JP5324093B2 - 負電荷を有する疎水性基で官能基化された分岐鎖ポリアミノ酸、及びその応用、特に治療への応用 - Google Patents
負電荷を有する疎水性基で官能基化された分岐鎖ポリアミノ酸、及びその応用、特に治療への応用 Download PDFInfo
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Classifications
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- 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
- C08G69/08—Polyamides derived from amino-carboxylic acids or from polyamines and polycarboxylic acids derived from amino-carboxylic acids
- C08G69/10—Alpha-amino-carboxylic acids
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/72—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds
- A61K8/84—Cosmetics or similar toiletry preparations characterised by the composition containing organic macromolecular compounds obtained by reactions otherwise than those involving only carbon-carbon unsaturated bonds
- A61K8/88—Polyamides
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q19/00—Preparations for care of the skin
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- 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
- C08G69/48—Polymers modified by chemical after-treatment
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2800/00—Properties of cosmetic compositions or active ingredients thereof or formulation aids used therein and process related aspects
- A61K2800/40—Chemical, physico-chemical or functional or structural properties of particular ingredients
- A61K2800/57—Compounds covalently linked to a(n inert) carrier molecule, e.g. conjugates, pro-fragrances
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Birds (AREA)
- General Chemical & Material Sciences (AREA)
- Epidemiology (AREA)
- Dermatology (AREA)
- Medicinal Preparation (AREA)
- Polyamides (AREA)
- Cosmetics (AREA)
- Coloring Foods And Improving Nutritive Qualities (AREA)
- Materials For Medical Uses (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| FR0408478 | 2004-07-30 | ||
| FR0408478A FR2873704B1 (fr) | 2004-07-30 | 2004-07-30 | Polyaminoacides fonctionnalises par des greffons hydrophobes portant une charge anionique et leurs applications notamment therapeutiques |
| PCT/FR2005/050610 WO2006021710A1 (fr) | 2004-07-30 | 2005-07-25 | Polyaminoacides fonctionnalises par des greffons hydrophobes portant une charge anionique et leurs applications notamment therapeutiques |
Publications (3)
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| JP2008508389A JP2008508389A (ja) | 2008-03-21 |
| JP2008508389A5 JP2008508389A5 (enExample) | 2012-08-23 |
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| EP (1) | EP1773914B9 (enExample) |
| JP (1) | JP5324093B2 (enExample) |
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| CA (1) | CA2573612A1 (enExample) |
| DE (1) | DE602005017903D1 (enExample) |
| FR (1) | FR2873704B1 (enExample) |
| WO (1) | WO2006021710A1 (enExample) |
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| EP1878766B1 (en) * | 2005-05-02 | 2020-01-01 | The University of Tokyo | Electrostatic bonding type polymer vesicle |
| FR2915684B1 (fr) * | 2007-05-03 | 2011-01-14 | Flamel Tech Sa | Particules a base de polyelectrolytes et de principe actif a liberation modifiee et formulations pharmaceutiques contenant ces particules |
| US7999040B2 (en) | 2007-09-25 | 2011-08-16 | Nanochem Solutions, Inc. | Method of making graft copolymers from sodium poly(aspartate) and the resulting graft copolymer |
| WO2009041913A1 (en) * | 2007-09-26 | 2009-04-02 | Thorsson Limited | Colloidal fertilizer and related methods |
| WO2009133968A1 (ja) * | 2008-04-30 | 2009-11-05 | 国立大学法人東京大学 | 電荷変換型三元系ポリプレックス |
| WO2011097727A1 (en) | 2010-02-10 | 2011-08-18 | Queen's University At Kingston | Water with switchable ionic strength |
| JP2013234207A (ja) * | 2010-08-31 | 2013-11-21 | Jsr Corp | 新規重合体及び新規ｎ−カルボキシアミノ酸無水物、ならびにそれらの製造方法 |
| CN103459439B (zh) | 2010-12-15 | 2017-09-12 | 金斯顿女王大学 | 使用具有可转换的离子强度的水的系统和方法 |
| CN111698999A (zh) * | 2017-12-06 | 2020-09-22 | 阿道恰公司 | 包含至少一种pi在5.8与8.5之间的基础胰岛素和带有羧酸根电荷及疏水基的共聚氨基酸的ph为7的可注射溶液 |
| KR20200106890A (ko) * | 2017-12-07 | 2020-09-15 | 아도시아 | 아밀린, 아밀린 작용제 수용체 또는 아밀린 유사체 및 코-폴리아미노산을 포함하는 주사용 수용액 형태의 조성물 |
| EP3740195A1 (fr) * | 2017-12-07 | 2020-11-25 | Adocia | Compositions sous forme d'une solution aqueuse injectable comprenant de l'amyline, un agoniste au recepteur de l'amyline ou un analogue d'amyline et un co-polyaminoacide |
| BR112020011570A2 (pt) | 2017-12-07 | 2020-12-08 | Adocia | Solução injetável a um ph 7 compreendendo pelo menos uma insulina basal apresentando um pi entre 5,8 e 8,5 e um co-poliaminoácido contendo cargas de carboxilato e radicais hidrofóbicos |
| IL275146B2 (en) | 2017-12-07 | 2025-01-01 | Adocia | Preparations in the form of an aqueous solution for injection comprising amylin, an amylin receptor agonist or an amylin analog and a copolyamino acid |
| KR20240171197A (ko) | 2017-12-07 | 2024-12-06 | 아도시아 | pI가 5.8 내지 8.5인 적어도 1종의 기저 인슐린, 및 카복실산염 전하 및 소수성 라디칼을 보유하는 코-폴리아미노산을 포함하는 pH 7의 주사용 용액 |
| CN109498548B (zh) * | 2018-12-11 | 2021-09-24 | 吉林化工学院 | 一种蛋白质与光敏剂共传递pH响应性聚氨基酸纳米凝胶及其制备方法 |
| WO2022194759A1 (en) * | 2021-03-18 | 2022-09-22 | Agfa-Gevaert Nv | Poly(amino acid) based capsules |
Family Cites Families (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4351337A (en) * | 1973-05-17 | 1982-09-28 | Arthur D. Little, Inc. | Biodegradable, implantable drug delivery device, and process for preparing and using the same |
| JPS60100516A (ja) * | 1983-11-04 | 1985-06-04 | Takeda Chem Ind Ltd | 徐放型マイクロカプセルの製造法 |
| DE3581471D1 (de) * | 1984-10-19 | 1991-02-28 | Battelle Memorial Institute | Durch mikroorganismen abbaubares polypeptid und seine verwendung fuer die fortschreitende abgabe von medikamenten. |
| CH667874A5 (fr) * | 1985-12-19 | 1988-11-15 | Battelle Memorial Institute | Polypeptide synthetique biodegradable et son utilisation pour la preparation de medicaments. |
| KR940003548U (ko) * | 1992-08-14 | 1994-02-21 | 김형술 | 세탁물 건조기 |
| US6153193A (en) * | 1993-04-28 | 2000-11-28 | Supratek Pharma Inc. | Compositions for targeting biological agents |
| 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 |
| FR2786098B1 (fr) * | 1998-11-20 | 2003-05-30 | Flamel Tech Sa | Particules a base de polyaminoacide(s) et susceptibles d'etre utilisees comme vecteurs de principe(s) actif(s), suspension colloidale les comprenant et leurs procedes de fabrication |
| BR0211650A (pt) * | 2001-08-03 | 2004-07-13 | Procter & Gamble | Derivados de poliaspartato para uso em composições detergentes |
| JP2003327693A (ja) * | 2002-05-15 | 2003-11-19 | Mitsuru Akashi | 親−疎水性修飾ポリ（γ−グルタミン酸） |
| FR2840614B1 (fr) * | 2002-06-07 | 2004-08-27 | Flamel Tech Sa | Polyaminoacides fonctionnalises par de l'alpha-tocopherol et leurs applications notamment therapeutiques |
| FR2843117B1 (fr) * | 2002-07-30 | 2004-10-15 | Flamel Tech Sa | Polyaminoacides fonctionnalises par au moins un groupement hydrophobe et leurs applications notamment therapeutiques |
| AU2003294056A1 (en) * | 2002-12-04 | 2004-07-29 | Flamel Technologies | Polyamino acids functionalized by at least one (oligo)amino acid group and therapeutic uses |
| FR2855521B1 (fr) * | 2003-05-28 | 2005-08-05 | Flamel Tech Sa | Polyaminoacides fonctionnalises par au moins un groupement h ydrophobe et leurs applications notamment therapeutiques. |
| FR2873703B1 (fr) * | 2004-07-30 | 2006-12-08 | Flamel Technologies Sa | Polyaminoacides branches, fonctionnalises par des groupements hydrophobes et leurs applications notamment therapeutiques |
-
2004
- 2004-07-30 FR FR0408478A patent/FR2873704B1/fr not_active Expired - Fee Related
-
2005
- 2005-07-25 DE DE602005017903T patent/DE602005017903D1/de not_active Expired - Lifetime
- 2005-07-25 US US11/658,803 patent/US20100098656A1/en not_active Abandoned
- 2005-07-25 CA CA002573612A patent/CA2573612A1/fr not_active Abandoned
- 2005-07-25 WO PCT/FR2005/050610 patent/WO2006021710A1/fr not_active Ceased
- 2005-07-25 AT AT05792029T patent/ATE449806T1/de not_active IP Right Cessation
- 2005-07-25 EP EP05792029A patent/EP1773914B9/fr not_active Expired - Lifetime
- 2005-07-25 JP JP2007523129A patent/JP5324093B2/ja not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CA2573612A1 (fr) | 2006-03-02 |
| FR2873704B1 (fr) | 2006-12-08 |
| DE602005017903D1 (de) | 2010-01-07 |
| JP2008508389A (ja) | 2008-03-21 |
| FR2873704A1 (fr) | 2006-02-03 |
| EP1773914B9 (fr) | 2010-03-31 |
| US20100098656A1 (en) | 2010-04-22 |
| WO2006021710A1 (fr) | 2006-03-02 |
| EP1773914A1 (fr) | 2007-04-18 |
| ATE449806T1 (de) | 2009-12-15 |
| EP1773914B1 (fr) | 2009-11-25 |
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