CN1886151B - 持续释放活性成分的药物制剂及其应用,尤其是治疗学应用 - Google Patents
持续释放活性成分的药物制剂及其应用,尤其是治疗学应用 Download PDFInfo
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-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/16—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof
- A61K38/17—Peptides having more than 20 amino acids; Gastrins; Somatostatins; Melanotropins; Derivatives thereof from animals; from humans
- A61K38/19—Cytokines; Lymphokines; Interferons
- A61K38/21—Interferons [IFN]
- A61K38/212—IFN-alpha
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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
- A61K47/42—Proteins; Polypeptides; Degradation products thereof; Derivatives thereof, e.g. albumin, gelatin or zein
-
- 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
- A61K47/62—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 a protein, peptide or polyamino acid
- A61K47/64—Drug-peptide, drug-protein or drug-polyamino acid conjugates, i.e. the modifying agent being a peptide, protein or polyamino acid which is covalently bonded or complexed to a therapeutically active agent
- A61K47/645—Polycationic or polyanionic oligopeptides, polypeptides or polyamino acids, e.g. polylysine, polyarginine, polyglutamic acid or peptide TAT
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K51/00—Preparations containing radioactive substances for use in therapy or testing in vivo
- A61K51/12—Preparations containing radioactive substances for use in therapy or testing in vivo characterised by a special physical form, e.g. emulsion, microcapsules, liposomes, characterized by a special physical form, e.g. emulsions, dispersions, microcapsules
- A61K51/1217—Dispersions, suspensions, colloids, emulsions, e.g. perfluorinated emulsion, sols
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Abstract
Description
实施例 | 聚合物 | 结合等级(%) |
1 | 聚[(谷酰胺-O-Na)0.63-嵌段-(谷酰胺-O-甲基)0.37] | 55 |
2 | 聚[(谷酰胺-O-Na)0.66-嵌段-(谷酰胺-O-乙基)0.34] | 26 |
3 | 聚[(谷酰胺-O-Na)0.65-嵌段-(谷酰胺-O-十六烷基)0.35] | 36 |
4 | 聚[(谷酰胺-O-Na)0.88-嵌段-(谷酰胺-O-十二烷基)0.12] | >90 |
聚合物 | 聚谷氨酸的分子量1g/mol | 疏水基 | %连接率(NMR)2 | 聚合物的分子量1g/mol |
P1 | 10000 | α-维生素3 | 7 | 13900 |
P2 | 10000 | α-维生素3 | 4 | 14400 |
P3 | 16900 | α-维生素3 | 4 | 15200 |
P4 | 10000 | 胆固醇 | 5 | 11500 |
P5 | 16900 | 胆固醇 | 5 | 12900 |
P6 | 10000 | n-十二烷醇 | 15 | 11500 |
聚合物 | P1 | P2 | P3 | P4 | P6 |
IFN浓度(mg/ml) | 0.3 | 0.15 | 0.15 | 0.15 | 0.3 |
浓度C1(mg/ml) | 17 | >30 | 16 | 17 | >50 |
聚合物 | P1 | P3 | P6 |
IL2浓度(mg/ml) | 2.5 | 2.5 | 2.5 |
浓度C1(mg/ml) | 17 | 17 | >50 |
代号 | 聚合物 | 聚合物浓度(mg/ml) | IFN浓度(mg/ml) | 释放时间Tr(秒) |
A | P1 | 30 | 0.3 | >10 |
B | P1 | 10.5 | 0.15 | <0.3 |
C | P2 | 15 | 0.15 | <0.03 |
D | P6 | 40 | 0.3 | 0.4 |
制剂代号 | Tmax(h) | T50(h) |
A | 48 | 54.2 |
B | 5 | 16.7 |
C | 11 | 19.3 |
D | 5 | 17.3 |
代号 | 聚合物 | 聚合物浓度(mg/ml) | IL2浓度(mg/ml) |
E | P1 | 30 | 2.5 |
F | P3 | 20 | 2.5 |
G | P6 | 40 | 2.5 |
制剂代号 | Tmax(h) | T50(h) |
E | 32 | 34.5 |
F | 32 | 37.5 |
G | 4 | 10.5 |
Claims (36)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
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FR0350887 | 2003-11-21 | ||
FR0350887A FR2862536B1 (fr) | 2003-11-21 | 2003-11-21 | Formulations pharmaceutiques pour la liberation prolongee de principe(s) actif(s), ainsi que leurs applications notamment therapeutiques |
PCT/FR2004/050603 WO2005051416A1 (fr) | 2003-11-21 | 2004-11-19 | Formulations pharmaceutiques pour la libération prolongée de principe(s) actif(s), ainsi que leurs applications notamment therapeutiques |
Publications (2)
Publication Number | Publication Date |
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CN1886151A CN1886151A (zh) | 2006-12-27 |
CN1886151B true CN1886151B (zh) | 2012-08-29 |
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CN2004800352005A Active CN1886151B (zh) | 2003-11-21 | 2004-11-19 | 持续释放活性成分的药物制剂及其应用,尤其是治疗学应用 |
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US (1) | US8084045B2 (zh) |
EP (1) | EP1689425B8 (zh) |
JP (1) | JP4988352B2 (zh) |
KR (1) | KR101092547B1 (zh) |
CN (1) | CN1886151B (zh) |
AT (1) | ATE451116T1 (zh) |
AU (1) | AU2004292369B2 (zh) |
BR (1) | BRPI0416779B8 (zh) |
CA (1) | CA2546675C (zh) |
CY (1) | CY1110612T1 (zh) |
DE (1) | DE602004024571D1 (zh) |
DK (1) | DK1689425T3 (zh) |
ES (1) | ES2338012T3 (zh) |
FR (1) | FR2862536B1 (zh) |
IL (1) | IL175768A (zh) |
MX (1) | MXPA06005717A (zh) |
PL (1) | PL1689425T3 (zh) |
PT (1) | PT1689425E (zh) |
SI (1) | SI1689425T1 (zh) |
TW (1) | TW200518775A (zh) |
WO (1) | WO2005051416A1 (zh) |
ZA (1) | ZA200603950B (zh) |
Families Citing this family (56)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR2822834B1 (fr) * | 2001-04-02 | 2005-02-25 | Flamel Tech Sa | Suspension colloidale de nanoparticules a base de copolymeres amphiphile pour la vectorisation de principes actifs et leur mode de preparation |
FR2830447B1 (fr) * | 2001-10-09 | 2004-04-16 | Flamel Tech Sa | Forme galenique orale microparticulaire pour la liberation retardee et controlee de principes actifs pharmaceutiques |
CN100577164C (zh) * | 2002-04-09 | 2010-01-06 | 弗拉梅技术公司 | 可改进释放阿莫西林的微囊含水混悬液形式的口服药物制剂 |
EP1492511B3 (fr) | 2002-04-09 | 2012-05-02 | Flamel Technologies | Formulation pharmaceutique orale sous forme de suspension aqueuse de microcapsules permettant la liberation modifiee de principe(s) actif(s) |
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 |
PL1604687T3 (pl) * | 2003-03-20 | 2011-04-29 | Nippon Kayaku Kk | Preparat micelarny zawierający słabo rozpuszczalny w wodzie lek przeciwnowotworowy oraz nowy kopolimer blokowy |
FR2860516B1 (fr) * | 2003-10-03 | 2006-01-13 | Flamel Tech Sa | Homopolyaminoacides telecheliques fonctionnalises par des groupements hydrophobes et leurs applications notamment therapeutiques |
FR2862536B1 (fr) | 2003-11-21 | 2007-11-23 | Flamel Tech Sa | Formulations pharmaceutiques pour la liberation prolongee de principe(s) actif(s), ainsi que leurs applications notamment therapeutiques |
FR2862535B1 (fr) * | 2003-11-21 | 2007-11-23 | Flamel Tech Sa | Formulations pharmaceutiques pour la liberation prolongee d'interleukines et leurs applications therapeutiques |
FR2862541B1 (fr) * | 2003-11-21 | 2007-04-20 | Flamel Tech Sa | Formulations pharmaceutiques pour la liberation prolongee d'interferons et leurs applications therapeutiques |
CA2581125C (en) | 2004-09-22 | 2013-04-23 | Nippon Kayaku Kabushiki Kaisha | Modified poly(ethylene oxide-amino acid) copolymer, micelle preparation, and anticancer agent containing the same |
DE102005028080A1 (de) * | 2005-06-17 | 2006-12-21 | Bayer Technology Services Gmbh | Verfahren zur zeitlich gesteuerten intravenösen Verabreichung des Narkosemittels Propofol |
WO2007111211A1 (ja) | 2006-03-28 | 2007-10-04 | Nippon Kayaku Kabushiki Kaisha | タキサン類の高分子結合体 |
RU2447095C2 (ru) | 2006-05-18 | 2012-04-10 | Ниппон Каяку Кабусики Кайся | Высокомолекулярный конъюгат подофиллотоксинов |
FR2902007B1 (fr) * | 2006-06-09 | 2012-01-13 | Flamel Tech Sa | Formulations pharmaceutiques pour la liberation prolongee de principe(s) actif(s) ainsi que leurs applications notamment therapeutiques |
US8679540B2 (en) | 2006-06-09 | 2014-03-25 | Flamel Technologies | Pharmaceutical formulations for the prolonged release of active principle(s), and their applications, especially therapeutic applications |
FR2904219B1 (fr) * | 2006-07-28 | 2010-08-13 | Flamel Tech Sa | Microparticules a base de copolymere amphiphile et de principe(s) actif(s) a liberation modifiee et formulations pharmaceutiques en contenant |
WO2008041610A1 (fr) * | 2006-10-03 | 2008-04-10 | Nippon Kayaku Kabushiki Kaisha | Mélange d'un dérivé de résorcinol avec un polymère |
US8334364B2 (en) * | 2006-11-06 | 2012-12-18 | Nipon Kayaku Kabushiki Kaisha | High-molecular weight derivative of nucleic acid antimetabolite |
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 |
FR2915683B1 (fr) * | 2007-05-03 | 2009-08-07 | Flamel Technologies Sa | Formulations pharmaceutiques auto-precipitantes pour la liberation modifiee de principe actif |
US8703878B2 (en) | 2007-09-28 | 2014-04-22 | Nippon Kayaku Kabushiki Kaisha | High-molecular weight conjugate of steroids |
JP5584132B2 (ja) * | 2007-11-15 | 2014-09-03 | ザ ユニバーシティ オブ ノース カロライナ アット チャペル ヒル | 疼痛の治療のための前立腺酸性ホスファターゼ |
US8920788B2 (en) * | 2008-03-18 | 2014-12-30 | Nippon Kayaku Kabushiki Kaisha | High-molecular weight conjugate of physiologically active substances |
WO2009136572A1 (ja) | 2008-05-08 | 2009-11-12 | 日本化薬株式会社 | 葉酸若しくは葉酸誘導体の高分子結合体 |
US20100021549A1 (en) * | 2008-07-28 | 2010-01-28 | Flamel Technologies, S.A. | Microparticle oral form useful for the modified release of nanoparticles |
JP5542687B2 (ja) * | 2008-11-05 | 2014-07-09 | 国立大学法人 東京医科歯科大学 | ヒアルロン酸誘導体、およびその医薬組成物 |
WO2010056657A2 (en) * | 2008-11-16 | 2010-05-20 | Board Of Regents, The Univesity Of Texas System | Low viscosity highly concentrated suspensions |
FR2940619B1 (fr) | 2008-12-31 | 2012-02-10 | Flamel Technologies Sa | Composition comprenant un actif de solubilite aqueuse faible ou moyenne |
WO2010093873A2 (en) | 2009-02-12 | 2010-08-19 | Incept, Llc | Drug delivery through hydrogel plugs |
WO2010131675A1 (ja) * | 2009-05-15 | 2010-11-18 | 日本化薬株式会社 | 水酸基を有する生理活性物質の高分子結合体 |
JP4829351B2 (ja) * | 2010-02-05 | 2011-12-07 | ナノキャリア株式会社 | 易崩壊型ポリマーミセル組成物 |
CN101893619B (zh) * | 2010-02-10 | 2013-11-13 | 上海蓝怡科技有限公司 | 改进乳胶悬浊液稳定性的方法 |
TWI448485B (zh) * | 2010-08-03 | 2014-08-11 | Univ Nat Taiwan Normal | 半互穿網絡型水膠聚合物、其製造方法及包含其之水泥組成物 |
JP5856069B2 (ja) | 2010-11-17 | 2016-02-09 | 日本化薬株式会社 | 新規なシチジン系代謝拮抗剤の高分子誘導体 |
US9335195B2 (en) * | 2011-02-16 | 2016-05-10 | Baker Hughes Incorporated | Multiphase meter to provide data for production management |
DK2741765T3 (en) | 2011-08-10 | 2016-06-13 | Adocia | Injectable solution of at least one type of basal insulin |
ES2635117T3 (es) | 2011-09-11 | 2017-10-02 | Nippon Kayaku Kabushiki Kaisha | Método para la fabricación de un copolímero de bloques |
US10226417B2 (en) | 2011-09-16 | 2019-03-12 | Peter Jarrett | Drug delivery systems and applications |
CN113730555A (zh) | 2012-01-09 | 2021-12-03 | 阿道恰公司 | Ph为7且至少含pi为5.8至8.5之基础胰岛素和取代共聚(氨基酸)的可注射溶液 |
FR2985429B1 (fr) * | 2012-01-09 | 2016-07-29 | Adocia | Solution injectable a ph 7 comprenant au moins une insuline basale dont le pi est compris entre 5,8 et 8,5 et un polyaminoacide substitue obtenu par un procede de polymerisation controle |
FR2985428B1 (fr) * | 2012-01-09 | 2016-05-27 | Adocia | Solution injectable a ph 7 comprenant au moins une insuline basale dont le pi est compris entre 5,8 et 8,5 et un polyaminoacide substitue |
US20150314003A2 (en) | 2012-08-09 | 2015-11-05 | Adocia | Injectable solution at ph 7 comprising at least one basal insulin the isoelectric point of which is between 5.8 and 8.5 and a hydrophobized anionic polymer |
WO2015032971A1 (en) * | 2013-09-09 | 2015-03-12 | Lek Pharmaceuticals D.D. | Polymer selection for preparation of nps with high protein loading |
US10037359B2 (en) * | 2016-05-23 | 2018-07-31 | Microsoft Technology Licensing, Llc | Search results using social routing of content |
UY37341A (es) | 2016-07-22 | 2017-11-30 | Flamel Ireland Ltd | Formulaciones de gamma-hidroxibutirato de liberación modificada con farmacocinética mejorada |
US11602513B1 (en) | 2016-07-22 | 2023-03-14 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11986451B1 (en) | 2016-07-22 | 2024-05-21 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11602512B1 (en) | 2016-07-22 | 2023-03-14 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11504347B1 (en) | 2016-07-22 | 2022-11-22 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
JP7178341B2 (ja) | 2016-08-01 | 2022-11-25 | ザ ブリガム アンド ウィメンズ ホスピタル インコーポレイテッド | タンパク質およびペプチドの送達のための粒子 |
BR112021013766A2 (pt) | 2019-03-01 | 2021-09-21 | Flamel Ireland Limited | Composições de gama-hidroxibutirato com farmacocinética melhorada no estado alimentado |
CN114469803B (zh) * | 2022-01-26 | 2024-03-19 | 乐彩华年(广州)电子商务有限公司 | 一种超分子组合物及其制备方法与应用 |
US11779557B1 (en) | 2022-02-07 | 2023-10-10 | Flamel Ireland Limited | Modified release gamma-hydroxybutyrate formulations having improved pharmacokinetics |
US11583510B1 (en) | 2022-02-07 | 2023-02-21 | Flamel Ireland Limited | Methods of administering gamma hydroxybutyrate formulations after a high-fat meal |
Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1183040A (zh) * | 1995-03-28 | 1998-05-27 | 弗拉梅技术公司 | 用作活性成分载体的多聚氨基酸基颗粒和其制备方法 |
CN1282345A (zh) * | 1997-10-03 | 2001-01-31 | 麦克罗梅德公司 | 具有可逆热胶凝性质的可生物降解低分子量三嵌段聚(丙交酯-co-乙交酯)聚乙二醇共聚物 |
US6630171B1 (en) * | 1998-11-20 | 2003-10-07 | Flamel Technologies | Particles based on polyamino-acid(s) and methods for preparing same |
Family Cites Families (104)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US2680749A (en) * | 1951-12-01 | 1954-06-08 | Eastman Kodak Co | Water-soluble tocopherol derivatives |
DE1189636B (de) | 1959-12-28 | 1965-03-25 | Licentia Gmbh | UEberspannungsableiter erniedrigter Bauhoehe mit Loeschfunkenstrecke und spannungsabhaengigen Widerstaenden |
GB1024393A (en) | 1963-03-30 | 1966-03-30 | Asahi Chemical Ind | Process for polymerizing n-carboxy-ª-amino acid anhydrides |
GB1202765A (en) | 1967-07-20 | 1970-08-19 | Kyowa Hakko Kogyo Kk | PROCESS FOR THE POLYMERIZATION OF alpha-AMINO ACID-N-CARBOXY ANHYDRIDES |
US3536672A (en) * | 1968-10-04 | 1970-10-27 | Kyowa Hakko Kogyo Kk | Process for the polymerization of alpha-amino acid - n - carboxy anhydrides using imidazole initiators |
US4450150A (en) * | 1973-05-17 | 1984-05-22 | Arthur D. Little, Inc. | Biodegradable, implantable drug delivery depots, and method for preparing and using the same |
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 |
FR2313915A1 (fr) | 1976-01-26 | 1977-01-07 | Corneille Gilbert | Nouvelle forme galenique d'administration de la vincamine et de ses derives, son procede de preparation et medicaments comprenant cette nouvelle forme |
US4126628A (en) * | 1977-03-28 | 1978-11-21 | Canadian Patents And Development Limited | Acylation of amino acids |
DE3000483A1 (de) | 1979-01-09 | 1980-07-17 | Fuji Photo Film Co Ltd | Mikrokapseln fuer immunologische bestimmungen |
US4321253A (en) * | 1980-08-22 | 1982-03-23 | Beatty Morgan L | Suspension of microencapsulated bacampicillin acid addition salt for oral, especially pediatric, administration |
US4443549A (en) * | 1981-10-19 | 1984-04-17 | Molecular Genetics, Inc. | Production of monoclonal antibodies against bacterial adhesins |
FR2533209B1 (fr) | 1982-09-22 | 1985-11-08 | Centre Nat Rech Scient | Lipopeptides, leur obtention et leur application comme emulsifiants |
HU187215B (en) * | 1983-01-26 | 1985-11-28 | Egyt Gyogyszervegyeszeti Gyar | Method for producing pharmaceutical product of high actor content and prolonged effect |
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 |
JPH0830004B2 (ja) * | 1983-11-14 | 1996-03-27 | コロンビア ラボラトリーズ インコーポレイテッド | 生物接着性組成物およびそれにより治療する方法 |
US4894240A (en) * | 1983-12-22 | 1990-01-16 | Elan Corporation Plc | Controlled absorption diltiazem formulation for once-daily administration |
EP0179023B1 (fr) | 1984-10-19 | 1991-01-23 | Battelle Memorial Institute | Polypeptide biodégradable et son utilisation pour le relargage progressif de médicaments |
US4661345A (en) * | 1985-02-26 | 1987-04-28 | The Rockefeller University | Method for treating pertussis |
EP0198769A3 (en) | 1985-04-12 | 1987-09-02 | Forest Laboratories, Inc. | Floating sustained release therapeutic compositions |
MX9203291A (es) * | 1985-06-26 | 1992-08-01 | Liposome Co Inc | Metodo para acoplamiento de liposomas. |
US4766106A (en) * | 1985-06-26 | 1988-08-23 | Cetus Corporation | Solubilization of proteins for pharmaceutical compositions using polymer conjugation |
US5102872A (en) * | 1985-09-20 | 1992-04-07 | Cetus Corporation | Controlled-release formulations of interleukin-2 |
CH667874A5 (fr) * | 1985-12-19 | 1988-11-15 | Battelle Memorial Institute | Polypeptide synthetique biodegradable et son utilisation pour la preparation de medicaments. |
GB8601100D0 (en) * | 1986-01-17 | 1986-02-19 | Cosmas Damian Ltd | Drug delivery system |
US4835293A (en) * | 1987-02-24 | 1989-05-30 | E. I. Du Pont De Nemours And Company | Atmospheric pressure process for preparing pure cyclic esters |
GB8723846D0 (en) * | 1987-10-10 | 1987-11-11 | Danbiosyst Ltd | Bioadhesive microsphere drug delivery system |
DE3837825A1 (de) * | 1988-11-08 | 1990-05-10 | Hoechst Ag | Neue insulinderivate, ihre verwendung und eine sie enthaltende pharmazeutische zubereitung |
IT1227899B (it) | 1988-12-23 | 1991-05-14 | Poli Ind Chimica Spa | Rivestimento totale o parziale di principi attivi farmaceutici e relative composizioni |
US4976968A (en) * | 1989-02-24 | 1990-12-11 | Clinical Technologies Associates, Inc. | Anhydrous delivery systems for pharmacological agents |
US5084278A (en) * | 1989-06-02 | 1992-01-28 | Nortec Development Associates, Inc. | Taste-masked pharmaceutical compositions |
CA1340681C (en) * | 1989-07-07 | 1999-07-27 | Robert Deziel | Antiherpes tetrapeptides having a substituted aspartic acid side chain |
IT1256651B (it) | 1992-12-11 | 1995-12-12 | Giancarlo Santus | Composizione farmaceutica a rilascio controllato in sospensione liquida |
GB2240547A (en) | 1990-01-31 | 1991-08-07 | Ciba Geigy Ag | New compositions |
US5023349A (en) * | 1990-05-08 | 1991-06-11 | E. I. Du Pont De Nemours And Company | Continuous process for rapid conversion of oligomers to cyclic esters |
SE9002684D0 (sv) * | 1990-08-17 | 1990-08-17 | Malvac Foundation C O Peter Pe | New peptides and their use |
FI922107A0 (fi) | 1991-05-10 | 1992-05-08 | Faulding F H & Co Ltd | Mikrokapselkomposition och foerfarande. |
US5286497A (en) * | 1991-05-20 | 1994-02-15 | Carderm Capital L.P. | Diltiazem formulation |
FR2686899B1 (fr) * | 1992-01-31 | 1995-09-01 | Rhone Poulenc Rorer Sa | Nouveaux polypeptides biologiquement actifs, leur preparation et compositions pharmaceutiques les contenant. |
US5286495A (en) * | 1992-05-11 | 1994-02-15 | University Of Florida | Process for microencapsulating cells |
FR2692263B1 (fr) | 1992-06-15 | 1994-09-23 | Flamel Tech Sa | Procédé de préparation d'esters cycliques d'acides-alpha-hydroxycarboxyliques. |
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 |
WO1994012158A1 (en) * | 1992-12-02 | 1994-06-09 | Alkermes Controlled Therapeutics, Inc. | Controlled release growth hormone containing microspheres |
FR2702373B1 (fr) * | 1993-03-08 | 1996-06-07 | Rhone Merieux | Emulsions vaccinales fluides eau-dans-l'huile contenant une huile métabolisable. |
EP0698040A4 (en) * | 1993-05-20 | 1999-01-07 | Biotech Australia Pty Ltd | LHRH ANTAGONISTS |
DK72793D0 (da) * | 1993-06-21 | 1993-06-21 | Novo Nordisk As | Nyt produkt |
FR2708932B1 (fr) * | 1993-08-10 | 1995-11-10 | Flamel Tech Sa | Procédé de préparation de polyaminoacides. |
KR0141431B1 (ko) * | 1994-05-17 | 1998-07-01 | 김상웅 | 생분해성 하이드로겔 고분자 |
JP3460340B2 (ja) * | 1994-09-09 | 2003-10-27 | Jsr株式会社 | ポリ−α−アミノ酸のエマルジョンおよびその製造方法並びにポリ−α−アミノ酸の中空ポリマー粒子 |
KR0167613B1 (ko) * | 1994-12-28 | 1999-01-15 | 한스 루돌프 하우스, 니콜 케르커 | 사이클로스포린-함유 연질캅셀제 조성물 |
JP2690276B2 (ja) | 1995-01-10 | 1997-12-10 | 科学技術振興事業団 | 静電結合型高分子ミセル薬物担体とその薬剤 |
US5939485A (en) * | 1995-06-19 | 1999-08-17 | Medlogic Global Corporation | Responsive polymer networks and methods of their use |
FR2738835B1 (fr) * | 1995-09-18 | 1997-10-17 | Oreal | Composition epaissie en milieu aqueux, procede d'epaississement d'un milieu aqueux et utilisations en cosmetique |
US5872210A (en) * | 1995-10-05 | 1999-02-16 | The United States Of America As Represented By The Department Of Health And Human Services | Transframe peptide inhibitor of viral protease |
FR2746035B1 (fr) | 1996-03-15 | 1998-06-12 | Microparticules de gel composite susceptibles d'etre utilisees comme vecteur(s) de principe(s) actif(s), l'un de leurs procedes de preparation et leurs applications | |
US6284267B1 (en) * | 1996-08-14 | 2001-09-04 | Nutrimed Biotech | Amphiphilic materials and liposome formulations thereof |
US6083484A (en) * | 1996-10-17 | 2000-07-04 | Molecular Biosystems, Inc. | Microparticles stabilized by polynuclear chromium complexes and their use as ultrasound contrast agents |
US5981761A (en) * | 1997-03-27 | 1999-11-09 | Solutia Inc. | Crosslinked polyaspartate salts a process for their production |
KR100195291B1 (ko) * | 1997-07-12 | 1999-06-15 | 서경배 | 비이온성 비타민 |
US5933269A (en) * | 1997-08-22 | 1999-08-03 | Lucent Technologies Inc. | Common-lens reflective magneto-optical switch |
US6201072B1 (en) * | 1997-10-03 | 2001-03-13 | Macromed, Inc. | Biodegradable low molecular weight triblock poly(lactide-co- glycolide) polyethylene glycol copolymers having reverse thermal gelation properties |
US6320017B1 (en) * | 1997-12-23 | 2001-11-20 | Inex Pharmaceuticals Corp. | Polyamide oligomers |
US6197535B1 (en) * | 1998-02-10 | 2001-03-06 | University Of Utah Research Foundation | Methods for purifying and assaying a conus γ-carboxylase |
EP0963758A3 (en) | 1998-05-07 | 2000-03-22 | Universiteit Gent | Synthetic polyaminoacid complexes for delivery of nucleic acids to target cells |
DE19822600C2 (de) * | 1998-05-20 | 2003-08-21 | Goldschmidt Ag Th | Copolymere, hydrophob modifizierte Polyasparaginsäureester mit erhöhter Molekularmasse |
GB9811059D0 (en) * | 1998-05-23 | 1998-07-22 | Univ Strathclyde | Polyamino acid vesicles |
US7030155B2 (en) * | 1998-06-05 | 2006-04-18 | Sonus Pharmaceuticals, Inc. | Emulsion vehicle for poorly soluble drugs |
US6143314A (en) * | 1998-10-28 | 2000-11-07 | Atrix Laboratories, Inc. | Controlled release liquid delivery compositions with low initial drug burst |
US7060708B2 (en) * | 1999-03-10 | 2006-06-13 | New River Pharmaceuticals Inc. | Active agent delivery systems and methods for protecting and administering active agents |
US6309663B1 (en) * | 1999-08-17 | 2001-10-30 | Lipocine Inc. | Triglyceride-free compositions and methods for enhanced absorption of hydrophilic therapeutic agents |
FR2801226B1 (fr) * | 1999-11-23 | 2002-01-25 | Flamel Tech Sa | Suspension colloidale de particules submicroniques de vectorisation de principes actifs et son mode de preparation |
US7785625B2 (en) * | 2000-01-14 | 2010-08-31 | Lg Life Sciences, Limited | Lipophilic-coated microparticle containing a protein drug and formulation comprising same |
FR2814952B1 (fr) * | 2000-10-06 | 2004-01-02 | Flamel Tech Sa | Suspension colloidale de particules submicromiques de vectorisation de principes actifs et leur mode de preparation |
US6541014B2 (en) * | 2000-10-13 | 2003-04-01 | Advancis Pharmaceutical Corp. | Antiviral product, use and formulation thereof |
FR2816840B1 (fr) * | 2000-11-17 | 2004-04-09 | Flamel Tech Sa | Medicament a base de microcapsules d'anti-hyperclycemiant a liberation prolongee et son procede de preparation |
JP4775985B2 (ja) | 2000-12-27 | 2011-09-21 | 三井化学株式会社 | 重合体及びその製造方法 |
JP4585114B2 (ja) | 2000-12-27 | 2010-11-24 | 三井化学株式会社 | 重合体及びその製造方法 |
WO2002067899A1 (en) * | 2001-02-28 | 2002-09-06 | Akzo Nobel N.V. | Injectable water-in-oil emulsions |
FR2822834B1 (fr) * | 2001-04-02 | 2005-02-25 | Flamel Tech Sa | Suspension colloidale de nanoparticules a base de copolymeres amphiphile pour la vectorisation de principes actifs et leur mode de preparation |
US6946146B2 (en) * | 2001-04-18 | 2005-09-20 | Nostrum Pharmaceuticals Inc. | Coating for a sustained release pharmaceutical composition |
RU2197586C1 (ru) * | 2001-07-25 | 2003-01-27 | Гунгер Юрий Робертович | Опорная конструкция для линии электропередачи |
CA2451368A1 (en) | 2001-08-03 | 2003-02-20 | The Procter & Gamble Company | Polyaspartate derivatives for use in detergent compositions |
EP1443907A1 (en) * | 2001-11-12 | 2004-08-11 | Alkermes Controlled Therapeutics, Inc. | Biocompatible polymer blends and uses thereof |
US7261875B2 (en) * | 2001-12-21 | 2007-08-28 | Board Of Regents, The University Of Texas System | Dendritic poly (amino acid) carriers and methods of use |
FR2838964B1 (fr) * | 2002-04-26 | 2004-07-09 | Flamel Tech Sa | Suspension colloidale de particules submicroniques de vectorisation de principes actifs et leur mode de preparation |
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) |
AR040149A1 (es) * | 2002-06-07 | 2005-03-16 | Novartis Ag | Compuestos de aminoacetonitrilo, un proceso para su preparacion, composicion, y uso del compuesto |
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 |
EP1567578B1 (fr) * | 2002-12-04 | 2008-06-25 | Flamel Technologies | Polyaminoacides fonctionnalises par au moins un groupement (oligo)aminoacide et leurs applications notamment therapeutiques |
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. |
FR2860516B1 (fr) * | 2003-10-03 | 2006-01-13 | Flamel Tech Sa | Homopolyaminoacides telecheliques fonctionnalises par des groupements hydrophobes et leurs applications notamment therapeutiques |
US7311901B2 (en) * | 2003-10-10 | 2007-12-25 | Samyang Corporation | Amphiphilic block copolymer and polymeric composition comprising the same for drug delivery |
FR2862536B1 (fr) | 2003-11-21 | 2007-11-23 | Flamel Tech Sa | Formulations pharmaceutiques pour la liberation prolongee de principe(s) actif(s), ainsi que leurs applications notamment therapeutiques |
FR2862541B1 (fr) * | 2003-11-21 | 2007-04-20 | Flamel Tech Sa | Formulations pharmaceutiques pour la liberation prolongee d'interferons et leurs applications therapeutiques |
FR2862535B1 (fr) * | 2003-11-21 | 2007-11-23 | Flamel Tech Sa | Formulations pharmaceutiques pour la liberation prolongee d'interleukines et leurs applications therapeutiques |
FR2873040B1 (fr) * | 2004-07-19 | 2007-11-30 | Flamel Technologies Sa | Formulation colloidale d'insuline longue action et sa preparation |
FR2881140B1 (fr) | 2005-01-27 | 2007-04-06 | Flamel Technologies Sa | Copolyhydroxyalkylglutamines fonctionnalises par des groupements hydrophobes et leurs applications notamment therapeutiques |
FR2891149B1 (fr) * | 2005-09-26 | 2007-11-30 | Biodex Sarl | Composition pharmaceutique a action cicatrisante comprenant un derive de dextrane soluble et un facteur de croissance derive des plaquettes. |
MX2008012837A (es) * | 2006-04-07 | 2008-10-17 | Adocia | Polisacaridos bifuncionalizados. |
US8679540B2 (en) * | 2006-06-09 | 2014-03-25 | Flamel Technologies | Pharmaceutical formulations for the prolonged release of active principle(s), and their applications, especially therapeutic applications |
US20080102128A1 (en) * | 2006-07-28 | 2008-05-01 | Flamel Technologies, Inc. | Modified-release microparticles based on amphiphilic copolymer and on active principles(s) and pharmaceutical formulations comprising them |
FR2915748B1 (fr) * | 2007-05-03 | 2012-10-19 | Flamel Tech Sa | Acides polyglutamiques fonctionnalises par des groupes cationiques et des groupements hydrophobes et leurs applications, notamment therapeutiques |
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Patent Citations (3)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN1183040A (zh) * | 1995-03-28 | 1998-05-27 | 弗拉梅技术公司 | 用作活性成分载体的多聚氨基酸基颗粒和其制备方法 |
CN1282345A (zh) * | 1997-10-03 | 2001-01-31 | 麦克罗梅德公司 | 具有可逆热胶凝性质的可生物降解低分子量三嵌段聚(丙交酯-co-乙交酯)聚乙二醇共聚物 |
US6630171B1 (en) * | 1998-11-20 | 2003-10-07 | Flamel Technologies | Particles based on polyamino-acid(s) and methods for preparing same |
Also Published As
Publication number | Publication date |
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US8084045B2 (en) | 2011-12-27 |
JP2007511586A (ja) | 2007-05-10 |
ATE451116T1 (de) | 2009-12-15 |
BRPI0416779A (pt) | 2007-03-06 |
US20070196497A1 (en) | 2007-08-23 |
TW200518775A (en) | 2005-06-16 |
AU2004292369A1 (en) | 2005-06-09 |
FR2862536A1 (fr) | 2005-05-27 |
ES2338012T3 (es) | 2010-05-03 |
KR101092547B1 (ko) | 2011-12-09 |
IL175768A (en) | 2012-06-28 |
FR2862536B1 (fr) | 2007-11-23 |
DK1689425T3 (da) | 2010-04-19 |
EP1689425A1 (fr) | 2006-08-16 |
CN1886151A (zh) | 2006-12-27 |
CA2546675C (fr) | 2014-01-07 |
BRPI0416779B1 (pt) | 2017-01-17 |
EP1689425B1 (fr) | 2009-12-09 |
PT1689425E (pt) | 2010-04-05 |
EP1689425B8 (fr) | 2010-02-17 |
IL175768A0 (en) | 2006-09-05 |
ZA200603950B (en) | 2008-01-08 |
WO2005051416A1 (fr) | 2005-06-09 |
KR20060130076A (ko) | 2006-12-18 |
SI1689425T1 (sl) | 2010-04-30 |
PL1689425T3 (pl) | 2010-07-30 |
CY1110612T1 (el) | 2015-04-29 |
BRPI0416779B8 (pt) | 2021-05-25 |
CA2546675A1 (fr) | 2005-06-09 |
AU2004292369B2 (en) | 2010-12-09 |
DE602004024571D1 (de) | 2010-01-21 |
JP4988352B2 (ja) | 2012-08-01 |
MXPA06005717A (es) | 2007-01-30 |
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