JP6720447B2 - 酸感受性薬剤の送達のための薬剤送達系 - Google Patents
酸感受性薬剤の送達のための薬剤送達系 Download PDFInfo
- Publication number
- JP6720447B2 JP6720447B2 JP2017527282A JP2017527282A JP6720447B2 JP 6720447 B2 JP6720447 B2 JP 6720447B2 JP 2017527282 A JP2017527282 A JP 2017527282A JP 2017527282 A JP2017527282 A JP 2017527282A JP 6720447 B2 JP6720447 B2 JP 6720447B2
- Authority
- JP
- Japan
- Prior art keywords
- drug delivery
- delivery system
- drug
- polymer
- fibers
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Active
Links
- 238000012377 drug delivery Methods 0.000 title claims description 60
- 239000002253 acid Substances 0.000 title claims description 9
- 239000003814 drug Substances 0.000 title description 68
- 229940079593 drug Drugs 0.000 title description 67
- 239000000835 fiber Substances 0.000 claims description 90
- 229920000642 polymer Polymers 0.000 claims description 78
- 229960001160 latanoprost Drugs 0.000 claims description 36
- 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 claims description 35
- 229920006149 polyester-amide block copolymer Polymers 0.000 claims description 28
- 239000012867 bioactive agent Substances 0.000 claims description 22
- 229920001606 poly(lactic acid-co-glycolic acid) Polymers 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 15
- 208000010412 Glaucoma Diseases 0.000 claims description 13
- 238000009472 formulation Methods 0.000 claims description 11
- 239000012634 fragment Substances 0.000 claims description 11
- 125000002947 alkylene group Chemical group 0.000 claims description 10
- 229960002470 bimatoprost Drugs 0.000 claims description 9
- 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 claims description 9
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 230000002378 acidificating effect Effects 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 229920000954 Polyglycolide Polymers 0.000 claims description 6
- 125000002619 bicyclic group Chemical group 0.000 claims description 6
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical group C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims description 5
- 125000004450 alkenylene group Chemical group 0.000 claims description 5
- 125000000524 functional group Chemical group 0.000 claims description 5
- 229920001432 poly(L-lactide) Polymers 0.000 claims description 5
- 230000001225 therapeutic effect Effects 0.000 claims description 5
- 206010012689 Diabetic retinopathy Diseases 0.000 claims description 4
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 claims description 4
- 206010030043 Ocular hypertension Diseases 0.000 claims description 4
- 208000002780 macular degeneration Diseases 0.000 claims description 4
- 229920000728 polyester Polymers 0.000 claims description 4
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 3
- 125000000041 C6-C10 aryl group Chemical group 0.000 claims description 3
- 229960003876 ranibizumab Drugs 0.000 claims description 3
- 229960002368 travoprost Drugs 0.000 claims description 3
- 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 claims description 3
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 2
- 108010008165 Etanercept Proteins 0.000 claims description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 2
- 125000003545 alkoxy group Chemical group 0.000 claims description 2
- 229960000397 bevacizumab Drugs 0.000 claims description 2
- 229960000403 etanercept Drugs 0.000 claims description 2
- 239000001257 hydrogen Substances 0.000 claims description 2
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 claims description 2
- 229920001610 polycaprolactone Polymers 0.000 claims description 2
- 125000000896 monocarboxylic acid group Chemical group 0.000 claims 2
- 239000004633 polyglycolic acid Substances 0.000 claims 2
- 125000006719 (C6-C10) aryl (C1-C6) alkyl group Chemical group 0.000 claims 1
- 125000004185 ester group Chemical group 0.000 claims 1
- 239000004632 polycaprolactone Substances 0.000 claims 1
- 239000004626 polylactic acid Substances 0.000 claims 1
- -1 poly(caprolactone) Polymers 0.000 description 33
- 238000000034 method Methods 0.000 description 24
- 239000000243 solution Substances 0.000 description 17
- 239000011159 matrix material Substances 0.000 description 16
- 239000011258 core-shell material Substances 0.000 description 15
- 230000008569 process Effects 0.000 description 15
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 12
- 238000001125 extrusion Methods 0.000 description 12
- 230000001186 cumulative effect Effects 0.000 description 10
- 239000002904 solvent Substances 0.000 description 10
- 238000000576 coating method Methods 0.000 description 9
- 230000000694 effects Effects 0.000 description 9
- 238000011068 loading method Methods 0.000 description 9
- 239000003795 chemical substances by application Substances 0.000 description 8
- 108090000623 proteins and genes Proteins 0.000 description 8
- 238000011282 treatment Methods 0.000 description 8
- 239000007853 buffer solution Substances 0.000 description 7
- 238000006243 chemical reaction Methods 0.000 description 7
- 230000004406 elevated intraocular pressure Effects 0.000 description 7
- 230000004410 intraocular pressure Effects 0.000 description 7
- 235000018102 proteins Nutrition 0.000 description 7
- 102000004169 proteins and genes Human genes 0.000 description 7
- 239000013543 active substance Substances 0.000 description 6
- 239000011248 coating agent Substances 0.000 description 6
- 239000003889 eye drop Substances 0.000 description 6
- 230000007062 hydrolysis Effects 0.000 description 6
- 238000006460 hydrolysis reaction Methods 0.000 description 6
- 239000007924 injection Substances 0.000 description 6
- 238000002347 injection Methods 0.000 description 6
- 108090000765 processed proteins & peptides Proteins 0.000 description 6
- 239000000427 antigen Substances 0.000 description 5
- 102000036639 antigens Human genes 0.000 description 5
- 108091007433 antigens Proteins 0.000 description 5
- 229940012356 eye drops Drugs 0.000 description 5
- 125000001183 hydrocarbyl group Chemical group 0.000 description 5
- KDXKERNSBIXSRK-YFKPBYRVSA-N L-lysine Chemical compound NCCCC[C@H](N)C(O)=O KDXKERNSBIXSRK-YFKPBYRVSA-N 0.000 description 4
- 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 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 235000008206 alpha-amino acids Nutrition 0.000 description 4
- 125000003118 aryl group Chemical group 0.000 description 4
- 229920002988 biodegradable polymer Polymers 0.000 description 4
- 239000004621 biodegradable polymer Substances 0.000 description 4
- 238000000354 decomposition reaction Methods 0.000 description 4
- 238000006731 degradation reaction Methods 0.000 description 4
- 230000003628 erosive effect Effects 0.000 description 4
- 150000002148 esters Chemical class 0.000 description 4
- 230000001965 increasing effect Effects 0.000 description 4
- 238000004519 manufacturing process Methods 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 238000002156 mixing Methods 0.000 description 4
- 229920000747 poly(lactic acid) Polymers 0.000 description 4
- 102000004196 processed proteins & peptides Human genes 0.000 description 4
- 150000003431 steroids Chemical class 0.000 description 4
- 210000001519 tissue Anatomy 0.000 description 4
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- COLNVLDHVKWLRT-QMMMGPOBSA-N L-phenylalanine Chemical compound OC(=O)[C@@H](N)CC1=CC=CC=C1 COLNVLDHVKWLRT-QMMMGPOBSA-N 0.000 description 3
- OUYCCCASQSFEME-QMMMGPOBSA-N L-tyrosine Chemical compound OC(=O)[C@@H](N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-QMMMGPOBSA-N 0.000 description 3
- KDXKERNSBIXSRK-UHFFFAOYSA-N Lysine Natural products NCCCCC(N)C(O)=O KDXKERNSBIXSRK-UHFFFAOYSA-N 0.000 description 3
- 239000004472 Lysine Substances 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 239000003242 anti bacterial agent Substances 0.000 description 3
- 229940088710 antibiotic agent Drugs 0.000 description 3
- 230000015556 catabolic process Effects 0.000 description 3
- 239000007795 chemical reaction product Substances 0.000 description 3
- 229920001577 copolymer Polymers 0.000 description 3
- 238000003618 dip coating Methods 0.000 description 3
- 229940088597 hormone Drugs 0.000 description 3
- 239000005556 hormone Substances 0.000 description 3
- 230000007774 longterm Effects 0.000 description 3
- 229920001223 polyethylene glycol Polymers 0.000 description 3
- 238000012667 polymer degradation Methods 0.000 description 3
- 238000005507 spraying Methods 0.000 description 3
- 238000011200 topical administration Methods 0.000 description 3
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 3
- QCHFTSOMWOSFHM-WPRPVWTQSA-N (+)-Pilocarpine Chemical compound C1OC(=O)[C@@H](CC)[C@H]1CC1=CN=CN1C QCHFTSOMWOSFHM-WPRPVWTQSA-N 0.000 description 2
- GVJHHUAWPYXKBD-UHFFFAOYSA-N (±)-α-Tocopherol Chemical compound OC1=C(C)C(C)=C2OC(CCCC(C)CCCC(C)CCCC(C)C)(C)CCC2=C1C GVJHHUAWPYXKBD-UHFFFAOYSA-N 0.000 description 2
- 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 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
- GIKNHHRFLCDOEU-UHFFFAOYSA-N 4-(2-aminopropyl)phenol Chemical compound CC(N)CC1=CC=C(O)C=C1 GIKNHHRFLCDOEU-UHFFFAOYSA-N 0.000 description 2
- FQYRLEXKXQRZDH-UHFFFAOYSA-N 4-aminoquinoline Chemical compound C1=CC=C2C(N)=CC=NC2=C1 FQYRLEXKXQRZDH-UHFFFAOYSA-N 0.000 description 2
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 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
- DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 2
- AEMRFAOFKBGASW-UHFFFAOYSA-N Glycolic acid Chemical compound OCC(O)=O AEMRFAOFKBGASW-UHFFFAOYSA-N 0.000 description 2
- QCHFTSOMWOSFHM-UHFFFAOYSA-N SJ000285536 Natural products C1OC(=O)C(CC)C1CC1=CN=CN1C QCHFTSOMWOSFHM-UHFFFAOYSA-N 0.000 description 2
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
- 125000000217 alkyl group Chemical group 0.000 description 2
- 150000001370 alpha-amino acid derivatives Chemical class 0.000 description 2
- 150000001371 alpha-amino acids Chemical class 0.000 description 2
- 235000001014 amino acid Nutrition 0.000 description 2
- 229940024606 amino acid Drugs 0.000 description 2
- 150000001413 amino acids Chemical class 0.000 description 2
- 239000000739 antihistaminic agent Substances 0.000 description 2
- 229940125715 antihistaminic agent Drugs 0.000 description 2
- 239000003443 antiviral agent Substances 0.000 description 2
- 210000001742 aqueous humor Anatomy 0.000 description 2
- 239000012298 atmosphere Substances 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 230000000975 bioactive effect Effects 0.000 description 2
- 229920000249 biocompatible polymer Polymers 0.000 description 2
- 229960000074 biopharmaceutical Drugs 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229960004484 carbachol Drugs 0.000 description 2
- AIXAANGOTKPUOY-UHFFFAOYSA-N carbachol Chemical compound [Cl-].C[N+](C)(C)CCOC(N)=O AIXAANGOTKPUOY-UHFFFAOYSA-N 0.000 description 2
- 238000003776 cleavage reaction Methods 0.000 description 2
- OROGSEYTTFOCAN-DNJOTXNNSA-N codeine Chemical compound C([C@H]1[C@H](N(CC[C@@]112)C)C3)=C[C@H](O)[C@@H]1OC1=C2C3=CC=C1OC OROGSEYTTFOCAN-DNJOTXNNSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002131 composite material Substances 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000002872 contrast media Substances 0.000 description 2
- 238000013267 controlled drug release Methods 0.000 description 2
- 238000013270 controlled release Methods 0.000 description 2
- 238000005520 cutting process Methods 0.000 description 2
- 239000000850 decongestant Substances 0.000 description 2
- 229940124581 decongestants Drugs 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000009792 diffusion process Methods 0.000 description 2
- 238000000578 dry spinning Methods 0.000 description 2
- LZCLXQDLBQLTDK-UHFFFAOYSA-N ethyl 2-hydroxypropanoate Chemical compound CCOC(=O)C(C)O LZCLXQDLBQLTDK-UHFFFAOYSA-N 0.000 description 2
- 230000001747 exhibiting effect Effects 0.000 description 2
- 238000002474 experimental method Methods 0.000 description 2
- 239000003102 growth factor Substances 0.000 description 2
- 238000004128 high performance liquid chromatography Methods 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
- 230000001077 hypotensive effect Effects 0.000 description 2
- 238000001727 in vivo Methods 0.000 description 2
- 238000001746 injection moulding Methods 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000002074 melt spinning Methods 0.000 description 2
- 238000002844 melting Methods 0.000 description 2
- 230000008018 melting Effects 0.000 description 2
- 230000003547 miosis Effects 0.000 description 2
- 150000007523 nucleic acids Chemical class 0.000 description 2
- 108020004707 nucleic acids Proteins 0.000 description 2
- 102000039446 nucleic acids Human genes 0.000 description 2
- 210000001328 optic nerve Anatomy 0.000 description 2
- XQYZDYMELSJDRZ-UHFFFAOYSA-N papaverine Chemical compound C1=C(OC)C(OC)=CC=C1CC1=NC=CC2=CC(OC)=C(OC)C=C12 XQYZDYMELSJDRZ-UHFFFAOYSA-N 0.000 description 2
- 239000000546 pharmaceutical excipient Substances 0.000 description 2
- 229960005190 phenylalanine Drugs 0.000 description 2
- 230000004962 physiological condition Effects 0.000 description 2
- 229960001416 pilocarpine Drugs 0.000 description 2
- 238000001556 precipitation Methods 0.000 description 2
- 229960003387 progesterone Drugs 0.000 description 2
- 239000000186 progesterone Substances 0.000 description 2
- 230000007017 scission Effects 0.000 description 2
- 241000894007 species Species 0.000 description 2
- 238000009987 spinning Methods 0.000 description 2
- 230000003637 steroidlike Effects 0.000 description 2
- UCSJYZPVAKXKNQ-HZYVHMACSA-N streptomycin Chemical compound CN[C@H]1[C@H](O)[C@@H](O)[C@H](CO)O[C@H]1O[C@@H]1[C@](C=O)(O)[C@H](C)O[C@H]1O[C@@H]1[C@@H](NC(N)=N)[C@H](O)[C@@H](NC(N)=N)[C@H](O)[C@H]1O UCSJYZPVAKXKNQ-HZYVHMACSA-N 0.000 description 2
- 238000004781 supercooling Methods 0.000 description 2
- 238000013268 sustained release Methods 0.000 description 2
- 239000012730 sustained-release form Substances 0.000 description 2
- 208000024891 symptom Diseases 0.000 description 2
- 230000000007 visual effect Effects 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- 238000002166 wet spinning Methods 0.000 description 2
- DNXHEGUUPJUMQT-UHFFFAOYSA-N (+)-estrone Natural products OC1=CC=C2C3CCC(C)(C(CC4)=O)C4C3CCC2=C1 DNXHEGUUPJUMQT-UHFFFAOYSA-N 0.000 description 1
- DBPWSSGDRRHUNT-SJFWLOONSA-N (8r,9s,10r,13s,14s,17s)-17-acetyl-17-hydroxy-10,13-dimethyl-2,6,7,8,9,11,12,14,15,16-decahydro-1h-cyclopenta[a]phenanthren-3-one Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C(=O)C)(O)[C@@]1(C)CC2 DBPWSSGDRRHUNT-SJFWLOONSA-N 0.000 description 1
- PXGPLTODNUVGFL-BRIYLRKRSA-N (E,Z)-(1R,2R,3R,5S)-7-(3,5-Dihydroxy-2-((3S)-(3-hydroxy-1-octenyl))cyclopentyl)-5-heptenoic acid Chemical group CCCCC[C@H](O)C=C[C@H]1[C@H](O)C[C@H](O)[C@@H]1CC=CCCCC(O)=O PXGPLTODNUVGFL-BRIYLRKRSA-N 0.000 description 1
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 1
- 229930182837 (R)-adrenaline Natural products 0.000 description 1
- WHTVZRBIWZFKQO-AWEZNQCLSA-N (S)-chloroquine Chemical compound ClC1=CC=C2C(N[C@@H](C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-AWEZNQCLSA-N 0.000 description 1
- ICGQLNMKJVHCIR-UHFFFAOYSA-N 1,3,2-dioxazetidin-4-one Chemical compound O=C1ONO1 ICGQLNMKJVHCIR-UHFFFAOYSA-N 0.000 description 1
- LDJPOUDDDULZPN-UHFFFAOYSA-N 1,4-dioxane-2,5-dione 2-hydroxypropanoic acid Chemical compound O1C(COC(C1)=O)=O.C(C(O)C)(=O)O LDJPOUDDDULZPN-UHFFFAOYSA-N 0.000 description 1
- RPOUGULCGNMIBX-UHFFFAOYSA-N 1-chlorophenazine Chemical compound C1=CC=C2N=C3C(Cl)=CC=CC3=NC2=C1 RPOUGULCGNMIBX-UHFFFAOYSA-N 0.000 description 1
- FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 1
- BFPYWIDHMRZLRN-UHFFFAOYSA-N 17alpha-ethynyl estradiol Natural products OC1=CC=C2C3CCC(C)(C(CC4)(O)C#C)C4C3CCC2=C1 BFPYWIDHMRZLRN-UHFFFAOYSA-N 0.000 description 1
- GCKMFJBGXUYNAG-UHFFFAOYSA-N 17alpha-methyltestosterone Natural products C1CC2=CC(=O)CCC2(C)C2C1C1CCC(C)(O)C1(C)CC2 GCKMFJBGXUYNAG-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
- RSQBNHDRXUMNPM-UHFFFAOYSA-N 3,4-dihydro-2h-phosphole;hydroiodide Chemical class I.C1CC=PC1 RSQBNHDRXUMNPM-UHFFFAOYSA-N 0.000 description 1
- JJCZGVLYNIVKKD-UHFFFAOYSA-N 3-hydroxy-2-phenylpropanamide Chemical compound NC(=O)C(CO)C1=CC=CC=C1 JJCZGVLYNIVKKD-UHFFFAOYSA-N 0.000 description 1
- WREVVZMUNPAPOV-UHFFFAOYSA-N 8-aminoquinoline Chemical compound C1=CN=C2C(N)=CC=CC2=C1 WREVVZMUNPAPOV-UHFFFAOYSA-N 0.000 description 1
- 229930008281 A03AD01 - Papaverine Natural products 0.000 description 1
- 229930000680 A04AD01 - Scopolamine Natural products 0.000 description 1
- 208000035285 Allergic Seasonal Rhinitis Diseases 0.000 description 1
- 206010002091 Anaesthesia Diseases 0.000 description 1
- 108020000948 Antisense Oligonucleotides Proteins 0.000 description 1
- BSYNRYMUTXBXSQ-UHFFFAOYSA-N Aspirin Chemical compound CC(=O)OC1=CC=CC=C1C(O)=O BSYNRYMUTXBXSQ-UHFFFAOYSA-N 0.000 description 1
- 229930003347 Atropine Natural products 0.000 description 1
- 108010001478 Bacitracin Proteins 0.000 description 1
- 201000004569 Blindness Diseases 0.000 description 1
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 1
- JZUFKLXOESDKRF-UHFFFAOYSA-N Chlorothiazide Chemical compound C1=C(Cl)C(S(=O)(=O)N)=CC2=C1NCNS2(=O)=O JZUFKLXOESDKRF-UHFFFAOYSA-N 0.000 description 1
- 206010051625 Conjunctival hyperaemia Diseases 0.000 description 1
- MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 1
- MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 1
- 229920001651 Cyanoacrylate Polymers 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- ZZZCUOFIHGPKAK-UHFFFAOYSA-N D-erythro-ascorbic acid Natural products OCC1OC(=O)C(O)=C1O ZZZCUOFIHGPKAK-UHFFFAOYSA-N 0.000 description 1
- 229940090898 Desensitizer Drugs 0.000 description 1
- 108090000371 Esterases Proteins 0.000 description 1
- DNXHEGUUPJUMQT-CBZIJGRNSA-N Estrone Chemical compound OC1=CC=C2[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CCC2=C1 DNXHEGUUPJUMQT-CBZIJGRNSA-N 0.000 description 1
- BFPYWIDHMRZLRN-SLHNCBLASA-N Ethinyl estradiol Chemical compound OC1=CC=C2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 BFPYWIDHMRZLRN-SLHNCBLASA-N 0.000 description 1
- 206010015946 Eye irritation Diseases 0.000 description 1
- 229910052688 Gadolinium Inorganic materials 0.000 description 1
- 239000004471 Glycine Substances 0.000 description 1
- 108090000288 Glycoproteins Proteins 0.000 description 1
- 102000003886 Glycoproteins Human genes 0.000 description 1
- 108010026389 Gramicidin Proteins 0.000 description 1
- 102100020948 Growth hormone receptor Human genes 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
- RKUNBYITZUJHSG-UHFFFAOYSA-N Hyosciamin-hydrochlorid Natural products CN1C(C2)CCC1CC2OC(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-UHFFFAOYSA-N 0.000 description 1
- STECJAGHUSJQJN-GAUPFVANSA-N Hyoscine Natural products C1([C@H](CO)C(=O)OC2C[C@@H]3N([C@H](C2)[C@@H]2[C@H]3O2)C)=CC=CC=C1 STECJAGHUSJQJN-GAUPFVANSA-N 0.000 description 1
- 208000001953 Hypotension Diseases 0.000 description 1
- XQFRJNBWHJMXHO-RRKCRQDMSA-N IDUR Chemical compound C1[C@H](O)[C@@H](CO)O[C@H]1N1C(=O)NC(=O)C(I)=C1 XQFRJNBWHJMXHO-RRKCRQDMSA-N 0.000 description 1
- QNAYBMKLOCPYGJ-REOHCLBHSA-N L-alanine Chemical compound C[C@H](N)C(O)=O QNAYBMKLOCPYGJ-REOHCLBHSA-N 0.000 description 1
- AGPKZVBTJJNPAG-WHFBIAKZSA-N L-isoleucine Chemical compound CC[C@H](C)[C@H](N)C(O)=O AGPKZVBTJJNPAG-WHFBIAKZSA-N 0.000 description 1
- ROHFNLRQFUQHCH-YFKPBYRVSA-N L-leucine Chemical compound CC(C)C[C@H](N)C(O)=O ROHFNLRQFUQHCH-YFKPBYRVSA-N 0.000 description 1
- FFEARJCKVFRZRR-BYPYZUCNSA-N L-methionine Chemical compound CSCC[C@H](N)C(O)=O FFEARJCKVFRZRR-BYPYZUCNSA-N 0.000 description 1
- KZSNJWFQEVHDMF-BYPYZUCNSA-N L-valine Chemical compound CC(C)[C@H](N)C(O)=O KZSNJWFQEVHDMF-BYPYZUCNSA-N 0.000 description 1
- ROHFNLRQFUQHCH-UHFFFAOYSA-N Leucine Natural products CC(C)CC(N)C(O)=O ROHFNLRQFUQHCH-UHFFFAOYSA-N 0.000 description 1
- 102000004895 Lipoproteins Human genes 0.000 description 1
- 108090001030 Lipoproteins Proteins 0.000 description 1
- 241000124008 Mammalia Species 0.000 description 1
- UDKABVSQKJNZBH-DWNQPYOZSA-N Melengestrol acetate Chemical compound C1=C(C)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC(=C)[C@](OC(=O)C)(C(C)=O)[C@@]1(C)CC2 UDKABVSQKJNZBH-DWNQPYOZSA-N 0.000 description 1
- 241001465754 Metazoa Species 0.000 description 1
- GZHFODJQISUKAY-UHFFFAOYSA-N Methantheline Chemical compound C1=CC=C2C(C(=O)OCC[N+](C)(CC)CC)C3=CC=CC=C3OC2=C1 GZHFODJQISUKAY-UHFFFAOYSA-N 0.000 description 1
- GCKMFJBGXUYNAG-HLXURNFRSA-N Methyltestosterone Chemical compound C1CC2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@](C)(O)[C@@]1(C)CC2 GCKMFJBGXUYNAG-HLXURNFRSA-N 0.000 description 1
- 229920001410 Microfiber Polymers 0.000 description 1
- 102000001621 Mucoproteins Human genes 0.000 description 1
- 108010093825 Mucoproteins Proteins 0.000 description 1
- STECJAGHUSJQJN-UHFFFAOYSA-N N-Methyl-scopolamin Natural products C1C(C2C3O2)N(C)C3CC1OC(=O)C(CO)C1=CC=CC=C1 STECJAGHUSJQJN-UHFFFAOYSA-N 0.000 description 1
- 229930193140 Neomycin Natural products 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- ICTXHFFSOAJUMG-SLHNCBLASA-N Norethynodrel Chemical compound C1CC(=O)CC2=C1[C@H]1CC[C@](C)([C@](CC3)(O)C#C)[C@@H]3[C@@H]1CC2 ICTXHFFSOAJUMG-SLHNCBLASA-N 0.000 description 1
- 102000011931 Nucleoproteins Human genes 0.000 description 1
- 108010061100 Nucleoproteins Proteins 0.000 description 1
- 108091034117 Oligonucleotide Proteins 0.000 description 1
- 239000004100 Oxytetracycline Substances 0.000 description 1
- 229910019142 PO4 Inorganic materials 0.000 description 1
- 229930182555 Penicillin Natural products 0.000 description 1
- JGSARLDLIJGVTE-MBNYWOFBSA-N Penicillin G Chemical compound N([C@H]1[C@H]2SC([C@@H](N2C1=O)C(O)=O)(C)C)C(=O)CC1=CC=CC=C1 JGSARLDLIJGVTE-MBNYWOFBSA-N 0.000 description 1
- 239000004793 Polystyrene Substances 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
- 102000000471 Prostaglandin F receptors Human genes 0.000 description 1
- 108050008995 Prostaglandin F receptors Proteins 0.000 description 1
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- ABBQHOQBGMUPJH-UHFFFAOYSA-M Sodium salicylate Chemical compound [Na+].OC1=CC=CC=C1C([O-])=O ABBQHOQBGMUPJH-UHFFFAOYSA-M 0.000 description 1
- 108010068542 Somatotropin Receptors Proteins 0.000 description 1
- NHUHCSRWZMLRLA-UHFFFAOYSA-N Sulfisoxazole Chemical compound CC1=NOC(NS(=O)(=O)C=2C=CC(N)=CC=2)=C1C NHUHCSRWZMLRLA-UHFFFAOYSA-N 0.000 description 1
- 239000000150 Sympathomimetic Substances 0.000 description 1
- 239000004098 Tetracycline Substances 0.000 description 1
- UFLGIAIHIAPJJC-UHFFFAOYSA-N Tripelennamine Chemical compound C=1C=CC=NC=1N(CCN(C)C)CC1=CC=CC=C1 UFLGIAIHIAPJJC-UHFFFAOYSA-N 0.000 description 1
- KZSNJWFQEVHDMF-UHFFFAOYSA-N Valine Natural products CC(C)C(N)C(O)=O KZSNJWFQEVHDMF-UHFFFAOYSA-N 0.000 description 1
- 229930003268 Vitamin C Natural products 0.000 description 1
- 229930003427 Vitamin E Natural products 0.000 description 1
- 208000027418 Wounds and injury Diseases 0.000 description 1
- HOBWAPHTEJGALG-JKCMADFCSA-N [(1r,5s)-8-methyl-8-azoniabicyclo[3.2.1]octan-3-yl] 3-hydroxy-2-phenylpropanoate;sulfate Chemical compound [O-]S([O-])(=O)=O.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1.C([C@H]1CC[C@@H](C2)[NH+]1C)C2OC(=O)C(CO)C1=CC=CC=C1 HOBWAPHTEJGALG-JKCMADFCSA-N 0.000 description 1
- JLCPHMBAVCMARE-UHFFFAOYSA-N [3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[3-[[3-[[3-[[3-[[3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-[[5-(2-amino-6-oxo-1H-purin-9-yl)-3-hydroxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxyoxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(5-methyl-2,4-dioxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(6-aminopurin-9-yl)oxolan-2-yl]methoxy-hydroxyphosphoryl]oxy-5-(4-amino-2-oxopyrimidin-1-yl)oxolan-2-yl]methyl [5-(6-aminopurin-9-yl)-2-(hydroxymethyl)oxolan-3-yl] hydrogen phosphate Polymers Cc1cn(C2CC(OP(O)(=O)OCC3OC(CC3OP(O)(=O)OCC3OC(CC3O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c3nc(N)[nH]c4=O)C(COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3COP(O)(=O)OC3CC(OC3CO)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3ccc(N)nc3=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cc(C)c(=O)[nH]c3=O)n3cc(C)c(=O)[nH]c3=O)n3ccc(N)nc3=O)n3cc(C)c(=O)[nH]c3=O)n3cnc4c3nc(N)[nH]c4=O)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)n3cnc4c(N)ncnc34)O2)c(=O)[nH]c1=O JLCPHMBAVCMARE-UHFFFAOYSA-N 0.000 description 1
- CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 description 1
- 239000006096 absorbing agent Substances 0.000 description 1
- TUQLBJAHRWROHB-UHFFFAOYSA-N acetic acid;1-(1h-indol-3-yl)butan-2-amine Chemical class CC(O)=O.C1=CC=C2C(CC(N)CC)=CNC2=C1 TUQLBJAHRWROHB-UHFFFAOYSA-N 0.000 description 1
- NMZSAMXFINECBQ-UHFFFAOYSA-N acetic acid;1-(1h-indol-3-yl)propan-2-amine Chemical compound CC([O-])=O.C1=CC=C2C(CC([NH3+])C)=CNC2=C1 NMZSAMXFINECBQ-UHFFFAOYSA-N 0.000 description 1
- 229960001138 acetylsalicylic acid Drugs 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 230000003213 activating effect Effects 0.000 description 1
- 239000002671 adjuvant Substances 0.000 description 1
- 239000000556 agonist Substances 0.000 description 1
- 235000004279 alanine Nutrition 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000304 alkynyl group Chemical group 0.000 description 1
- 230000037005 anaesthesia Effects 0.000 description 1
- 230000001548 androgenic effect Effects 0.000 description 1
- 229940035674 anesthetics Drugs 0.000 description 1
- 238000000137 annealing Methods 0.000 description 1
- 230000003110 anti-inflammatory effect Effects 0.000 description 1
- 230000001028 anti-proliverative effect Effects 0.000 description 1
- 230000001754 anti-pyretic effect Effects 0.000 description 1
- 230000000692 anti-sense effect Effects 0.000 description 1
- 230000002921 anti-spasmodic effect Effects 0.000 description 1
- 239000000043 antiallergic agent Substances 0.000 description 1
- 229940055075 anticholinesterase parasympathomimetics Drugs 0.000 description 1
- 239000003146 anticoagulant agent Substances 0.000 description 1
- 229940127219 anticoagulant drug Drugs 0.000 description 1
- 229940121375 antifungal agent Drugs 0.000 description 1
- 239000000030 antiglaucoma agent Substances 0.000 description 1
- 229960005475 antiinfective agent Drugs 0.000 description 1
- 239000003430 antimalarial agent Substances 0.000 description 1
- 229940033495 antimalarials Drugs 0.000 description 1
- 239000004599 antimicrobial Substances 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 239000003963 antioxidant agent Substances 0.000 description 1
- 235000006708 antioxidants Nutrition 0.000 description 1
- 239000000164 antipsychotic agent Substances 0.000 description 1
- 229940005529 antipsychotics Drugs 0.000 description 1
- 239000002221 antipyretic Substances 0.000 description 1
- 229940125716 antipyretic agent Drugs 0.000 description 1
- 239000000074 antisense oligonucleotide Substances 0.000 description 1
- 238000012230 antisense oligonucleotides Methods 0.000 description 1
- 229940124575 antispasmodic agent Drugs 0.000 description 1
- 229940121357 antivirals Drugs 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 229960000396 atropine Drugs 0.000 description 1
- RKUNBYITZUJHSG-SPUOUPEWSA-N atropine Chemical compound O([C@H]1C[C@H]2CC[C@@H](C1)N2C)C(=O)C(CO)C1=CC=CC=C1 RKUNBYITZUJHSG-SPUOUPEWSA-N 0.000 description 1
- 229960002028 atropine sulfate Drugs 0.000 description 1
- 229960004099 azithromycin Drugs 0.000 description 1
- MQTOSJVFKKJCRP-BICOPXKESA-N azithromycin Chemical compound O([C@@H]1[C@@H](C)C(=O)O[C@@H]([C@@]([C@H](O)[C@@H](C)N(C)C[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 MQTOSJVFKKJCRP-BICOPXKESA-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
- 230000004888 barrier function Effects 0.000 description 1
- XXAYGJGDVLSEML-LBPRGKRZSA-N benzyl (2s)-2,6-diaminohexanoate Chemical compound NCCCC[C@H](N)C(=O)OCC1=CC=CC=C1 XXAYGJGDVLSEML-LBPRGKRZSA-N 0.000 description 1
- 238000006065 biodegradation reaction Methods 0.000 description 1
- DQXBYHZEEUGOBF-UHFFFAOYSA-N but-3-enoic acid;ethene Chemical compound C=C.OC(=O)CC=C DQXBYHZEEUGOBF-UHFFFAOYSA-N 0.000 description 1
- 238000011088 calibration curve Methods 0.000 description 1
- 239000004202 carbamide Substances 0.000 description 1
- 150000001720 carbohydrates Chemical class 0.000 description 1
- 235000014633 carbohydrates Nutrition 0.000 description 1
- 239000011203 carbon fibre reinforced carbon Substances 0.000 description 1
- 125000002843 carboxylic acid group Chemical group 0.000 description 1
- 108010015046 cell aggregation factors Proteins 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 229960005091 chloramphenicol Drugs 0.000 description 1
- WIIZWVCIJKGZOK-RKDXNWHRSA-N chloramphenicol Chemical compound ClC(Cl)C(=O)N[C@H](CO)[C@H](O)C1=CC=C([N+]([O-])=O)C=C1 WIIZWVCIJKGZOK-RKDXNWHRSA-N 0.000 description 1
- 229960003996 chlormadinone Drugs 0.000 description 1
- VUHJZBBCZGVNDZ-TTYLFXKOSA-N chlormadinone Chemical compound C1=C(Cl)C2=CC(=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CC[C@@](C(=O)C)(O)[C@@]1(C)CC2 VUHJZBBCZGVNDZ-TTYLFXKOSA-N 0.000 description 1
- 229960003677 chloroquine Drugs 0.000 description 1
- WHTVZRBIWZFKQO-UHFFFAOYSA-N chloroquine Natural products ClC1=CC=C2C(NC(C)CCCN(CC)CC)=CC=NC2=C1 WHTVZRBIWZFKQO-UHFFFAOYSA-N 0.000 description 1
- CYDMQBQPVICBEU-UHFFFAOYSA-N chlorotetracycline Natural products C1=CC(Cl)=C2C(O)(C)C3CC4C(N(C)C)C(O)=C(C(N)=O)C(=O)C4(O)C(O)=C3C(=O)C2=C1O CYDMQBQPVICBEU-UHFFFAOYSA-N 0.000 description 1
- 229960002155 chlorothiazide Drugs 0.000 description 1
- SOYKEARSMXGVTM-UHFFFAOYSA-N chlorphenamine Chemical compound C=1C=CC=NC=1C(CCN(C)C)C1=CC=C(Cl)C=C1 SOYKEARSMXGVTM-UHFFFAOYSA-N 0.000 description 1
- 229960003291 chlorphenamine 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
- 239000000544 cholinesterase inhibitor Substances 0.000 description 1
- 230000001684 chronic effect Effects 0.000 description 1
- PMMYEEVYMWASQN-IMJSIDKUSA-N cis-4-Hydroxy-L-proline Chemical class O[C@@H]1CN[C@H](C(O)=O)C1 PMMYEEVYMWASQN-IMJSIDKUSA-N 0.000 description 1
- 229960004126 codeine Drugs 0.000 description 1
- 239000002299 complementary DNA Substances 0.000 description 1
- 210000004087 cornea Anatomy 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
- 229960004544 cortisone Drugs 0.000 description 1
- NLCKLZIHJQEMCU-UHFFFAOYSA-N cyano prop-2-enoate Chemical class C=CC(=O)OC#N NLCKLZIHJQEMCU-UHFFFAOYSA-N 0.000 description 1
- 125000004122 cyclic group Chemical group 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 229940127089 cytotoxic agent Drugs 0.000 description 1
- 229920006237 degradable polymer Polymers 0.000 description 1
- 229960003957 dexamethasone Drugs 0.000 description 1
- UREBDLICKHMUKA-CXSFZGCWSA-N dexamethasone Chemical compound C1CC2=CC(=O)C=C[C@]2(C)[C@]2(F)[C@@H]1[C@@H]1C[C@@H](C)[C@@](C(=O)CO)(O)[C@@]1(C)C[C@@H]2O UREBDLICKHMUKA-CXSFZGCWSA-N 0.000 description 1
- 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
- RGLYKWWBQGJZGM-ISLYRVAYSA-N diethylstilbestrol Chemical compound C=1C=C(O)C=CC=1C(/CC)=C(\CC)C1=CC=C(O)C=C1 RGLYKWWBQGJZGM-ISLYRVAYSA-N 0.000 description 1
- 229960000452 diethylstilbestrol Drugs 0.000 description 1
- 229960004993 dimenhydrinate Drugs 0.000 description 1
- MZDOIJOUFRQXHC-UHFFFAOYSA-N dimenhydrinate Chemical compound O=C1N(C)C(=O)N(C)C2=NC(Cl)=N[C]21.C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 MZDOIJOUFRQXHC-UHFFFAOYSA-N 0.000 description 1
- 229960000520 diphenhydramine Drugs 0.000 description 1
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical compound C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 1
- 239000006196 drop Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 239000000428 dust Substances 0.000 description 1
- 229960002017 echothiophate Drugs 0.000 description 1
- BJOLKYGKSZKIGU-UHFFFAOYSA-N ecothiopate Chemical compound CCOP(=O)(OCC)SCC[N+](C)(C)C BJOLKYGKSZKIGU-UHFFFAOYSA-N 0.000 description 1
- 238000005538 encapsulation Methods 0.000 description 1
- 230000002708 enhancing effect Effects 0.000 description 1
- 230000007515 enzymatic degradation Effects 0.000 description 1
- 229960005139 epinephrine Drugs 0.000 description 1
- 229960003276 erythromycin Drugs 0.000 description 1
- UDKIYKILOKEDQK-UHFFFAOYSA-N esperin Chemical compound OC(=O)C(C)NC(=O)C(CC(C)C)NC(=O)C1CC(=O)OC(C)CC(=O)NC(CCC(O)=O)C(=O)NC(CC(C)C)C(=O)NC(CC(C)C)C(=O)NC(C(C)C)C(=O)N1 UDKIYKILOKEDQK-UHFFFAOYSA-N 0.000 description 1
- 229960005309 estradiol Drugs 0.000 description 1
- 229940011871 estrogen Drugs 0.000 description 1
- 239000000262 estrogen Substances 0.000 description 1
- 229960003399 estrone Drugs 0.000 description 1
- 229960002568 ethinylestradiol Drugs 0.000 description 1
- CHNXZKVNWQUJIB-CEGNMAFCSA-N ethisterone Chemical compound O=C1CC[C@]2(C)[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 CHNXZKVNWQUJIB-CEGNMAFCSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 229940116333 ethyl lactate Drugs 0.000 description 1
- 239000005038 ethylene vinyl acetate Substances 0.000 description 1
- 229950002420 eucatropine Drugs 0.000 description 1
- 231100000013 eye irritation Toxicity 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 229940043075 fluocinolone Drugs 0.000 description 1
- FEBLZLNTKCEFIT-VSXGLTOVSA-N fluocinolone acetonide Chemical compound C1([C@@H](F)C2)=CC(=O)C=C[C@]1(C)[C@]1(F)[C@@H]2[C@@H]2C[C@H]3OC(C)(C)O[C@@]3(C(=O)CO)[C@@]2(C)C[C@@H]1O FEBLZLNTKCEFIT-VSXGLTOVSA-N 0.000 description 1
- UIWYJDYFSGRHKR-UHFFFAOYSA-N gadolinium atom Chemical compound [Gd] UIWYJDYFSGRHKR-UHFFFAOYSA-N 0.000 description 1
- WIGCFUFOHFEKBI-UHFFFAOYSA-N gamma-tocopherol Natural products CC(C)CCCC(C)CCCC(C)CCCC1CCC2C(C)C(O)C(C)C(C)C2O1 WIGCFUFOHFEKBI-UHFFFAOYSA-N 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 239000003193 general anesthetic agent Substances 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 150000004676 glycans 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
- 238000000227 grinding Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 150000002402 hexoses Chemical class 0.000 description 1
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229960000857 homatropine Drugs 0.000 description 1
- OROGSEYTTFOCAN-UHFFFAOYSA-N hydrocodone Natural products C1C(N(CCC234)C)C2C=CC(O)C3OC2=C4C1=CC=C2OC OROGSEYTTFOCAN-UHFFFAOYSA-N 0.000 description 1
- 229960000890 hydrocortisone Drugs 0.000 description 1
- 229960001067 hydrocortisone acetate Drugs 0.000 description 1
- 239000000017 hydrogel Substances 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 229950005360 hydroxyamfetamine Drugs 0.000 description 1
- 239000005554 hypnotics and sedatives Substances 0.000 description 1
- 208000021822 hypotensive Diseases 0.000 description 1
- 229960004716 idoxuridine Drugs 0.000 description 1
- 238000007654 immersion Methods 0.000 description 1
- 239000000367 immunologic factor Substances 0.000 description 1
- 229960003444 immunosuppressant agent Drugs 0.000 description 1
- 239000003018 immunosuppressive agent Substances 0.000 description 1
- 239000007943 implant Substances 0.000 description 1
- 238000000338 in vitro Methods 0.000 description 1
- 238000003780 insertion Methods 0.000 description 1
- 230000037431 insertion Effects 0.000 description 1
- 230000001788 irregular Effects 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 229960000310 isoleucine Drugs 0.000 description 1
- AGPKZVBTJJNPAG-UHFFFAOYSA-N isoleucine Natural products CCC(C)C(N)C(O)=O AGPKZVBTJJNPAG-UHFFFAOYSA-N 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 150000002632 lipids Chemical class 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 229960004616 medroxyprogesterone Drugs 0.000 description 1
- FRQMUZJSZHZSGN-HBNHAYAOSA-N medroxyprogesterone Chemical compound C([C@@]12C)CC(=O)C=C1[C@@H](C)C[C@@H]1[C@@H]2CC[C@]2(C)[C@@](O)(C(C)=O)CC[C@H]21 FRQMUZJSZHZSGN-HBNHAYAOSA-N 0.000 description 1
- 230000001802 melanotrophic effect Effects 0.000 description 1
- 229960004805 melengestrol Drugs 0.000 description 1
- 238000010128 melt processing Methods 0.000 description 1
- 230000004060 metabolic process Effects 0.000 description 1
- 229960001470 methantheline Drugs 0.000 description 1
- 229930182817 methionine Natural products 0.000 description 1
- LZCOQTDXKCNBEE-IKIFYQGPSA-N methscopolamine Chemical compound C1([C@@H](CO)C(=O)O[C@H]2C[C@@H]3[N+]([C@H](C2)[C@@H]2[C@H]3O2)(C)C)=CC=CC=C1 LZCOQTDXKCNBEE-IKIFYQGPSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229960001383 methylscopolamine Drugs 0.000 description 1
- 229960001566 methyltestosterone Drugs 0.000 description 1
- 239000003658 microfiber Substances 0.000 description 1
- 239000011859 microparticle Substances 0.000 description 1
- 235000013336 milk Nutrition 0.000 description 1
- 239000008267 milk Substances 0.000 description 1
- 210000004080 milk Anatomy 0.000 description 1
- 239000003604 miotic agent Substances 0.000 description 1
- 239000000178 monomer Substances 0.000 description 1
- 150000002772 monosaccharides Chemical class 0.000 description 1
- PHFJZKMLXDFUNB-UHFFFAOYSA-N n-[4-[(4-methylpyrimidin-2-yl)sulfamoyl]phenyl]acetamide Chemical compound C1=CC(NC(=O)C)=CC=C1S(=O)(=O)NC1=NC=CC(C)=N1 PHFJZKMLXDFUNB-UHFFFAOYSA-N 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 229960005016 naphazoline Drugs 0.000 description 1
- 125000001624 naphthyl group Chemical group 0.000 description 1
- 229960004927 neomycin Drugs 0.000 description 1
- 230000008764 nerve damage Effects 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
- 125000006501 nitrophenyl group Chemical group 0.000 description 1
- 229940053934 norethindrone Drugs 0.000 description 1
- VIKNJXKGJWUCNN-XGXHKTLJSA-N norethisterone Chemical compound O=C1CC[C@@H]2[C@H]3CC[C@](C)([C@](CC4)(O)C#C)[C@@H]4[C@@H]3CCC2=C1 VIKNJXKGJWUCNN-XGXHKTLJSA-N 0.000 description 1
- 229960001858 norethynodrel Drugs 0.000 description 1
- 239000002777 nucleoside Substances 0.000 description 1
- 125000003835 nucleoside group Chemical group 0.000 description 1
- 239000002773 nucleotide Substances 0.000 description 1
- 125000003729 nucleotide group Chemical group 0.000 description 1
- 229920001778 nylon Polymers 0.000 description 1
- 229960000988 nystatin Drugs 0.000 description 1
- VQOXZBDYSJBXMA-NQTDYLQESA-N nystatin A1 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/CC/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)C[C@H](O)CC[C@@H](O)[C@H](O)C[C@](O)(C[C@H](O)[C@H]2C(O)=O)O[C@H]2C1 VQOXZBDYSJBXMA-NQTDYLQESA-N 0.000 description 1
- 201000005111 ocular hyperemia Diseases 0.000 description 1
- 229920001542 oligosaccharide Polymers 0.000 description 1
- 150000002482 oligosaccharides Chemical class 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 238000006864 oxidative decomposition reaction Methods 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
- 229960001789 papaverine Drugs 0.000 description 1
- 239000000734 parasympathomimetic agent Substances 0.000 description 1
- 230000001499 parasympathomimetic effect Effects 0.000 description 1
- 229940005542 parasympathomimetics Drugs 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 230000001991 pathophysiological effect Effects 0.000 description 1
- 230000000149 penetrating effect Effects 0.000 description 1
- 230000035515 penetration Effects 0.000 description 1
- 229940049954 penicillin Drugs 0.000 description 1
- 229960001412 pentobarbital Drugs 0.000 description 1
- WEXRUCMBJFQVBZ-UHFFFAOYSA-N pentobarbital Chemical compound CCCC(C)C1(CC)C(=O)NC(=O)NC1=O WEXRUCMBJFQVBZ-UHFFFAOYSA-N 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 229960002695 phenobarbital Drugs 0.000 description 1
- DDBREPKUVSBGFI-UHFFFAOYSA-N phenobarbital Chemical compound C=1C=CC=CC=1C1(CC)C(=O)NC(=O)NC1=O DDBREPKUVSBGFI-UHFFFAOYSA-N 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- COLNVLDHVKWLRT-UHFFFAOYSA-N phenylalanine Natural products OC(=O)C(N)CC1=CC=CC=C1 COLNVLDHVKWLRT-UHFFFAOYSA-N 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
- 239000010452 phosphate Substances 0.000 description 1
- 229920001200 poly(ethylene-vinyl acetate) Polymers 0.000 description 1
- 229920002627 poly(phosphazenes) Polymers 0.000 description 1
- 238000006068 polycondensation reaction Methods 0.000 description 1
- 238000006116 polymerization reaction Methods 0.000 description 1
- 229920001184 polypeptide Polymers 0.000 description 1
- 229920000379 polypropylene carbonate Polymers 0.000 description 1
- 229920001282 polysaccharide Polymers 0.000 description 1
- 239000005017 polysaccharide Substances 0.000 description 1
- 229920002223 polystyrene Polymers 0.000 description 1
- 229920000166 polytrimethylene carbonate Polymers 0.000 description 1
- 229920002635 polyurethane Polymers 0.000 description 1
- 239000004814 polyurethane Substances 0.000 description 1
- 229920002689 polyvinyl acetate Polymers 0.000 description 1
- 239000011118 polyvinyl acetate Substances 0.000 description 1
- 239000000843 powder 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
- 238000004321 preservation Methods 0.000 description 1
- 230000002265 prevention Effects 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- 229940002612 prodrug Drugs 0.000 description 1
- 239000000651 prodrug Substances 0.000 description 1
- 230000000069 prophylactic effect Effects 0.000 description 1
- 150000003180 prostaglandins Chemical class 0.000 description 1
- 229940127293 prostanoid Drugs 0.000 description 1
- 150000003814 prostanoids Chemical group 0.000 description 1
- 239000003368 psychostimulant agent Substances 0.000 description 1
- 238000004080 punching Methods 0.000 description 1
- WKSAUQYGYAYLPV-UHFFFAOYSA-N pyrimethamine Chemical compound CCC1=NC(N)=NC(N)=C1C1=CC=C(Cl)C=C1 WKSAUQYGYAYLPV-UHFFFAOYSA-N 0.000 description 1
- 229960000611 pyrimethamine Drugs 0.000 description 1
- 238000004445 quantitative analysis Methods 0.000 description 1
- 239000006100 radiation absorber Substances 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 239000000018 receptor agonist Substances 0.000 description 1
- 229940044601 receptor agonist Drugs 0.000 description 1
- 238000007151 ring opening polymerisation reaction Methods 0.000 description 1
- 125000006413 ring segment Chemical group 0.000 description 1
- 229960000581 salicylamide Drugs 0.000 description 1
- 229960001860 salicylate Drugs 0.000 description 1
- YGSDEFSMJLZEOE-UHFFFAOYSA-M salicylate Chemical compound OC1=CC=CC=C1C([O-])=O YGSDEFSMJLZEOE-UHFFFAOYSA-M 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
- 238000007789 sealing Methods 0.000 description 1
- 229960003141 secobarbital sodium Drugs 0.000 description 1
- 229940125723 sedative agent Drugs 0.000 description 1
- 239000000932 sedative agent Substances 0.000 description 1
- 150000003384 small molecules Chemical class 0.000 description 1
- 239000001632 sodium acetate Substances 0.000 description 1
- 235000017281 sodium acetate Nutrition 0.000 description 1
- JXKPEJDQGNYQSM-UHFFFAOYSA-M sodium propionate Chemical compound [Na+].CCC([O-])=O JXKPEJDQGNYQSM-UHFFFAOYSA-M 0.000 description 1
- 229960003212 sodium propionate Drugs 0.000 description 1
- 239000004324 sodium propionate Substances 0.000 description 1
- 235000010334 sodium propionate Nutrition 0.000 description 1
- 229960004025 sodium salicylate Drugs 0.000 description 1
- FKKAEMQFOIDZNY-WYMSNYCCSA-M sodium;4-[2-[(10r,13s,17r)-11,17-dihydroxy-10,13-dimethyl-3-oxo-7,8,9,11,12,14,15,16-octahydro-6h-cyclopenta[a]phenanthren-17-yl]-2-oxoethoxy]-4-oxobutanoate Chemical compound [Na+].O=C1C=C[C@]2(C)C3C(O)C[C@](C)([C@@](CC4)(O)C(=O)COC(=O)CCC([O-])=O)C4C3CCC2=C1 FKKAEMQFOIDZNY-WYMSNYCCSA-M 0.000 description 1
- AXXJTNXVUHVOJW-UHFFFAOYSA-M sodium;5-pentan-2-yl-5-prop-2-enylpyrimidin-3-ide-2,4,6-trione Chemical compound [Na+].CCCC(C)C1(CC=C)C(=O)NC(=O)[N-]C1=O AXXJTNXVUHVOJW-UHFFFAOYSA-M 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 238000000807 solvent casting Methods 0.000 description 1
- 239000007921 spray Substances 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 229960005322 streptomycin Drugs 0.000 description 1
- 238000007920 subcutaneous administration Methods 0.000 description 1
- 239000000126 substance Substances 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
- 229960002135 sulfadimidine Drugs 0.000 description 1
- 229960000654 sulfafurazole Drugs 0.000 description 1
- ASWVTGNCAZCNNR-UHFFFAOYSA-N sulfamethazine Chemical compound CC1=CC(C)=NC(NS(=O)(=O)C=2C=CC(N)=CC=2)=N1 ASWVTGNCAZCNNR-UHFFFAOYSA-N 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
- 238000004381 surface treatment Methods 0.000 description 1
- 238000001356 surgical procedure Methods 0.000 description 1
- 230000002459 sustained effect Effects 0.000 description 1
- 230000001975 sympathomimetic effect Effects 0.000 description 1
- 229940064707 sympathomimetics Drugs 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 230000009885 systemic effect Effects 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
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 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
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 229920001169 thermoplastic Polymers 0.000 description 1
- 230000000699 topical effect Effects 0.000 description 1
- 210000001585 trabecular meshwork Anatomy 0.000 description 1
- 239000003204 tranquilizing agent Substances 0.000 description 1
- 230000002936 tranquilizing effect Effects 0.000 description 1
- 229960005294 triamcinolone Drugs 0.000 description 1
- 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 1
- 229960003223 tripelennamine Drugs 0.000 description 1
- 239000004474 valine Substances 0.000 description 1
- 239000011782 vitamin Substances 0.000 description 1
- 229930003231 vitamin Natural products 0.000 description 1
- 235000013343 vitamin Nutrition 0.000 description 1
- 229940088594 vitamin Drugs 0.000 description 1
- 235000019154 vitamin C Nutrition 0.000 description 1
- 239000011718 vitamin C Substances 0.000 description 1
- 235000019165 vitamin E Nutrition 0.000 description 1
- 229940046009 vitamin E Drugs 0.000 description 1
- 239000011709 vitamin E Substances 0.000 description 1
- 239000003643 water by type Substances 0.000 description 1
- 230000003442 weekly effect Effects 0.000 description 1
Images
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/70—Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
-
- 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
-
- 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
- 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
- A61F9/007—Methods or devices for eye surgery
- A61F9/00781—Apparatus for modifying intraocular pressure, e.g. for glaucoma treatment
-
- 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
- A61K31/557—Eicosanoids, e.g. leukotrienes or prostaglandins
- A61K31/5575—Eicosanoids, e.g. leukotrienes or prostaglandins having a cyclopentane, e.g. prostaglandin E2, prostaglandin F2-alpha
-
- 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
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0048—Eye, e.g. artificial tears
- A61K9/0051—Ocular inserts, ocular implants
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0087—Galenical forms not covered by A61K9/02 - A61K9/7023
- A61K9/0092—Hollow drug-filled fibres, tubes of the core-shell type, coated fibres, coated rods, microtubules or nanotubes
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
-
- 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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
- A61K9/5107—Excipients; Inactive ingredients
- A61K9/513—Organic macromolecular compounds; Dendrimers
- A61K9/5146—Organic macromolecular compounds; Dendrimers obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyamines, polyanhydrides
- A61K9/5153—Polyesters, e.g. poly(lactide-co-glycolide)
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P27/00—Drugs for disorders of the senses
- A61P27/02—Ophthalmic agents
- A61P27/06—Antiglaucoma agents or miotics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/02—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids
- C08G69/36—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino acids, polyamines and polycarboxylic acids
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G69/00—Macromolecular compounds obtained by reactions forming a carboxylic amide link in the main chain of the macromolecule
- C08G69/44—Polyester-amides
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08L—COMPOSITIONS OF MACROMOLECULAR COMPOUNDS
- C08L77/00—Compositions of polyamides obtained by reactions forming a carboxylic amide link in the main chain; Compositions of derivatives of such polymers
- C08L77/12—Polyester-amides
-
- 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
- A61F9/007—Methods or devices for eye surgery
- A61F9/008—Methods or devices for eye surgery using laser
- A61F2009/00861—Methods or devices for eye surgery using laser adapted for treatment at a particular location
- A61F2009/00872—Cornea
-
- 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
- A61F9/007—Methods or devices for eye surgery
- A61F9/008—Methods or devices for eye surgery using laser
- A61F2009/00885—Methods or devices for eye surgery using laser for treating a particular disease
- A61F2009/00891—Glaucoma
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Ophthalmology & Optometry (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Chemistry (AREA)
- Polymers & Plastics (AREA)
- Biomedical Technology (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Vascular Medicine (AREA)
- Heart & Thoracic Surgery (AREA)
- Inorganic Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Nanotechnology (AREA)
- Physics & Mathematics (AREA)
- Optics & Photonics (AREA)
- Surgery (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Description
を含み、式中、
− m+pは0.9〜0.1で変動し、qは0.1〜0.9で変動し、
− m+p+q=1、mまたはpは0となり得、
− nは5〜300で変動し、
− R1は、(C2〜C20)アルキレン、(C2〜C20)アルケニレン、およびその組み合わせからなる群から独立して選択され、
− 単一骨格単位mまたはp中のR3およびR4は、それぞれ水素、(C1〜C6)アルキル、(C2〜C6)アルケニル、(C2〜C6)アルキニル、(C6〜C10)アリール、(C1〜C6)アルキル、−(CH2)SH、−(CH2)2S(CH3)、−CH2OH、−CH(OH)CH3、−(CH2)4NH3+、−(CH2)3NHC(=NH2+)NH2、−CH2COOH、−CH2−CO−NH2、−CH2CH2−CO−NH2、−CH2CH2COOH、CH3−CH2−CH(CH3)−、(CH3)2−CH−CH2−、H2N−(CH2)4−、Ph−CH2−、CH=C−CH2−、HO−p−Ph−CH2−、(CH3)2−CH−、Ph−NH−、NH−(CH2)3−C−、NH−CH=N−CH=C−CH2−からなる群から独立して選択され、
− R5は、(C2〜C20)アルキレン、(C2〜C20)アルケニレン、アルキルオキシ、またはオリゴエチレングリコールからなる群から選択され、
− R6は、構造式(II)
の1,4:3,6−ジアンヒドロヘキシトールの二環式断片;1,4−シクロヘキサンジオール誘導体などのシクロアルキル断片、ヘキソース由来断片などの芳香族断片または複素環式断片から選択され、
− R7は、(C6〜C10)アリール、(C1〜C6)アルキルからなる群から選択され、
− R8は−(CH2)4−であり、aは少なくとも0.05であり、bは少なくとも0.05であり、かつa+b=1である。
[実施例1:PEA−III−X25/PLGAを含むコアシェル繊維およびシェルを含まないPEA−III−X25の繊維からのラタノプロストの放出]
10%ラタノプロストの負荷パーセンテージを有するPEA−III−X25から作製した繊維を押出しによって調製し、PLGAによりコーティングした。240μmの直径および5mm長を有する4本の個々の繊維を37℃の1.2ml PBSバッファー溶液中に置いた。様々な時点で、シンク条件を保証するために0.9mL PBS溶液を新しいものにし、薬剤濃度を続いて測定した。典型的に、サンプルは、第1の週では毎日およびその後の時点では毎週測定した。ラタノプロストサンプルの放出の定量分析については、フォトダイオードアレイ検出器を有するWaters e2695 Alliance HPLCを使用した。定組成HPLC方法をAgilent Zorbax Eclipse XBD−C18 4.6×250mm、5μmカラムと共に使用した。移動相は、アセトニトリル/H2O(60/40、0.05%TFAを含有)とし、流量は1.0ml/分とした。カラム温度は25℃におよびサンプル温度は15℃にセットした。サンプルは、210nmの波長で測定した。ラタノプロストの系は、検量線にも使用した範囲とした1μg〜200μgの範囲で直線性を示した。図1は、PEA−III−X25コア、シェルなしが噴出放出を呈するが、PEA−III−X25コア−シェル繊維については一定の薬剤放出を示すラタノプロストの累積的な放出パーセンテージを示す。図2では、ラタノプロストの1日用量が示され、シェルを含まない繊維は放出の最初の20日間で著しい噴出を見せる。
15%ラタノプロストの負荷パーセンテージを有するPEA−III−X25から作製した繊維を溶融射出(melt injection)によって調製し、PLLAによりコーティングした。200μmの直径および5mm長を有する4本の個々の繊維を37℃の1.2ml PBSバッファー溶液中に置いた。様々な時点で、シンク条件を保証するために0.9mL PBS溶液を新しいものにし、薬剤濃度を続いて測定した。図3は、140日間の0.05μg/日のラタノプロストの一定の1日用量を示す。
10%ラタノプロストの負荷パーセンテージを有するPEA−III−X25から作製した繊維を溶融射出によって調製し、PEA−III−X25およびPEA−III−AcBzによりコーティングした。200μmの直径および5mm長を有する3本の個々の繊維を37℃の1.2ml PBSバッファー溶液中に置いた。様々な時点で、シンク条件を保証するために0.9mL PBS溶液を新しいものにし、薬剤濃度を続いて測定した。
15%ラタノプロストの負荷パーセンテージを有するPEA−III−X25から作製した繊維を射出成形によって調製し、PLGAによりコーティングした。4つの個々の繊維を37℃の1.4ml PBSバッファー溶液中に置いた。選択した時点で、繊維を、4×倍率でOlympus CX−41光学顕微鏡を使用し、PBS中に浸漬させて画像化した。図10〜13は、1週間、1か月、3か月、および8か月の繊維の形態を示す。PEA−III−X25コアが分解し、コーティングから浸出するにつれて、繊維末端の表面積が増加し、薬剤拡散に利用可能な表面を増加させる。観察された効果により、薬剤濃度勾配の減少が補われ、より一定の薬剤放出プロファイルをもたらす。
30%ビマトプロストの負荷パーセンテージを有するPEA−III−X25から作製した繊維を溶融射出によって調製し、PLLAによりコーティングした。200μmの直径および1.2mm長を有する5本の個々の繊維を37℃の0.25ml PBSバッファー溶液中に置いた。様々な時点で、シンク条件を保証するために0.15mL PBS溶液を新しいものにし、薬剤濃度を続いて測定した。図14は、PEA−III−X25コア、シェルなしが噴出放出を呈するが、PEA−III−X25コア−シェル繊維については制御された薬剤放出を示すビマトプロストの累積的な放出パーセンテージを示す。図15では、ビマトプロストの1日用量が示され、シェルを含まない繊維は放出の最初の10日間で著しい噴出を見せることを示す。
10%ラタノプロストの負荷パーセンテージを有するPEA−III−AcBzから作製される繊維[(ポリ−8−[(L−Leu−DAS)0.45(L−Leu−6)0.3−[L−Lys(Bz)]0.25・]構造物を式IIIに示し、押出しによって調製し、PLGAによりコーティングした。10%ラタノプロストの負荷パーセンテージを有するPEA−III−X25繊維を押出しによって調製し、PLGAによりコーティングした。250μmの直径および5mm長を有する4本の個々の繊維を37℃の1.2ml PBSバッファー溶液中に置いた。様々な時点で、シンク条件を保証するために0.9mL PBS溶液を新しいものにし、薬剤濃度を続いて測定した。
10%ラタノプロストの負荷パーセンテージを有するPLGAの薬剤負荷ディスクを、フィルムを溶媒キャストし、フィルムからサンプルを打ち抜くことによって調製した。7mmの直径を有する3枚の個々のディスクを37℃の5.0ml PBSバッファー溶液中に置いた。様々な時点で、シンク条件を保証するために全PBS溶液を新しいものにし、薬剤濃度を続いて測定した。図6および図7は、PLGAからのラタノプロストの累積的な放出曲線および1日用量を示し、ポリマーマトリックスが分解したときの高度なラタノプロスト噴出により1日用量に対する制御が不十分であることを示す。
Claims (16)
- (a)ペンダント官能基としてエステル基および酸性基を含むポリマー骨格を有するポリエステルアミドを含むポリマーの円柱状のコア、
(b)0.5μm〜5μmの厚さを有する、ポリエステルを含むポリマーシェル、および
(c)前記コア中の生理活性剤
を含む薬剤送達系であって、
前記ポリエステルアミドが、式(I)のポリエステルアミドコポリマーを含み、
式(I)中、
m+pは0.9〜0.1であり、qは0.1〜0.9であり、
m+p+q=1であり、ただしmまたはpは0であることができ、
nは5〜300であり、
m単位、p単位、a単位およびb単位は、それぞれランダムに分布し、
R 1 は独立して、(C 2 〜C 20 )アルキレン、(C 2 〜C 20 )アルケニレン、およびその組み合わせからなる群から選択され、
単一主鎖単位mまたはpにおけるR 3 およびR 4 はそれぞれ独立して、水素、(C 1 〜C 6 )アルキル、(C 2 〜C 6 )アルケニル、(C 2 〜C 6 )アルキニル、(C 6 〜C 10 )アリール、−(CH 2 )SH、−(CH 2 ) 2 S(CH 3 )、−CH 2 OH、−CH(OH)CH 3 、−(CH 2 ) 4 NH 3 + 、−(CH 2 ) 3 NHC(=NH 2 + )NH 2 、−CH 2 COOH、−CH 2 −CO−NH 2 、−CH 2 CH 2 −CO−NH 2 、−CH 2 CH 2 COOH、CH 3 −CH 2 −CH(CH 3 )−、(CH 3 ) 2 −CH−CH 2 −、H 2 N−(CH 2 ) 4 −、Ph−CH 2 −、CH 2 =CH−CH 2 −、HO−p−Ph−CH 2 −、(CH 3 ) 2 −CH−、Ph−NH−、NH 2 −(CH 2 ) 3 −CH 2 −、およびNH 2 −CH=N−CH=CH−CH 2 −からなる群から選択され、
R 5 は、(C 2 〜C 20 )アルキレン、(C 2 〜C 20 )アルケニレン、アルキルオキシ、およびオリゴエチレングリコールからなる群から選択され、
R 6 は、式(II)
の1,4:3,6−ジアンヒドロヘキシトールの二環式断片であり、
R 7 は、(C 6 〜C 10 )アリール(C 1 〜C 6 )アルキルであり、
R 8 は−(CH 2 ) 4 −であり、
aは少なくとも0.05であり、bは少なくとも0.05であり、かつa+b=1である、薬剤送達系。 - 前記ポリエステルアミドが、前記ペンダント官能基の合計に基づいて少なくとも15%の酸性基を含む、請求項1に記載の薬剤送達系。
- 前記ポリエステルが、PLLA、PLGA、またはポリカプロラクトンである、請求項1に記載の薬剤送達系。
- 前記ポリエステルが、ポリ乳酸(PLA)、ポリグリコール酸(PGA)またはポリ(ラクチド−コ−グリコリド)(PLGA)である、請求項1に記載の薬剤送達系。
- 前記生理活性剤が酸感受性の生理活性剤である、請求項1に記載の薬剤送達系。
- 少なくとも1つの開放された末端を含む、請求項1〜5のいずれか一項に記載の薬剤送達系。
- 2つの開放された末端を含む、請求項6に記載の薬剤送達系。
- 2つの開放された末端を含む繊維であり、結膜下腔中に注入できる、請求項1〜7のいずれか一項に記載の薬剤送達系。
- 前記式(I)中、aが少なくとも0.5である、請求項1〜8のいずれか一項に記載の薬剤送達系。
- 前記式(I)中、
m+p+q=1、q=0.25、p=0.45、およびm=0.3であり、
aが0.75であり、かつa+b=1であり、
R 1 が−(CH 2 ) 8 −であり、R 4 が(CH 3 ) 2 −CH−CH 2 −であり、R 7 がベンジルであり、R 8 が−(CH 2 ) 4 −であり、R 5 が(C 2 〜C 20 )アルキレンである、請求項1〜8のいずれか一項に記載の薬剤送達系。 - 前記式(I)中、
m+p+q=1、q=0.1、p=0.3、およびm=0.6であり、
aが0.5であり、かつa+b=1であり、
R 1 が−(CH 2 ) 4 −であり、R 3 およびR 4 がそれぞれ(CH 3 ) 2 −CH−CH 2 −であり、R 5 が(C 2 〜C 20 )アルキレンであり、R 7 がベンジルであり、R 8 が−(CH 2 ) 4 −である、請求項1〜8のいずれか一項に記載の薬剤送達系。 - 前記生理活性剤が、エタネルセプト、ラニビズマブ、ベバシズマブ、ラタノプロスト、ビマトプロスト、またはトラボプロストである、請求項5に記載の薬剤送達系。
- 50μm〜500μmの平均直径を有する繊維である、請求項1〜12のいずれか一項に記載の薬剤送達系。
- 100μm〜300μmの平均直径を有する繊維である、請求項1〜12のいずれか一項に記載の薬剤送達系。
- 前記生理活性剤が、ラニビズマブ、ラタノプロスト、ビマトプロスト、またはトラボプロストであり、前記生理活性剤を眼に投与することにより、緑内障、高眼圧症、糖尿病性網膜症、または黄斑変性症を治療するために用いられる、請求項1〜14のいずれか一項に記載の薬剤送達系。
- 請求項1〜13のいずれか一項に記載の薬剤送達系を含む、緑内障、高眼圧症、糖尿病性網膜症、または黄斑変性症の治療用製剤。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP14198912 | 2014-12-18 | ||
EP14198912.9 | 2014-12-18 | ||
PCT/EP2015/080503 WO2016097297A1 (en) | 2014-12-18 | 2015-12-18 | Drug delivery system for delivery of acid sensitive drugs |
Publications (2)
Publication Number | Publication Date |
---|---|
JP2017537903A JP2017537903A (ja) | 2017-12-21 |
JP6720447B2 true JP6720447B2 (ja) | 2020-07-08 |
Family
ID=52146214
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP2017527282A Active JP6720447B2 (ja) | 2014-12-18 | 2015-12-18 | 酸感受性薬剤の送達のための薬剤送達系 |
Country Status (7)
Country | Link |
---|---|
US (3) | US10434071B2 (ja) |
EP (1) | EP3233067B1 (ja) |
JP (1) | JP6720447B2 (ja) |
CN (1) | CN107106509B (ja) |
AU (1) | AU2015366355B2 (ja) |
CA (1) | CA2969171C (ja) |
WO (1) | WO2016097297A1 (ja) |
Families Citing this family (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN110022794A (zh) * | 2016-10-05 | 2019-07-16 | 泰坦医药品公司 | 具有减少的突释的用于药物递送的可植入装置 |
DE102017106216A1 (de) * | 2017-03-22 | 2018-09-27 | Amw Gmbh | Extrudierte Depotform zur anhaltenden Wirkstofffreisetzung |
US20200306182A1 (en) * | 2019-03-05 | 2020-10-01 | Aerie Pharmaceuticals, Inc. | Pharmaceutical compositions for treating ocular diseases or disorders |
CN110051650A (zh) * | 2019-04-29 | 2019-07-26 | 南京锐利施生物技术有限公司 | 用于玻璃体注射的贝伐单抗和地塞米松共载的纳米粒药物 |
WO2022235906A1 (en) | 2021-05-05 | 2022-11-10 | Aerie Pharmaceuticals, Inc. | Pharmaceutical preparation |
Family Cites Families (223)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
SE505703C2 (sv) | 1995-12-15 | 1997-09-29 | Polyrand Ab | Linjär blockpolymer innefattande urea- och uretangrupper, förfarande för framställning av linjära blockpolymerer samt användning av blockpolymererna som implantat |
US4129594A (en) | 1977-10-27 | 1978-12-12 | Allied Chemical Corporation | Process for the manufacture of aromatic dicarboxylic acid chlorides |
US4221787A (en) | 1978-03-28 | 1980-09-09 | Interx Research Corporation | Esteramide prodrugs of anti-inflammatory corticosteroids |
US4550730A (en) | 1981-12-07 | 1985-11-05 | Ethicon, Inc. | Flexible monofilament surgical sutures comprising poly(polymethylene terephthalate, isophthalate or cyclohexane-1,4-dicarboxylate-co-dimerate) |
US4443563A (en) | 1983-06-08 | 1984-04-17 | The Dow Chemical Company | Polyurethanes based on 1;4-3:6 dianhydrohexitols |
EP0147780A3 (en) | 1984-01-03 | 1987-03-11 | Merck & Co. Inc. | Drug delivery device |
US5057313A (en) | 1986-02-25 | 1991-10-15 | The Center For Molecular Medicine And Immunology | Diagnostic and therapeutic antibody conjugates |
US5721131A (en) | 1987-03-06 | 1998-02-24 | United States Of America As Represented By The Secretary Of The Navy | Surface modification of polymers with self-assembled monolayers that promote adhesion, outgrowth and differentiation of biological cells |
US5482700A (en) | 1987-03-31 | 1996-01-09 | Schering Aktiengesellschaft | Substituted polyamino, polycarboxy complexing agent dimers for MRI and X-ray contrast |
US4994551A (en) | 1987-12-23 | 1991-02-19 | Pfizer Inc. | Bioabsorbable co-polydepsipeptide |
US5091560A (en) | 1988-03-14 | 1992-02-25 | The Clorox Company | Method for synthesizing acyloxycarboxylic acids |
IL90193A (en) | 1989-05-04 | 1993-02-21 | Biomedical Polymers Int | Polurethane-based polymeric materials and biomedical articles and pharmaceutical compositions utilizing the same |
DE69004415D1 (de) | 1990-03-05 | 1993-12-09 | Minnesota Mining & Mfg | Vorrichtung zur verzögerten Abgabe von pharmakologisch aktiven Verbindungen ins Ohr. |
CA2038605C (en) | 1990-06-15 | 2000-06-27 | Leonard Pinchuk | Crack-resistant polycarbonate urethane polymer prostheses and the like |
US5736371A (en) | 1991-06-04 | 1998-04-07 | A Et S Biovecteurs | Biodegradable particulate vector for transporting molecules having biological activity |
HU222501B1 (hu) | 1991-06-28 | 2003-07-28 | Endorecherche Inc. | MPA-t vagy MGA-t tartalmazó nyújtott hatóanyag-felszabadulású gyógyászati készítmény és eljárás előállítására |
US5206341A (en) | 1991-11-21 | 1993-04-27 | Southern Research Institute | Polymers from hydroxy acids and polycarboxylic acids |
US5286837A (en) | 1992-01-15 | 1994-02-15 | Minnesota Mining And Manufacturing Company | Process for increasing stability of poly(esteramides) |
US5599352A (en) | 1992-03-19 | 1997-02-04 | Medtronic, Inc. | Method of making a drug eluting stent |
US5178635A (en) | 1992-05-04 | 1993-01-12 | Allergan, Inc. | Method for determining amount of medication in an implantable device |
DE4224401A1 (de) | 1992-07-21 | 1994-01-27 | Pharmatech Gmbh | Neue biologisch abbaubare Polymere für die Arzneistoffgalenik |
US5514379A (en) | 1992-08-07 | 1996-05-07 | The General Hospital Corporation | Hydrogel compositions and methods of use |
KR940003548U (ko) | 1992-08-14 | 1994-02-21 | 김형술 | 세탁물 건조기 |
WO1994004642A2 (en) | 1992-08-21 | 1994-03-03 | Colgate-Palmolive Company | Fabric conditioning composition |
ES2105332T3 (es) | 1992-10-14 | 1997-10-16 | Nycomed Imaging As | Polimeros quelantes. |
ES2070076B1 (es) | 1993-04-20 | 1996-04-16 | Cusi Lab | Metodo para aumentar la estabilidad de las nanocapsulas durante su almacenamiento. |
ES2370937T3 (es) | 1993-09-13 | 2011-12-23 | Protein Sciences Corporation | Un método para producir vacunas antigripales polivalentes a base de hemaglutinina. |
US5762939A (en) | 1993-09-13 | 1998-06-09 | Mg-Pmc, Llc | Method for producing influenza hemagglutinin multivalent vaccines using baculovirus |
WO1995008289A2 (en) | 1993-09-16 | 1995-03-30 | Scimed Life Systems, Inc. | Percutaneous repair of cardiovascular anomalies and repair compositions |
US5554692A (en) | 1994-01-06 | 1996-09-10 | Ferro Corporation | Blocked isocyanate crosslinkers based on pentaerythritol for use in thermosetting coatings |
US6551618B2 (en) | 1994-03-15 | 2003-04-22 | University Of Birmingham | Compositions and methods for delivery of agents for neuronal regeneration and survival |
DE69530553T2 (de) | 1994-05-13 | 2004-03-25 | KURARAY CO., LTD, Kurashiki | Medizinisches polymergel |
US5516881A (en) | 1994-08-10 | 1996-05-14 | Cornell Research Foundation, Inc. | Aminoxyl-containing radical spin labeling in polymers and copolymers |
DE4432378A1 (de) | 1994-09-12 | 1996-03-14 | Bayer Ag | Injizierbare liposomale Arzneizubereitungen |
US5485496A (en) | 1994-09-22 | 1996-01-16 | Cornell Research Foundation, Inc. | Gamma irradiation sterilizing of biomaterial medical devices or products, with improved degradation and mechanical properties |
DE19500756A1 (de) | 1995-01-13 | 1996-07-18 | Basf Ag | Biologisch abbaubare Polymere, Verfahren zu deren Herstellung sowie deren Verwendung zur Herstellung bioabbaubarer Formkörper |
AU4620596A (en) | 1995-02-03 | 1996-08-21 | Novartis Ag | Crosslinked polymers containing ester or amide groups |
US5852155A (en) | 1995-03-01 | 1998-12-22 | General Electric Company | Compositions of polyesteramides |
US5906934A (en) | 1995-03-14 | 1999-05-25 | Morphogen Pharmaceuticals, Inc. | Mesenchymal stem cells for cartilage repair |
KR100201352B1 (ko) | 1995-03-16 | 1999-06-15 | 성재갑 | 단일주사 백신 제형 |
FR2732218B1 (fr) | 1995-03-28 | 1997-08-01 | Flamel Tech Sa | Particules a base de polyaminoacide(s) et susceptibles d'etre utilisees comme vecteurs de principe(s) actif(s) et leurs procedes de preparation |
AUPN443995A0 (en) | 1995-07-27 | 1995-08-17 | Csl Limited | Papillomavirus polyprotein |
EP0882085B1 (en) | 1996-02-20 | 2002-07-24 | Massachusetts Institute Of Technology | Biodegradable polymer networks for use in orthopedic and dental applications |
PT932399E (pt) | 1996-03-12 | 2006-05-31 | Pg Txl Co Lp | Pro-farmacos de paclitaxel hidrossoluveis |
KR19990028597A (ko) | 1996-04-30 | 1999-04-15 | 마에다 가쯔노스께 | 폴리에스테르아미드공중합체및그것의제조방법,폴리에스테르아미드단량체및그것의제조방법,그리고폴리에스테르아미드수지조성물 |
US6228391B1 (en) | 1996-05-02 | 2001-05-08 | Terumo Kabushiki Kaisha | Amidine derivatives and drug carriers comprising the same |
US5610241A (en) | 1996-05-07 | 1997-03-11 | Cornell Research Foundation, Inc. | Reactive graft polymer with biodegradable polymer backbone and method for preparing reactive biodegradable polymers |
US5874064A (en) | 1996-05-24 | 1999-02-23 | Massachusetts Institute Of Technology | Aerodynamically light particles for pulmonary drug delivery |
US5916585A (en) | 1996-06-03 | 1999-06-29 | Gore Enterprise Holdings, Inc. | Materials and method for the immobilization of bioactive species onto biodegradable polymers |
US7041785B1 (en) | 1996-08-19 | 2006-05-09 | UNIVERSITé DE SHERBROOKE | B1-bradykinin receptor antagonists and use thereof |
WO1998016201A1 (en) | 1996-10-11 | 1998-04-23 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method |
US6056973A (en) | 1996-10-11 | 2000-05-02 | Sequus Pharmaceuticals, Inc. | Therapeutic liposome composition and method of preparation |
CA2275587C (en) | 1996-12-20 | 2006-10-24 | Alza Corporation | Injectable depot gel composition and method of preparing the composition |
EP0967933B1 (en) | 1997-01-28 | 2004-12-29 | United States Surgical Corporation | Polyesteramide, its preparation and surgical devices fabricated therefrom |
US7062219B2 (en) | 1997-01-31 | 2006-06-13 | Odyssey Thera Inc. | Protein fragment complementation assays for high-throughput and high-content screening |
US5827533A (en) | 1997-02-06 | 1998-10-27 | Duke University | Liposomes containing active agents aggregated with lipid surfactants |
AUPO517897A0 (en) | 1997-02-19 | 1997-04-11 | Csl Limited | Chelating immunostimulating complexes |
US6982249B1 (en) | 1997-04-23 | 2006-01-03 | The Regents Of The University Of Michigan | Bradykinin analogs as selective inhibitors of cell activation |
US6221997B1 (en) | 1997-04-28 | 2001-04-24 | Kimberly Ann Woodhouse | Biodegradable polyurethanes |
US5972027A (en) | 1997-09-30 | 1999-10-26 | Scimed Life Systems, Inc | Porous stent drug delivery system |
US6004573A (en) | 1997-10-03 | 1999-12-21 | Macromed, Inc. | Biodegradable low molecular weight triblock poly(lactide-co-glycolide) polyethylene glycol copolymers having reverse thermal gelation properties |
US20020164374A1 (en) | 1997-10-29 | 2002-11-07 | John Jackson | Polymeric systems for drug delivery and uses thereof |
SE513149C2 (sv) | 1997-12-05 | 2000-07-17 | Katarina Edwards | Läkemedelsdistributionssystem med tvåstegsmålsökning, till specifika celler eller vävnad och till dess cellkärna |
ZA9811376B (en) | 1997-12-12 | 1999-06-28 | Expression Genetics Inc | Biodegradable mixed polymeric micelles for gene delivery |
EP0926184A1 (en) | 1997-12-25 | 1999-06-30 | Mitsui Chemicals, Inc. | Process for production of polyamino acid derivative |
US6541606B2 (en) | 1997-12-31 | 2003-04-01 | Altus Biologics Inc. | Stabilized protein crystals formulations containing them and methods of making them |
US6841617B2 (en) | 2000-09-28 | 2005-01-11 | Battelle Memorial Institute | Thermogelling biodegradable aqueous polymer solution |
US7658727B1 (en) | 1998-04-20 | 2010-02-09 | Medtronic, Inc | Implantable medical device with enhanced biocompatibility and biostability |
US6171610B1 (en) | 1998-04-24 | 2001-01-09 | University Of Massachusetts | Guided development and support of hydrogel-cell compositions |
EP0963758A3 (en) | 1998-05-07 | 2000-03-22 | Universiteit Gent | Synthetic polyaminoacid complexes for delivery of nucleic acids to target cells |
EP1080370A4 (en) | 1998-05-29 | 2003-07-30 | Epimmune Inc | IDENTIFICATION OF RESILIENT DR EPITOPES LARGELY REACTIVE |
US6153252A (en) | 1998-06-30 | 2000-11-28 | Ethicon, Inc. | Process for coating stents |
NZ509186A (en) | 1998-07-17 | 2005-01-28 | Skyepharma Inc | Biodegradable compositions for the controlled release of encapsulated substances |
WO2000012619A1 (en) | 1998-08-31 | 2000-03-09 | Cornell Research Foundation, Inc. | Dextran-maleic acid monoesters and hydrogels based thereon |
US6103526A (en) | 1998-10-08 | 2000-08-15 | Protein Sciences Corporation | Spodoptera frugiperda single cell suspension cell line in serum-free media, methods of producing and using |
US7026156B1 (en) | 1999-02-04 | 2006-04-11 | The University Of Georgia Research Foundation, Inc. | Diagnostic and protective antigen gene sequences of ichthyophthirius |
RU2001125666A (ru) | 1999-02-19 | 2004-02-20 | Биозерв Аг (De) | Биоразлагаемые композиты для получения микрокапсул |
US6342300B1 (en) | 1999-02-20 | 2002-01-29 | Celanese Ventures Gmbh | Biodegradable polymers based on natural and renewable raw materials especially isosorbite |
GB9904627D0 (en) | 1999-03-02 | 1999-04-21 | Danbiosyst Uk | Polymer compositions for polynucleotide delivery |
US6716445B2 (en) | 1999-04-12 | 2004-04-06 | Cornell Research Foundation, Inc. | Hydrogel entrapping therapeutic agent and stent with coating comprising this |
US7238368B2 (en) | 1999-04-23 | 2007-07-03 | Alza Corporation | Releasable linkage and compositions containing same |
US6521431B1 (en) | 1999-06-22 | 2003-02-18 | Access Pharmaceuticals, Inc. | Biodegradable cross-linkers having a polyacid connected to reactive groups for cross-linking polymer filaments |
US6352667B1 (en) | 1999-08-24 | 2002-03-05 | Absorbable Polymer Technologies, Inc. | Method of making biodegradable polymeric implants |
US9289487B2 (en) | 1999-09-14 | 2016-03-22 | Antigen Express, Inc. | II-key/antigenic epitope hybrid peptide vaccines |
US20030130185A1 (en) | 2000-09-29 | 2003-07-10 | David Bar-Or | Metal-binding compounds and uses therefor |
US7582311B1 (en) | 1999-10-15 | 2009-09-01 | Genentech, Inc. | Injection vehicle for polymer-based formulations |
US6902935B2 (en) | 1999-12-15 | 2005-06-07 | Medispectra, Inc. | Methods of monitoring effects of chemical agents on a sample |
US6703040B2 (en) | 2000-01-11 | 2004-03-09 | Intralytix, Inc. | Polymer blends as biodegradable matrices for preparing biocomposites |
EP1250053A2 (en) | 2000-01-11 | 2002-10-23 | Intralytix Inc. | Method for produce sanitation using bacteriophages |
US20030229393A1 (en) | 2001-03-15 | 2003-12-11 | Kutryk Michael J. B. | Medical device with coating that promotes cell adherence and differentiation |
US20070055367A1 (en) | 2000-03-15 | 2007-03-08 | Orbus Medical Technologies, Inc. | Medical device with coating that promotes endothelial cell adherence and differentiation |
US20050271701A1 (en) | 2000-03-15 | 2005-12-08 | Orbus Medical Technologies, Inc. | Progenitor endothelial cell capturing with a drug eluting implantable medical device |
US20070141107A1 (en) | 2000-03-15 | 2007-06-21 | Orbusneich Medical, Inc. | Progenitor Endothelial Cell Capturing with a Drug Eluting Implantable Medical Device |
KR100860860B1 (ko) | 2000-03-15 | 2008-09-29 | 오르버스네이치 메디칼 인코포레이티드 | 내피 세포 부착을 촉진하는 코팅 |
US9522217B2 (en) | 2000-03-15 | 2016-12-20 | Orbusneich Medical, Inc. | Medical device with coating for capturing genetically-altered cells and methods for using same |
US20070191932A1 (en) | 2000-03-15 | 2007-08-16 | Orbusneich Medical, Inc. | Medical device with coating for capturing genetically-altered cells and methods for using same |
WO2001070266A2 (en) | 2000-03-17 | 2001-09-27 | Millennium Pharmaceuticals, Inc. | Method of inhibiting stenosis and restenosis with a mixture of antibodies anti cd18 and anti ccr2 |
WO2001091703A2 (en) | 2000-05-26 | 2001-12-06 | Color Access, Inc. | Low emulsifier multiple emulsions |
AU2001263946A1 (en) | 2000-05-31 | 2001-12-11 | Mnemoscience Gmbh | Shape memory thermoplastics and polymer networks for tissue engineering |
US20040258702A1 (en) | 2000-06-22 | 2004-12-23 | Blonder Joan P. | Vaccine delivery |
US20020165347A1 (en) | 2000-06-30 | 2002-11-07 | Amgen, Inc. | B7-like molecules and uses thereof |
US6503538B1 (en) | 2000-08-30 | 2003-01-07 | Cornell Research Foundation, Inc. | Elastomeric functional biodegradable copolyester amides and copolyester urethanes |
US20060286064A1 (en) | 2000-08-30 | 2006-12-21 | Medivas, Llc | Therapeutic polymers and methods |
AU2006204654B2 (en) | 2000-08-30 | 2008-06-05 | Cornell Research Foundation, Inc. | Elastomeric functional biodegradable copolyester amides and copolyester urethanes |
US20060177416A1 (en) | 2003-10-14 | 2006-08-10 | Medivas, Llc | Polymer particle delivery compositions and methods of use |
US7304122B2 (en) | 2001-08-30 | 2007-12-04 | Cornell Research Foundation, Inc. | Elastomeric functional biodegradable copolyester amides and copolyester urethanes |
CN1119172C (zh) | 2000-12-12 | 2003-08-27 | 天津大学 | 脂肪族聚酯表面的壳聚糖/明胶网络修饰方法 |
FR2820145B1 (fr) | 2001-01-31 | 2004-01-23 | Aventis Pharma Sa | Souche de levure produisant des steroides de facon autonome |
CA2747159A1 (en) | 2001-05-07 | 2002-11-07 | Queen's University At Kingston | Biodegradable elastomer and method of preparing same |
EP1392751B1 (en) | 2001-05-07 | 2007-07-04 | Cornell Research Foundation, Inc. | Biodegradable copolymers linked to segment with a plurality of functional groups |
US20030064053A1 (en) | 2001-08-31 | 2003-04-03 | Shengjiang Liu | Multivalent protein conjugate with multiple ligand-binding domains of receptors |
US7030082B2 (en) | 2001-09-07 | 2006-04-18 | Nobex Corporation | Pharmaceutical compositions of drug-oligomer conjugates and methods of treating disease therewith |
GB0122318D0 (en) | 2001-09-14 | 2001-11-07 | Novartis Ag | Organic compounds |
FR2831165B1 (fr) | 2001-10-23 | 2005-06-17 | Mane Fils V | Nouveaux derives du norbornane et du norbornene, leur utilisation et produits parfumes les contenant |
GB0126157D0 (en) | 2001-10-31 | 2002-01-02 | Univ Aberdeen | Therapeutic compounds |
WO2003062298A1 (en) | 2002-01-17 | 2003-07-31 | Polyrava Llc | Co-poly(ester amide) and co-poly(ester urethane) compositions which exhibit biodegradability, methods for making same and uses for same |
ATE441706T1 (de) | 2002-02-20 | 2009-09-15 | Gen Hospital Corp | Konjugate mit biologisch abbaubarem polymer und verwendung dafür |
US20050260259A1 (en) | 2004-04-23 | 2005-11-24 | Bolotin Elijah M | Compositions for treatment with glucagon-like peptide, and methods of making and using the same |
WO2003073993A2 (en) | 2002-03-01 | 2003-09-12 | Colb Mark A | Binding of red blood cell to exposed subendothelial surfaces to impede platelet deposition thereon and/or for use in targeted drug delivery thereto |
WO2003099359A1 (en) | 2002-05-09 | 2003-12-04 | Kurve Technology, Inc. | Particle dispersion chamber for nasal nebulizer |
DE60306769T2 (de) | 2002-05-15 | 2006-11-16 | Rutgers, The State University | Triblockpolymere für arzneistoff- oder genzufuhr auf nanokugelbasis |
US20040057958A1 (en) | 2002-05-17 | 2004-03-25 | Waggoner David W. | Immunogenicity-enhancing carriers and compositions thereof and methods of using the same |
US6994867B1 (en) | 2002-06-21 | 2006-02-07 | Advanced Cardiovascular Systems, Inc. | Biocompatible carrier containing L-arginine |
CA2494342A1 (en) | 2002-07-31 | 2004-02-12 | Alza Corporation | Injectable depot compositions and uses thereof |
US20050019404A1 (en) | 2003-06-30 | 2005-01-27 | Hsing-Wen Sung | Drug-eluting biodegradable stent |
US8591782B2 (en) | 2002-08-23 | 2013-11-26 | National Cerebral And Cardiovascular Center | Process for producing stent |
US7794494B2 (en) | 2002-10-11 | 2010-09-14 | Boston Scientific Scimed, Inc. | Implantable medical devices |
WO2004040339A1 (en) | 2002-11-01 | 2004-05-13 | Koninklijke Philips Electronics N.V. | Method of manufacturing of a cholesteric layer |
WO2004049907A2 (en) | 2002-11-27 | 2004-06-17 | University Of Louisville Research Foundation | Compositions and methods for treating transplants |
WO2004060920A1 (en) | 2002-12-31 | 2004-07-22 | Altus Pharmaceuticals Inc. | Complexes of protein crystals and ionic polymers |
US20050019366A1 (en) | 2002-12-31 | 2005-01-27 | Zeldis Jerome B. | Drug-coated stents and methods of use therefor |
US20040170685A1 (en) | 2003-02-26 | 2004-09-02 | Medivas, Llc | Bioactive stents and methods for use thereof |
US20040253293A1 (en) | 2003-06-16 | 2004-12-16 | Afshin Shafiee | Rate controlled release of a pharmaceutical agent in a biodegradable device |
US20050053667A1 (en) | 2003-07-09 | 2005-03-10 | Darrell Irvine | Programmed immune responses using a vaccination node |
US20050013812A1 (en) | 2003-07-14 | 2005-01-20 | Dow Steven W. | Vaccines using pattern recognition receptor-ligand:lipid complexes |
LT1675622T (lt) | 2003-09-17 | 2017-09-11 | Nektar Therapeutics | Daugiašakio polimero provaistai |
KR20060085246A (ko) | 2003-09-18 | 2006-07-26 | 마커사이트, 인코포레이티드 | 경공막 전달 |
US20060188469A1 (en) | 2003-10-14 | 2006-08-24 | Medivas, Llc | Vaccine delivery compositions and methods of use |
US20060188486A1 (en) | 2003-10-14 | 2006-08-24 | Medivas, Llc | Wound care polymer compositions and methods for use thereof |
US20080160089A1 (en) | 2003-10-14 | 2008-07-03 | Medivas, Llc | Vaccine delivery compositions and methods of use |
US7794706B2 (en) | 2003-10-14 | 2010-09-14 | Medivas, Llc | Bioactive wound dressings and implantable devices and methods of use |
WO2005046519A1 (en) | 2003-11-07 | 2005-05-26 | Gp Medical, Inc. | Drug-eluting biodegradable stent |
JP2005139139A (ja) | 2003-11-07 | 2005-06-02 | Idemitsu Technofine Co Ltd | 化粧料組成物 |
EP1696822B1 (en) * | 2003-11-13 | 2010-03-17 | PSivida US Inc. | Injectable sustained release implant having a bioerodible matrix core and a bioerodible skin |
WO2005065121A2 (en) | 2003-12-02 | 2005-07-21 | Cytimmune Sciences, Inc. | Methods and compositions for the production of monoclonal antibodies |
US7220816B2 (en) | 2003-12-16 | 2007-05-22 | Advanced Cardiovascular Systems, Inc. | Biologically absorbable coatings for implantable devices based on poly(ester amides) and methods for fabricating the same |
US8685431B2 (en) | 2004-03-16 | 2014-04-01 | Advanced Cardiovascular Systems, Inc. | Biologically absorbable coatings for implantable devices based on copolymers having ester bonds and methods for fabricating the same |
US20060013855A1 (en) | 2004-04-05 | 2006-01-19 | Medivas, Llc | Bioactive stents for type II diabetics and methods for use thereof |
US8163269B2 (en) | 2004-04-05 | 2012-04-24 | Carpenter Kenneth W | Bioactive stents for type II diabetics and methods for use thereof |
US20080288057A1 (en) | 2004-04-05 | 2008-11-20 | Carpenter Kenneth W | Bioactive Stents For Type II Diabetics and Methods for Use Thereof |
EP1737379A4 (en) | 2004-04-05 | 2011-08-17 | Medivas Llc | BIOACTIVE VASCULAR STENTS FOR DIABETES TYPE II AND METHODS OF USE |
KR101148445B1 (ko) | 2004-04-28 | 2012-07-05 | 안지오디바이스 인터내셔널 게엠베하 | 가교된 생합성물질을 형성하기 위한 조성물 및 시스템, 및 이와 관련된 제조 및 사용 방법 |
US20050288481A1 (en) | 2004-04-30 | 2005-12-29 | Desnoyer Jessica R | Design of poly(ester amides) for the control of agent-release from polymeric compositions |
US7799336B2 (en) * | 2004-04-30 | 2010-09-21 | Allergan, Inc. | Hypotensive lipid-containing biodegradable intraocular implants and related methods |
US7820732B2 (en) | 2004-04-30 | 2010-10-26 | Advanced Cardiovascular Systems, Inc. | Methods for modulating thermal and mechanical properties of coatings on implantable devices |
KR20070008714A (ko) | 2004-04-30 | 2007-01-17 | 오르버스네이치 메디칼 인코포레이티드 | 유전적으로-변형된 세포 포획용 코팅을 갖는 의료 장치 및이의 사용 방법 |
US7771742B2 (en) | 2004-04-30 | 2010-08-10 | Allergan, Inc. | Sustained release intraocular implants containing tyrosine kinase inhibitors and related methods |
US20050265960A1 (en) | 2004-05-26 | 2005-12-01 | Pacetti Stephen D | Polymers containing poly(ester amides) and agents for use with medical articles and methods of fabricating the same |
AU2005244848A1 (en) | 2004-05-12 | 2005-12-01 | Medivas, Llc | Wound healing polymer compositions and methods for use thereof |
US8821859B2 (en) * | 2004-05-19 | 2014-09-02 | Agency For Science, Technology And Research | Methods and articles for the delivery of therapeutic agents |
WO2005121250A2 (en) | 2004-06-03 | 2005-12-22 | Cornell Research Foundation, Inc. | Unsaturated poly(ester-amide) biomaterials |
US20050271700A1 (en) | 2004-06-03 | 2005-12-08 | Desnoyer Jessica R | Poly(ester amide) coating composition for implantable devices |
US20050287184A1 (en) | 2004-06-29 | 2005-12-29 | Hossainy Syed F A | Drug-delivery stent formulations for restenosis and vulnerable plaque |
JP2008505978A (ja) | 2004-07-12 | 2008-02-28 | アラーガン、インコーポレイテッド | 眼病用組成物および眼病治療法 |
US8980300B2 (en) | 2004-08-05 | 2015-03-17 | Advanced Cardiovascular Systems, Inc. | Plasticizers for coating compositions |
US7166680B2 (en) | 2004-10-06 | 2007-01-23 | Advanced Cardiovascular Systems, Inc. | Blends of poly(ester amide) polymers |
US20060115455A1 (en) | 2004-10-22 | 2006-06-01 | Reed Kenneth C | Therapeutic RNAi agents for treating psoriasis |
CA2585740A1 (en) | 2004-10-28 | 2006-05-11 | Medivas, Llc | Bioactive wound dressings and implantable devices and methods of use |
US7390497B2 (en) | 2004-10-29 | 2008-06-24 | Advanced Cardiovascular Systems, Inc. | Poly(ester amide) filler blends for modulation of coating properties |
US20060159918A1 (en) | 2004-12-22 | 2006-07-20 | Fiber Innovation Technology, Inc. | Biodegradable fibers exhibiting storage-stable tenacity |
EP1865983A2 (en) | 2005-02-01 | 2007-12-19 | Medivas, LLC | Vaccine delivery compositions and methods of use |
CA2596011C (en) | 2005-02-17 | 2013-05-14 | Medivas, Llc | Polymer particle delivery compositions and methods of use |
CN100551950C (zh) | 2005-03-21 | 2009-10-21 | 中国科学院成都有机化学有限公司 | 一种可降解聚酯酰胺共聚物的制备方法 |
KR100696125B1 (ko) | 2005-03-30 | 2007-03-22 | 엘지전자 주식회사 | 스크롤 압축기의 고정스크롤 |
WO2006110487A1 (en) * | 2005-04-08 | 2006-10-19 | Surmodics, Inc. | Sustained release implants for subretinal delivery |
JP2008542393A (ja) | 2005-06-03 | 2008-11-27 | メディバス エルエルシー | 治療用ポリマーおよび使用方法 |
JP5122460B2 (ja) | 2005-09-16 | 2013-01-16 | アラーガン、インコーポレイテッド | 治療薬の眼内輸送のための組成物および方法 |
EP1926780B1 (en) | 2005-09-22 | 2013-08-14 | Medivas, LLC | Bis-( -amino)-diol-diester-containing poly(ester amide) and poly(ester urethane) compositions and methods of use |
US8652504B2 (en) | 2005-09-22 | 2014-02-18 | Medivas, Llc | Solid polymer delivery compositions and methods for use thereof |
US20070071790A1 (en) | 2005-09-28 | 2007-03-29 | Northwestern University | Biodegradable nanocomposites with enhance mechanical properties for soft tissue |
WO2007050415A2 (en) | 2005-10-21 | 2007-05-03 | Medivas, Llc | Poly(ester urea) polymers and methods of use |
US20070106035A1 (en) | 2005-10-26 | 2007-05-10 | Medivas, Llc | Aromatic di-acid-containing poly (ester amide) polymers and methods of use |
US20070134332A1 (en) | 2005-11-21 | 2007-06-14 | Medivas, Llc | Polymer particles for delivery of macromolecules and methods of use |
WO2007067744A2 (en) | 2005-12-07 | 2007-06-14 | Medivas, Llc | Method for assembling a polymer-biologic delivery composition |
US8974815B2 (en) | 2005-12-16 | 2015-03-10 | Cornell University | Fibrous membrane for biomedical application based on poly(ester-amide)s |
WO2007089870A2 (en) | 2006-01-31 | 2007-08-09 | Medivas, Llc | Vaccine delivery compositions and methods of use |
TWI376239B (en) | 2006-02-01 | 2012-11-11 | Andrew Xian Chen | Vitamin e succinate stabilized pharmaceutical compositions, methods for the preparation and the use thereof |
EP2004145A4 (en) | 2006-03-24 | 2013-07-03 | Medivas Llc | ALKYLENE DICARBOXYLATE-CONTAINING BIODEGRADABLE POLY (ESTER AMIDE) AND METHOD OF USE |
EP2019645A4 (en) | 2006-05-02 | 2013-03-06 | Medivas Llc | RELEASE OF OPHTHALMOLOGICAL ACTIVITIES OUTSIDE OR WITHIN THE EYE |
US20070282011A1 (en) | 2006-05-09 | 2007-12-06 | Medivas, Llc | Biodegradable water soluble polymers |
US7779625B2 (en) | 2006-05-11 | 2010-08-24 | Kalypto Medical, Inc. | Device and method for wound therapy |
CA2690878A1 (en) | 2006-06-09 | 2007-12-21 | Medivas, Llc | Biodegradable polymer adhesion barriers |
JP2008027269A (ja) | 2006-07-24 | 2008-02-07 | Matsushita Electric Ind Co Ltd | 通信機器およびプログラム更新方法 |
US20080050419A1 (en) | 2006-08-18 | 2008-02-28 | Medivas, Llc | Epoxy-containing poly(ester amides) and method of use |
US8936780B2 (en) | 2006-08-30 | 2015-01-20 | Advanced Cardiovascular Systems, Inc. | Stimuli responsive polyester amide particles |
JP2010502822A (ja) | 2006-09-05 | 2010-01-28 | メディバス エルエルシー | ポリマー安定化リポソーム組成物および使用方法 |
CN101168595A (zh) | 2006-10-27 | 2008-04-30 | 湖南大学 | 可降解的不饱和聚酯酰胺树脂及其合成方法 |
CA2685965A1 (en) | 2007-03-30 | 2008-10-09 | Medivas, Llc | Bioabsorbable elastomeric polymer networks, cross-linkers and methods of use |
US9737638B2 (en) | 2007-06-20 | 2017-08-22 | Abbott Cardiovascular Systems, Inc. | Polyester amide copolymers having free carboxylic acid pendant groups |
JP2010533548A (ja) | 2007-07-17 | 2010-10-28 | メディバス エルエルシー | 生体吸収性エラストマー動脈支持装置および使用方法 |
EP2170419A1 (en) | 2007-07-18 | 2010-04-07 | Board Of Trustees Of The University Of Illinois | Temporal release of growth factors from 3d micro rod scaffolds for tissue regeneration |
CA2709412A1 (en) | 2007-07-24 | 2009-01-29 | Medivas, Llc | Biodegradable cationic polymer gene transfer compositions and methods of use |
US20090068743A1 (en) | 2007-08-23 | 2009-03-12 | Medivas, Llc | Cationic alpha-amino acid-containing biodegradable polymer gene transfer compositions |
US20110027379A1 (en) | 2007-12-06 | 2011-02-03 | Cornell University | Oligo-Ethylene Glycol-Based Polymer Compositions and Methods of Use |
JP2011523669A (ja) | 2008-05-07 | 2011-08-18 | メディバス エルエルシー | 生分解性金属キレート化ポリマーおよびワクチン |
CA2733686A1 (en) | 2008-08-13 | 2010-02-18 | Medivas, Llc | Aabb-poly(depsipeptide) biodegradable polymers and methods of use |
US20120027859A1 (en) | 2008-10-15 | 2012-02-02 | Turnell William G | Biodegradable Proline-Based Polymers |
US20100291182A1 (en) * | 2009-01-21 | 2010-11-18 | Arsenal Medical, Inc. | Drug-Loaded Fibers |
US20100247606A1 (en) | 2009-03-25 | 2010-09-30 | Allergan, Inc. | Intraocular sustained release drug delivery systems and methods for treating ocular conditions |
WO2011045443A1 (en) | 2009-10-16 | 2011-04-21 | Dsm Ip Assets B.V. | Coatings comprising bis-(alpha-amino-diol-diester) containing polyesteramide |
US20110104069A1 (en) * | 2009-10-30 | 2011-05-05 | The Ohio State University | Multi-functional biodegradable particles for selectable targeting, imaging, and therapeutic delivery and use thereof for treating ocular disorders |
EP2571526B1 (en) | 2010-05-17 | 2019-03-13 | Novaer Holdings, Inc. | Drug delivery devices for delivery of ocular therapeutic agents |
US20140179802A1 (en) | 2011-05-02 | 2014-06-26 | Dsm Ip Assets B.V. | Fiber comprising a biodegradable polymer |
WO2012150255A1 (en) * | 2011-05-02 | 2012-11-08 | Dsm Ip Assets B.V. | Bis-(alpha-amino-diol-diester) containing polyesteramide for ophtamology |
EP2723800B1 (en) | 2011-06-23 | 2015-10-07 | DSM IP Assets B.V. | Micro- or nanoparticles comprising a biodegradable polyesteramide copolymer for use in the delivery of bioactive agents |
CN102397258B (zh) * | 2011-11-18 | 2013-04-10 | 中国科学院长春应用化学研究所 | 胰岛素载药微球及其制备方法 |
US20150038415A1 (en) | 2011-12-16 | 2015-02-05 | Dsm Ip Assets B.V. | Process for the manufacturing of a drug delivery system based on a polymer comprising a dispersed bioactive agent |
WO2013181022A1 (en) * | 2012-05-30 | 2013-12-05 | Boston Scientific Scimed, Inc. | Injectable biodegradable particles for controlled therapeutic agent release |
US9789189B2 (en) | 2012-10-02 | 2017-10-17 | Dsm Ip Assets Bv | Drug delivery composition comprising proteins and biodegradable polyesteramides |
EP2911647B1 (en) | 2012-10-23 | 2018-03-07 | DSM IP Assets B.V. | Process for the manufacturing of a multilayer drug delivery construct |
EP3702394B1 (en) * | 2012-10-24 | 2023-11-22 | DSM IP Assets B.V. | Fibers comprising polyesteramide copolymers for drug delivery |
US10538864B2 (en) | 2012-10-24 | 2020-01-21 | Dsm Ip Assets, B.V. | Fibers comprising polyesteramide copolymers for drug delivery |
EP2934614B1 (en) | 2012-12-20 | 2021-03-17 | DSM IP Assets B.V. | Coating comprising polyesteramide copolymers for drug delivery |
-
2015
- 2015-12-18 WO PCT/EP2015/080503 patent/WO2016097297A1/en active Application Filing
- 2015-12-18 CA CA2969171A patent/CA2969171C/en active Active
- 2015-12-18 AU AU2015366355A patent/AU2015366355B2/en active Active
- 2015-12-18 US US15/534,499 patent/US10434071B2/en active Active
- 2015-12-18 CN CN201580069239.7A patent/CN107106509B/zh active Active
- 2015-12-18 JP JP2017527282A patent/JP6720447B2/ja active Active
- 2015-12-18 EP EP15816455.8A patent/EP3233067B1/en active Active
-
2019
- 2019-08-23 US US16/549,127 patent/US10888531B2/en active Active
-
2020
- 2020-11-04 US US17/088,700 patent/US11202762B2/en active Active
Also Published As
Publication number | Publication date |
---|---|
EP3233067A1 (en) | 2017-10-25 |
CN107106509A (zh) | 2017-08-29 |
US10434071B2 (en) | 2019-10-08 |
US20200038337A1 (en) | 2020-02-06 |
JP2017537903A (ja) | 2017-12-21 |
US10888531B2 (en) | 2021-01-12 |
CA2969171C (en) | 2023-12-12 |
US20210052509A1 (en) | 2021-02-25 |
US11202762B2 (en) | 2021-12-21 |
AU2015366355A1 (en) | 2017-06-29 |
US20170367992A1 (en) | 2017-12-28 |
EP3233067B1 (en) | 2019-11-06 |
WO2016097297A1 (en) | 2016-06-23 |
AU2015366355B2 (en) | 2020-05-28 |
CN107106509B (zh) | 2021-11-30 |
CA2969171A1 (en) | 2016-06-23 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
US11202762B2 (en) | Drug delivery system for delivery of acid sensitivity drugs | |
TWI332846B (en) | Ocular implant made by a double extrusion process | |
KR101430760B1 (ko) | 후안부 조직으로 선택적으로 침투하는 글루코코르티코이드유도체를 사용한 안과 요법 | |
US20060024350A1 (en) | Biodegradable ocular devices, methods and systems | |
US20080095822A1 (en) | Active Substance Delivery System Comprising A Hydrogel Atrix And Microcarriers | |
JP6282231B2 (ja) | 固化するデポー形成の注入可能な薬物製剤に懸濁される持続放出された生分解性または生体侵食性微小球または微小粒子 | |
US20110238036A1 (en) | Sustained release delivery devices | |
AU2019240562B2 (en) | Intravitreal drug delivery systems for the treatment of ocular conditions | |
KR20030003095A (ko) | 생흡수성 중합체성 왁스를 사용한 조성물 및 의료 장치 | |
CN111481513A (zh) | 缓释微球药物递送系统及其制备方法 | |
JPH11508224A (ja) | 多重ドラッグデリバリーシステム | |
WO2008025111A2 (en) | Biodegradable device for intraocular drug delivery | |
Marques et al. | PKPD of PLGA-PEG-PLGA Copolymeric Micelles | |
JP6303199B2 (ja) | 薬物送達のためのポリエステルアミドコポリマーを含む繊維 | |
Letchford et al. | Lactide and glycolide polymers | |
Sinha et al. | Current polyesteric systems for advanced drug delivery | |
JP2023500035A (ja) | 高いガラス転移温度を有するポリエステルアミドコポリマー | |
Pawar et al. | 17 Injectable Polymers for Regional Drug Delivery | |
Kompella | Nagesh Bandi GlaxoSmithKline, Parsippany, New Jersey, USA Christopher B. Roberts and Ram B. Gupta Department of Chemical Engineering, Auburn University, Auburn, Alabama, USA | |
WO2002038183A2 (en) | Delivery devices |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
A621 | Written request for application examination |
Free format text: JAPANESE INTERMEDIATE CODE: A621 Effective date: 20181204 |
|
A977 | Report on retrieval |
Free format text: JAPANESE INTERMEDIATE CODE: A971007 Effective date: 20190913 |
|
A131 | Notification of reasons for refusal |
Free format text: JAPANESE INTERMEDIATE CODE: A131 Effective date: 20191001 |
|
A521 | Request for written amendment filed |
Free format text: JAPANESE INTERMEDIATE CODE: A523 Effective date: 20191224 |
|
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: 20200519 |
|
A61 | First payment of annual fees (during grant procedure) |
Free format text: JAPANESE INTERMEDIATE CODE: A61 Effective date: 20200522 |
|
R150 | Certificate of patent or registration of utility model |
Ref document number: 6720447 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 |