JP2014217769A - 治療装置 - Google Patents
治療装置 Download PDFInfo
- Publication number
- JP2014217769A JP2014217769A JP2014140048A JP2014140048A JP2014217769A JP 2014217769 A JP2014217769 A JP 2014217769A JP 2014140048 A JP2014140048 A JP 2014140048A JP 2014140048 A JP2014140048 A JP 2014140048A JP 2014217769 A JP2014217769 A JP 2014217769A
- Authority
- JP
- Japan
- Prior art keywords
- therapeutic agent
- porous structure
- treatment device
- therapeutic
- 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
- 230000001225 therapeutic effect Effects 0.000 title claims abstract description 247
- 239000003814 drug Substances 0.000 claims abstract description 826
- 229940124597 therapeutic agent Drugs 0.000 claims abstract description 736
- 239000007924 injection Substances 0.000 claims description 194
- 238000002347 injection Methods 0.000 claims description 194
- 210000004127 vitreous body Anatomy 0.000 claims description 188
- 239000000463 material Substances 0.000 claims description 166
- 210000003786 sclera Anatomy 0.000 claims description 118
- 230000004888 barrier function Effects 0.000 claims description 114
- 229940079593 drug Drugs 0.000 claims description 84
- 229960003876 ranibizumab Drugs 0.000 claims description 80
- 239000002245 particle Substances 0.000 claims description 58
- -1 Arsitumomab Proteins 0.000 claims description 47
- 229910052751 metal Inorganic materials 0.000 claims description 33
- 239000002184 metal Substances 0.000 claims description 33
- 210000000795 conjunctiva Anatomy 0.000 claims description 31
- 239000011521 glass Substances 0.000 claims description 21
- 238000002513 implantation Methods 0.000 claims description 20
- 229960000397 bevacizumab Drugs 0.000 claims description 13
- 239000000919 ceramic Substances 0.000 claims description 12
- 108010050904 Interferons Proteins 0.000 claims description 11
- 102000014150 Interferons Human genes 0.000 claims description 11
- 229940079322 interferon Drugs 0.000 claims description 11
- 239000000560 biocompatible material Substances 0.000 claims description 9
- 210000003161 choroid Anatomy 0.000 claims description 9
- 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 claims description 6
- 239000012669 liquid formulation Substances 0.000 claims description 5
- 108010069236 Goserelin Proteins 0.000 claims description 4
- 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 claims description 4
- 108010071390 Serum Albumin Proteins 0.000 claims description 4
- 102000007562 Serum Albumin Human genes 0.000 claims description 4
- 229960002913 goserelin Drugs 0.000 claims description 4
- 108010051696 Growth Hormone Proteins 0.000 claims description 3
- 108090001061 Insulin Proteins 0.000 claims description 3
- 102000004877 Insulin Human genes 0.000 claims description 3
- 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 claims description 3
- 108010004977 Vasopressins Proteins 0.000 claims description 3
- 102000002852 Vasopressins Human genes 0.000 claims description 3
- 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 claims description 3
- 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 claims description 3
- 229960005395 cetuximab Drugs 0.000 claims description 3
- 229940125396 insulin Drugs 0.000 claims description 3
- 230000000149 penetrating effect Effects 0.000 claims description 3
- 229960003726 vasopressin Drugs 0.000 claims description 3
- 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 claims description 2
- 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 claims description 2
- 102100022712 Alpha-1-antitrypsin Human genes 0.000 claims description 2
- 108010058207 Anistreplase Proteins 0.000 claims description 2
- 108010039627 Aprotinin Proteins 0.000 claims description 2
- 102000015790 Asparaginase Human genes 0.000 claims description 2
- 108010024976 Asparaginase Proteins 0.000 claims description 2
- 101800000407 Brain natriuretic peptide 32 Proteins 0.000 claims description 2
- 102100026735 Coagulation factor VIII Human genes 0.000 claims description 2
- 108010000437 Deamino Arginine Vasopressin Proteins 0.000 claims description 2
- 108010032976 Enfuvirtide Proteins 0.000 claims description 2
- 108010074604 Epoetin Alfa Proteins 0.000 claims description 2
- 108010056764 Eptifibatide Proteins 0.000 claims description 2
- 108010008165 Etanercept Proteins 0.000 claims description 2
- 108010011459 Exenatide Proteins 0.000 claims description 2
- 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 claims description 2
- 108010054265 Factor VIIa Proteins 0.000 claims description 2
- 108010029961 Filgrastim Proteins 0.000 claims description 2
- 108010072051 Glatiramer Acetate Proteins 0.000 claims description 2
- 102000006395 Globulins Human genes 0.000 claims description 2
- 108010044091 Globulins Proteins 0.000 claims description 2
- 108060003199 Glucagon Proteins 0.000 claims description 2
- 102100039619 Granulocyte colony-stimulating factor Human genes 0.000 claims description 2
- 102000018997 Growth Hormone Human genes 0.000 claims description 2
- 101000911390 Homo sapiens Coagulation factor VIII Proteins 0.000 claims description 2
- 108010003272 Hyaluronate lyase Proteins 0.000 claims description 2
- 102000001974 Hyaluronidases Human genes 0.000 claims description 2
- 102100029199 Iduronate 2-sulfatase Human genes 0.000 claims description 2
- 108060003951 Immunoglobulin Proteins 0.000 claims description 2
- 108010057186 Insulin Glargine Proteins 0.000 claims description 2
- 108010065920 Insulin Lispro Proteins 0.000 claims description 2
- 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 claims description 2
- 108010078049 Interferon alpha-2 Proteins 0.000 claims description 2
- 102100040018 Interferon alpha-2 Human genes 0.000 claims description 2
- 108010079944 Interferon-alpha2b Proteins 0.000 claims description 2
- 102000051628 Interleukin-1 receptor antagonist Human genes 0.000 claims description 2
- 108700021006 Interleukin-1 receptor antagonist Proteins 0.000 claims description 2
- 108010000817 Leuprolide Proteins 0.000 claims description 2
- 108010016076 Octreotide Proteins 0.000 claims description 2
- 108700006640 OspA Proteins 0.000 claims description 2
- 102400000050 Oxytocin Human genes 0.000 claims description 2
- 101800000989 Oxytocin Proteins 0.000 claims description 2
- XNOPRXBHLZRZKH-UHFFFAOYSA-N Oxytocin Natural products N1C(=O)C(N)CSSCC(C(=O)N2C(CCC2)C(=O)NC(CC(C)C)C(=O)NCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(CCC(N)=O)NC(=O)C(C(C)CC)NC(=O)C1CC1=CC=C(O)C=C1 XNOPRXBHLZRZKH-UHFFFAOYSA-N 0.000 claims description 2
- 108010005991 Pork Regular Insulin Proteins 0.000 claims description 2
- 108010086019 Secretin Proteins 0.000 claims description 2
- 102100037505 Secretin Human genes 0.000 claims description 2
- 108010039185 Tenecteplase Proteins 0.000 claims description 2
- 108010049264 Teriparatide Proteins 0.000 claims description 2
- 108090000373 Tissue Plasminogen Activator Proteins 0.000 claims description 2
- 102000003978 Tissue Plasminogen Activator Human genes 0.000 claims description 2
- 108010057266 Type A Botulinum Toxins Proteins 0.000 claims description 2
- 102000003990 Urokinase-type plasminogen activator Human genes 0.000 claims description 2
- 108090000435 Urokinase-type plasminogen activator Proteins 0.000 claims description 2
- 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 claims description 2
- 229960002184 abarelix Drugs 0.000 claims description 2
- 108010023617 abarelix Proteins 0.000 claims description 2
- 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 claims description 2
- 229960003697 abatacept Drugs 0.000 claims description 2
- 229960000446 abciximab Drugs 0.000 claims description 2
- FHEAIOHRHQGZPC-KIWGSFCNSA-N acetic acid;(2s)-2-amino-3-(4-hydroxyphenyl)propanoic acid;(2s)-2-aminopentanedioic acid;(2s)-2-aminopropanoic acid;(2s)-2,6-diaminohexanoic acid Chemical compound CC(O)=O.C[C@H](N)C(O)=O.NCCCC[C@H](N)C(O)=O.OC(=O)[C@@H](N)CCC(O)=O.OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 FHEAIOHRHQGZPC-KIWGSFCNSA-N 0.000 claims description 2
- 229960002964 adalimumab Drugs 0.000 claims description 2
- 229960005310 aldesleukin Drugs 0.000 claims description 2
- 108700025316 aldesleukin Proteins 0.000 claims description 2
- 229960002459 alefacept Drugs 0.000 claims description 2
- 229960000548 alemtuzumab Drugs 0.000 claims description 2
- 108010050122 alpha 1-Antitrypsin Proteins 0.000 claims description 2
- 229960003318 alteplase Drugs 0.000 claims description 2
- 229960004238 anakinra Drugs 0.000 claims description 2
- 229960000983 anistreplase Drugs 0.000 claims description 2
- 230000001494 anti-thymocyte effect Effects 0.000 claims description 2
- 229960004405 aprotinin Drugs 0.000 claims description 2
- 229960003272 asparaginase Drugs 0.000 claims description 2
- DCXYFEDJOCDNAF-UHFFFAOYSA-M asparaginate Chemical compound [O-]C(=O)C(N)CC(N)=O DCXYFEDJOCDNAF-UHFFFAOYSA-M 0.000 claims description 2
- 229960004669 basiliximab Drugs 0.000 claims description 2
- 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 claims description 2
- 229940094657 botulinum toxin type a Drugs 0.000 claims description 2
- 229960003773 calcitonin (salmon synthetic) Drugs 0.000 claims description 2
- 229950001178 capromab Drugs 0.000 claims description 2
- 229960003230 cetrorelix Drugs 0.000 claims description 2
- 108700008462 cetrorelix Proteins 0.000 claims description 2
- 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 claims description 2
- 229960004120 defibrotide Drugs 0.000 claims description 2
- 108010017271 denileukin diftitox Proteins 0.000 claims description 2
- 229960002923 denileukin diftitox Drugs 0.000 claims description 2
- 229960004281 desmopressin Drugs 0.000 claims description 2
- 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 claims description 2
- 108010067396 dornase alfa Proteins 0.000 claims description 2
- 229960002224 eculizumab Drugs 0.000 claims description 2
- 229960000284 efalizumab Drugs 0.000 claims description 2
- 229960002062 enfuvirtide Drugs 0.000 claims description 2
- 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 claims description 2
- 229960003388 epoetin alfa Drugs 0.000 claims description 2
- 229960004468 eptifibatide Drugs 0.000 claims description 2
- 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 claims description 2
- 229960000403 etanercept Drugs 0.000 claims description 2
- 229960001519 exenatide Drugs 0.000 claims description 2
- 229960004177 filgrastim Drugs 0.000 claims description 2
- 108010081934 follitropin beta Proteins 0.000 claims description 2
- 229960002907 follitropin beta Drugs 0.000 claims description 2
- 229960005390 galsulfase Drugs 0.000 claims description 2
- 108010089296 galsulfase Proteins 0.000 claims description 2
- 229960003297 gemtuzumab ozogamicin Drugs 0.000 claims description 2
- 229960003776 glatiramer acetate Drugs 0.000 claims description 2
- 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 claims description 2
- 229960004666 glucagon Drugs 0.000 claims description 2
- 239000000122 growth hormone Substances 0.000 claims description 2
- 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 claims description 2
- 229960002773 hyaluronidase Drugs 0.000 claims description 2
- 108010072166 idursulfase Proteins 0.000 claims description 2
- 229960002396 idursulfase Drugs 0.000 claims description 2
- 102000018358 immunoglobulin Human genes 0.000 claims description 2
- 229960000598 infliximab Drugs 0.000 claims description 2
- 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 claims description 2
- 229960002869 insulin glargine Drugs 0.000 claims description 2
- 229960002068 insulin lispro Drugs 0.000 claims description 2
- 229960003161 interferon beta-1b Drugs 0.000 claims description 2
- 229940028862 interferon gamma-1b Drugs 0.000 claims description 2
- 108010042414 interferon gamma-1b Proteins 0.000 claims description 2
- 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 claims description 2
- 229960004338 leuprorelin Drugs 0.000 claims description 2
- 108010000594 mecasermin Proteins 0.000 claims description 2
- 229960001311 mecasermin Drugs 0.000 claims description 2
- 229960005027 natalizumab Drugs 0.000 claims description 2
- 229960001267 nesiritide Drugs 0.000 claims description 2
- 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 claims description 2
- 229960002700 octreotide Drugs 0.000 claims description 2
- 229960000470 omalizumab Drugs 0.000 claims description 2
- XNOPRXBHLZRZKH-DSZYJQQASA-N oxytocin Chemical compound C([C@H]1C(=O)N[C@H](C(N[C@@H](CCC(N)=O)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)=O)[C@@H](C)CC)C1=CC=C(O)C=C1 XNOPRXBHLZRZKH-DSZYJQQASA-N 0.000 claims description 2
- 229960001723 oxytocin Drugs 0.000 claims description 2
- 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 claims description 2
- 229960001373 pegfilgrastim Drugs 0.000 claims description 2
- 108010044644 pegfilgrastim Proteins 0.000 claims description 2
- 229960002995 pegvisomant Drugs 0.000 claims description 2
- 108700037519 pegvisomant Proteins 0.000 claims description 2
- 229960003611 pramlintide Drugs 0.000 claims description 2
- 108010029667 pramlintide Proteins 0.000 claims description 2
- 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 claims description 2
- 229960000424 rasburicase Drugs 0.000 claims description 2
- 108010084837 rasburicase Proteins 0.000 claims description 2
- 238000005215 recombination Methods 0.000 claims description 2
- 230000006798 recombination Effects 0.000 claims description 2
- 108010051412 reteplase Proteins 0.000 claims description 2
- 229960002917 reteplase Drugs 0.000 claims description 2
- 108010074523 rimabotulinumtoxinB Proteins 0.000 claims description 2
- 229960004641 rituximab Drugs 0.000 claims description 2
- 108010068072 salmon calcitonin Proteins 0.000 claims description 2
- 229960002101 secretin Drugs 0.000 claims description 2
- OWMZNFCDEHGFEP-NFBCVYDUSA-N secretin human Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CO)C(=O)N[C@@H](CCC(O)=O)C(=O)N[C@@H](CC(C)C)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](CCCNC(N)=N)C(=O)N[C@@H](CCC(O)=O)C(=O)NCC(=O)N[C@@H](C)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCC(N)=O)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)N[C@@H](CCC(N)=O)C(=O)NCC(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C(C)C)C(N)=O)[C@@H](C)O)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)C1=CC=CC=C1 OWMZNFCDEHGFEP-NFBCVYDUSA-N 0.000 claims description 2
- 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 claims description 2
- 229960002758 sermorelin Drugs 0.000 claims description 2
- 229960000216 tenecteplase Drugs 0.000 claims description 2
- 229960005460 teriparatide Drugs 0.000 claims description 2
- 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 claims description 2
- 229960000575 trastuzumab Drugs 0.000 claims description 2
- 229960005356 urokinase Drugs 0.000 claims description 2
- 101150010725 Dro gene Proteins 0.000 claims 1
- 102000051325 Glucagon Human genes 0.000 claims 1
- 239000007769 metal material Substances 0.000 claims 1
- 239000011800 void material Substances 0.000 claims 1
- 230000014759 maintenance of location Effects 0.000 abstract description 43
- 210000001508 eye Anatomy 0.000 description 246
- 108091006146 Channels Proteins 0.000 description 222
- 229940076783 lucentis Drugs 0.000 description 158
- 239000000203 mixture Substances 0.000 description 129
- 239000000243 solution Substances 0.000 description 68
- 239000011230 binding agent Substances 0.000 description 67
- 238000009472 formulation Methods 0.000 description 59
- 230000000875 corresponding effect Effects 0.000 description 57
- 108091003079 Bovine Serum Albumin Proteins 0.000 description 54
- 229940098773 bovine serum albumin Drugs 0.000 description 48
- 210000001525 retina Anatomy 0.000 description 48
- 238000012360 testing method Methods 0.000 description 48
- 230000001186 cumulative effect Effects 0.000 description 47
- 239000002609 medium Substances 0.000 description 47
- 239000012528 membrane Substances 0.000 description 47
- 238000000034 method Methods 0.000 description 45
- 229940120638 avastin Drugs 0.000 description 40
- 238000001802 infusion Methods 0.000 description 37
- 239000002953 phosphate buffered saline Substances 0.000 description 33
- 239000011148 porous material Substances 0.000 description 33
- 238000013268 sustained release Methods 0.000 description 32
- 239000012730 sustained-release form Substances 0.000 description 32
- 230000002401 inhibitory effect Effects 0.000 description 31
- 239000007788 liquid Substances 0.000 description 31
- 210000001519 tissue Anatomy 0.000 description 31
- 238000009792 diffusion process Methods 0.000 description 30
- 230000007774 longterm Effects 0.000 description 30
- 239000000725 suspension Substances 0.000 description 30
- 239000012530 fluid Substances 0.000 description 27
- 150000003384 small molecules Chemical class 0.000 description 27
- 239000010935 stainless steel Substances 0.000 description 26
- 229910001220 stainless steel Inorganic materials 0.000 description 26
- 102000004169 proteins and genes Human genes 0.000 description 25
- 108090000623 proteins and genes Proteins 0.000 description 25
- 238000012014 optical coherence tomography Methods 0.000 description 24
- 238000002474 experimental method Methods 0.000 description 23
- 230000007246 mechanism Effects 0.000 description 22
- 239000010936 titanium Substances 0.000 description 22
- 241000282414 Homo sapiens Species 0.000 description 21
- RTAQQCXQSZGOHL-UHFFFAOYSA-N Titanium Chemical compound [Ti] RTAQQCXQSZGOHL-UHFFFAOYSA-N 0.000 description 21
- 238000004364 calculation method Methods 0.000 description 21
- 238000012377 drug delivery Methods 0.000 description 21
- 238000005259 measurement Methods 0.000 description 21
- 229940126585 therapeutic drug Drugs 0.000 description 21
- 229910052719 titanium Inorganic materials 0.000 description 21
- 210000000695 crystalline len Anatomy 0.000 description 20
- 230000007423 decrease Effects 0.000 description 20
- 239000004480 active ingredient Substances 0.000 description 19
- 229920000642 polymer Polymers 0.000 description 19
- 238000010586 diagram Methods 0.000 description 18
- 239000007789 gas Substances 0.000 description 18
- 238000011049 filling Methods 0.000 description 17
- 238000003780 insertion Methods 0.000 description 17
- 230000037431 insertion Effects 0.000 description 17
- 239000000872 buffer Substances 0.000 description 16
- 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 16
- 230000000694 effects Effects 0.000 description 15
- 229960002143 fluorescein Drugs 0.000 description 15
- 229920002521 macromolecule Polymers 0.000 description 15
- 108010073929 Vascular Endothelial Growth Factor A Proteins 0.000 description 14
- 206010064930 age-related macular degeneration Diseases 0.000 description 14
- 150000001875 compounds Chemical class 0.000 description 14
- 238000004088 simulation Methods 0.000 description 14
- 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 14
- 239000000017 hydrogel Substances 0.000 description 13
- 239000003112 inhibitor Substances 0.000 description 13
- 230000002829 reductive effect Effects 0.000 description 13
- 229960002117 triamcinolone acetonide Drugs 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Chemical compound O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 108010021625 Immunoglobulin Fragments Proteins 0.000 description 12
- 102000008394 Immunoglobulin Fragments Human genes 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
- 210000004027 cell Anatomy 0.000 description 12
- 238000003860 storage Methods 0.000 description 12
- 239000000126 substance Substances 0.000 description 12
- 229920001296 polysiloxane Polymers 0.000 description 11
- 230000002207 retinal effect Effects 0.000 description 11
- 239000007787 solid Substances 0.000 description 11
- 238000002560 therapeutic procedure Methods 0.000 description 11
- 241000282693 Cercopithecidae Species 0.000 description 10
- 241000283973 Oryctolagus cuniculus Species 0.000 description 10
- 230000008859 change Effects 0.000 description 10
- 230000001886 ciliary effect Effects 0.000 description 10
- 208000015181 infectious disease Diseases 0.000 description 10
- 230000003902 lesion Effects 0.000 description 10
- 229920003023 plastic Polymers 0.000 description 10
- 239000004033 plastic Substances 0.000 description 10
- 239000004417 polycarbonate Substances 0.000 description 10
- 229920000515 polycarbonate Polymers 0.000 description 10
- 239000002525 vasculotropin inhibitor Substances 0.000 description 10
- 230000008901 benefit Effects 0.000 description 9
- 239000003246 corticosteroid Substances 0.000 description 9
- 230000004438 eyesight Effects 0.000 description 9
- 230000037361 pathway Effects 0.000 description 9
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 8
- 230000001580 bacterial effect Effects 0.000 description 8
- 230000015572 biosynthetic process Effects 0.000 description 8
- 210000001124 body fluid Anatomy 0.000 description 8
- 239000010839 body fluid Substances 0.000 description 8
- 238000005755 formation reaction Methods 0.000 description 8
- 230000006870 function Effects 0.000 description 8
- 239000007943 implant Substances 0.000 description 8
- 238000013508 migration Methods 0.000 description 8
- 230000005012 migration Effects 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
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 239000003242 anti bacterial agent Substances 0.000 description 7
- 239000004599 antimicrobial Substances 0.000 description 7
- 230000009286 beneficial effect Effects 0.000 description 7
- 210000004240 ciliary body Anatomy 0.000 description 7
- 239000002131 composite material Substances 0.000 description 7
- 238000011161 development Methods 0.000 description 7
- 201000010099 disease Diseases 0.000 description 7
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 7
- 238000001727 in vivo Methods 0.000 description 7
- 238000005342 ion exchange Methods 0.000 description 7
- 230000033001 locomotion Effects 0.000 description 7
- 238000001000 micrograph Methods 0.000 description 7
- 239000011236 particulate material Substances 0.000 description 7
- 230000004044 response Effects 0.000 description 7
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
- 208000005590 Choroidal Neovascularization Diseases 0.000 description 6
- 206010060823 Choroidal neovascularisation Diseases 0.000 description 6
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
- 206010038848 Retinal detachment Diseases 0.000 description 6
- 238000004458 analytical method Methods 0.000 description 6
- 210000004087 cornea Anatomy 0.000 description 6
- 239000013013 elastic material Substances 0.000 description 6
- 230000009368 gene silencing by RNA Effects 0.000 description 6
- 102000006495 integrins Human genes 0.000 description 6
- 108010044426 integrins Proteins 0.000 description 6
- 210000002540 macrophage Anatomy 0.000 description 6
- 230000003204 osmotic effect Effects 0.000 description 6
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 6
- 230000001681 protective effect Effects 0.000 description 6
- 238000011160 research Methods 0.000 description 6
- 239000011780 sodium chloride Substances 0.000 description 6
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- QWOJMRHUQHTCJG-UHFFFAOYSA-N CC([CH2-])=O Chemical compound CC([CH2-])=O QWOJMRHUQHTCJG-UHFFFAOYSA-N 0.000 description 5
- 206010061218 Inflammation Diseases 0.000 description 5
- 206010028980 Neoplasm Diseases 0.000 description 5
- PXHVJJICTQNCMI-UHFFFAOYSA-N Nickel Chemical compound [Ni] PXHVJJICTQNCMI-UHFFFAOYSA-N 0.000 description 5
- 239000004696 Poly ether ether ketone Substances 0.000 description 5
- 239000004743 Polypropylene Substances 0.000 description 5
- 229940022663 acetate Drugs 0.000 description 5
- 229910045601 alloy Inorganic materials 0.000 description 5
- 239000000956 alloy Substances 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 5
- 229940043075 fluocinolone Drugs 0.000 description 5
- 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 5
- 238000010438 heat treatment Methods 0.000 description 5
- 238000000338 in vitro Methods 0.000 description 5
- 238000010348 incorporation Methods 0.000 description 5
- 230000004054 inflammatory process Effects 0.000 description 5
- 239000002090 nanochannel Substances 0.000 description 5
- 230000000737 periodic effect Effects 0.000 description 5
- 229920002530 polyetherether ketone Polymers 0.000 description 5
- 229920001155 polypropylene Polymers 0.000 description 5
- 239000004810 polytetrafluoroethylene Substances 0.000 description 5
- 229920002981 polyvinylidene fluoride Polymers 0.000 description 5
- 239000000047 product Substances 0.000 description 5
- 150000003180 prostaglandins Chemical class 0.000 description 5
- 239000000758 substrate Substances 0.000 description 5
- 210000002435 tendon Anatomy 0.000 description 5
- 210000001585 trabecular meshwork Anatomy 0.000 description 5
- 229960005294 triamcinolone Drugs 0.000 description 5
- 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 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
- 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 4
- 208000002177 Cataract Diseases 0.000 description 4
- 108010035532 Collagen Proteins 0.000 description 4
- 102000008186 Collagen Human genes 0.000 description 4
- 102100022337 Integrin alpha-V Human genes 0.000 description 4
- 206010029113 Neovascularisation Diseases 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
- 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
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-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
- 108010048673 Vitronectin Receptors Proteins 0.000 description 4
- 239000011324 bead Substances 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
- 229920001436 collagen Polymers 0.000 description 4
- 238000013270 controlled release Methods 0.000 description 4
- 229960001334 corticosteroids Drugs 0.000 description 4
- 239000012153 distilled water Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 230000008020 evaporation Effects 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 4
- 238000007689 inspection Methods 0.000 description 4
- 229940043355 kinase inhibitor Drugs 0.000 description 4
- 208000002780 macular degeneration Diseases 0.000 description 4
- 239000002086 nanomaterial Substances 0.000 description 4
- 230000007935 neutral effect Effects 0.000 description 4
- 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 4
- 229910001000 nickel titanium Inorganic materials 0.000 description 4
- 239000013618 particulate matter Substances 0.000 description 4
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 4
- 229920003229 poly(methyl methacrylate) Polymers 0.000 description 4
- 239000004926 polymethyl methacrylate Substances 0.000 description 4
- 239000005373 porous glass Substances 0.000 description 4
- 239000000843 powder Substances 0.000 description 4
- 108090000765 processed proteins & peptides Proteins 0.000 description 4
- 210000001747 pupil Anatomy 0.000 description 4
- 238000003908 quality control method Methods 0.000 description 4
- 230000000717 retained effect Effects 0.000 description 4
- 230000004264 retinal detachment Effects 0.000 description 4
- 229960000371 rofecoxib Drugs 0.000 description 4
- 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 description 4
- 229940126586 small molecule drug Drugs 0.000 description 4
- 239000001488 sodium phosphate Substances 0.000 description 4
- 229910000162 sodium phosphate Inorganic materials 0.000 description 4
- 239000003381 stabilizer Substances 0.000 description 4
- RYFMWSXOAZQYPI-UHFFFAOYSA-K trisodium phosphate Chemical compound [Na+].[Na+].[Na+].[O-]P([O-])([O-])=O RYFMWSXOAZQYPI-UHFFFAOYSA-K 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
- 241000894006 Bacteria Species 0.000 description 3
- 102000000521 Immunophilins Human genes 0.000 description 3
- 108010016648 Immunophilins Proteins 0.000 description 3
- 239000002147 L01XE04 - Sunitinib Substances 0.000 description 3
- 239000005511 L01XE05 - Sorafenib Substances 0.000 description 3
- 239000004677 Nylon Substances 0.000 description 3
- 239000004698 Polyethylene Substances 0.000 description 3
- 239000004642 Polyimide 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
- BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 3
- 208000000208 Wet Macular Degeneration Diseases 0.000 description 3
- 239000000853 adhesive Substances 0.000 description 3
- 230000001070 adhesive effect Effects 0.000 description 3
- 210000003484 anatomy Anatomy 0.000 description 3
- 238000010171 animal model Methods 0.000 description 3
- 210000005252 bulbus oculi Anatomy 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 238000005341 cation exchange Methods 0.000 description 3
- 239000000544 cholinesterase inhibitor Substances 0.000 description 3
- 238000007906 compression Methods 0.000 description 3
- 230000006835 compression Effects 0.000 description 3
- 238000011109 contamination Methods 0.000 description 3
- 230000008878 coupling Effects 0.000 description 3
- 238000010168 coupling process Methods 0.000 description 3
- 238000005859 coupling reaction Methods 0.000 description 3
- 230000006378 damage Effects 0.000 description 3
- 238000006731 degradation reaction Methods 0.000 description 3
- 229960003957 dexamethasone Drugs 0.000 description 3
- 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 3
- KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 3
- 239000003862 glucocorticoid Substances 0.000 description 3
- 239000003102 growth factor Substances 0.000 description 3
- 230000002209 hydrophobic effect Effects 0.000 description 3
- 229910052588 hydroxylapatite Inorganic materials 0.000 description 3
- 229940027941 immunoglobulin g Drugs 0.000 description 3
- 150000002605 large molecules Chemical class 0.000 description 3
- 229940092110 macugen Drugs 0.000 description 3
- 238000012423 maintenance Methods 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 229920001778 nylon Polymers 0.000 description 3
- XYJRXVWERLGGKC-UHFFFAOYSA-D pentacalcium;hydroxide;triphosphate Chemical compound [OH-].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[Ca+2].[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O.[O-]P([O-])([O-])=O XYJRXVWERLGGKC-UHFFFAOYSA-D 0.000 description 3
- 239000000546 pharmaceutical excipient Substances 0.000 description 3
- 230000000649 photocoagulation Effects 0.000 description 3
- 229920000058 polyacrylate Polymers 0.000 description 3
- 229920000573 polyethylene Polymers 0.000 description 3
- 229920001721 polyimide Polymers 0.000 description 3
- 229920005597 polymer membrane Polymers 0.000 description 3
- 239000000256 polyoxyethylene sorbitan monolaurate Substances 0.000 description 3
- 235000010486 polyoxyethylene sorbitan monolaurate Nutrition 0.000 description 3
- 229940068977 polysorbate 20 Drugs 0.000 description 3
- 229920002635 polyurethane Polymers 0.000 description 3
- 239000004814 polyurethane Substances 0.000 description 3
- 239000012255 powdered metal Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 230000002265 prevention Effects 0.000 description 3
- 102000004196 processed proteins & peptides Human genes 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
- 108020003175 receptors Proteins 0.000 description 3
- 239000012781 shape memory material Substances 0.000 description 3
- 229910052709 silver Inorganic materials 0.000 description 3
- 239000004332 silver Substances 0.000 description 3
- 150000003431 steroids Chemical class 0.000 description 3
- 230000002459 sustained effect Effects 0.000 description 3
- 238000010998 test method Methods 0.000 description 3
- 239000012815 thermoplastic material Substances 0.000 description 3
- 238000012546 transfer Methods 0.000 description 3
- 230000032258 transport Effects 0.000 description 3
- 230000000007 visual effect Effects 0.000 description 3
- 238000009736 wetting Methods 0.000 description 3
- WMBWREPUVVBILR-WIYYLYMNSA-N (-)-Epigallocatechin-3-o-gallate Chemical compound O([C@@H]1CC2=C(O)C=C(C=C2O[C@@H]1C=1C=C(O)C(O)=C(O)C=1)O)C(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-WIYYLYMNSA-N 0.000 description 2
- 229930014124 (-)-epigallocatechin gallate Natural products 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
- FAWLNURBQMTKEB-URDPEVQOSA-N 213546-53-3 Chemical compound N([C@@H](C)C(=O)N[C@H](C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](C)C(=O)N1CCC[C@H]1C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CCCNC(N)=N)C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CCCCN)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N1[C@@H](CCC1)C(O)=O)C(C)C)C(C)C)C(=O)[C@@H]1CCCN1C(=O)[C@H](CC(C)C)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](C)NC(=O)[C@@H](NC(=O)[C@H](C)NC(=O)[C@H](C)N)C(C)C FAWLNURBQMTKEB-URDPEVQOSA-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
- 239000005541 ACE inhibitor Substances 0.000 description 2
- 229940100578 Acetylcholinesterase inhibitor Drugs 0.000 description 2
- NIXOWILDQLNWCW-UHFFFAOYSA-M Acrylate Chemical compound [O-]C(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-M 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
- 229910000684 Cobalt-chrome Inorganic materials 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
- 238000002965 ELISA Methods 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
- 108091011114 FK506 binding proteins Proteins 0.000 description 2
- WMBWREPUVVBILR-UHFFFAOYSA-N GCG Natural products C=1C(O)=C(O)C(O)=CC=1C1OC2=CC(O)=CC(O)=C2CC1OC(=O)C1=CC(O)=C(O)C(O)=C1 WMBWREPUVVBILR-UHFFFAOYSA-N 0.000 description 2
- 208000010412 Glaucoma Diseases 0.000 description 2
- 102000003745 Hepatocyte Growth Factor Human genes 0.000 description 2
- 108090000100 Hepatocyte Growth Factor Proteins 0.000 description 2
- 102100021866 Hepatocyte growth factor Human genes 0.000 description 2
- 241000282412 Homo Species 0.000 description 2
- 101000808011 Homo sapiens Vascular endothelial growth factor A Proteins 0.000 description 2
- 101000851007 Homo sapiens Vascular endothelial growth factor receptor 2 Proteins 0.000 description 2
- 108010054477 Immunoglobulin Fab Fragments Proteins 0.000 description 2
- 102000001706 Immunoglobulin Fab Fragments Human genes 0.000 description 2
- 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 2
- 101100481410 Mus musculus Tek gene Proteins 0.000 description 2
- KTDZCOWXCWUPEO-UHFFFAOYSA-N NS-398 Chemical compound CS(=O)(=O)NC1=CC=C([N+]([O-])=O)C=C1OC1CCCCC1 KTDZCOWXCWUPEO-UHFFFAOYSA-N 0.000 description 2
- 206010061876 Obstruction Diseases 0.000 description 2
- 208000022873 Ocular disease Diseases 0.000 description 2
- 239000002033 PVDF binder Substances 0.000 description 2
- 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 description 2
- 108091005804 Peptidases Proteins 0.000 description 2
- PIJVFDBKTWXHHD-UHFFFAOYSA-N Physostigmine Natural products C12=CC(OC(=O)NC)=CC=C2N(C)C2C1(C)CCN2C PIJVFDBKTWXHHD-UHFFFAOYSA-N 0.000 description 2
- 102100035846 Pigment epithelium-derived factor Human genes 0.000 description 2
- 239000004952 Polyamide Substances 0.000 description 2
- 239000004695 Polyether sulfone Substances 0.000 description 2
- 239000004793 Polystyrene Substances 0.000 description 2
- 102000004257 Potassium Channel Human genes 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
- 239000004365 Protease Substances 0.000 description 2
- 102100037486 Reverse transcriptase/ribonuclease H Human genes 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
- 229920006356 Teflon™ FEP Polymers 0.000 description 2
- 108091008605 VEGF receptors Proteins 0.000 description 2
- 102000009524 Vascular Endothelial Growth Factor A Human genes 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
- HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 2
- 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 2
- 238000002835 absorbance Methods 0.000 description 2
- 230000032900 absorption of visible light Effects 0.000 description 2
- 238000009825 accumulation Methods 0.000 description 2
- 239000008351 acetate buffer Substances 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
- 230000002378 acidificating effect Effects 0.000 description 2
- 229960002833 aflibercept Drugs 0.000 description 2
- 108010081667 aflibercept Proteins 0.000 description 2
- WYTGDNHDOZPMIW-RCBQFDQVSA-N alstonine Natural products C1=CC2=C3C=CC=CC3=NC2=C2N1C[C@H]1[C@H](C)OC=C(C(=O)OC)[C@H]1C2 WYTGDNHDOZPMIW-RCBQFDQVSA-N 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 230000033115 angiogenesis Effects 0.000 description 2
- 239000002870 angiogenesis inducing agent Substances 0.000 description 2
- 229940044094 angiotensin-converting-enzyme inhibitor Drugs 0.000 description 2
- 229940124599 anti-inflammatory drug Drugs 0.000 description 2
- 239000002246 antineoplastic agent Substances 0.000 description 2
- 239000000158 apoptosis inhibitor Substances 0.000 description 2
- 210000001742 aqueous humor Anatomy 0.000 description 2
- 238000000149 argon plasma sintering Methods 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
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
- 230000008952 bacterial invasion Effects 0.000 description 2
- 230000004071 biological effect Effects 0.000 description 2
- 230000000740 bleeding effect Effects 0.000 description 2
- 229960001467 bortezomib Drugs 0.000 description 2
- 230000003139 buffering effect Effects 0.000 description 2
- 210000001217 buttock Anatomy 0.000 description 2
- 201000011510 cancer Diseases 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
- 229960000830 captopril Drugs 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
- 229960000590 celecoxib Drugs 0.000 description 2
- 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 description 2
- 229920002301 cellulose acetate Polymers 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
- 239000003795 chemical substances by application Substances 0.000 description 2
- 238000004587 chromatography analysis Methods 0.000 description 2
- 239000012501 chromatography medium 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
- 239000011248 coating agent Substances 0.000 description 2
- 238000000576 coating method Methods 0.000 description 2
- 239000010952 cobalt-chrome Substances 0.000 description 2
- 229960001338 colchicine Drugs 0.000 description 2
- 230000000295 complement effect Effects 0.000 description 2
- 230000001276 controlling effect Effects 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 230000003247 decreasing effect Effects 0.000 description 2
- 238000013461 design Methods 0.000 description 2
- 229960003657 dexamethasone acetate Drugs 0.000 description 2
- 229960001259 diclofenac Drugs 0.000 description 2
- DCOPUUMXTXDBNB-UHFFFAOYSA-N diclofenac Chemical compound OC(=O)CC1=CC=CC=C1NC1=C(Cl)C=CC=C1Cl DCOPUUMXTXDBNB-UHFFFAOYSA-N 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
- 238000009826 distribution Methods 0.000 description 2
- 239000012990 dithiocarbamate Substances 0.000 description 2
- 239000013583 drug formulation Substances 0.000 description 2
- 230000009977 dual effect Effects 0.000 description 2
- 229920001971 elastomer Polymers 0.000 description 2
- 229910000701 elgiloys (Co-Cr-Ni Alloy) Inorganic materials 0.000 description 2
- 239000003995 emulsifying agent Substances 0.000 description 2
- 238000005530 etching Methods 0.000 description 2
- 238000013265 extended release Methods 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
- 239000000835 fiber Substances 0.000 description 2
- 239000006260 foam Substances 0.000 description 2
- 230000002496 gastric effect Effects 0.000 description 2
- 239000011491 glass wool 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
- 229910000856 hastalloy Inorganic materials 0.000 description 2
- 102000058223 human VEGFA Human genes 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
- 230000007062 hydrolysis Effects 0.000 description 2
- 238000006460 hydrolysis reaction Methods 0.000 description 2
- 229920001477 hydrophilic polymer Polymers 0.000 description 2
- 210000002865 immune cell Anatomy 0.000 description 2
- 238000011065 in-situ storage Methods 0.000 description 2
- 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 description 2
- 239000007972 injectable composition Substances 0.000 description 2
- 208000014674 injury Diseases 0.000 description 2
- 230000003993 interaction Effects 0.000 description 2
- 229960005280 isotretinoin Drugs 0.000 description 2
- 210000005067 joint tissue Anatomy 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
- 230000001404 mediated effect Effects 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- 230000000813 microbial effect Effects 0.000 description 2
- 244000005700 microbiome Species 0.000 description 2
- 239000011859 microparticle Substances 0.000 description 2
- 150000004682 monohydrates Chemical class 0.000 description 2
- 210000003205 muscle Anatomy 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 230000017128 negative regulation of NF-kappaB transcription factor activity Effects 0.000 description 2
- 208000015122 neurodegenerative disease Diseases 0.000 description 2
- 229910052759 nickel Inorganic materials 0.000 description 2
- 230000003287 optical effect Effects 0.000 description 2
- 210000000056 organ Anatomy 0.000 description 2
- 239000001301 oxygen Substances 0.000 description 2
- 229910052760 oxygen Inorganic materials 0.000 description 2
- 230000035515 penetration Effects 0.000 description 2
- 229960001476 pentoxifylline Drugs 0.000 description 2
- 238000005325 percolation Methods 0.000 description 2
- 230000035699 permeability Effects 0.000 description 2
- 238000002428 photodynamic therapy Methods 0.000 description 2
- 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 2
- 229960001697 physostigmine Drugs 0.000 description 2
- 108090000102 pigment epithelium-derived factor Proteins 0.000 description 2
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 2
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 description 2
- 229920002647 polyamide Polymers 0.000 description 2
- 229920006393 polyether sulfone Polymers 0.000 description 2
- 229920000139 polyethylene terephthalate Polymers 0.000 description 2
- 239000005020 polyethylene terephthalate Substances 0.000 description 2
- 229920001184 polypeptide Polymers 0.000 description 2
- 229920002223 polystyrene Polymers 0.000 description 2
- 229920002451 polyvinyl alcohol Polymers 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 108020001213 potassium channel Proteins 0.000 description 2
- 239000003755 preservative agent Substances 0.000 description 2
- 230000008569 process Effects 0.000 description 2
- 239000002599 prostaglandin synthase inhibitor Substances 0.000 description 2
- 235000019419 proteases Nutrition 0.000 description 2
- 150000003212 purines Chemical class 0.000 description 2
- 229940044551 receptor antagonist Drugs 0.000 description 2
- 239000002464 receptor antagonist Substances 0.000 description 2
- 239000004627 regenerated cellulose Substances 0.000 description 2
- 108091092562 ribozyme Proteins 0.000 description 2
- 229960004586 rosiglitazone Drugs 0.000 description 2
- 239000005060 rubber Substances 0.000 description 2
- 229960001860 salicylate Drugs 0.000 description 2
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 0.000 description 2
- 238000007789 sealing Methods 0.000 description 2
- 239000000377 silicon dioxide Substances 0.000 description 2
- 239000002002 slurry Substances 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
- 238000001179 sorption measurement Methods 0.000 description 2
- 229950001248 squalamine Drugs 0.000 description 2
- 210000002301 subretinal fluid Anatomy 0.000 description 2
- 235000000346 sugar Nutrition 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
- 230000001629 suppression Effects 0.000 description 2
- 238000001356 surgical procedure Methods 0.000 description 2
- 230000009885 systemic effect Effects 0.000 description 2
- 230000008685 targeting Effects 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- BYJAVTDNIXVSPW-UHFFFAOYSA-N tetryzoline Chemical compound N1CCN=C1C1C2=CC=CC=C2CCC1 BYJAVTDNIXVSPW-UHFFFAOYSA-N 0.000 description 2
- 238000011287 therapeutic dose Methods 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
- 229960001641 troglitazone Drugs 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
- 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
- 230000002792 vascular Effects 0.000 description 2
- 229940099039 velcade Drugs 0.000 description 2
- 238000012800 visualization Methods 0.000 description 2
- 229910052725 zinc Inorganic materials 0.000 description 2
- 239000011701 zinc Substances 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
- 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 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
- 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
- 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
- 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 1
- LDVVTQMJQSCDMK-UHFFFAOYSA-N 1,3-dihydroxypropan-2-yl formate Chemical compound OCC(CO)OC=O LDVVTQMJQSCDMK-UHFFFAOYSA-N 0.000 description 1
- OGYGFUAIIOPWQD-UHFFFAOYSA-N 1,3-thiazolidine Chemical compound C1CSCN1 OGYGFUAIIOPWQD-UHFFFAOYSA-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
- ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 2,3-dimethylbutane Chemical group CC(C)C(C)C ZFFMLCVRJBZUDZ-UHFFFAOYSA-N 0.000 description 1
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-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
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- HRPVXLWXLXDGHG-UHFFFAOYSA-N Acrylamide Chemical compound NC(=O)C=C HRPVXLWXLXDGHG-UHFFFAOYSA-N 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
- 208000023275 Autoimmune disease Diseases 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 208000023328 Basedow disease Diseases 0.000 description 1
- 201000004569 Blindness Diseases 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
- 208000016057 CHAND syndrome Diseases 0.000 description 1
- 108060001064 Calcitonin Proteins 0.000 description 1
- 102400000113 Calcitonin Human genes 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
- 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 description 1
- 239000004099 Chlortetracycline Substances 0.000 description 1
- 208000002691 Choroiditis Diseases 0.000 description 1
- 206010010099 Combined immunodeficiency Diseases 0.000 description 1
- 229940110338 Complement factor inhibitor Drugs 0.000 description 1
- 108010047041 Complementarity Determining Regions 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
- 206010011732 Cyst Diseases 0.000 description 1
- 201000003883 Cystic fibrosis Diseases 0.000 description 1
- 101100481404 Danio rerio tie1 gene 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
- 208000036829 Device dislocation Diseases 0.000 description 1
- 229920002307 Dextran Polymers 0.000 description 1
- 206010012689 Diabetic retinopathy Diseases 0.000 description 1
- 241000551547 Dione <red algae> Species 0.000 description 1
- 208000030453 Drug-Related Side Effects and Adverse reaction Diseases 0.000 description 1
- 102400001368 Epidermal growth factor Human genes 0.000 description 1
- 101800003838 Epidermal growth factor Proteins 0.000 description 1
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 description 1
- 206010015967 Eye swelling Diseases 0.000 description 1
- 229910001200 Ferrotitanium Inorganic materials 0.000 description 1
- 102000018233 Fibroblast Growth Factor Human genes 0.000 description 1
- 108050007372 Fibroblast Growth Factor Proteins 0.000 description 1
- 108010067306 Fibronectins Proteins 0.000 description 1
- 102000016359 Fibronectins Human genes 0.000 description 1
- GHASVSINZRGABV-UHFFFAOYSA-N Fluorouracil Chemical compound FC1=CNC(=O)NC1=O GHASVSINZRGABV-UHFFFAOYSA-N 0.000 description 1
- 206010017993 Gastrointestinal neoplasms Diseases 0.000 description 1
- 108010010803 Gelatin Proteins 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
- 229930182566 Gentamicin Natural products 0.000 description 1
- 102400000321 Glucagon Human genes 0.000 description 1
- WQZGKKKJIJFFOK-GASJEMHNSA-N Glucose Natural products OC[C@H]1OC(O)[C@H](O)[C@@H](O)[C@@H]1O WQZGKKKJIJFFOK-GASJEMHNSA-N 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- 208000015023 Graves' disease Diseases 0.000 description 1
- 208000031886 HIV Infections Diseases 0.000 description 1
- 208000037357 HIV infectious disease Diseases 0.000 description 1
- 208000031220 Hemophilia Diseases 0.000 description 1
- 208000009292 Hemophilia A Diseases 0.000 description 1
- 208000032843 Hemorrhage Diseases 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
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 206010020880 Hypertrophy Diseases 0.000 description 1
- HEFNNWSXXWATRW-UHFFFAOYSA-N Ibuprofen Chemical compound CC(C)CC1=CC=C(C(C)C(O)=O)C=C1 HEFNNWSXXWATRW-UHFFFAOYSA-N 0.000 description 1
- 208000026350 Inborn Genetic disease Diseases 0.000 description 1
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 1
- 108010005714 Interferon beta-1b Proteins 0.000 description 1
- 108010074328 Interferon-gamma Proteins 0.000 description 1
- 102000008070 Interferon-gamma Human genes 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
- 239000002136 L01XE07 - Lapatinib 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
- 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 1
- 235000010643 Leucaena leucocephala Nutrition 0.000 description 1
- 240000007472 Leucaena leucocephala Species 0.000 description 1
- 241000282567 Macaca fascicularis Species 0.000 description 1
- 206010025421 Macule Diseases 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- VVQNEPGJFQJSBK-UHFFFAOYSA-N Methyl methacrylate Chemical compound COC(=O)C(C)=C VVQNEPGJFQJSBK-UHFFFAOYSA-N 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
- 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
- WHNWPMSKXPGLAX-UHFFFAOYSA-N N-Vinyl-2-pyrrolidone Chemical compound C=CN1CCCC1=O WHNWPMSKXPGLAX-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 239000004100 Oxytetracycline Substances 0.000 description 1
- 208000002193 Pain Diseases 0.000 description 1
- 108090000445 Parathyroid hormone Proteins 0.000 description 1
- 102000003982 Parathyroid hormone Human genes 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- 229940083963 Peptide antagonist Drugs 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
- 229920002845 Poly(methacrylic acid) Polymers 0.000 description 1
- 239000004962 Polyamide-imide Substances 0.000 description 1
- 108010040201 Polymyxins Proteins 0.000 description 1
- 206010067268 Post procedural infection Diseases 0.000 description 1
- 208000003971 Posterior uveitis Diseases 0.000 description 1
- LRJOMUJRLNCICJ-JZYPGELDSA-N Prednisolone acetate Chemical compound C1CC2=CC(=O)C=C[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 LRJOMUJRLNCICJ-JZYPGELDSA-N 0.000 description 1
- 208000037111 Retinal Hemorrhage Diseases 0.000 description 1
- 206010038910 Retinitis Diseases 0.000 description 1
- 201000000582 Retinoblastoma Diseases 0.000 description 1
- 206010038934 Retinopathy proliferative 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
- 102100038803 Somatotropin Human genes 0.000 description 1
- 229920002472 Starch Polymers 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
- 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
- 239000004098 Tetracycline Substances 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
- 206010046851 Uveitis Diseases 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
- 238000002679 ablation Methods 0.000 description 1
- 230000002159 abnormal effect Effects 0.000 description 1
- 229960000571 acetazolamide Drugs 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
- 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
- 238000001994 activation Methods 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 201000009628 adenosine deaminase deficiency Diseases 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 229960001686 afatinib Drugs 0.000 description 1
- ULXXDDBFHOBEHA-CWDCEQMOSA-N afatinib Chemical compound N1=CN=C2C=C(O[C@@H]3COCC3)C(NC(=O)/C=C/CN(C)C)=CC2=C1NC1=CC=C(F)C(Cl)=C1 ULXXDDBFHOBEHA-CWDCEQMOSA-N 0.000 description 1
- 238000013019 agitation Methods 0.000 description 1
- 229940003677 alphagan 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
- 208000007502 anemia Diseases 0.000 description 1
- 238000005349 anion exchange Methods 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
- 239000002260 anti-inflammatory agent Substances 0.000 description 1
- 230000003431 anti-prostaglandin Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- 229940055075 anticholinesterase parasympathomimetics Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000003429 antifungal agent Substances 0.000 description 1
- 229940006133 antiglaucoma drug and miotics carbonic anhydrase inhibitors Drugs 0.000 description 1
- 229940034982 antineoplastic agent Drugs 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 239000003443 antiviral agent Substances 0.000 description 1
- 239000012736 aqueous medium Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 229960002028 atropine sulfate Drugs 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
- 238000005452 bending Methods 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
- 229960004347 betaxolol hydrochloride Drugs 0.000 description 1
- 229960002470 bimatoprost Drugs 0.000 description 1
- AQOKCDNYWBIDND-FTOWTWDKSA-N bimatoprost Chemical compound CCNC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1\C=C\[C@@H](O)CCC1=CC=CC=C1 AQOKCDNYWBIDND-FTOWTWDKSA-N 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- 230000003115 biocidal effect Effects 0.000 description 1
- 229920000249 biocompatible polymer Polymers 0.000 description 1
- 229920002988 biodegradable polymer Polymers 0.000 description 1
- 239000004621 biodegradable polymer Substances 0.000 description 1
- 208000034158 bleeding Diseases 0.000 description 1
- 230000036770 blood supply Effects 0.000 description 1
- 230000036760 body temperature Effects 0.000 description 1
- 229960003679 brimonidine Drugs 0.000 description 1
- 229960000722 brinzolamide Drugs 0.000 description 1
- 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 1
- 239000006172 buffering agent Substances 0.000 description 1
- 235000014121 butter Nutrition 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229960004015 calcitonin 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
- 239000003489 carbonate dehydratase inhibitor Substances 0.000 description 1
- 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 description 1
- 229960005243 carmustine Drugs 0.000 description 1
- 210000002421 cell wall Anatomy 0.000 description 1
- 230000001413 cellular effect Effects 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
- 210000004720 cerebrum Anatomy 0.000 description 1
- 229960001803 cetirizine Drugs 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
- 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
- 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
- 239000000515 collagen sponge Substances 0.000 description 1
- 239000004074 complement inhibitor Substances 0.000 description 1
- 230000001143 conditioned effect Effects 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
- 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
- 208000031513 cyst Diseases 0.000 description 1
- 238000013016 damping Methods 0.000 description 1
- 229960002448 dasatinib Drugs 0.000 description 1
- 238000013480 data collection Methods 0.000 description 1
- 239000000850 decongestant Substances 0.000 description 1
- 229940124581 decongestants Drugs 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 238000007872 degassing Methods 0.000 description 1
- 230000003111 delayed effect Effects 0.000 description 1
- 230000001419 dependent effect Effects 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
- 229910001873 dinitrogen Inorganic materials 0.000 description 1
- 238000002845 discoloration Methods 0.000 description 1
- VLARUOGDXDTHEH-UHFFFAOYSA-L disodium cromoglycate Chemical compound [Na+].[Na+].O1C(C([O-])=O)=CC(=O)C2=C1C=CC=C2OCC(O)COC1=CC=CC2=C1C(=O)C=C(C([O-])=O)O2 VLARUOGDXDTHEH-UHFFFAOYSA-L 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
- 239000006185 dispersion Substances 0.000 description 1
- 238000010494 dissociation reaction Methods 0.000 description 1
- 230000005593 dissociations Effects 0.000 description 1
- 208000002173 dizziness Diseases 0.000 description 1
- 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 1
- 229960003933 dorzolamide Drugs 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 238000007923 drug release testing Methods 0.000 description 1
- 238000002651 drug therapy Methods 0.000 description 1
- 208000011325 dry age related macular degeneration Diseases 0.000 description 1
- 230000004064 dysfunction Effects 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
- 239000007772 electrode material Substances 0.000 description 1
- 230000004406 elevated intraocular pressure Effects 0.000 description 1
- 230000008030 elimination Effects 0.000 description 1
- 238000003379 elimination reaction Methods 0.000 description 1
- 206010014801 endophthalmitis Diseases 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
- 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
- 230000003628 erosive effect Effects 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
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229950002420 eucatropine Drugs 0.000 description 1
- 229960005167 everolimus Drugs 0.000 description 1
- 230000007717 exclusion Effects 0.000 description 1
- 208000030533 eye disease Diseases 0.000 description 1
- 230000004424 eye movement Effects 0.000 description 1
- 210000000744 eyelid Anatomy 0.000 description 1
- 229950003662 fenretinide Drugs 0.000 description 1
- 229940126864 fibroblast growth factor Drugs 0.000 description 1
- 239000000945 filler Substances 0.000 description 1
- 238000005429 filling process Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229940020947 fluorescein sodium Drugs 0.000 description 1
- 229960001048 fluorometholone Drugs 0.000 description 1
- FAOZLTXFLGPHNG-KNAQIMQKSA-N fluorometholone Chemical compound C([C@@]12C)=CC(=O)C=C1[C@@H](C)C[C@@H]1[C@]2(F)[C@@H](O)C[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FAOZLTXFLGPHNG-KNAQIMQKSA-N 0.000 description 1
- 229960002949 fluorouracil Drugs 0.000 description 1
- 229960002390 flurbiprofen Drugs 0.000 description 1
- SYTBZMRGLBWNTM-UHFFFAOYSA-N flurbiprofen Chemical compound FC1=CC(C(C(O)=O)C)=CC=C1C1=CC=CC=C1 SYTBZMRGLBWNTM-UHFFFAOYSA-N 0.000 description 1
- 239000012537 formulation buffer Substances 0.000 description 1
- 239000012634 fragment Substances 0.000 description 1
- 125000002446 fucosyl group Chemical group C1([C@@H](O)[C@H](O)[C@H](O)[C@@H](O1)C)* 0.000 description 1
- 229960000936 fumagillin Drugs 0.000 description 1
- 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 1
- 230000002538 fungal effect Effects 0.000 description 1
- 229940044627 gamma-interferon Drugs 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
- 210000001035 gastrointestinal tract Anatomy 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
- 208000016361 genetic disease Diseases 0.000 description 1
- 229960002518 gentamicin Drugs 0.000 description 1
- 102000034238 globular proteins Human genes 0.000 description 1
- 108091005896 globular proteins Proteins 0.000 description 1
- 239000008103 glucose Substances 0.000 description 1
- 239000003292 glue Substances 0.000 description 1
- 150000002334 glycols Chemical class 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
- 230000005484 gravity Effects 0.000 description 1
- 208000037824 growth disorder Diseases 0.000 description 1
- 210000003128 head Anatomy 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
- 229960000857 homatropine Drugs 0.000 description 1
- 229940125697 hormonal agent Drugs 0.000 description 1
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 229960001067 hydrocortisone acetate Drugs 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
- 229950005360 hydroxyamfetamine Drugs 0.000 description 1
- 230000002267 hypothalamic effect Effects 0.000 description 1
- 229960001680 ibuprofen Drugs 0.000 description 1
- 238000003384 imaging method Methods 0.000 description 1
- NBZBKCUXIYYUSX-UHFFFAOYSA-N iminodiacetic acid Chemical compound OC(=O)CNCC(O)=O NBZBKCUXIYYUSX-UHFFFAOYSA-N 0.000 description 1
- 210000000987 immune system Anatomy 0.000 description 1
- 239000000677 immunologic agent Substances 0.000 description 1
- 229940124541 immunological agent Drugs 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
- 230000006872 improvement Effects 0.000 description 1
- 229960000905 indomethacin Drugs 0.000 description 1
- 238000012966 insertion method Methods 0.000 description 1
- 230000010354 integration Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 238000007912 intraperitoneal administration Methods 0.000 description 1
- 238000001990 intravenous administration Methods 0.000 description 1
- 238000010253 intravenous injection Methods 0.000 description 1
- 230000009545 invasion Effects 0.000 description 1
- 238000004255 ion exchange chromatography 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
- 210000003734 kidney Anatomy 0.000 description 1
- 229960004891 lapatinib Drugs 0.000 description 1
- 229960001160 latanoprost Drugs 0.000 description 1
- GGXICVAJURFBLW-CEYXHVGTSA-N latanoprost Chemical compound CC(C)OC(=O)CCC\C=C/C[C@H]1[C@@H](O)C[C@@H](O)[C@@H]1CC[C@@H](O)CCC1=CC=CC=C1 GGXICVAJURFBLW-CEYXHVGTSA-N 0.000 description 1
- 208000032839 leukemia Diseases 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
- 238000003754 machining Methods 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000011159 matrix material Substances 0.000 description 1
- 229940127554 medical product Drugs 0.000 description 1
- 238000002483 medication Methods 0.000 description 1
- YECBIJXISLIIDS-UHFFFAOYSA-N mepyramine Chemical compound C1=CC(OC)=CC=C1CN(CCN(C)C)C1=CC=CC=N1 YECBIJXISLIIDS-UHFFFAOYSA-N 0.000 description 1
- 229960000582 mepyramine Drugs 0.000 description 1
- 229910052753 mercury Inorganic materials 0.000 description 1
- 150000002739 metals Chemical class 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
- 239000004005 microsphere Substances 0.000 description 1
- 230000003547 miosis Effects 0.000 description 1
- 239000003604 miotic agent Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- MEFBJEMVZONFCJ-UHFFFAOYSA-N molybdate Chemical compound [O-][Mo]([O-])(=O)=O MEFBJEMVZONFCJ-UHFFFAOYSA-N 0.000 description 1
- 229940045641 monobasic sodium phosphate Drugs 0.000 description 1
- 238000000465 moulding Methods 0.000 description 1
- 201000006417 multiple sclerosis Diseases 0.000 description 1
- 239000002637 mydriatic agent Substances 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
- KUDPGZONDFORKU-UHFFFAOYSA-N n-chloroaniline Chemical compound ClNC1=CC=CC=C1 KUDPGZONDFORKU-UHFFFAOYSA-N 0.000 description 1
- 229960005016 naphazoline Drugs 0.000 description 1
- 229920001206 natural gum Polymers 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 229960001002 nepafenac Drugs 0.000 description 1
- QEFAQIPZVLVERP-UHFFFAOYSA-N nepafenac Chemical compound NC(=O)CC1=CC=CC(C(=O)C=2C=CC=CC=2)=C1N QEFAQIPZVLVERP-UHFFFAOYSA-N 0.000 description 1
- 210000005036 nerve Anatomy 0.000 description 1
- 239000004090 neuroprotective agent Substances 0.000 description 1
- 229940080607 nexavar 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
- 229960001346 nilotinib Drugs 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
- 229940021182 non-steroidal anti-inflammatory drug Drugs 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 235000019198 oils Nutrition 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
- 229960001972 panitumumab Drugs 0.000 description 1
- 229960001319 parathyroid hormone Drugs 0.000 description 1
- 239000000199 parathyroid hormone Substances 0.000 description 1
- 230000036961 partial effect Effects 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
- 229960003407 pegaptanib Drugs 0.000 description 1
- 230000002093 peripheral effect Effects 0.000 description 1
- 239000000825 pharmaceutical preparation Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 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
- 239000008363 phosphate buffer Substances 0.000 description 1
- 229940100008 phospholine iodide Drugs 0.000 description 1
- 238000001259 photo etching Methods 0.000 description 1
- 239000003504 photosensitizing agent Substances 0.000 description 1
- 230000000704 physical effect Effects 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
- 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 description 1
- 229960002702 piroxicam Drugs 0.000 description 1
- 229910052697 platinum Inorganic materials 0.000 description 1
- 229920002492 poly(sulfone) Polymers 0.000 description 1
- 229920000070 poly-3-hydroxybutyrate Polymers 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 229920002312 polyamide-imide Polymers 0.000 description 1
- 229920001610 polycaprolactone Polymers 0.000 description 1
- 239000004632 polycaprolactone Substances 0.000 description 1
- 229920000728 polyester Polymers 0.000 description 1
- 229920006254 polymer film Polymers 0.000 description 1
- 229920000193 polymethacrylate Polymers 0.000 description 1
- 239000000244 polyoxyethylene sorbitan monooleate Substances 0.000 description 1
- 235000010482 polyoxyethylene sorbitan monooleate Nutrition 0.000 description 1
- 229940068968 polysorbate 80 Drugs 0.000 description 1
- 229920000053 polysorbate 80 Polymers 0.000 description 1
- 230000008092 positive effect Effects 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 229960005205 prednisolone Drugs 0.000 description 1
- 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 1
- 229960002800 prednisolone acetate Drugs 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
- 230000002335 preservative effect Effects 0.000 description 1
- 238000003825 pressing Methods 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
- 201000007914 proliferative diabetic retinopathy Diseases 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000002510 pyrogen Substances 0.000 description 1
- 230000005855 radiation Effects 0.000 description 1
- 230000008707 rearrangement Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 238000012552 review Methods 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
- 150000003839 salts Chemical class 0.000 description 1
- 238000001878 scanning electron micrograph Methods 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
- 230000028327 secretion Effects 0.000 description 1
- 230000036303 septic shock Effects 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
- 235000012239 silicon dioxide Nutrition 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
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 239000002195 soluble material Substances 0.000 description 1
- 238000001228 spectrum Methods 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
- 230000001954 sterilising effect Effects 0.000 description 1
- 238000004659 sterilization and disinfection Methods 0.000 description 1
- 230000003637 steroidlike Effects 0.000 description 1
- 238000007920 subcutaneous administration Methods 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
- FIAFUQMPZJWCLV-UHFFFAOYSA-N suramin Chemical class OS(=O)(=O)C1=CC(S(O)(=O)=O)=C2C(NC(=O)C3=CC=C(C(=C3)NC(=O)C=3C=C(NC(=O)NC=4C=C(C=CC=4)C(=O)NC=4C(=CC=C(C=4)C(=O)NC=4C5=C(C=C(C=C5C(=CC=4)S(O)(=O)=O)S(O)(=O)=O)S(O)(=O)=O)C)C=CC=3)C)=CC=C(S(O)(=O)=O)C2=C1 FIAFUQMPZJWCLV-UHFFFAOYSA-N 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 229940034785 sutent Drugs 0.000 description 1
- 230000002889 sympathetic effect Effects 0.000 description 1
- 208000024891 symptom Diseases 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
- 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
- CXVCSRUYMINUSF-UHFFFAOYSA-N tetrathiomolybdate(2-) Chemical compound [S-][Mo]([S-])(=S)=S CXVCSRUYMINUSF-UHFFFAOYSA-N 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
- 238000007725 thermal activation Methods 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 239000004416 thermosoftening plastic Substances 0.000 description 1
- 229960004605 timolol Drugs 0.000 description 1
- 229960005221 timolol maleate 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
- 229940113006 travatan Drugs 0.000 description 1
- 229960002368 travoprost 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
- 230000001228 trophic effect Effects 0.000 description 1
- 229960004791 tropicamide 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
- 150000003668 tyrosines Chemical class 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
- 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
- 208000019553 vascular disease Diseases 0.000 description 1
- 238000013022 venting Methods 0.000 description 1
- 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 1
- 230000004304 visual acuity Effects 0.000 description 1
- 230000004393 visual impairment Effects 0.000 description 1
- 238000011179 visual inspection Methods 0.000 description 1
- 229940061392 visudyne Drugs 0.000 description 1
- 230000003442 weekly effect Effects 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- 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
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/57—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone
- A61K31/573—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids substituted in position 17 beta by a chain of two carbon atoms, e.g. pregnane or progesterone substituted in position 21, e.g. cortisone, dexamethasone, prednisone or aldosterone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/56—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids
- A61K31/58—Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids containing heterocyclic rings, e.g. danazol, stanozolol, pancuronium or digitogenin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/38—Albumins
- A61K38/385—Serum albumin
-
- 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
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
- A61K47/38—Cellulose; Derivatives thereof
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/22—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against growth factors ; against growth regulators
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N33/00—Investigating or analysing materials by specific methods not covered by groups G01N1/00 - G01N31/00
- G01N33/48—Biological material, e.g. blood, urine; Haemocytometers
- G01N33/50—Chemical analysis of biological material, e.g. blood, urine; Testing involving biospecific ligand binding methods; Immunological testing
- G01N33/53—Immunoassay; Biospecific binding assay; Materials therefor
- G01N33/558—Immunoassay; Biospecific binding assay; Materials therefor using diffusion or migration of antigen or antibody
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T29/00—Metal working
- Y10T29/49—Method of mechanical manufacture
- Y10T29/49826—Assembling or joining
Abstract
【解決手段】 治療装置は、送達装置の管腔から送達可能であるように、保持構造部及び貯蔵部を有していてもよい。治療装置は、これが患者内に埋め込まれたときに治療装置内へ治療薬を注入するポート部を有していてもよい。
【選択図】図7B−2
Description
また、公知の半透膜の少なくとも幾つかは時間とともに変化し得る高分子の透過性を有し、更には公知の半透膜の少なくとも幾つかは幾分脆弱であり得るため、長期間の薬物放出が少なくとも幾つかの例では理想を下回る場合があることも本発明の実施形態に係る研究は示唆している。毛細管が薬物放出用として提案されてきているが、本発明の実施形態に係る研究は、例えば場合によって気泡形成や部分的な目詰まりにより、毛細管を通る流れが少なくとも幾つかの例では理想を下回り得ることも示唆している。
たとえば、市販治療薬の容積は治療期間、例えば1カ月を有するボーラス注入に対応し得、組成容量を受容するように調整された貯蔵部の容積及び放出速度は、少なくとも約2の倍数で、注入容積の治療持続期間を例えば1か月から2カ月以上まで延ばすことができる。
注入ポート部は、結膜下に配置されるようにされた滑らかな上面を有していてもよい。
容器は貫通可能な障壁を有していてもよく、貫通可能な障壁及び保持構造部の各々は、これらが眼内に位置決めされるときに周囲の組織のびらんを最小にするよう構成されている。保持構造部は、装置が補充間に眼内へ移動することを抑制又は防止できる。保持構造部は、容器から外側に延びていてもよく、かつ、標準的な縫合糸によって強膜に取り付けるための少なくとも1つの縫合穴を有していてもよい。
治療するための網膜の標的位置が同定される。治療薬の治療量を有する容器が位置決めされる。容器は長期間に少なくとも1つの治療薬の治療量を放出する多孔質構造体を有する。硝子体液の対流により標的位置に治療薬を送達するように、多孔質構造体は網膜から離れた位置の硝子体液中に位置決めされる。
保持構造部が、長期間に患者の眼の強膜に連結するように容器に取り付けられている。
保持構造部が、長期間に患者の眼の強膜に連結するように容器に取り付けられている。
容器は、貯蔵部に連結された障壁であって、貯蔵部内に治療薬を収容するように貯蔵部の少なくとも一部に沿って配置された障壁を有する。多孔質構造体が、貯蔵部に連結された第1の側と、硝子体液に連結するための第2の側とを有する。多孔質構造体は、第1の側と第2の側との間を延びる厚みと、第1の側の領域及び第2の側の領域に対応する断面寸法とを有する。多孔質構造体の断面寸法は、長期間に治療薬を放出する容器の断面寸法の少なくとも約10パーセントを有する。保持構造部が、長期間に患者の眼の強膜に連結するように容器に取り付けられている。
れている。
治療装置が、患者の眼の硝子体液中へ少なくとも1つの治療薬を放出するように供給される。治療装置は、容器と容器に取り付けられた保持構造部とを有する。保持構造部は、第1の方向に延びる第1の長い距離幅と第2の方向に延びる第2の短い距離幅とを有する狭部を有する。第1の長い距離幅は第2の短い距離幅よりも広い。細長い切開部が強膜内に形成され、切開部は眼の扁平部に沿って延びる長さと幅とを有し、長さは幅よりも大きい。治療薬を放出するように眼内に容器が位置決めされる。第1の長い距離幅の部分が実質的に細長い切開部に沿って延びるように、かつ第2の短い距離幅の部分が実質的に切開部の幅の部分を横切って延びるように保持構造部の狭部が細長い切開部と並べられる。
治療装置内へ組成の容積を注入することで眼を治療するよう治療装置が供給され、装置は、治療薬の容積を収容するチャンバーを有する容器と、チャンバーから硝子体液に治療薬を放出するメカニズムとを有する。容器の容積及び放出メカニズムは、組成の容積の各注入にて範囲内の治療薬の治療濃度を用いて眼を長期間治療するように調整され、長期間は期間の少なくとも約2倍を成す。
治療装置。
長期間は少なくとも90日以上、例えば少なくとも180日、又は少なくとも1年、少なくとも2年若しくは少なくとも3年以上を有していてもよい。硝子体内のルセンティス(商標)などの治療薬の治療濃度の目標閾値は、少なくとも0.1μg/mLの治療濃度を有していてもよい。たとえば、目標閾値濃度は、長期間に約0.1μg/mLから約5μg/mLの濃度を有していてもよく、その上限値は刊行されたデータを用いた実施例9に示す計算に基づいている。目標閾値濃度は薬物に依存するため、他の治療薬では変化可能である。
注入器187の注射器188に連結された注射針189は、容器110Cから治療薬110を引き込むために用いることができる。容器110Cは、隔膜を有するボトル、単回送達分の容器、又は組成を混合するに適した容器などの市販容器を有していてもよい。治療薬110の容量110Vが、眼内に位置決めされた治療装置100内へ注入するための注入器187内へ引き込むことができる。容量110Vは、所定の量、例えば治療装置110の容器の容積や硝子体液中への意図された注入量に基づいた容量を有していてもよい。
容量110Vの実施例は、治療装置を介して硝子体液中へ容量110Vの第1部分を注入するように、かつ治療装置110の容器内の容量110Vの第2部分を含むように容器の容積を超えていてもよい。容器110Cは治療薬110の組成110Fを有していてもよい。組成110Fは治療薬の市販組成、例えば表1Aを参照して本明細書で述べるような治療薬を有していてもよい。本明細書で述べる実施形態に係り使用するに適合可能な市販組成の非限定的な実施例は、例えばルセンティス(商標)及びトリアムシノロンを含む。
組成110Fは市販治療薬、例えばアバスチン(商標)の濃縮又は希釈組成であってもよい。硝子体液のオスモル濃度及び緊張性は約290から約320の範囲内にすることができる。たとえば、硝子体液のオスモル濃度及び緊張性と実質的に類似するオスモル濃度及び緊張性、例えば約280から約340、例えば約300mOsmの組成を有するように、アバスチン(商標)の市販組成を希釈できる。治療薬110は硝子体液と実質的に類似するオスモル濃度及び緊張性を有することができる一方で、治療薬110は、硝子体液に対して高い浸透圧の溶液又は硝子体液に対して低い浸透圧の溶液を有することができる。
長期間に治療薬を放出するための治療薬の組成及びオスモル濃度を実験して求めるように、当業者は本明細書で述べる教示に基づき実験を実施できる。
(a)免疫グロブリンG 150キロダルトン 10.5nm(b)ウシ血清アルブミン 69キロダルトン 7.2nm(c)免疫グロブリンGのFab片 49キロダルトン 流体力学的直径について報告なし
多孔質構造体は、厚さ105Tを備えていてもよい。多孔質構造体は、直径150Dを備えていてもよい。
放出速度 = (D P / F)A(cR − cV)/L
但し、
cR = 貯蔵部内の濃度
cV = 貯蔵部外、すなわち硝子体内の濃度
D = 貯蔵部溶液における治療薬の拡散係数
P = 多孔質構造体の多孔率
F = 多孔質構造体のチャネルのねじれパラメータに対応し得るチャネル・パラメータ
A = 多孔質構造体の面積
L = 多孔質構造体の厚さ(長さ)
蓄積放出 = 1−cR/cR0=1−exp((−D PA/FL VR)t)
但し、
t = 時間、
Vr = 貯蔵部容積
DTA,37℃ = DBSA,20C = (η20C/η37℃)(MWBSA/MWTA)1/3
但し、MWは、BSAまたはテスト化合物の分子量を指し、ηは水の粘性である。以下は、関心タンパク質の拡散係数を表にしたものである。
cR = cR0 exp ((−D PA/FL VR)t)
および
累積放出 = 1−cR/cRO
この状況では、装置からの放出速度(上記の方程式によって説明されている)を眼からの排出速度とする質量バランスk cV VVから、モデルを導くことができる。再配列によって、硝子体の濃度に対して以下の方程式を得る。すなわち、
cV =装置からの放出速度/k VV.
非線形部材は、貯蔵部622を備えるために、治療薬で充填される管腔621を含んでいてもよい。多孔質構造体623は、非線形部材の遠位端624に配置され、治療薬を放出することが可能である。多孔質構造体は、非線形部材のさらなる位置または代替の位置に設置されてもよい。たとえば、キャップが強膜に対して配置される場合に硝子体液に治療薬を放出するように、複数の多孔質構造体が、非線形部材に沿って、キャップと遠位端との間に配置される位置に配置されてもよい。
浸透性障壁は、浸透性障壁がアクセスポート180に挿入可能なようにサイズ設定された弾性体を含んでいてもよい。浸透性障壁は、たとえば、シロキサンまたはゴムなど1つ以上の弾性体を含んでいてもよい。浸透性障壁は、浸透性障壁をアクセスポートに保持するタブ184Tを含んでいてもよい。浸透性障壁184は、アクセスポート180を封止するようサイズ設定された、面取りされた上側リム184Rを含んでいてもよい。貯蔵部容器130のアクセスポート180は、タブ184Tがアクセスポートの環状または細長い内側チャネルを係合する場合に、面取りされたリムを係合し、浸透性障壁をアクセスポート180に封止する面取りされた上表面を含んでいてもよい。浸透性障壁が患者および治療医によって明視化されるように、浸透性障壁184は、不透明材料、たとえば灰色の材料、たとえばシリコーンを含んでいてもよい。
貯蔵部容器は、たとえばアクリル酸塩、ポリメチルメタクリレート、シロキサン、金属、チタン、ステンレス鋼、ポリカーボネート、ポリエーテルエーテルケトン(PEEK)、ポリエチレン、ポリエチレンテレフタレート(PET)、ポリイミド、ポリアミドイミド、ポリプロピレン、ポリスルホン、ポリウレタン、ポリフッ化ビニリデン、またはポリテトラフルオルエチレン(PTFE)など、多くの生体適合性材料のうちの1つ以上を含んでいてもよい。貯蔵部容器の生体適合性材料は、たとえばアクリル酸塩、ポリアクリレート、メタアクリル酸メチル、ポリメタクリル酸メチル(PMMA)、ポリカーボネートまたはシロキサンのうちの1つ以上など、光透過性材料を含んでいてもよい。貯蔵部容器130は、フランジ122および細長い狭部120NEを含む保持構造部120を形成するように、1片の材料から機械加工されることができるか、または射出成形されることができる。フランジ122は、半透明材料を含んでいてもよいので、医師がフランジの下にある組織を明視化して患者を判断し、移植時に装置100が見えるのを減少させることができる。貯蔵部容器130は、軸100Aに沿ってアクセスポート180から多孔質構造体150まで延在するチャネルを含んでいてもよく、本願明細書に記載されているように、貯蔵部の容積および多孔質構造体150の放出速度に従って、装置100に注入される製剤を放出することができる。多孔質構造体150は、たとえば接着剤で、治療装置100の遠位端に固定されることができる。代わりに、または組み合わせて、貯蔵部容器130の遠位端は、多孔質構造体150を受けるようにサイズ設定された内径を含んでいてもよく、貯蔵部容器130は、貯蔵部140の所定サイズを規定するために、遠位端の所定位置に多孔質構造体150を配置するストッパを含んでもよい。
代替として、拡張式支持部は拡張時に湾曲してもよい。拡張式装置は、遠位端に配置され、拡張式支持部に固定されている多孔質構造体150を含む。拡張式装置は、たとえば浸透性障壁184を備えたアクセスポート180を含んでいてもよい。拡張式構成では、患者の光路OPの大部分から装置が実質的にはっきり見える。
率 = Vr(dCr/dt)=−D(PA/TL)Cr
但し、率 = 装置からの治療薬放出速度
Cr =貯蔵部における治療薬濃度
Vr =貯蔵部容積
D =拡散定数
PA/TL =RRI
P =多孔率
A=面積
T =ねじれ= F =チャネル・パラメータ
実質的に一定の容積注入では、
Cr0 =(注入容積)(製剤濃度)/Vr
但し、Cr0 =製剤の注入に伴う貯蔵部内の初期濃度
注入容積=50μLでは、
Cr0 = (0.05 mL)(10 mg/mL)/Vr (1000 μg/ 1mg) = 500 μg/Vr
速度 = x(500 μg)exp(−xt)
但し、t =時間
x = (D/Vr)(PA/TL)
硝子体の質量バランスに関しては、
Vv(dCv/dt) =装置からの率= kVvCv
但し、Vv =硝子体容積(約4.5ml)
Cv =硝子体における治療薬濃度
k =硝子体からの薬の率(1/硝子体内の薬の半減期に比例する)
本願明細書において記載されている、Cvが実質的に一定のままであり、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)実施形態に適切な条件では、
Cv=(装置からの率)/(kVv)
kVvが実質的に一定であるので、Cvの最大値は、装置からの率を最大化する条件に対応することとなる。装置への注入から所与の時間(たとえば180日)で、最大値Cvは、最大率をもたらすxの値であることがわかる。xの最適値は、所与の時間で、
d(率)/dx= 0を満たす。
率= 500(x)exp(−xt) = f(x)g(x)
但し、f(x)=500x、およびg(x)=exp(−xt)
d(率)/dx = f’(x)g(x)+ f(x)g’(x)= 500(1−xt)exp(−xt)
所与の時間では、1−xt = 0かつxt = 1の場合、t,d(率)/dx = 0
(D/Vr)(P A/TL)t = 1の場合、率は最大となる。
所与の容積では、最適PA/TL =最適RRI= Vr/(Dt)
それゆえに、所与の時間tでの最も高いCvは、
所与のVrでは、最適RRI =(PA/FL)として生じる。
また、率(Vr)/(RRI) = (Vr)/(PA/TL) = Dtは、その時の最適率を決定することになる。
たとえば、多孔質構造体の最適放出速度指数および最適貯蔵部容積は、所定の長期間、たとえば90日間、最小阻止濃度を超える治療濃度を達成するために、治療薬の所定量、たとえば50μLを受容するようにサイズ設定されている。貯蔵部の最大容積は、最適容積の約2倍以下に制限されることができる。貯蔵部容積および多孔質構造体を市販の製剤の注入容積に合わせることによって、同じ容積の市販の注入可能な製剤を受けるより大きな貯蔵部容積と比較して、装置からの治療量の放出時間を増加させることができる。本願明細書において記載されている多数の例は、製剤量を受容し長期間放出するように共に調整されている多孔質フリット構造体および貯蔵部容積を示しているが、貯蔵部に合わせられる多孔質構造体は、多孔質フリット、透過性膜、半透過性膜、毛細管または蛇行チャネル、ナノ構造体、ナノチャネル、または焼結ナノ粒子のうちの1つ以上を含んでもよく、そして、当業者は、製剤量を受容し、治療量を連続した期間放出するように1つ以上の多孔質構造体および容積を調整するために、放出速度の特徴、たとえば放出速度指数を決定することができる。
実施例1
図8は、Luer−Lok(登録商標)の先端および様々な直径の針を有する1mlの注射器から製造される規定された直径の出口ポートを備えた貯蔵部を示す。針は、全長8mmに調整したが、ここでは2mmが針ハブを越えて延在している。金属性のバリを顕微鏡下で除去した。図8−1は、注射器に取り付けられる針を示し、ついで、リン酸緩衝液(Spectrum Chemicals, B−210)における、フルオレセインナトリウムの溶液2.4mg/mL、分子量376Daで注射器を充填した。気泡を除去し、0.05mlを計量分配することができるように注射器を調整した。結果として生じた貯蔵部の形状を図8−1に示す。第1の拡張領域は、針ハブの内側と注射器の先端とによって画定されている。第2の拡張領域は、注射器内部である。貯蔵部の全容積は、0.14mlである。
実施例1
表1C 出口ポートを通るフルオレセインの放出
図11は、1mLの注射器にあるLuer−Lokの先端を切断することによって製造した多孔質膜を備えた貯蔵部を示す。注射器の端部を平滑化し、面取りした。0.2μmの孔径を備えたナイロン膜を注射器の端部を覆って配置し、1片のシリコーン管で固定した。注射器の内径は4.54mmであり、露出した膜面積16mm2を得た。PBSにおけるウシ血清アルブミン(Sigma A7906−100G)約300mg/mlのうち約100mlを添加できるように、ピストンを除去した。ピストンを交換して、空気を除去し膜を通るわずかな量の液体を押すように動かした。短時間水に浸すことによって、膜および注射器の外側を洗浄した。ついで、PBS 5mLを含む15mLバイアルに貯蔵部を配置した。蒸発を回避するために、バイアルの頂部をパラフィルムで封止した。0.5から1日の周期的な間隔で、PBSを含む新規のバイアルに貯蔵部を移動した。バイアルに蓄積したBSA量を可視光(280nm)の吸収を介して測定することによって、膜を通る拡散を測定した。2つの複製からの送達速度を図11−1に示す。このデータは、次数100kDaの分子量を備えた関心の治療薬が、孔径0.2μmの多孔質膜を通って容易に移送するであろうことを示唆している。
視野に対する干渉を最小限に抑えるために、少なくともいくつかの装置設計は、約6mmを超えて硝子体内に延びることはない。さらに、装置を硝子体内に延在させることは有益であり得る。というのは、ついで、眼球の壁からの距離だけ、薬を放出することができるからである。抗体などの高分子は、拡散プロセスではなく対流プロセスによって、硝子体から主に除去される(Computer SimμLation of Convective and Diffusive Transport of Controlled−Release Drμgs in the vitreous Hμmor, by Stay, MS; Xu, J, Randolph, TW; and VH Barocas, Pharm Res 2003, 20(1), pp. 96−102を参照)。毛様体による眼房水の分泌によって生じる圧力によって、対流を駆動することができ、硝子体中の流れは網膜に向かっている。周縁網膜に対してより多くの治療薬を送達すると考えられる、眼球と平坦なポートを有する装置とは対照的に、硝子体に延びている出口ポートでは、眼の後ろで網膜の中心に向かって薬が対流によって移動するとより考えられ得る。
23本および30本のゲージ針を使用している実施例1に記載の放出の研究を10週にわたり続けた。結果を、フィックの拡散法則に基づいて、貯蔵部内の濃度の貯蔵部からの放出速度への変化と関連するモデルと比較する。この単純なモデルは、貯蔵部の濃度が均一であり、受容液体、すなわち硝子体の濃度が無視できると想定している。微分方程式を解くことによって、1つのオリフィスを備えた貯蔵部からの以下の治療薬の累積放出を得る。すなわち、
累積放出 = 1−cR/cRO = 1−exp ((−DA/L VR)t)
但し、
cR = 貯蔵部濃度
VR = 貯蔵部容積
D = 拡散係数
A = オリフィスの面積
L = オリフィスの厚さ
t = 時間
注射器および焼結多孔質のチタン・シリンダ(Applied Porous Technologies, Inc., Mott CorporationまたはChand Eisenmann Metallurgicalから入手可能)から、貯蔵部を製造した。これらは、チタン粒子から加工された、直径が0.062インチ、厚さが0.039インチの焼結多孔質シリンダであった。多孔率は0.17であり、約3から5マイクロメートルの平均孔径を備えている。多孔質シリンダは、気泡位置の測定に従って媒質グレード0.2と特徴づけられる。多孔質シリンダを、デルリン(Delrin)(登録商標)から機械加工されたスリーブに圧入した。スリーブは、1つの平坦面全体を貯蔵部の溶液に、他の平坦面全体を面積1.9平方ミリメートルに対応するバイアルの受容溶液に露出させた。1mLのポリプロピレン注射器の先端を切断し、注射器の内径よりもわずかに大きな外径を備えたポリマースリーブを受けるように機械加工した。多孔質シリンダ/スリーブを、改変した注射器に圧入した。
多孔質シリンダは、貯蔵部と受容溶液とに露出する面積が等しいので、チャネル・パラメータは、効果的経路長のチャネル・パラメータ1.6に対応し、媒質グレード0.2から調製された多孔質のチタン・シリンダに対して1.6のねじれを示唆する。
貯蔵部を、実施例5に記載したのと同様に注射器および多孔質の焼結チタン・シリンダから製造した。多孔質の焼結チタン・シリンダ(Applied Porous Technologies, Inc., Mott CorporationまたはChand Eisenmann Metallurgicalから入手可能)は、直径が0.082インチ、厚さが0.039インチ、媒質グレードが0.2であり、チタン粒子から加工された。多孔率は0.17であり、約3から5マイクロメートルの平均孔径を備えている。多孔質シリンダは、気泡位置の測定に従って媒質グレード0.2と特徴づけられる。
多孔質シリンダを、デルリンから機械加工されたスリーブに圧入した。スリーブは、1つの平坦面全体を貯蔵部の溶液に、他の平坦面全体を面積3.4平方ミリメートルに対応するバイアルの受容溶液に露出させた。1mLのポリプロピレン注射器の先端を切断し、注射器の内径よりもわずかに大きな外径を備えたポリマースリーブを受けるように機械加工した。多孔質シリンダ/スリーブを、改変した注射器に圧入した。接着剤を備えたカプトン膜を、受容溶液に露出する表面に貼付けて、マスクを作製し、被露出領域を減少させた。第1の場合では、マスクの直径は0.062インチであり、面積1.9平方ミリメートルが受容溶液に露出していた。第2の場合では、マスクの直径は0.027インチであり、面積0.37平方ミリメートルが受容溶液に露出していた。
プロトタイプ装置を、316Lのステンレス鋼粒子から加工された、直径が0.155インチ直径、厚さが0.188インチの円筒形の、管状にした焼結多孔質ステンレス鋼シリンダ(Applied Porous Technologies, Inc., Mott CorporationまたはChand Eisenmann Metallurgicalから入手可能)から製造した。多孔質シリンダは、気泡位置の測定による0.1の媒質グレードとして特徴づけられる。媒質グレード0.1のステンレス鋼の抵抗特性を特徴づけるために、面積が12mm2のこれらの大きな既製の多孔質シリンダで、この研究を行った。
プロトタイプ装置を、316Lのステンレス鋼粒子から加工された、直径が0.031インチ直径、厚さが0.049インチの円筒形の、管状にした焼結多孔質ステンレス鋼シリンダ(Applied Porous Technologies, Inc., Mott CorporationまたはChand Eisenmann Metallurgicalから入手可能)から製造した。多孔質シリンダは、気泡位置の測定により0.2の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を特注として得た。大径で媒質グレード0.2の多孔質ステンレス鋼のシリンダを用いた(データを示さず)先の研究と、本願明細書において記載されているモデルに基づく予測とから、特性を決定した。この多孔質体シリンダの各表面積は、0.5mm2である。
本願明細書に記載されている方程式に基づいて、治療薬の硝子体濃度を予測することができる。表4は、各々のシミュレーション1、シミュレーション2、シミュレーション3、シミュレーション4およびシミュレーション5のそれぞれに適用されるパラメータ値を示す。半減期および硝子体容積は、サルのモデルに対応する(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 abstract D906)。放出速度プロファイルを決定するために、パラメータPA/FLを変更することができる。たとえば、Aの値が約1mm2とすることができ、多孔率が約0.1(PA=0.1mm2)とすることができ、長さが約1mmであってもよく、ねじれに対応し得るチャネルフィットパラメータが約2(FL=2 mm)であってもよいので、PA/TLは、約0.05mmとなる。当業者は、本願明細書に記載されている教示に基づいて、長期間治療薬を延長して放出するための面積、多孔率、長さ、およびチャネルフィットパラメータを経験的に決定することができる。
500μgの単回注射は、毎月の間隔で与えることのできるLucentis(商標)の50μLボーラス注射に対応し、硝子体のLucentis(商標)(ラニビズマブ)の治療濃度の範囲は、たとえば約1ヵ月で約100μg/mLから約0.1μg/mLの最小抑制(治療)濃度に及ぶ。硝子体の治療濃度の範囲の下位に対応する最小阻止濃度は、本願明細書に記載されている実施例に従って、当業者によって経験的に決定されることができる。たとえば、硝子体の濃度を少なくとも約1μg/mLにするように、一連の6つのLucentis(商標)のそれぞれ5μgの低用量の研究を行うことができ、注入の治療上の利益は本願明細書において記載されていると判断される。
所定量は、毎月のボーラス注射量、たとえば50μLに相当する。治療装置は、容積が25μLの実質的に一定の容積の容器貯蔵部を含んでもよいので、継続および/または制御して放出するために、50μL注入のうちの最初の25μLの部分が貯蔵部に含まれ、50μLの注入のうちの第2の25μLの部分が多孔質構造体を通過して、25μLのボーラスで硝子体内に放出される。装置に注入する充填効率は、100%未満を含んでいてもよく、その充填効率に基づいて、本願明細書において記載されている教示に従って貯蔵部容積および注入容積を調整することができる。たとえば、充填効率は約90%を含んでいてもよいので、治療装置に注入される50μLに対して、第1の部分は、容器貯蔵部のチャンバに含有されている約22.5μLを含み、第2の部分は、装置を通過する約27.5μLを含む。硝子体液のLucentis(商標)の初期濃度は、貯蔵部装置に注入後すぐの約60μg/mLに相当する。硝子体液のLucentis(商標)濃度は、90日で約3.2μg/mLまで減少する。第1の注入から約90日後のLucentis(商標)の第2の50μLの注入によって、濃度が約63μg/mLまで増加する。硝子体液のLucentis(商標)濃度は、第1の注入後180日、および第2の注入後90日で約3.2μg/mLまで減少する。これらの計算値が示すのは、50μLを装置に注入した状態で、Lucentis(商標)濃度を、1mlにつき約3μgの最小阻止濃度を超えて連続的に維持することができることである。患者を治療するために、たとえば数年間で90日ごとに追加的に注入して、治療薬を送達することができる。
濃度は、360日で約0.6μg/mLとなり、最小阻止濃度約0.5に基づいて、1年に及んで単回注射での治療に適することができる。本願明細書において記載されている教示に基づいて、最小阻止濃度を当業者によって経験的に決定することができる。
硝子体内の180日のラニビズマブ濃度は、約3.128μg/mLである。
硝子体内の180日のラニビズマブ濃度は、約3.174μg/mLである。
硝子体内の180日のラニビズマブ濃度は、約3.185μg/mLである。
硝子体内の180日のラニビズマブ濃度は、約3.152μg/mLである。
硝子体内の180日のラニビズマブ濃度は、約3.065μg/mLである。
図20は、実施例10のように貯蔵部内における治療薬懸濁液の算出された時間放出プロファイルを示す。RRIが1.2mmである10μLの装置として、ヒトの硝子体中のトリアムシノロンアセトニド濃度を測定し、示した。計算は、懸濁液に対する上記の方程式に基づくものであった。プロファイルを数値シミュレーションによって作成した。T=0から即座に始まる一定の送達速度1μg/日を想定すると、ヒトの眼の硝子体中の濃度は、1日で定常状態の値の99%以内に到達することができる。薬物放出プロファイルの反対側の末端では、シミュレーションは、固体薬物すべてが実質的に無くなった場合の硝子体濃度を示す。すなわち、溶解薬物の99%以上が1日以内に送達される。
図21は、実質的に同様の多孔質フリット構造体および16μLの貯蔵部および33μLの貯蔵部を含む治療装置の放出速度プロファイルを示す。各フリットの放出速度指数は、約0.02であった。16μL貯蔵部をそれぞれ含む2つの治療装置と、33μLの貯蔵部をそれぞれ含む2つの治療装置とに対する放出速度が示されている。33μLの貯蔵部を含む装置が、16μLの貯蔵部を含む装置の約2倍の速度で、Avastin(商標)を放出した。これらの測定データが示すのは、放出速度指数および貯蔵部のサイズが、放出速度プロファイルを決定することができるので、連続した時間治療薬を放出するように放出速度指数および貯蔵部を構成することができることである。
25mg/mLのAvastin(商標);
フリット#2(0.031x 0.049”、媒質グレード0.2μm、316L SS, Mott Corporation);
上の実施例8と実質的に同様の材料(テフロン熱収縮チュービングおよびシリコーン隔壁);
37℃;
2つの複製のうちの1つが気泡を形成した場合、データを切り捨てる。下記の表5Aのデータを参照。
25mg/mLのAvastin(商標);
フリット#2(0.031x 0.049”、媒質グレード0.2μm、316L SS, Mott Corporation);
固体ビーズから機械加工され、金属棒によって閉止された;
37℃;
2つの複製のうちの1つが気泡を形成した場合、データを切り捨てる。
表5A.測定されたAvastin(商標)の放出およびRRI
図22Aは、厚さが0.049”の多孔質フリット構造体を備えたAvastin(商標)に対する累積放出を示す。実験が使用したのは、
25mg/mLのAvastin(商標);
フリット#2(0.031x 0.049”、媒質グレード0.2μm、316L SS,Mott Corporation);
ネジを有する機械加工されたポリカーボネート代用薬;
貯蔵部容積37μL;
37℃。
装置番号およびそれぞれに対応するRRIの検査済みの装置が、下の表5Bにおいて一覧を示す。計測に基づく測定RRIは0.02であり、本願明細書において記載されている治療薬の放出のモデルと一致している。各試験装置の測定RRIに関するいくつかの可変性が記されているが、各装置のRRIは、治療薬の放出を測定するのに使用されることができ、多孔質構造体は、本願明細書において記載されている気体流によってさらに特徴づけられて、患者に装着する前にRRIを測定することができる。
25mg/mLのAvastin(商標);
フリット#3(0.038x 0.029”、媒質グレード0.2μm、316L SS, Mott Corporation);
ネジを有する機械加工されたポリカーボネート代用薬;
貯蔵部容積37μL;
37℃。
装置番号およびそれぞれに対応するRRIの検査済みの装置が、下の表5Cにおいて一覧を示す。計測に基づく測定RRIは、0.034であり、本願明細書において記載されている治療薬の放出のモデルと一致している。各試験装置の測定RRIに関するいくつかの可変性が記されているが、各装置のRRIは、治療薬の放出を測定するのに使用されることができ、多孔質構造体は、本願明細書において記載されているように、気体流によってさらに特徴づけられて、患者に装着する前にRRIを測定することができる。
25mg/mLのAvastin(商標);
フリット#6(0.038x 0.029”、媒質グレード0.2μm、316L SS,Mott Corporation);
ネジを有する機械加工されたポリカーボネート代用薬;
37℃。
計測に基づく測定RRIは、0.05mmであり、本願明細書において記載されている治療薬の放出のモデルと一致している。
25mg/mLのAvastin(商標);
フリット#5(0.038x 0.029”、媒質グレード0.1μm、316L SS,Mott Corporation);
ネジを有する機械加工されたポリカーボネート代用薬;
貯蔵部容積20μL;
37℃。
計測に基づく測定RRIは、0.03であり、本願明細書において記載されている治療薬の放出のモデルと一致している。
これらの数値データはまた、現在の臨床ボーラス注射の範囲内で装置から放出される治療薬の濃度を示す。たとえば、Lucentis(商標)のような治療薬の最大の放出が患者にとって安全な範囲内にあるように、Cmaxは、0.01から0.1までのRRIに基づいて、それぞれ2.1から11.9まで変化する。
表6A.MICを超える時間(日)の計算(20μLの貯蔵部容積、T 1/2=9日、貯蔵部内の薬物濃度=10mg/ml)
表6B.MICを超える時間(日)の計算(20μLの貯蔵部容積、T 1/2=9日、貯蔵部内の薬物濃度=40mg/ml)
表6C.MICを超える時間(日)の計算(50μLの貯蔵部容積、T 1/2 = 9日、貯蔵部内の薬物濃度 = 40mg/ml)
所望の連続した期間放出するよう、貯蔵部および/または治療薬の量を調整することができる。
多孔質フリット構造体を通る小分子薬物の放出を測定するために、多孔質フリット構造体を通る貯蔵部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・モデルが示しているのは、本願明細書において記載されている多孔質フリット構造体および貯蔵部が、小分子薬物を送達する用途に適していることである。フルオレセイン・データと関連してAvastin(商標)、Lucentis(商標)およびBSAの放出プロファイルが示しているのは、多孔質フリット構造体および貯蔵部が、多くの薬物、分子、ならびに多くの分子量および分子サイズの治療薬の徐放性のために使用されることができることである。
2mg/mlのフルオレセインナトリウム;
フリット#2(0.031x0.049”、媒質グレード0.2μm、316L ss、Mott Corporation);
ネジを有する機械加工されたポリカーボネート代用薬;
37℃。
プレートリーダを用いてフルオレセインのサンプルを492nmでUV吸光度によって分析した。計測に基づく測定RRIは0.02であり、本願明細書において記載されている治療薬の放出モデルと一致している。
実験が使用したのは:
10mg/mlのLucentis(商標);
ネジを有する機械加工されたポリ(メタクリル酸メチル)代用薬;および、
貯蔵部容積30μL;
37℃。
あらゆる多孔質フリット構造体は、316L SS, Mott Corporationである。示されるデータは、気泡の成長または少ない容器容積を示した少しのサンプルを除いて、あらゆる装置からの測定データである。
図26Aおよび図26Bは、それぞれ、0.2の媒質グレードおよび0.5の媒質グレードの多孔質材料の多孔質フリット構造体の破断縁部からの走査型電子顕微鏡画像を示す。市販のサンプルは、Mott Corporationから入手し、316Lステンレス鋼を含んでいた。治療薬を放出するために材料内の多孔質構造体および相互接続チャネルを示すように、サンプルを機械的に破断した。顕微鏡写真画像は、第1の表面の開口部と第2の表面の開口部との間に配置されている複数の相互接続チャネルを示している。
圧力減衰および流れを含むがこれに限定されない多くの機械試験をフリットに受けさせることによって、サンプル要素の相対的特徴を測定することができる。これらの試験は、装置の放出プロファイルを測定するために、たとえばRRIなどの薬物放出速度の情報と組み合わせ可能である。これらの試験は、装置の多孔質構造体を通る流れを定量化し、多孔質構造体の適合性を判定するために、治療装置に配置されている多孔質構造体で使用されることができる。同様の試験を使用して、治療装置への取付け前に多孔質構造体を定量化することができる。少なくともいくつかの治療装置は、部分的に組み立てられた治療装置に装着した多孔質構造体の気体流によって、たとえば品質管理チェックとして評価されることができる。いくつかの実施形態では、多孔質構造体が治療薬を放出するのに適しており、たとえば治療装置の支持など装置に固定されることを保証するために、貯蔵部に治療薬を挿入する前に、かつ患者に挿入する前に、部分的に組み立てられているか、または実質的に組立てられた治療装置に、流れ試験を行うことができる。
上記の試験方法はそれぞれ、試験片の試験ハードウェアへの機械的接続を使用してもよく、多くの技術が探究されて利用されてきた。これらの取付け具は、確実に試験片を固定する手段(たとえば熱回収管、弾性管、比較的硬質の構成要素へのプレス嵌めなど)と、結合手段(たとえばルアー、蛇腹式取付け具、クイック連結カップリングなど)との両方を含み、試験ハードウェアに便利よく反復可能に取付けることができる。
市販の溶液を使用し、あるいは容易に入手できる機器を組み立ててカスタマイズした試験装置を作製することによって、各々の所望の試験を開発することができる。ここでも、これらの方法の両方が評価されている。作動システムは、試験片を接続する手段と、制御可能な供給源(通常は圧力であるが、これに限定されない)と、マノメータ(または他の圧力計測装置)と、試験条件を判定し、かつ/またはさらなる分析のデータを集めるのに使用される1つ以上のトランスデューサ(圧力、流れなど)から成る。
治療薬送達装置の用途に適した多孔質構造体を特定するための、圧力減衰試験 図28は、本願明細書において記載されている実施形態に従って治療装置の用途に適した多孔質フリット構造体を特定するための、多孔質構造体に使用する圧力減衰試験および試験装置を示す。
治療薬送達装置の用途に適した多孔質構造体を特定するための、圧力減衰試験 図29は、本願明細書において記載されている実施形態に従って、治療装置の用途に適した多孔質フリット構造体を特定するための、多孔質構造体に使用する圧流試験および試験装置を示す。
表7は、多孔質構造体を通る酸素または窒素などの気体の流れに基づいて、たとえばRRIなどの治療薬の放出を測定するのに使用可能な表を示す。本願明細書に記載されているように、多孔質フリット構造体にわたる圧力が低下した多孔質構造体全体の流量で、多孔質構造体を通る流れを気体の圧力の減衰時間で測定することができる。たとえばMott Corp.から入手可能な市販の媒質グレード材料のような材料の媒質グレードに基づいて、流量およびRRIを測定することができる。治療薬は、多孔質構造体または同様の試験分子を通って測定されることができる。初期の測定値は、示されている多孔質フリット構造体を備えた、Avastin(商標)に対するRRIを測定した。本願明細書において記載されている教示に基づいて、当業者は実験を行って、気体を備えた流量と治療薬の放出速度との対応を経験的に決定することができる。
直接的な硝子体内注入を介するLucentis(商標)(500μg)の標準量の投与が、滲出性加齢黄班変性(wet AMD)を患う患者の症状を減少させるのに有効であるということが証明されているが、下記の臨床研究は、滲出性加齢黄班変性を治療するためにより低濃度を使用することができることを示している。本願明細書において記載されている装置は、毎月のボーラス注射500μgに対応するより少ない量でのヒト患者のin vivoの最小阻止濃度(以下「MIC」)で、AMDを治療するために使用することができる。たとえば、表4Dおよび上の図19Aに従って、ヒトのin situの濃度プロファイルを得るために、Lucentis(商標)注入5μgを投与されることができる。
Claims (25)
- 硝子体液および強膜を持つ患者の目を治療するための、埋め込み可能な、治療装置であって、前記治療装置は、
治療薬を保持し、長期間にわたって、治療に必要な量の前記治療薬を前記硝子体液中に放出するように構成された容器を備え、
前記容器は、生体適合材料から成る硬質の不透過性の壁により形成されるとともに、
前記強膜の上側に連結するように構成された近位の延長部と、
前記近位の延長部の下に前記強膜を受容するように構成された中間の峡部と、
前記硝子体液の中に設置され、治療薬の液体製剤を含むように構成された遠位の補充可能な貯蔵部とを備え、
前記中間の峡部は、第1の方向にわたる第1の断面の距離幅と、前記第1の断面の距離幅よりも小さい第2の方向にわたる第2の断面の距離幅を有し、
前記近位の延長部は、注入可能な表面を通じて前記遠位の補充可能な貯蔵部への前記治療薬の注入を受け入れ、
前記治療装置は、硬質多孔質構造体であって、前記硬質多孔質構造体内の空隙部の割合に対応する多孔率を有する硬質多孔質構造体をさらに備え、前記硬質多孔質構造体は、前記遠位の補充可能な貯蔵部の端部に連結され、治療に必要な量の治療薬を、長期間にわたって、前記硝子体液に放出するように調整されており、
前記治療装置が埋め込まれ使用されている間は、前記遠位の補充可能な貯蔵部の容積は固定されていることを特徴とする、治療装置。 - 前記硬質多孔質構造体の前記空隙部は、固定された複数の相互接続チャネルにより形成されていることを特徴とする請求項1に記載の治療装置。
- 前記治療薬が前記遠位の補充可能な貯蔵部内へ少なくとも所定の圧力により注入されるとき、前記遠位の補充可能な貯蔵部の容積は固定されたままであり、前記硬質多孔質構造体はその硬質を維持し、前記複数の相互チャネルは固定されたままであることを特徴とする請求項2に記載の治療装置。
- 前記遠位の補充可能な貯蔵部は、結膜の下部に設置された際に、前記強膜および脈絡膜を通じて延在し、前記近位の延長部は、貫通可能な障壁を備え、前記強膜あるいは前記脈絡膜に注射針を貫通させなくても、結膜および前記貫通可能な障壁を介して注射針を進入させることによって前記遠位の補充可能な貯蔵部へ前記治療薬を補充することを特徴とする、請求項1に記載の治療装置。
- 前記複数の相互接続チャネルのうち少なくとも一部は、複数の相互接続を有することを特徴とする、請求項2に記載の治療装置。
- 前記硬質多孔質構造体は、焼結材料から成ることを特徴とする請求項1に記載の治療装置。
- 前記硬質多孔質構造体は、金属の焼結材料の多孔質の円板から成ることを特徴とする請求項1に記載の治療装置。
- 前記硬質多孔質構造体は、金属、セラミック、ガラスのうち少なくとも1つから成ることを特徴とする請求項1に記載の治療装置。
- 前記硬質多孔質構造体は、長期間にわたって前記治療薬を放出するよう構成された厚み及び断面積を有し、前記硬質多孔質構造体は、前記硬質多孔質構造体の多孔率と前記断面積の積を前記硬質多孔質構造体のチャネルパラメータと前記厚みの積で除算した値により定まる放出速度指数を有することを特徴とする請求項2に記載の治療装置。
- 前記厚みは前記硬質多孔質構造体の第1の側と第2の側に亘っており、前記複数の相互接続チャネルは前記第1の側と前記第2の側の間に伸び、前記硬質多孔質構造体の前記複数の相互接続チャネルは、相互に接続された、前記第1の側から前記第2の側に伸びる有効な長さを持つ固定された蛇行状のチャネルであって、前記有効な長さは前記硬質多孔質構造体の前記厚みよりも大きいことを特徴とする請求項9に記載の治療装置。
- 前記硬質多孔質構造体の前記複数の相互接続チャネルは、前記治療薬が前記複数の相互接続チャネルを通るように構成されることを特徴とする請求項2に記載の治療装置。
- 前記硬質多孔質構造体は硬質の焼結材料粒子を備え、前記相互接続チャネルは少なくとも部分的に前記硬質の焼結材料粒子の周囲に伸びているため、前記治療薬は前記硬質多孔質構造体を介し通過することを特徴とする請求項2に記載の治療装置。
- 前記近位の延長部は、前記遠位の補充可能な貯蔵部に連結され且つ前記遠位の補充可能な貯蔵部の外側に伸び、前記強膜と結膜の間に伸びているため、縫合することなく埋め込み位置に前記治療装置を保持するように構成されることを特徴とする請求項1に記載の治療装置。
- 前記治療装置が埋め込まれている間、前記治療薬は前記遠位の補充可能な貯蔵部内において少なくとも20日の半減期を有し、前記治療装置は、少なくとも90日の間、前記目の中に埋め込まれて前記治療薬によって前記目を治療するように構成されることを特徴とする請求項1に記載の治療装置。
- 前記治療装置が埋め込まれている間、前記治療薬は前記遠位の補充可能な貯蔵部内において少なくとも30日の半減期を有し、前記治療装置は少なくとも120日の間、前記目の中に埋め込まれ、前記治療薬によって前記目を治療するように構成されることを特徴とする請求項1に記載の治療装置。
- 前記治療装置が埋め込まれている間、前記遠位の補充可能な貯蔵部の容積は一定であり、前記硬質多孔質構造体は、前記遠位の補充可能な貯蔵部内での半減期を伴う治療薬の放出速度指数を有し、前記硝子体液中に直接治療薬を注入する際は、前記遠位の補充可能な貯蔵部内での半減期は、対応する前記治療薬の半減期より長く、少なくとも120日分の治療薬の量の放出に相当することを特徴とする請求項1に記載の治療装置。
- 前記硬質多孔質構造体は、前記長時間にわたって治療薬を放出するように構成された厚み、チャネルパラメータおよび表面積を有することを特徴とする請求項2に記載の治療装置。
- 前記チャネルパラメータは、前記硬質多孔質構造体の第1の側から第2の側に伸びる相互接続チャネルの有効な長さに対応するフィットパラメータを有することを特徴とする請求項17に記載の治療装置。
- 少なくとも1つの前記治療薬の放出速度は、前記チャネルパラメータに対する多孔率の比に対応しており、前記硬質多孔質構造体が長期間にわたって少なくとも1つの治療薬を放出するように、前記チャネルパラメータに対する多孔率の比は、0.5未満であることを特徴とする請求項18に記載の治療装置。
- 前記硬質多孔質構造体は、5.0mm以下の放出速度指標を有することを特徴とする請求項1に記載の治療装置。
- 前記遠位の補充可能な貯蔵部は、所定の長い時間に放出する治療薬の量を貯蔵するための容積を備え、前記硬質多孔質構造体は、所定の厚みと断面積と前記硬質多孔質構造体の多孔率と前記断面積の積を前記硬質多孔質構造体のチャネルパラメータと前記厚みの積で除算した値により決定される放出速度指数を備え、前記容積と前記放出速度指数は前記遠位の補充可能な貯蔵部内の半減期を達成することを特徴とする請求項2に記載の治療装置。
- 前記治療薬を所定の治療濃度で提供できるように、前記半減期は、前記所定の長い時間において最大速度に達した時に対応することを特徴とする請求項21に記載の治療装置。
- 前記目に埋め込む前に、前記治療装置は前記遠位の補充可能な貯蔵部内に充填された初期量の前記治療薬をさらに含むことを特徴とする請求項1に記載の治療装置。
- 前記硬質多孔質構造体は、第1の領域を有する第1の側と、前記第1の領域に対応する第2の領域を有する第2の側と、前記第1の側と前記第2の側の間の厚みと、多孔率と、チャネルパラメータを備えることを特徴とする請求項2に記載の治療装置。
- 前記治療薬は、次の薬物すなわちアバレリックス、アバタセプト、アブシキシマブ、アダリムマブ、アルデスロイキン、アレファセプト、アレムツズマブ、α1プロテイナーゼ阻害剤、アルテプラーゼ、アナキンラ、アニストレプラーゼ、抗血友病因子、抗胸腺細胞グロブリン、アプロチニン、アルシツモマブ、アスパラギナーゼ、バシリキシマブ、ベカプレルミン、ベバシズマブ、ビバリルジン、ボツリヌス毒素タイプA、ボツリヌス毒素タイプB、カプロマブ、セトロレリクス、セツキシマブ、コリオゴナドトロピンα、凝固因子IX、凝固因子VIIa、コラゲナーゼ、コルチコトロピン、コシントロピン、シクロスポリン、ダクリズマブ、ダルベポエチンα、デフィブロチド、デニロイキンジフチトクス、デスモプレシン、ドルナーゼα、ドロトレコギンα、エクリズマブ、エファリズマブ、エンフビルチド、エポエチンα、エプチフィバチド、エタネルセプト、エクセナチド、フェリプレシン、フィルグラスチム、フォリトロピンβ、ガルスルファーゼ、ゲムツズマブオゾガマイシン、グラチラマーアセテート、組換えグルカゴン、ゴセレリン、ヒト血清アルブミン、ヒアルロンダーゼ、イブリツモマブ、イデュルスルファーゼ、免疫グロブリン、インフリキシマブ、組換えインスリングラルギン、組換えインスリンリスプロ、組換えインシュリン、インシュリン、ブタ(porcine)、インターフェロンα‐2a、組換え、インターフェロンα‐2b、組換え、インターフェロンアルファコン‐1、インターフェロンα‐n1、インターフェロンα‐n3、インターフェロンβ‐1b、インターフェロンγ‐1b、レピルジン、ロイプロリド、ルトルピンα、メカセルミン、メノトロピン、ムロモナブ、ナタリズマブ、ネシリチド、オクトレオチド、オマリズマブ、オプレルベキン、OspAリポタンパク質、オキシトシン、パリフェルミン、パリビズマブ、パニツムマブ、ウシペガデマーゼ、ペガプタニブ、ペガスパルガーゼ、ペグフィルグラスチム、ペグインターフェロンα‐2a、ペグインターフェロンα‐2b、ペグビソマント、プラムリンチド、ラニビズマブ、ラスブリカーゼ、レテプラーゼ、リツキシマブ、サーモンカルシトニン、サルグラモスチム、セクレチン、セルモレリン、ヨウ化血清アルブミン、組換えソマトロピン、ストレプトキナーゼ、テネクテプラーゼ、テリパラチド、チロトピンα、トシツモマブ、トラスツズマブ、ウロフォリトロピン、ウロキナーゼ、又はバソプレシンの1つまたは複数を含んでもよいことを特徴とする請求項1に記載の治療装置。
Applications Claiming Priority (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US14837509P | 2009-01-29 | 2009-01-29 | |
US61/148,375 | 2009-01-29 | ||
US17488709P | 2009-05-01 | 2009-05-01 | |
US61/174,887 | 2009-05-01 | ||
US26171709P | 2009-11-16 | 2009-11-16 | |
US61/261,717 | 2009-11-16 | ||
US28483209P | 2009-12-24 | 2009-12-24 | |
US61/284,832 | 2009-12-24 | ||
US29928210P | 2010-01-28 | 2010-01-28 | |
US61/299,282 | 2010-01-28 |
Related Parent Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011548352A Division JP5577354B2 (ja) | 2009-01-29 | 2010-01-29 | 治療装置 |
Related Child Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016046673A Division JP6171036B2 (ja) | 2009-01-29 | 2016-03-10 | 眼球インプラントに治療薬を注入するためのシステム |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2014217769A true JP2014217769A (ja) | 2014-11-20 |
JP5902766B2 JP5902766B2 (ja) | 2016-04-13 |
Family
ID=42396045
Family Applications (3)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011548352A Active JP5577354B2 (ja) | 2009-01-29 | 2010-01-29 | 治療装置 |
JP2014140048A Active JP5902766B2 (ja) | 2009-01-29 | 2014-07-07 | 眼球インプラントに治療薬を注入するためのシステム |
JP2016046673A Active JP6171036B2 (ja) | 2009-01-29 | 2016-03-10 | 眼球インプラントに治療薬を注入するためのシステム |
Family Applications Before (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2011548352A Active JP5577354B2 (ja) | 2009-01-29 | 2010-01-29 | 治療装置 |
Family Applications After (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2016046673A Active JP6171036B2 (ja) | 2009-01-29 | 2016-03-10 | 眼球インプラントに治療薬を注入するためのシステム |
Country Status (10)
Country | Link |
---|---|
US (10) | US8399006B2 (ja) |
EP (1) | EP2391419B1 (ja) |
JP (3) | JP5577354B2 (ja) |
CN (2) | CN102365109B (ja) |
AU (1) | AU2010208046B2 (ja) |
CA (2) | CA3045436A1 (ja) |
ES (1) | ES2747755T3 (ja) |
PL (1) | PL2391419T3 (ja) |
SG (2) | SG2014007389A (ja) |
WO (1) | WO2010088548A1 (ja) |
Families Citing this family (155)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US7867186B2 (en) | 2002-04-08 | 2011-01-11 | Glaukos Corporation | Devices and methods for treatment of ocular disorders |
EP1418868B1 (en) | 2001-04-07 | 2008-03-26 | Glaukos Corporation | Glaucoma stent for glaucoma treatment |
US7431710B2 (en) | 2002-04-08 | 2008-10-07 | Glaukos Corporation | Ocular implants with anchors and methods thereof |
US8308701B2 (en) | 2010-11-15 | 2012-11-13 | Aquesys, Inc. | Methods for deploying intraocular shunts |
US8663303B2 (en) | 2010-11-15 | 2014-03-04 | Aquesys, Inc. | Methods for deploying an intraocular shunt from a deployment device and into an eye |
US10085884B2 (en) | 2006-06-30 | 2018-10-02 | Aquesys, Inc. | Intraocular devices |
US8721702B2 (en) | 2010-11-15 | 2014-05-13 | Aquesys, Inc. | Intraocular shunt deployment devices |
US8852256B2 (en) | 2010-11-15 | 2014-10-07 | Aquesys, Inc. | Methods for intraocular shunt placement |
US8974511B2 (en) | 2010-11-15 | 2015-03-10 | Aquesys, Inc. | Methods for treating closed angle glaucoma |
US8801766B2 (en) | 2010-11-15 | 2014-08-12 | Aquesys, Inc. | Devices for deploying intraocular shunts |
US9095411B2 (en) | 2010-11-15 | 2015-08-04 | Aquesys, Inc. | Devices for deploying intraocular shunts |
US20120123316A1 (en) | 2010-11-15 | 2012-05-17 | Aquesys, Inc. | Intraocular shunts for placement in the intra-tenon's space |
US8506515B2 (en) | 2006-11-10 | 2013-08-13 | Glaukos Corporation | Uveoscleral shunt and methods for implanting same |
US9877973B2 (en) | 2008-05-12 | 2018-01-30 | University Of Utah Research Foundation | Intraocular drug delivery device and associated methods |
EP2276439A4 (en) | 2008-05-12 | 2013-11-27 | Univ Utah Res Found | INTRAOCULAR DRUG DELIVERY DEVICE AND ASSOCIATED METHODS |
US9095404B2 (en) | 2008-05-12 | 2015-08-04 | University Of Utah Research Foundation | Intraocular drug delivery device and associated methods |
US10064819B2 (en) | 2008-05-12 | 2018-09-04 | University Of Utah Research Foundation | Intraocular drug delivery device and associated methods |
PL2391419T3 (pl) | 2009-01-29 | 2019-12-31 | Forsight Vision4, Inc. | Dostarczanie leku do tylnego odcinka |
US8623395B2 (en) | 2010-01-29 | 2014-01-07 | Forsight Vision4, Inc. | Implantable therapeutic device |
WO2010135369A1 (en) * | 2009-05-18 | 2010-11-25 | Dose Medical Corporation | Drug eluting ocular implant |
US10206813B2 (en) * | 2009-05-18 | 2019-02-19 | Dose Medical Corporation | Implants with controlled drug delivery features and methods of using same |
WO2011075481A1 (en) * | 2009-12-16 | 2011-06-23 | Allergan, Inc. | Intracameral devices for sustained delivery |
US10166142B2 (en) | 2010-01-29 | 2019-01-01 | Forsight Vision4, Inc. | Small molecule delivery with implantable therapeutic device |
US8430853B2 (en) * | 2010-02-05 | 2013-04-30 | Johnson & Johnson Vision Care, Inc. | Implantation instruments, system, and kit for punctal implants |
EP3861969A1 (en) | 2010-08-05 | 2021-08-11 | ForSight Vision4, Inc. | Injector apparatus for drug delivery |
AU2014202463B2 (en) * | 2010-08-05 | 2015-09-17 | Forsight Vision4, Inc. | Combined drug delivery methods and apparatus |
WO2012019139A1 (en) | 2010-08-05 | 2012-02-09 | Forsight Vision4, Inc. | Combined drug delivery methods and apparatus |
SI2600812T1 (sl) * | 2010-08-05 | 2021-12-31 | ForSight Vision4, Inc., | Naprava za zdravljenje očesa |
US9605663B2 (en) * | 2010-08-24 | 2017-03-28 | Qwtip Llc | System and method for separating fluids and creating magnetic fields |
US8920335B2 (en) * | 2010-09-01 | 2014-12-30 | Alcon Research, Ltd. | Methods and systems for posterior segment volume measurement |
US9333331B2 (en) * | 2010-11-08 | 2016-05-10 | Cendres+Metaux Sa | Method for implanting an access port |
WO2012065006A2 (en) | 2010-11-11 | 2012-05-18 | Forsight Vision4, Inc. | Methods and apparatus to determine porous structures for drug delivery |
US10842671B2 (en) | 2010-11-15 | 2020-11-24 | Aquesys, Inc. | Intraocular shunt placement in the suprachoroidal space |
CA2818612C (en) * | 2010-11-19 | 2020-12-29 | Forsight Vision4, Inc. | Therapeutic agent formulations for implanted devices |
US9668915B2 (en) | 2010-11-24 | 2017-06-06 | Dose Medical Corporation | Drug eluting ocular implant |
US8783451B2 (en) * | 2011-02-18 | 2014-07-22 | Allergan, Inc. | Unit dose breakable vial with integrated brush applicator |
WO2012131583A2 (en) * | 2011-03-27 | 2012-10-04 | Microsert Ltd. | Miniature implanted drug delivery devices and inserter systems for introducing such devices |
WO2012144980A1 (en) * | 2011-04-18 | 2012-10-26 | Johnson & Johnson Vision Care, Inc. | Implantation instruments, system, and kit for punctal implants |
US10245178B1 (en) | 2011-06-07 | 2019-04-02 | Glaukos Corporation | Anterior chamber drug-eluting ocular implant |
EP4249059A3 (en) | 2011-06-28 | 2023-11-29 | ForSight Vision4, Inc. | An apparatus for collecting a sample of fluid from a reservoir chamber of a therapeutic device for the eye |
US8815278B2 (en) * | 2011-07-19 | 2014-08-26 | Abbott Cardiovascular Systems Inc. | Drug delivery device and method |
SI2755600T1 (sl) | 2011-09-16 | 2021-08-31 | Forsight Vision4, Inc. | Naprava za izmenjavo tekočine |
EP2771296B1 (en) | 2011-10-25 | 2017-09-27 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US10350139B2 (en) | 2011-10-25 | 2019-07-16 | Corning Incorporated | Pharmaceutical glass packaging assuring pharmaceutical sterility |
US8685106B2 (en) | 2011-11-15 | 2014-04-01 | Abraham Lin | Method of a pharmaceutical delivery system for use within a joint replacement |
EP2790681B9 (en) | 2011-11-18 | 2023-07-26 | Regeneron Pharmaceuticals, Inc. | Method of manufacturing an extended release pharmaceutical formulation comprising polymer coated protein microparticles using spray-drying |
US8765210B2 (en) | 2011-12-08 | 2014-07-01 | Aquesys, Inc. | Systems and methods for making gelatin shunts |
US9808373B2 (en) | 2013-06-28 | 2017-11-07 | Aquesys, Inc. | Intraocular shunt implantation |
US9610195B2 (en) | 2013-02-27 | 2017-04-04 | Aquesys, Inc. | Intraocular shunt implantation methods and devices |
US10080682B2 (en) | 2011-12-08 | 2018-09-25 | Aquesys, Inc. | Intrascleral shunt placement |
US8852136B2 (en) | 2011-12-08 | 2014-10-07 | Aquesys, Inc. | Methods for placing a shunt into the intra-scleral space |
US9241829B2 (en) | 2011-12-20 | 2016-01-26 | Abbott Medical Optics Inc. | Implantable intraocular drug delivery apparatus, system and method |
US10010448B2 (en) | 2012-02-03 | 2018-07-03 | Forsight Vision4, Inc. | Insertion and removal methods and apparatus for therapeutic devices |
JP6465490B2 (ja) | 2012-03-26 | 2019-02-06 | グローコス コーポレーション | インプラント送達装置 |
EP2787941A1 (en) * | 2012-10-30 | 2014-10-15 | WaveLight GmbH | Stabilizing lenticules used for refractive correction |
DE102012025143A1 (de) * | 2012-11-07 | 2014-05-08 | Heraeus Medical Gmbh | Verfahren zur Wirkstofffreisetzung und Wirkstofffreisetzungssysteme |
US9265458B2 (en) | 2012-12-04 | 2016-02-23 | Sync-Think, Inc. | Application of smooth pursuit cognitive testing paradigms to clinical drug development |
US9125723B2 (en) | 2013-02-19 | 2015-09-08 | Aquesys, Inc. | Adjustable glaucoma implant |
US10159600B2 (en) | 2013-02-19 | 2018-12-25 | Aquesys, Inc. | Adjustable intraocular flow regulation |
US9380976B2 (en) | 2013-03-11 | 2016-07-05 | Sync-Think, Inc. | Optical neuroinformatics |
JP6259510B2 (ja) * | 2013-03-14 | 2018-01-10 | ケーシーアイ ライセンシング インコーポレイテッド | 多微孔質導管 |
AU2014236455B2 (en) * | 2013-03-14 | 2018-07-12 | Forsight Vision4, Inc. | Systems for sustained intraocular delivery of low solubility compounds from a port delivery system implant |
US9597227B2 (en) * | 2013-03-15 | 2017-03-21 | Abbott Medical Optics Inc. | Trans-sclera portal for delivery of therapeutic agents |
US10517759B2 (en) | 2013-03-15 | 2019-12-31 | Glaukos Corporation | Glaucoma stent and methods thereof for glaucoma treatment |
EP4302736A3 (en) | 2013-03-28 | 2024-04-03 | ForSight Vision4, Inc. | Ophthalmic implant for delivering therapeutic substances |
US9849066B2 (en) | 2013-04-24 | 2017-12-26 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9707155B2 (en) | 2013-04-24 | 2017-07-18 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9717649B2 (en) | 2013-04-24 | 2017-08-01 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9713572B2 (en) | 2013-04-24 | 2017-07-25 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9707153B2 (en) | 2013-04-24 | 2017-07-18 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9717648B2 (en) | 2013-04-24 | 2017-08-01 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9603775B2 (en) | 2013-04-24 | 2017-03-28 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9700485B2 (en) | 2013-04-24 | 2017-07-11 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9700486B2 (en) | 2013-04-24 | 2017-07-11 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9707154B2 (en) | 2013-04-24 | 2017-07-18 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
US9839579B2 (en) | 2013-04-24 | 2017-12-12 | Corning Incorporated | Delamination resistant pharmaceutical glass containers containing active pharmaceutical ingredients |
WO2014179615A2 (en) * | 2013-05-01 | 2014-11-06 | Dae Won Park | Biodegradable copolymers, systems including the copolymers, and methods of forming and using same |
WO2014203181A1 (en) | 2013-06-20 | 2014-12-24 | Novartis Ag | Treatment of polypoidal choroidal vasculopathy |
JP2016522250A (ja) | 2013-06-20 | 2016-07-28 | ノバルティス アーゲー | 黄斑浮腫の治療におけるvegfアンタゴニストの使用 |
JP2016522249A (ja) | 2013-06-20 | 2016-07-28 | ノバルティス アーゲー | 脈絡膜血管新生の治療におけるvegfアンタゴニストの使用 |
CN105377891A (zh) | 2013-07-11 | 2016-03-02 | 诺华股份有限公司 | Vegf拮抗剂在治疗儿童患者的脉络膜视网膜新生血管和通透性疾病中的应用 |
US10093978B2 (en) | 2013-08-12 | 2018-10-09 | Genentech, Inc. | Compositions for detecting complement factor H (CFH) and complement factor I (CFI) polymorphisms |
BR122020011777B1 (pt) | 2013-11-14 | 2022-01-25 | AqueSys, Inc | Dispositivo de inserção para o tratamento de glaucoma |
US20160302965A1 (en) | 2013-12-06 | 2016-10-20 | Forsight Vision4, Inc. | Implantable therapeutic devices |
CN106413642B (zh) * | 2014-04-23 | 2019-03-08 | 塞罗斯医学有限责任公司 | 真空辅助药物递送装置 |
BR112016025312A2 (pt) | 2014-05-01 | 2017-10-17 | Genentech Inc | variantes de anticorpo, anticorpo anti-fator d, formulação farmacêutica, dispositivo de distribuição, utilização da formulação e de uma composição, composição e método de tratamento de uma desordem |
AU2015266850B2 (en) | 2014-05-29 | 2019-12-05 | Glaukos Corporation | Implants with controlled drug delivery features and methods of using same |
US10258503B2 (en) | 2014-07-15 | 2019-04-16 | Forsight Vision4, Inc. | Ocular implant delivery device and method |
MY182793A (en) | 2014-08-08 | 2021-02-05 | 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 |
US10500091B2 (en) * | 2014-11-10 | 2019-12-10 | Forsight Vision4, Inc. | Expandable drug delivery devices and methods of use |
FR3028410A1 (fr) | 2014-11-18 | 2016-05-20 | Pierre Coulon | Implant capsulaire multifonctionnel |
EP3233056B1 (en) | 2014-12-15 | 2023-11-15 | The Johns Hopkins University | Sunitinib formulations and methods for use thereof in treatment of ocular disorders |
US9687526B2 (en) | 2015-01-30 | 2017-06-27 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
US9750785B2 (en) | 2015-01-30 | 2017-09-05 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
US9375478B1 (en) | 2015-01-30 | 2016-06-28 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
US9925233B2 (en) | 2015-01-30 | 2018-03-27 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
US9744209B2 (en) | 2015-01-30 | 2017-08-29 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
US9937223B2 (en) | 2015-01-30 | 2018-04-10 | Par Pharmaceutical, Inc. | Vasopressin formulations for use in treatment of hypotension |
NZ737997A (en) | 2015-06-03 | 2019-03-29 | Aquesys Inc | Ab externo intraocular shunt placement |
AR106018A1 (es) | 2015-08-26 | 2017-12-06 | Achillion Pharmaceuticals Inc | Compuestos de arilo, heteroarilo y heterocíclicos para el tratamiento de trastornos médicos |
EP3340982B1 (en) | 2015-08-26 | 2021-12-15 | Achillion Pharmaceuticals, Inc. | Compounds for treatment of immune and inflammatory disorders |
WO2017035405A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Amino compounds for treatment of immune and inflammatory disorders |
WO2017035401A1 (en) | 2015-08-26 | 2017-03-02 | Achillion Pharmaceuticals, Inc. | Amide compounds for treatment of immune and inflammatory disorders |
US11925578B2 (en) | 2015-09-02 | 2024-03-12 | Glaukos Corporation | Drug delivery implants with bi-directional delivery capacity |
TWI799366B (zh) | 2015-09-15 | 2023-04-21 | 美商建南德克公司 | 胱胺酸結骨架平臺 |
WO2017053807A2 (en) | 2015-09-23 | 2017-03-30 | Genentech, Inc. | Optimized variants of anti-vegf antibodies |
WO2017053885A1 (en) | 2015-09-25 | 2017-03-30 | Glaukos Corporation | Punctal implants with controlled drug delivery features and methods of using same |
CA3001346A1 (en) * | 2015-10-16 | 2017-04-20 | Regeneron Pharmaceuticals, Inc. | Stable protein compositions |
EP3368074A2 (en) | 2015-10-30 | 2018-09-05 | Hoffmann-La Roche AG | Anti-factor d antibodies and conjugates |
EP3368090A1 (en) | 2015-10-30 | 2018-09-05 | H. Hoffnabb-La Roche Ag | Anti-factor d antibody variant conjugates and uses thereof |
EA038755B1 (ru) | 2015-11-12 | 2021-10-14 | Грейбаг Вижн, Инк. | Агрегирующие микрочастицы для обеспечения замедленного высвобождения терапевтического агента для внутриглазной доставки |
CN108430405B (zh) * | 2015-11-20 | 2021-04-13 | 弗赛特影像4股份有限公司 | 用于缓释药物递送装置的多孔结构 |
US11617680B2 (en) | 2016-04-05 | 2023-04-04 | Forsight Vision4, Inc. | Implantable ocular drug delivery devices |
AU2017252294B2 (en) * | 2016-04-20 | 2021-12-02 | Dose Medical Corporation | Bioresorbable ocular drug delivery device |
WO2017210316A1 (en) | 2016-05-31 | 2017-12-07 | Qura, Inc. | Implantable intraocular pressure sensors and methods of use |
BR112018074389A2 (pt) | 2016-06-02 | 2019-03-06 | Aquesys, Inc. | envio de fármaco intraocular |
AU2017290593A1 (en) | 2016-06-27 | 2019-01-03 | Achillion Pharmaceuticals, Inc. | Quinazoline and indole compounds to treat medical disorders |
TW202247855A (zh) | 2016-09-13 | 2022-12-16 | 美商愛力根公司 | 非蛋白梭菌毒素組成物 |
CN110087570B (zh) | 2016-11-14 | 2022-08-02 | 金尼恩公司 | 用于向子宫腔输送治疗剂的系统和方法 |
US11096993B2 (en) | 2016-12-08 | 2021-08-24 | Gary E. Borodic | Method of treating macular degeneration using botulinum toxin-based pharmaceuticals |
WO2018129056A1 (en) | 2017-01-04 | 2018-07-12 | The Research Foundation For The State University Of New York | Biomarker detection device |
US11523940B2 (en) | 2017-03-17 | 2022-12-13 | W. L. Gore & Associates, Inc. | Delivery aids for glaucoma shunts |
MX2019011141A (es) | 2017-03-22 | 2019-11-05 | Genentech Inc | Composiciones de anticuerpo optimizadas para el tratamiento de trastornos oculares. |
CN111201040A (zh) | 2017-05-10 | 2020-05-26 | 灰色视觉公司 | 用于医学疗法的缓释微粒及其悬浮液 |
JP6883257B2 (ja) * | 2017-05-16 | 2021-06-09 | 株式会社豊田中央研究所 | 還元反応用固体触媒 |
CN111065359A (zh) | 2017-06-16 | 2020-04-24 | 埃斯库莱泰克股份有限公司 | 热反应性聚合物及其用途 |
US11534283B2 (en) * | 2017-09-06 | 2022-12-27 | Children's National Medical Center | Porous implantable devices |
CN113893085A (zh) | 2017-10-06 | 2022-01-07 | 格劳科斯公司 | 用于递送多个眼部植入物的系统和方法 |
EP3476384A1 (en) * | 2017-10-25 | 2019-05-01 | F. Hoffmann-La Roche AG | Artificial vitreous humor for the investigation of drugs and drug formulations |
USD846738S1 (en) | 2017-10-27 | 2019-04-23 | Glaukos Corporation | Implant delivery apparatus |
US11246753B2 (en) | 2017-11-08 | 2022-02-15 | Aquesys, Inc. | Manually adjustable intraocular flow regulation |
WO2019103906A1 (en) | 2017-11-21 | 2019-05-31 | Forsight Vision4, Inc. | Fluid exchange apparatus for expandable port delivery system and methods of use |
US11135089B2 (en) | 2018-03-09 | 2021-10-05 | Aquesys, Inc. | Intraocular shunt inserter |
US10952898B2 (en) | 2018-03-09 | 2021-03-23 | Aquesys, Inc. | Intraocular shunt inserter |
CN112218528B (zh) * | 2018-03-16 | 2022-10-21 | 诺埃尔·埃尔曼 | 物质可控的释放的装置 |
JP2021519337A (ja) | 2018-03-26 | 2021-08-10 | シー4 セラピューティクス, インコーポレイテッド | Ikarosの分解のためのセレブロン結合剤 |
CN112702983B (zh) | 2018-04-19 | 2023-06-30 | 斯皮拉尔诊疗有限公司 | 内耳药物递送装置和使用方法 |
US20210315735A1 (en) * | 2018-08-03 | 2021-10-14 | The Johns Hopkins University | Retinal implantation device |
JP2021535112A (ja) | 2018-08-20 | 2021-12-16 | アキリオン ファーマシューティカルズ,インコーポレーテッド | 補体d因子の医学的障害の治療のための医薬化合物 |
CN117159273A (zh) * | 2018-08-31 | 2023-12-05 | 新世界医学有限公司 | 用于眼部植入过程的插入器装置 |
BR112021004263A2 (pt) | 2018-09-06 | 2021-05-25 | Achillion Pharmaceuticals, Inc. | formas mórficas de danicopano |
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 |
US11779739B2 (en) * | 2018-12-21 | 2023-10-10 | Perfect Ip, Llc | Drug delivery system and method |
CA3125155A1 (en) * | 2018-12-28 | 2020-07-02 | Mott Corporation | Devices, systems and methods for an implantable drug delivery device |
WO2021183555A1 (en) * | 2020-03-10 | 2021-09-16 | Achillion Pharmaceuticals, Inc. | Ocular drug depot for complement-mediated disorders |
CA3169967A1 (en) | 2020-03-24 | 2021-09-30 | Genentech, Inc. | Tie2-binding agents and methods of use |
KR20230061458A (ko) | 2020-09-04 | 2023-05-08 | 에프. 호프만-라 로슈 아게 | Vegf-a 및 ang2에 결합하는 항체 및 사용 방법 |
EP3978065A1 (de) | 2020-10-02 | 2022-04-06 | Heraeus Medical GmbH | Implantat zur lokalen wirkstofffreisetzung |
US20220126077A1 (en) * | 2020-10-26 | 2022-04-28 | Christopher Green | Treatment for Dry Eyes |
WO2023196623A1 (en) | 2022-04-08 | 2023-10-12 | Genentech, Inc. | Incision guide tool for ocular device implantation and methods of use |
WO2023217933A1 (en) | 2022-05-11 | 2023-11-16 | F. Hoffmann-La Roche Ag | Antibody that binds to vegf-a and il6 and methods of use |
US20240108501A1 (en) * | 2022-09-30 | 2024-04-04 | FUJIFILM Cellular Dynamics, Inc. | Apparatus and methods for delivery of cell compositions |
US11779553B1 (en) | 2022-11-28 | 2023-10-10 | Atif B. D. Collins | Methods and devices for treatment of eyelid ptosis |
Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5466233A (en) * | 1994-04-25 | 1995-11-14 | Escalon Ophthalmics, Inc. | Tack for intraocular drug delivery and method for inserting and removing same |
US5972369A (en) * | 1997-03-31 | 1999-10-26 | Alza Corporation | Diffusional implantable delivery system |
US20030014036A1 (en) * | 2001-06-12 | 2003-01-16 | Varner Signe Erickson | Reservoir device for intraocular drug delivery |
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 |
JP2006526430A (ja) * | 2003-02-18 | 2006-11-24 | (オーエスアイ) アイテック インク. | 薬物送達装置およびその装置を充填するためのシリンジ |
Family Cites Families (435)
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 |
US3986510A (en) * | 1971-09-09 | 1976-10-19 | Alza Corporation | Bioerodible ocular device |
US3828777A (en) | 1971-11-08 | 1974-08-13 | Alza Corp | Microporous ocular device |
US3826258A (en) | 1972-02-07 | 1974-07-30 | S Abraham | Gradual release medicine carrier |
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 |
US4057619A (en) | 1975-06-30 | 1977-11-08 | Alza Corporation | Ocular therapeutic system with selected membranes for administering ophthalmic drug |
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 |
US4008719A (en) | 1976-02-02 | 1977-02-22 | Alza Corporation | Osmotic system having laminar arrangement for programming delivery of active agent |
US4014334A (en) | 1976-02-02 | 1977-03-29 | Alza Corporation | Laminated osmotic system for dispensing beneficial agent |
US4111203A (en) | 1976-11-22 | 1978-09-05 | Alza Corporation | Osmotic system with means for improving delivery kinetics of system |
US4111201A (en) | 1976-11-22 | 1978-09-05 | Alza Corporation | Osmotic system for delivering selected beneficial agents having varying degrees of solubility |
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 |
ATE9059T1 (de) | 1980-01-28 | 1984-09-15 | Merck & Co. Inc. | Ophthalmische kohlensaure anhydrase-inhibitoren enthaltende einlagen zur verringerung intraokularer hypertension. |
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 |
US4475916A (en) | 1982-03-18 | 1984-10-09 | Merck & Co., Inc. | Osmotic drug delivery system |
US4439196A (en) | 1982-03-18 | 1984-03-27 | 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 |
US5053030A (en) | 1984-11-07 | 1991-10-01 | Herrick Robert S | Intracanalicular implant for horizontal canalicular blockade treatment of the eye |
US5049142A (en) | 1984-11-07 | 1991-09-17 | 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 |
FR2582221B1 (fr) | 1985-05-21 | 1987-09-25 | Applied Precision Ltd | Dispositif implantable d'injection chronique d'une substance, notamment therapeutique |
CA1314481C (en) | 1986-12-23 | 1993-03-16 | Marcel B. Bally | Liposomal preparation and antibiotic |
US4840615A (en) | 1985-09-30 | 1989-06-20 | Mcghan Medical Corporation | Self-sealing injection reservoir |
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 |
US4781680A (en) | 1987-03-02 | 1988-11-01 | Vir Engineering | Resealable injection site |
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 |
AU4951690A (en) | 1988-12-30 | 1990-08-01 | David M. Anderson | 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 |
US5013459A (en) | 1989-11-09 | 1991-05-07 | Dow Corning Corporation | Opthalmic fluid dispensing method |
US5164188A (en) | 1989-11-22 | 1992-11-17 | Visionex, Inc. | Biodegradable ocular implants |
US5092837A (en) | 1989-12-20 | 1992-03-03 | Robert Ritch | Method for the treatment of glaucoma |
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 |
US5197882A (en) | 1990-05-14 | 1993-03-30 | Gary R. Jernberg | Periodontal barrier and method for aiding periodontal tissue regeneration agents |
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 |
US5213576A (en) | 1991-06-11 | 1993-05-25 | Cordis Corporation | Therapeutic porous balloon catheter |
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 |
US5830492A (en) | 1992-02-24 | 1998-11-03 | Encelle, Inc. | Bioartificial devices and cellular matrices therefor |
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 |
US5576480A (en) | 1992-11-06 | 1996-11-19 | Pall Corporation | System and method for testing the integrity of porous elements |
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 |
US5516522A (en) * | 1994-03-14 | 1996-05-14 | Board Of Supervisors Of Louisiana State University | Biodegradable porous device for long-term drug delivery with constant rate release and method of making the same |
US5578042A (en) | 1994-03-14 | 1996-11-26 | Cumming; J. Stuart | Ophthalmic kit and method for lens insertion |
AUPM897594A0 (en) | 1994-10-25 | 1994-11-17 | Daratech Pty Ltd | Controlled release container |
AU708529B2 (en) | 1994-11-10 | 1999-08-05 | University Of Kentucky Research Foundation, The | 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 |
US5704915A (en) | 1995-02-14 | 1998-01-06 | Therex Limited Partnership | Hemodialysis access device |
US5651979A (en) | 1995-03-30 | 1997-07-29 | Gel Sciences, Inc. | Apparatus and method for delivering a biologically active compound into a biological environment |
US5554132A (en) | 1995-03-30 | 1996-09-10 | Abbott Laboratories | Hand grip for use with syringe |
CN1283324C (zh) | 1995-05-14 | 2006-11-08 | 奥普通诺尔有限公司 | 眼内植入物、植入装置、以及植入方法 |
IL113723A (en) | 1995-05-14 | 2002-11-10 | Optonol Ltd | Intraocular implant |
US5609629A (en) * | 1995-06-07 | 1997-03-11 | Med Institute, Inc. | Coated implantable medical device |
US5989216A (en) | 1995-06-29 | 1999-11-23 | Sims Deltec, Inc. | Access portal and method |
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 |
US6283951B1 (en) * | 1996-10-11 | 2001-09-04 | Transvascular, Inc. | Systems and methods for delivering drugs to selected locations within 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 |
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 |
DE69917484T2 (de) | 1998-12-14 | 2005-05-12 | Tre Esse Progettazione Biomedica S.R.L. | Kathetersystem zur durchführung einer intramyokardialen therapeutischen behandlung |
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 |
AU770975B2 (en) | 1999-06-18 | 2004-03-11 | Alcon Laboratories, Inc. | Topical ophthalmic mast cell stabilizers for treating allergic eye diseases |
US6551291B1 (en) | 1999-08-04 | 2003-04-22 | Johns Hopkins University | Non-traumatic infusion cannula and treatment methods using same |
US6638263B1 (en) | 1999-10-12 | 2003-10-28 | Durect Corporation | Regulation of drug delivery through flow diversion |
US6416777B1 (en) | 1999-10-21 | 2002-07-09 | Alcon Universal Ltd. | Ophthalmic drug delivery device |
ATE283013T1 (de) | 1999-10-21 | 2004-12-15 | Alcon Inc | Medikamentenzuführvorrichtung |
US6331313B1 (en) | 1999-10-22 | 2001-12-18 | Oculex Pharmaceticals, Inc. | Controlled-release biocompatible ocular drug delivery implant devices and methods |
US20050119737A1 (en) | 2000-01-12 | 2005-06-02 | Bene Eric A. | Ocular implant and methods for making and using same |
US20030212383A1 (en) | 2001-01-05 | 2003-11-13 | Dana Cote | System and methods for reducing intraocular pressure |
RU2262331C2 (ru) | 2000-01-12 | 2005-10-20 | Бектон, Дикинсон Энд Компани | Шунт, имплантат, система и способ снижения внутриглазного давления, способ изготовления имплантата для роговицы (варианты) |
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 |
WO2001068377A1 (fr) | 2000-03-13 | 2001-09-20 | Seiko Epson Corporation | Procede de traitement de surface, article traite en surface et dispositif de traitement de surface |
US7141152B2 (en) | 2000-03-16 | 2006-11-28 | Le Febre David A | Analyte species separation system |
US6945969B1 (en) | 2000-03-31 | 2005-09-20 | Medtronic, Inc. | Catheter for target specific drug delivery |
US20050277864A1 (en) | 2000-04-14 | 2005-12-15 | David Haffner | Injectable gel implant for glaucoma treatment |
US7708711B2 (en) | 2000-04-14 | 2010-05-04 | Glaukos Corporation | Ocular implant with therapeutic agents and methods thereof |
US20040208910A1 (en) | 2000-04-26 | 2004-10-21 | Control Delivery Systems, Inc. | Sustained release device and method for ocular delivery of adrenergic agents |
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 |
DE60131773T2 (de) | 2000-09-06 | 2008-04-10 | Alcon Inc. | Beschichtungsmittel mit veränderbarer klebrigkeit für augenimplantate |
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 |
US6756058B2 (en) | 2001-01-03 | 2004-06-29 | Bausch & Lomb Incorporated | Sustained release drug delivery devices with multiple agents |
WO2002053129A1 (en) | 2001-01-03 | 2002-07-11 | Bausch & Lomb Incorporated | Sustained release drug delivery devices with prefabricated permeable plugs |
DE60130928T2 (de) | 2001-01-03 | 2008-07-17 | Bausch & Lomb Inc. | Vorrichtung zur verzögerten wirkstofffreisetzung mit beschichteten medikamentenkernen |
JP4657577B2 (ja) | 2001-01-09 | 2011-03-23 | マイクロチップス・インコーポレーテッド | 眼への適用および他への適用のための可撓性マイクロチップデバイス |
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 |
JP4426286B2 (ja) | 2001-07-10 | 2010-03-03 | テバ ファーマシューティカル インダストリーズ リミティド | 0次、0次−二相性、上昇型又は下降型薬物放出のための薬物送達システム |
IL144446A0 (en) * | 2001-07-19 | 2002-05-23 | Prochon Biotech Ltd | Plasma protein matrices and methods for their preparation |
EP1409065B1 (en) | 2001-07-23 | 2007-01-17 | Alcon, Inc. | Ophthalmic drug delivery device |
AU2002319606B2 (en) | 2001-07-23 | 2006-09-14 | Alcon, Inc. | Ophthalmic drug delivery device |
CN1538826A (zh) | 2001-08-03 | 2004-10-20 | 青光眼研究科技公司 | 治疗青光眼及老花眼的方法及其内巩膜植入物 |
RU2311892C2 (ru) | 2001-08-29 | 2007-12-10 | КАРВАЛХО Рикардо А. П. ДЕ | Имплантируемая и герметизируемая система для однонаправленной доставки терапевтических препаратов в ткани |
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 |
CN1585627A (zh) | 2001-09-14 | 2005-02-23 | 弗朗西斯J·马丁 | 用于持续释放治疗剂的显微制作的纳米微孔装置 |
KR20040039428A (ko) | 2001-09-28 | 2004-05-10 | 산텐 세이야꾸 가부시키가이샤 | 약물-폴리에틸렌글리콜 결합체를 함유하는 안조직 내 주입제 |
US20030118649A1 (en) | 2001-10-04 | 2003-06-26 | Jinming Gao | Drug delivery devices and methods |
US8663687B2 (en) | 2001-10-12 | 2014-03-04 | Monosol Rx, Llc | Film compositions for delivery of actives |
US20070088335A1 (en) | 2001-10-24 | 2007-04-19 | Med-El Elektromedizinische Geraete Gmbh | Implantable neuro-stimulation electrode with fluid reservoir |
US7003405B1 (en) | 2001-10-25 | 2006-02-21 | Sandia Corporation | Methods for characterizing subsurface volatile contaminants using in-situ sensors |
JP2005509883A (ja) | 2001-11-15 | 2005-04-14 | アリックス,インコーポレーテッド | 試料チップ |
US20030120217A1 (en) | 2001-12-21 | 2003-06-26 | Abergel R. Patrick | Methods and devices for sclerotherapy |
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 |
MXPA04008903A (es) | 2002-03-11 | 2004-11-26 | Alcon Inc | Sistema de suministro de farmaco implantable. |
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 |
US6936033B2 (en) | 2002-06-14 | 2005-08-30 | Medtronic, Inc. | Multiple ratio fluid dispenser |
US7939094B2 (en) | 2002-06-19 | 2011-05-10 | Boston Scientific Scimed, Inc. | Multiphase polymeric drug release region |
WO2004006889A1 (en) | 2002-07-15 | 2004-01-22 | Alcon, Inc. | Bioerodible film for ophthalmic drug delivery |
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 |
US20070219632A1 (en) * | 2002-08-02 | 2007-09-20 | David Castillejos | Method and intra-sclera implant for treatment of glaucoma and presbyopia |
US7468065B2 (en) | 2002-09-18 | 2008-12-23 | Allergan, Inc. | Apparatus for delivery of ocular implants |
AU2003272575B2 (en) | 2002-09-18 | 2007-11-08 | Allergan, Inc. | Methods and apparatus for delivery of ocular implants |
US20050143363A1 (en) | 2002-09-29 | 2005-06-30 | Innorx, Inc. | Method for subretinal administration of therapeutics including steroids; method for localizing pharmacodynamic action at the choroid of the retina; and related methods for treatment and/or prevention of retinal diseases |
US7794437B2 (en) | 2003-01-24 | 2010-09-14 | Doheny Retina Institute | Reservoirs with subretinal cannula for subretinal drug delivery |
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 |
CA2524271C (en) | 2003-05-02 | 2012-09-04 | Surmodics, Inc. | Controlled release bioactive agent delivery device |
CA2529048A1 (en) | 2003-06-13 | 2005-02-24 | Becton, Dickinson And Company | Improved intra-dermal delivery of biologically active 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 |
US20040260380A1 (en) | 2003-06-18 | 2004-12-23 | D-Crown Ltd | Devices for delivering 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 |
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 |
ZA200508654B (en) | 2003-07-10 | 2007-01-31 | Alcon Inc | Ophthalmic drug delivery device |
FI120333B (fi) | 2003-08-20 | 2009-09-30 | Bioretec Oy | Huokoinen lääketieteellinen väline ja menetelmä sen valmistamiseksi |
AU2004274026A1 (en) | 2003-09-18 | 2005-03-31 | Macusight, Inc. | Transscleral delivery |
US20050181018A1 (en) * | 2003-09-19 | 2005-08-18 | Peyman Gholam A. | Ocular drug delivery |
NZ546730A (en) | 2003-09-24 | 2008-04-30 | Medi Stream Pty Ltd | Medication holder |
AU2006225241B2 (en) | 2003-09-24 | 2008-07-17 | Tianda Pharmaceuticals (Australia) Pty Limited | 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 |
BRPI0507690A (pt) | 2004-02-12 | 2007-07-24 | Neovista Inc | métodos e aparelho para a braquiterapia intra-ocular |
US7276050B2 (en) | 2004-03-02 | 2007-10-02 | Alan Franklin | Trans-scleral drug delivery method and apparatus |
US20050256499A1 (en) | 2004-03-03 | 2005-11-17 | Pettis Ronald J | Methods and devices for improving delivery of a substance to skin |
US20070059336A1 (en) | 2004-04-30 | 2007-03-15 | Allergan, Inc. | Anti-angiogenic sustained release intraocular implants and related methods |
US8685435B2 (en) | 2004-04-30 | 2014-04-01 | Allergan, Inc. | Extended release biodegradable ocular implants |
US20060182783A1 (en) | 2004-04-30 | 2006-08-17 | Allergan, Inc. | Sustained release intraocular drug delivery systems |
US20050244472A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Intraocular drug delivery systems containing excipients with reduced toxicity and related methods |
US20050244469A1 (en) | 2004-04-30 | 2005-11-03 | Allergan, Inc. | Extended therapeutic effect ocular implant treatments |
US8591885B2 (en) | 2004-04-30 | 2013-11-26 | Allergan, Inc. | Carbonic anhydrase inhibitor sustained release intraocular drug delivery systems |
WO2006085908A2 (en) | 2004-06-01 | 2006-08-17 | Microchips, Inc. | Devices and methods for measuring and enhancing drug or analyte transport to/from medical implant |
US20060110428A1 (en) | 2004-07-02 | 2006-05-25 | Eugene Dejuan | Methods and devices for the treatment of ocular conditions |
US20060020253A1 (en) * | 2004-07-26 | 2006-01-26 | Prescott Anthony D | Implantable device having reservoir with controlled release of medication and method of manufacturing the same |
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 |
WO2006015385A2 (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 |
AU2005292145C1 (en) | 2004-10-01 | 2011-07-21 | Ramscor, Inc. | Conveniently implantable sustained release drug compositions |
US20080038316A1 (en) | 2004-10-01 | 2008-02-14 | Wong Vernon G | Conveniently implantable sustained release drug compositions |
CN101437478A (zh) | 2004-10-04 | 2009-05-20 | Qlt美国有限公司 | 聚合送递制剂的眼部送递 |
WO2006044614A2 (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 . |
EP1817003B1 (en) * | 2004-10-29 | 2018-02-21 | The Regents of The University of California | Porous silicon microparticles 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 |
WO2006082588A2 (en) | 2005-02-07 | 2006-08-10 | Pharmalight Inc. | Method and device for ophthalmic administration of active pharmaceutical ingredients |
US8663639B2 (en) | 2005-02-09 | 2014-03-04 | Santen Pharmaceutical Co., Ltd. | Formulations for treating ocular diseases and conditions |
TW200640443A (en) | 2005-02-23 | 2006-12-01 | Alcon Inc | Methods for treating ocular angiogenesis, retinal edema, retinal ischemia, and diabetic retinopathy using selective RTK inhibitors |
US20060233858A1 (en) | 2005-03-08 | 2006-10-19 | Allergan, Inc. | Systems and methods providing targeted intraocular drug delivery |
KR20070121754A (ko) | 2005-03-21 | 2007-12-27 | 마커사이트, 인코포레이티드 | 질환 또는 상태의 치료를 위한 약물 송달 시스템 |
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 |
US20070066138A1 (en) | 2005-04-05 | 2007-03-22 | The Ohio State University Research Foundation | Diffusion Delivery Systems and Methods of Fabrication |
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 |
US20070088414A1 (en) | 2005-05-25 | 2007-04-19 | Campbell Robert L | Particulate formulations for intradermal delivery of biologically active agents |
JP2009501700A (ja) | 2005-06-17 | 2009-01-22 | ダイナミス・セラピユーテイクス・インコーポレーテツド | 炎症状態の治療 |
US20060292222A1 (en) * | 2005-06-21 | 2006-12-28 | Matthew Jonasse | Drug delivery device having zero or near zero-order release kinetics |
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 |
US20110076278A1 (en) | 2005-08-02 | 2011-03-31 | Mehran Khodadoust | Modulators of Hypoxia Inducible Factor-1 and Related Uses for the Treatment of Ocular Disorders |
WO2007021671A2 (en) | 2005-08-10 | 2007-02-22 | 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 |
EP1924306A2 (en) | 2005-09-16 | 2008-05-28 | BG Implant, Inc. | Glaucoma treatment devices and methods |
JP2009508593A (ja) | 2005-09-16 | 2009-03-05 | (オーエスアイ)アイテツク・インコーポレーテツド | 眼科用シリンジ |
US20070072933A1 (en) | 2005-09-26 | 2007-03-29 | Peyman Gholam A | Delivery of an ocular agent |
US20080003219A1 (en) | 2005-09-26 | 2008-01-03 | Minu, L.L.C. | Delivery of an ocular agent |
US20070071756A1 (en) | 2005-09-26 | 2007-03-29 | Peyman Gholam A | Delivery of an agent to ameliorate inflammation |
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 |
US20080167600A1 (en) | 2005-09-26 | 2008-07-10 | Peyman Gholam A | Device for delivery of an agent to the eye and other sites |
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 |
WO2007047744A2 (en) | 2005-10-14 | 2007-04-26 | Alcon, Inc. | Method for treating primary and secondary forms of glaucoma |
US20080125406A1 (en) | 2005-10-14 | 2008-05-29 | Robin Alan L | Method for Treating Primary and Secondary Forms of Glaucoma |
PL2500030T5 (pl) | 2005-11-04 | 2019-02-28 | Genentech, Inc. | Zastosowanie inhibitorów drogi aktywacji dopełniacza w leczeniu chorób oczu |
MX2008006379A (es) | 2005-11-29 | 2009-03-03 | Smithkline Beecham Corp | Metodo de tratamiento. |
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 |
WO2007066339A1 (en) | 2005-12-07 | 2007-06-14 | Ramot At Tel Aviv University Ltd. | Drug-delivering composite structures |
US20070131611A1 (en) | 2005-12-13 | 2007-06-14 | General Electric Company | Membrane-based article and associated method |
US20070131610A1 (en) | 2005-12-13 | 2007-06-14 | General Electric Company | Membrane-based apparatus and associated method |
EP3632385A1 (en) | 2006-01-17 | 2020-04-08 | Novartis AG | Glaucoma treatment device |
US9084662B2 (en) | 2006-01-17 | 2015-07-21 | Transcend Medical, Inc. | Drug delivery treatment device |
US20080216736A1 (en) | 2006-01-19 | 2008-09-11 | Takeda San Diego, Inc. | Microfluidic device with diffusion between adjacent lumens |
WO2007100986A2 (en) | 2006-02-24 | 2007-09-07 | Rosetta Inpharmatics Llc | 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 |
US20070212388A1 (en) | 2006-03-08 | 2007-09-13 | Sahajanand Medical Technologies Pvt. Ltd. | Compositions comprising porous articles and uses in implantable medical devices |
EP1998829B1 (en) | 2006-03-14 | 2011-02-09 | University Of Southern California | Mems device for delivery of therapeutic agents |
TW200800230A (en) | 2006-03-31 | 2008-01-01 | Dynamis Therapeutics Inc | Composition and method related to fructosamine-3-kinase inhibitors |
KR20110038144A (ko) | 2006-03-31 | 2011-04-13 | 큐엘티 플러그 딜리버리, 인코포레이티드 | 비루관계에 대한 약물 전달 방법, 구조, 및 조성물 |
US7547300B2 (en) | 2006-04-12 | 2009-06-16 | Icu Medical, Inc. | Vial adaptor for regulating pressure |
US8007461B2 (en) | 2006-04-18 | 2011-08-30 | Pingan Huo | Sterile drug-mixing syringe |
US20080027304A1 (en) | 2006-04-18 | 2008-01-31 | Pardo Geoffrey B | Intraocular pressure attenuation device |
US8197435B2 (en) | 2006-05-02 | 2012-06-12 | Emory University | Methods and devices for drug delivery to ocular tissue using microneedle |
WO2007131050A2 (en) | 2006-05-02 | 2007-11-15 | Georgia Tech Research Corporation | Method 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 |
CN101448534B (zh) | 2006-05-17 | 2012-10-03 | 生物技术公司 | 用于医疗植入物的各向异性纳米多孔涂层 |
US20080124372A1 (en) | 2006-06-06 | 2008-05-29 | Hossainy Syed F A | Morphology profiles for control of agent release rates from polymer matrices |
EP2037882B1 (en) | 2006-06-28 | 2014-12-10 | SurModics, Inc. | Combination degradable and non-degradable matrices for active agent delivery |
TW200815045A (en) | 2006-06-29 | 2008-04-01 | Jazz Pharmaceuticals Inc | Pharmaceutical compositions of ropinirole and methods of use thereof |
WO2008009120A2 (en) | 2006-07-19 | 2008-01-24 | Noab Biodiscoveries Inc. | Method and device to extract components contained in a fluid |
CA2657380A1 (en) | 2006-07-20 | 2008-01-24 | 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 |
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 |
US9149750B2 (en) | 2006-09-29 | 2015-10-06 | Mott Corporation | Sinter bonded porous metallic coatings |
US20080089923A1 (en) | 2006-09-29 | 2008-04-17 | Burkstrand Michael J | Biodegradable ocular implants and methods for treating ocular conditions |
TW200817039A (en) | 2006-10-06 | 2008-04-16 | 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 |
US8784898B2 (en) | 2006-10-25 | 2014-07-22 | Revalesio Corporation | Methods of wound care and treatment |
AU2007349224B2 (en) | 2006-10-25 | 2014-04-03 | Revalesio Corporation | Methods of wound care and treatment |
US8784897B2 (en) | 2006-10-25 | 2014-07-22 | Revalesio Corporation | Methods of therapeutic treatment of eyes |
WO2008052145A2 (en) | 2006-10-25 | 2008-05-02 | Revalesio Corporation | Methods of therapeutic treatment of eyes and other human tissues using an oxygen-enriched solution |
US8609148B2 (en) | 2006-10-25 | 2013-12-17 | Revalesio Corporation | Methods of therapeutic treatment of eyes |
US8506515B2 (en) | 2006-11-10 | 2013-08-13 | Glaukos Corporation | Uveoscleral shunt and methods for implanting same |
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 |
US20090263346A1 (en) | 2006-12-05 | 2009-10-22 | David Taft | Systems and methods for delivery of drugs |
WO2008070118A1 (en) | 2006-12-05 | 2008-06-12 | Landec Corporation | Drug delivery |
WO2008073295A2 (en) | 2006-12-07 | 2008-06-19 | Surmodics, Inc. | Latent stabilization of bioactive agents releasable from implantable medical articles |
US20080147021A1 (en) | 2006-12-15 | 2008-06-19 | Jani Dharmendra M | Drug delivery devices |
WO2008076544A2 (en) | 2006-12-18 | 2008-06-26 | Alcon Research, Ltd. | Devices and methods for ophthalmic drug delivery |
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 |
JP5201744B2 (ja) | 2007-01-09 | 2013-06-05 | フォヴェア ファルマシューティカル | 眼内注射装置 |
AU2008206953A1 (en) | 2007-01-19 | 2008-07-24 | 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 |
EP2236518B1 (en) | 2007-03-14 | 2014-08-06 | Alexion Cambridge Corporation | Humaneered anti-factor B antibody |
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 |
KR20100014486A (ko) | 2007-04-30 | 2010-02-10 | 알콘 리서치, 리미티드 | 보체 인자 d의 저해제를 사용한 연령 관련 황반변성의 치료 |
US20080286338A1 (en) | 2007-05-15 | 2008-11-20 | Boston Foundation For Sight | Drug delivery system with scleral lens |
AR066660A1 (es) | 2007-05-23 | 2009-09-02 | Genentech Inc | Prevencion y tratamiento de condiciones del ojo asociadas con su complemento |
US8231892B2 (en) | 2007-05-24 | 2012-07-31 | Allergan, Inc. | Biodegradable drug delivery system |
CA2688344C (en) | 2007-05-29 | 2019-09-03 | Angiochem, Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
US9365634B2 (en) | 2007-05-29 | 2016-06-14 | Angiochem Inc. | Aprotinin-like polypeptides for delivering agents conjugated thereto to tissues |
CN101327356A (zh) | 2007-06-21 | 2008-12-24 | 庄臣及庄臣视力保护公司 | 用于输送活性剂的泪点塞 |
US20090036827A1 (en) | 2007-07-31 | 2009-02-05 | Karl Cazzini | Juxtascleral Drug Delivery and Ocular Implant System |
WO2009023615A1 (en) | 2007-08-10 | 2009-02-19 | Trustees Of Tufts College | Tubular silk compositions and methods of use thereof |
US7901726B2 (en) | 2007-08-31 | 2011-03-08 | Boston Scientific Scimed, Inc. | Porous medical articles for therapeutic agent delivery |
CA2698580C (en) | 2007-09-07 | 2016-10-11 | Qlt Plug Delivery, Inc. | Lacrimal implant detection |
KR101996336B1 (ko) | 2007-09-07 | 2019-07-04 | 마티 테라퓨틱스 인코포레이티드 | 치료 약제의 서방성 약물 코어 |
EP2205192A2 (en) | 2007-09-07 | 2010-07-14 | QLT Plug Delivery, Inc. | Insertion and extraction tools for lacrimal implants |
US8974809B2 (en) * | 2007-09-24 | 2015-03-10 | Boston Scientific Scimed, Inc. | Medical devices having a filter insert for controlled diffusion |
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 |
GB0718737D0 (en) | 2007-09-25 | 2007-11-07 | Glaxo Group Ltd | Antibodies |
US20090214601A1 (en) | 2007-09-28 | 2009-08-27 | Chappa Ralph A | Porous Drug Delivery Devices and Related Methods |
US20100100043A1 (en) | 2007-10-05 | 2010-04-22 | Racenet Danyel J | Flexible Access Device For Use In Surgical Procedure |
KR101511497B1 (ko) | 2007-10-05 | 2015-04-13 | 코비디엔 엘피 | 수술 절차에 사용하기 위한 밀봉부 고정구 |
US20100310665A1 (en) | 2007-10-25 | 2010-12-09 | Revalesio Corporation | Bacteriostatic or bacteriocidal compositions and methods |
US20100303917A1 (en) | 2007-10-25 | 2010-12-02 | Revalesio Corporation | Compositions and methods for treating cystic fibrosis |
US10125359B2 (en) | 2007-10-25 | 2018-11-13 | Revalesio Corporation | Compositions and methods for treating inflammation |
AU2008316708A1 (en) | 2007-10-25 | 2009-04-30 | Revalesio Corporation | Bacteriostatic or bacteriocidal compositions and methods |
US9523090B2 (en) | 2007-10-25 | 2016-12-20 | Revalesio Corporation | Compositions and methods for treating inflammation |
US20100004189A1 (en) | 2007-10-25 | 2010-01-07 | Revalesio Corporation | Compositions and methods for treating cystic fibrosis |
US20090227018A1 (en) | 2007-10-25 | 2009-09-10 | Revalesio Corporation | Compositions and methods for modulating cellular membrane-mediated intracellular signal transduction |
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 |
WO2010062628A1 (en) | 2008-10-27 | 2010-06-03 | Revalesio Corporation | Compositions and methods for treating asthma and other lung disorders |
US20100303918A1 (en) | 2007-10-25 | 2010-12-02 | Revalesio Corporation | Compositions and methods for treating asthma and other lung disorders |
US20100008997A1 (en) | 2007-10-25 | 2010-01-14 | Revalesio Corporation | Compositions and methods for treating asthma and other lung disorders |
BRPI0819175A2 (pt) | 2007-11-05 | 2015-05-05 | Bausch & Lomb | Composição farmacêutica oftálmica, e, método para proporcionar disponibilidade estendida de um componente farmacêutico em um ambiente ocular de um indivíduo, e, uso de pelo menos um componente farmacêutico, pelo menos um material imiscível em água e opcionalmente um composto modificador de viscosidade |
US8545457B2 (en) | 2007-11-08 | 2013-10-01 | Terumo Kabushiki Kaisha | Sprayer |
US8114883B2 (en) | 2007-12-04 | 2012-02-14 | Landec Corporation | Polymer formulations for delivery of bioactive materials |
EP2666510B1 (en) | 2007-12-20 | 2017-10-18 | University Of Southern California | Apparatus for controlled delivery of therapeutic agents |
US8414646B2 (en) | 2007-12-27 | 2013-04-09 | Forsight Labs, Llc | Intraocular, accommodating lens and methods of use |
US20090192493A1 (en) | 2008-01-03 | 2009-07-30 | University Of Southern California | Implantable drug-delivery devices, and apparatus and methods for refilling the devices |
WO2009089409A2 (en) | 2008-01-10 | 2009-07-16 | 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 |
WO2009097468A2 (en) | 2008-01-29 | 2009-08-06 | Kliman Gilbert H | Drug delivery devices, kits and methods therefor |
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 |
WO2009117112A2 (en) | 2008-03-21 | 2009-09-24 | Novartis Ag | Powder dispersion apparatus, method of making and using the apparatus, components that can be used on the apparatus and other devices, and various active agents |
KR101674492B1 (ko) | 2008-03-31 | 2016-11-09 | 닛토덴코 가부시키가이샤 | 침투제 전달 시스템 및 그의 사용방법 |
DK2285439T3 (en) | 2008-04-04 | 2014-03-24 | Nektar Therapeutics | Aerosoliseringsanorning |
US8801665B2 (en) | 2008-04-10 | 2014-08-12 | Henry Ford Health System | Apparatus and method for controlled depth of injection into myocardial tissue |
US20090258069A1 (en) | 2008-04-15 | 2009-10-15 | John Burnier | Delivery of LFA-1 antagonists to the gastrointestinal system |
CA2722002C (en) | 2008-04-30 | 2018-06-19 | Qlt Plug Delivery, Inc. | Composite lacrimal insert and related methods |
WO2009134929A2 (en) | 2008-05-01 | 2009-11-05 | Revalesio Corporation | Compositions and methods for treating digestive disorders |
CN103394142B (zh) | 2008-05-08 | 2015-08-19 | 迷你泵有限责任公司 | 可植入药物传送装置与用于填充该装置的设备和方法 |
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 |
EP2312993A4 (en) | 2008-07-21 | 2015-03-11 | Arstasis Inc | DEVICES, METHODS AND KITS FOR FORMING TISSUE TRAYS |
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 |
US20100075950A1 (en) | 2008-08-26 | 2010-03-25 | Auspex Pharmaceuticals, Inc. | Phenylpropanone modulators of dopamine receptor |
US8221353B2 (en) | 2008-10-21 | 2012-07-17 | KMG Pharma, Inc | Intravitreal injection device and system |
US7678078B1 (en) | 2008-10-21 | 2010-03-16 | KMG Pharma LLC | Intravitreal injection device, system and method |
WO2010062394A2 (en) | 2008-11-26 | 2010-06-03 | Surmodics, Inc. | Implantable ocular drug delivery device and methods |
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 |
US20100174272A1 (en) | 2009-01-02 | 2010-07-08 | Weiner Alan L | In-situ refillable ophthalmic implant |
US8545554B2 (en) | 2009-01-16 | 2013-10-01 | Allergan, Inc. | Intraocular injector |
PL2391419T3 (pl) | 2009-01-29 | 2019-12-31 | Forsight Vision4, Inc. | Dostarczanie leku do tylnego odcinka |
US8623395B2 (en) | 2010-01-29 | 2014-01-07 | Forsight Vision4, Inc. | Implantable therapeutic device |
WO2010093945A2 (en) | 2009-02-13 | 2010-08-19 | Glaukos Corporation | Uveoscleral drug delivery implant and methods for implanting the same |
TR201908314T4 (tr) | 2009-02-20 | 2019-06-21 | 2 Bbb Medicines B V | Glutatyon bazlı ilaç dağıtım sistemi. |
US8912236B2 (en) | 2009-03-03 | 2014-12-16 | Alcon Research, Ltd. | Pharmaceutical composition for delivery of receptor tyrosine kinase inhibiting (RTKi) compounds to the eye |
US8424367B2 (en) | 2009-03-04 | 2013-04-23 | University Of South Carolina | Systems and methods for measurement of gas permeation through polymer films |
TW201043211A (en) | 2009-03-31 | 2010-12-16 | Johnson & Johnson Vision Care Inc | Punctal plugs |
WO2010125416A1 (en) | 2009-04-27 | 2010-11-04 | Raouf Rekik | Drug delivery to the anterior and posterior segments of the eye |
US8815292B2 (en) | 2009-04-27 | 2014-08-26 | Revalesio Corporation | Compositions and methods for treating insulin resistance and diabetes mellitus |
JP2012525396A (ja) | 2009-04-27 | 2012-10-22 | レバレジオ コーポレイション | インスリン耐性および真性糖尿病を治療するための組成物および方法 |
CN102802541A (zh) | 2009-05-15 | 2012-11-28 | 阿尔斯塔西斯公司 | 在组织中形成管道的装置、方法和成套用具 |
WO2010135369A1 (en) | 2009-05-18 | 2010-11-25 | Dose Medical Corporation | Drug eluting ocular implant |
ES2921527T3 (es) | 2009-06-03 | 2022-08-29 | Forsight Vision5 Inc | Administración de fármaco en segmento anterior |
WO2011008896A2 (en) | 2009-07-14 | 2011-01-20 | Board Of Regents, The University Of Texas System | Therapeutic methods using 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 |
AT514675B1 (de) | 2009-07-23 | 2019-05-15 | Baxalta Inc | Herstellung von faktor h (fh) und fh-derivaten aus plasma |
US20110117083A1 (en) | 2009-08-14 | 2011-05-19 | Genentech, Inc. | Biological markers for monitoring patient response to vegf antagonists |
WO2011028850A1 (en) | 2009-09-01 | 2011-03-10 | Northwestern University | Delivery of therapeutic agents using oligonucleotide-modified nanoparticles as carriers |
EP2480270A4 (en) | 2009-09-21 | 2015-07-08 | Harvard Apparatus Regenerative Technology Inc | METHODS AND APPARATUSES FOR INTRODUCING CELLS INTO A TISSUE SITE |
ES2695907T3 (es) | 2009-11-17 | 2019-01-11 | Bard Inc C R | Puerto de acceso sobremoldeado que incluye características de anclaje e identificación |
US20110238036A1 (en) | 2009-12-23 | 2011-09-29 | Psivida Us, Inc. | Sustained release delivery devices |
CN102762746B (zh) | 2010-02-23 | 2015-04-29 | 克里斯托弗·戈登·阿特伍德 | 检测生物相关分子及其相互作用性质的方法 |
AU2011235002B2 (en) | 2010-03-31 | 2016-08-11 | Ocuject, Llc | Device and method for intraocular drug delivery |
EP2600920A4 (en) | 2010-08-05 | 2017-10-04 | Forsight Vision4, Inc. | Subconjunctival implant for posterior segment drug delivery |
EP3861969A1 (en) | 2010-08-05 | 2021-08-11 | ForSight Vision4, Inc. | Injector apparatus for drug delivery |
SI2600812T1 (sl) | 2010-08-05 | 2021-12-31 | ForSight Vision4, Inc., | Naprava za zdravljenje očesa |
EP4249059A3 (en) | 2011-06-28 | 2023-11-29 | ForSight Vision4, Inc. | An apparatus for collecting a sample of fluid from a reservoir chamber of a therapeutic device for the eye |
US10258503B2 (en) | 2014-07-15 | 2019-04-16 | Forsight Vision4, Inc. | Ocular implant delivery device and method |
MY182793A (en) | 2014-08-08 | 2021-02-05 | Forsight Vision4 Inc | Stable and soluble formulations of receptor tyrosine kinase inhibitors, and methods of preparation thereof |
-
2010
- 2010-01-29 PL PL10736495T patent/PL2391419T3/pl unknown
- 2010-01-29 CN CN201080014840.3A patent/CN102365109B/zh active Active
- 2010-01-29 EP EP10736495.2A patent/EP2391419B1/en active Active
- 2010-01-29 SG SG2014007389A patent/SG2014007389A/en unknown
- 2010-01-29 AU AU2010208046A patent/AU2010208046B2/en active Active
- 2010-01-29 US US12/696,678 patent/US8399006B2/en active Active
- 2010-01-29 CA CA3045436A patent/CA3045436A1/en active Pending
- 2010-01-29 CN CN201510221854.7A patent/CN104887389B/zh active Active
- 2010-01-29 JP JP2011548352A patent/JP5577354B2/ja active Active
- 2010-01-29 ES ES10736495T patent/ES2747755T3/es active Active
- 2010-01-29 SG SG2011054350A patent/SG173167A1/en unknown
- 2010-01-29 CA CA2757037A patent/CA2757037C/en active Active
- 2010-01-29 WO PCT/US2010/022631 patent/WO2010088548A1/en active Application Filing
-
2011
- 2011-10-04 US US13/252,998 patent/US8277830B2/en active Active
- 2011-10-04 US US13/252,942 patent/US8298578B2/en active Active
-
2013
- 2013-03-15 US US13/831,695 patent/US8808727B2/en active Active
- 2013-05-07 US US13/889,339 patent/US8795712B2/en active Active
- 2013-11-14 US US14/080,700 patent/US9417238B2/en active Active
-
2014
- 2014-07-07 JP JP2014140048A patent/JP5902766B2/ja active Active
-
2015
- 2015-12-17 US US14/973,311 patent/US9851351B2/en active Active
-
2016
- 2016-03-10 JP JP2016046673A patent/JP6171036B2/ja active Active
-
2017
- 2017-11-08 US US15/807,396 patent/US10656152B2/en active Active
-
2020
- 2020-04-07 US US16/842,059 patent/US11642310B2/en active Active
-
2023
- 2023-03-22 US US18/187,898 patent/US20230338282A1/en active Pending
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5466233A (en) * | 1994-04-25 | 1995-11-14 | Escalon Ophthalmics, Inc. | Tack for intraocular drug delivery and method for inserting and removing same |
US5972369A (en) * | 1997-03-31 | 1999-10-26 | Alza Corporation | Diffusional implantable delivery system |
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 |
US20030014036A1 (en) * | 2001-06-12 | 2003-01-16 | Varner Signe Erickson | Reservoir device for intraocular drug delivery |
JP2006526430A (ja) * | 2003-02-18 | 2006-11-24 | (オーエスアイ) アイテック インク. | 薬物送達装置およびその装置を充填するためのシリンジ |
Also Published As
Similar Documents
Publication | Publication Date | Title |
---|---|---|
JP6171036B2 (ja) | 眼球インプラントに治療薬を注入するためのシステム | |
AU2016202327B2 (en) | Implantable therapeutic device | |
US20150297402A1 (en) | Implantable Therapeutic Device | |
JP6326124B2 (ja) | 薬剤送達のための注入用装置 | |
AU2011285637B2 (en) | Subconjunctival implant for posterior segment drug delivery | |
JP6111194B2 (ja) | 組み合わせ薬物送達方法および装置 | |
WO2013022801A1 (en) | Small molecule delivery with implantable therapeutic device |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20140806 |
|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20140806 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20150623 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20150624 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20150924 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20151023 |
|
A601 | Written request for extension of time |
Free format text: JAPANESE INTERMEDIATE CODE: A601 Effective date: 20151124 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20151224 |
|
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: 20160209 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20160310 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 5902766 Country of ref document: JP Free format text: JAPANESE INTERMEDIATE CODE: R150 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |
|
R250 | Receipt of annual fees |
Free format text: JAPANESE INTERMEDIATE CODE: R250 |