KR930001305B1 - 당 응답형 고분자 복합체(Polymer Complexes of Sugar Response Type) - Google Patents
당 응답형 고분자 복합체(Polymer Complexes of Sugar Response Type) Download PDFInfo
- Publication number
- KR930001305B1 KR930001305B1 KR1019900016644A KR900016644A KR930001305B1 KR 930001305 B1 KR930001305 B1 KR 930001305B1 KR 1019900016644 A KR1019900016644 A KR 1019900016644A KR 900016644 A KR900016644 A KR 900016644A KR 930001305 B1 KR930001305 B1 KR 930001305B1
- Authority
- KR
- South Korea
- Prior art keywords
- polymer
- sugar
- acid
- boronic acid
- complex
- Prior art date
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- 229920000642 polymer Polymers 0.000 title claims description 155
- 235000000346 sugar Nutrition 0.000 title claims description 60
- 230000004044 response Effects 0.000 title claims description 7
- NOESYZHRGYRDHS-UHFFFAOYSA-N insulin Chemical compound N1C(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(NC(=O)CN)C(C)CC)CSSCC(C(NC(CO)C(=O)NC(CC(C)C)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CCC(N)=O)C(=O)NC(CC(C)C)C(=O)NC(CCC(O)=O)C(=O)NC(CC(N)=O)C(=O)NC(CC=2C=CC(O)=CC=2)C(=O)NC(CSSCC(NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2C=CC(O)=CC=2)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)C(CCC(O)=O)NC(=O)C(C(C)C)NC(=O)C(CC(C)C)NC(=O)C(CC=2NC=NC=2)NC(=O)C(CO)NC(=O)CNC2=O)C(=O)NCC(=O)NC(CCC(O)=O)C(=O)NC(CCCNC(N)=N)C(=O)NCC(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC=CC=3)C(=O)NC(CC=3C=CC(O)=CC=3)C(=O)NC(C(C)O)C(=O)N3C(CCC3)C(=O)NC(CCCCN)C(=O)NC(C)C(O)=O)C(=O)NC(CC(N)=O)C(O)=O)=O)NC(=O)C(C(C)CC)NC(=O)C(CO)NC(=O)C(C(C)O)NC(=O)C1CSSCC2NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C(CCC(N)=O)NC(=O)C(CC(N)=O)NC(=O)C(NC(=O)C(N)CC=1C=CC=CC=1)C(C)C)CC1=CN=CN1 NOESYZHRGYRDHS-UHFFFAOYSA-N 0.000 claims description 59
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- HXITXNWTGFUOAU-UHFFFAOYSA-N phenylboronic acid Chemical compound OB(O)C1=CC=CC=C1 HXITXNWTGFUOAU-UHFFFAOYSA-N 0.000 claims description 25
- GBBUBIKYAQLESK-UHFFFAOYSA-N [3-(2-methylprop-2-enoylamino)phenyl]boronic acid Chemical group CC(=C)C(=O)NC1=CC=CC(B(O)O)=C1 GBBUBIKYAQLESK-UHFFFAOYSA-N 0.000 claims description 19
- -1 isotarin Chemical compound 0.000 claims description 18
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- STVZJERGLQHEKB-UHFFFAOYSA-N ethylene glycol dimethacrylate Substances CC(=C)C(=O)OCCOC(=O)C(C)=C STVZJERGLQHEKB-UHFFFAOYSA-N 0.000 claims description 11
- DBCAQXHNJOFNGC-UHFFFAOYSA-N 4-bromo-1,1,1-trifluorobutane Chemical compound FC(F)(F)CCCBr DBCAQXHNJOFNGC-UHFFFAOYSA-N 0.000 claims description 10
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- YLGYACDQVQQZSW-UHFFFAOYSA-N n,n-dimethylprop-2-enamide Chemical compound CN(C)C(=O)C=C YLGYACDQVQQZSW-UHFFFAOYSA-N 0.000 claims description 9
- 229940088644 n,n-dimethylacrylamide Drugs 0.000 claims description 8
- ULVXDHIJOKEBMW-UHFFFAOYSA-N [3-(prop-2-enoylamino)phenyl]boronic acid Chemical compound OB(O)C1=CC=CC(NC(=O)C=C)=C1 ULVXDHIJOKEBMW-UHFFFAOYSA-N 0.000 claims description 7
- MYRTYDVEIRVNKP-UHFFFAOYSA-N 1,2-Divinylbenzene Chemical compound C=CC1=CC=CC=C1C=C MYRTYDVEIRVNKP-UHFFFAOYSA-N 0.000 claims description 6
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- 238000006116 polymerization reaction Methods 0.000 claims description 6
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- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 claims description 3
- OMDQUFIYNPYJFM-XKDAHURESA-N (2r,3r,4s,5r,6s)-2-(hydroxymethyl)-6-[[(2r,3s,4r,5s,6r)-4,5,6-trihydroxy-3-[(2s,3s,4s,5s,6r)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxan-2-yl]methoxy]oxane-3,4,5-triol Chemical compound O[C@@H]1[C@@H](O)[C@@H](O)[C@@H](CO)O[C@@H]1OC[C@@H]1[C@@H](O[C@H]2[C@H]([C@@H](O)[C@H](O)[C@@H](CO)O2)O)[C@H](O)[C@H](O)[C@H](O)O1 OMDQUFIYNPYJFM-XKDAHURESA-N 0.000 claims description 3
- QWMJEUJXWVZSAG-UHFFFAOYSA-N (4-ethenylphenyl)boronic acid Chemical compound OB(O)C1=CC=C(C=C)C=C1 QWMJEUJXWVZSAG-UHFFFAOYSA-N 0.000 claims description 3
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- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 3
- KMICWMXRUOETFR-UHFFFAOYSA-N 1-[4-[2-(diethylamino)ethoxy]phenyl]-3-phenylpropan-1-one Chemical compound C1=CC(OCCN(CC)CC)=CC=C1C(=O)CCC1=CC=CC=C1 KMICWMXRUOETFR-UHFFFAOYSA-N 0.000 claims description 2
- SJIXRGNQPBQWMK-UHFFFAOYSA-N 2-(diethylamino)ethyl 2-methylprop-2-enoate Chemical compound CCN(CC)CCOC(=O)C(C)=C SJIXRGNQPBQWMK-UHFFFAOYSA-N 0.000 claims description 2
- 108060003199 Glucagon Proteins 0.000 claims description 2
- 102000051325 Glucagon Human genes 0.000 claims description 2
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- MPMBRWOOISTHJV-UHFFFAOYSA-N but-1-enylbenzene Chemical compound CCC=CC1=CC=CC=C1 MPMBRWOOISTHJV-UHFFFAOYSA-N 0.000 claims description 2
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- 229960001334 corticosteroids Drugs 0.000 claims description 2
- MASNOZXLGMXCHN-ZLPAWPGGSA-N glucagon Chemical compound C([C@@H](C(=O)N[C@H](C(=O)N[C@@H](CCC(N)=O)C(=O)N[C@@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@@H](CC(C)C)C(=O)N[C@@H](CCSC)C(=O)N[C@@H](CC(N)=O)C(=O)N[C@@H]([C@@H](C)O)C(O)=O)C(C)C)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](C)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CCCNC(N)=N)NC(=O)[C@H](CO)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CCCCN)NC(=O)[C@H](CO)NC(=O)[C@H](CC=1C=CC(O)=CC=1)NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](NC(=O)[C@H](CC=1C=CC=CC=1)NC(=O)[C@@H](NC(=O)CNC(=O)[C@H](CCC(N)=O)NC(=O)[C@H](CO)NC(=O)[C@@H](N)CC=1NC=NC=1)[C@@H](C)O)[C@@H](C)O)C1=CC=CC=C1 MASNOZXLGMXCHN-ZLPAWPGGSA-N 0.000 claims description 2
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- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/0012—Galenical forms characterised by the site of application
- A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
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- A—HUMAN NECESSITIES
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- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/32—Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers, poly(meth)acrylates, or polyvinyl pyrrolidone
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/58—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. poly[meth]acrylate, polyacrylamide, polystyrene, polyvinylpyrrolidone, polyvinylalcohol or polystyrene sulfonic acid resin
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- 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
- A61K47/50—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
- A61K47/51—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
- A61K47/56—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule
- A61K47/61—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 the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an organic macromolecular compound, e.g. an oligomeric, polymeric or dendrimeric molecule the organic macromolecular compound being a polysaccharide or a derivative thereof
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- Dermatology (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
Description
Claims (14)
- 폴리머중에 보론산기를 함유함을 특징으로 하는 당 응답형 고분자 복합체.
- 제1항에 있어서, 1종 또는 2종 이상의 약물이 상기 복합체에 포함되거나 결합되는 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제2항에 있어서, 보론산기를 함유하는 폴리머와 다가 수산기를 함유하는 약물이 보론산 에스테르 결합으로 결합된 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제1항에 있어서, 다가 수산기를 함유하는 1종 또는 2종 이상의 폴리머와 보론산기를 함유하는 폴리머가 함유됨을 특징으로 하는 당 응답형 고분자 복합체.
- 제1항에 있어서, 보론산기를 함유하는 폴리머가 3-아크릴로일아미노 벤젠보론산, 3-메타크릴로일 아미노벤젠보론산 또는 4-비닐벤젠보론산의 폴리머 또는 코폴리머인 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제4항에 있어서, 다가 수산기를 함유하는 폴리머가 중합도 100∼10,000인 폴리비닐알코올, 갈락토만난, 풀루란, 덱스트란 또는 아밀로오즈인 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제4항에 있어서, 보론산기를 함유하는 폴리머와 다가 수산기를 함유하는 폴리머의 중량비가 1 : 10∼10 : 1인 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제4항에 있어서, 보론산기기를 함유하는 폴리머가 3-아크릴로일아미노벤젠보론산과 N-비닐피롤리돈의 코폴리머이고 다가 수산기를 함유하는 폴리머는 폴리비닐알코올인 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제1항에 있어서, 폴리머가 가교 폴리머인 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제4항에 있어서, 폴리머가 가교 폴리머인 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제9항에 있어서, 가교 폴리머가 3-메타크릴로일아미노벤젠보론산/2-하이드록시에틸메타크릴레이트/에틸렌글리콜디메타크릴레이트, 3-메타크릴로일아미노벤젠보론산/2-하이드록시에틸메타크릴레이트/디에틸아미노에틸메타크릴레이트, 3-메타크릴로일아미노벤젠보론산/N,N-디메틸아크릴아미드/에틸렌글리콜디메타크릴레이트, 3-메타크릴로일아미노벤젠보론산/N,N-디메틸아크릴아미드/글리세롤 모노메타크릴레이트/에틸렌글리콜디메타크릴레이트, 3-아크릴로일아미노벤젠보론산/N,N-디메틸아크릴아미드글리세롤모노메타크릴레이트/이틸렌글리콜디메타크릴레이트, 3-메타크릴로일아미노벤젠보론산/N,N-디메틸아크릴아미드/N,N'-메틸렌비스아크릴아미드, 3-메타크릴로일아미노벤젠보론산/N,N-디메틸아크릴아미드/에틸렌글리콜디메타크릴레이트 또는 3-메타크릴로일아미노벤젠보론산/아크릴아미드/글리세롤 모노메타크릴레이트/N,N'-메틸렌비스아크릴아미드의 코폴리머인 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제2항에 있어서, 약물이 인슐린, 글루카곤, 소마토스타틴, 부신피질 호르몬, 이소프로테레놀, 이소에타린, 에피린, 부탄에프린, 트리메토키놀, 키노킨, 카나마이신, 리비토마이신, 스트렙토마이신, 제암제, 염료 및 지시약으로부터 선택됨을 특징으로 하는 당 응답형 고분자 복합체.
- 제3항에 있어서, 다가 수산기를 함유하는 약물이 글루코실화 인슐린 또는 트리스(하이드록시메틸)아미노메탄 인슐린인 것을 특징으로 하는 당 응답형 고분자 복합체.
- 제3항에 있어서, 폴리머가 3-메타크릴로일아미노벤젠보론산/아크릴아미드/비스아크릴아미드, 4-비닐벤젠보론산/에틸비닐벤젠/디비닐벤젠 또는 3-메타크릴로일아미노벤젠보론산/아크릴아미드/N,N'-에틸렌비스아크릴아미드의 코폴리머인 것을 특징으로 하는 당 응답형 고분자 복합체.
Applications Claiming Priority (9)
Application Number | Priority Date | Filing Date | Title |
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JP?1-270215 | 1989-10-19 | ||
JP27021589 | 1989-10-19 | ||
JP1-270215 | 1989-10-19 | ||
JP2-241192 | 1990-09-13 | ||
JP?2-241191 | 1990-09-13 | ||
JP2-241191 | 1990-09-13 | ||
JP02241192A JP3087293B2 (ja) | 1990-09-13 | 1990-09-13 | 糖応答型高分子複合体 |
JP?2-241192 | 1990-09-13 | ||
JP2241191A JP2874309B2 (ja) | 1990-09-13 | 1990-09-13 | 糖応答性高分子複合体 |
Publications (2)
Publication Number | Publication Date |
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KR910007545A KR910007545A (ko) | 1991-05-30 |
KR930001305B1 true KR930001305B1 (ko) | 1993-02-25 |
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KR1019900016644A KR930001305B1 (ko) | 1989-10-19 | 1990-10-18 | 당 응답형 고분자 복합체(Polymer Complexes of Sugar Response Type) |
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US (1) | US5478575A (ko) |
EP (1) | EP0424168B1 (ko) |
KR (1) | KR930001305B1 (ko) |
AU (1) | AU628674B2 (ko) |
CA (1) | CA2027930C (ko) |
DE (1) | DE69003068T2 (ko) |
DK (1) | DK0424168T3 (ko) |
TW (1) | TW218353B (ko) |
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1990
- 1990-10-18 KR KR1019900016644A patent/KR930001305B1/ko not_active IP Right Cessation
- 1990-10-18 AU AU64754/90A patent/AU628674B2/en not_active Ceased
- 1990-10-18 CA CA002027930A patent/CA2027930C/en not_active Expired - Fee Related
- 1990-10-19 TW TW079108866A patent/TW218353B/zh active
- 1990-10-19 DE DE90311485T patent/DE69003068T2/de not_active Expired - Fee Related
- 1990-10-19 DK DK90311485.8T patent/DK0424168T3/da active
- 1990-10-19 EP EP90311485A patent/EP0424168B1/en not_active Expired - Lifetime
-
1993
- 1993-03-26 US US08/037,383 patent/US5478575A/en not_active Expired - Fee Related
Also Published As
Publication number | Publication date |
---|---|
US5478575A (en) | 1995-12-26 |
KR910007545A (ko) | 1991-05-30 |
DK0424168T3 (da) | 1993-12-13 |
CA2027930A1 (en) | 1991-04-20 |
EP0424168A1 (en) | 1991-04-24 |
DE69003068T2 (de) | 1993-12-16 |
TW218353B (ko) | 1994-01-01 |
EP0424168B1 (en) | 1993-09-01 |
CA2027930C (en) | 1998-06-30 |
AU628674B2 (en) | 1992-09-17 |
AU6475490A (en) | 1991-07-11 |
DE69003068D1 (de) | 1993-10-07 |
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