKWCTUITO-UHFFFAOYSA-N 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 210000003556 vascular endothelial cell Anatomy 0.000 description 1
- 208000021331 vascular occlusion disease Diseases 0.000 description 1
- 229940124549 vasodilator Drugs 0.000 description 1
- 239000003071 vasodilator agent Substances 0.000 description 1
- 229960003048 vinblastine Drugs 0.000 description 1
- JXLYSJRDGCGARV-XQKSVPLYSA-N vincaleukoblastine Chemical compound C([C@@H](C[C@]1(C(=O)OC)C=2C(=CC3=C([C@]45[C@H]([C@@]([C@H](OC(C)=O)[C@]6(CC)C=CCN([C@H]56)CC4)(O)C(=O)OC)N3C)C=2)OC)C[C@@](C2)(O)CC)N2CCC2=C1NC1=CC=CC=C21 JXLYSJRDGCGARV-XQKSVPLYSA-N 0.000 description 1
- OGWKCGZFUXNPDA-XQKSVPLYSA-N vincristine Chemical compound C([N@]1C[C@@H](C[C@]2(C(=O)OC)C=3C(=CC4=C([C@]56[C@H]([C@@]([C@H](OC(C)=O)[C@]7(CC)C=CCN([C@H]67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)C[C@@](C1)(O)CC)CC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-XQKSVPLYSA-N 0.000 description 1
- 229960004528 vincristine Drugs 0.000 description 1
- OGWKCGZFUXNPDA-UHFFFAOYSA-N vincristine Natural products C1C(CC)(O)CC(CC2(C(=O)OC)C=3C(=CC4=C(C56C(C(C(OC(C)=O)C7(CC)C=CCN(C67)CC5)(O)C(=O)OC)N4C=O)C=3)OC)CN1CCC1=C2NC2=CC=CC=C12 OGWKCGZFUXNPDA-UHFFFAOYSA-N 0.000 description 1
- 229940054953 vitrase Drugs 0.000 description 1
- 208000000318 vitreous detachment Diseases 0.000 description 1
- 238000009736 wetting Methods 0.000 description 1
- 229940109235 zymar Drugs 0.000 description 1
- PAPBSGBWRJIAAV-UHFFFAOYSA-N ε-Caprolactone Chemical compound O=C1CCCCCO1 PAPBSGBWRJIAAV-UHFFFAOYSA-N 0.000 description 1
Images
Classifications
-
- 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
- A61K9/0051—Ocular inserts, ocular implants
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- 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
- 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
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/08—Antiallergic agents
-
- 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
- A61K9/20—Pills, tablets, discs, rods
- A61K9/2004—Excipients; Inactive ingredients
- A61K9/2022—Organic macromolecular compounds
- A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
- A61K9/204—Polyesters, e.g. poly(lactide-co-glycolide)
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Animal Behavior & Ethology (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Engineering & Computer Science (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Inorganic Chemistry (AREA)
- Immunology (AREA)
- Pulmonology (AREA)
- Rheumatology (AREA)
- Pain & Pain Management (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
Description
本明細書において使用される下記の用語は、下記の意味を有する。
「約」は、「およそ」または「ほぼ」を意味し、本明細書に示されている数値または範囲に関して、列挙されているまたは特許請求されている数値または範囲の±10%を意味する。
「複数」は、2またはそれ以上を意味する。
本発明のインプラントは、生分解性ポリマーと混合された、またはそれに分散された活性剤を含有することができる。インプラント組成は、選択された薬剤放出プロフィール、使用される特定の活性剤、治療される眼疾患、および患者の病歴によって変化させることができる。使用しうる活性剤は下記物質を包含するがそれらに限定されない(本発明の範囲内のインプラント中に単独でまたは他の活性剤と組み合わせて使用):ACE(アンジオテンシン転換酵素)阻害薬、内因性サイトカイン、基底膜に影響を与える物質、内皮細胞の増殖に影響を与える物質、アドレナリン作動薬または遮断薬、コリン作動薬または遮断薬、アルドースレダクターゼ阻害薬、鎮痛薬、麻酔薬、抗アレルギー薬、抗炎症薬、抗高血圧薬、昇圧薬、抗細菌薬、抗ウイルス薬、抗真菌薬、抗原虫薬、抗感染薬、抗腫瘍薬、代謝拮抗薬、抗血管新生薬、チロシンキナーゼ阻害薬、抗生物質、例えばアミノグリコシド、例えば、ゲンタマイシン、カナマイシン、ネオマイシンおよびバンコマイシン;アムフェニコール、例えばクロラムフェニコール;セファロスポリン、例えば塩酸セファゾリン;ペニシリン系抗生物質、例えば、アンピシリン、ペニシリン、カルベニシリン、オキシリン、メチシリン;リンコサミド、例えばリンコマイシン;ポリぺプチド抗生物質、例えばポリミキシンおよびバシトラシン;テトラサイクリン系抗生物質、例えばテトラサイクリン;キノロン類、例えばシプロフラキシン等;スルホンアミド、例えばクロラミンT;およびスルホン、例えば親水性物質としてのスルファニル酸、抗ウイルス薬、例えば、アシクロビル、ガンシクロビル、ビダラビン、アジドチミジン、ジデオキシイノシン、ジデオキシシトシン、デキサメタゾン、シプロフラキシン、水溶性抗生物質、例えば、アシクロビル、ガンシクロビル、ビダラビン、アジドチミジン、ジデオキシイノシン、ジデオキシシトシン;エピネフリン;イソフルロフェート;アドリアミシン;ブレオマイシン;マイトマイシン;ara-C;アクチノマイシンD;スコポラミン等;鎮痛薬、例えば、コデイン、モルフィン、ケテロラク、ナプロキセン等、麻酔薬、例えばリドカイン;β−アドレナリン遮断薬またはβ−アドレナリン作動薬、例えば、エピドリン、エピネフリン等;アルドースレダクターゼ阻害薬、例えば、エパルレスタット、ポナルレスタット、ソルビニル、トルレスタット;抗アレルギー薬、例えば、クロモリン、ベクロメタゾン、デキサメタゾンおよびフルニソリド;コルヒチン、駆虫薬、例えば、イベルメクチンおよびスラミンナトリウム;抗アメーバ薬、例えばクロロキンおよびクロルテトラサイクリン;および抗真菌薬、例えば、アンホテリシン等;抗血管新生化合物、例えば、アネコルターブアセテート、レチノイド、例えばTazarotene;抗緑内障薬、例えば、ブリモニジン(AlphaganおよびAlphagan P)、アセトゾラミド、ビマトプロスト(Lumigan)、チモロール、メベフノロール;メマンチン;α−2アドレナリン受容体作動薬;2−メトキシエストラジオール;抗腫瘍薬、例えば、ビンブラスチン、ビンクリスチン、インターフェロンα、β、γ、代謝拮抗薬、例えば、葉酸類似体、プリン類似体およびピリミジン類似体;免疫抑制薬、例えば、アザチオプリン、シクロスポリンおよびミゾリビン;縮瞳薬、例えばカルバコール、散瞳薬、例えばアトロピン等、プロテアーゼ阻害薬、アプロチニン、カモスタット、ガベキサート、血管拡張薬、例えばブラジキニン等、および種々の増殖因子、例えば、上皮増殖因子、塩基性線維芽細胞増殖因子、神経生長因子等。
眼インプラントに使用しうるステロイド性抗炎症薬は、下記物質を包含するが、それらに限定されない:21−アセトキシプレグネノロン、アルクロメタゾン、アルゲストン、アムシノニド、ベクロメタゾン、ベタメタゾン、ブデソニド、クロロプレドニゾン、クロベタゾール、クロベタゾン、クロコルトロン、クロプレドノール、コルチコステロン、コルチゾン、コルチバゾール、デフラザコート、デソニド、デスオキシメタゾン、デキサメタゾン、ジフロラゾン、ジフルコルトロン、ジフルプレドネート、エノキソロン、フルアザコート、フルクロロニド、フルメタゾン、フルニソリド、フルオシノロンアセトニド、フルオシノニド、フルオコルチンブチル、フルオコルトロン、フルオロメトロン、フルペロロンアセテート、フルプレドニデンアセテート、フルプレドニソロン、フルランドレノリド、フルチカソンプロピオネート、ホルモコルタール、ハルシノリド、ハロベタソールプロピオネート、ハロメタゾン、ハロプレドンアセテート、ヒドロコルタメート、ヒドロコルチゾン、ロテプレドノールエタボネート、マジプレドン、メドリゾン、メプレドニゾン、メチルプレドニゾロン、モメタゾンフロエート、パラメタゾン、プレドニカルベート、プレドニゾロン、プレドニゾロン25−ジエチルアミノ−アセテート、燐酸プレドニゾロンナトリウム、プレドニゾン、プレドニバル、プレドニリデン、リメキソロン、チキソコルトール、トリアムシノロン、トリアムシノロンアセトニド、トリアムシノロンベネトニド、トリアムシノロンヘキサアセトニド、およびそれらの任意誘導体。
1つの変形例において、活性剤を、インプラントの生分解性ポリマーに均一に分散させることができる。インプラントは、例えば、逐次(sequential)または二段(double)押出法によって製造することができる。使用される生分解性ポリマーの選択は、所望の放出動態、患者の耐容能(tolerance)、治療される疾患の種類等によって変化しうる。考慮されるポリマー特性は、埋め込み部位における生体適合性および生分解性、対象活性剤との適合性、および加工温度を包含するが、それらに限定されない。生分解性ポリマーマトリックスは、インプラントの少なくとも約10wt%、少なくとも約20wt%、少なくとも約30wt%、少なくとも約40wt%、少なくとも約50wt%、少なくとも約60wt%、少なくとも約70wt%、少なくとも約80wt%、または少なくとも約90wt%を一般に占める。1つの変形例において、生分解性ポリマーマトリックスは、インプラントの約40〜50wt%を占める。
種々の目的のために、他の物質を配合物に使用しうる。例えば、緩衝剤および防腐剤を使用してよい。使用しうる防腐剤は、亜硫酸水素ナトリウム、硫酸水素ナトリウム、チオ硫酸ナトリウム、塩化ベンザルコニウム、クロロブタノール、チメロサール、酢酸フェニル水銀、硝酸フェニル水銀、メチルパラベン、ポリビニルアルコールおよびフェニルエチルアルコールを包含するが、それらに限定されない。使用しうる緩衝剤の例は、所望の投与経路に関してFDAで認可されている炭酸ナトリウム、硼酸ナトリウム、燐酸ナトリウム、酢酸ナトリウム、炭酸水素ナトリウム等を包含する。塩化ナトリウムおよび塩化カリウムのような電解質も配合物に含有させてよい。
本発明のインプラントは、生分解性ポリマーマトリックス内に分散された活性剤の粒子を用いて配合することができる。理論に縛られるものではないが、活性剤の放出は、生分解性ポリマーマトリックスの侵食、かつ、眼液、例えば硝子体液への粒状剤の拡散、次に、ポリマーマトリックスの溶解および活性剤の放出によって達成できると考えられる。インプラントからの活性剤の放出動態に影響を与える要素は、インプラントの大きさおよび形、活性剤粒子の大きさ、活性剤の溶解性、活性剤/ポリマーの比、製造方法、露出される表面積、およびポリマーの侵食速度のような特性を包含しうる。この活性剤放出形態によって得られる放出動態は、例えば架橋ヒドロゲルの場合のような、ポリマー膨潤によって活性剤を放出する配合物によって得られるものとは異なる。その場合、活性剤は、ポリマー侵食によってではなく、ポリマー膨潤および薬剤拡散によって放出され、露出された経路を通って液体が拡散すると共に活性剤を放出する。
本発明のインプラントおよび方法によって治療できる眼疾患の例は、緑内障、ブドウ膜炎、黄斑浮腫、黄斑変性、網膜剥離、後眼腫瘍、真菌またはウイルス感染症、多病巣性脈絡膜炎、糖尿病性網膜症、増殖性硝子体網膜症(PVR)、交感性眼炎、フォークト−コヤナギ−ハラダ(VKH)症候群、ヒストプラスマ症、ブドウ膜拡散および血管閉塞であるが、それらに限定されない。1つの変形例において、インプラントは、ブドウ膜炎、黄斑浮腫、血管閉塞性疾患、増殖性硝子体網膜症(PVR)および種々の他の網膜症のような疾患を治療するのに特に有効である。
生分解性インプラントは、強膜における切開の形成後に、鉗子、トロカール、または他の種類のアプリケーターによる配置を包含する種々の方法によって、眼に挿入できる。ある場合には、切開を形成せずにトロカールまたはアプリケーターを使用しうる。好ましい変形例において、手動操作型アプリケーターを使用して、1つまたはそれ以上の生分解性インプラントを眼に挿入する。手動操作型アプリケーターは一般に、18〜30GAステンレス鋼針、レバー、アクチュエーターおよびプランジャーを有して成る。1つまたはそれ以上のインプラントを後眼領域または部位に挿入するのに好適な装置は、米国特許出願第10/666872号に開示されている装置を包含する。
種々の方法を使用して、本発明のインプラントを製造しうる。有用な方法は、相分離法、界面法、押出法、圧縮法、成型法、射出成形法、ヒートプレス法等を包含する。
活性剤デキサメタゾン(Pharmacia Corp., Peapack, NJ)を、下記の3種類のポリマーのそれぞれと個々に混合して、3種類のデキサメタゾン−ポリマーミックスを形成することによって、デキサメタゾンの長時間送達用の生侵食性インプラントシステムを製造した:
1. ポリ(D,L−ラクチド)(R104、Boehringer Ingelheim GmbH, Germany);
2. ラクチド/グリコリドの75:25(wt%/wt%)ブレンドとしての、ポリ(D,L−ラクチド−コ−グリコリド)(RG755、Boehringer Ingelheim GmbH, Germany);および
3. ポリ(D,L−ラクチド)(R203、Boehringer Ingelheim GmbH, Germany)。
実施例1の三インプラントシステムからのデキサメタゾンの累積放出を、生体外で測定した。受容媒質(0.1M燐酸塩溶液、pH4.4、37℃)を充填したガラス瓶に、三インプラントシステムを入れた。「無限沈下」条件を可能にするために、濃度が飽和の5%を超えないように受容媒質容量を選択した。二次輸送現象、例えば、停滞境界層における濃度分極を最小限にするために、ガラス瓶を37℃において振とう水浴に入れた。HPLC分析のために、試料を、所定時点でガラス瓶から採取した。表1および対応する図1に示すように、濃度値を使用して、累積放出データを計算した。表1において、「日数」は、3つのインプラントから放出されたデキサメタゾン累積量の生体外測定日であり、「Cum.」は、累積の略語であり、「Dex」はデキサメタゾンの略語である。
実施例1の三インプラントシステムを、8匹のウサギの眼の硝子体に埋め込んだ。これは、試料ホルダーおよびプランジャー付きの単純トロカールに実施例1の3つのインプラントを装填し、下方前強膜を切開し、トロカールを強膜切開に挿入し、トロカールプランジャーを押し下げて、実施例1の3つのインプラントを硝子体に配置することによって行った。デキサメタゾンの生体内硝子体濃度を、硝子体試料採取によって、LC/MS(液体クロマトグラフィーおよび質量分析)を使用して追跡した。各眼のデキサメタゾン濃度を、実施例1の三インプラントシステムについて、7、30、60、90、120、150、180、210、240および360日目に測定した。1混合濃度測定の平均結果を、表2の左側の2つの欄に示す。
A. デキサメタゾンを含有する長時間送達インプラントを以下のように製造した。5つの別々のバッチにおいて、活性剤デキサメタゾンと選択ポリマーとを、60wt%デキサメタゾンおよび40wt%ポリマーの比で先ず充分に混合し、以下の5種類の生侵食性ポリマーのそれぞれを使用した:
1. ポリ(D,L−ラクチド)(R203、Boehringer Ingelheim GmbH, Germany);
2. 50%ラクチド/50%グリコール酸(50/50)におけるポリ(D,L−ラクチド−コ−グリコリド)(PLGA)(RG502、Boehringer Ingelheim GmbH, Germany);
3. PLGA遊離酸末端(50/50)(RG502H、Boehringer Ingelheim GmbH, Germany);
4. PLGA(50/50)(R503、Boehringer Ingelheim GmbH, Germany);および
5. PLGA75%ラクチド/25%グリコール酸(RG755、Boehringer Ingelheim GmbH, Germany)。
R203: 分子量約14,000、ラクチド=100%;
RG503: 分子量約28.300、ラクチド=50%、グリコリド=50%;
RG502: 分子量約11,700、ラクチド=50%、グリコリド=50%;
RG502H: 分子量約8,500、ラクチド=50%、グリコリド=50%、ポリマー鎖末端に遊離酸。
実施例4の選択インプラントからのデキサメタゾンの放出を、生体外で測定した。対照インプラントも製造し試験し、対照インプラントは単一ポリマーおよびデキサメタゾン混合物を押し出すことによって製造した。全ての対照群において、試料を50/50wt% デキサメタゾンおよび各ポリマーによって製造し、各1mgインプラントにデキサメタゾン500μgが存在していた。受容媒質(0.1M燐酸塩溶液、pH4.4、37℃)を充填したガラス瓶にインプラントを入れた。「無限沈下」条件を可能にするために、濃度が飽和の5%を超えないように受容媒質容量を選択した。二次輸送現象、例えば、停滞境界層における濃度分極を最小限にするために、ガラス瓶を37℃において振とう水浴に入れた。HPLC分析のために、試料を、1、4、7、14、21、28、35、42および49日目にガラス瓶から採取した。いくつかの試料を、63および77日目にも採取した。表3および図3および4に示すように、濃度値を使用して、累積放出データを計算した。
実施例4のインプラントを、14匹のウサギの各眼の硝子体に埋め込んだ。これは、トロカールにインプラントを装填し、強膜を切開し、トロカールを強膜切開に挿入し、トロカールプランジャーを押し下げて、実施例5の各インプラントを各眼の硝子体に配置することによって行った。デキサメタゾンの生体内硝子体濃度を、硝子体試料採取によって、LC/MSを使用して監視した。各眼について、デキサメタゾン濃度を、7、21、35、49、63、77および112日目に測定した。測定の平均結果を、RG755ポリマー3mg(1500μgデキサメタゾン)インプラント、およびR203(島部)/RG502H(海部)3mg(1500μgデキサメタゾン)インプラントについて、表4に示す。
長時間放出インプラントシステムを使用して、眼疾患を治療することができる。インプラントは、ステロイド、例えば抗炎症性ステロイド、例えばデキサメタゾンを、活性剤として含有することができる。選択的にまたは付加的に、活性剤は、非ステロイド性抗炎症薬、例えばケトララク(Allergan, Irvine, Californiaから、ケトララクトロメタミン眼用液として入手可能)であってもよい。従って、例えば、実施例1または実施例4のデキサメタゾンまたはケトララク長時間放出インプラントシステムを、所望の治療作用のために、眼疾患患者の眼の領域または部位(即ち、硝子体)に埋め込むことができる。眼疾患は、ブドウ膜炎のような炎症性疾患であってよく、または患者が下記疾患の1つまたはそれ以上に罹患していてもよい:黄斑変性(非滲出性老化関連黄斑変性および滲出性老化関連黄斑変性を包含する);脈絡膜新生血管;急性斑状視神経網膜症;黄斑浮腫(類嚢胞黄斑浮腫および糖尿病性黄斑浮腫を包含する);ベーチェット病;糖尿病性網膜症(増殖性糖尿病性網膜症を包含する);網膜動脈閉鎖性疾患;網膜中心静脈閉鎖;ブドウ膜炎網膜疾患;網膜剥離;網膜症;網膜上膜疾患;網膜枝静脈閉鎖;前虚血性視神経障害(anterior ischemic optic neuropathy);非網膜症糖尿病性網膜機能不全;色素性網膜炎および緑内障。インプラントは、実施例2および6に記載した手順(トロカール埋め込み)を使用して、硝子体に挿入することができる。インプラントは、例えばデキサメタゾンまたはケトロラクの治療量を、長時間にわたって放出することができ、それによって眼疾患の症状を治療することができる。
本発明の眼疾患治療用インプラントは、ステロイド、例えば抗血管新生ステロイド、例えばアネコルターブを、活性剤として含有することができる。従って、アネコルターブアセテート(血管新生阻害ステロイド(angiostatic steroid))の長時間送達用の生侵食性インプラントシステムは、実施例1の方法または実施例4の方法を使用し、デキサメタゾンの代わりにアネコルターブアセテートを活性剤として使用して、製造することができる。1つまたはそれ以上のインプラントに、合計約15mgのアネコルターブを装填することができる(即ち、5mgのアネコルターブを、実施例1の方法によって製造した3つのインプラントのそれぞれに装填することができる)。
VEGF(血管内皮成長因子)(VEGF-Aとしても既知)は、血管内皮細胞の成長、生存および増殖を刺激することができる成長因子である。VEGFは、新血管の発生(新脈管形成)および未熟血管の生存(血管維持)において中心的役割を果たしていると考えられる。VEGFの腫瘍発現は、血管網の発生および維持を生じ、これは腫瘍成長および転移を促進する。従って、増加したVEGF発現は、多くの腫瘍型において悪い予後に関係している。VEGFの阻害は、単独でまたは現在の治療法(例えば、放射線療法、化学療法、対象生物学療法)を補うために使用される抗癌療法となりうる。
眼疾患を治療するための長時間放出インプラントシステムは、β−アドレナリン受容体拮抗薬(即ち、「β遮断薬」)、例えば、レボブノロール、ベタキソロール、カルテオロール、チモロール半水和物およびチモロールを含有することができる。マレイン酸チモロールは、開放隅角緑内障の治療に一般に使用される。従って、マレイン酸チモロール(Timoptic, TimopolまたはLoptomitの商品名で種々の供給源から入手可能)を活性剤として含有する長時間放出生侵食性インプラントシステムを、実施例1の方法または実施例4の方法を使用し、デキサメタゾンの代わりにマレイン酸チモロールを使用して製造することができる。例えば、マレイン酸チモロール約50μg〜150μgを、実施例1の方法によって製造された3つの各インプラントに装填することができる。
眼疾患を治療するための長時間放出インプラントシステムは、プロスタミドを含有することができる。プロスタミドは、COX2を包含する経路におけるアナンダミドから生合成される天然物質である。ビマトプロスト(Lumigan;ルミガン)は、プロスタミドFに化学的に関連した合成プロスタミド類似体である。ルミガンは、他のIOP降下薬に不耐性または不充分に反応性の開放隅角緑内障または眼高圧の患者における高い眼内圧(IOP)の減少に関して、FDAによって認可されている。ルミガンは、房水の流出を増加させることによって眼内圧を降下させると考えられる。
α−2アドレナリン受容体作動薬、例えば、クロニジン、アプラクロニジンまたはブリモニジンを活性剤として含有する長時間放出インプラントシステムを使用して、眼疾患を治療することができる。従って、実施例1の方法または実施例4の方法を使用し、デキサメタゾンの代わりにAlphaganを使用して、ブリモニジン(Allergan, Irvine, California;AlphaganまたはAlphagan P)を活性剤として含有する長時間放出生侵食性インプラントシステムを、製造することができる。例えば、Alphagan約50μg〜100μgを、実施例1の方法によって製造された3つの各インプラントに装填することができる。
長時間放出インプラントシステムを使用して眼疾患を治療することができる。インプラントは、エチルニコチネートのようなレチノイド、例えばタザロテンを含有することができる。従って、実施例1の方法または実施例4の方法を使用し、デキサメタゾンの代わりにタザロテンを使用して、タザロテン(Allergan, Irvine, California)を活性剤として含有する長時間放出生侵食性インプラントシステムを製造することができる。例えば、タザロテン約100μg〜500μgを、実施例1の方法によって製造された3つの各インプラントに装填することができる。
一般に、チロシンキナーゼ阻害薬は、成長因子シグナル伝達の小分子阻害薬である。タンパク質チロシンキナーゼ(PTK)は、酵素活性を有する大きくかつ多様な種類のタンパク質を含んで成る。PTKは、細胞増殖および分化の調節において重要な役割を果たしている。例えば、受容体チロシンキナーゼ仲介シグナル伝達は、ある成長因子(リガンド)との細胞外相互作用、次に、受容体二量化、内在性タンパク質チロシンキナーゼ活性の一過性刺激、およびリン酸化によって開始される。それによって、細胞内シグナル伝達分子のために結合部位が形成され、適切な細胞反応(例えば、細胞分裂、代謝性ホメオスタシス、および細胞外微小環境への反応)を促進する細胞質シグナル伝達分子のスペクトラム(a spectrum of cytoplasmic signaling molecules)との複合体を形成する。
グルタメートによるN−メチル−D−アスパルテート(NMDA)受容体の過剰刺激が、種々の疾患に関与していると考えられる。メマンチンはNMDA拮抗薬であり、これを使用して、NMDA受容体複合体によって仲介される神経損傷を減少させることができる。メマンチンは、Merz Pharmaceuticals, Greensboro, North CarolinaからAxuraの商品名で入手できる。長時間放出インプラントシステムを使用して、眼疾患を治療することができる。インプラントは、メマンチンのようなNMDA拮抗薬を含有することができる。従って、メマンチンを活性剤として含有する長時間放出生侵食性インプラントシステムを、実施例1の方法または実施例4の方法を使用し、デキサメタゾンの代わりにメマンチンを使用して製造することができる。例えば、メマンチン約400μg〜700μgを、実施例1の方法によって製造された3つの各インプラントに装填することができる。
あるエストラトロポンは、抗血管新生、抗腫瘍および関連した有用な治療活性を有する。長時間放出インプラントシステムを使用して、眼疾患を治療することができる。インプラントは、2−メトキシエストラジオール(Entremed, Inc., Rockville, Marylandから、Panzemの商品名で入手可能)のようなエストラトロポンを含有することができる。従って、実施例1の方法または実施例4の方法を使用し、デキサメタゾンの代わりに2−メトキシエストラジオールを使用して、メマンチンを活性剤として含有する長時間放出生侵食性インプラントシステムを製造することができる。2−メトキシエストラジオールは、眼の後部における異常血管形成をブロックする小分子血管新生阻害薬として使用することができる。従って、2−メトキシエストラジオール約400μg〜700μgを、実施例1の方法によって製造した3つの各インプラントに装填することができる。
Claims (1)
- 眼疾患の治療用薬剤送達システムであって、該薬剤送達システムが、眼領域または部位に挿入するのに適した第一、第二および第三生侵食性インプラントを含んで成り、
第一生侵食性インプラントは、デキサメタゾンおよび約3500ダルトンの平均分子量を有するポリ(D,L−ラクチド)を含んでなり、
第二生侵食性インプラントは、デキサメタゾンおよびラクチド/グリコリドの75:25(wt%/wt%)ブレンドとしての約40000ダルトンの平均分子量を有するポリ(D,L−ラクチド−コ−グリコリド)を含んでなり、
第三生侵食性インプラントは、デキサメタゾンおよび約14000ダルトンの平均分子量を有するポリ(D,L−ラクチド)を含んでなり、
該薬剤送達システムが、眼領域または部位に挿入された時、治療レベルのデキサメタゾンを、眼領域または部位に、30日〜1年の期間にわたって放出することができる薬剤送達システム。
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US10/837,355 US8685435B2 (en) | 2004-04-30 | 2004-04-30 | Extended release biodegradable ocular implants |
US10/837,355 | 2004-04-30 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007510790A Division JP5128274B2 (ja) | 2004-04-30 | 2005-04-14 | 長時間放出特性を有する生分解性眼インプラント |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2012012408A JP2012012408A (ja) | 2012-01-19 |
JP5552102B2 true JP5552102B2 (ja) | 2014-07-16 |
Family
ID=34966124
Family Applications (4)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007510790A Active JP5128274B2 (ja) | 2004-04-30 | 2005-04-14 | 長時間放出特性を有する生分解性眼インプラント |
JP2011216499A Active JP5552102B2 (ja) | 2004-04-30 | 2011-09-30 | 長時間放出特性を有する生分解性眼インプラント |
JP2012144950A Pending JP2012207028A (ja) | 2004-04-30 | 2012-06-28 | 長時間放出特性を有する生分解性眼インプラント |
JP2014091044A Active JP5706020B2 (ja) | 2004-04-30 | 2014-04-25 | 生分解性眼インプラントの製造方法 |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2007510790A Active JP5128274B2 (ja) | 2004-04-30 | 2005-04-14 | 長時間放出特性を有する生分解性眼インプラント |
Family Applications After (2)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2012144950A Pending JP2012207028A (ja) | 2004-04-30 | 2012-06-28 | 長時間放出特性を有する生分解性眼インプラント |
JP2014091044A Active JP5706020B2 (ja) | 2004-04-30 | 2014-04-25 | 生分解性眼インプラントの製造方法 |
Country Status (10)
Country | Link |
---|---|
US (6) | US8685435B2 (ja) |
EP (2) | EP2777693A1 (ja) |
JP (4) | JP5128274B2 (ja) |
AR (1) | AR048773A1 (ja) |
AU (1) | AU2005244195B2 (ja) |
BR (1) | BRPI0509332A (ja) |
CA (1) | CA2565329C (ja) |
ES (1) | ES2501942T3 (ja) |
TW (1) | TW200603838A (ja) |
WO (1) | WO2005110362A1 (ja) |
Families Citing this family (186)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6726918B1 (en) | 2000-07-05 | 2004-04-27 | Oculex Pharmaceuticals, Inc. | Methods for treating inflammation-mediated conditions of the eye |
ATE306951T1 (de) | 2000-11-29 | 2005-11-15 | Allergan Inc | Verhinderung von transplantatabstossung im auge |
US7431710B2 (en) | 2002-04-08 | 2008-10-07 | Glaukos Corporation | Ocular implants with anchors and methods thereof |
US20050048099A1 (en) | 2003-01-09 | 2005-03-03 | Allergan, Inc. | Ocular implant made by a double extrusion process |
US8685435B2 (en) | 2004-04-30 | 2014-04-01 | Allergan, Inc. | Extended release biodegradable ocular implants |
US7993634B2 (en) | 2004-04-30 | 2011-08-09 | Allergan, Inc. | Oil-in-oil emulsified polymeric implants containing a hypotensive lipid and related methods |
US20050244469A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Extended therapeutic effect ocular implant treatments |
US7799336B2 (en) | 2004-04-30 | 2010-09-21 | Allergan, Inc. | Hypotensive lipid-containing biodegradable intraocular implants and related methods |
US8673341B2 (en) | 2004-04-30 | 2014-03-18 | Allergan, Inc. | Intraocular pressure reduction with intracameral bimatoprost implants |
US8722097B2 (en) | 2004-04-30 | 2014-05-13 | Allergan, Inc. | Oil-in-water method for making polymeric implants containing a hypotensive lipid |
US9498457B2 (en) | 2004-04-30 | 2016-11-22 | Allergan, Inc. | Hypotensive prostamide-containing biodegradable intraocular implants and related implants |
US8529927B2 (en) * | 2004-04-30 | 2013-09-10 | Allergan, Inc. | Alpha-2 agonist polymeric drug delivery systems |
CA2575988C (en) | 2004-08-04 | 2014-02-18 | Brookwood Pharmaceuticals, Inc. | Methods for manufacturing delivery devices and devices thereof |
AU2016228285B2 (en) * | 2004-08-13 | 2018-06-28 | Allergan, Inc. | Ocular implant made by a double extrusion process |
AU2014201844B2 (en) * | 2004-08-13 | 2016-06-16 | Allergan, Inc | Ocular implant made by a double extrusion process |
AU2012216644B2 (en) * | 2004-08-13 | 2014-04-10 | Allergan, Inc. | Ocular implant made by a double extrusion process |
US7931909B2 (en) | 2005-05-10 | 2011-04-26 | Allergan, Inc. | Ocular therapy using alpha-2 adrenergic receptor compounds having enhanced anterior clearance rates |
CA2850858A1 (en) | 2005-09-16 | 2007-04-05 | Allergan, Inc. | Compositions and methods for the intraocular transport of therapeutic agents |
WO2007038453A2 (en) * | 2005-09-26 | 2007-04-05 | Advanced Ocular Systems Limited | Use of an anti-vascular endothelial growth factor (vegf) agent to ameliorate inflammation |
EP1959925B1 (en) * | 2005-12-02 | 2016-11-23 | (OSI) Eyetech, Inc. | Controlled release microparticles |
US20070202186A1 (en) | 2006-02-22 | 2007-08-30 | Iscience Interventional Corporation | Apparatus and formulations for suprachoroidal drug delivery |
DK2010184T3 (da) | 2006-04-06 | 2013-03-25 | Nupathe Inc | Implatanter til behandlingen af dopamin associerede tilstande |
US20070260203A1 (en) * | 2006-05-04 | 2007-11-08 | Allergan, Inc. | Vasoactive agent intraocular implant |
CN101522187A (zh) * | 2006-08-07 | 2009-09-02 | 博士伦公司 | 用于治疗、减轻、改善或缓解后段眼病的组合物和方法 |
CA2664879C (en) * | 2006-09-29 | 2015-03-24 | Surmodics, Inc. | Biodegradable ocular implants and methods for treating ocular conditions |
US20080103368A1 (en) * | 2006-10-17 | 2008-05-01 | Ari Craine | Methods, devices, and computer program products for detecting syndromes |
US8039010B2 (en) | 2006-11-03 | 2011-10-18 | Allergan, Inc. | Sustained release intraocular drug delivery systems comprising a water soluble therapeutic agent and a release modifier |
US8969415B2 (en) * | 2006-12-01 | 2015-03-03 | Allergan, Inc. | Intraocular drug delivery systems |
US20100233194A1 (en) * | 2007-03-30 | 2010-09-16 | Jean-Philippe Combal | Treatment of neovascular ocular disease states |
US8642067B2 (en) | 2007-04-02 | 2014-02-04 | Allergen, Inc. | Methods and compositions for intraocular administration to treat ocular conditions |
US20080317805A1 (en) * | 2007-06-19 | 2008-12-25 | Mckay William F | Locally administrated low doses of corticosteroids |
US9125807B2 (en) * | 2007-07-09 | 2015-09-08 | Incept Llc | Adhesive hydrogels for ophthalmic drug delivery |
US20170360609A9 (en) | 2007-09-24 | 2017-12-21 | Ivantis, Inc. | Methods and devices for increasing aqueous humor outflow |
WO2009085952A1 (en) | 2007-12-20 | 2009-07-09 | Brookwood Pharmaceuticals, Inc. | Process for preparing microparticles having a low residual solvent volume |
AU2009221859B2 (en) | 2008-03-05 | 2013-04-18 | Alcon Inc. | Methods and apparatus for treating glaucoma |
US8524267B2 (en) * | 2008-04-18 | 2013-09-03 | Warsaw Orthopedic, Inc. | Dexamethasone formulations in a biodegradable material |
US9610243B2 (en) | 2008-04-18 | 2017-04-04 | Warsaw Orthopedic, Inc. | Clonidine compounds in a biodegradable polymer |
US8946277B2 (en) * | 2008-04-18 | 2015-02-03 | Warsaw Orthopedic, Inc. | Clonidine formulations in a biodegradable polymer carrier |
US8557273B2 (en) * | 2008-04-18 | 2013-10-15 | Medtronic, Inc. | Medical devices and methods including polymers having biologically active agents therein |
USRE48948E1 (en) | 2008-04-18 | 2022-03-01 | Warsaw Orthopedic, Inc. | Clonidine compounds in a biodegradable polymer |
US8889173B2 (en) | 2008-04-18 | 2014-11-18 | Warsaw Orthopedic, Inc. | Alpha adrenergic receptor agonists for treatment of pain and/or inflammation |
US10588855B2 (en) | 2008-05-12 | 2020-03-17 | University Of Utah Research Foundation | Intraocular drug delivery device and associated methods |
US9877973B2 (en) | 2008-05-12 | 2018-01-30 | University Of Utah Research Foundation | Intraocular drug delivery device and associated methods |
US10064819B2 (en) | 2008-05-12 | 2018-09-04 | University Of Utah Research Foundation | Intraocular drug delivery device and associated methods |
JP5591226B2 (ja) | 2008-05-12 | 2014-09-17 | ユニバーシティ・オブ・ユタ・リサーチ・ファウンデイション | 眼内薬物送達装置および関連する方法 |
US9095404B2 (en) | 2008-05-12 | 2015-08-04 | University Of Utah Research Foundation | Intraocular drug delivery device and associated methods |
PT2894165T (pt) | 2008-11-10 | 2023-03-17 | Alexion Pharma Inc | Métodos e composições para o tratamento de distúrbios associados ao complemento |
US20120232649A1 (en) | 2008-11-20 | 2012-09-13 | Insight Innovations, Llc | Intraocular Lens Cell Migration Inhibition System |
US9943402B2 (en) | 2008-11-20 | 2018-04-17 | Insight Innovations, Llc | Micropatterned intraocular implant |
US8551167B2 (en) | 2008-11-20 | 2013-10-08 | Insight Innovations, Llc | Intraocular implant cell migration inhibition system |
MX2011005272A (es) * | 2008-11-20 | 2011-06-21 | Insight Innovations Llc | Sistema de implante intraocular biocompatible biodegradable. |
US8623395B2 (en) | 2010-01-29 | 2014-01-07 | Forsight Vision4, Inc. | Implantable therapeutic device |
EP2391419B1 (en) | 2009-01-29 | 2019-06-12 | ForSight Vision4, Inc. | Posterior segment drug delivery |
JP5890182B2 (ja) | 2009-02-12 | 2016-03-22 | インセプト エルエルシー | ヒドロゲルプラグによる薬物送達 |
WO2010093945A2 (en) | 2009-02-13 | 2010-08-19 | Glaukos Corporation | Uveoscleral drug delivery implant and methods for implanting the same |
SG173680A1 (en) | 2009-02-24 | 2011-09-29 | Alexion Pharma Inc | Antibodies containing therapeutic tpo/epo mimetic peptides |
US20100239632A1 (en) | 2009-03-23 | 2010-09-23 | Warsaw Orthopedic, Inc. | Drug depots for treatment of pain and inflammation in sinus and nasal cavities or cardiac tissue |
US20100278897A1 (en) * | 2009-05-01 | 2010-11-04 | Allergan, Inc. | Intraocular bioactive agent delivery system with molecular partitioning system |
US10206813B2 (en) | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
US20100314162A1 (en) * | 2009-06-10 | 2010-12-16 | Ppg Industries Ohio, Inc. | Microporous material derived from renewable polymers and articles prepared therefrom |
RU2012102021A (ru) | 2009-06-23 | 2013-07-27 | Алексион Фармасьютикалз, Инк. | Биспецифические антитела, которые связываются с белками комплемента |
AU2010271274B2 (en) | 2009-07-09 | 2015-05-21 | Alcon Inc. | Single operator device for delivering an ocular implant |
EP2451503B1 (en) | 2009-07-09 | 2018-10-24 | Ivantis, Inc. | Ocular implants and methods for delivering ocular implants into the eye |
US9399018B2 (en) * | 2009-09-17 | 2016-07-26 | Evonik Corporation | Implant devices that differ by release profile and methods of making and using same |
WO2011053979A1 (en) * | 2009-11-02 | 2011-05-05 | Nupathe, Inc. | Methods for treating parkinson's disease |
KR101769637B1 (ko) | 2009-11-09 | 2017-08-18 | 알러간, 인코포레이티드 | 모발 성장을 촉진하기 위한 조성물 및 방법 |
US8529492B2 (en) | 2009-12-23 | 2013-09-10 | Trascend Medical, Inc. | Drug delivery devices and methods |
US9011852B2 (en) | 2010-04-30 | 2015-04-21 | Alexion Pharmaceuticals, Inc. | Anti-C5a antibodies |
AU2011270959A1 (en) | 2010-06-22 | 2013-01-10 | Musc Foundation For Research Development | Antibodies to the C3d fragment of complement component 3 |
EP2595602B1 (en) | 2010-07-21 | 2018-05-23 | Allergan, Inc. | SUSTAINED RELEASE siRNA FOR OCULAR DRUG DELIVERY |
PT2600812T (pt) | 2010-08-05 | 2021-11-09 | Forsight Vision4 Inc | Aparelho para tratar um olho |
AU2011285545B2 (en) | 2010-08-05 | 2014-03-13 | Forsight Vision4, Inc. | Injector apparatus and method for drug delivery |
JP6111194B2 (ja) | 2010-08-05 | 2017-04-05 | フォーサイト・ビジョン フォー・インコーポレーテッド | 組み合わせ薬物送達方法および装置 |
JP5996544B2 (ja) | 2010-10-15 | 2016-09-21 | クリアサイド・バイオメディカル・インコーポレーテッドClearside Biomedical Incorporated | 眼球アクセス用装置 |
EP2640360A2 (en) | 2010-11-19 | 2013-09-25 | Forsight Vision4, Inc. | Therapeutic agent formulations for implanted devices |
US9668915B2 (en) | 2010-11-24 | 2017-06-06 | Dose Medical Corporation | Drug eluting ocular implant |
AU2012212066A1 (en) | 2011-02-03 | 2013-08-15 | Alexion Pharmaceuticals, Inc. | Use of an anti-CD200 antibody for prolonging the survival of allografts |
US10245178B1 (en) | 2011-06-07 | 2019-04-02 | Glaukos Corporation | Anterior chamber drug-eluting ocular implant |
SI2717914T1 (sl) * | 2011-06-10 | 2020-07-31 | Ramscor Inc. | Formulacije z zadržanim sproščanjem za dostavo proteinov v oko in postopki njihove priprave |
US8657776B2 (en) | 2011-06-14 | 2014-02-25 | Ivantis, Inc. | Ocular implants for delivery into the eye |
EP4249059A3 (en) | 2011-06-28 | 2023-11-29 | ForSight Vision4, Inc. | An apparatus for collecting a sample of fluid from a reservoir chamber of a therapeutic device for the eye |
EP2739252A4 (en) | 2011-08-05 | 2015-08-12 | Forsight Vision4 Inc | SMALL MOLECULE ADMINISTRATION USING AN IMPLANTABLE THERAPEUTIC DEVICE |
US10226417B2 (en) | 2011-09-16 | 2019-03-12 | Peter Jarrett | Drug delivery systems and applications |
HUE054578T2 (hu) | 2011-09-16 | 2021-09-28 | Forsight Vision4 Inc | Fluidumcserélõ berendezés |
US8663150B2 (en) | 2011-12-19 | 2014-03-04 | Ivantis, Inc. | Delivering ocular implants into the eye |
US10010448B2 (en) | 2012-02-03 | 2018-07-03 | Forsight Vision4, Inc. | Insertion and removal methods and apparatus for therapeutic devices |
EP2812372B1 (en) | 2012-02-09 | 2018-09-26 | Novus International Inc. | Heteroatom containing cyclic dimers |
US9358156B2 (en) | 2012-04-18 | 2016-06-07 | Invantis, Inc. | Ocular implants for delivery into an anterior chamber of the eye |
US9452143B2 (en) | 2012-07-12 | 2016-09-27 | Novus International, Inc. | Matrix and layer compositions for protection of bioactives |
AU2013302441B2 (en) | 2012-08-17 | 2018-05-10 | The Regents Of The University Of Colorado, A Body Corporate | Compositions and methods for detecting complement activation |
US10413620B2 (en) | 2012-08-17 | 2019-09-17 | The Regents Of The University Of Colorado, A Body Corporate | Light-emitting versions of the monoclonal antibody to C3D (MAB 3D29) for imaging |
RU2676102C2 (ru) | 2012-09-27 | 2018-12-26 | Аллерган, Инк. | Биодеградируемые системы доставки лекарственных средств для долговременного высвобождения белков |
WO2014066658A1 (en) * | 2012-10-26 | 2014-05-01 | Allergan, Inc. | Ketorolac-containing sustained release drug delivery systems |
WO2014066653A1 (en) * | 2012-10-26 | 2014-05-01 | Allergan, Inc. | Ketorolac-containing sustained release intraocular drug delivery systems |
WO2014066644A1 (en) * | 2012-10-26 | 2014-05-01 | Allergan, Inc. | Ketorolac-containing sustained release drug delivery systems |
CN104884049A (zh) | 2012-11-08 | 2015-09-02 | 克莱尔塞德生物医学股份有限公司 | 用于在人类受试者中治疗眼部疾病的方法和装置 |
US10617558B2 (en) | 2012-11-28 | 2020-04-14 | Ivantis, Inc. | Apparatus for delivering ocular implants into an anterior chamber of the eye |
BR112015019546A2 (pt) | 2013-02-15 | 2017-07-18 | Allergan Inc | implante de distribuição de drogas prolongado |
WO2014152959A1 (en) | 2013-03-14 | 2014-09-25 | Forsight Vision4, Inc. | Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant |
US10517759B2 (en) | 2013-03-15 | 2019-12-31 | Glaukos Corporation | Glaucoma stent and methods thereof for glaucoma treatment |
EP2978393B1 (en) | 2013-03-28 | 2023-12-27 | ForSight Vision4, Inc. | Ophthalmic implant for delivering therapeutic substances |
ES2768648T3 (es) | 2013-03-29 | 2020-06-23 | Alexion Pharma Inc | Composiciones y métodos para aumentar la semivida en suero de un agente terapéutico dirigido a C5 del complemento |
MX2015015282A (es) | 2013-05-03 | 2016-02-26 | Clearside Biomedical Inc | Aparatos y metodos para inyeccion ocular. |
US10188550B2 (en) | 2013-06-03 | 2019-01-29 | Clearside Biomedical, Inc. | Apparatus and methods for drug delivery using multiple reservoirs |
KR101834469B1 (ko) | 2013-08-07 | 2018-03-06 | 알렉시온 파마슈티칼스, 인코포레이티드 | 비정형적 용혈성 요독증후군 (ahus) 바이오마커 단백질 |
JP6543431B2 (ja) * | 2013-10-10 | 2019-07-10 | ユニバーシティー オブ ユタ リサーチ ファウンデーションUniversity of Utah Research Foundation | 眼内薬物送達デバイスおよび付随する方法 |
MY177958A (en) | 2013-10-31 | 2020-09-28 | Allergan Inc | Prostamide-containing intraocular implants and methods of use thereof |
EP3065793B1 (en) * | 2013-11-08 | 2021-04-14 | Hollister Incorporated | Oleophilic lubricated catheters |
EP3714875A1 (en) * | 2013-11-15 | 2020-09-30 | Allergan, Inc. | Methods of treatment of ocular conditions with a sustained drug delivery implant |
NZ631007A (en) | 2014-03-07 | 2015-10-30 | Alexion Pharma Inc | Anti-c5 antibodies having improved pharmacokinetics |
JP6655610B2 (ja) | 2014-05-29 | 2020-02-26 | グローコス コーポレーション | 制御された薬物送達機能を備えるインプラント及びそれを使用する方法 |
US20180042765A1 (en) * | 2014-06-17 | 2018-02-15 | Clearside Biomedical, Inc. | Methods and devices for treating posterior ocular disorders |
MX2016017028A (es) | 2014-06-20 | 2017-08-07 | Clearside Biomedical Inc | Canula de diametro variable y metodos para el control de la profundidad de insercion para administracion de medicamentos. |
US10709547B2 (en) | 2014-07-14 | 2020-07-14 | Ivantis, Inc. | Ocular implant delivery system and method |
WO2016011191A1 (en) | 2014-07-15 | 2016-01-21 | Forsight Vision4, Inc. | Ocular implant delivery device and method |
EP3177289A4 (en) | 2014-08-08 | 2018-03-21 | Forsight Vision4, Inc. | Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof |
BR112017006552A2 (pt) | 2014-10-03 | 2017-12-19 | Ntercept Llc | composições e métodos para inibir a atividade biológica de biomoléculas solúveis |
SG11201703726XA (en) | 2014-11-10 | 2017-06-29 | Forsight Vision4 Inc | Expandable drug delivery devices and method of use |
FR3028410A1 (fr) | 2014-11-18 | 2016-05-20 | Pierre Coulon | Implant capsulaire multifonctionnel |
JP6882186B2 (ja) * | 2014-12-15 | 2021-06-02 | ザ ジョーンズ ホプキンズ ユニバーシティThe Johns Hopkins University | スニチニブ製剤及び眼の障害の治療におけるその使用に対する方法 |
CN107428818A (zh) | 2015-01-29 | 2017-12-01 | 密西根州立大学校董会 | 隐藏多肽及其用途 |
CA2978600A1 (en) | 2015-03-06 | 2016-09-15 | Envisia Therapeutics, Inc. | Implant applicators and methods of administering implants |
CA2979397A1 (en) | 2015-03-12 | 2016-09-15 | Board Of Trustees Of Michigan State University | Compositions and methods for measuring c-peptide binding and diagnosing immune-mediated diseases |
US20180104331A1 (en) | 2015-05-11 | 2018-04-19 | The Johns Hopkins University | Autoimmune antibodies for use in inhibiting cancer cell growth |
EP4279064A3 (en) | 2015-05-12 | 2024-02-28 | Incept, LLC | Drug delivery from hydrogels |
JP2018525078A (ja) | 2015-07-22 | 2018-09-06 | インセプト・リミテッド・ライアビリティ・カンパニーIncept,Llc | 被覆された涙点プラグ |
AU2016297187A1 (en) | 2015-07-23 | 2018-02-15 | Aerie Pharmaceuticals, Inc. | Intravitreal drug delivery systems for the treatment of ocular conditions |
CA2995240A1 (en) | 2015-08-14 | 2017-02-23 | Ivantis, Inc. | Ocular implant with pressure sensor and delivery system |
US11925578B2 (en) | 2015-09-02 | 2024-03-12 | Glaukos Corporation | Drug delivery implants with bi-directional delivery capacity |
US11564833B2 (en) | 2015-09-25 | 2023-01-31 | Glaukos Corporation | Punctal implants with controlled drug delivery features and methods of using same |
GB201519811D0 (en) * | 2015-11-10 | 2015-12-23 | Univ Belfast | Ocular compositions |
BR112018009644A2 (pt) | 2015-11-12 | 2018-11-06 | Graybug Vision Inc | micropartículas agregantes sólidas modificadas na superfície, material injetável, processo para preparação de micropartículas agregantes sólidas modificadas na superfície, método para tratamento de um distúrbio ocular, e, uso de micropartículas agregantes sólidas modificadas na superfície |
CN108430405B (zh) | 2015-11-20 | 2021-04-13 | 弗赛特影像4股份有限公司 | 用于缓释药物递送装置的多孔结构 |
US11938058B2 (en) | 2015-12-15 | 2024-03-26 | Alcon Inc. | Ocular implant and delivery system |
US10390901B2 (en) | 2016-02-10 | 2019-08-27 | Clearside Biomedical, Inc. | Ocular injection kit, packaging, and methods of use |
PT109154B (pt) * | 2016-02-12 | 2019-11-05 | Univ De Coimbra | Tecnologia não-invasiva de inserto ocular para libertação controlada de fármacos |
WO2017176886A1 (en) | 2016-04-05 | 2017-10-12 | Forsight Vision4, Inc. | Implantable ocular drug delivery devices |
WO2017176762A1 (en) | 2016-04-06 | 2017-10-12 | Nanotics, Llc | Particles comprising subparticles or nucleic acid scaffolds |
US11318043B2 (en) | 2016-04-20 | 2022-05-03 | Dose Medical Corporation | Bioresorbable ocular drug delivery device |
EP3452165A1 (en) | 2016-05-02 | 2019-03-13 | Clearside Biomedical, Inc. | Systems and methods for ocular drug delivery |
CN110177527B (zh) | 2016-08-12 | 2022-02-01 | 科尼尔赛德生物医学公司 | 用于调节药剂递送用针的插入深度的装置和方法 |
RU2019133337A (ru) | 2017-03-23 | 2021-04-23 | Грейбуг Вижн, Инк. | Лекарственные средства и композиции для лечения глазных нарушений |
AU2018265415A1 (en) | 2017-05-10 | 2019-10-31 | Graybug Vision, Inc. | Extended release microparticles and suspensions thereof for medical therapy |
CA3077101A1 (en) | 2017-06-13 | 2018-12-20 | Innfocus, Inc. | Systems, methods, and apparatus for treatment of glaucoma |
US20190062428A1 (en) | 2017-06-19 | 2019-02-28 | Surface Oncology, Inc. | Combination of anti-cd47 antibodies and cell death-inducing agents, and uses thereof |
KR20200035966A (ko) | 2017-07-11 | 2020-04-06 | 콤파스 테라퓨틱스 엘엘씨 | 인간 cd137에 결합하는 작동자 항체 및 이의 용도 |
EP4218813A3 (en) | 2017-07-27 | 2023-08-16 | Alexion Pharmaceuticals, Inc. | High concentration anti-c5 antibody formulations |
US10584306B2 (en) | 2017-08-11 | 2020-03-10 | Board Of Regents Of The University Of Oklahoma | Surfactant microemulsions |
WO2019036605A2 (en) | 2017-08-17 | 2019-02-21 | Massachusetts Institute Of Technology | MULTIPLE SPECIFICITY BINDING AGENTS OF CXC CHEMOKINES AND USES THEREOF |
SG11202001379WA (en) | 2017-09-08 | 2020-03-30 | Bristol Myers Squibb Co | Modified fibroblast growth factor 21 (fgf-21) for use in methods for treating nonalcoholic steatohepatitis (nash) |
WO2019067499A1 (en) | 2017-09-27 | 2019-04-04 | Alexion Pharmaceuticals, Inc. | BIOMARKER SIGNATURE FOR PREDICTING A TUMOR RESPONSE TO ANTI-CD200 THERAPY |
WO2019089753A2 (en) | 2017-10-31 | 2019-05-09 | Compass Therapeutics Llc | Cd137 antibodies and pd-1 antagonists and uses thereof |
EP3713961A2 (en) | 2017-11-20 | 2020-09-30 | Compass Therapeutics LLC | Cd137 antibodies and tumor antigen-targeting antibodies and uses thereof |
WO2019103906A1 (en) | 2017-11-21 | 2019-05-31 | Forsight Vision4, Inc. | Fluid exchange apparatus for expandable port delivery system and methods of use |
KR20230020023A (ko) | 2018-03-14 | 2023-02-09 | 서피스 온콜로지, 인크. | Cd39에 결합하는 항체 및 이의 용도 |
JP7328983B2 (ja) | 2018-03-22 | 2023-08-17 | サーフィス オンコロジー インコーポレイテッド | 抗il-27抗体及びその使用 |
WO2019200357A1 (en) | 2018-04-12 | 2019-10-17 | Surface Oncology, Inc. | Biomarker for cd47 targeting therapeutics and uses therefor |
CN112105733A (zh) | 2018-04-19 | 2020-12-18 | 查美特制药公司 | 合成rig-i样受体激动剂 |
CA3099308A1 (en) | 2018-05-21 | 2019-11-28 | Compass Therapeutics Llc | Compositions and methods for enhancing the killing of target cells by nk cells |
WO2019226658A1 (en) | 2018-05-21 | 2019-11-28 | Compass Therapeutics Llc | Multispecific antigen-binding compositions and methods of use |
WO2020018715A1 (en) | 2018-07-17 | 2020-01-23 | Massachusetts Institute Of Technology | Soluble multimeric immunoglobulin-scaffold based fusion proteins and uses thereof |
WO2020033925A2 (en) | 2018-08-09 | 2020-02-13 | Compass Therapeutics Llc | Antibodies that bind cd277 and uses thereof |
WO2020033923A1 (en) | 2018-08-09 | 2020-02-13 | Compass Therapeutics Llc | Antigen binding agents that bind cd277 and uses thereof |
WO2020033926A2 (en) | 2018-08-09 | 2020-02-13 | Compass Therapeutics Llc | Antibodies that bind cd277 and uses thereof |
AU2019379576A1 (en) | 2018-11-13 | 2021-06-03 | Compass Therapeutics Llc | Multispecific binding constructs against checkpoint molecules and uses thereof |
BR112021013571A2 (pt) | 2019-01-16 | 2021-09-21 | Compass Therapeutics Llc | Formulações de anticorpos que se ligam a cd137 humano e usos das mesmas |
WO2020163782A2 (en) | 2019-02-08 | 2020-08-13 | The Uab Research Foundation | Immunotherapy for the treatment and prevention of inflammatory bowel disease |
US11883525B2 (en) * | 2019-05-31 | 2024-01-30 | Dose Medical Corporation | Bioerodible polyester polymer axitinib ocular implants and related methods of use |
GB2601922B (en) | 2019-06-27 | 2024-04-24 | Layerbio Inc | Ocular device drub delivery systems |
BR112022002351A2 (pt) | 2019-09-16 | 2022-07-19 | Surface Oncology Inc | Composições e métodos de anticorpo anti-cd39 |
WO2021062244A1 (en) | 2019-09-25 | 2021-04-01 | Surface Oncology, Inc. | Anti-il-27 antibodies and uses thereof |
US20220356234A1 (en) | 2019-10-02 | 2022-11-10 | Alexion Pharmaceuticals, Inc. | Complement inhibitors for treating drug-induced complement-mediated response |
CA3155202A1 (en) | 2019-10-23 | 2021-04-29 | Arthur M. Krieg | Synthetic rig-i-like receptor agonists |
US11459389B2 (en) | 2019-10-24 | 2022-10-04 | Massachusetts Institute Of Technology | Monoclonal antibodies that bind human CD161 |
JP7451732B2 (ja) | 2020-02-06 | 2024-03-18 | オキュラ セラピューティクス,インコーポレイテッド | 眼疾患を治療するための組成物及び方法 |
BR112022018815A2 (pt) | 2020-03-25 | 2022-11-29 | Ocular Therapeutix Inc | Implante ocular contendo um inibidor de tirosina cinase |
US20230349887A1 (en) | 2020-05-15 | 2023-11-02 | Alexion Pharmaceuticals, Inc. | Method of using extracellular vesicles to detect complement activation, and uses thereof to assess and/or monitor treatment of a complement-mediated disease |
AU2021313151A1 (en) | 2020-07-21 | 2023-03-16 | Allergan, Inc. | Intraocular implant with high loading of a prostamide |
WO2022150684A1 (en) | 2021-01-11 | 2022-07-14 | Ivantis, Inc. | Systems and methods for viscoelastic delivery |
IL308198A (en) | 2021-05-07 | 2024-01-01 | Surface Oncology Llc | Anti-IL-27 antibodies and uses thereof |
EP4348263A1 (en) | 2021-05-28 | 2024-04-10 | Alexion Pharmaceuticals, Inc. | Methods for detecting cm-tma biomarkers |
WO2023230116A1 (en) | 2022-05-25 | 2023-11-30 | Surface Oncology, Inc. | Use of anti-il-27 antibodies |
WO2023230128A1 (en) | 2022-05-25 | 2023-11-30 | Surface Oncology, Inc. | Use of anti-il-27 antibodies |
WO2024037982A1 (en) | 2022-08-16 | 2024-02-22 | Boehringer Ingelheim International Gmbh | Pharmaceutical formulations of nintedanib for intraocular use |
WO2024054436A1 (en) | 2022-09-06 | 2024-03-14 | Alexion Pharmaceuticals, Inc. | Diagnostic and prognostic biomarker profiles in patients with hematopoietic stem cell transplant-associated thrombotic microangiopathy (hsct-tma) |
WO2024086306A1 (en) * | 2022-10-19 | 2024-04-25 | Vitakey Inc. | Formulated food products |
Family Cites Families (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US19098A (en) * | 1858-01-12 | Valve arrangement for steam-engines | ||
DE430539C (de) | 1922-04-21 | 1926-06-23 | J G Farbenindustrie Akt Ges | Verfahren zur Darstellung von AEthylenchlorid |
US3986510A (en) | 1971-09-09 | 1976-10-19 | Alza Corporation | Bioerodible ocular device |
US3976071A (en) * | 1974-01-07 | 1976-08-24 | Dynatech Corporation | Methods of improving control of release rates and products useful in same |
US3985510A (en) * | 1974-05-28 | 1976-10-12 | Taylor Fred W | Flash reactor unit |
US4304765A (en) | 1980-10-14 | 1981-12-08 | Alza Corporation | Ocular insert housing steroid in two different therapeutic forms |
US5286763A (en) * | 1983-03-22 | 1994-02-15 | Massachusetts Institute Of Technology | Bioerodible polymers for drug delivery in bone |
JPS6050051U (ja) | 1983-09-14 | 1985-04-08 | 日産車体株式会社 | 自動車のリヤスピ−カ取付け構造 |
US6309669B1 (en) | 1984-03-16 | 2001-10-30 | The United States Of America As Represented By The Secretary Of The Army | Therapeutic treatment and prevention of infections with a bioactive materials encapsulated within a biodegradable-biocompatible polymeric matrix |
US4966849A (en) | 1985-09-20 | 1990-10-30 | President And Fellows Of Harvard College | CDNA and genes for human angiogenin (angiogenesis factor) and methods of expression |
JPH01500034A (ja) | 1986-04-10 | 1989-01-12 | ダラテック プロプライエタリー リミテッド | ワクチンおよび植込剤 |
US4863457A (en) | 1986-11-24 | 1989-09-05 | Lee David A | Drug delivery device |
US4997652A (en) | 1987-12-22 | 1991-03-05 | Visionex | Biodegradable ocular implants |
US4853224A (en) | 1987-12-22 | 1989-08-01 | Visionex | Biodegradable ocular implants |
JP2702729B2 (ja) | 1988-02-24 | 1998-01-26 | エーザイ株式会社 | 徐放性埋込剤 |
JPH0216917A (ja) | 1988-07-05 | 1990-01-19 | Iseki & Co Ltd | 脱穀装置の拡散装置 |
US5164188A (en) | 1989-11-22 | 1992-11-17 | Visionex, Inc. | Biodegradable ocular implants |
WO1991015495A1 (en) | 1990-04-02 | 1991-10-17 | Pfizer Inc. | Benzylphosphonic acid tyrosine kinase inhibitors |
KR0185215B1 (ko) * | 1990-11-30 | 1999-05-01 | 요시다 쇼오지 | 서방성 안구삽입용 약제 |
US5378475A (en) | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
EP0586608A1 (en) | 1991-05-29 | 1994-03-16 | Pfizer Inc. | Tricyclic polyhydroxylic tyrosine kinase inhibitors |
CA2140440A1 (en) | 1992-08-06 | 1994-02-17 | Ellen M. Dobrusin | 2-thioindoles (selenoindoles) and related disulfides (selenides) which inhibit protein tyrosine kinases and which have antitumor properties |
US5330992A (en) | 1992-10-23 | 1994-07-19 | Sterling Winthrop Inc. | 1-cyclopropyl-4-pyridyl-quinolinones |
RO119721B1 (ro) | 1992-10-28 | 2005-02-28 | Genentech Inc. | Antagonişti ai factorului de creştere al celulelor vasculare endoteliale |
GB9226855D0 (en) | 1992-12-23 | 1993-02-17 | Erba Carlo Spa | Vinylene-azaindole derivatives and process for their preparation |
DE69425411T2 (de) | 1993-02-26 | 2001-02-08 | Santen Pharmaceutical Co Ltd | Biologisch abbaubarer sklerastopfen |
US5443505A (en) | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
AU4611496A (en) | 1995-02-28 | 1996-09-18 | Innapharma, Inc. | Elcatonin controlled release microsphere formulation for treatment of osteoporosis |
US6369116B1 (en) | 1995-06-02 | 2002-04-09 | Oculex Pharmaceuticals, Inc. | Composition and method for treating glaucoma |
US5869079A (en) | 1995-06-02 | 1999-02-09 | Oculex Pharmaceuticals, Inc. | Formulation for controlled release of drugs by combining hydrophilic and hydrophobic agents |
US6046187A (en) | 1996-09-16 | 2000-04-04 | Children's Medical Center Corporation | Formulations and methods for providing prolonged local anesthesia |
WO1999001156A1 (fr) | 1997-07-02 | 1999-01-14 | Santen Pharmaceutical Co., Ltd. | Bouchons scleraux d'acide polylactique |
JPH1170138A (ja) * | 1997-07-02 | 1999-03-16 | Santen Pharmaceut Co Ltd | ポリ乳酸強膜プラグ |
US6306426B1 (en) | 1997-08-11 | 2001-10-23 | Allergan Sales, Inc. | Implant device with a retinoid for improved biocompatibility |
US6217895B1 (en) | 1999-03-22 | 2001-04-17 | Control Delivery Systems | Method for treating and/or preventing retinal diseases with sustained release corticosteroids |
US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
US20040208910A1 (en) * | 2000-04-26 | 2004-10-21 | Control Delivery Systems, Inc. | Sustained release device and method for ocular delivery of adrenergic agents |
US6726918B1 (en) * | 2000-07-05 | 2004-04-27 | Oculex Pharmaceuticals, Inc. | Methods for treating inflammation-mediated conditions of the eye |
EP1550471A1 (en) | 2000-11-29 | 2005-07-06 | Allergan Inc. | Intraocular implants for preventing transplant rejection in the eye |
ATE306951T1 (de) | 2000-11-29 | 2005-11-15 | Allergan Inc | Verhinderung von transplantatabstossung im auge |
DE60238665D1 (de) * | 2001-02-27 | 2011-02-03 | Senju Pharma Co | Arzneimittelfreisetzungssystem aus einem biologisch abbaubaren polymer |
US6713081B2 (en) * | 2001-03-15 | 2004-03-30 | The United States Of America As Represented By The Department Of Health And Human Services | Ocular therapeutic agent delivery devices and methods for making and using such devices |
CA2451187C (en) * | 2001-06-22 | 2012-08-14 | Southern Biosystems, Inc. | Zero-order prolonged release coaxial implants |
US6488952B1 (en) * | 2001-08-28 | 2002-12-03 | John P. Kennedy | Semisolid therapeutic delivery system and combination semisolid, multiparticulate, therapeutic delivery system |
US20030134810A1 (en) | 2001-10-09 | 2003-07-17 | Chris Springate | Methods and compositions comprising biocompatible materials useful for the administration of therapeutic agents |
WO2003051328A1 (en) | 2001-12-18 | 2003-06-26 | Novo Nordisk A/S | Solid dose micro implant |
US6541504B1 (en) | 2002-04-03 | 2003-04-01 | Allergan Sales, Llc | (3Z)-3-(2,3-dihydro-1H-inden-1-ylidene)-1,3-dihydro-2H-indol-2-ones as kinase inhibitors |
BR0309844A (pt) | 2002-05-07 | 2005-02-15 | Control Delivery Sys Inc | Processos para formação de um dispositivo para a distribuição de droga |
TWI282271B (en) | 2002-09-18 | 2007-06-11 | Allergan Inc | Apparatus for delivery of ocular implants |
AU2003295409B2 (en) * | 2002-11-06 | 2010-02-11 | Durect Corporation | Controlled release depot formulations |
US20040137059A1 (en) | 2003-01-09 | 2004-07-15 | Thierry Nivaggioli | Biodegradable ocular implant |
US20050244469A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Extended therapeutic effect ocular implant treatments |
US8685435B2 (en) | 2004-04-30 | 2014-04-01 | Allergan, Inc. | Extended release biodegradable ocular implants |
US20050244500A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Intravitreal implants in conjuction with photodynamic therapy to improve vision |
US20050244466A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Photodynamic therapy in conjunction with intraocular implants |
US8119154B2 (en) | 2004-04-30 | 2012-02-21 | Allergan, Inc. | Sustained release intraocular implants and related methods |
-
2004
- 2004-04-30 US US10/837,355 patent/US8685435B2/en active Active
-
2005
- 2005-04-14 BR BRPI0509332-5A patent/BRPI0509332A/pt not_active IP Right Cessation
- 2005-04-14 CA CA2565329A patent/CA2565329C/en active Active
- 2005-04-14 EP EP14172330.4A patent/EP2777693A1/en active Pending
- 2005-04-14 WO PCT/US2005/013143 patent/WO2005110362A1/en not_active Application Discontinuation
- 2005-04-14 EP EP05735919.2A patent/EP1740153B2/en active Active
- 2005-04-14 ES ES05735919.2T patent/ES2501942T3/es active Active
- 2005-04-14 JP JP2007510790A patent/JP5128274B2/ja active Active
- 2005-04-14 AU AU2005244195A patent/AU2005244195B2/en not_active Ceased
- 2005-04-29 TW TW094113990A patent/TW200603838A/zh unknown
- 2005-05-02 AR ARP050101753A patent/AR048773A1/es not_active Application Discontinuation
-
2008
- 2008-05-01 US US12/113,434 patent/US20080241223A1/en not_active Abandoned
-
2011
- 2011-09-30 JP JP2011216499A patent/JP5552102B2/ja active Active
-
2012
- 2012-06-28 JP JP2012144950A patent/JP2012207028A/ja active Pending
-
2013
- 2013-10-08 US US14/048,255 patent/US8895049B2/en not_active Expired - Lifetime
-
2014
- 2014-02-26 US US14/191,165 patent/US8974812B2/en not_active Expired - Lifetime
- 2014-04-25 JP JP2014091044A patent/JP5706020B2/ja active Active
-
2015
- 2015-01-30 US US14/610,780 patent/US10154960B2/en not_active Expired - Lifetime
-
2018
- 2018-12-17 US US16/222,886 patent/US10874605B2/en not_active Expired - Lifetime
Also Published As
Publication number | Publication date |
---|---|
JP5706020B2 (ja) | 2015-04-22 |
AU2005244195B2 (en) | 2011-06-30 |
US10154960B2 (en) | 2018-12-18 |
US20150209276A1 (en) | 2015-07-30 |
US8895049B2 (en) | 2014-11-25 |
US20190254964A1 (en) | 2019-08-22 |
JP2014133772A (ja) | 2014-07-24 |
WO2005110362A1 (en) | 2005-11-24 |
ES2501942T3 (es) | 2014-10-02 |
JP5128274B2 (ja) | 2013-01-23 |
EP2777693A1 (en) | 2014-09-17 |
JP2012207028A (ja) | 2012-10-25 |
JP2012012408A (ja) | 2012-01-19 |
US20050244467A1 (en) | 2005-11-03 |
CA2565329A1 (en) | 2005-11-24 |
TW200603838A (en) | 2006-02-01 |
US20080241223A1 (en) | 2008-10-02 |
US20140035184A1 (en) | 2014-02-06 |
US8974812B2 (en) | 2015-03-10 |
US20140249123A1 (en) | 2014-09-04 |
US8685435B2 (en) | 2014-04-01 |
AR048773A1 (es) | 2006-05-24 |
AU2005244195A1 (en) | 2005-11-24 |
EP1740153B1 (en) | 2014-06-25 |
US10874605B2 (en) | 2020-12-29 |
EP1740153A1 (en) | 2007-01-10 |
CA2565329C (en) | 2014-10-07 |
JP2007535535A (ja) | 2007-12-06 |
EP1740153B2 (en) | 2017-08-09 |
BRPI0509332A (pt) | 2007-09-04 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US10874605B2 (en) | Extended release biodegradable ocular implants | |
US9233071B2 (en) | Methods for treating retinopathy with extended therapeutic effect | |
US8956655B2 (en) | Biodegradable drug delivery system | |
AU2011226867B2 (en) | Biodegradable ocular implants with long-term release characteristics |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20130613 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20130618 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20130917 |
|
TRDD | Decision of grant or rejection written | ||
A01 | Written decision to grant a patent or to grant a registration (utility model) |
Free format text: JAPANESE INTERMEDIATE CODE: A01 Effective date: 20140507 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20140523 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5552102 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |