JP2013538082A - 組み合わせ薬物送達方法および装置 - Google Patents
組み合わせ薬物送達方法および装置 Download PDFInfo
- Publication number
- JP2013538082A JP2013538082A JP2013523372A JP2013523372A JP2013538082A JP 2013538082 A JP2013538082 A JP 2013538082A JP 2013523372 A JP2013523372 A JP 2013523372A JP 2013523372 A JP2013523372 A JP 2013523372A JP 2013538082 A JP2013538082 A JP 2013538082A
- Authority
- JP
- Japan
- Prior art keywords
- therapeutic agent
- therapeutic
- inhibitor
- release
- reservoir
- 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.)
- Granted
Links
- 238000000034 method Methods 0.000 title claims abstract description 70
- 238000012377 drug delivery Methods 0.000 title claims description 18
- 229940000425 combination drug Drugs 0.000 title 1
- 239000003814 drug Substances 0.000 claims abstract description 686
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 620
- 230000001225 therapeutic effect Effects 0.000 claims abstract description 350
- 239000002525 vasculotropin inhibitor Substances 0.000 claims abstract description 27
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 claims abstract description 14
- 229940122204 Cyclooxygenase inhibitor Drugs 0.000 claims abstract description 12
- 210000004127 vitreous body Anatomy 0.000 claims description 144
- 239000000203 mixture Substances 0.000 claims description 133
- 238000009472 formulation Methods 0.000 claims description 132
- 238000001802 infusion Methods 0.000 claims description 90
- 229960003876 ranibizumab Drugs 0.000 claims description 87
- 210000003786 sclera Anatomy 0.000 claims description 75
- 239000003112 inhibitor Substances 0.000 claims description 65
- -1 siproxyphan Chemical compound 0.000 claims description 32
- 239000007787 solid Substances 0.000 claims description 28
- 229940124638 COX inhibitor Drugs 0.000 claims description 26
- 229960000590 celecoxib Drugs 0.000 claims description 20
- RZEKVGVHFLEQIL-UHFFFAOYSA-N celecoxib Chemical compound C1=CC(C)=CC=C1C1=CC(C(F)(F)F)=NN1C1=CC=C(S(N)(=O)=O)C=C1 RZEKVGVHFLEQIL-UHFFFAOYSA-N 0.000 claims description 20
- 230000028709 inflammatory response Effects 0.000 claims description 20
- 102000003820 Lipoxygenases Human genes 0.000 claims description 18
- 108090000128 Lipoxygenases Proteins 0.000 claims description 18
- 239000003795 chemical substances by application Substances 0.000 claims description 17
- 102000004005 Prostaglandin-endoperoxide synthases Human genes 0.000 claims description 15
- 108090000459 Prostaglandin-endoperoxide synthases Proteins 0.000 claims description 15
- 239000000739 antihistaminic agent Substances 0.000 claims description 14
- 239000003966 growth inhibitor Substances 0.000 claims description 14
- 230000006444 vascular growth Effects 0.000 claims description 14
- GUGOEEXESWIERI-UHFFFAOYSA-N Terfenadine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 GUGOEEXESWIERI-UHFFFAOYSA-N 0.000 claims description 13
- 230000001387 anti-histamine Effects 0.000 claims description 13
- 108060008682 Tumor Necrosis Factor Proteins 0.000 claims description 12
- 230000001886 ciliary effect Effects 0.000 claims description 12
- 102000003390 tumor necrosis factor Human genes 0.000 claims description 12
- 239000002246 antineoplastic agent Substances 0.000 claims description 11
- CGIGDMFJXJATDK-UHFFFAOYSA-N indomethacin Chemical compound CC1=C(CC(O)=O)C2=CC(OC)=CC=C2N1C(=O)C1=CC=C(Cl)C=C1 CGIGDMFJXJATDK-UHFFFAOYSA-N 0.000 claims description 10
- 229940111134 coxibs Drugs 0.000 claims description 9
- 239000003255 cyclooxygenase 2 inhibitor Substances 0.000 claims description 9
- 229920000642 polymer Polymers 0.000 claims description 9
- 239000002253 acid Substances 0.000 claims description 7
- 229960000397 bevacizumab Drugs 0.000 claims description 7
- 229960002390 flurbiprofen Drugs 0.000 claims description 7
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 claims description 7
- BYPFEZZEUUWMEJ-UHFFFAOYSA-N Pentoxifylline Chemical compound O=C1N(CCCCC(=O)C)C(=O)N(C)C2=C1N(C)C=N2 BYPFEZZEUUWMEJ-UHFFFAOYSA-N 0.000 claims description 6
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 6
- 229960000371 rofecoxib Drugs 0.000 claims description 6
- RZJQGNCSTQAWON-UHFFFAOYSA-N rofecoxib Chemical compound C1=CC(S(=O)(=O)C)=CC=C1C1=C(C=2C=CC=CC=2)C(=O)OC1 RZJQGNCSTQAWON-UHFFFAOYSA-N 0.000 claims description 6
- 230000002459 sustained effect Effects 0.000 claims description 6
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 claims description 5
- ZRVUJXDFFKFLMG-UHFFFAOYSA-N Meloxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=NC=C(C)S1 ZRVUJXDFFKFLMG-UHFFFAOYSA-N 0.000 claims description 5
- 229960001259 diclofenac Drugs 0.000 claims description 5
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 0.000 claims description 5
- ZWJINEZUASEZBH-UHFFFAOYSA-N fenamic acid Chemical class OC(=O)C1=CC=CC=C1NC1=CC=CC=C1 ZWJINEZUASEZBH-UHFFFAOYSA-N 0.000 claims description 5
- 229960001680 ibuprofen Drugs 0.000 claims description 5
- 229960000905 indomethacin Drugs 0.000 claims description 5
- 229960001929 meloxicam Drugs 0.000 claims description 5
- 229960002702 piroxicam Drugs 0.000 claims description 5
- QYSPLQLAKJAUJT-UHFFFAOYSA-N piroxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC1=CC=CC=N1 QYSPLQLAKJAUJT-UHFFFAOYSA-N 0.000 claims description 5
- RDJGLLICXDHJDY-NSHDSACASA-N (2s)-2-(3-phenoxyphenyl)propanoic acid Chemical compound OC(=O)[C@@H](C)C1=CC=CC(OC=2C=CC=CC=2)=C1 RDJGLLICXDHJDY-NSHDSACASA-N 0.000 claims description 4
- MBUVEWMHONZEQD-UHFFFAOYSA-N Azeptin Chemical compound C1CN(C)CCCC1N1C(=O)C2=CC=CC=C2C(CC=2C=CC(Cl)=CC=2)=N1 MBUVEWMHONZEQD-UHFFFAOYSA-N 0.000 claims description 4
- SBDNJUWAMKYJOX-UHFFFAOYSA-N Meclofenamic Acid Chemical compound CC1=CC=C(Cl)C(NC=2C(=CC=CC=2)C(O)=O)=C1Cl SBDNJUWAMKYJOX-UHFFFAOYSA-N 0.000 claims description 4
- QKDDJDBFONZGBW-UHFFFAOYSA-N N-Cyclohexy-4-(imidazol-4-yl)-1-piperidinecarbothioamide Chemical compound C1CC(C=2NC=NC=2)CCN1C(=S)NC1CCCCC1 QKDDJDBFONZGBW-UHFFFAOYSA-N 0.000 claims description 4
- CMWTZPSULFXXJA-UHFFFAOYSA-N Naproxen Natural products C1=C(C(C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-UHFFFAOYSA-N 0.000 claims description 4
- 229960004574 azelastine Drugs 0.000 claims description 4
- 230000008878 coupling Effects 0.000 claims description 4
- 238000010168 coupling process Methods 0.000 claims description 4
- 238000005859 coupling reaction Methods 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- OEHFRZLKGRKFAS-UHFFFAOYSA-N droxicam Chemical compound C12=CC=CC=C2S(=O)(=O)N(C)C(C2=O)=C1OC(=O)N2C1=CC=CC=N1 OEHFRZLKGRKFAS-UHFFFAOYSA-N 0.000 claims description 4
- 229960001850 droxicam Drugs 0.000 claims description 4
- 230000009977 dual effect Effects 0.000 claims description 4
- 229960005293 etodolac Drugs 0.000 claims description 4
- XFBVBWWRPKNWHW-UHFFFAOYSA-N etodolac Chemical compound C1COC(CC)(CC(O)=O)C2=N[C]3C(CC)=CC=CC3=C21 XFBVBWWRPKNWHW-UHFFFAOYSA-N 0.000 claims description 4
- 229960001419 fenoprofen Drugs 0.000 claims description 4
- 229960004369 flufenamic acid Drugs 0.000 claims description 4
- LPEPZBJOKDYZAD-UHFFFAOYSA-N flufenamic acid Chemical compound OC(=O)C1=CC=CC=C1NC1=CC=CC(C(F)(F)F)=C1 LPEPZBJOKDYZAD-UHFFFAOYSA-N 0.000 claims description 4
- 239000003485 histamine H2 receptor antagonist Substances 0.000 claims description 4
- 239000003395 histamine H3 receptor antagonist Substances 0.000 claims description 4
- 239000003396 histamine H4 receptor antagonist Substances 0.000 claims description 4
- YYUAYBYLJSNDCX-UHFFFAOYSA-N isoxicam Chemical compound OC=1C2=CC=CC=C2S(=O)(=O)N(C)C=1C(=O)NC=1C=C(C)ON=1 YYUAYBYLJSNDCX-UHFFFAOYSA-N 0.000 claims description 4
- 229950002252 isoxicam Drugs 0.000 claims description 4
- DKYWVDODHFEZIM-UHFFFAOYSA-N ketoprofen Chemical compound OC(=O)C(C)C1=CC=CC(C(=O)C=2C=CC=CC=2)=C1 DKYWVDODHFEZIM-UHFFFAOYSA-N 0.000 claims description 4
- 229960000991 ketoprofen Drugs 0.000 claims description 4
- OXROWJKCGCOJDO-JLHYYAGUSA-N lornoxicam Chemical compound O=C1C=2SC(Cl)=CC=2S(=O)(=O)N(C)\C1=C(\O)NC1=CC=CC=N1 OXROWJKCGCOJDO-JLHYYAGUSA-N 0.000 claims description 4
- 229960002202 lornoxicam Drugs 0.000 claims description 4
- 229960003803 meclofenamic acid Drugs 0.000 claims description 4
- 229960003464 mefenamic acid Drugs 0.000 claims description 4
- HYYBABOKPJLUIN-UHFFFAOYSA-N mefenamic acid Chemical compound CC1=CC=CC(NC=2C(=CC=CC=2)C(O)=O)=C1C HYYBABOKPJLUIN-UHFFFAOYSA-N 0.000 claims description 4
- 229960002009 naproxen Drugs 0.000 claims description 4
- 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 claims description 4
- 229960001002 nepafenac Drugs 0.000 claims description 4
- QEFAQIPZVLVERP-UHFFFAOYSA-N nepafenac Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N QEFAQIPZVLVERP-UHFFFAOYSA-N 0.000 claims description 4
- 229960002739 oxaprozin Drugs 0.000 claims description 4
- OFPXSFXSNFPTHF-UHFFFAOYSA-N oxaprozin Chemical compound O1C(CCC(=O)O)=NC(C=2C=CC=CC=2)=C1C1=CC=CC=C1 OFPXSFXSNFPTHF-UHFFFAOYSA-N 0.000 claims description 4
- 229960004662 parecoxib Drugs 0.000 claims description 4
- TZRHLKRLEZJVIJ-UHFFFAOYSA-N parecoxib Chemical compound C1=CC(S(=O)(=O)NC(=O)CC)=CC=C1C1=C(C)ON=C1C1=CC=CC=C1 TZRHLKRLEZJVIJ-UHFFFAOYSA-N 0.000 claims description 4
- 229960001476 pentoxifylline Drugs 0.000 claims description 4
- 150000005599 propionic acid derivatives Chemical class 0.000 claims description 4
- 238000001179 sorption measurement Methods 0.000 claims description 4
- 229960002871 tenoxicam Drugs 0.000 claims description 4
- WZWYJBNHTWCXIM-UHFFFAOYSA-N tenoxicam Chemical compound O=C1C=2SC=CC=2S(=O)(=O)N(C)C1=C(O)NC1=CC=CC=N1 WZWYJBNHTWCXIM-UHFFFAOYSA-N 0.000 claims description 4
- 229960002905 tolfenamic acid Drugs 0.000 claims description 4
- YEZNLOUZAIOMLT-UHFFFAOYSA-N tolfenamic acid Chemical compound CC1=C(Cl)C=CC=C1NC1=CC=CC=C1C(O)=O YEZNLOUZAIOMLT-UHFFFAOYSA-N 0.000 claims description 4
- 229940046728 tumor necrosis factor alpha inhibitor Drugs 0.000 claims description 4
- 239000002451 tumor necrosis factor inhibitor Substances 0.000 claims description 4
- 229960002004 valdecoxib Drugs 0.000 claims description 4
- LNPDTQAFDNKSHK-UHFFFAOYSA-N valdecoxib Chemical compound CC=1ON=C(C=2C=CC=CC=2)C=1C1=CC=C(S(N)(=O)=O)C=C1 LNPDTQAFDNKSHK-UHFFFAOYSA-N 0.000 claims description 4
- ZKLPARSLTMPFCP-UHFFFAOYSA-N Cetirizine Chemical compound C1CN(CCOCC(=O)O)CCN1C(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-UHFFFAOYSA-N 0.000 claims description 3
- 108010008165 Etanercept Proteins 0.000 claims description 3
- 229960002964 adalimumab Drugs 0.000 claims description 3
- 229960001803 cetirizine Drugs 0.000 claims description 3
- 229960003291 chlorphenamine Drugs 0.000 claims description 3
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 claims description 3
- 229960000403 etanercept Drugs 0.000 claims description 3
- 239000000938 histamine H1 antagonist Substances 0.000 claims description 3
- 229960000598 infliximab Drugs 0.000 claims description 3
- 229960000994 lumiracoxib Drugs 0.000 claims description 3
- KHPKQFYUPIUARC-UHFFFAOYSA-N lumiracoxib Chemical compound OC(=O)CC1=CC(C)=CC=C1NC1=C(F)C=CC=C1Cl KHPKQFYUPIUARC-UHFFFAOYSA-N 0.000 claims description 3
- 229940044551 receptor antagonist Drugs 0.000 claims description 3
- 239000002464 receptor antagonist Substances 0.000 claims description 3
- 229960000894 sulindac Drugs 0.000 claims description 3
- MLKXDPUZXIRXEP-MFOYZWKCSA-N sulindac Chemical compound CC1=C(CC(O)=O)C2=CC(F)=CC=C2\C1=C/C1=CC=C(S(C)=O)C=C1 MLKXDPUZXIRXEP-MFOYZWKCSA-N 0.000 claims description 3
- HUQJRYMLJBBEDO-UHFFFAOYSA-N (5-chloro-1h-indol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound C1CN(C)CCN1C(=O)C1=CC2=CC(Cl)=CC=C2N1 HUQJRYMLJBBEDO-UHFFFAOYSA-N 0.000 claims description 2
- KOTJFAYEELTYCZ-BTJKTKAUSA-N (z)-but-2-enedioic acid;(6-chloro-1h-benzimidazol-2-yl)-(4-methylpiperazin-1-yl)methanone Chemical compound OC(=O)\C=C/C(O)=O.C1CN(C)CCN1C(=O)C1=NC2=CC(Cl)=CC=C2N1 KOTJFAYEELTYCZ-BTJKTKAUSA-N 0.000 claims description 2
- ZKLPARSLTMPFCP-OAQYLSRUSA-N 2-[2-[4-[(R)-(4-chlorophenyl)-phenylmethyl]-1-piperazinyl]ethoxy]acetic acid Chemical compound C1CN(CCOCC(=O)O)CCN1[C@@H](C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 ZKLPARSLTMPFCP-OAQYLSRUSA-N 0.000 claims description 2
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 claims description 2
- 101000620009 Homo sapiens Polyunsaturated fatty acid 5-lipoxygenase Proteins 0.000 claims description 2
- PWWVAXIEGOYWEE-UHFFFAOYSA-N Isophenergan Chemical compound C1=CC=C2N(CC(C)N(C)C)C3=CC=CC=C3SC2=C1 PWWVAXIEGOYWEE-UHFFFAOYSA-N 0.000 claims description 2
- KMZQAVXSMUKBPD-DJWKRKHSSA-N Lafutidine Chemical compound C=1C=COC=1C[S+]([O-])CC(=O)NC\C=C/COC(N=CC=1)=CC=1CN1CCCCC1 KMZQAVXSMUKBPD-DJWKRKHSSA-N 0.000 claims description 2
- OCJYIGYOJCODJL-UHFFFAOYSA-N Meclizine Chemical compound CC1=CC=CC(CN2CCN(CC2)C(C=2C=CC=CC=2)C=2C=CC(Cl)=CC=2)=C1 OCJYIGYOJCODJL-UHFFFAOYSA-N 0.000 claims description 2
- IJHNSHDBIRRJRN-UHFFFAOYSA-N N,N-dimethyl-3-phenyl-3-(2-pyridinyl)-1-propanamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=CC=C1 IJHNSHDBIRRJRN-UHFFFAOYSA-N 0.000 claims description 2
- BLXXJMDCKKHMKV-UHFFFAOYSA-N Nabumetone Chemical compound C1=C(CCC(C)=O)C=CC2=CC(OC)=CC=C21 BLXXJMDCKKHMKV-UHFFFAOYSA-N 0.000 claims description 2
- JAUOIFJMECXRGI-UHFFFAOYSA-N Neoclaritin Chemical compound C=1C(Cl)=CC=C2C=1CCC1=CC=CN=C1C2=C1CCNCC1 JAUOIFJMECXRGI-UHFFFAOYSA-N 0.000 claims description 2
- 102100022364 Polyunsaturated fatty acid 5-lipoxygenase Human genes 0.000 claims description 2
- SMTZFNFIKUPEJC-UHFFFAOYSA-N Roxane Chemical compound CC(=O)OCC(=O)NCCCOC1=CC=CC(CN2CCCCC2)=C1 SMTZFNFIKUPEJC-UHFFFAOYSA-N 0.000 claims description 2
- KFHYZKCRXNRKRC-MRXNPFEDSA-N abt-239 Chemical compound C[C@@H]1CCCN1CCC1=CC2=CC(C=3C=CC(=CC=3)C#N)=CC=C2O1 KFHYZKCRXNRKRC-MRXNPFEDSA-N 0.000 claims description 2
- 229960001138 acetylsalicylic acid Drugs 0.000 claims description 2
- 229960002833 aflibercept Drugs 0.000 claims description 2
- 108010081667 aflibercept Proteins 0.000 claims description 2
- 230000003510 anti-fibrotic effect Effects 0.000 claims description 2
- 229960003655 bromfenac Drugs 0.000 claims description 2
- ZBPLOVFIXSTCRZ-UHFFFAOYSA-N bromfenac Chemical compound NC1=C(CC(O)=O)C=CC=C1C(=O)C1=CC=C(Br)C=C1 ZBPLOVFIXSTCRZ-UHFFFAOYSA-N 0.000 claims description 2
- SNPPWIUOZRMYNY-UHFFFAOYSA-N bupropion Chemical compound CC(C)(C)NC(C)C(=O)C1=CC=CC(Cl)=C1 SNPPWIUOZRMYNY-UHFFFAOYSA-N 0.000 claims description 2
- 229960001058 bupropion Drugs 0.000 claims description 2
- 229960001380 cimetidine Drugs 0.000 claims description 2
- CCGSUNCLSOWKJO-UHFFFAOYSA-N cimetidine Chemical compound N#CNC(=N/C)\NCCSCC1=NC=N[C]1C CCGSUNCLSOWKJO-UHFFFAOYSA-N 0.000 claims description 2
- 229960002881 clemastine Drugs 0.000 claims description 2
- YNNUSGIPVFPVBX-NHCUHLMSSA-N clemastine Chemical compound CN1CCC[C@@H]1CCO[C@@](C)(C=1C=CC(Cl)=CC=1)C1=CC=CC=C1 YNNUSGIPVFPVBX-NHCUHLMSSA-N 0.000 claims description 2
- UCAIEVHKDLMIFL-UHFFFAOYSA-N clobenpropit Chemical compound C1=CC(Cl)=CC=C1CNC(=N)SCCCC1=CNC=N1 UCAIEVHKDLMIFL-UHFFFAOYSA-N 0.000 claims description 2
- 229960001271 desloratadine Drugs 0.000 claims description 2
- 229960001992 dimetindene Drugs 0.000 claims description 2
- MVMQESMQSYOVGV-UHFFFAOYSA-N dimetindene Chemical compound CN(C)CCC=1CC2=CC=CC=C2C=1C(C)C1=CC=CC=N1 MVMQESMQSYOVGV-UHFFFAOYSA-N 0.000 claims description 2
- 229960000520 diphenhydramine Drugs 0.000 claims description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 claims description 2
- 229960005178 doxylamine Drugs 0.000 claims description 2
- HCFDWZZGGLSKEP-UHFFFAOYSA-N doxylamine Chemical compound C=1C=CC=NC=1C(C)(OCCN(C)C)C1=CC=CC=C1 HCFDWZZGGLSKEP-UHFFFAOYSA-N 0.000 claims description 2
- 229960001971 ebastine Drugs 0.000 claims description 2
- MJJALKDDGIKVBE-UHFFFAOYSA-N ebastine Chemical compound C1=CC(C(C)(C)C)=CC=C1C(=O)CCCN1CCC(OC(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 MJJALKDDGIKVBE-UHFFFAOYSA-N 0.000 claims description 2
- 229960001596 famotidine Drugs 0.000 claims description 2
- XUFQPHANEAPEMJ-UHFFFAOYSA-N famotidine Chemical compound NC(N)=NC1=NC(CSCCC(N)=NS(N)(=O)=O)=CS1 XUFQPHANEAPEMJ-UHFFFAOYSA-N 0.000 claims description 2
- 229960003592 fexofenadine Drugs 0.000 claims description 2
- RWTNPBWLLIMQHL-UHFFFAOYSA-N fexofenadine Chemical compound C1=CC(C(C)(C(O)=O)C)=CC=C1C(O)CCCN1CCC(C(O)(C=2C=CC=CC=2)C=2C=CC=CC=2)CC1 RWTNPBWLLIMQHL-UHFFFAOYSA-N 0.000 claims description 2
- 229960003303 lafutidine Drugs 0.000 claims description 2
- 229960001508 levocetirizine Drugs 0.000 claims description 2
- 229960003088 loratadine Drugs 0.000 claims description 2
- JCCNYMKQOSZNPW-UHFFFAOYSA-N loratadine Chemical compound C1CN(C(=O)OCC)CCC1=C1C2=NC=CC=C2CCC2=CC(Cl)=CC=C21 JCCNYMKQOSZNPW-UHFFFAOYSA-N 0.000 claims description 2
- 229960001474 meclozine Drugs 0.000 claims description 2
- 239000000693 micelle Substances 0.000 claims description 2
- 229960004270 nabumetone Drugs 0.000 claims description 2
- 229960004872 nizatidine Drugs 0.000 claims description 2
- SGXXNSQHWDMGGP-IZZDOVSWSA-N nizatidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CSC(CN(C)C)=N1 SGXXNSQHWDMGGP-IZZDOVSWSA-N 0.000 claims description 2
- 229960004114 olopatadine Drugs 0.000 claims description 2
- JBIMVDZLSHOPLA-LSCVHKIXSA-N olopatadine Chemical compound C1OC2=CC=C(CC(O)=O)C=C2C(=C/CCN(C)C)\C2=CC=CC=C21 JBIMVDZLSHOPLA-LSCVHKIXSA-N 0.000 claims description 2
- 230000037361 pathway Effects 0.000 claims description 2
- 229960001190 pheniramine Drugs 0.000 claims description 2
- 229960003910 promethazine Drugs 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- 229960004431 quetiapine Drugs 0.000 claims description 2
- URKOMYMAXPYINW-UHFFFAOYSA-N quetiapine Chemical compound C1CN(CCOCCO)CCN1C1=NC2=CC=CC=C2SC2=CC=CC=C12 URKOMYMAXPYINW-UHFFFAOYSA-N 0.000 claims description 2
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 claims description 2
- 229960000620 ranitidine Drugs 0.000 claims description 2
- VMXUWOKSQNHOCA-LCYFTJDESA-N ranitidine Chemical compound [O-][N+](=O)/C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-LCYFTJDESA-N 0.000 claims description 2
- 229960003320 roxatidine Drugs 0.000 claims description 2
- 150000003872 salicylic acid derivatives Chemical class 0.000 claims description 2
- 239000000758 substrate Substances 0.000 claims description 2
- 238000011287 therapeutic dose Methods 0.000 claims description 2
- 229960005332 zileuton Drugs 0.000 claims description 2
- MWLSOWXNZPKENC-SSDOTTSWSA-N zileuton Chemical compound C1=CC=C2SC([C@H](N(O)C(N)=O)C)=CC2=C1 MWLSOWXNZPKENC-SSDOTTSWSA-N 0.000 claims description 2
- 229960004993 dimenhydrinate Drugs 0.000 claims 2
- MZDOIJOUFRQXHC-UHFFFAOYSA-N dimenhydrinate Chemical compound O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 MZDOIJOUFRQXHC-UHFFFAOYSA-N 0.000 claims 2
- 102000003834 Histamine H1 Receptors Human genes 0.000 claims 1
- 108090000110 Histamine H1 Receptors Proteins 0.000 claims 1
- 229940111131 antiinflammatory and antirheumatic product propionic acid derivative Drugs 0.000 claims 1
- 229940058287 salicylic acid derivative anticestodals Drugs 0.000 claims 1
- 238000011282 treatment Methods 0.000 abstract description 29
- 229940121363 anti-inflammatory agent Drugs 0.000 abstract description 11
- 239000002260 anti-inflammatory agent Substances 0.000 abstract description 11
- 239000000041 non-steroidal anti-inflammatory agent Substances 0.000 abstract description 6
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 abstract description 6
- 229940076783 lucentis Drugs 0.000 description 152
- 108091006146 Channels Proteins 0.000 description 145
- 210000001508 eye Anatomy 0.000 description 126
- 238000002347 injection Methods 0.000 description 121
- 239000007924 injection Substances 0.000 description 121
- 229940079593 drug Drugs 0.000 description 64
- 239000000463 material Substances 0.000 description 64
- 238000012360 testing method Methods 0.000 description 53
- 239000000243 solution Substances 0.000 description 45
- 238000013268 sustained release Methods 0.000 description 44
- 239000012730 sustained-release form Substances 0.000 description 42
- 230000000875 corresponding effect Effects 0.000 description 39
- 230000001186 cumulative effect Effects 0.000 description 39
- 229940120638 avastin Drugs 0.000 description 37
- 230000004888 barrier function Effects 0.000 description 35
- 230000002401 inhibitory effect Effects 0.000 description 32
- 206010064930 age-related macular degeneration Diseases 0.000 description 29
- 239000002953 phosphate buffered saline Substances 0.000 description 28
- 238000004364 calculation method Methods 0.000 description 27
- 239000012530 fluid Substances 0.000 description 25
- 239000002245 particle Substances 0.000 description 23
- 239000011148 porous material Substances 0.000 description 23
- 150000003384 small molecules Chemical class 0.000 description 23
- 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 23
- 210000000795 conjunctiva Anatomy 0.000 description 22
- 239000000725 suspension Substances 0.000 description 22
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 21
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 21
- 239000012528 membrane Substances 0.000 description 21
- 229960002117 triamcinolone acetonide Drugs 0.000 description 21
- 239000007788 liquid Substances 0.000 description 20
- 229910052751 metal Inorganic materials 0.000 description 20
- 239000002184 metal Substances 0.000 description 20
- 210000001525 retina Anatomy 0.000 description 20
- 238000009792 diffusion process Methods 0.000 description 19
- 238000005259 measurement Methods 0.000 description 19
- 239000010935 stainless steel Substances 0.000 description 19
- 229910001220 stainless steel Inorganic materials 0.000 description 19
- 239000010936 titanium Substances 0.000 description 19
- 229910052719 titanium Inorganic materials 0.000 description 19
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 18
- 238000002474 experimental method Methods 0.000 description 18
- 238000004088 simulation Methods 0.000 description 17
- 238000011049 filling Methods 0.000 description 16
- 241000282414 Homo sapiens Species 0.000 description 15
- 238000003780 insertion Methods 0.000 description 15
- 230000037431 insertion Effects 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 13
- 230000007246 mechanism Effects 0.000 description 13
- 102000004169 proteins and genes Human genes 0.000 description 13
- 108090000623 proteins and genes Proteins 0.000 description 13
- 229910000619 316 stainless steel Inorganic materials 0.000 description 12
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 12
- 102000005789 Vascular Endothelial Growth Factors Human genes 0.000 description 12
- 108010019530 Vascular Endothelial Growth Factors Proteins 0.000 description 12
- 230000008901 benefit Effects 0.000 description 12
- 150000001875 compounds Chemical class 0.000 description 12
- 230000007423 decrease Effects 0.000 description 12
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 12
- 239000011230 binding agent Substances 0.000 description 11
- 201000010099 disease Diseases 0.000 description 11
- 230000004438 eyesight Effects 0.000 description 11
- 230000014759 maintenance of location Effects 0.000 description 11
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 11
- 241000282693 Cercopithecidae Species 0.000 description 10
- 108010050904 Interferons Proteins 0.000 description 10
- 102000014150 Interferons Human genes 0.000 description 10
- 230000000694 effects Effects 0.000 description 10
- 239000011521 glass Substances 0.000 description 10
- 238000002513 implantation Methods 0.000 description 10
- 229940079322 interferon Drugs 0.000 description 10
- 230000003204 osmotic effect Effects 0.000 description 10
- GNBHRKFJIUUOQI-UHFFFAOYSA-N fluorescein Chemical compound O1C(=O)C2=CC=CC=C2C21C1=CC=C(O)C=C1OC1=CC(O)=CC=C21 GNBHRKFJIUUOQI-UHFFFAOYSA-N 0.000 description 9
- 239000007789 gas Substances 0.000 description 9
- 239000000843 powder Substances 0.000 description 9
- 210000001519 tissue Anatomy 0.000 description 9
- 206010061218 Inflammation Diseases 0.000 description 8
- 239000006260 foam Substances 0.000 description 8
- 239000000017 hydrogel Substances 0.000 description 8
- 208000015181 infectious disease Diseases 0.000 description 8
- 239000002090 nanochannel Substances 0.000 description 8
- 229920001296 polysiloxane Polymers 0.000 description 8
- ZAHRKKWIAAJSAO-UHFFFAOYSA-N rapamycin Natural products COCC(O)C(=C/C(C)C(=O)CC(OC(=O)C1CCCCN1C(=O)C(=O)C2(O)OC(CC(OC)C(=CC=CC=CC(C)CC(C)C(=O)C)C)CCC2C)C(C)CC3CCC(O)C(C3)OC)C ZAHRKKWIAAJSAO-UHFFFAOYSA-N 0.000 description 8
- 229960002930 sirolimus Drugs 0.000 description 8
- QFJCIRLUMZQUOT-HPLJOQBZSA-N sirolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 QFJCIRLUMZQUOT-HPLJOQBZSA-N 0.000 description 8
- 229960005294 triamcinolone Drugs 0.000 description 8
- 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 8
- 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 7
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 7
- 230000033115 angiogenesis Effects 0.000 description 7
- 230000009286 beneficial effect Effects 0.000 description 7
- 230000004054 inflammatory process Effects 0.000 description 7
- 229960004752 ketorolac Drugs 0.000 description 7
- OZWKMVRBQXNZKK-UHFFFAOYSA-N ketorolac Chemical compound OC(=O)C1CCN2C1=CC=C2C(=O)C1=CC=CC=C1 OZWKMVRBQXNZKK-UHFFFAOYSA-N 0.000 description 7
- 238000001000 micrograph Methods 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- 206010028980 Neoplasm Diseases 0.000 description 6
- 241000283973 Oryctolagus cuniculus Species 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 6
- 229940034982 antineoplastic agent Drugs 0.000 description 6
- 239000003246 corticosteroid Substances 0.000 description 6
- 230000009368 gene silencing by RNA Effects 0.000 description 6
- 230000007774 longterm Effects 0.000 description 6
- 229920002521 macromolecule Polymers 0.000 description 6
- 230000002829 reductive effect Effects 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- 208000031481 Pathologic Constriction Diseases 0.000 description 5
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 5
- 229940022663 acetate Drugs 0.000 description 5
- 230000015572 biosynthetic process Effects 0.000 description 5
- 239000000919 ceramic Substances 0.000 description 5
- 230000008859 change Effects 0.000 description 5
- 238000010438 heat treatment Methods 0.000 description 5
- 239000002086 nanomaterial Substances 0.000 description 5
- 239000004033 plastic Substances 0.000 description 5
- 229920003023 plastic Polymers 0.000 description 5
- 229920000515 polycarbonate Polymers 0.000 description 5
- 239000004417 polycarbonate Substances 0.000 description 5
- 239000011780 sodium chloride Substances 0.000 description 5
- 230000036262 stenosis Effects 0.000 description 5
- 208000037804 stenosis Diseases 0.000 description 5
- 210000002435 tendon Anatomy 0.000 description 5
- 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 4
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 4
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 4
- 102000008394 Immunoglobulin Fragments Human genes 0.000 description 4
- SHGAZHPCJJPHSC-NUEINMDLSA-N Isotretinoin Chemical compound OC(=O)C=C(C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C SHGAZHPCJJPHSC-NUEINMDLSA-N 0.000 description 4
- 102100035846 Pigment epithelium-derived factor Human genes 0.000 description 4
- 102000003923 Protein Kinase C Human genes 0.000 description 4
- 108090000315 Protein Kinase C Proteins 0.000 description 4
- 238000012228 RNA interference-mediated gene silencing Methods 0.000 description 4
- 206010038848 Retinal detachment Diseases 0.000 description 4
- YASAKCUCGLMORW-UHFFFAOYSA-N Rosiglitazone Chemical compound C=1C=CC=NC=1N(C)CCOC(C=C1)=CC=C1CC1SC(=O)NC1=O YASAKCUCGLMORW-UHFFFAOYSA-N 0.000 description 4
- PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 4
- 102000013530 TOR Serine-Threonine Kinases Human genes 0.000 description 4
- 108010065917 TOR Serine-Threonine Kinases Proteins 0.000 description 4
- 239000013543 active substance Substances 0.000 description 4
- 230000003110 anti-inflammatory effect Effects 0.000 description 4
- GXJABQQUPOEUTA-RDJZCZTQSA-N bortezomib Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)B(O)O)NC(=O)C=1N=CC=NC=1)C1=CC=CC=C1 GXJABQQUPOEUTA-RDJZCZTQSA-N 0.000 description 4
- 210000003161 choroid Anatomy 0.000 description 4
- 239000002131 composite material Substances 0.000 description 4
- 210000004087 cornea Anatomy 0.000 description 4
- 229960001334 corticosteroids Drugs 0.000 description 4
- 238000013016 damping Methods 0.000 description 4
- 230000001419 dependent effect Effects 0.000 description 4
- 238000011161 development Methods 0.000 description 4
- 238000005516 engineering process Methods 0.000 description 4
- 238000013265 extended release Methods 0.000 description 4
- 239000003102 growth factor Substances 0.000 description 4
- 238000000338 in vitro Methods 0.000 description 4
- 238000001727 in vivo Methods 0.000 description 4
- 230000005764 inhibitory process Effects 0.000 description 4
- 229960005280 isotretinoin Drugs 0.000 description 4
- 230000003902 lesion Effects 0.000 description 4
- 238000011068 loading method Methods 0.000 description 4
- 208000002780 macular degeneration Diseases 0.000 description 4
- 229960003407 pegaptanib Drugs 0.000 description 4
- 108090000102 pigment epithelium-derived factor Proteins 0.000 description 4
- 230000004264 retinal detachment Effects 0.000 description 4
- YGSDEFSMJLZEOE-UHFFFAOYSA-N salicylic acid Chemical compound OC(=O)C1=CC=CC=C1O YGSDEFSMJLZEOE-UHFFFAOYSA-N 0.000 description 4
- 229940126586 small molecule drug Drugs 0.000 description 4
- 230000008685 targeting Effects 0.000 description 4
- DPVHGFAJLZWDOC-PVXXTIHASA-N (2r,3s,4s,5r,6r)-2-(hydroxymethyl)-6-[(2r,3r,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxane-3,4,5-triol;dihydrate Chemical compound O.O.O[C@@H]1[C@@H](O)[C@H](O)[C@@H](CO)O[C@@H]1O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 DPVHGFAJLZWDOC-PVXXTIHASA-N 0.000 description 3
- MLDQJTXFUGDVEO-UHFFFAOYSA-N BAY-43-9006 Chemical compound C1=NC(C(=O)NC)=CC(OC=2C=CC(NC(=O)NC=3C=C(C(Cl)=CC=3)C(F)(F)F)=CC=2)=C1 MLDQJTXFUGDVEO-UHFFFAOYSA-N 0.000 description 3
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 3
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 3
- 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 3
- 102000000521 Immunophilins Human genes 0.000 description 3
- 108010016648 Immunophilins Proteins 0.000 description 3
- 102100022337 Integrin alpha-V Human genes 0.000 description 3
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 3
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 3
- 239000002136 L01XE07 - Lapatinib Substances 0.000 description 3
- XNRVGTHNYCNCFF-UHFFFAOYSA-N Lapatinib ditosylate monohydrate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1.CC1=CC=C(S(O)(=O)=O)C=C1.O1C(CNCCS(=O)(=O)C)=CC=C1C1=CC=C(N=CN=C2NC=3C=C(Cl)C(OCC=4C=C(F)C=CC=4)=CC=3)C2=C1 XNRVGTHNYCNCFF-UHFFFAOYSA-N 0.000 description 3
- 241000282567 Macaca fascicularis Species 0.000 description 3
- 206010025421 Macule Diseases 0.000 description 3
- 239000004743 Polypropylene Substances 0.000 description 3
- 229920001213 Polysorbate 20 Polymers 0.000 description 3
- 108090000412 Protein-Tyrosine Kinases Proteins 0.000 description 3
- 102000004022 Protein-Tyrosine Kinases Human genes 0.000 description 3
- 108010048673 Vitronectin Receptors Proteins 0.000 description 3
- 229910045601 alloy Inorganic materials 0.000 description 3
- 239000000956 alloy Substances 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 239000011324 bead Substances 0.000 description 3
- 230000005540 biological transmission Effects 0.000 description 3
- 229940098773 bovine serum albumin Drugs 0.000 description 3
- 201000011510 cancer Diseases 0.000 description 3
- 210000004027 cell Anatomy 0.000 description 3
- 239000000544 cholinesterase inhibitor Substances 0.000 description 3
- 238000002648 combination therapy Methods 0.000 description 3
- 230000000295 complement effect Effects 0.000 description 3
- 230000004154 complement system Effects 0.000 description 3
- 238000011109 contamination Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 229940043075 fluocinolone Drugs 0.000 description 3
- 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 3
- 238000011010 flushing procedure Methods 0.000 description 3
- 229960004716 idoxuridine Drugs 0.000 description 3
- 238000007913 intrathecal administration Methods 0.000 description 3
- 229940043355 kinase inhibitor Drugs 0.000 description 3
- 239000012669 liquid formulation Substances 0.000 description 3
- 229940092110 macugen Drugs 0.000 description 3
- 239000002105 nanoparticle Substances 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 230000035515 penetration Effects 0.000 description 3
- 230000000737 periodic effect Effects 0.000 description 3
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 229920001155 polypropylene Polymers 0.000 description 3
- 229940068977 polysorbate 20 Drugs 0.000 description 3
- 239000005373 porous glass Substances 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 230000002035 prolonged effect Effects 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 230000036573 scar formation Effects 0.000 description 3
- 239000001488 sodium phosphate Substances 0.000 description 3
- 229910000162 sodium phosphate Inorganic materials 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 238000002560 therapeutic procedure Methods 0.000 description 3
- WYWHKKSPHMUBEB-UHFFFAOYSA-N tioguanine Chemical compound N1C(N)=NC(=S)C2=C1N=CN2 WYWHKKSPHMUBEB-UHFFFAOYSA-N 0.000 description 3
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 0.000 description 3
- 239000008215 water for injection Substances 0.000 description 3
- 238000009736 wetting Methods 0.000 description 3
- NGGMYCMLYOUNGM-UHFFFAOYSA-N (-)-fumagillin Natural products O1C(CC=C(C)C)C1(C)C1C(OC)C(OC(=O)C=CC=CC=CC=CC(O)=O)CCC21CO2 NGGMYCMLYOUNGM-UHFFFAOYSA-N 0.000 description 2
- 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 2
- IXPNQXFRVYWDDI-UHFFFAOYSA-N 1-methyl-2,4-dioxo-1,3-diazinane-5-carboximidamide Chemical compound CN1CC(C(N)=N)C(=O)NC1=O IXPNQXFRVYWDDI-UHFFFAOYSA-N 0.000 description 2
- PCNWSHKCOYOECO-UHFFFAOYSA-N 1-methylsulfonyl-4-(1-phenylethyl)benzene Chemical compound CS(=O)(=O)C1=CC=C(C=C1)C(C)C1=CC=CC=C1 PCNWSHKCOYOECO-UHFFFAOYSA-N 0.000 description 2
- IIZPXYDJLKNOIY-JXPKJXOSSA-N 1-palmitoyl-2-arachidonoyl-sn-glycero-3-phosphocholine Chemical compound CCCCCCCCCCCCCCCC(=O)OC[C@H](COP([O-])(=O)OCC[N+](C)(C)C)OC(=O)CCC\C=C/C\C=C/C\C=C/C\C=C/CCCCC IIZPXYDJLKNOIY-JXPKJXOSSA-N 0.000 description 2
- CNIIGCLFLJGOGP-UHFFFAOYSA-N 2-(1-naphthalenylmethyl)-4,5-dihydro-1H-imidazole Chemical compound C=1C=CC2=CC=CC=C2C=1CC1=NCCN1 CNIIGCLFLJGOGP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- GIKNHHRFLCDOEU-UHFFFAOYSA-N 4-(2-aminopropyl)phenol Chemical compound CC(N)CC1=CC=C(O)C=C1 GIKNHHRFLCDOEU-UHFFFAOYSA-N 0.000 description 2
- XYLJNLCSTIOKRM-UHFFFAOYSA-N Alphagan Chemical compound C1=CC2=NC=CN=C2C(Br)=C1NC1=NCCN1 XYLJNLCSTIOKRM-UHFFFAOYSA-N 0.000 description 2
- 102400000068 Angiostatin Human genes 0.000 description 2
- 108010079709 Angiostatins Proteins 0.000 description 2
- 229940088872 Apoptosis inhibitor Drugs 0.000 description 2
- 108010082340 Arginine deiminase Proteins 0.000 description 2
- 102400000730 Canstatin Human genes 0.000 description 2
- 101800000626 Canstatin Proteins 0.000 description 2
- 102000053642 Catalytic RNA Human genes 0.000 description 2
- 108090000994 Catalytic RNA Proteins 0.000 description 2
- 208000002177 Cataract Diseases 0.000 description 2
- 208000002691 Choroiditis Diseases 0.000 description 2
- 108010069514 Cyclic Peptides Proteins 0.000 description 2
- 102000001189 Cyclic Peptides Human genes 0.000 description 2
- 101100481408 Danio rerio tie2 gene Proteins 0.000 description 2
- 229920004943 Delrin® Polymers 0.000 description 2
- 229920002307 Dextran Polymers 0.000 description 2
- 102400001047 Endostatin Human genes 0.000 description 2
- 108010079505 Endostatins Proteins 0.000 description 2
- ULGZDMOVFRHVEP-RWJQBGPGSA-N Erythromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)C(=O)[C@H](C)C[C@@](C)(O)[C@H](O[C@H]2[C@@H]([C@H](C[C@@H](C)O2)N(C)C)O)[C@H]1C)(C)O)CC)[C@H]1C[C@@](C)(OC)[C@@H](O)[C@H](C)O1 ULGZDMOVFRHVEP-RWJQBGPGSA-N 0.000 description 2
- HKVAMNSJSFKALM-GKUWKFKPSA-N Everolimus Chemical compound C1C[C@@H](OCCO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 HKVAMNSJSFKALM-GKUWKFKPSA-N 0.000 description 2
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 2
- 108010086677 Gonadotropins Proteins 0.000 description 2
- 102000006771 Gonadotropins Human genes 0.000 description 2
- 208000031220 Hemophilia Diseases 0.000 description 2
- 208000009292 Hemophilia A Diseases 0.000 description 2
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 2
- 206010020772 Hypertension Diseases 0.000 description 2
- 102000012355 Integrin beta1 Human genes 0.000 description 2
- 108010022222 Integrin beta1 Proteins 0.000 description 2
- 102000008607 Integrin beta3 Human genes 0.000 description 2
- 108010020950 Integrin beta3 Proteins 0.000 description 2
- 108010006035 Metalloproteases Proteins 0.000 description 2
- 102000005741 Metalloproteases Human genes 0.000 description 2
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- 239000004696 Poly ether ether ketone Substances 0.000 description 2
- 208000003971 Posterior uveitis Diseases 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- RJKFOVLPORLFTN-LEKSSAKUSA-N Progesterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@H](C(=O)C)[C@@]1(C)CC2 RJKFOVLPORLFTN-LEKSSAKUSA-N 0.000 description 2
- 229920002385 Sodium hyaluronate Polymers 0.000 description 2
- UIRKNQLZZXALBI-MSVGPLKSSA-N Squalamine Chemical compound C([C@@H]1C[C@H]2O)[C@@H](NCCCNCCCCN)CC[C@]1(C)[C@@H]1[C@@H]2[C@@H]2CC[C@H]([C@H](C)CC[C@H](C(C)C)OS(O)(=O)=O)[C@@]2(C)CC1 UIRKNQLZZXALBI-MSVGPLKSSA-N 0.000 description 2
- UIRKNQLZZXALBI-UHFFFAOYSA-N Squalamine Natural products OC1CC2CC(NCCCNCCCCN)CCC2(C)C2C1C1CCC(C(C)CCC(C(C)C)OS(O)(=O)=O)C1(C)CC2 UIRKNQLZZXALBI-UHFFFAOYSA-N 0.000 description 2
- 102000018679 Tacrolimus Binding Proteins Human genes 0.000 description 2
- 108010027179 Tacrolimus Binding Proteins Proteins 0.000 description 2
- 229920006356 Teflon™ FEP Polymers 0.000 description 2
- 229940123464 Thiazolidinedione Drugs 0.000 description 2
- 102400000731 Tumstatin Human genes 0.000 description 2
- DRTQHJPVMGBUCF-XVFCMESISA-N Uridine Chemical compound O[C@@H]1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-XVFCMESISA-N 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000009484 Vascular Endothelial Growth Factor Receptors Human genes 0.000 description 2
- 102100033177 Vascular endothelial growth factor receptor 2 Human genes 0.000 description 2
- GXBMIBRIOWHPDT-UHFFFAOYSA-N Vasopressin Natural products N1C(=O)C(CC=2C=C(O)C=CC=2)NC(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CCCN=C(N)N)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C1CC1=CC=CC=C1 GXBMIBRIOWHPDT-UHFFFAOYSA-N 0.000 description 2
- 102000002852 Vasopressins Human genes 0.000 description 2
- 108010004977 Vasopressins Proteins 0.000 description 2
- DPXJVFZANSGRMM-UHFFFAOYSA-N acetic acid;2,3,4,5,6-pentahydroxyhexanal;sodium Chemical compound [Na].CC(O)=O.OCC(O)C(O)C(O)C(O)C=O DPXJVFZANSGRMM-UHFFFAOYSA-N 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 239000004037 angiogenesis inhibitor Substances 0.000 description 2
- 239000003242 anti bacterial agent Substances 0.000 description 2
- 239000000158 apoptosis inhibitor Substances 0.000 description 2
- KBZOIRJILGZLEJ-LGYYRGKSSA-N argipressin Chemical compound C([C@H]1C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@@H](C(N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)=O)N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCN=C(N)N)C(=O)NCC(N)=O)C1=CC=CC=C1 KBZOIRJILGZLEJ-LGYYRGKSSA-N 0.000 description 2
- FZCSTZYAHCUGEM-UHFFFAOYSA-N aspergillomarasmine B Natural products OC(=O)CNC(C(O)=O)CNC(C(O)=O)CC(O)=O FZCSTZYAHCUGEM-UHFFFAOYSA-N 0.000 description 2
- 238000003556 assay Methods 0.000 description 2
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000001580 bacterial effect Effects 0.000 description 2
- 238000005452 bending Methods 0.000 description 2
- WQZGKKKJIJFFOK-VFUOTHLCSA-N beta-D-glucose Chemical compound OC[C@H]1O[C@@H](O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-VFUOTHLCSA-N 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 229960001467 bortezomib Drugs 0.000 description 2
- 229960000722 brinzolamide Drugs 0.000 description 2
- HCRKCZRJWPKOAR-JTQLQIEISA-N brinzolamide Chemical compound CCN[C@H]1CN(CCCOC)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 HCRKCZRJWPKOAR-JTQLQIEISA-N 0.000 description 2
- 229960000830 captopril Drugs 0.000 description 2
- FAKRSMQSSFJEIM-RQJHMYQMSA-N captopril Chemical compound SC[C@@H](C)C(=O)N1CCC[C@H]1C(O)=O FAKRSMQSSFJEIM-RQJHMYQMSA-N 0.000 description 2
- DKVNPHBNOWQYFE-UHFFFAOYSA-N carbamodithioic acid Chemical compound NC(S)=S DKVNPHBNOWQYFE-UHFFFAOYSA-N 0.000 description 2
- 239000001768 carboxy methyl cellulose Substances 0.000 description 2
- 239000004359 castor oil Substances 0.000 description 2
- 235000019438 castor oil Nutrition 0.000 description 2
- 210000002421 cell wall Anatomy 0.000 description 2
- SEERZIQQUAZTOL-ANMDKAQQSA-N cerivastatin Chemical compound COCC1=C(C(C)C)N=C(C(C)C)C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)=C1C1=CC=C(F)C=C1 SEERZIQQUAZTOL-ANMDKAQQSA-N 0.000 description 2
- 229960005110 cerivastatin Drugs 0.000 description 2
- 229960005395 cetuximab Drugs 0.000 description 2
- 239000011651 chromium Substances 0.000 description 2
- MYSWGUAQZAJSOK-UHFFFAOYSA-N ciprofloxacin Chemical compound C12=CC(N3CCNCC3)=C(F)C=C2C(=O)C(C(=O)O)=CN1C1CC1 MYSWGUAQZAJSOK-UHFFFAOYSA-N 0.000 description 2
- 230000015271 coagulation Effects 0.000 description 2
- 238000005345 coagulation Methods 0.000 description 2
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 229960001338 colchicine Drugs 0.000 description 2
- 238000011284 combination treatment Methods 0.000 description 2
- 238000007906 compression Methods 0.000 description 2
- 230000006835 compression Effects 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 230000007812 deficiency Effects 0.000 description 2
- 229960003957 dexamethasone Drugs 0.000 description 2
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 2
- 239000008121 dextrose Substances 0.000 description 2
- 235000014113 dietary fatty acids Nutrition 0.000 description 2
- LOKCTEFSRHRXRJ-UHFFFAOYSA-I dipotassium trisodium dihydrogen phosphate hydrogen phosphate dichloride Chemical compound P(=O)(O)(O)[O-].[K+].P(=O)(O)([O-])[O-].[Na+].[Na+].[Cl-].[K+].[Cl-].[Na+] LOKCTEFSRHRXRJ-UHFFFAOYSA-I 0.000 description 2
- 239000012990 dithiocarbamate Substances 0.000 description 2
- IAVUPMFITXYVAF-XPUUQOCRSA-N dorzolamide Chemical compound CCN[C@H]1C[C@H](C)S(=O)(=O)C2=C1C=C(S(N)(=O)=O)S2 IAVUPMFITXYVAF-XPUUQOCRSA-N 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000005530 etching Methods 0.000 description 2
- 238000001704 evaporation Methods 0.000 description 2
- 230000008020 evaporation Effects 0.000 description 2
- 208000030533 eye disease Diseases 0.000 description 2
- 239000000194 fatty acid Substances 0.000 description 2
- 229930195729 fatty acid Natural products 0.000 description 2
- 150000004665 fatty acids Chemical class 0.000 description 2
- 229960000936 fumagillin Drugs 0.000 description 2
- NGGMYCMLYOUNGM-CSDLUJIJSA-N fumagillin Chemical compound C([C@H]([C@H]([C@@H]1[C@]2(C)[C@H](O2)CC=C(C)C)OC)OC(=O)\C=C\C=C\C=C\C=C\C(O)=O)C[C@@]21CO2 NGGMYCMLYOUNGM-CSDLUJIJSA-N 0.000 description 2
- 230000006870 function Effects 0.000 description 2
- 229940074391 gallic acid Drugs 0.000 description 2
- 239000003862 glucocorticoid Substances 0.000 description 2
- ZEMPKEQAKRGZGQ-XOQCFJPHSA-N glycerol triricinoleate Natural products CCCCCC[C@@H](O)CC=CCCCCCCCC(=O)OC[C@@H](COC(=O)CCCCCCCC=CC[C@@H](O)CCCCCC)OC(=O)CCCCCCCC=CC[C@H](O)CCCCCC ZEMPKEQAKRGZGQ-XOQCFJPHSA-N 0.000 description 2
- 239000002622 gonadotropin Substances 0.000 description 2
- 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 2
- 230000006872 improvement Effects 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 238000010348 incorporation Methods 0.000 description 2
- 230000002757 inflammatory effect Effects 0.000 description 2
- 230000008798 inflammatory stress Effects 0.000 description 2
- 208000014674 injury Diseases 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
- 102000006495 integrins Human genes 0.000 description 2
- 108010044426 integrins Proteins 0.000 description 2
- 210000000936 intestine Anatomy 0.000 description 2
- 229960004891 lapatinib Drugs 0.000 description 2
- 150000002605 large molecules Chemical class 0.000 description 2
- 238000002386 leaching Methods 0.000 description 2
- 239000000787 lecithin Substances 0.000 description 2
- 235000010445 lecithin Nutrition 0.000 description 2
- 229940067606 lecithin Drugs 0.000 description 2
- 210000002540 macrophage Anatomy 0.000 description 2
- 230000001404 mediated effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- PXHVJJICTQNCMI-UHFFFAOYSA-N nickel Substances [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 230000036542 oxidative stress Effects 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 229960001972 panitumumab Drugs 0.000 description 2
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 2
- 230000036961 partial effect Effects 0.000 description 2
- 229960002582 perindopril Drugs 0.000 description 2
- IPVQLZZIHOAWMC-QXKUPLGCSA-N perindopril Chemical compound C1CCC[C@H]2C[C@@H](C(O)=O)N(C(=O)[C@H](C)N[C@@H](CCC)C(=O)OCC)[C@H]21 IPVQLZZIHOAWMC-QXKUPLGCSA-N 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 230000000649 photocoagulation Effects 0.000 description 2
- 238000002428 photodynamic therapy Methods 0.000 description 2
- 230000003169 placental effect Effects 0.000 description 2
- 229920002530 polyetherether ketone Polymers 0.000 description 2
- 229920005597 polymer membrane Polymers 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 2
- 210000003488 posterior eye segment Anatomy 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 239000003450 potassium channel blocker Substances 0.000 description 2
- 229960005205 prednisolone Drugs 0.000 description 2
- 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 2
- 239000003755 preservative agent Substances 0.000 description 2
- 150000003180 prostaglandins Chemical class 0.000 description 2
- 238000002731 protein assay Methods 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 229960001455 quinapril Drugs 0.000 description 2
- JSDRRTOADPPCHY-HSQYWUDLSA-N quinapril Chemical compound C([C@@H](C(=O)OCC)N[C@@H](C)C(=O)N1[C@@H](CC2=CC=CC=C2C1)C(O)=O)CC1=CC=CC=C1 JSDRRTOADPPCHY-HSQYWUDLSA-N 0.000 description 2
- 238000011160 research Methods 0.000 description 2
- 230000004044 response Effects 0.000 description 2
- 230000000717 retained effect Effects 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 229960004586 rosiglitazone Drugs 0.000 description 2
- 229960004889 salicylic acid Drugs 0.000 description 2
- 235000010413 sodium alginate Nutrition 0.000 description 2
- 239000000661 sodium alginate Substances 0.000 description 2
- 229940005550 sodium alginate Drugs 0.000 description 2
- 235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 2
- 229940010747 sodium hyaluronate Drugs 0.000 description 2
- YWIVKILSMZOHHF-QJZPQSOGSA-N sodium;(2s,3s,4s,5r,6r)-6-[(2s,3r,4r,5s,6r)-3-acetamido-2-[(2s,3s,4r,5r,6r)-6-[(2r,3r,4r,5s,6r)-3-acetamido-2,5-dihydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-2-carboxy-4,5-dihydroxyoxan-3-yl]oxy-5-hydroxy-6-(hydroxymethyl)oxan-4-yl]oxy-3,4,5-trihydroxyoxane-2- Chemical compound [Na+].CC(=O)N[C@H]1[C@H](O)O[C@H](CO)[C@@H](O)[C@@H]1O[C@H]1[C@H](O)[C@@H](O)[C@H](O[C@H]2[C@@H]([C@@H](O[C@H]3[C@@H]([C@@H](O)[C@H](O)[C@H](O3)C(O)=O)O)[C@H](O)[C@@H](CO)O2)NC(C)=O)[C@@H](C(O)=O)O1 YWIVKILSMZOHHF-QJZPQSOGSA-N 0.000 description 2
- 229960003787 sorafenib Drugs 0.000 description 2
- 229950001248 squalamine Drugs 0.000 description 2
- 150000003431 steroids Chemical class 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 229960001796 sunitinib Drugs 0.000 description 2
- WINHZLLDWRZWRT-ATVHPVEESA-N sunitinib Chemical compound CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C WINHZLLDWRZWRT-ATVHPVEESA-N 0.000 description 2
- 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 2
- BYJAVTDNIXVSPW-UHFFFAOYSA-N tetryzoline Chemical compound N1CCN=C1C1C2=CC=CC=C2CCC1 BYJAVTDNIXVSPW-UHFFFAOYSA-N 0.000 description 2
- 229940126585 therapeutic drug Drugs 0.000 description 2
- 150000001467 thiazolidinediones Chemical class 0.000 description 2
- 229960003087 tioguanine Drugs 0.000 description 2
- 229960000575 trastuzumab Drugs 0.000 description 2
- 230000008733 trauma Effects 0.000 description 2
- MKPLKVHSHYCHOC-AHTXBMBWSA-N travoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)COC1=CC=CC(C(F)(F)F)=C1 MKPLKVHSHYCHOC-AHTXBMBWSA-N 0.000 description 2
- GXPHKUHSUJUWKP-UHFFFAOYSA-N troglitazone Chemical compound C1CC=2C(C)=C(O)C(C)=C(C)C=2OC1(C)COC(C=C1)=CC=C1CC1SC(=O)NC1=O GXPHKUHSUJUWKP-UHFFFAOYSA-N 0.000 description 2
- 229960001641 troglitazone Drugs 0.000 description 2
- GXPHKUHSUJUWKP-NTKDMRAZSA-N troglitazone Natural products C([C@@]1(OC=2C(C)=C(C(=C(C)C=2CC1)O)C)C)OC(C=C1)=CC=C1C[C@H]1SC(=O)NC1=O GXPHKUHSUJUWKP-NTKDMRAZSA-N 0.000 description 2
- 230000005740 tumor formation Effects 0.000 description 2
- 108010012374 type IV collagen alpha3 chain Proteins 0.000 description 2
- 229960003726 vasopressin Drugs 0.000 description 2
- 229940099039 velcade Drugs 0.000 description 2
- YTZALCGQUPRCGW-ZSFNYQMMSA-N verteporfin Chemical compound N1C(C=C2C(=C(CCC(O)=O)C(C=C3C(CCC(=O)OC)=C(C)C(N3)=C3)=N2)C)=C(C=C)C(C)=C1C=C1C2=CC=C(C(=O)OC)[C@@H](C(=O)OC)[C@@]2(C)C3=N1 YTZALCGQUPRCGW-ZSFNYQMMSA-N 0.000 description 2
- 229940061392 visudyne Drugs 0.000 description 2
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 1
- ZDRRIRUAESZNIH-BZGUUIOASA-N (2s)-1-[(4r,7s,10s,13s,16s,19r)-19-amino-7-(2-amino-2-oxoethyl)-13-[(2s)-butan-2-yl]-10-[(1r)-1-hydroxyethyl]-16-[(4-hydroxyphenyl)methyl]-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carbonyl]-n-[(2s)-1-[(2-amino-2-oxoethyl)amino]- Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@H](C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSC[C@H](N)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)NCC(N)=O)[C@@H](C)O)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 ZDRRIRUAESZNIH-BZGUUIOASA-N 0.000 description 1
- QZNNVYOVQUKYSC-JEDNCBNOSA-N (2s)-2-amino-3-(1h-imidazol-5-yl)propanoic acid;hydron;chloride Chemical compound Cl.OC(=O)[C@@H](N)CC1=CN=CN1 QZNNVYOVQUKYSC-JEDNCBNOSA-N 0.000 description 1
- DEQANNDTNATYII-OULOTJBUSA-N (4r,7s,10s,13r,16s,19r)-10-(4-aminobutyl)-19-[[(2r)-2-amino-3-phenylpropanoyl]amino]-16-benzyl-n-[(2r,3r)-1,3-dihydroxybutan-2-yl]-7-[(1r)-1-hydroxyethyl]-13-(1h-indol-3-ylmethyl)-6,9,12,15,18-pentaoxo-1,2-dithia-5,8,11,14,17-pentazacycloicosane-4-carboxa Chemical compound C([C@@H](N)C(=O)N[C@H]1CSSC[C@H](NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCCCN)NC(=O)[C@@H](CC=2C3=CC=CC=C3NC=2)NC(=O)[C@H](CC=2C=CC=CC=2)NC1=O)C(=O)N[C@H](CO)[C@H](O)C)C1=CC=CC=C1 DEQANNDTNATYII-OULOTJBUSA-N 0.000 description 1
- HMLGSIZOMSVISS-ONJSNURVSA-N (7r)-7-[[(2z)-2-(2-amino-1,3-thiazol-4-yl)-2-(2,2-dimethylpropanoyloxymethoxyimino)acetyl]amino]-3-ethenyl-8-oxo-5-thia-1-azabicyclo[4.2.0]oct-2-ene-2-carboxylic acid Chemical compound N([C@@H]1C(N2C(=C(C=C)CSC21)C(O)=O)=O)C(=O)\C(=N/OCOC(=O)C(C)(C)C)C1=CSC(N)=N1 HMLGSIZOMSVISS-ONJSNURVSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 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
- 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 1
- VOXZDWNPVJITMN-ZBRFXRBCSA-N 17β-estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@H](CC4)O)[C@@H]4[C@@H]3CCC2=C1 VOXZDWNPVJITMN-ZBRFXRBCSA-N 0.000 description 1
- QXLQZLBNPTZMRK-UHFFFAOYSA-N 2-[(dimethylamino)methyl]-1-(2,4-dimethylphenyl)prop-2-en-1-one Chemical compound CN(C)CC(=C)C(=O)C1=CC=C(C)C=C1C QXLQZLBNPTZMRK-UHFFFAOYSA-N 0.000 description 1
- QSAVEGSLJISCDF-UHFFFAOYSA-N 2-hydroxy-2-phenylacetic acid (1,2,2,6-tetramethyl-4-piperidinyl) ester Chemical compound C1C(C)(C)N(C)C(C)CC1OC(=O)C(O)C1=CC=CC=C1 QSAVEGSLJISCDF-UHFFFAOYSA-N 0.000 description 1
- AKJHMTWEGVYYSE-AIRMAKDCSA-N 4-HPR Chemical compound C=1C=C(O)C=CC=1NC(=O)/C=C(\C)/C=C/C=C(C)C=CC1=C(C)CCCC1(C)C AKJHMTWEGVYYSE-AIRMAKDCSA-N 0.000 description 1
- 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 1
- NFLLKCVHYJRNRH-UHFFFAOYSA-N 8-chloro-1,3-dimethyl-7H-purine-2,6-dione 2-(diphenylmethyl)oxy-N,N-dimethylethanamine Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC(Cl)=N2.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 NFLLKCVHYJRNRH-UHFFFAOYSA-N 0.000 description 1
- NOESYZHRGYRDHS-ZYCCASTOSA-N 8a-l-threonine-10a-l-isoleucine-insulin Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 NOESYZHRGYRDHS-ZYCCASTOSA-N 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- 239000005541 ACE inhibitor Substances 0.000 description 1
- 244000215068 Acacia senegal Species 0.000 description 1
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 0.000 description 1
- ULXXDDBFHOBEHA-ONEGZZNKSA-N Afatinib Chemical compound N1=CN=C2C=C(OC3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-ONEGZZNKSA-N 0.000 description 1
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 description 1
- APKFDSVGJQXUKY-KKGHZKTASA-N Amphotericin-B Natural products O[C@H]1[C@@H](N)[C@H](O)[C@@H](C)O[C@H]1O[C@H]1C=CC=CC=CC=CC=CC=CC=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-KKGHZKTASA-N 0.000 description 1
- 108010058207 Anistreplase Proteins 0.000 description 1
- 108010039627 Aprotinin Proteins 0.000 description 1
- 108010024976 Asparaginase Proteins 0.000 description 1
- 102000015790 Asparaginase Human genes 0.000 description 1
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 241000894006 Bacteria Species 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- 241000283690 Bos taurus Species 0.000 description 1
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 description 1
- 102100032957 C5a anaphylatoxin chemotactic receptor 1 Human genes 0.000 description 1
- 101710098483 C5a anaphylatoxin chemotactic receptor 1 Proteins 0.000 description 1
- 101150071146 COX2 gene Proteins 0.000 description 1
- 101100114534 Caenorhabditis elegans ctc-2 gene Proteins 0.000 description 1
- 102400000113 Calcitonin Human genes 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- UXVMQQNJUSDDNG-UHFFFAOYSA-L Calcium chloride Chemical compound [Cl-].[Cl-].[Ca+2] UXVMQQNJUSDDNG-UHFFFAOYSA-L 0.000 description 1
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 1
- 229920002134 Carboxymethyl cellulose Polymers 0.000 description 1
- DLGOEMSEDOSKAD-UHFFFAOYSA-N Carmustine Chemical compound ClCCNC(=O)N(N=O)CCCl DLGOEMSEDOSKAD-UHFFFAOYSA-N 0.000 description 1
- 239000004099 Chlortetracycline Substances 0.000 description 1
- 108010005939 Ciliary Neurotrophic Factor Proteins 0.000 description 1
- 102100031614 Ciliary neurotrophic factor Human genes 0.000 description 1
- 229910000684 Cobalt-chrome Inorganic materials 0.000 description 1
- 102000029816 Collagenase Human genes 0.000 description 1
- 108060005980 Collagenase Proteins 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 102400000739 Corticotropin Human genes 0.000 description 1
- 101800000414 Corticotropin Proteins 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 102000001493 Cyclophilins Human genes 0.000 description 1
- 108010068682 Cyclophilins Proteins 0.000 description 1
- PMATZTZNYRCHOR-CGLBZJNRSA-N Cyclosporin A Chemical compound CC[C@@H]1NC(=O)[C@H]([C@H](O)[C@H](C)C\C=C\C)N(C)C(=O)[C@H](C(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](CC(C)C)N(C)C(=O)[C@@H](C)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)N(C)C(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)N(C)C(=O)CN(C)C1=O PMATZTZNYRCHOR-CGLBZJNRSA-N 0.000 description 1
- 108010036949 Cyclosporine Proteins 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 101100481404 Danio rerio tie1 gene Proteins 0.000 description 1
- 108010019673 Darbepoetin alfa Proteins 0.000 description 1
- ZBNZXTGUTAYRHI-UHFFFAOYSA-N Dasatinib Chemical compound C=1C(N2CCN(CCO)CC2)=NC(C)=NC=1NC(S1)=NC=C1C(=O)NC1=C(C)C=CC=C1Cl ZBNZXTGUTAYRHI-UHFFFAOYSA-N 0.000 description 1
- 108010000437 Deamino Arginine Vasopressin Proteins 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 102400001099 Endorepellin Human genes 0.000 description 1
- 101800001739 Endorepellin Proteins 0.000 description 1
- 108010032976 Enfuvirtide Proteins 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- 108010074604 Epoetin Alfa Proteins 0.000 description 1
- 108010056764 Eptifibatide Proteins 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 108010011459 Exenatide Proteins 0.000 description 1
- HTQBXNHDCUEHJF-XWLPCZSASA-N Exenatide Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)NCC(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CO)C(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCSC)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)CNC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 HTQBXNHDCUEHJF-XWLPCZSASA-N 0.000 description 1
- 206010015943 Eye inflammation Diseases 0.000 description 1
- 108010054265 Factor VIIa Proteins 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 102100037362 Fibronectin Human genes 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 206010016654 Fibrosis Diseases 0.000 description 1
- 108010029961 Filgrastim Proteins 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 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
- 108010072051 Glatiramer Acetate Proteins 0.000 description 1
- 102000006395 Globulins Human genes 0.000 description 1
- 108010044091 Globulins Proteins 0.000 description 1
- BLCLNMBMMGCOAS-URPVMXJPSA-N Goserelin Chemical compound C([C@@H](C(=O)N[C@H](COC(C)(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCN=C(N)N)C(=O)N1[C@@H](CCC1)C(=O)NNC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H]1NC(=O)CC1)C1=CC=C(O)C=C1 BLCLNMBMMGCOAS-URPVMXJPSA-N 0.000 description 1
- 108010069236 Goserelin Proteins 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 108010051696 Growth Hormone Proteins 0.000 description 1
- 229920000084 Gum arabic Polymers 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 0.000 description 1
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 1
- ZTVIKZXZYLEVOL-MCOXGKPRSA-N Homatropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(O)C1=CC=CC=C1 ZTVIKZXZYLEVOL-MCOXGKPRSA-N 0.000 description 1
- 241000282412 Homo Species 0.000 description 1
- 108091006905 Human Serum Albumin Proteins 0.000 description 1
- 102000008100 Human Serum Albumin Human genes 0.000 description 1
- 108010003272 Hyaluronate lyase Proteins 0.000 description 1
- 102000001974 Hyaluronidases Human genes 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
- 102100029199 Iduronate 2-sulfatase Human genes 0.000 description 1
- 108060003951 Immunoglobulin Proteins 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 108090001061 Insulin Proteins 0.000 description 1
- 102000004877 Insulin Human genes 0.000 description 1
- 108010065920 Insulin Lispro Proteins 0.000 description 1
- COCFEDIXXNGUNL-RFKWWTKHSA-N Insulin glargine Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(O)=O)C(=O)NCC(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 COCFEDIXXNGUNL-RFKWWTKHSA-N 0.000 description 1
- 108010078049 Interferon alpha-2 Proteins 0.000 description 1
- 102100040018 Interferon alpha-2 Human genes 0.000 description 1
- 108010047761 Interferon-alpha Proteins 0.000 description 1
- 102000006992 Interferon-alpha Human genes 0.000 description 1
- 108010079944 Interferon-alpha2b Proteins 0.000 description 1
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 description 1
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 description 1
- 239000005517 L01XE01 - Imatinib Substances 0.000 description 1
- 239000005411 L01XE02 - Gefitinib Substances 0.000 description 1
- 239000005551 L01XE03 - Erlotinib Substances 0.000 description 1
- 239000002067 L01XE06 - Dasatinib Substances 0.000 description 1
- 239000005536 L01XE08 - Nilotinib Substances 0.000 description 1
- 239000003798 L01XE11 - Pazopanib Substances 0.000 description 1
- 239000002118 L01XE12 - Vandetanib Substances 0.000 description 1
- 201000010538 Lactose Intolerance Diseases 0.000 description 1
- 108010000817 Leuprolide Proteins 0.000 description 1
- 102000009151 Luteinizing Hormone Human genes 0.000 description 1
- 108010073521 Luteinizing Hormone Proteins 0.000 description 1
- 208000024556 Mendelian disease Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- BYBLEWFAAKGYCD-UHFFFAOYSA-N Miconazole Chemical compound ClC1=CC(Cl)=CC=C1COC(C=1C(=CC(Cl)=CC=1)Cl)CN1C=NC=C1 BYBLEWFAAKGYCD-UHFFFAOYSA-N 0.000 description 1
- 101100481406 Mus musculus Tie1 gene Proteins 0.000 description 1
- 101100046669 Mus musculus Tox gene Proteins 0.000 description 1
- 241001553014 Myrsine salicina Species 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
- MKYBYDHXWVHEJW-UHFFFAOYSA-N N-[1-oxo-1-(2,4,6,7-tetrahydrotriazolo[4,5-c]pyridin-5-yl)propan-2-yl]-2-[[3-(trifluoromethoxy)phenyl]methylamino]pyrimidine-5-carboxamide Chemical compound O=C(C(C)NC(=O)C=1C=NC(=NC=1)NCC1=CC(=CC=C1)OC(F)(F)F)N1CC2=C(CC1)NN=N2 MKYBYDHXWVHEJW-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 239000004677 Nylon Substances 0.000 description 1
- 206010061876 Obstruction Diseases 0.000 description 1
- 108010016076 Octreotide Proteins 0.000 description 1
- 108700006640 OspA Proteins 0.000 description 1
- 239000004100 Oxytetracycline Substances 0.000 description 1
- 101150000187 PTGS2 gene Proteins 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- 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 1
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 1
- 108010038512 Platelet-Derived Growth Factor Proteins 0.000 description 1
- 102000010780 Platelet-Derived Growth Factor Human genes 0.000 description 1
- 239000004952 Polyamide Substances 0.000 description 1
- 239000004695 Polyether sulfone Substances 0.000 description 1
- 239000004698 Polyethylene Substances 0.000 description 1
- 239000004642 Polyimide Substances 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 239000004793 Polystyrene Substances 0.000 description 1
- 206010067268 Post procedural infection Diseases 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- 208000001647 Renal Insufficiency Diseases 0.000 description 1
- 208000037111 Retinal Hemorrhage Diseases 0.000 description 1
- 201000007737 Retinal degeneration Diseases 0.000 description 1
- 206010057430 Retinal injury Diseases 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 1
- 206010040070 Septic Shock Diseases 0.000 description 1
- 108010071390 Serum Albumin Proteins 0.000 description 1
- 102000007562 Serum Albumin Human genes 0.000 description 1
- 102100038803 Somatotropin Human genes 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- 108010023197 Streptokinase Proteins 0.000 description 1
- 208000007271 Substance Withdrawal Syndrome Diseases 0.000 description 1
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- QJJXYPPXXYFBGM-LFZNUXCKSA-N Tacrolimus Chemical compound C1C[C@@H](O)[C@H](OC)C[C@@H]1\C=C(/C)[C@@H]1[C@H](C)[C@@H](O)CC(=O)[C@H](CC=C)/C=C(C)/C[C@H](C)C[C@H](OC)[C@H]([C@H](C[C@H]2C)OC)O[C@@]2(O)C(=O)C(=O)N2CCCC[C@H]2C(=O)O1 QJJXYPPXXYFBGM-LFZNUXCKSA-N 0.000 description 1
- 239000004809 Teflon Substances 0.000 description 1
- 229920006362 Teflon® Polymers 0.000 description 1
- CBPNZQVSJQDFBE-FUXHJELOSA-N Temsirolimus Chemical compound C1C[C@@H](OC(=O)C(C)(CO)CO)[C@H](OC)C[C@@H]1C[C@@H](C)[C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@](O)(O2)[C@H](C)CC[C@H]2C[C@H](OC)/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C1 CBPNZQVSJQDFBE-FUXHJELOSA-N 0.000 description 1
- 108010039185 Tenecteplase Proteins 0.000 description 1
- 108010049264 Teriparatide Proteins 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 description 1
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 description 1
- 102000004887 Transforming Growth Factor beta Human genes 0.000 description 1
- 108090001012 Transforming Growth Factor beta Proteins 0.000 description 1
- BGDKAVGWHJFAGW-UHFFFAOYSA-N Tropicamide Chemical compound C=1C=CC=CC=1C(CO)C(=O)N(CC)CC1=CC=NC=C1 BGDKAVGWHJFAGW-UHFFFAOYSA-N 0.000 description 1
- 108010057266 Type A Botulinum Toxins Proteins 0.000 description 1
- 108010047196 Urofollitropin Proteins 0.000 description 1
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 description 1
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 description 1
- 206010046851 Uveitis Diseases 0.000 description 1
- 108010031318 Vitronectin Proteins 0.000 description 1
- 102100035140 Vitronectin Human genes 0.000 description 1
- JPKKQJKQTPNWTR-BRYCGAMXSA-N [(1r,5s)-8-methyl-8-azabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfuric acid;hydrate Chemical compound O.OS(O)(=O)=O.C([C@H]1CC[C@@H](C2)N1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)N1C)C2OC(=O)C(CO)C1=CC=CC=C1 JPKKQJKQTPNWTR-BRYCGAMXSA-N 0.000 description 1
- DPHFJXVKASDMBW-RQRKFSSASA-N [2-[(8s,9r,10s,11s,13s,14s,16r,17r)-9-fluoro-11,17-dihydroxy-10,13,16-trimethyl-3-oxo-6,7,8,11,12,14,15,16-octahydrocyclopenta[a]phenanthren-17-yl]-2-oxoethyl] acetate;hydrate Chemical compound O.C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)COC(C)=O)(O)[C@@]1(C)C[C@@H]2O DPHFJXVKASDMBW-RQRKFSSASA-N 0.000 description 1
- JNWFIPVDEINBAI-UHFFFAOYSA-N [5-hydroxy-4-[4-(1-methylindol-5-yl)-5-oxo-1H-1,2,4-triazol-3-yl]-2-propan-2-ylphenyl] dihydrogen phosphate Chemical compound C1=C(OP(O)(O)=O)C(C(C)C)=CC(C=2N(C(=O)NN=2)C=2C=C3C=CN(C)C3=CC=2)=C1O JNWFIPVDEINBAI-UHFFFAOYSA-N 0.000 description 1
- WAIPAZQMEIHHTJ-UHFFFAOYSA-N [Cr].[Co] Chemical compound [Cr].[Co] WAIPAZQMEIHHTJ-UHFFFAOYSA-N 0.000 description 1
- 229960002184 abarelix Drugs 0.000 description 1
- 108010023617 abarelix Proteins 0.000 description 1
- AIWRTTMUVOZGPW-HSPKUQOVSA-N abarelix Chemical compound C([C@@H](C(=O)N[C@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCCNC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)N(C)C(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 AIWRTTMUVOZGPW-HSPKUQOVSA-N 0.000 description 1
- 229960003697 abatacept Drugs 0.000 description 1
- 229960000446 abciximab Drugs 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 235000010489 acacia gum Nutrition 0.000 description 1
- 239000000205 acacia gum Substances 0.000 description 1
- BZKPWHYZMXOIDC-UHFFFAOYSA-N acetazolamide Chemical compound CC(=O)NC1=NN=C(S(N)(=O)=O)S1 BZKPWHYZMXOIDC-UHFFFAOYSA-N 0.000 description 1
- 229960000571 acetazolamide Drugs 0.000 description 1
- JUGOREOARAHOCO-UHFFFAOYSA-M acetylcholine chloride Chemical compound [Cl-].CC(=O)OCC[N+](C)(C)C JUGOREOARAHOCO-UHFFFAOYSA-M 0.000 description 1
- 229960004266 acetylcholine chloride Drugs 0.000 description 1
- 229960004150 aciclovir Drugs 0.000 description 1
- MKUXAQIIEYXACX-UHFFFAOYSA-N aciclovir Chemical compound N1C(N)=NC(=O)C2=C1N(COCCO)C=N2 MKUXAQIIEYXACX-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 201000009628 adenosine deaminase deficiency Diseases 0.000 description 1
- 239000000853 adhesive Substances 0.000 description 1
- 230000001070 adhesive effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229960005310 aldesleukin Drugs 0.000 description 1
- 108700025316 aldesleukin Proteins 0.000 description 1
- 229960002459 alefacept Drugs 0.000 description 1
- 229960000548 alemtuzumab Drugs 0.000 description 1
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 description 1
- 229940003677 alphagan Drugs 0.000 description 1
- 229960003318 alteplase 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
- 229960003942 amphotericin b Drugs 0.000 description 1
- 229960004238 anakinra Drugs 0.000 description 1
- 238000004873 anchoring Methods 0.000 description 1
- 208000007502 anemia Diseases 0.000 description 1
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 1
- 229960000983 anistreplase Drugs 0.000 description 1
- 229960002469 antazoline Drugs 0.000 description 1
- REYFJDPCWQRWAA-UHFFFAOYSA-N antazoline Chemical compound N=1CCNC=1CN(C=1C=CC=CC=1)CC1=CC=CC=C1 REYFJDPCWQRWAA-UHFFFAOYSA-N 0.000 description 1
- 230000000118 anti-neoplastic effect Effects 0.000 description 1
- 230000003431 anti-prostaglandin Effects 0.000 description 1
- 230000001494 anti-thymocyte effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940125715 antihistaminic agent Drugs 0.000 description 1
- 229940045686 antimetabolites antineoplastic purine analogs Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 230000006907 apoptotic process Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960004405 aprotinin Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960003272 asparaginase Drugs 0.000 description 1
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 229960002028 atropine sulfate Drugs 0.000 description 1
- 230000003190 augmentative effect Effects 0.000 description 1
- 208000036556 autosomal recessive T cell-negative B cell-negative NK cell-negative due to adenosine deaminase deficiency severe combined immunodeficiency Diseases 0.000 description 1
- 229960003005 axitinib Drugs 0.000 description 1
- RITAVMQDGBJQJZ-FMIVXFBMSA-N axitinib Chemical compound CNC(=O)C1=CC=CC=C1SC1=CC=C(C(\C=C\C=2N=CC=CC=2)=NN2)C2=C1 RITAVMQDGBJQJZ-FMIVXFBMSA-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
- 229960004669 basiliximab Drugs 0.000 description 1
- 239000002876 beta blocker Substances 0.000 description 1
- DRTQHJPVMGBUCF-PSQAKQOGSA-N beta-L-uridine Natural products O[C@H]1[C@@H](O)[C@H](CO)O[C@@H]1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-PSQAKQOGSA-N 0.000 description 1
- 229940098085 betagan Drugs 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
- 239000000560 biocompatible material Substances 0.000 description 1
- 230000033228 biological regulation Effects 0.000 description 1
- 108010055460 bivalirudin Proteins 0.000 description 1
- 229960001500 bivalirudin Drugs 0.000 description 1
- OIRCOABEOLEUMC-GEJPAHFPSA-N bivalirudin Chemical compound C([C@@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CC(N)=O)NC(=O)CNC(=O)CNC(=O)CNC(=O)CNC(=O)[C@H]1N(CCC1)C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H]1N(CCC1)C(=O)[C@H](N)CC=1C=CC=CC=1)C1=CC=CC=C1 OIRCOABEOLEUMC-GEJPAHFPSA-N 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 210000001124 body fluid Anatomy 0.000 description 1
- 239000010839 body fluid Substances 0.000 description 1
- 229940094657 botulinum toxin type a Drugs 0.000 description 1
- 210000004556 brain Anatomy 0.000 description 1
- 229960003679 brimonidine Drugs 0.000 description 1
- 229960004015 calcitonin Drugs 0.000 description 1
- BBBFJLBPOGFECG-VJVYQDLKSA-N calcitonin Chemical compound N([C@H](C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(N)=O)C(C)C)C(=O)[C@@H]1CSSC[C@H](N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1 BBBFJLBPOGFECG-VJVYQDLKSA-N 0.000 description 1
- 239000001110 calcium chloride Substances 0.000 description 1
- 229910001628 calcium chloride Inorganic materials 0.000 description 1
- 229950001178 capromab Drugs 0.000 description 1
- 229960004484 carbachol 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
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 229960004424 carbon dioxide Drugs 0.000 description 1
- 235000011089 carbon dioxide Nutrition 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 230000004663 cell proliferation Effects 0.000 description 1
- 230000001413 cellular effect Effects 0.000 description 1
- 229920002301 cellulose acetate Polymers 0.000 description 1
- 229940106164 cephalexin Drugs 0.000 description 1
- AVGYWQBCYZHHPN-CYJZLJNKSA-N cephalexin monohydrate Chemical compound O.C1([C@@H](N)C(=O)N[C@H]2[C@@H]3N(C2=O)C(=C(CS3)C)C(O)=O)=CC=CC=C1 AVGYWQBCYZHHPN-CYJZLJNKSA-N 0.000 description 1
- 229960003230 cetrorelix Drugs 0.000 description 1
- 108700008462 cetrorelix Proteins 0.000 description 1
- SBNPWPIBESPSIF-MHWMIDJBSA-N cetrorelix Chemical compound C([C@@H](C(=O)N[C@H](CCCNC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@H](C)C(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](CC=1C=NC=CC=1)NC(=O)[C@@H](CC=1C=CC(Cl)=CC=1)NC(=O)[C@@H](CC=1C=C2C=CC=CC2=CC=1)NC(C)=O)C1=CC=C(O)C=C1 SBNPWPIBESPSIF-MHWMIDJBSA-N 0.000 description 1
- WMEMLXDTLKSUOD-OGCOPIPOSA-N chembl436844 Chemical compound C([C@H]1C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CSSC[C@@H](C(N[C@H](C(=O)N[C@@H](CC=2C3=CC=CC=C3N(C)C=2)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=2C3=CC=CC=C3NC=2)C(=O)NCC(=O)N[C@@H](C)C(=O)N1)C(C)C)=O)NC(=O)[C@@H](NC(C)=O)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(N)=O)C1=CN=CN1 WMEMLXDTLKSUOD-OGCOPIPOSA-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
- 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
- 229960001265 ciclosporin Drugs 0.000 description 1
- 210000004240 ciliary body Anatomy 0.000 description 1
- 229960003405 ciprofloxacin Drugs 0.000 description 1
- DQLATGHUWYMOKM-UHFFFAOYSA-L cisplatin Chemical compound N[Pt](N)(Cl)Cl DQLATGHUWYMOKM-UHFFFAOYSA-L 0.000 description 1
- 229960004316 cisplatin Drugs 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- AGVAZMGAQJOSFJ-WZHZPDAFSA-M cobalt(2+);[(2r,3s,4r,5s)-5-(5,6-dimethylbenzimidazol-1-yl)-4-hydroxy-2-(hydroxymethyl)oxolan-3-yl] [(2r)-1-[3-[(1r,2r,3r,4z,7s,9z,12s,13s,14z,17s,18s,19r)-2,13,18-tris(2-amino-2-oxoethyl)-7,12,17-tris(3-amino-3-oxopropyl)-3,5,8,8,13,15,18,19-octamethyl-2 Chemical compound [Co+2].N#[C-].[N-]([C@@H]1[C@H](CC(N)=O)[C@@]2(C)CCC(=O)NC[C@@H](C)OP(O)(=O)O[C@H]3[C@H]([C@H](O[C@@H]3CO)N3C4=CC(C)=C(C)C=C4N=C3)O)\C2=C(C)/C([C@H](C\2(C)C)CCC(N)=O)=N/C/2=C\C([C@H]([C@@]/2(CC(N)=O)C)CCC(N)=O)=N\C\2=C(C)/C2=N[C@]1(C)[C@@](C)(CC(N)=O)[C@@H]2CCC(N)=O AGVAZMGAQJOSFJ-WZHZPDAFSA-M 0.000 description 1
- 239000010952 cobalt-chrome Substances 0.000 description 1
- 229960002424 collagenase Drugs 0.000 description 1
- 230000024203 complement activation Effects 0.000 description 1
- 239000004074 complement inhibitor Substances 0.000 description 1
- 230000001143 conditioned effect Effects 0.000 description 1
- 235000009508 confectionery Nutrition 0.000 description 1
- 230000001276 controlling effect Effects 0.000 description 1
- 229940038717 copaxone Drugs 0.000 description 1
- 239000002285 corn oil Substances 0.000 description 1
- 235000005687 corn oil Nutrition 0.000 description 1
- 230000002596 correlated effect Effects 0.000 description 1
- 230000001054 cortical effect Effects 0.000 description 1
- 229960000258 corticotropin Drugs 0.000 description 1
- IDLFZVILOHSSID-OVLDLUHVSA-N corticotropin Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(N)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)NC(=O)[C@@H](N)CO)C1=CC=C(O)C=C1 IDLFZVILOHSSID-OVLDLUHVSA-N 0.000 description 1
- ALEXXDVDDISNDU-JZYPGELDSA-N cortisol 21-acetate Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)COC(=O)C)(O)[C@@]1(C)C[C@@H]2O ALEXXDVDDISNDU-JZYPGELDSA-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
- 229930182912 cyclosporin Natural products 0.000 description 1
- 229960002806 daclizumab Drugs 0.000 description 1
- 229960005029 darbepoetin alfa Drugs 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 229940124581 decongestants Drugs 0.000 description 1
- 229960004120 defibrotide Drugs 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 238000011118 depth filtration Methods 0.000 description 1
- 229960004281 desmopressin Drugs 0.000 description 1
- NFLWUMRGJYTJIN-NXBWRCJVSA-N desmopressin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CC(N)=O)C(=O)N[C@@H](CSSCCC(=O)N[C@@H](CC=2C=CC(O)=CC=2)C(=O)N1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(N)=O)=O)CCC(=O)N)C1=CC=CC=C1 NFLWUMRGJYTJIN-NXBWRCJVSA-N 0.000 description 1
- 229960003657 dexamethasone acetate Drugs 0.000 description 1
- VQODGRNSFPNSQE-CXSFZGCWSA-N dexamethasone phosphate 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)COP(O)(O)=O)(O)[C@@]1(C)C[C@@H]2O VQODGRNSFPNSQE-CXSFZGCWSA-N 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 229940061607 dibasic sodium phosphate Drugs 0.000 description 1
- MUCZHBLJLSDCSD-UHFFFAOYSA-N diisopropyl fluorophosphate Chemical compound CC(C)OP(F)(=O)OC(C)C MUCZHBLJLSDCSD-UHFFFAOYSA-N 0.000 description 1
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000007598 dipping method Methods 0.000 description 1
- NJDNXYGOVLYJHP-UHFFFAOYSA-L disodium;2-(3-oxido-6-oxoxanthen-9-yl)benzoate Chemical compound [Na+].[Na+].[O-]C(=O)C1=CC=CC=C1C1=C2C=CC(=O)C=C2OC2=CC([O-])=CC=C21 NJDNXYGOVLYJHP-UHFFFAOYSA-L 0.000 description 1
- LVXHNCUCBXIIPE-UHFFFAOYSA-L disodium;hydrogen phosphate;hydrate Chemical compound O.[Na+].[Na+].OP([O-])([O-])=O LVXHNCUCBXIIPE-UHFFFAOYSA-L 0.000 description 1
- 208000035475 disorder Diseases 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 229960000533 dornase alfa Drugs 0.000 description 1
- 108010067396 dornase alfa Proteins 0.000 description 1
- 229960003933 dorzolamide Drugs 0.000 description 1
- 229940056176 drotrecogin alfa Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 229940126534 drug product Drugs 0.000 description 1
- 238000007923 drug release testing Methods 0.000 description 1
- 208000011325 dry age related macular degeneration Diseases 0.000 description 1
- OVXQHPWHMXOFRD-UHFFFAOYSA-M ecothiopate iodide Chemical compound [I-].CCOP(=O)(OCC)SCC[N+](C)(C)C OVXQHPWHMXOFRD-UHFFFAOYSA-M 0.000 description 1
- 229960002224 eculizumab Drugs 0.000 description 1
- 229960000284 efalizumab Drugs 0.000 description 1
- 229910000701 elgiloys (Co-Cr-Ni Alloy) Inorganic materials 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 238000010828 elution Methods 0.000 description 1
- 229950000472 embramine Drugs 0.000 description 1
- URSRSKSNFPUKGH-UHFFFAOYSA-N embramine Chemical compound C=1C=C(Br)C=CC=1C(C)(OCCN(C)C)C1=CC=CC=C1 URSRSKSNFPUKGH-UHFFFAOYSA-N 0.000 description 1
- 206010014801 endophthalmitis Diseases 0.000 description 1
- 229960002062 enfuvirtide Drugs 0.000 description 1
- PEASPLKKXBYDKL-FXEVSJAOSA-N enfuvirtide Chemical compound C([C@@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](C)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(C)=O)[C@@H](C)O)[C@@H](C)CC)C1=CN=CN1 PEASPLKKXBYDKL-FXEVSJAOSA-N 0.000 description 1
- 239000002532 enzyme inhibitor Substances 0.000 description 1
- 229940116977 epidermal growth factor Drugs 0.000 description 1
- 102000052116 epidermal growth factor receptor activity proteins Human genes 0.000 description 1
- 108700015053 epidermal growth factor receptor activity proteins Proteins 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229960003388 epoetin alfa Drugs 0.000 description 1
- 229960004468 eptifibatide Drugs 0.000 description 1
- GLGOPUHVAZCPRB-LROMGURASA-N eptifibatide Chemical compound N1C(=O)[C@H](CC(O)=O)NC(=O)CNC(=O)[C@H](CCCCNC(=N)N)NC(=O)CCSSC[C@@H](C(N)=O)NC(=O)[C@@H]2CCCN2C(=O)[C@@H]1CC1=CN=C2[C]1C=CC=C2 GLGOPUHVAZCPRB-LROMGURASA-N 0.000 description 1
- 229960001433 erlotinib Drugs 0.000 description 1
- AAKJLRGGTJKAMG-UHFFFAOYSA-N erlotinib Chemical compound C=12C=C(OCCOC)C(OCCOC)=CC2=NC=NC=1NC1=CC=CC(C#C)=C1 AAKJLRGGTJKAMG-UHFFFAOYSA-N 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229930182833 estradiol Natural products 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229950002420 eucatropine Drugs 0.000 description 1
- 238000011156 evaluation Methods 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 230000029142 excretion Effects 0.000 description 1
- 229960001519 exenatide Drugs 0.000 description 1
- 229950003662 fenretinide Drugs 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 230000004761 fibrosis Effects 0.000 description 1
- 229960004177 filgrastim Drugs 0.000 description 1
- 238000005429 filling process Methods 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
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960005051 fluostigmine Drugs 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229960002963 ganciclovir Drugs 0.000 description 1
- IRSCQMHQWWYFCW-UHFFFAOYSA-N ganciclovir Chemical compound O=C1NC(N)=NC2=C1N=CN2COC(CO)CO IRSCQMHQWWYFCW-UHFFFAOYSA-N 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 229960002584 gefitinib Drugs 0.000 description 1
- XGALLCVXEZPNRQ-UHFFFAOYSA-N gefitinib Chemical compound C=12C=C(OCCCN3CCOCC3)C(OC)=CC2=NC=NC=1NC1=CC=C(F)C(Cl)=C1 XGALLCVXEZPNRQ-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 229960000578 gemtuzumab Drugs 0.000 description 1
- 230000002068 genetic effect Effects 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 239000011491 glass wool Substances 0.000 description 1
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 description 1
- 229960004666 glucagon Drugs 0.000 description 1
- 150000002334 glycols Chemical class 0.000 description 1
- 229960002913 goserelin Drugs 0.000 description 1
- 229960004905 gramicidin Drugs 0.000 description 1
- ZWCXYZRRTRDGQE-SORVKSEFSA-N gramicidina Chemical compound C1=CC=C2C(C[C@H](NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@@H](CC(C)C)NC(=O)[C@H](CC=3C4=CC=CC=C4NC=3)NC(=O)[C@H](C(C)C)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](C(C)C)NC(=O)[C@H](C)NC(=O)[C@H](NC(=O)[C@H](C)NC(=O)CNC(=O)[C@@H](NC=O)C(C)C)CC(C)C)C(=O)NCCO)=CNC2=C1 ZWCXYZRRTRDGQE-SORVKSEFSA-N 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 208000014951 hematologic disease Diseases 0.000 description 1
- 208000006454 hepatitis Diseases 0.000 description 1
- 231100000283 hepatitis Toxicity 0.000 description 1
- 210000003494 hepatocyte Anatomy 0.000 description 1
- 230000004371 high visual acuity Effects 0.000 description 1
- 229960000857 homatropine Drugs 0.000 description 1
- 229940125697 hormonal agent Drugs 0.000 description 1
- WNRQPCUGRUFHED-DETKDSODSA-N humalog Chemical compound C([C@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CO)NC(=O)[C@H](CS)NC(=O)[C@H]([C@@H](C)CC)NC(=O)[C@H](CO)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CS)NC(=O)[C@H](CS)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(N)=O)C(O)=O)C1=CC=C(O)C=C1.C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CS)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 WNRQPCUGRUFHED-DETKDSODSA-N 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 229960002773 hyaluronidase Drugs 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 229960001067 hydrocortisone acetate Drugs 0.000 description 1
- 229950005360 hydroxyamfetamine Drugs 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 108010072166 idursulfase Proteins 0.000 description 1
- 229960002396 idursulfase Drugs 0.000 description 1
- 229960002411 imatinib Drugs 0.000 description 1
- KTUFNOKKBVMGRW-UHFFFAOYSA-N imatinib Chemical compound C1CN(C)CCN1CC1=CC=C(C(=O)NC=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)C=C1 KTUFNOKKBVMGRW-UHFFFAOYSA-N 0.000 description 1
- 210000002865 immune cell Anatomy 0.000 description 1
- 230000001900 immune effect Effects 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 102000018358 immunoglobulin Human genes 0.000 description 1
- 229960001438 immunostimulant agent Drugs 0.000 description 1
- 239000003022 immunostimulating agent Substances 0.000 description 1
- 230000003308 immunostimulating effect Effects 0.000 description 1
- 230000001771 impaired effect Effects 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000099 in vitro assay Methods 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
- 239000007972 injectable composition Substances 0.000 description 1
- 238000012966 insertion method Methods 0.000 description 1
- 238000007689 inspection Methods 0.000 description 1
- 229940125396 insulin Drugs 0.000 description 1
- PBGKTOXHQIOBKM-FHFVDXKLSA-N insulin (human) Chemical compound C([C@@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@H]1CSSC[C@H]2C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@H](C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=3C=CC(O)=CC=3)C(=O)N[C@@H](CSSC[C@H](NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3C=CC(O)=CC=3)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=3NC=NC=3)NC(=O)[C@H](CO)NC(=O)CNC1=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)NCC(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(=O)N[C@@H](CC(N)=O)C(O)=O)=O)CSSC[C@@H](C(N2)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](C(C)C)NC(=O)[C@@H](NC(=O)CN)[C@@H](C)CC)[C@@H](C)CC)[C@@H](C)O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC=1C=CC=CC=1)C(C)C)C1=CN=CN1 PBGKTOXHQIOBKM-FHFVDXKLSA-N 0.000 description 1
- 229960002068 insulin lispro Drugs 0.000 description 1
- 229940047124 interferons Drugs 0.000 description 1
- 230000016507 interphase Effects 0.000 description 1
- 230000000968 intestinal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 230000004410 intraocular pressure Effects 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 230000001788 irregular Effects 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
- 201000006370 kidney failure Diseases 0.000 description 1
- 229960004408 lepirudin Drugs 0.000 description 1
- OTQCKZUSUGYWBD-BRHMIFOHSA-N lepirudin Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CS)C(=O)N[C@H](C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CS)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@H](C(=O)N[C@@H](CS)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CS)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CS)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H]([C@@H](C)O)C(=O)NCC(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H]([C@@H](C)O)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCCN)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)NCC(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(O)=O)C(C)C)[C@@H](C)O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)[C@@H](N)CC(C)C)[C@@H](C)O)C1=CC=C(O)C=C1 OTQCKZUSUGYWBD-BRHMIFOHSA-N 0.000 description 1
- 208000032839 leukemia Diseases 0.000 description 1
- GFIJNRVAKGFPGQ-LIJARHBVSA-N leuprolide Chemical compound CCNC(=O)[C@@H]1CCCN1C(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](CC(C)C)NC(=O)[C@@H](NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H](CC=1N=CNC=1)NC(=O)[C@H]1NC(=O)CC1)CC1=CC=C(O)C=C1 GFIJNRVAKGFPGQ-LIJARHBVSA-N 0.000 description 1
- 229960004338 leuprorelin Drugs 0.000 description 1
- 229960000831 levobunolol Drugs 0.000 description 1
- IXHBTMCLRNMKHZ-LBPRGKRZSA-N levobunolol Chemical compound O=C1CCCC2=C1C=CC=C2OC[C@@H](O)CNC(C)(C)C IXHBTMCLRNMKHZ-LBPRGKRZSA-N 0.000 description 1
- DNTDOBSIBZKFCP-YDALLXLXSA-N levobunolol hydrochloride Chemical compound [Cl-].O=C1CCCC2=C1C=CC=C2OC[C@@H](O)C[NH2+]C(C)(C)C DNTDOBSIBZKFCP-YDALLXLXSA-N 0.000 description 1
- 230000000670 limiting effect Effects 0.000 description 1
- 238000003754 machining Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 230000000873 masking effect Effects 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- FLOSMHQXBMRNHR-DAXSKMNVSA-N methazolamide Chemical compound CC(=O)\N=C1/SC(S(N)(=O)=O)=NN1C FLOSMHQXBMRNHR-DAXSKMNVSA-N 0.000 description 1
- 229960004083 methazolamide Drugs 0.000 description 1
- 229920000609 methyl cellulose Polymers 0.000 description 1
- 239000001923 methylcellulose Substances 0.000 description 1
- 229960002509 miconazole Drugs 0.000 description 1
- 230000000813 microbial effect Effects 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 239000003604 miotic agent Substances 0.000 description 1
- 238000002156 mixing Methods 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000004682 monohydrates Chemical class 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 210000003205 muscle Anatomy 0.000 description 1
- 230000002911 mydriatic effect Effects 0.000 description 1
- LBWFXVZLPYTWQI-IPOVEDGCSA-N n-[2-(diethylamino)ethyl]-5-[(z)-(5-fluoro-2-oxo-1h-indol-3-ylidene)methyl]-2,4-dimethyl-1h-pyrrole-3-carboxamide;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.CCN(CC)CCNC(=O)C1=C(C)NC(\C=C/2C3=CC(F)=CC=C3NC\2=O)=C1C LBWFXVZLPYTWQI-IPOVEDGCSA-N 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
- 229960005016 naphazoline Drugs 0.000 description 1
- 229960005027 natalizumab Drugs 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 229960001267 nesiritide Drugs 0.000 description 1
- HPNRHPKXQZSDFX-OAQDCNSJSA-N nesiritide Chemical compound C([C@H]1C(=O)NCC(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@H](C(N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)N[C@@H](CO)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CSSC[C@@H](C(=O)N1)NC(=O)CNC(=O)[C@H](CO)NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CCCCN)NC(=O)[C@H]1N(CCC1)C(=O)[C@@H](N)CO)C(C)C)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC=1N=CNC=1)C(O)=O)=O)[C@@H](C)CC)C1=CC=CC=C1 HPNRHPKXQZSDFX-OAQDCNSJSA-N 0.000 description 1
- 229940080607 nexavar Drugs 0.000 description 1
- 229910052759 nickel Inorganic materials 0.000 description 1
- 229910001000 nickel titanium Inorganic materials 0.000 description 1
- HLXZNVUGXRDIFK-UHFFFAOYSA-N nickel titanium Chemical compound [Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ti].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni].[Ni] HLXZNVUGXRDIFK-UHFFFAOYSA-N 0.000 description 1
- 229960001346 nilotinib Drugs 0.000 description 1
- HHZIURLSWUIHRB-UHFFFAOYSA-N nilotinib Chemical compound C1=NC(C)=CN1C1=CC(NC(=O)C=2C=C(NC=3N=C(C=CN=3)C=3C=NC=CC=3)C(C)=CC=2)=CC(C(F)(F)F)=C1 HHZIURLSWUIHRB-UHFFFAOYSA-N 0.000 description 1
- IAIWVQXQOWNYOU-FPYGCLRLSA-N nitrofural Chemical compound NC(=O)N\N=C\C1=CC=C([N+]([O-])=O)O1 IAIWVQXQOWNYOU-FPYGCLRLSA-N 0.000 description 1
- 229960001907 nitrofurazone Drugs 0.000 description 1
- 238000009659 non-destructive testing Methods 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229960002700 octreotide Drugs 0.000 description 1
- 229960000470 omalizumab Drugs 0.000 description 1
- 210000001328 optic nerve Anatomy 0.000 description 1
- 229960000625 oxytetracycline Drugs 0.000 description 1
- IWVCMVBTMGNXQD-PXOLEDIWSA-N oxytetracycline Chemical compound C1=CC=C2[C@](O)(C)[C@H]3[C@H](O)[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 IWVCMVBTMGNXQD-PXOLEDIWSA-N 0.000 description 1
- 235000019366 oxytetracycline Nutrition 0.000 description 1
- 229940094443 oxytocics prostaglandins Drugs 0.000 description 1
- 238000012856 packing Methods 0.000 description 1
- 230000036407 pain Effects 0.000 description 1
- 229960000402 palivizumab Drugs 0.000 description 1
- 229960000639 pazopanib Drugs 0.000 description 1
- CUIHSIWYWATEQL-UHFFFAOYSA-N pazopanib Chemical compound C1=CC2=C(C)N(C)N=C2C=C1N(C)C(N=1)=CC=NC=1NC1=CC=C(C)C(S(N)(=O)=O)=C1 CUIHSIWYWATEQL-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- HQQSBEDKMRHYME-UHFFFAOYSA-N pefloxacin mesylate Chemical compound [H+].CS([O-])(=O)=O.C1=C2N(CC)C=C(C(O)=O)C(=O)C2=CC(F)=C1N1CCN(C)CC1 HQQSBEDKMRHYME-UHFFFAOYSA-N 0.000 description 1
- 229960001218 pegademase Drugs 0.000 description 1
- 108010027841 pegademase bovine Proteins 0.000 description 1
- 229960001744 pegaspargase Drugs 0.000 description 1
- 108010001564 pegaspargase Proteins 0.000 description 1
- 229960001373 pegfilgrastim Drugs 0.000 description 1
- 108010044644 pegfilgrastim Proteins 0.000 description 1
- 108010092853 peginterferon alfa-2a Proteins 0.000 description 1
- 229960003930 peginterferon alfa-2a Drugs 0.000 description 1
- 108010092851 peginterferon alfa-2b Proteins 0.000 description 1
- 229960003931 peginterferon alfa-2b Drugs 0.000 description 1
- 229960002995 pegvisomant Drugs 0.000 description 1
- 108700037519 pegvisomant Proteins 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960001802 phenylephrine Drugs 0.000 description 1
- SONNWYBIRXJNDC-VIFPVBQESA-N phenylephrine Chemical compound CNC[C@H](O)C1=CC=CC(O)=C1 SONNWYBIRXJNDC-VIFPVBQESA-N 0.000 description 1
- 229940100008 phospholine iodide Drugs 0.000 description 1
- 150000003904 phospholipids Chemical class 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000000704 physical effect Effects 0.000 description 1
- 229960001697 physostigmine Drugs 0.000 description 1
- PIJVFDBKTWXHHD-HIFRSBDPSA-N physostigmine Chemical compound C12=CC(OC(=O)NC)=CC=C2N(C)[C@@H]2[C@@]1(C)CCN2C PIJVFDBKTWXHHD-HIFRSBDPSA-N 0.000 description 1
- 229960001416 pilocarpine Drugs 0.000 description 1
- KASDHRXLYQOAKZ-ZPSXYTITSA-N pimecrolimus Chemical compound C/C([C@H]1OC(=O)[C@@H]2CCCCN2C(=O)C(=O)[C@]2(O)O[C@@H]([C@H](C[C@H]2C)OC)[C@@H](OC)C[C@@H](C)C/C(C)=C/[C@H](C(C[C@H](O)[C@H]1C)=O)CC)=C\[C@@H]1CC[C@@H](Cl)[C@H](OC)C1 KASDHRXLYQOAKZ-ZPSXYTITSA-N 0.000 description 1
- 229960005330 pimecrolimus Drugs 0.000 description 1
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 1
- 229920000058 polyacrylate Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920002647 polyamide Polymers 0.000 description 1
- 229920006393 polyether sulfone Polymers 0.000 description 1
- 229920000573 polyethylene Polymers 0.000 description 1
- 229920001721 polyimide Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000004926 polymethyl methacrylate Substances 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229940125422 potassium channel blocker Drugs 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 229960003611 pramlintide Drugs 0.000 description 1
- 108010029667 pramlintide Proteins 0.000 description 1
- NRKVKVQDUCJPIZ-MKAGXXMWSA-N pramlintide acetate Chemical compound C([C@@H](C(=O)NCC(=O)N1CCC[C@H]1C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](C(C)C)C(=O)NCC(=O)N[C@@H](CO)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1NC=NC=1)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](CS)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CS)NC(=O)[C@@H](N)CCCCN)[C@@H](C)O)[C@@H](C)O)[C@@H](C)O)C(C)C)C1=CC=CC=C1 NRKVKVQDUCJPIZ-MKAGXXMWSA-N 0.000 description 1
- 239000002243 precursor 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
- 239000000955 prescription drug Substances 0.000 description 1
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 0.000 description 1
- 102000004196 processed proteins & peptides Human genes 0.000 description 1
- 108090000765 processed proteins & peptides Proteins 0.000 description 1
- 238000012545 processing Methods 0.000 description 1
- 230000001072 progestational effect Effects 0.000 description 1
- 229960003387 progesterone Drugs 0.000 description 1
- 239000000186 progesterone Substances 0.000 description 1
- 230000002250 progressing effect Effects 0.000 description 1
- 230000002062 proliferating effect Effects 0.000 description 1
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 1
- 238000003908 quality control method Methods 0.000 description 1
- 229960000424 rasburicase Drugs 0.000 description 1
- 108010084837 rasburicase Proteins 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 239000004627 regenerated cellulose Substances 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 230000003252 repetitive effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 230000004258 retinal degeneration Effects 0.000 description 1
- 230000002441 reversible effect Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 229960001225 rifampicin Drugs 0.000 description 1
- JQXXHWHPUNPDRT-WLSIYKJHSA-N rifampicin Chemical compound O([C@](C1=O)(C)O/C=C/[C@@H]([C@H]([C@@H](OC(C)=O)[C@H](C)[C@H](O)[C@H](C)[C@@H](O)[C@@H](C)\C=C\C=C(C)/C(=O)NC=2C(O)=C3C([O-])=C4C)C)OC)C4=C1C3=C(O)C=2\C=N\N1CC[NH+](C)CC1 JQXXHWHPUNPDRT-WLSIYKJHSA-N 0.000 description 1
- 108010074523 rimabotulinumtoxinB Proteins 0.000 description 1
- 229960002646 scopolamine Drugs 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
- MEGPURSNXMUDAE-RLMOJYMMSA-N scopoline Chemical compound C([C@H](O1)C2)[C@@H]3N(C)[C@H]2[C@H]1[C@H]3O MEGPURSNXMUDAE-RLMOJYMMSA-N 0.000 description 1
- 230000036303 septic shock Effects 0.000 description 1
- WGWPRVFKDLAUQJ-MITYVQBRSA-N sermorelin Chemical compound C([C@H](N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CC=1C=CC(O)=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CO)C(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(N)=O)C1=CC=C(O)C=C1 WGWPRVFKDLAUQJ-MITYVQBRSA-N 0.000 description 1
- 229960002758 sermorelin Drugs 0.000 description 1
- 239000008159 sesame oil Substances 0.000 description 1
- 235000011803 sesame oil Nutrition 0.000 description 1
- 230000035939 shock Effects 0.000 description 1
- 238000005245 sintering Methods 0.000 description 1
- 229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
- AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
- 229960003212 sodium propionate Drugs 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 239000007779 soft material Substances 0.000 description 1
- 241000894007 species Species 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 239000008223 sterile water Substances 0.000 description 1
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 239000002294 steroidal antiinflammatory agent Substances 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 229960005202 streptokinase Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 235000000346 sugar Nutrition 0.000 description 1
- SKIVFJLNDNKQPD-UHFFFAOYSA-N sulfacetamide Chemical compound CC(=O)NS(=O)(=O)C1=CC=C(N)C=C1 SKIVFJLNDNKQPD-UHFFFAOYSA-N 0.000 description 1
- 229960002673 sulfacetamide Drugs 0.000 description 1
- SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 description 1
- 229960004306 sulfadiazine Drugs 0.000 description 1
- 229960000654 sulfafurazole Drugs 0.000 description 1
- VACCAVUAMIDAGB-UHFFFAOYSA-N sulfamethizole Chemical compound S1C(C)=NN=C1NS(=O)(=O)C1=CC=C(N)C=C1 VACCAVUAMIDAGB-UHFFFAOYSA-N 0.000 description 1
- 229960005158 sulfamethizole Drugs 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
- 229960005314 suramin Drugs 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 229940034785 sutent Drugs 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 229940064707 sympathomimetics Drugs 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 229940037128 systemic glucocorticoids Drugs 0.000 description 1
- 201000000596 systemic lupus erythematosus Diseases 0.000 description 1
- 229960001967 tacrolimus Drugs 0.000 description 1
- QJJXYPPXXYFBGM-SHYZHZOCSA-N tacrolimus Natural products CO[C@H]1C[C@H](CC[C@@H]1O)C=C(C)[C@H]2OC(=O)[C@H]3CCCCN3C(=O)C(=O)[C@@]4(O)O[C@@H]([C@H](C[C@H]4C)OC)[C@@H](C[C@H](C)CC(=C[C@@H](CC=C)C(=O)C[C@H](O)[C@H]2C)C)OC QJJXYPPXXYFBGM-SHYZHZOCSA-N 0.000 description 1
- 230000002123 temporal effect Effects 0.000 description 1
- 229960000235 temsirolimus Drugs 0.000 description 1
- 229960000216 tenecteplase Drugs 0.000 description 1
- 229960005460 teriparatide Drugs 0.000 description 1
- OGBMKVWORPGQRR-UMXFMPSGSA-N teriparatide Chemical compound C([C@H](NC(=O)[C@H](CCSC)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@@H](N)CO)C(C)C)[C@@H](C)CC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC(C)C)C(=O)NCC(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC(O)=O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1N=CNC=1)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CC=1C=CC=CC=1)C(O)=O)C1=CNC=N1 OGBMKVWORPGQRR-UMXFMPSGSA-N 0.000 description 1
- IWVCMVBTMGNXQD-UHFFFAOYSA-N terramycin dehydrate Natural products C1=CC=C2C(O)(C)C3C(O)C4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O IWVCMVBTMGNXQD-UHFFFAOYSA-N 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
- 150000003522 tetracyclines Chemical class 0.000 description 1
- 229960000337 tetryzoline Drugs 0.000 description 1
- ZRKFYGHZFMAOKI-QMGMOQQFSA-N tgfbeta Chemical compound C([C@H](NC(=O)[C@H](C(C)C)NC(=O)CNC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CC(N)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H]([C@@H](C)O)NC(=O)[C@H](CC(C)C)NC(=O)CNC(=O)[C@H](C)NC(=O)[C@H](CO)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](CC(C)C)NC(=O)[C@@H](N)CCSC)C(C)C)[C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](C(C)C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](C)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H]([C@@H](C)O)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](C)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N1[C@@H](CCC1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CO)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(O)=O)C1=CC=C(O)C=C1 ZRKFYGHZFMAOKI-QMGMOQQFSA-N 0.000 description 1
- 239000005495 thyroid hormone Substances 0.000 description 1
- 229940036555 thyroid hormone Drugs 0.000 description 1
- 230000036962 time dependent Effects 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 229960005221 timolol maleate Drugs 0.000 description 1
- 229940034744 timoptic Drugs 0.000 description 1
- 229960000707 tobramycin Drugs 0.000 description 1
- NLVFBUXFDBBNBW-PBSUHMDJSA-N tobramycin Chemical compound N[C@@H]1C[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 NLVFBUXFDBBNBW-PBSUHMDJSA-N 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 229960005267 tositumomab Drugs 0.000 description 1
- 230000007704 transition Effects 0.000 description 1
- 229940113006 travatan Drugs 0.000 description 1
- 229960002368 travoprost Drugs 0.000 description 1
- 229940126307 triamcinolone acetate Drugs 0.000 description 1
- 229940038017 triesence Drugs 0.000 description 1
- VSQQQLOSPVPRAZ-RRKCRQDMSA-N trifluridine Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(C(F)(F)F)=C1 VSQQQLOSPVPRAZ-RRKCRQDMSA-N 0.000 description 1
- 229960003962 trifluridine Drugs 0.000 description 1
- 229960004791 tropicamide Drugs 0.000 description 1
- 229940108420 trusopt Drugs 0.000 description 1
- 229940094060 tykerb Drugs 0.000 description 1
- 229940121358 tyrosine kinase inhibitor Drugs 0.000 description 1
- 239000005483 tyrosine kinase inhibitor Substances 0.000 description 1
- 150000004917 tyrosine kinase inhibitor derivatives Chemical class 0.000 description 1
- DRTQHJPVMGBUCF-UHFFFAOYSA-N uracil arabinoside Natural products OC1C(O)C(CO)OC1N1C(=O)NC(=O)C=C1 DRTQHJPVMGBUCF-UHFFFAOYSA-N 0.000 description 1
- 229940045145 uridine Drugs 0.000 description 1
- 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 1
- 229960004371 urofollitropin Drugs 0.000 description 1
- 229960005356 urokinase Drugs 0.000 description 1
- 229960005486 vaccine Drugs 0.000 description 1
- 229960000241 vandetanib Drugs 0.000 description 1
- UHTHHESEBZOYNR-UHFFFAOYSA-N vandetanib Chemical compound COC1=CC(C(/N=CN2)=N/C=3C(=CC(Br)=CC=3)F)=C2C=C1OCC1CCN(C)CC1 UHTHHESEBZOYNR-UHFFFAOYSA-N 0.000 description 1
- 230000002792 vascular Effects 0.000 description 1
- 208000019553 vascular disease Diseases 0.000 description 1
- 239000003981 vehicle Substances 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 230000004304 visual acuity Effects 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 238000003466 welding Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
- CGTADGCBEXYWNE-JUKNQOCSSA-N zotarolimus Chemical compound N1([C@H]2CC[C@@H](C[C@@H](C)[C@H]3OC(=O)[C@@H]4CCCCN4C(=O)C(=O)[C@@]4(O)[C@H](C)CC[C@H](O4)C[C@@H](/C(C)=C/C=C/C=C/[C@@H](C)C[C@@H](C)C(=O)[C@H](OC)[C@H](O)/C(C)=C/[C@@H](C)C(=O)C3)OC)C[C@H]2OC)C=NN=N1 CGTADGCBEXYWNE-JUKNQOCSSA-N 0.000 description 1
- 229950009819 zotarolimus Drugs 0.000 description 1
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F9/00—Methods or devices for treatment of the eyes; Devices for putting-in contact lenses; Devices to correct squinting; Apparatus to guide the blind; Protective devices for the eyes, carried on the body or in the hand
- A61F9/0008—Introducing ophthalmic products into the ocular cavity or retaining products therein
- A61F9/0017—Introducing ophthalmic products into the ocular cavity or retaining products therein implantable in, or in contact with, the eye, e.g. ocular inserts
-
- 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
- A61K31/74—Synthetic polymeric materials
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- 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
- A61F—FILTERS IMPLANTABLE INTO BLOOD VESSELS; PROSTHESES; DEVICES PROVIDING PATENCY TO, OR PREVENTING COLLAPSING OF, TUBULAR STRUCTURES OF THE BODY, e.g. STENTS; ORTHOPAEDIC, NURSING OR CONTRACEPTIVE DEVICES; FOMENTATION; TREATMENT OR PROTECTION OF EYES OR EARS; BANDAGES, DRESSINGS OR ABSORBENT PADS; FIRST-AID KITS
- A61F2250/00—Special features of prostheses classified in groups A61F2/00 - A61F2/26 or A61F2/82 or A61F9/00 or A61F11/00 or subgroups thereof
- A61F2250/0058—Additional features; Implant or prostheses properties not otherwise provided for
- A61F2250/0067—Means for introducing or releasing pharmaceutical products into the body
- A61F2250/0068—Means for introducing or releasing pharmaceutical products into the body the pharmaceutical product being in a reservoir
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Ophthalmology & Optometry (AREA)
- Engineering & Computer Science (AREA)
- Heart & Thoracic Surgery (AREA)
- Biomedical Technology (AREA)
- Vascular Medicine (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Organic Chemistry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicinal Preparation (AREA)
Abstract
Description
本PCT出願は、2010年8月5日に出願された米国仮特許出願第61/371168号に対する優先権を主張し、その全開示は本明細書において参考として組み込まれる。
非適用
本発明は、後眼部への治療剤の送達に関する。抗体または抗体フラグメントを含む高分子の後眼部への送達について具体的な言及がなされるが、本発明の態様は、多くの治療剤を身体の多くの組織へと送達するために用いることができる。例えば、本発明の態様は、治療剤を以下の組織:血管内、関節内、髄腔内、心嚢内、腔内および腸の1または2以上へ送達するために用いることができる。
本発明の態様は、第1の治療剤または第2の治療剤の1または2以上の治療的量を、長時間にわたり、例えば少なくとも約1か月間の長時間にわたり、後眼部へ送達する、治療用デバイスを提供する。第1の治療剤は、血管新生を阻害する剤、例えばVEGF阻害剤などの抗腫瘍剤を含み得る。第2の治療剤は、抗炎症性の、例えばシクロオキシゲナーゼ(本明細書において以下「COX」)阻害剤を含み得る。第1の治療剤および第2の治療剤は多くの方法により長時間にわたり送達することができるが、治療用デバイスは、疼痛、網膜剥離、出血および感染などの直接的な眼内注入に関連する負の副作用の頻度を低減するために役立ち得る。なぜならば、注入が、より低頻度であり、眼内へではなくデバイスのリザーバチャンバー中へ行うことができるからである。治療用デバイスは、デバイスが少なくとも部分的に患者の眼内に移植された場合に治療剤を置き換えるように、構成することができる。治療用デバイスは、眼の強膜を通して伸長するように、眼内へ移植することができ、治療用デバイスは、ある量の治療剤を受け取るよう構成された容器およびポートまたは透過障壁を備える。治療剤は、多くの方法において、例えば、ポートを通して容器の内部へ固体のインサートを配置することにより、または、透過障壁を通して容器中に治療剤の処方物を注入することにより、容器中に配置することができる。
抗体または抗体フラグメントを含む高分子の後眼部への送達について具体的な言及がなされるが、本発明の態様は、多くの治療剤を身体の多くの組織へ送達するために用いることができる。例えば、本発明の態様は、治療剤を長期間にわたり以下の組織の1または2以上に送達するために用いることができる:血管内、関節内、髄腔内、心嚢内、腔内および腸。
速度=Vr(dCr/dt)=−D(PA/TL)Cr
ここで、速度=デバイスからの治療剤の放出の速度
Cr=リザーバ中の治療剤の濃度
Vr=リザーバの容積
D=拡散定数
PA/TL=RRI
P=多孔度
A=面積
T=屈曲度=F=チャネルパラメーター。
実質的に固定された容積の注入について、
Cr0=(注入容積)(処方物の濃度)/Vr
ここで、Cr0=処方物の注入の後でのリザーバ中の最初の濃度。
注入容積=50 uLについて、
Cr0=(0.05 mL)(10 mg/ml)/Vr (1000 ug/ 1 mg)=500 ug / Vr
速度=x(500 ug)exp(-xt)
ここで、t=時間
x=(D/Vr)(PA/TL)。
硝子体における物質収支により、
Vv(dCv/dt)=デバイスからの速度=kVvCv
ここで、Vv=硝子体中の容積(約4.5ml)
Cv=硝子体中の治療剤の濃度
k=硝子体からの薬物の速度(1/硝子体中の薬物の半減期に比例する)
Cvが実質的に一定であり続け、時間とともにゆっくりと変化する(すなわち、dCv/dtが約0である)、本明細書において記載される態様のために適切な状況について、
Cv=(デバイスからの速度)/(kVv)
kVvが実質的に一定であるので、Cvの最大値は、デバイスからの速度を最大化する条件に対応する。デバイスからの注入から所与の時点において、(例えば180日目)、最大Cvは、最高速度を提供するxの値において見出される。xの最適値は、
所与の時点におけるd(速度)/dx=0
を満たす。
速度=500(x)exp(-xt)=f(x)g(x)、ここで、f(x)=500xおよびg(x)=exp (-xt)
d(速度)/dx=f'(x)g(x) + f(x)g'(x)=500(1-xt)exp(-xt)
所与の時点tについて、1-xt=0およびxt=1の場合、 d(速度)/dx=0
速度は、(D/Vr)(PA/TL)t=1である場合に最大である。
所与の容積について、最適PA/TL=最適RRI=Vr/(Dt)
したがって、所与の時間tにおける最大Cvは、所与のVrについての最適RRI=(PA/FL)について起こる。
また、比(Vr)/(RRI)=(Vr)/(PA/TL)=Dtは、その時間における最適速度を決定する。
1.AMD患者は、幾つかの異なる疾患のステージを通過し得、治療用デバイスまたは剤の1または2以上の組み合わせは、疾患の各々のステージを処置するために用いることができる。眼の状態に適合する1または2以上の対応する治療剤を、血管新生および炎症を処置するために注入することができる。
a.早期/中間期AMD−主にドルーゼの存在により顕化する(また萎縮型AMDとして言及される)
b.進行期AMD(また滲出型AMDとして言及される)
i.CNV
1.新規CNV
2.良好な処置サイクルの後でのCNV再発
ii.地図状萎縮
2.炎症は、全てのこれらのステージにおいて役割を果たし得、抗炎症処置剤は、各々のステージにおいて用いることができる。
a.補体システムの遺伝的多様性は、補体システムの不完全な調節を引き起こし得る。増強された補体の活性は、炎症を増大させる場合があり、これは次いで、VEGFの発現およびCNVの発症を増大させる。デバイス100中に注入される治療剤は、処置に対する患者の応答に基づいて注入することができる。
b.補体因子は、ドルーゼおよびCNVの両方において見出されており、細胞のアポトーシスに寄与し得る。
c.炎症性成分は、CNVが退縮している間に存在し、瘢痕形成に寄与し得、これは、さらなる網膜の損傷を引き起こし得る。瘢痕形成を阻害するために、抗炎症剤を注入することができる。
3.酸化ストレスは、早期AMDを引き起こし得、かつ、中間期から進行期AMDへの転換に関与し得る。
4.滲出期のAMDに対して効果を有し、治療用デバイス100中への注入のために好適な抗炎症剤として、以下の1または2以上が挙げられる:
a.ステロイド
b.腫瘍壊死因子(本明細書において以下「TNF」)阻害剤
c.COX阻害剤
5.早期、中間期および進行期のAMDの処置のために、補体システム阻害剤を、本明細書において記載される態様により組み合わせることができる。
表2
表3
表3A
例1−4(例5−17Cと共に)は、2010年8月5日に出願された優先の米国仮特許出願第61/371,168号;2010年1月29日に出願された米国仮出願第12/696,678号、表題「Posterior Segment Drug Delivery」、米国仮出願公開第2010/0255061(代理人整理番号026322-003750US)として公開;および2010年8月5日にW02010/088548として公開されたPCT/US2010/022631、表題「Posterior Segment Drug Delivery」において記載される。
リザーバは、シリンジおよび焼結多孔質チタンシリンダー(Applied Porous Technologies, Inc., Mott CorporationまたはChand Eisenmann Metallurgicalから入手可能)から製造した。これらは、チタン粒子から製造された直径0.062インチおよび厚み0.039インチの焼結多孔質シリンダーである。多孔度は0.17であり、平均孔サイズは約3〜5マイクロメーターである。多孔質シリンダーは、泡立ち点の測定に従って、0.2の媒質グレードとして特徴づけられる。多孔質シリンダーを、Delrin製の機械加工のスリーブに圧入した。スリーブは、1.9平方ミリメートルの面積に相当する一方の全平面をリザーバ中の溶液に、他方の全平面をバイアル中のレシーバ溶液に露出した。先端は、1mLのポリプロピレンシリンジを切除したものであり、シリンジの内側の直径よりも僅かに大きな外側の直径を有するポリマーのスリーブを受容するように機械加工した。多孔質シリンダー/スリーブを、改変シリンジ中に圧入した。
例5におけるものと同様のシリンジおよび多孔質焼結チタンシリンダーからリザーバを製造した。多孔質焼結チタンシリンダー(Applied Porous Technologies, Inc., Mott CorporationまたはChand Eisenmann Metallurgicalから入手可能)は、0.082インチの直径および0.039インチの厚みを有し、媒質グレードは0.2であり、チタン粒子から調製される。多孔度は0.17であり、平均孔サイズは約3〜5マイクロメートルである。多孔質シリンダーは、泡立ち点の測定に従って、0.2の媒質グレードとして特徴づけられる。多孔質シリンダーを、Delrin製の機械加工のスリーブに圧入した。スリーブは、3.4平方ミリメートルの面積に相当する一方の全平面をリザーバ中の溶液に、他方の全平面をバイアル中のレシーバ溶液に露出した。先端は、1mLのポリプロピレンシリンジを切除したものであり、シリンジの内側の直径よりも僅かに大きな外側の直径を有するポリマーのスリーブを受容するように機械加工した。多孔質シリンダー/スリーブを、改変シリンジ中に圧入した。粘着剤を有するカプトン膜を、露出した表面に添付して、マスクを作り、露出面積を減少させた。第1の場合において、マスクの直径は0.062インチであり、1.9平方ミリメートルの面積をリザーバ溶液に対して露出した。第2の場合において、マスクの直径は0.027インチであり、0.37平方ミリメートルの面積をリザーバ溶液に対して露出した。
チューブおよび焼結多孔質ステンレス鋼シリンダー(Applied Porous Technologies, Inc., Mott CorporationまたはChand Eisenmann Metallurgicalから入手可能)から、試作のデバイスを製造し、これは、直径0.155インチおよび厚み0.188インチの円筒形であり、316Lステンレス鋼粒子から製造した。多孔質シリンダーは、泡立ち点の測定に従って、0.1媒質グレードとして特徴づけられる。12mm2の面積を有するこれらの大きな既製品の多孔質シリンダーにより、0.1媒質グレードのステンレス鋼の耐性の特性を特徴づけるために、この研究を行った。
チューブおよび焼結多孔質ステンレス鋼シリンダー(Applied Porous Technologies, Inc., Mott CorporationまたはChand Eisenmann Metallurgicalから入手可能)から試作のデバイスを製造し、これは、直径0.031インチおよび厚み0.049インチの円筒形であり、316Lステンレス鋼粒子から製造した。多孔質シリンダーは、泡立ち点の測定に従って、0.2媒質グレードとして特徴づけられる。この多孔質シリンダーを、先の研究から決定された特性を有する特別注文品の大直径を有する0.2媒質グレード多孔質ステンレス鋼シリンダー(データは示さず)、および本明細書において記載されるモデルに基づく予測として得た。この多孔質シリンダーの各々の面の面積は、0.5mm2である。
治療剤の硝子体濃度は、本明細書において記載される式に基づいて予測することができる。表4は、シュミレーション1、シュミレーション2、シュミレーション3、シュミレーション4およびシュミレーション5の各々について適用されるパラメーターの値を示す。サルモデルに対応する半減期および硝子体容積(J. Gaudreault et al.., Preclinical Pharmacokinetics of Ranibizumab (rhuFabV2) after a Single Intravitreal Administration, Invest Ophthalmol Vis Sci 2005; 46: 726-733)(Z. Yao et al., Prevention of Laser Photocoagulation Induced Choroidal Neovascularization Lesions by Intravitreal Doses of Ranibizumab in Cynomolgus Monkeys, ARVO 2009年抄録D906)。パラメーターPA/FLは、放出速度プロフィールを決定するために変化させることができる。例えば、PA/TLが約0.05mmとなるように、Aの値は約1mm2であってもよく、多孔度は約0.1であってもよく(PA=0.1mm2)、長さは約1mmであり、屈曲度に相当し得るチャネル適合パラメーターは約2であってよい(FL=2mm)。当業者は、長期間にわたる治療剤の持続放出のための面積、多孔度、長さおよびチャネル適合パラメーターを、本明細書において記載される教示に従って、実験的に決定することができる。
表4A
表4B
表4C1
表4D
表4E
トリアムシノロンアセトニドは、ブドウ膜炎および眼の炎症を伴う他の疾患の処置のために用いられる副腎皮質ステロイドである。4mgのトリアムシノロンアセトニドの懸濁液の硝子体内注入は、局所副腎皮質ステロイドに応答しない患者に投与することができる。本明細書において記載される計算は、治療的量を長時間にわたり放出するであろうデバイスの特徴を決定するために行った。
図20は、例10におけるもののような治療剤懸濁液の計算された時間放出プロフィールを示す。1.2mmのRRIを有する10uLのデバイスについて、ヒトの硝子体中のトリアムシノロンアセトニド濃度を決定し、示す。計算は、懸濁液について上で示す式に基づいた。数値シュミレーションによりプロフィールを作製した。1ug/日の定量送達速度が、T=0において瞬時に開始することを仮定して、ヒトの眼の硝子体内の濃度は、1日において、定常状態値の99%以内に達し得る。薬物放出プロフィールの対極において、シュミレーションは、実質的に全ての固体薬物が失われたときの硝子体内濃度を示す。溶解した薬物の99%より多くが、1日以内に送達された。
図21は、実質的に類似の多孔質フリット構造と、16uLのリザーバおよび33uLのリザーバとを備える、治療用デバイスの放出速度プロフィールを示す。各々のフリットの放出速度指標は約0.02であった。各々16uLのリザーバを備える2つの治療用デバイス、および各々33uLのリザーバを備える2つの治療用デバイスについての放出速度を示す。33uLのリザーバを備えるデバイスは、16uLのリザーバを備えるデバイスの約2倍の速度でAvastin(商標)を放出した。これらの測定データは、治療剤を長時間にわたり放出するように放出速度指標およびリザーバを構成することができるように、放出速度指標およびリザーバのサイズにより放出速度プロフィールを決定することができることを示す。
表5A
図22Aは、0.049”の厚みを有する多孔質フリット構造によるAvastin(商標)についての累積放出を示す。実験は、以下を用いた:25mg/mlのAvastin(商標);フリット#2(0.031×0.049”、媒質グレード0.2um、316L SS、Mott Corporation);機械加工されたねじを有するポリカーボネート代用品;リザーバ容積37uL;37C。デバイスの数および各々の試験されたデバイスについての対応するRRIを、以下の表5Bにおいて列記する。測定に基づいて決定されたRRIは、0.02であり、これは、本明細書において記載される治療剤の放出についてのモデルと一致する。各々の試験デバイスについて測定されたRRIに関して幾つかの変数が記述されるが、各々のデバイスについてのRRIを、治療剤の放出を決定するために用いることができ、患者への配置に先立ちRRIを決定するために、本明細書において記載される気体の流動により、多孔構造をさらに特徴づけることができる。
表5B
表5C
表5D
治療用デバイスのサイズ、放出速度プロフィールおよび予想される治療剤リザーバ中の濃度を決定するために、数値的計算を行った。リザーバ中の濃度は、デバイスの有用な寿命、またはリザーバ中への治療剤の注入もしくは治療剤の他の交換の間の時間に相当し得る。
表6A
表6B
表6C
表6D
多孔質フリット構造を通しての低分子薬物の放出を決定するために、多孔質フリット構造を通してのリザーバからのフルオレセインの放出の研究を行った。フルオレセインのモデルは、本明細書において記載される多孔質フリット構造およびリザーバが、低分子薬物の送達のために好適であることを示す。Avastin(商標)、Lucentis(商標)およびBSAの放出プロフィールと、フルオレセインのデータとの組合せは、多くの分子量およびサイズの多くの薬物、分子および治療剤の持続放出のために多孔質フリット構造およびリザーバを用いることができることを示す。
実験は以下を用いた:10mg/mlのLucentis(商標);ねじを有する機械加工されたポリ(メチルメタクリレート)代用品;およびリザーバ容積30uL;37C。全ての多孔質フリット構造は、316L SS(Mott Corporation)である。示されるデータは、泡の発生または低いレシーバ容積のいずれかを示した数個の試料を除いて、全てのデバイスからの測定データである。
図26Aおよび26Bは、それぞれ、0.2媒質グレードおよび0.5媒質グレードの多孔質材料の多孔質フリット構造の破砕された端部からの走査型電子顕微鏡画像を示す。Mott Corporationから市販の試料を得、これは、316Lステンレススチールを含んだ。試料を、治療剤を放出するための材料中の多孔構造および互いに連結するチャネルを示すように、機械的に破砕した。顕微鏡画像は、第1の表面の開口と第2の表面の開口との間に配置された複数の互いに連結するチャネルを示す。
フリットを、圧減衰および流動を含むがこれらに限定されない多数の機械的試験に供することにより、試料エレメントの相対的特徴を決定することができる。これらの試験は、デバイスの放出プロフィールを決定するために、薬物放出速度情報、例えばRRIと組み合わせることができる。デバイスの多孔構造を通しての流動を定量し、多孔構造のうちの好適なものを決定するために、治療用デバイス上に配置された多孔構造について、これらの試験を用いることができる。類似の試験を用いて、治療用デバイスのマウントの前に多孔構造を定量することができる。例えば品質管理チェックとして、部分的に組み立てられた治療用デバイス上にマウントされた多孔構造の気体流動により、治療用デバイスの少なくとも一部を評価することができる。一部の態様において、多孔構造が治療剤の放出のために好適であり、デバイス、例えば治療用デバイスの支持体に装着されていることを確認するために、部分的に組み立てられたまたは実質的に組み立てられた治療用デバイスに対して、リザーバ中への治療剤の挿入の前に、および患者への挿入の前に、流動試験を行うことができる。
上記の試験方法の各々は、試験標本と試験ハードウェアとの機械的結合を用い得、多数の技術が開発され使用されてきている。これらの固定手段は、標本を確実に固定する手段(熱回収チューブ、伸縮チューブ、相対的に強固な成分中への圧入など)およびカップリングの手段(ルアー、かかりのついた固定具、急速継ぎ手カップリングなど)の両方のものであって、試験ハードウェアへの便利かつ繰り返しの結合を可能にするものを含む。
所望の試験の各々は、市販のソリューションを用いて開発しても、容易に利用可能な器具を集積して特注の試験配置を作製することにより開発してもよい。やはり、これらのアプローチのいずれも、評価されている。作動するシステムは、試験標本、制御可能なソース(通常は圧力であるがこれに限定されない)、圧力計(または他の圧力測定デバイス)および1または2以上のトランスデューサー(圧力、流動など)を結合するための手段からなり、試験条件を測定する、および/またはさらなる分析のためのデータを集めるために用いられる。
図28は、本明細書において記載される態様による治療用デバイスによる使用のために好適な多孔質フリット構造を同定するために、多孔構造に関して用いるための圧減衰試験および試験装置を示す。
図29は、本明細書において記載される態様による治療用デバイスによる使用のために好適な多孔質フリット構造を同定するための、多孔構造による使用のために好適な圧力流試験および試験装置を示す。
表7は、多孔構造を通しての酸素または窒素などの気体の流動に基づいて治療剤の放出、例えばRRIを決定するために用いることができる表を示す。多孔構造を通しての流動は、多孔構造にかかる流動速度について、本明細書において記載される多孔質フリット構造にかかる圧力低下による、気圧の減衰時間により測定することができる。流動速度およびRRIは、例えばMott Corp.から入手される市販の媒質グレードの材料などの材料の媒質グレードに基づいて決定することができる。治療剤を、多孔構造または類似の試験分子を通して、測定することができる。最初の測定は、示される多孔質フリット構造を通してのAvastin(商標)についてのRRIを測定した。本明細書において記載される教示に従って、当業者は、治療剤の放出速度に対する、気体による流動速度の対応を実験的に決定する実験を行うことができる。
表7
a)フリットの検査的試験を受けるQC
b)最終デバイス組み立て試験のQC
Claims (74)
- 強膜および硝子体液を有する眼を処置する方法であって、
第1の治療剤の第1の治療的量を眼の硝子体液へ送達すること、ここで、第1の治療剤は、第1の長時間にわたり有効である;および
第2の治療剤の第2の治療的量を眼の硝子体液へ送達すること、ここで、第2の治療剤は、第2の長時間にわたり有効である、
を含む、前記方法。 - 第1の治療剤が、抗腫瘍剤を含み、第1の長時間にわたり有効であり、第2の治療剤が、COX阻害剤、LOX阻害剤、TNF阻害剤または抗ヒスタミン剤の1または2以上を含む、請求項1の方法。
- 第1の治療剤が第1の長時間にわたり有効な血管増殖阻害剤を含み、第2の治療剤が第2の長時間にわたり有効な炎症応答阻害剤を含む、請求項1の方法。
- 血管増殖阻害剤がVEGF阻害剤の1または2以上を含む、請求項3の方法。
- 炎症応答阻害剤がシクロオキシゲナーゼ(以下「COX」)阻害剤を含む、請求項3の方法。
- COX阻害剤が、サリチル酸誘導体、プロピオン酸誘導体、酢酸誘導体、およびエノール酸(以下「Oxicam」)誘導体、フェナム酸誘導体、選択的COX-2阻害剤(以下「Coxibs」)の1または2以上を含む、請求項5の方法。
- 炎症応答阻害剤がプロピオン酸誘導体を含み、ここでプロピオン酸阻害剤が、イブプロフェン、ナプロキセン、フェノプロフェン、ケトプロフェン、フルルビプロフェンまたはオキサプロジンの1または2以上を含む、請求項6の方法。
- 炎症応答阻害剤が酢酸誘導体を含み、ここで、前記酢酸誘導体が、インドメタシン、スリンダク、エトドラク、ジクロフェナクまたはナブメトンの1または2以上を含む、請求項6の方法。
- 炎症応答阻害剤がエノール酸(以下「Oxicam」)誘導体を含み、ここで、前記エノール酸誘導体が、ピロキシカム、メロキシカム、テノキシカム、ドロキシカム、ロルノキシカム、またはイソキシカムの1または2以上を含む、請求項6の方法。
- 炎症応答阻害剤がフェナム酸誘導体を含み、ここで、前記フェナム酸誘導体が、メフェナム酸、メクロフェナム酸、フルフェナム酸またはトルフェナム酸の1または2以上を含む、請求項6の方法。
- 炎症応答阻害剤が選択的COX-2阻害剤(以下「Coxibs」)を含み、ここで、前記選択的COX-2阻害剤が、セレコキシブ、ロフェコキシブ、バルデコキシブ、パレコキシブ、ルミラコキシブまたはエトリコキシブの1または2以上を含む、請求項6の方法。
- 第1の治療剤が眼の硝子体液中へ注入される、請求項3の方法。
- 第2の治療剤が眼の硝子体液中へ注入される、請求項3の方法。
- 容器を硝子体液および強膜と連結するために、少なくとも部分的に強膜を通して容器を導入すること、
をさらに含む、請求項3の方法。 - 請求項14の方法であって、第1の治療剤は、容器が硝子体液および強膜に連結されるときに、容器のチャンバー中へ注入され、ここで、前記容器は、第1の治療剤の第1の治療的量をチャンバーから硝子体液中へ第1の長時間にわたり放出するための多孔構造および容積により構成される、前記方法。
- 容器が硝子体液および強膜に連結されるときに第2の治療剤が容器のチャンバーへ注入される、請求項14の方法。
- 第1の治療剤がVEGF阻害剤を含み、第2の治療剤がシクロオキシゲナーゼ阻害剤を含む、請求項15の方法。
- シクロオキシゲナーゼ阻害剤は、第2の治療剤を長時間にわたり放出するために容器に連結した固体を含む、請求項17の方法。
- 固体のシクロオキシゲナーゼ阻害剤は、容器のチャンバー内に配置され、多孔構造を通して放出される、請求項18の方法。
- 固体のシクロオキシゲナーゼ阻害剤は、容器の第2のチャンバー内に配置され、第2の多孔構造を通して放出される、請求項18の方法。
- 第2のチャンバーが第1のチャンバーから分離している、請求項20の方法。
- 第1の治療剤が第1の多孔構造および第2の多孔構造を通過して硝子体液に到達するように、第2のチャンバーは、第1の多孔構造により第1のチャンバーに連結し、第2の多孔構造により硝子体に連結される、請求項20の方法。
- 固体のシクロオキシゲナーゼ阻害剤は、チャンバーから離れて配置され、硝子体液と連結している、請求項18の方法。
- 容器は、第1の治療剤の治療的量を硝子体液中に第1の長時間にわたり放出するように構成される、請求項14の方法。
- 請求項1の方法であって、第1の治療剤は、第1の長時間にわたり有効な血管増殖阻害剤を含み、ここで、第2の治療剤は、第2の長時間にわたり有効なリポキシゲナーゼ経路(以下「LOX」)阻害剤を含む、前記方法。
- LOX阻害剤が5-LOX阻害剤を含む、請求項25の方法。
- 第1の治療剤は、第1の長時間にわたり有効な血管増殖阻害剤を含み、第2の治療剤は、第2の長時間にわたり有効な抗線維化剤を含む、請求項1の方法。
- 第1の治療剤は、第1の長時間にわたり有効な血管増殖阻害剤を含み、第2の治療剤は、第2の長時間にわたり有効な腫瘍壊死因子(以下「TNF」)阻害剤を含む、請求項1の方法。
- TNF阻害剤が、第2の長時間にわたり有効なペントキシフィリンを含む、請求項28の方法。
- 第1の治療剤は、第1の長時間にわたり有効な血管増殖阻害剤を含み、第2の治療剤は、第2の長時間にわたり有効な二重COX/LOX阻害剤を含む、請求項1の方法。
- 二重COX/LOX阻害剤がリコフェロンを含む、請求項30の方法。
- 第1の治療剤は、第1の長時間にわたり有効な血管増殖阻害剤を含み、第2の治療剤は、抗ヒスタミン剤を含む、請求項1の方法。
- 抗ヒスタミン剤がアゼラスチンを含む、請求項30の方法。
- 抗ヒスタミン剤がH1受容体アンタゴニストを含む、請求項30の方法。
- H1受容体アンタゴニストは、クレマスチン、ジフェンヒドラミン(ベネドリル)、ドキシラミン、ロラタジン、デスロラタジン、フェキソフェナジン、フェニラミン、セチリジン、エバスチン、プロメタジン、クロルフェニラミン、レボセチリジン、オロパタジン、クエチアピン、メクリジン、ジメンヒドリナート、エンブラミン、ジメチンデンまたはデスクロルフェニラミンの1または2以上を含む、請求項34の方法。
- 抗ヒスタミン剤がH2受容体アンタゴニストを含む、請求項30の方法。
- H2受容体アンタゴニストが、シメチジン、ファモチジン、ラニチジン、ニザチジン、ロキサチジン、ラフチジンの1または2以上を含む、請求項36の方法。
- 抗ヒスタミン剤がH3受容体アンタゴニストを含む、請求項30の方法。
- H3受容体アンタゴニストが、A-349,821、ABT-239、シプロキシファン、クロベンプロピットまたはチオペラミドの1または2以上を含む、請求項38の方法。
- 抗ヒスタミン剤が、H4受容体アンタゴニストを含む、請求項30の方法。
- H4受容体アンタゴニストが、チオペラミド、JNJ 7777120またはVUF-6002の1または2以上を含む、請求項40の方法。
- 強膜および硝子体液を有する眼を処置する装置であって:
強膜に連結するように構成され、第1の治療剤を保持するための第1の容器を備える、治療用デバイスであって、前記第1の容器は、治療用デバイスが眼中に挿入された場合に第2の治療剤の治療的量を硝子体液中へ第2の長時間にわたり放出するための容器内に第2の治療剤を有する、前記治療用デバイス、
を備える、前記装置。 - 強膜および硝子体液を有する眼を処置する装置であって:
強膜に連結するように構成され、第1の治療剤を保持するための第1の容器および第2の治療剤を保持するための第2の容器を備える、治療用デバイスであって、前記第1の容器は、前記第1の治療剤の第1の治療的量を硝子体液中へ第1の長時間にわたり放出するように構成され、前記第2の容器は、前記第2の治療剤の第2の治療的量を硝子体液中へ第2の長時間にわたり放出するように構成される、前記治療用デバイス、
を備える、前記装置。 - 強膜および硝子体液を有する眼を処置する装置であって:
強膜に連結して第1の治療剤を保持するように構成された第1の容器を備える、第1の治療用デバイスであって、前記第1の容器は、第1の治療剤の第1の治療的量を硝子体液中へ第1の長時間にわたり放出するように構成される、前記第1の治療用デバイス;および
強膜に連結して第2の治療剤を保持するように構成された第2の容器を備える、第2の治療用デバイスであって、前記第2の容器は、第2の治療剤の第2の治療的量を硝子体液中へ第2の長時間にわたり放出するように構成される、前記第2の治療用デバイス、
を備える、前記装置。 - 第1の治療用デバイスおよび第2の治療用デバイスが、各々、強膜に連結するための、毛様体扁平部に沿って伸長する切開に適合するサイズの長円形の断面を有する部分を備える、請求項44のいずれかの装置。
- 第1の治療剤はVEGF阻害剤を含み、第2の治療剤はCOX阻害剤を含む、請求項42、43または44のいずれか1項の装置。
- 治療用デバイスが、第1の治療剤の注入を受ける第1のチャンバーを備え、前記第1のチャンバーは、第1の治療剤を含み、該第1の治療剤の治療的量を第1の放出速度プロフィールにより第1の長時間にわたり放出するための第1の多孔構造に連結する、請求項46の装置。
- COX阻害剤が、治療剤を第2の放出速度プロフィールにより第2の長時間にわたり放出するために、非水溶性COX阻害剤を含む、請求項47の装置。
- 非水溶性COX阻害剤に対する第2のチャンバー、および、前記非水溶性COX阻害剤を第2の多孔構造を通して放出するための、前記第2のチャンバーに連結する第2の多孔構造をさらに備える、請求項48の装置。
- 第1のチャンバーは第1の多孔構造により第2のチャンバーに連結され、前記第1の多孔構造は第1の放出速度指標を有し、第2の多孔構造は第2の放出速度指標を有し、ここで、第1の治療剤の放出速度プロフィールが実質的に前記第1の放出速度指標に基づいて決定され、第2の治療剤の放出速度プロフィールが実質的に前記第2の放出速度指標に基づいて決定されるように、前記第1の放出速度指標は前記第2の放出速度指標より小さい、請求項49の装置。
- 患者を処置するための治療用デバイスであって:
治療剤の治療的量を長期間にわたり放出するための手段
を備える、前記治療用デバイス。 - 第1および第2の治療剤を含む持続的薬物送達処方物であって、ここで、前記第1および第2の治療剤は、請求項42〜51のいずれか1項の少なくとも1つの装置/治療用デバイス中のリザーバ中に含まれ/配置され、前記第1および第2の治療剤のうち少なくとも1つは、移植された場合にリザーバ内での半減期を有し、前記リザーバ内での半減期は、眼の硝子体中に直接注入された場合の前記第1および第2の治療剤の少なくとも1つの対応する半減期よりも実質的に長い、前記持続的薬物送達処方物。
- リザーバ容積と、所望の有効な半減期を達成するために適切な放出速度指数を有する多孔構造との選択により、デバイスを構成することができる、請求項52の処方物。
- 放出速度指数が約0.01〜約5である、請求項53の処方物。
- 第1の治療剤がVEGF阻害剤であり、第2の治療剤が炎症応答阻害剤である、請求項52の処方物。
- VEGF阻害剤が、ラニビズマブ、ベバシズマブおよびアフリベルセプト(商標)からなる群より選択される、請求項55の処方物。
- VEGF阻害剤がラニビズマブである、請求項56の処方物。
- 炎症応答阻害剤が、ピロキシカム、メロキシカム、テノキシカム、ドロキシカム、ロルノキシカム、イソキシカム、メフェナム酸、メクロフェナム酸、フルフェナム酸およびトルフェナム酸からなる群より選択される、請求項55の処方物。
- 炎症応答阻害剤が、シクロオキシゲナーゼ(COX)阻害剤、リポキシゲナーゼ(LOX)阻害剤および腫瘍壊死因子(TNF)からなる群より選択される、請求項55の処方物。
- COX阻害剤が、セレコキシブ、バルデコキシブ、ロフェコキシブ、パレコキシブ、ルミラコキシブ、エトリコキシブ、アスピリン、イブプロフェン、ナプロキセン、フェノプロフェン、ケトプロフェン、フルルビプロフェン、オキサプロジン、インドメタシン、スリンダク、エトドラク、ジクロフェナク、ナブメトン、メロキシカム、ケトロラック、フルルビプロフェン、ブロムフェナク、ネパフェナクおよびアンフェナクからなる群より選択される、請求項59の処方物。
- LOX阻害剤が、アゼラスチンおよびジロートンからなる群より選択される、請求項59の処方物。
- TNFが、ブプロピオン、ペントキシフィリン、インフリキシマブ、アダリムマブおよびエタネルセプトからなる群より選択される、請求項59の処方物。
- 第1の治療剤の濃度が約40mg/mlよりも高い、請求項57の処方物。
- 第1の治療剤の濃度が約50mg/ml〜約300mg/mlである、請求項63の処方物。
- 第1の治療剤の濃度が 約100mg/ml〜約250mg/mlである、請求項64の処方物。
- 第1の治療剤の濃度が 約150mg/ml〜約200mg/mlである、請求項65の処方物。
- 第1の治療剤の量が、約50mgよりも多い、請求項57の処方物。
- 第1または第2の治療剤の少なくとも1つは、治療的投与量未満において投与される、請求項52の処方物。
- 第1または第2の治療剤の少なくとも1つは、ミセル中に含まれる/配置される、請求項52の処方物。
- 第1および第2の治療剤のうち少なくとも1つは、眼から洗い流すことができる固体基質または高分子上への吸着により安定化される、請求項52の処方物。
- 第1および第2の治療剤が、1つの装置/治療用デバイス中に含まれる/配置される、請求項52の処方物。
- 第1の治療剤は第1の装置/治療用デバイス中に含まれ/配置され、第2の治療剤は第2の装置/治療用デバイス中に含まれる/配置される、請求項52の処方物。
- 第1および第2の治療剤が同時に投与される、請求項52の処方物。
- 第1および第2の治療剤が連続的に投与される、請求項52の処方物。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US37116810P | 2010-08-05 | 2010-08-05 | |
US61/371,168 | 2010-08-05 | ||
PCT/US2011/046817 WO2012019139A1 (en) | 2010-08-05 | 2011-08-05 | Combined drug delivery methods and apparatus |
Publications (3)
Publication Number | Publication Date |
---|---|
JP2013538082A true JP2013538082A (ja) | 2013-10-10 |
JP2013538082A5 JP2013538082A5 (ja) | 2014-09-25 |
JP6111194B2 JP6111194B2 (ja) | 2017-04-05 |
Family
ID=45559845
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2013523372A Active JP6111194B2 (ja) | 2010-08-05 | 2011-08-05 | 組み合わせ薬物送達方法および装置 |
Country Status (7)
Country | Link |
---|---|
US (2) | US10617557B2 (ja) |
EP (1) | EP2600876B1 (ja) |
JP (1) | JP6111194B2 (ja) |
CN (1) | CN103153316B (ja) |
AU (1) | AU2011285548B2 (ja) |
CA (1) | CA2807537C (ja) |
WO (1) | WO2012019139A1 (ja) |
Families Citing this family (29)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US8623395B2 (en) | 2010-01-29 | 2014-01-07 | Forsight Vision4, Inc. | Implantable therapeutic device |
WO2012019139A1 (en) | 2010-08-05 | 2012-02-09 | Forsight Vision4, Inc. | Combined drug delivery methods and apparatus |
US9033911B2 (en) | 2010-08-05 | 2015-05-19 | Forsight Vision4, Inc. | Injector apparatus and method for drug delivery |
EP2640360A2 (en) | 2010-11-19 | 2013-09-25 | Forsight Vision4, Inc. | Therapeutic agent formulations for implanted devices |
WO2013003620A2 (en) | 2011-06-28 | 2013-01-03 | Forsight Vision4, Inc. | Diagnostic methods and apparatus |
EP3903733A1 (en) | 2011-09-16 | 2021-11-03 | ForSight Vision4, Inc. | Fluid exchange apparatus |
WO2013116061A1 (en) | 2012-02-03 | 2013-08-08 | Forsight Vision4, Inc. | Insertion and removal methods and apparatus for therapeutic devices |
EP2968113B8 (en) * | 2013-03-14 | 2020-10-28 | Forsight Vision4, Inc. | Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant |
CA2907681C (en) | 2013-03-28 | 2022-11-22 | Forsight Vision4, Inc. | Ophthalmic implant for delivering therapeutic substances |
CN111374821B (zh) * | 2014-06-19 | 2022-05-03 | 加州理工学院 | 用于输送药物或排除废物的小分子运输设备 |
RU2695563C2 (ru) | 2014-07-15 | 2019-07-24 | Форсайт Вижн4, Инк. | Способ и устройство для доставки глазного имплантата |
US9474756B2 (en) | 2014-08-08 | 2016-10-25 | Forsight Vision4, Inc. | Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof |
US10507101B2 (en) | 2014-10-13 | 2019-12-17 | W. L. Gore & Associates, Inc. | Valved conduit |
CN114587774A (zh) | 2014-11-10 | 2022-06-07 | 弗赛特影像4股份有限公司 | 治疗眼睛的系统 |
WO2016210346A1 (en) * | 2015-06-24 | 2016-12-29 | Healionics Corporation | Injectable porous device for treatment of dry and wet age-related macular degeneration or diabetic retinopathy |
AR106018A1 (es) | 2015-08-26 | 2017-12-06 | Achillion Pharmaceuticals Inc | Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos |
WO2017035408A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Compounds for treatment of immune and inflammatory disorders |
US11013403B2 (en) | 2015-09-29 | 2021-05-25 | The Regents Of The University Of California | Methods of diagnosing diseases of mucosal surfaces |
KR20180084104A (ko) | 2015-11-20 | 2018-07-24 | 포사이트 비젼4, 인크. | 연장 방출 약물 전달 장치를 위한 다공성 구조물 |
AR108177A1 (es) | 2016-04-05 | 2018-07-25 | Forsight Vision4 Inc | Dispositivos de suministro de fármacos oculares implantables |
WO2018005552A1 (en) | 2016-06-27 | 2018-01-04 | Achillion Pharmaceuticals, Inc. | Quinazoline and indole compounds to treat medical disorders |
US11351058B2 (en) | 2017-03-17 | 2022-06-07 | W. L. Gore & Associates, Inc. | Glaucoma treatment systems and methods |
IL271195B2 (en) | 2017-06-14 | 2024-04-01 | Semma Therapeutics Inc | Devices and methods for drug administration |
BR112020010053A2 (pt) | 2017-11-21 | 2020-11-03 | Forsight Vision4, Inc. | aparelho para troca de fluido para sistema de liberação de porta expansível e métodos de uso do mesmo |
KR20210018199A (ko) | 2018-03-26 | 2021-02-17 | 씨4 테라퓨틱스, 인코포레이티드 | 이카로스의 분해를 위한 세레블론 결합제 |
WO2020041301A1 (en) | 2018-08-20 | 2020-02-27 | Achillion Pharmaceuticals, Inc. | Pharmaceutical compounds for the treatment of complement factor d medical disorders |
EP3866773A4 (en) | 2018-10-16 | 2022-10-26 | Georgia State University Research Foundation, Inc. | CARBON MONOXIDE PRODRUGS FOR THE TREATMENT OF MEDICAL CONDITIONS |
US11678983B2 (en) | 2018-12-12 | 2023-06-20 | W. L. Gore & Associates, Inc. | Implantable component with socket |
JPWO2021020252A1 (ja) * | 2019-07-26 | 2021-02-04 |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004524866A (ja) * | 2000-08-30 | 2004-08-19 | ジョンズ・ホプキンス・ユニバーシティ | 眼内薬剤送達装置 |
JP2010514517A (ja) * | 2006-12-26 | 2010-05-06 | キューエルティー プラグ デリバリー,インク. | 視覚欠損の抑制のための薬物送達インプラント |
WO2010062394A2 (en) * | 2008-11-26 | 2010-06-03 | Surmodics, Inc. | Implantable ocular drug delivery device and methods |
Family Cites Families (389)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2585815A (en) | 1947-01-16 | 1952-02-12 | Mclintock Duncan Menzies | Injection syringe |
US2564977A (en) | 1949-01-19 | 1951-08-21 | Hu Quang Hsi | Medical injecting apparatus |
US2886497A (en) | 1957-04-12 | 1959-05-12 | United States Steel Corp | Method for determining the permeability of steel to hydrogen |
US3232117A (en) | 1962-09-14 | 1966-02-01 | Roger Gilmont Instr Inc | Micrometer buret |
US3416530A (en) | 1966-03-02 | 1968-12-17 | Richard A. Ness | Eyeball medication dispensing tablet |
US3618604A (en) | 1969-06-09 | 1971-11-09 | Alza Corp | Ocular insert |
US3641237A (en) | 1970-09-30 | 1972-02-08 | Nat Patent Dev Corp | Zero order release constant elution rate drug dosage |
US4034756A (en) | 1971-01-13 | 1977-07-12 | Alza Corporation | Osmotically driven fluid dispenser |
US3831583A (en) | 1971-03-05 | 1974-08-27 | Univ California | Implantable bulb for inflation of surgical implements |
US3995635A (en) | 1971-09-09 | 1976-12-07 | Alza Corporation | Ocular insert |
US3828777A (en) | 1971-11-08 | 1974-08-13 | Alza Corp | Microporous ocular device |
US3845201A (en) | 1972-04-24 | 1974-10-29 | S Loucas | Solid state ophthalmic medication delivery method |
US3916899A (en) | 1973-04-25 | 1975-11-04 | Alza Corp | Osmotic dispensing device with maximum and minimum sizes for the passageway |
US3914402A (en) | 1973-06-14 | 1975-10-21 | Alza Corp | Ophthalmic dosage form, for releasing medication over time |
US4179497A (en) | 1973-12-17 | 1979-12-18 | Merck & Co., Inc. | Solid state ophthalmic medication |
US3902495A (en) | 1974-01-28 | 1975-09-02 | Cavitron Corp | Flow control system |
US3961628A (en) | 1974-04-10 | 1976-06-08 | Alza Corporation | Ocular drug dispensing system |
US3949748A (en) | 1974-09-26 | 1976-04-13 | Oscar Malmin | Injection syringe having aspirating and metering capabilities |
US3949750A (en) | 1974-10-07 | 1976-04-13 | Freeman Jerre M | Punctum plug and method for treating keratoconjunctivitis sicca (dry eye) and other ophthalmic aliments using same |
US3926188A (en) | 1974-11-14 | 1975-12-16 | Alza Corp | Laminated drug dispenser |
US4096238A (en) | 1974-12-23 | 1978-06-20 | Alza Corporation | Method for administering drug to the gastrointestinal tract |
US4014335A (en) | 1975-04-21 | 1977-03-29 | Alza Corporation | Ocular drug delivery device |
NL188266C (nl) | 1975-07-29 | 1992-05-18 | Merck & Co Inc | Werkwijze ter bereiding van een oogheelkundig inplantaat. |
US4034758A (en) | 1975-09-08 | 1977-07-12 | Alza Corporation | Osmotic therapeutic system for administering medicament |
US3977404A (en) | 1975-09-08 | 1976-08-31 | Alza Corporation | Osmotic device having microporous reservoir |
US4014333A (en) | 1975-09-22 | 1977-03-29 | Mcintyre David J | Instrument for aspirating and irrigating during ophthalmic surgery |
US4077407A (en) | 1975-11-24 | 1978-03-07 | Alza Corporation | Osmotic devices having composite walls |
US4014334A (en) | 1976-02-02 | 1977-03-29 | Alza Corporation | Laminated osmotic system for dispensing beneficial agent |
US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
US4111201A (en) | 1976-11-22 | 1978-09-05 | Alza Corporation | Osmotic system for delivering selected beneficial agents having varying degrees of solubility |
US4111203A (en) | 1976-11-22 | 1978-09-05 | Alza Corporation | Osmotic system with means for improving delivery kinetics of system |
US4160452A (en) | 1977-04-07 | 1979-07-10 | Alza Corporation | Osmotic system having laminated wall comprising semipermeable lamina and microporous lamina |
US4256108A (en) | 1977-04-07 | 1981-03-17 | Alza Corporation | Microporous-semipermeable laminated osmotic system |
US4164559A (en) | 1977-09-21 | 1979-08-14 | Cornell Research Foundation, Inc. | Collagen drug delivery device |
US4186184A (en) | 1977-12-27 | 1980-01-29 | Alza Corporation | Selective administration of drug with ocular therapeutic system |
US4220153A (en) | 1978-05-08 | 1980-09-02 | Pfizer Inc. | Controlled release delivery system |
US4220152A (en) | 1978-05-08 | 1980-09-02 | Pfizer Inc. | Delivery system |
US4200098A (en) | 1978-10-23 | 1980-04-29 | Alza Corporation | Osmotic system with distribution zone for dispensing beneficial agent |
US4298000A (en) | 1978-11-08 | 1981-11-03 | Minnesota Mining And Manufacturing Company | Fluid dispensing device |
US4300557A (en) | 1980-01-07 | 1981-11-17 | The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method for treating intraocular malignancies |
EP0033042B1 (en) | 1980-01-28 | 1984-08-22 | Merck & Co. Inc. | Ophthalmic inserts for lowering intraocular pressure comprising carbonic anhydrase inhibitors |
US4309776A (en) | 1980-05-13 | 1982-01-12 | Ramon Berguer | Intravascular implantation device and method of using the same |
US4326525A (en) | 1980-10-14 | 1982-04-27 | Alza Corporation | Osmotic device that improves delivery properties of agent in situ |
US4327725A (en) | 1980-11-25 | 1982-05-04 | Alza Corporation | Osmotic device with hydrogel driving member |
US4484922A (en) | 1981-06-25 | 1984-11-27 | Rosenwald Peter L | Occular device |
US4439198A (en) | 1981-07-09 | 1984-03-27 | University Of Illinois Foundation | Biodegradable ocular insert for controlled delivery of ophthalmic medication |
US4730013A (en) | 1981-10-08 | 1988-03-08 | Merck & Co., Inc. | Biosoluble ocular insert |
US4439196A (en) | 1982-03-18 | 1984-03-27 | Merck & Co., Inc. | Osmotic drug delivery system |
US4475916A (en) | 1982-03-18 | 1984-10-09 | Merck & Co., Inc. | Osmotic drug delivery system |
US4519801A (en) | 1982-07-12 | 1985-05-28 | Alza Corporation | Osmotic device with wall comprising cellulose ether and permeability enhancer |
US4673405A (en) | 1983-03-04 | 1987-06-16 | Alza Corporation | Osmotic system with instant drug availability |
US4883459A (en) | 1983-07-29 | 1989-11-28 | Reynaldo Calderon | Retrograde perfusion |
US4774091A (en) | 1983-10-14 | 1988-09-27 | Sumitomo Pharmaceuticals Company, Ltd. | Long-term sustained-release preparation |
US4627850A (en) | 1983-11-02 | 1986-12-09 | Alza Corporation | Osmotic capsule |
US4777049A (en) | 1983-12-01 | 1988-10-11 | Alza Corporation | Constant release system with pulsed release |
US4634418A (en) | 1984-04-06 | 1987-01-06 | Binder Perry S | Hydrogel seton |
US4851228A (en) | 1984-06-20 | 1989-07-25 | Merck & Co., Inc. | Multiparticulate controlled porosity osmotic |
US4634427A (en) | 1984-09-04 | 1987-01-06 | American Hospital Supply Company | Implantable demand medication delivery assembly |
US5049142A (en) | 1984-11-07 | 1991-09-17 | Herrick Robert S | Intracanalicular implant for horizontal canalicular blockade treatment of the eye |
US5053030A (en) | 1984-11-07 | 1991-10-01 | Herrick Robert S | Intracanalicular implant for horizontal canalicular blockade treatment of the eye |
US4712550A (en) | 1985-04-08 | 1987-12-15 | Sinnett Kevin B | Retinal tack |
US4693886A (en) | 1985-04-22 | 1987-09-15 | Alza Corporation | Osmotic device with inert core |
US4609374A (en) | 1985-04-22 | 1986-09-02 | Alza Corporation | Osmotic device comprising means for governing initial time of agent release therefrom |
EP0201611A1 (de) | 1985-05-10 | 1986-11-20 | B. Braun-SSC AG | Zwei-Kanülen-Spritze |
US4781675A (en) | 1985-11-27 | 1988-11-01 | White Thomas C | Infusion cannula |
DE3672981D1 (de) | 1985-11-27 | 1990-08-30 | Thomas C White | Gewebeimplantierbare fluessigkeitsverteileinrichtung. |
US4959217A (en) | 1986-05-22 | 1990-09-25 | Syntex (U.S.A.) Inc. | Delayed/sustained release of macromolecules |
US5322691A (en) | 1986-10-02 | 1994-06-21 | Sohrab Darougar | Ocular insert with anchoring protrusions |
US5147647A (en) | 1986-10-02 | 1992-09-15 | Sohrab Darougar | Ocular insert for the fornix |
US4863457A (en) | 1986-11-24 | 1989-09-05 | Lee David A | Drug delivery device |
DE3785198T3 (de) | 1986-12-23 | 1999-09-02 | Liposome Co Inc | Liposomes präparat und antibiotikum. |
US4853229A (en) | 1987-10-26 | 1989-08-01 | Alza Corporation | Method for adminstering tiny pills |
JP2702953B2 (ja) | 1988-01-30 | 1998-01-26 | オリンパス光学工業株式会社 | 薬液含浸セラミックス |
US4865846A (en) | 1988-06-03 | 1989-09-12 | Kaufman Herbert E | Drug delivery system |
US5174999A (en) | 1988-12-13 | 1992-12-29 | Alza Corporation | Delivery system comprising fluid ingress and drug egress |
WO1990007575A1 (en) | 1988-12-30 | 1990-07-12 | Anderson David M | Stabilized microporous materials and hydrogel materials |
US5141748A (en) | 1989-02-17 | 1992-08-25 | Hoffmann-La Roche, Inc. | Implant drug delivery device |
US5098443A (en) | 1989-03-23 | 1992-03-24 | University Of Miami | Method of implanting intraocular and intraorbital implantable devices for the controlled release of pharmacological agents |
US4979938A (en) | 1989-05-11 | 1990-12-25 | Iomed, Inc. | Method of iontophoretically treating acne, furuncles and like skin disorders |
US5164188A (en) | 1989-11-22 | 1992-11-17 | Visionex, Inc. | Biodegradable ocular implants |
US5171270A (en) | 1990-03-29 | 1992-12-15 | Herrick Robert S | Canalicular implant having a collapsible flared section and method |
US5324280A (en) | 1990-04-02 | 1994-06-28 | Alza Corporation | Osmotic dosage system for delivering a formulation comprising liquid carrier and drug |
US5128145A (en) | 1990-06-13 | 1992-07-07 | Alza Corporation | Dosage form for Parkinson's disease, spasticity and muscle spasms |
US5238687A (en) | 1990-07-11 | 1993-08-24 | Alza Corporation | Delivery device with a protective sleeve |
US5084021A (en) | 1990-11-02 | 1992-01-28 | Baldwin Brian E | Patient controlled infusion apparatus and method |
US5378475A (en) | 1991-02-21 | 1995-01-03 | University Of Kentucky Research Foundation | Sustained release drug delivery devices |
AU650113B2 (en) | 1991-04-05 | 1994-06-09 | Eli Lilly And Company | Sustained release capsule and formulations |
US5334189A (en) | 1991-06-03 | 1994-08-02 | Wade Stephen E | Device for controlled diffusion of a chemical substance |
US5282829A (en) | 1991-08-15 | 1994-02-01 | United States Surgical Corporation | Hollow body implants |
FR2682090B1 (fr) | 1991-10-03 | 1993-12-31 | Holzstoff Holding Sa | Systeme-reservoir pour diffusion prolongee d'un principe actif. |
US5681572A (en) | 1991-10-18 | 1997-10-28 | Seare, Jr.; William J. | Porous material product and process |
US5178635A (en) | 1992-05-04 | 1993-01-12 | Allergan, Inc. | Method for determining amount of medication in an implantable device |
US6096756A (en) | 1992-09-21 | 2000-08-01 | Albert Einstein College Of Medicine Of Yeshiva University | Method of simultaneously enhancing analgesic potency and attenuating dependence liability caused by morphine and other bimodally-acting opioid agonists |
US5336175A (en) | 1992-10-29 | 1994-08-09 | Mames Robert N | Method for the treatment of retinal detachments |
US5443505A (en) | 1993-11-15 | 1995-08-22 | Oculex Pharmaceuticals, Inc. | Biocompatible ocular implants |
CA2140053C (en) | 1994-02-09 | 2000-04-04 | Joel S. Rosenblatt | Collagen-based injectable drug delivery system and its use |
US5770076A (en) | 1994-03-07 | 1998-06-23 | The Regents Of The University Of California | Micromachined capsules having porous membranes and bulk supports |
US5985328A (en) | 1994-03-07 | 1999-11-16 | Regents Of The University Of California | Micromachined porous membranes with bulk support |
US5578042A (en) | 1994-03-14 | 1996-11-26 | Cumming; J. Stuart | Ophthalmic kit and method for lens insertion |
US5466233A (en) | 1994-04-25 | 1995-11-14 | Escalon Ophthalmics, Inc. | Tack for intraocular drug delivery and method for inserting and removing same |
AUPM897594A0 (en) | 1994-10-25 | 1994-11-17 | Daratech Pty Ltd | Controlled release container |
CA2204789C (en) | 1994-11-10 | 2002-11-12 | Paul Ashton | Implantable refillable controlled release device to deliver drugs directly to an internal portion of the body |
US5725493A (en) | 1994-12-12 | 1998-03-10 | Avery; Robert Logan | Intravitreal medicine delivery |
US5554132A (en) | 1995-03-30 | 1996-09-10 | Abbott Laboratories | Hand grip for use with syringe |
IL113723A (en) | 1995-05-14 | 2002-11-10 | Optonol Ltd | Intraocular implant |
US6685940B2 (en) | 1995-07-27 | 2004-02-03 | Genentech, Inc. | Protein formulation |
US5773019A (en) | 1995-09-27 | 1998-06-30 | The University Of Kentucky Research Foundation | Implantable controlled release device to deliver drugs directly to an internal portion of the body |
US6641708B1 (en) | 1996-01-31 | 2003-11-04 | Board Of Regents, The University Of Texas System | Method and apparatus for fractionation using conventional dielectrophoresis and field flow fractionation |
GB2310149A (en) | 1996-02-15 | 1997-08-20 | Nomix Chipman Ltd | Spray gun |
US20090005864A1 (en) | 1996-03-18 | 2009-01-01 | Eggleston Harry C | Modular intraocular implant |
US5951512A (en) | 1996-05-28 | 1999-09-14 | Horizon Medical Products, Inc. | Infusion port with modified drug reservoir |
US5797898A (en) | 1996-07-02 | 1998-08-25 | Massachusetts Institute Of Technology | Microchip drug delivery devices |
US5928662A (en) | 1996-07-31 | 1999-07-27 | Phillips; Andrew F. | Ocular drug delivery device |
AU7533696A (en) | 1996-12-13 | 1998-06-18 | Ciba-Geigy Ag | New materials |
IL132040A (en) | 1997-03-31 | 2004-07-25 | Alza Corp | Prolonged release transfer system and method |
US7160687B1 (en) | 1997-05-29 | 2007-01-09 | Cellomics, Inc. | Miniaturized cell array methods and apparatus for cell-based screening |
US5968008A (en) | 1997-08-04 | 1999-10-19 | Grams; Guenter A. | Cannula with parallel channels and sliding sheath |
US5902598A (en) | 1997-08-28 | 1999-05-11 | Control Delivery Systems, Inc. | Sustained release drug delivery devices |
US6331523B1 (en) | 1998-03-12 | 2001-12-18 | Genentech, Inc. | Method of enhancing the survival of retinal neurons and treating ocular diseases using FGF-5 |
US6196993B1 (en) | 1998-04-20 | 2001-03-06 | Eyelab Group, Llc | Ophthalmic insert and method for sustained release of medication to the eye |
FR2784296B1 (fr) | 1998-09-18 | 2001-01-05 | Imedex Biomateriaux | Dispositif pour la formulation et la delivrance d'un melange, notamment pour l'application chirurgicale de ce melange |
US7973068B2 (en) | 1998-10-20 | 2011-07-05 | Omeros Corporation | Arthroscopic irrigation solution and method for peripheral vasoconstriction and inhibition of pain and inflammation |
DE19948783C2 (de) | 1999-02-18 | 2001-06-13 | Alcove Surfaces Gmbh | Implantat |
US7914442B1 (en) | 1999-03-01 | 2011-03-29 | Gazdzinski Robert F | Endoscopic smart probe and method |
US20050119601A9 (en) * | 1999-04-26 | 2005-06-02 | Lynch Mary G. | Shunt device and method for treating glaucoma |
US6395300B1 (en) | 1999-05-27 | 2002-05-28 | Acusphere, Inc. | Porous drug matrices and methods of manufacture thereof |
US6472162B1 (en) | 1999-06-04 | 2002-10-29 | Thermogenesis Corp. | Method for preparing thrombin for use in a biological glue |
JP4851035B2 (ja) | 1999-06-18 | 2012-01-11 | アルコン ラボラトリーズ,インコーポレイティド | アレルギー性眼疾患を処置するための局所的な眼マスト細胞安定剤 |
US6638263B1 (en) | 1999-10-12 | 2003-10-28 | Durect Corporation | Regulation of drug delivery through flow diversion |
EP1522289A3 (en) * | 1999-10-21 | 2008-01-23 | Alcon, Inc | Sub-tenon drug delivery |
US6416777B1 (en) | 1999-10-21 | 2002-07-09 | Alcon Universal Ltd. | Ophthalmic drug delivery device |
ES2231257T3 (es) | 1999-10-21 | 2005-05-16 | Alcon Inc. | Dispositivo para la administracion de farmacos. |
US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
US20030212383A1 (en) | 2001-01-05 | 2003-11-13 | Dana Cote | System and methods for reducing intraocular pressure |
IL150630A0 (en) | 2000-01-12 | 2003-02-12 | Becton Dickinson Co | Systems and methods for reducing intraocular pressure |
US20050119737A1 (en) * | 2000-01-12 | 2005-06-02 | Bene Eric A. | Ocular implant and methods for making and using same |
DE10008826C2 (de) | 2000-02-25 | 2002-03-14 | Disetronic Licensing Ag | Mikroperfusionsvorrichtung mit Sammelbehältnis |
US7077848B1 (en) | 2000-03-11 | 2006-07-18 | John Hopkins University | Sutureless occular surgical methods and instruments for use in such methods |
US7169444B2 (en) | 2000-03-13 | 2007-01-30 | Seiko Epson Corporation | Method for treating surface of ink jet recording medium having recorded image |
US7141152B2 (en) | 2000-03-16 | 2006-11-28 | Le Febre David A | Analyte species separation system |
US6375972B1 (en) | 2000-04-26 | 2002-04-23 | Control Delivery Systems, Inc. | Sustained release drug delivery devices, methods of use, and methods of manufacturing thereof |
JP2004508102A (ja) | 2000-09-06 | 2004-03-18 | アルコン,インコーポレイテッド | 眼用移植片用の切り替え可能な粘着性コーティング組成物 |
US6303290B1 (en) | 2000-09-13 | 2001-10-16 | The Trustees Of The University Of Pennsylvania | Encapsulation of biomaterials in porous glass-like matrices prepared via an aqueous colloidal sol-gel process |
WO2002056863A2 (en) | 2000-12-29 | 2002-07-25 | Bausch & Lomb Incorporated | Sustained release drug delivery devices |
WO2002053130A2 (en) | 2001-01-03 | 2002-07-11 | Bausch & Lomb Incorporated | Sustained release drug delivery devices with coated drug cores |
CA2432203C (en) | 2001-01-03 | 2008-03-25 | Michael J. Brubaker | Sustained release drug delivery devices with multiple agents |
US6964781B2 (en) | 2001-01-03 | 2005-11-15 | Bausch & Lomb Incorporated | Sustained release drug delivery devices with prefabricated permeable plugs |
WO2002055058A2 (en) | 2001-01-09 | 2002-07-18 | Microchips, Inc. | Flexible microchip devices for ophthalmic and other applications |
US6872198B1 (en) | 2001-01-24 | 2005-03-29 | Arrow International, Inc. | Double-y-shaped multi-lumen catheter with selectively attachable hubs |
JP2004520900A (ja) | 2001-01-26 | 2004-07-15 | ボシュ・アンド・ロム・インコーポレイテッド | 徐放薬剤送達装置の改良製造方法 |
US7181287B2 (en) | 2001-02-13 | 2007-02-20 | Second Sight Medical Products, Inc. | Implantable drug delivery device |
FR2821672B1 (fr) | 2001-03-02 | 2003-05-02 | Scp Dosagene R & D | Moyens pour l'extraction de produits a analyser et leurs applications en diagnostic et analyse |
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 |
DE60239868D1 (de) | 2001-06-12 | 2011-06-09 | Univ Johns Hopkins Med | Reservoirvorrichtung für die intraokulare arzneimittelabgabe |
IL159715A0 (en) | 2001-07-10 | 2004-06-20 | Teva Pharma | Drug delivery system for zero order, zero order-biphasic, ascending or descending drug delivery |
IL144446A0 (en) | 2001-07-19 | 2002-05-23 | Prochon Biotech Ltd | Plasma protein matrices and methods for their preparation |
DE60217679T2 (de) | 2001-07-23 | 2007-10-25 | Alcon Inc. | Vorrichtung zur freisetzung eines ophthalmischen arzneimittels |
JP4249611B2 (ja) | 2001-07-23 | 2009-04-02 | アルコン,インコーポレイティド | 眼薬剤送致装置 |
US7195774B2 (en) | 2001-08-29 | 2007-03-27 | Carvalho Ricardo Azevedo Ponte | Implantable and sealable system for unidirectional delivery of therapeutic agents to tissues |
US7749528B2 (en) | 2001-08-29 | 2010-07-06 | Ricardo Azevedo Pontes De Carvalho | Implantable and sealable medical device for unidirectional delivery of therapeutic agents to tissues |
CN1318093C (zh) | 2001-09-28 | 2007-05-30 | 参天制药株式会社 | 含与聚乙二醇结合的药物的眼组织注射剂 |
AU2002341959A1 (en) | 2001-10-04 | 2003-04-14 | Case Western Reserve University | Drug delivery devices and methods |
US8663687B2 (en) | 2001-10-12 | 2014-03-04 | Monosol Rx, Llc | Film compositions for delivery of actives |
EP1444338A4 (en) | 2001-11-15 | 2007-07-04 | Arryx Inc | PASTILLE WITH SAMPLES |
CA2473355C (en) | 2002-01-18 | 2012-01-03 | Michael E. Snyder | Sustained release ophthalmological device and method of making and using the same |
US8364229B2 (en) | 2003-07-25 | 2013-01-29 | Dexcom, Inc. | Analyte sensors having a signal-to-noise ratio substantially unaffected by non-constant noise |
CA2478772C (en) | 2002-03-11 | 2011-01-18 | Alcon, Inc. | Implantable drug delivery system |
US7074426B2 (en) | 2002-03-27 | 2006-07-11 | Frank Kochinke | Methods and drug delivery systems for the treatment of orofacial diseases |
US7968569B2 (en) | 2002-05-17 | 2011-06-28 | Celgene Corporation | Methods for treatment of multiple myeloma using 3-(4-amino-1-oxo-1,3-dihydro-isoindol-2-yl)-piperidine-2,6-dione |
US7939094B2 (en) | 2002-06-19 | 2011-05-10 | Boston Scientific Scimed, Inc. | Multiphase polymeric drug release region |
ATE424187T1 (de) | 2002-07-15 | 2009-03-15 | Alcon Inc | Bioerodierbare folie zur abgabe eines ophthalmischen arzneimittels |
US8425549B2 (en) | 2002-07-23 | 2013-04-23 | Reverse Medical Corporation | Systems and methods for removing obstructive matter from body lumens and treating vascular defects |
US20040019325A1 (en) | 2002-07-29 | 2004-01-29 | Medrip Ltd. | Syringe Pump |
US7468065B2 (en) | 2002-09-18 | 2008-12-23 | Allergan, Inc. | Apparatus for delivery of ocular implants |
CN1301692C (zh) | 2002-09-18 | 2007-02-28 | 阿勒根公司 | 眼植入物导入的器械 |
CA2689424A1 (en) | 2002-09-29 | 2004-04-08 | Surmodics, Inc. | Methods for treatment and/or prevention of retinal disease |
WO2004066871A2 (en) | 2003-01-24 | 2004-08-12 | Doheny Retina Institute | Reservoirs with subretinal cannula for subretinal drug delivery |
WO2004073551A2 (en) | 2003-02-18 | 2004-09-02 | Massachusetts Eye And Ear Infirmary | Transscleral drug delivery device and related methods |
US20060258000A1 (en) | 2003-02-26 | 2006-11-16 | Allen Jared W | Use of steady-state oxygen gradients to modulate animal cell functions |
US20050255144A1 (en) | 2003-04-09 | 2005-11-17 | Directcontact Llc | Methods and articles for the delivery of medicaments to the eye for the treatment of posterior segment diseases |
US20050074497A1 (en) | 2003-04-09 | 2005-04-07 | Schultz Clyde L. | Hydrogels used to deliver medicaments to the eye for the treatment of posterior segment diseases |
US7094222B1 (en) | 2003-04-28 | 2006-08-22 | The United States Of America As Represented By The Secretary Of Navy | Syringe device for simultaneous infusion and withdrawal |
EP1671624B1 (en) | 2003-05-02 | 2010-08-11 | SurModics, Inc. | Delivery device for a controlled drug release of an active agent into the posterior section of the eye |
ATE476960T1 (de) | 2003-05-02 | 2010-08-15 | Surmodics Inc | System zur kontrollierten freisetzung eines bioaktiven wirkstoffs im hinteren bereich des auges |
EP1635876A4 (en) | 2003-06-13 | 2009-05-06 | Becton Dickinson Co | IMPROVED INTRADERMAL ADMINISTRATION OF BIOACTIVE AGENTS |
WO2004112653A2 (en) | 2003-06-18 | 2004-12-29 | D-Crown Ltd. | Devices and methods for delivering and forming single and multiple stenting structures in situ |
US20040260381A1 (en) | 2003-06-18 | 2004-12-23 | D-Crown Ltd | Devices and methods for forming stenting structures in situ |
US20040260380A1 (en) | 2003-06-18 | 2004-12-23 | D-Crown Ltd | Devices for delivering multiple stenting structures in situ |
US8367410B2 (en) | 2003-06-20 | 2013-02-05 | Massachusetts Institute Of Technology | Application of electrical stimulation for functional tissue engineering in vitro and in vivo |
KR20060082792A (ko) | 2003-07-10 | 2006-07-19 | 알콘, 인코퍼레이티드 | 안과용 약물 전달 장치 |
FI120333B (fi) | 2003-08-20 | 2009-09-30 | Bioretec Oy | Huokoinen lääketieteellinen väline ja menetelmä sen valmistamiseksi |
US7585517B2 (en) | 2003-09-18 | 2009-09-08 | Macusight, Inc. | Transscleral delivery |
US20050181018A1 (en) | 2003-09-19 | 2005-08-18 | Peyman Gholam A. | Ocular drug delivery |
AU2006225241B2 (en) | 2003-09-24 | 2008-07-17 | Tianda Pharmaceuticals (Australia) Pty Limited | Medication Holder |
WO2005028006A1 (en) | 2003-09-24 | 2005-03-31 | Medi-Stream Pty Ltd | Medication holder |
US7615141B2 (en) | 2003-10-03 | 2009-11-10 | University Of Washington | Electrochemical micromanufacturing system and method |
US7211272B2 (en) | 2003-12-22 | 2007-05-01 | Bausch & Lomb Incorporated | Drug delivery device |
WO2005079915A1 (en) | 2004-02-12 | 2005-09-01 | Neo Vista, Inc. | Methods and apparatus for intraocular brachytherapy |
US7276050B2 (en) | 2004-03-02 | 2007-10-02 | Alan Franklin | Trans-scleral drug delivery method and apparatus |
WO2005091922A2 (en) | 2004-03-03 | 2005-10-06 | Becton, Dickinson And Company | Methods and devices for improving delivery of a substance to skin |
WO2005110374A1 (en) | 2004-04-30 | 2005-11-24 | Allergan, Inc. | Intraocular drug delivery systems containing a therapeutic component, a cyclodextrin, and a polymeric component |
US20070059336A1 (en) | 2004-04-30 | 2007-03-15 | Allergan, Inc. | Anti-angiogenic sustained release intraocular implants and related methods |
US8591885B2 (en) | 2004-04-30 | 2013-11-26 | Allergan, Inc. | Carbonic anhydrase inhibitor sustained release intraocular drug delivery systems |
US8685435B2 (en) | 2004-04-30 | 2014-04-01 | Allergan, Inc. | Extended release biodegradable ocular implants |
US20050244469A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Extended therapeutic effect ocular implant treatments |
US20060182783A1 (en) | 2004-04-30 | 2006-08-17 | Allergan, Inc. | Sustained release intraocular drug delivery systems |
US20060110428A1 (en) | 2004-07-02 | 2006-05-25 | Eugene Dejuan | Methods and devices for the treatment of ocular conditions |
US7117870B2 (en) | 2004-07-26 | 2006-10-10 | Clarity Corporation | Lacrimal insert having reservoir with controlled release of medication and method of manufacturing the same |
US20070281028A1 (en) * | 2004-08-04 | 2007-12-06 | Biocompatibles Uk Limited | Drug Delivery of a Cox Inhibitor from Embolic Agents |
CA2575622A1 (en) | 2004-08-06 | 2006-02-09 | Sopherion Therapeutics, Inc. | Anti-angiogenic peptides and methods of use thereof |
WO2006031358A2 (en) | 2004-08-13 | 2006-03-23 | Hyperbranch Medical Technology, Inc. | Dendritic polymers, crosslinked gels, and their uses as ophthalmic sealants and lenses |
WO2006023530A2 (en) | 2004-08-16 | 2006-03-02 | Massachusetts Institute Of Technology | Compositions and methods for enhancing structural and functional nervous system reorganization and recovery |
WO2006031388A2 (en) | 2004-08-20 | 2006-03-23 | Hyperbranch Medical Technology, Inc. | Dentritic polymers, crosslinked gels, and their uses in orthopedic applications |
US20060052754A1 (en) | 2004-09-04 | 2006-03-09 | Fields Douglas W | Thumb trigger syringe pole |
WO2006031532A2 (en) | 2004-09-10 | 2006-03-23 | Surmodics, Inc. | Methods, devices, and coatings for controlled active agent release |
US20080038316A1 (en) | 2004-10-01 | 2008-02-14 | Wong Vernon G | Conveniently implantable sustained release drug compositions |
MX366832B (es) | 2004-10-01 | 2019-07-24 | Ramscor Inc | Composiciones de farmaco de liberacion sostenida convenientemente implantables. |
CA2583399A1 (en) | 2004-10-14 | 2006-04-27 | Sopherion Therapeutics, Inc. | Anti-angiogenic peptides and methods of use thereof |
JO3000B1 (ar) | 2004-10-20 | 2016-09-05 | Genentech Inc | مركبات أجسام مضادة . |
US20090208556A1 (en) | 2004-10-29 | 2009-08-20 | Regents Of The University Of California, The | Porous photonic crystals for drug delivery to the eye |
US20060129215A1 (en) | 2004-12-09 | 2006-06-15 | Helmus Michael N | Medical devices having nanostructured regions for controlled tissue biocompatibility and drug delivery |
US20060154981A1 (en) | 2005-01-12 | 2006-07-13 | Alcon, Inc. | Method of reducing intraocular pressure and treating glaucoma |
EP1848541A4 (en) | 2005-02-07 | 2013-01-16 | Pharmalight Inc | METHOD AND DEVICE FOR OPHTHALMIC DELIVERY OF PHARMACEUTICALLY ACTIVE INGREDIENTS |
US20060257450A1 (en) | 2005-03-21 | 2006-11-16 | Sreenivasu Mudumba | Drug delivery systems for treatment of diseases or conditions |
US8663639B2 (en) * | 2005-02-09 | 2014-03-04 | Santen Pharmaceutical Co., Ltd. | Formulations for treating ocular diseases and conditions |
US20060233858A1 (en) | 2005-03-08 | 2006-10-19 | Allergan, Inc. | Systems and methods providing targeted intraocular drug delivery |
US20070077270A1 (en) | 2005-03-28 | 2007-04-05 | Clemson University | Delivery devices and methods for long-term, targeted delivery of therapeutic agents to the eye and ear |
WO2006108054A2 (en) | 2005-04-05 | 2006-10-12 | The Ohio State University | Diffusion delivery system and methods of fabrication |
US20060228390A1 (en) * | 2005-04-07 | 2006-10-12 | Williams David F | Intravitreal implant |
US20100168535A1 (en) | 2006-04-12 | 2010-07-01 | Mark Ries Robinson | Methods and apparatuses related to blood analyte measurement system |
US20060258994A1 (en) | 2005-05-12 | 2006-11-16 | Avery Robert L | Implantable delivery device for administering pharmacological agents to an internal portion of a body |
WO2006127962A2 (en) | 2005-05-25 | 2006-11-30 | Becton, Dickinson And Comapny | Particulate formulations for intradermal delivery of biologically active agents |
US20070021357A1 (en) | 2005-06-17 | 2007-01-25 | Dynamis Therapeutics, Inc. | Treatment of inflammatory conditions |
US7893040B2 (en) | 2005-07-22 | 2011-02-22 | Oculis Ehf | Cyclodextrin nanotechnology for ophthalmic drug delivery |
US8663673B2 (en) | 2005-07-29 | 2014-03-04 | Surmodics, Inc. | Devices, articles, coatings, and methods for controlled active agent release or hemocompatibility |
US7549972B2 (en) | 2005-08-10 | 2009-06-23 | Insight Instruments, Inc. | Tool for extracting vitreous samples from an eye |
US20070212397A1 (en) | 2005-09-15 | 2007-09-13 | Roth Daniel B | Pharmaceutical delivery device and method for providing ocular treatment |
WO2007035621A1 (en) | 2005-09-16 | 2007-03-29 | (Osi) Eyetech, Inc. | Ophthalmic syringe |
US20080167600A1 (en) * | 2005-09-26 | 2008-07-10 | Peyman Gholam A | Device for delivery of an agent to the eye and other sites |
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 |
US20070072933A1 (en) | 2005-09-26 | 2007-03-29 | Peyman Gholam A | Delivery of an ocular agent |
US20070071756A1 (en) | 2005-09-26 | 2007-03-29 | Peyman Gholam A | Delivery of an agent to ameliorate inflammation |
US20080003219A1 (en) | 2005-09-26 | 2008-01-03 | Minu, L.L.C. | Delivery of an ocular agent |
TW200732347A (en) | 2005-10-06 | 2007-09-01 | Trophogen Inc | VEGF analogs and methods of use |
US8168584B2 (en) | 2005-10-08 | 2012-05-01 | Potentia Pharmaceuticals, Inc. | Methods of treating age-related macular degeneration by compstatin and analogs thereof |
EP1948112A4 (en) | 2005-10-11 | 2011-04-13 | Podaima Blake | SMART MEDICAL COMPLIANCE PROCESS AND SYSTEM |
JP2009511604A (ja) | 2005-10-14 | 2009-03-19 | アルコン,インコーポレイテッド | 緑内障の原発性形態および続発性形態を処置するための方法 |
US20080125406A1 (en) | 2005-10-14 | 2008-05-29 | Robin Alan L | Method for Treating Primary and Secondary Forms of Glaucoma |
JP4721425B2 (ja) | 2005-12-01 | 2011-07-13 | キヤノン株式会社 | 流体移動方法および流体移動装置 |
JP5283509B2 (ja) | 2005-12-07 | 2013-09-04 | ラモット・アット・テル・アビブ・ユニバーシテイ・リミテッド | 薬物送達複合構造体 |
US20070131610A1 (en) | 2005-12-13 | 2007-06-14 | General Electric Company | Membrane-based apparatus and associated method |
US20070131611A1 (en) | 2005-12-13 | 2007-06-14 | General Electric Company | Membrane-based article and associated method |
PL2526910T3 (pl) | 2006-01-17 | 2016-01-29 | Novartis Ag | Urządzenie do leczenia jaskry |
WO2007084582A2 (en) | 2006-01-17 | 2007-07-26 | Forsight Labs, Llc | Drug delivery treatment device |
US20080216736A1 (en) | 2006-01-19 | 2008-09-11 | Takeda San Diego, Inc. | Microfluidic device with diffusion between adjacent lumens |
US8979770B2 (en) | 2006-02-24 | 2015-03-17 | Merck Sharp & Dohme Corp. | Extraction and diagnostic fluid devices, systems and methods of use |
WO2007101204A1 (en) | 2006-02-27 | 2007-09-07 | Alcon Research, Ltd. | Method of treating glaucoma |
US20070212393A1 (en) | 2006-03-08 | 2007-09-13 | Sahajanand Medical Technologies Pvt. Ltd. | Compositions and coatings for implantable medical devices |
TW200800230A (en) | 2006-03-31 | 2008-01-01 | Dynamis Therapeutics Inc | Composition and method related to fructosamine-3-kinase inhibitors |
JP2009532132A (ja) | 2006-03-31 | 2009-09-10 | キューエルティー プラグ デリバリー,インク. | 薬物治療用鼻涙排液系インプラント |
US7547300B2 (en) | 2006-04-12 | 2009-06-16 | Icu Medical, Inc. | Vial adaptor for regulating pressure |
EA013662B1 (ru) | 2006-04-18 | 2010-06-30 | Чжуншань Ботай Фармасьютик Инструментс Ко., Лтд. | Асептический шприц |
US7918814B2 (en) | 2006-05-02 | 2011-04-05 | Georgia Tech Research Corporation | Method for drug delivery to ocular tissue using microneedle |
US8197435B2 (en) | 2006-05-02 | 2012-06-12 | Emory University | Methods and devices for drug delivery to ocular tissue using microneedle |
US7981096B2 (en) | 2006-05-12 | 2011-07-19 | David Castillejos | Optic nerve head implant and medication delivery system |
US20070270750A1 (en) | 2006-05-17 | 2007-11-22 | Alcon, Inc. | Drug delivery device |
US20080124372A1 (en) | 2006-06-06 | 2008-05-29 | Hossainy Syed F A | Morphology profiles for control of agent release rates from polymer matrices |
JP2009542710A (ja) | 2006-06-28 | 2009-12-03 | サーモディクス,インコーポレイティド | 活性剤送達用分解性及び非分解性マトリックスの併用 |
TW200815045A (en) | 2006-06-29 | 2008-04-01 | Jazz Pharmaceuticals Inc | Pharmaceutical compositions of ropinirole and methods of use thereof |
CA2657064C (en) | 2006-07-19 | 2014-09-23 | Noab Biodiscoveries Inc. | Method and device to extract components contained in a fluid |
US20080152694A1 (en) | 2006-07-20 | 2008-06-26 | Neurosystec Corporation | Devices, Systems and Methods for Ophthalmic Drug Delivery |
US20080069854A1 (en) | 2006-08-02 | 2008-03-20 | Inframat Corporation | Medical devices and methods of making and using |
US20080097335A1 (en) | 2006-08-04 | 2008-04-24 | Allergan, Inc. | Ocular implant delivery assemblies |
JP2008054521A (ja) | 2006-08-29 | 2008-03-13 | Canon Inc | 細胞培養処理装置及び細胞培養処理方法 |
US20080057106A1 (en) * | 2006-08-29 | 2008-03-06 | Erickson Signe R | Low profile bioactive agent delivery device |
WO2008033924A2 (en) | 2006-09-12 | 2008-03-20 | Board Of Regents Of The University Of Nebraska | Methods and compositions for targeted delivery of therapeutic agents |
US20080066739A1 (en) | 2006-09-20 | 2008-03-20 | Lemahieu Edward | Methods and systems of delivering medication via inhalation |
JP5694664B2 (ja) | 2006-09-29 | 2015-04-01 | サーモディクス,インコーポレイティド | 生分解性眼用インプラント及び眼の病気を治療する方法 |
US9149750B2 (en) | 2006-09-29 | 2015-10-06 | Mott Corporation | Sinter bonded porous metallic coatings |
WO2008045272A2 (en) | 2006-10-06 | 2008-04-17 | Dynamis Therapeutics, Inc. | Compositions and methods for skin lightening |
US9022970B2 (en) | 2006-10-16 | 2015-05-05 | Alcon Research, Ltd. | Ophthalmic injection device including dosage control device |
US8784897B2 (en) | 2006-10-25 | 2014-07-22 | Revalesio Corporation | Methods of therapeutic treatment of eyes |
US8784898B2 (en) | 2006-10-25 | 2014-07-22 | Revalesio Corporation | Methods of wound care and treatment |
US8609148B2 (en) | 2006-10-25 | 2013-12-17 | Revalesio Corporation | Methods of therapeutic treatment of eyes |
AU2007308840C1 (en) | 2006-10-25 | 2014-09-25 | Revalesio Corporation | Methods of therapeutic treatment of eyes and other human tissues using an oxygen-enriched solution |
CA2667614A1 (en) | 2006-10-25 | 2008-09-25 | Revalesio Corporation | Method of wound care and treatment |
EP2088976B1 (en) | 2006-11-10 | 2019-07-03 | Glaukos Corporation | Uveoscleral shunt |
US20080111282A1 (en) | 2006-11-10 | 2008-05-15 | Baojun Xie | Process for Making Three Dimensional Objects From Dispersions of Polymer Colloidal Particles |
US20100286791A1 (en) | 2006-11-21 | 2010-11-11 | Goldsmith David S | Integrated system for the ballistic and nonballistic infixion and retrieval of implants |
WO2008070118A1 (en) | 2006-12-05 | 2008-06-12 | Landec Corporation | Drug delivery |
US20090263346A1 (en) | 2006-12-05 | 2009-10-22 | David Taft | Systems and methods for delivery of drugs |
US20080154241A1 (en) | 2006-12-07 | 2008-06-26 | Burkstrand Michael J | Latent stabilization of bioactive agents releasable from implantable medical articles |
US20080147021A1 (en) | 2006-12-15 | 2008-06-19 | Jani Dharmendra M | Drug delivery devices |
ZA200903649B (en) | 2006-12-18 | 2010-08-25 | Alcon Res Ltd | Devices and methods for ophthalmic drug delivery |
US9308125B2 (en) | 2007-01-09 | 2016-04-12 | Fovea Pharmaceuticals | Apparatus for intra-ocular injection |
EP2104473A1 (en) | 2007-01-19 | 2009-09-30 | Cinvention Ag | Porous, non-degradable implant made by powder molding |
UY30883A1 (es) | 2007-01-31 | 2008-05-31 | Alcon Res | Tapones punctales y metodos de liberacion de agentes terapeuticos |
GB0702864D0 (en) | 2007-02-14 | 2007-03-28 | Benoist Girard Sas | Prosthetic implant for use without bone cement |
WO2008116165A2 (en) | 2007-03-21 | 2008-09-25 | Next Safety, Inc. | Methods and systems of delivering medication via inhalation |
US20080249501A1 (en) | 2007-04-09 | 2008-10-09 | Medtronic Vascular, Inc. | Methods for Simultaneous Injection and Aspiration of Fluids During a Medical Procedure |
US20080286338A1 (en) | 2007-05-15 | 2008-11-20 | Boston Foundation For Sight | Drug delivery system with scleral lens |
US8231892B2 (en) | 2007-05-24 | 2012-07-31 | Allergan, Inc. | Biodegradable drug delivery system |
CN101815724B (zh) | 2007-05-29 | 2015-02-25 | 安吉奥开米公司 | 用于将轭合至其的试剂递送至组织的抑肽酶样多肽 |
US9365634B2 (en) | 2007-05-29 | 2016-06-14 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
US20090036827A1 (en) | 2007-07-31 | 2009-02-05 | Karl Cazzini | Juxtascleral Drug Delivery and Ocular Implant System |
US9808557B2 (en) | 2007-08-10 | 2017-11-07 | Trustees Of Tufts College | Tubular silk compositions and methods of use thereof |
MX2010002616A (es) * | 2007-09-07 | 2010-08-04 | Qlt Plug Delivery Inc | Nucleos de farmaco para la liberacion sostenida de agentes terapeuticos. |
RU2010112417A (ru) | 2007-09-07 | 2011-10-10 | Клт Плаг Диливери, Инк. (Us) | Обнаружение лакримальных имплантатов |
AU2008300018A1 (en) | 2007-09-07 | 2009-03-19 | Qlt Inc. | Insertion and extraction tools for lacrimal implants |
US8308755B2 (en) | 2007-09-24 | 2012-11-13 | Ethicon Endo-Surgery, Inc. | Elliptical retractor |
US20090081272A1 (en) | 2007-09-24 | 2009-03-26 | John Clarke | Medical devices having a metal particulate composition for controlled diffusion |
US8974809B2 (en) * | 2007-09-24 | 2015-03-10 | Boston Scientific Scimed, Inc. | Medical devices having a filter insert for controlled diffusion |
US20090214601A1 (en) | 2007-09-28 | 2009-08-27 | Chappa Ralph A | Porous Drug Delivery Devices and Related Methods |
RU2475282C2 (ru) | 2007-10-05 | 2013-02-20 | Тико Хелскеа Груп Лп | Герметизирующий фиксатор для использования при хирургических операциях |
US20100100043A1 (en) | 2007-10-05 | 2010-04-22 | Racenet Danyel J | Flexible Access Device For Use In Surgical Procedure |
US20100303918A1 (en) | 2007-10-25 | 2010-12-02 | Revalesio Corporation | Compositions and methods for treating asthma and other lung disorders |
WO2010062628A1 (en) | 2008-10-27 | 2010-06-03 | Revalesio Corporation | Compositions and methods for treating asthma and other lung disorders |
CA2703648A1 (en) | 2007-10-25 | 2009-04-30 | Revalesio Corporation | Bacteriostatic or bacteriocidal compositions and methods |
US20090263495A1 (en) | 2007-10-25 | 2009-10-22 | Revalesio Corporation | Bacteriostatic or bacteriocidal compositions and methods |
US20100009008A1 (en) | 2007-10-25 | 2010-01-14 | Revalesio Corporation | Bacteriostatic or bacteriocidal compositions and methods |
US20100008997A1 (en) | 2007-10-25 | 2010-01-14 | Revalesio Corporation | Compositions and methods for treating asthma and other lung disorders |
US20090227018A1 (en) | 2007-10-25 | 2009-09-10 | Revalesio Corporation | Compositions and methods for modulating cellular membrane-mediated intracellular signal transduction |
US10125359B2 (en) | 2007-10-25 | 2018-11-13 | Revalesio Corporation | Compositions and methods for treating inflammation |
US20100310665A1 (en) | 2007-10-25 | 2010-12-09 | Revalesio Corporation | Bacteriostatic or bacteriocidal compositions and methods |
US20100004189A1 (en) | 2007-10-25 | 2010-01-07 | Revalesio Corporation | Compositions and methods for treating cystic fibrosis |
US20100303917A1 (en) | 2007-10-25 | 2010-12-02 | Revalesio Corporation | Compositions and methods for treating cystic fibrosis |
US9523090B2 (en) | 2007-10-25 | 2016-12-20 | Revalesio Corporation | Compositions and methods for treating inflammation |
WO2009061607A2 (en) | 2007-11-05 | 2009-05-14 | Bausch & Lomb Incorporated | Water-immiscible materials as vehicles for drug delivery |
US8114883B2 (en) | 2007-12-04 | 2012-02-14 | Landec Corporation | Polymer formulations for delivery of bioactive materials |
ES2425769T5 (es) | 2007-12-20 | 2017-07-28 | University Of Southern California | Aparato para la administración de agentes terapéuticos |
US8414646B2 (en) | 2007-12-27 | 2013-04-09 | Forsight Labs, Llc | Intraocular, accommodating lens and methods of use |
EP2240220B1 (en) | 2008-01-03 | 2016-04-13 | University Of Southern California | Implantable drug-delivery devices, and apparatus for refilling the devices |
US20100305514A1 (en) | 2008-01-10 | 2010-12-02 | Bausch & Lomb Incorporated | Intravitreal injection system having coaxial cannulae and use thereof |
WO2009094466A2 (en) | 2008-01-22 | 2009-07-30 | University Of Florida Research Foundation, Inc. | Contact lenses for extended release of bioactive agents containing diffusion attenuators |
JP2011510750A (ja) | 2008-01-29 | 2011-04-07 | クライマン、ギルバート・エイチ | 薬物送達デバイス、キット及びそれらの方法 |
US8201752B2 (en) | 2008-03-10 | 2012-06-19 | Vapore, Inc. | Low energy vaporization of liquids: apparatus and methods |
TNSN08110A1 (en) | 2008-03-11 | 2009-07-14 | Rekik Raouf Dr | Drug delivery to the anterior and posterior segment of the eye from drops |
US20090240208A1 (en) * | 2008-03-19 | 2009-09-24 | Warsaw Orthopedic, Inc. | Microparticle delivery syringe and needle for placing particle suspensions and removing vehicle fluid |
EP2257326A2 (en) | 2008-03-21 | 2010-12-08 | Novartis AG | Powder dispersion apparatus |
NZ604092A (en) | 2008-03-31 | 2015-08-28 | Nitto Denko Corp | Permeant delivery system and methods for use thereof |
US8555874B2 (en) | 2008-04-04 | 2013-10-15 | Nektar Therapeutics | Aerosolization device |
US8801665B2 (en) | 2008-04-10 | 2014-08-12 | Henry Ford Health System | Apparatus and method for controlled depth of injection into myocardial tissue |
WO2009128932A1 (en) | 2008-04-15 | 2009-10-22 | Sarcode Corporation | Delivery of lfa-1 antagonists to the gastrointestinal system |
EP2276471B1 (en) | 2008-04-30 | 2018-08-08 | Mati Therapeutics Inc. | Composite lacrimal insert and related methods |
EP2285347A4 (en) | 2008-05-01 | 2011-09-21 | Revalesio Corp | COMPOSITIONS AND METHODS OF TREATING DISORDERS OF THE DIGESTION SYSTEM |
EP2320972B1 (en) | 2008-05-08 | 2020-07-01 | MiniPumps, LLC | Implantable drug-delivery devices |
CA2724607A1 (en) * | 2008-05-30 | 2009-12-31 | Fairfield Clinical Trials, Llc | Method and composition for skin inflammation and discoloration |
US10517839B2 (en) * | 2008-06-09 | 2019-12-31 | Cornell University | Mast cell inhibition in diseases of the retina and vitreous |
US20100197512A1 (en) | 2008-07-11 | 2010-08-05 | Intellicyt | Multi-Sample Particle Analyzer and Method for High Throughput Screening |
US8821870B2 (en) | 2008-07-18 | 2014-09-02 | Allergan, Inc. | Method for treating atrophic age related macular degeneration |
WO2010011695A1 (en) | 2008-07-21 | 2010-01-28 | Arstasis, Inc. | Devices, methods, and kits for forming tracts in tissue |
US20100023033A1 (en) | 2008-07-25 | 2010-01-28 | Medtronic Vescular, Inc. | Hydrodynamic Thrombectomy Catheter |
US20100022943A1 (en) | 2008-07-25 | 2010-01-28 | Medtronic Vascular, Inc. | Hydrodynamic Thrombectomy Catheter |
WO2010021993A1 (en) | 2008-08-19 | 2010-02-25 | Cytori Therapeutics, Inc. | Methods of using adipose tissue-derived cells in the treatment of the lymphatic system and malignant disease |
US7678078B1 (en) | 2008-10-21 | 2010-03-16 | KMG Pharma LLC | Intravitreal injection device, system and method |
US8221353B2 (en) | 2008-10-21 | 2012-07-17 | KMG Pharma, Inc | Intravitreal injection device and system |
DE102008054431B3 (de) | 2008-12-09 | 2010-06-17 | Pari Pharma Gmbh | Aerosoltherapievorrichtung |
US20100158980A1 (en) | 2008-12-18 | 2010-06-24 | Casey Kopczynski | Drug delivery devices for delivery of therapeutic agents |
AU2009333100B2 (en) * | 2009-01-02 | 2014-08-14 | Alcon Research, Ltd. | In-situ refillable ophthalmic implant |
US8545554B2 (en) | 2009-01-16 | 2013-10-01 | Allergan, Inc. | Intraocular injector |
CA3045436A1 (en) | 2009-01-29 | 2010-08-05 | Forsight Vision4, Inc. | Posterior segment drug delivery |
US8623395B2 (en) | 2010-01-29 | 2014-01-07 | Forsight Vision4, Inc. | Implantable therapeutic device |
US9636255B2 (en) | 2009-02-13 | 2017-05-02 | Dose Medical Corporation | Uveoscleral drug delivery implant and methods for implanting the same |
WO2010095940A2 (en) | 2009-02-20 | 2010-08-26 | To-Bbb Holding B.V. | Glutathione-based drug delivery system |
WO2010101989A1 (en) | 2009-03-03 | 2010-09-10 | Alcon Research, Ltd. | PHARMACEUTICAL COMPOSITION FOR DELIVERY OF RECEPTOR TYROSINE KINASE INHIBITING (RTKi) COMPOUNDS TO THE EYE |
US8815292B2 (en) | 2009-04-27 | 2014-08-26 | Revalesio Corporation | Compositions and methods for treating insulin resistance and diabetes mellitus |
WO2010125416A1 (en) | 2009-04-27 | 2010-11-04 | Raouf Rekik | Drug delivery to the anterior and posterior segments of the eye |
CA2758738A1 (en) | 2009-04-27 | 2010-11-04 | Revalesio Corporation | Compositions and methods for treating insulin resistance and diabetes mellitus |
CA2761677A1 (en) | 2009-05-15 | 2010-11-18 | Arstasis, Inc. | Devices, methods and kits for forming tracts in tissue |
JP5937004B2 (ja) | 2009-05-18 | 2016-06-22 | ドーズ メディカル コーポレーションDose Medical Corporation | 薬剤溶出眼内インプラント |
EP4108216A1 (en) | 2009-06-03 | 2022-12-28 | Forsight Vision5, Inc. | Anterior segment drug delivery |
US9005649B2 (en) | 2009-07-14 | 2015-04-14 | Board Of Regents, The University Of Texas System | Methods for making controlled delivery devices having zero order kinetics |
US20110033933A1 (en) | 2009-07-15 | 2011-02-10 | Morteza Gharib | Method applying hemodynamic forcing and klf2 to initiate the growth and development of cardiac valves |
KR20120059553A (ko) | 2009-08-14 | 2012-06-08 | 제넨테크, 인크. | Vegf 길항제에 대한 환자 반응을 모니터링하기 위한 생물학적 마커 |
CA2772660A1 (en) | 2009-09-01 | 2011-03-10 | Northwestern University | Delivery of therapeutic agents using oligonucleotide-modified nanoparticles as carriers |
US20130041265A1 (en) | 2009-09-21 | 2013-02-14 | Ron Sostek | Methods and apparatus for introducing cells at a tissue site |
EP2515864A4 (en) | 2009-12-23 | 2013-09-11 | Psivida Inc | DELAYED RELEASE DELIVERY DEVICES |
WO2013022801A1 (en) | 2011-08-05 | 2013-02-14 | Forsight Vision4, Inc. | Small molecule delivery with implantable therapeutic device |
US8821474B2 (en) | 2010-02-22 | 2014-09-02 | Microsert Ltd. | Slow release liquid drug delivery device |
US20110301555A1 (en) * | 2010-06-03 | 2011-12-08 | Gonzalez-Zugasti Javier P | Porous matrix drug core for lacrimal insert device |
AU2011285637B2 (en) | 2010-08-05 | 2014-10-30 | Forsight Vision4, Inc. | Subconjunctival implant for posterior segment drug delivery |
JP5907966B2 (ja) | 2010-08-05 | 2016-04-26 | フォーサイト・ビジョン フォー・インコーポレーテッド | 埋め込み型治療デバイス |
US9033911B2 (en) | 2010-08-05 | 2015-05-19 | Forsight Vision4, Inc. | Injector apparatus and method for drug delivery |
WO2012019139A1 (en) | 2010-08-05 | 2012-02-09 | Forsight Vision4, Inc. | Combined drug delivery methods and apparatus |
US20140033800A1 (en) | 2010-11-11 | 2014-02-06 | Forsight Vision4, Inc. | Methods and apparatus to determine diffusion properties of porous structures for drug delivery |
EP2640360A2 (en) | 2010-11-19 | 2013-09-25 | Forsight Vision4, Inc. | Therapeutic agent formulations for implanted devices |
WO2013003620A2 (en) * | 2011-06-28 | 2013-01-03 | Forsight Vision4, Inc. | Diagnostic methods and apparatus |
EP3903733A1 (en) | 2011-09-16 | 2021-11-03 | ForSight Vision4, Inc. | Fluid exchange apparatus |
WO2013116061A1 (en) | 2012-02-03 | 2013-08-08 | Forsight Vision4, Inc. | Insertion and removal methods and apparatus for therapeutic devices |
-
2011
- 2011-08-05 WO PCT/US2011/046817 patent/WO2012019139A1/en active Application Filing
- 2011-08-05 AU AU2011285548A patent/AU2011285548B2/en not_active Ceased
- 2011-08-05 JP JP2013523372A patent/JP6111194B2/ja active Active
- 2011-08-05 EP EP20110815389 patent/EP2600876B1/en active Active
- 2011-08-05 US US13/814,466 patent/US10617557B2/en active Active
- 2011-08-05 CA CA2807537A patent/CA2807537C/en not_active Expired - Fee Related
- 2011-08-05 CN CN201180048624.5A patent/CN103153316B/zh active Active
-
2020
- 2020-03-04 US US16/808,784 patent/US11679027B2/en active Active
Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004524866A (ja) * | 2000-08-30 | 2004-08-19 | ジョンズ・ホプキンス・ユニバーシティ | 眼内薬剤送達装置 |
JP2010514517A (ja) * | 2006-12-26 | 2010-05-06 | キューエルティー プラグ デリバリー,インク. | 視覚欠損の抑制のための薬物送達インプラント |
WO2010062394A2 (en) * | 2008-11-26 | 2010-06-03 | Surmodics, Inc. | Implantable ocular drug delivery device and methods |
Also Published As
Publication number | Publication date |
---|---|
WO2012019139A9 (en) | 2013-03-28 |
AU2011285548A1 (en) | 2013-03-07 |
WO2012019139A1 (en) | 2012-02-09 |
US11679027B2 (en) | 2023-06-20 |
JP6111194B2 (ja) | 2017-04-05 |
US20200405537A1 (en) | 2020-12-31 |
EP2600876A1 (en) | 2013-06-12 |
CA2807537C (en) | 2018-09-18 |
AU2011285548B2 (en) | 2014-02-06 |
US10617557B2 (en) | 2020-04-14 |
US20130274691A1 (en) | 2013-10-17 |
EP2600876A4 (en) | 2014-01-15 |
EP2600876B1 (en) | 2015-04-29 |
CA2807537A1 (en) | 2012-02-09 |
CN103153316A (zh) | 2013-06-12 |
CN103153316B (zh) | 2015-08-19 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6111194B2 (ja) | 組み合わせ薬物送達方法および装置 | |
US20230338282A1 (en) | Posterior segment drug delivery | |
AU2016202327B2 (en) | Implantable therapeutic device | |
AU2011285637B2 (en) | Subconjunctival implant for posterior segment drug delivery | |
US20150297402A1 (en) | Implantable Therapeutic Device | |
JP6063382B2 (ja) | 治療薬を眼の埋め込み体へと注入するためのシステム | |
EP2739252A1 (en) | Small molecule delivery with implantable therapeutic device | |
AU2014202463B2 (en) | Combined drug delivery methods and apparatus |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140805 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140805 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20150617 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150630 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150916 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20151102 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20151130 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20160104 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20160606 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20160905 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20161020 |
|
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: 20170220 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20170313 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6111194 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 |