PT98397B - Processo para a preparacao de microcapsulas para administracao de uma composicao farmaceutica com libertacao controlada duma proteina ou dum polipeptido mediante integracao com um polimero hidrofobico biodegradavel - Google Patents
Processo para a preparacao de microcapsulas para administracao de uma composicao farmaceutica com libertacao controlada duma proteina ou dum polipeptido mediante integracao com um polimero hidrofobico biodegradavel Download PDFInfo
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- PT98397B PT98397B PT98397A PT9839791A PT98397B PT 98397 B PT98397 B PT 98397B PT 98397 A PT98397 A PT 98397A PT 9839791 A PT9839791 A PT 9839791A PT 98397 B PT98397 B PT 98397B
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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
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/16—Agglomerates; Granulates; Microbeadlets ; Microspheres; Pellets; Solid products obtained by spray drying, spray freeze drying, spray congealing,(multiple) emulsion solvent evaporation or extraction
- A61K9/1605—Excipients; Inactive ingredients
- A61K9/1629—Organic macromolecular compounds
- A61K9/1641—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, poloxamers
- A61K9/1647—Polyesters, e.g. poly(lactide-co-glycolide)
-
- 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
-
- 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
- A61K47/59—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 otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyureas or polyurethanes
- A61K47/593—Polyesters, e.g. PLGA or polylactide-co-glycolide
Landscapes
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Animal Behavior & Ethology (AREA)
- Public Health (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Compositions Of Macromolecular Compounds (AREA)
- Adjustment And Processing Of Grains (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US55442790A | 1990-07-19 | 1990-07-19 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PT98397A PT98397A (pt) | 1992-05-29 |
| PT98397B true PT98397B (pt) | 1999-01-29 |
Family
ID=24213291
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PT98397A PT98397B (pt) | 1990-07-19 | 1991-07-19 | Processo para a preparacao de microcapsulas para administracao de uma composicao farmaceutica com libertacao controlada duma proteina ou dum polipeptido mediante integracao com um polimero hidrofobico biodegradavel |
Country Status (17)
| Country | Link |
|---|---|
| US (2) | US6306406B1 (https=) |
| EP (1) | EP0467389B1 (https=) |
| JP (1) | JPH05103838A (https=) |
| AT (1) | ATE185269T1 (https=) |
| AU (1) | AU656897B2 (https=) |
| CA (1) | CA2046830C (https=) |
| CS (1) | CS224891A3 (https=) |
| DE (1) | DE69131677T2 (https=) |
| DK (1) | DK0467389T3 (https=) |
| ES (1) | ES2138584T3 (https=) |
| FI (1) | FI104954B (https=) |
| GR (1) | GR3032056T3 (https=) |
| MX (1) | MX9100249A (https=) |
| NO (1) | NO304411B1 (https=) |
| NZ (1) | NZ238951A (https=) |
| PT (1) | PT98397B (https=) |
| ZA (1) | ZA915584B (https=) |
Families Citing this family (131)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US6099856A (en) | 1992-06-15 | 2000-08-08 | Emisphere Technologies, Inc. | Active agent transport systems |
| US5447728A (en) * | 1992-06-15 | 1995-09-05 | Emisphere Technologies, Inc. | Desferrioxamine oral delivery system |
| US5629020A (en) | 1994-04-22 | 1997-05-13 | Emisphere Technologies, Inc. | Modified amino acids for drug delivery |
| US5541155A (en) | 1994-04-22 | 1996-07-30 | Emisphere Technologies, Inc. | Acids and acid salts and their use in delivery systems |
| US5578323A (en) | 1992-06-15 | 1996-11-26 | Emisphere Technologies, Inc. | Proteinoid carriers and methods for preparation and use thereof |
| US6331318B1 (en) | 1994-09-30 | 2001-12-18 | Emisphere Technologies Inc. | Carbon-substituted diketopiperazine delivery systems |
| US5693338A (en) | 1994-09-29 | 1997-12-02 | Emisphere Technologies, Inc. | Diketopiperazine-based delivery systems |
| US5443841A (en) * | 1992-06-15 | 1995-08-22 | Emisphere Technologies, Inc. | Proteinoid microspheres and methods for preparation and use thereof |
| US6221367B1 (en) | 1992-06-15 | 2001-04-24 | Emisphere Technologies, Inc. | Active agent transport systems |
| US5451410A (en) * | 1993-04-22 | 1995-09-19 | Emisphere Technologies, Inc. | Modified amino acids for encapsulating active agents |
| US5714167A (en) | 1992-06-15 | 1998-02-03 | Emisphere Technologies, Inc. | Active agent transport systems |
| JPH05202177A (ja) * | 1991-09-06 | 1993-08-10 | Teijin Ltd | 生分解性共重合体、及びそれを含有する医薬品組成物 |
| GB9211268D0 (en) * | 1992-05-28 | 1992-07-15 | Ici Plc | Salts of basic peptides with carboxyterminated polyesters |
| US5792451A (en) | 1994-03-02 | 1998-08-11 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
| US5811127A (en) | 1992-06-15 | 1998-09-22 | Emisphere Technologies, Inc. | Desferrioxamine oral delivery system |
| FR2693905B1 (fr) * | 1992-07-27 | 1994-09-02 | Rhone Merieux | Procédé de préparation de microsphères pour la libération prolongée de l'hormone LHRH et ses analogues, microsphères et formulations obtenues. |
| ES2110573T3 (es) * | 1992-08-07 | 1998-02-16 | Takeda Chemical Industries Ltd | Produccion de microcapsulas de farmacos solubles en agua. |
| WO1994010980A1 (en) * | 1992-11-16 | 1994-05-26 | Corporation Of Mercer University | Compositions using microencapsulated neutralizing antibodies |
| TW333456B (en) * | 1992-12-07 | 1998-06-11 | Takeda Pharm Ind Co Ltd | A pharmaceutical composition of sustained-release preparation the invention relates to a pharmaceutical composition of sustained-release preparation which comprises a physiologically active peptide. |
| UA61046C2 (en) | 1992-12-07 | 2003-11-17 | Takeda Chemical Industries Ltd | Sustained-release preparation and method for its manufacture |
| US5401516A (en) | 1992-12-21 | 1995-03-28 | Emisphere Technologies, Inc. | Modified hydrolyzed vegetable protein microspheres and methods for preparation and use thereof |
| US5672659A (en) * | 1993-01-06 | 1997-09-30 | Kinerton Limited | Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides |
| US6221958B1 (en) | 1993-01-06 | 2001-04-24 | Societe De Conseils De Recherches Et D'applications Scientifiques, Sas | Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides |
| DK0678018T3 (da) * | 1993-01-06 | 2003-04-28 | Kinerton Ltd | Ion molekylærkonjugater af bionedbrydelige polyestere og bioaktive polypeptider |
| US5863985A (en) * | 1995-06-29 | 1999-01-26 | Kinerton Limited | Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides |
| US5958457A (en) | 1993-04-22 | 1999-09-28 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
| US5709861A (en) | 1993-04-22 | 1998-01-20 | Emisphere Technologies, Inc. | Compositions for the delivery of antigens |
| AU6819294A (en) | 1993-04-22 | 1994-11-08 | Emisphere Technologies, Inc. | Oral drug delivery compositions and methods |
| US5643957A (en) | 1993-04-22 | 1997-07-01 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US6087324A (en) * | 1993-06-24 | 2000-07-11 | Takeda Chemical Industries, Ltd. | Sustained-release preparation |
| KR100369764B1 (ko) * | 1994-07-20 | 2003-05-22 | 키너톤 리미티드 | 생분해성폴리에스테르및생활성폴리펩티드의이온성분자결합체 |
| US5989539A (en) | 1995-03-31 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5866536A (en) | 1995-03-31 | 1999-02-02 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| CN1151836C (zh) | 1995-03-31 | 2004-06-02 | 艾米斯菲尔技术有限公司 | 用作传送活性剂的化合物和组合物 |
| US5965121A (en) | 1995-03-31 | 1999-10-12 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5650386A (en) | 1995-03-31 | 1997-07-22 | Emisphere Technologies, Inc. | Compositions for oral delivery of active agents |
| US6001347A (en) | 1995-03-31 | 1999-12-14 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US6090958A (en) | 1995-03-31 | 2000-07-18 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5820881A (en) | 1995-04-28 | 1998-10-13 | Emisphere Technologies, Inc. | Microspheres of diamide-dicarboxylic acids |
| US5750147A (en) | 1995-06-07 | 1998-05-12 | Emisphere Technologies, Inc. | Method of solubilizing and encapsulating itraconazole |
| US5667806A (en) | 1995-06-07 | 1997-09-16 | Emisphere Technologies, Inc. | Spray drying method and apparatus |
| US5824345A (en) | 1995-06-07 | 1998-10-20 | Emisphere Technologies, Inc. | Fragrances and flavorants |
| US6051258A (en) | 1995-06-07 | 2000-04-18 | Emisphere Technologies, Inc. | Proteinoid emulsions and methods for preparation and use thereof |
| AU6242096A (en) | 1995-06-27 | 1997-01-30 | Takeda Chemical Industries Ltd. | Method of producing sustained-release preparation |
| GB2320248B (en) | 1995-09-11 | 1999-04-14 | Emisphere Tech Inc | Method for preparing omega-aminoalkanoic acid derivatives from cycloalkanones |
| DE69608122T3 (de) | 1995-11-09 | 2011-06-16 | Microbiological Research Authority Camr, Salisbury | Mikroverkapselte dna zur impfung und gentherapie |
| US6270795B1 (en) | 1995-11-09 | 2001-08-07 | Microbiological Research Authority | Method of making microencapsulated DNA for vaccination and gene therapy |
| IL126318A (en) | 1996-03-29 | 2004-09-27 | Emisphere Tech Inc | Compounds and compositions for delivering active agents and some novel carrier compounds |
| CA2258264A1 (en) | 1996-06-14 | 1997-12-18 | Emisphere Technologies, Inc. | Microencapsulated fragrances and method for preparation |
| AU779930B2 (en) * | 1996-12-11 | 2005-02-17 | Praecis Pharmaceuticals Incorporated | Pharmaceutical formulations for sustained drug delivery |
| US5968895A (en) | 1996-12-11 | 1999-10-19 | Praecis Pharmaceuticals, Inc. | Pharmaceutical formulations for sustained drug delivery |
| US5783567A (en) * | 1997-01-22 | 1998-07-21 | Pangaea Pharmaceuticals, Inc. | Microparticles for delivery of nucleic acid |
| US5939381A (en) | 1997-02-07 | 1999-08-17 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US6060513A (en) | 1997-02-07 | 2000-05-09 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5879681A (en) | 1997-02-07 | 1999-03-09 | Emisphere Technolgies Inc. | Compounds and compositions for delivering active agents |
| US6358504B1 (en) | 1997-02-07 | 2002-03-19 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5990166A (en) | 1997-02-07 | 1999-11-23 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US6313088B1 (en) | 1997-02-07 | 2001-11-06 | Emisphere Technologies, Inc. | 8-[(2-hydroxy-4-methoxy benzoyl) amino]-octanoic acid compositions for delivering active agents |
| US5876710A (en) | 1997-02-07 | 1999-03-02 | Emisphere Technologies Inc. | Compounds and compositions for delivering active agents |
| US5804688A (en) | 1997-02-07 | 1998-09-08 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5863944A (en) | 1997-04-30 | 1999-01-26 | Emisphere Technologies, Inc. | Compounds and compositions for delivering active agents |
| US5962710A (en) | 1997-05-09 | 1999-10-05 | Emisphere Technologies, Inc. | Method of preparing salicyloylamino acids |
| US6867181B1 (en) | 1997-06-02 | 2005-03-15 | Societe De Conseils De Recherches Et D'applications Scientifiques, S.A.S. | Ionic molecular conjugates of biodegradable polyesters and bioactive polypeptides |
| DE19723807C2 (de) * | 1997-06-06 | 2003-04-24 | Ferring Gmbh | Verfahren zur Herstellung von Copolyestern |
| JP2001510811A (ja) * | 1997-07-25 | 2001-08-07 | エスディージー インコーポレイテッド | 生物活性物質を標的に供給するための重合体ベースの薬剤組成物 |
| IL122933A (en) * | 1998-01-14 | 2005-03-20 | Efrat Biopolymers Ltd | Polymeric carrier for delivery of a bioactive molecule |
| DE69907870T2 (de) | 1998-01-29 | 2004-03-04 | Kinerton Ltd., Blanchardstown | Verfahren zur herstellung von absorbierbaren mikropartikeln |
| GB9810236D0 (en) | 1998-05-13 | 1998-07-08 | Microbiological Res Authority | Improvements relating to encapsulation of bioactive agents |
| US6406719B1 (en) | 1998-05-13 | 2002-06-18 | Microbiological Research Authority | Encapsulation of bioactive agents |
| US6548302B1 (en) | 1998-06-18 | 2003-04-15 | Johns Hopkins University School Of Medicine | Polymers for delivery of nucleic acids |
| US6916490B1 (en) | 1998-07-23 | 2005-07-12 | UAB Research Center | Controlled release of bioactive substances |
| US7193084B2 (en) | 2000-12-22 | 2007-03-20 | Baxter International Inc. | Polymorphic form of itraconazole |
| US9700866B2 (en) | 2000-12-22 | 2017-07-11 | Baxter International Inc. | Surfactant systems for delivery of organic compounds |
| US6977085B2 (en) | 2000-12-22 | 2005-12-20 | Baxter International Inc. | Method for preparing submicron suspensions with polymorph control |
| US6951656B2 (en) | 2000-12-22 | 2005-10-04 | Baxter International Inc. | Microprecipitation method for preparing submicron suspensions |
| US8067032B2 (en) | 2000-12-22 | 2011-11-29 | Baxter International Inc. | Method for preparing submicron particles of antineoplastic agents |
| US7037528B2 (en) | 2000-12-22 | 2006-05-02 | Baxter International Inc. | Microprecipitation method for preparing submicron suspensions |
| US6884436B2 (en) * | 2000-12-22 | 2005-04-26 | Baxter International Inc. | Method for preparing submicron particle suspensions |
| US20050048126A1 (en) | 2000-12-22 | 2005-03-03 | Barrett Rabinow | Formulation to render an antimicrobial drug potent against organisms normally considered to be resistant to the drug |
| ATE427760T1 (de) | 2001-02-23 | 2009-04-15 | Genentech Inc | Erodierbare polymere zur injektion |
| BR0212833A (pt) | 2001-09-26 | 2004-10-13 | Baxter Int | Preparação de nanopartìculas de tamanho submìcron através de dispersão e de remoção de solvente ou de fase lìquida |
| US20060003012A9 (en) | 2001-09-26 | 2006-01-05 | Sean Brynjelsen | Preparation of submicron solid particle suspensions by sonication of multiphase systems |
| US7112340B2 (en) | 2001-10-19 | 2006-09-26 | Baxter International Inc. | Compositions of and method for preparing stable particles in a frozen aqueous matrix |
| DE10206517A1 (de) * | 2002-02-16 | 2003-09-04 | Stoess & Co Gelatine | Depotarzneimittel, Trägermaterialien für Depotarzneimittel und Verfahren zu deren Herstellung |
| KR100405879B1 (ko) * | 2002-09-19 | 2003-11-14 | 키너톤 리미티드 | 생분해성 폴리에스테르 및 생활성 폴리펩티드의 이온성분자 결합체 |
| IL152574A (en) * | 2002-10-31 | 2009-09-22 | Transpharma Medical Ltd | A system for passing through the skin of dry items or dried medicines |
| US8133505B2 (en) | 2002-10-31 | 2012-03-13 | Transpharma Medical Ltd. | Transdermal delivery system for dried particulate or lyophilized medications |
| EP1911763B1 (en) | 2003-01-28 | 2010-08-11 | Ironwood Pharmaceuticals, Inc. | Compositions for the treatment of gastrointestinal disorders |
| US7772188B2 (en) | 2003-01-28 | 2010-08-10 | Ironwood Pharmaceuticals, Inc. | Methods and compositions for the treatment of gastrointestinal disorders |
| US7393537B2 (en) * | 2003-04-25 | 2008-07-01 | Allergan, Inc. | Botulinum toxin for treatment of obsessive compulsive finger biting disorder |
| DE602004017726D1 (de) | 2003-06-30 | 2008-12-24 | Domantis Ltd | Pegylierte Single-domain-antikörper (dAb) |
| CA2544678C (en) | 2003-11-05 | 2013-12-31 | Sunesis Pharmaceuticals, Inc. | Modulators of cellular adhesion |
| JP2007517911A (ja) * | 2004-01-13 | 2007-07-05 | バソジェニックス ファーマシューティカルズ， インコーポレイテッド | 心臓血管の適応症および腎臓の適応症に対してｃｇｒｐを使用する方法 |
| EP1703916A2 (en) * | 2004-01-13 | 2006-09-27 | Vasogenix Pharmaceuticals, Inc. | Methods for treating acute myocardial infarction by calcitonin gene related peptide and compositions containing the same |
| US7976847B2 (en) | 2004-01-13 | 2011-07-12 | Vasogenix Pharmaceuticals, Inc. | Controlled release CGRP delivery composition for cardiovascular and renal indications |
| JP2007520555A (ja) * | 2004-02-05 | 2007-07-26 | バクスター・インターナショナル・インコーポレイテッド | 自己安定化剤の使用により調製された分散剤 |
| US7563443B2 (en) | 2004-09-17 | 2009-07-21 | Domantis Limited | Monovalent anti-CD40L antibody polypeptides and compositions thereof |
| DK2444079T3 (en) | 2005-05-17 | 2017-01-30 | Sarcode Bioscience Inc | Compositions and Methods for the Treatment of Eye Diseases |
| US20070142287A1 (en) * | 2005-12-20 | 2007-06-21 | Biomed Solutions, Llc | Compositions And Methods For Treatment Of Cancer |
| US20100222875A1 (en) * | 2006-08-08 | 2010-09-02 | Abbott Cardiovascular Systems Inc. | Method for forming a porous stent coating |
| US8722736B2 (en) | 2007-05-22 | 2014-05-13 | Baxter International Inc. | Multi-dose concentrate esmolol with benzyl alcohol |
| US8426467B2 (en) | 2007-05-22 | 2013-04-23 | Baxter International Inc. | Colored esmolol concentrate |
| US8969514B2 (en) | 2007-06-04 | 2015-03-03 | Synergy Pharmaceuticals, Inc. | Agonists of guanylate cyclase useful for the treatment of hypercholesterolemia, atherosclerosis, coronary heart disease, gallstone, obesity and other cardiovascular diseases |
| MX354786B (es) | 2007-06-04 | 2018-03-21 | Synergy Pharmaceuticals Inc | Agonistas de guanilato ciclasa utiles para el tratamiento de trastornos gastrointestinales, inflamacion, cancer y otros trastornos. |
| ES2830024T3 (es) | 2007-10-19 | 2021-06-02 | Novartis Ag | Composiciones y métodos para el tratamiento del edema macular |
| WO2009139817A2 (en) | 2008-04-15 | 2009-11-19 | Sarcode Corporation | Crystalline pharmaceutical and methods of preparation and use thereof |
| ES2522968T3 (es) | 2008-06-04 | 2014-11-19 | Synergy Pharmaceuticals Inc. | Agonistas de guanilato ciclasa útiles para el tratamiento de trastornos gastrointestinales, inflamación, cáncer y otros trastornos |
| AU2009270833B2 (en) | 2008-07-16 | 2015-02-19 | Bausch Health Ireland Limited | Agonists of guanylate cyclase useful for the treatment of gastrointestinal, inflammation, cancer and other disorders |
| PE20110385A1 (es) | 2008-07-18 | 2011-06-22 | Bristol Myers Squibb Co | Anticuerpo de dominio (dab) que se une a cd28 y no reacciona en forma cruzada con ctla4 |
| WO2011050175A1 (en) | 2009-10-21 | 2011-04-28 | Sarcode Corporation | Crystalline pharmaceutical and methods of preparation and use thereof |
| CN107129538B (zh) * | 2010-04-27 | 2021-07-16 | 西兰制药公司 | Glp-1受体激动剂和胃泌素的肽缀合物及其用途 |
| GB201009037D0 (en) | 2010-05-28 | 2010-07-14 | Univ Surrey | Compositions and methods for treating disorders associated with atherosclerotic plaques |
| US8865220B2 (en) * | 2010-06-14 | 2014-10-21 | Kaohsiung Medical University | Method for controlled release of parathyroid hormone from encapsulated poly(lactic-glycolic)acid microspheres |
| BRPI1003424A2 (pt) * | 2010-09-08 | 2013-01-08 | Univ Rio De Janeiro | sistema polimÉtrico de confinamento de amilina humana e anÁlogos agonistas, processo e uso; processo de avaliaÇço funcional de amilina liberada |
| US9616097B2 (en) | 2010-09-15 | 2017-04-11 | Synergy Pharmaceuticals, Inc. | Formulations of guanylate cyclase C agonists and methods of use |
| CN107823706B (zh) | 2010-11-10 | 2022-02-01 | 因瑞金公司 | 用于器官增强的注射制剂 |
| WO2012151343A1 (en) | 2011-05-04 | 2012-11-08 | Balance Therapeutics, Inc. | Pentylenetetrazole derivatives |
| KR20200108932A (ko) | 2012-07-25 | 2020-09-21 | 에스에이알코드 바이오사이언스 인코포레이티드 | Lfa-1 저해제 및 그의 다형체 |
| SI2912165T1 (sl) | 2012-10-24 | 2019-11-29 | Inregen | Populacije ledvičnih celic in njihova uporaba |
| WO2014120916A1 (en) | 2013-02-01 | 2014-08-07 | Bristol-Myers Squibb Company | Pegylated domain antibodies monovalent for cd28 binding and methods of use |
| WO2014131024A2 (en) | 2013-02-25 | 2014-08-28 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| AU2014235209B2 (en) | 2013-03-15 | 2018-06-14 | Bausch Health Ireland Limited | Guanylate cyclase receptor agonists combined with other drugs |
| AU2014235215A1 (en) | 2013-03-15 | 2015-10-01 | Synergy Pharmaceuticals Inc. | Agonists of guanylate cyclase and their uses |
| JP6661531B2 (ja) | 2013-10-10 | 2020-03-11 | シナジー ファーマシューティカルズ インコーポレイテッド | オピオイド誘発性機能障害の治療に有用なグアニル酸シクラーゼのアゴニスト |
| US10653744B2 (en) | 2016-01-11 | 2020-05-19 | Bausch Health Ireland Limited | Formulations and methods for treating ulcerative colitis |
| MX2019014578A (es) | 2017-06-21 | 2020-12-01 | Timothy A Bertram | Celulas renales bioactivas inmunoprivilegiadas para el tratamiento de enfermedad renal. |
| JP2021533934A (ja) * | 2018-08-24 | 2021-12-09 | ノース カロライナ ステート ユニバーシティNorth Carolina State University | 閉ループインスリン送達用のグルコース応答性マトリックスを備えたマイクロニードルアレイパッチ |
| US12447179B2 (en) | 2018-08-31 | 2025-10-21 | Prokidney | Compositions comprising cell-delivered vesicles and uses thereof |
| CN120091828A (zh) * | 2022-10-12 | 2025-06-03 | 中外制药株式会社 | 含有肽、表面活性剂和聚合物的组合物 |
| WO2026050206A1 (en) | 2024-08-27 | 2026-03-05 | Ironwood Pharmaceuticals, Inc. | Combinations of glp-1 and guanylate cyclase c (gc-c) receptor agonists |
| CN121405779A (zh) * | 2025-10-17 | 2026-01-27 | 中国兵器工业火炸药工程与安全技术研究院 | 一种驱溶用多肽材料及其制备方法和在制备球形发射药的应用 |
Family Cites Families (34)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3773919A (en) * | 1969-10-23 | 1973-11-20 | Du Pont | Polylactide-drug mixtures |
| US3977941A (en) | 1971-04-20 | 1976-08-31 | Research Corporation | Protein-enzyme complex membranes |
| US3843446A (en) | 1971-04-20 | 1974-10-22 | Research Corp | Preparation of enzymatically active membranes |
| US4601981A (en) | 1971-04-20 | 1986-07-22 | Research Corporation | Enzymatically active protein-enzyme complex membranes |
| US3972776A (en) | 1973-02-26 | 1976-08-03 | Research Corporation | Preparation of protein membranes containing microbial cells |
| US5366734A (en) * | 1981-02-16 | 1994-11-22 | Zeneca Limited | Continuous release pharmaceutical compositions |
| IE52535B1 (en) * | 1981-02-16 | 1987-12-09 | Ici Plc | Continuous release pharmaceutical compositions |
| DE3107527A1 (de) | 1981-02-27 | 1982-09-16 | Klaus Prof. Dr. 8400 Regensburg Heckmann | Hyperfiltrationsmembranen mit trennschichten aus monomolekularen filmen von tensiden |
| US4585797A (en) | 1981-04-13 | 1986-04-29 | Seton Company | Cosmetic and pharmaceutical sheet material containing polypeptides |
| US4591501A (en) | 1981-04-13 | 1986-05-27 | Seton Company | Cosmetic and pharmaceutical sheet material containing polypeptides |
| DE3374837D1 (en) | 1982-02-17 | 1988-01-21 | Ciba Geigy Ag | Lipids in the aqueous phase |
| US4494994A (en) | 1983-03-28 | 1985-01-22 | Seton Company | Surface active agent compositions containing polypeptides and lignin sulfonic acid |
| US4557855A (en) | 1983-03-28 | 1985-12-10 | Seton Company | Surface active agent compositions |
| US4818542A (en) * | 1983-11-14 | 1989-04-04 | The University Of Kentucky Research Foundation | Porous microspheres for drug delivery and methods for making same |
| DE3413608A1 (de) * | 1984-04-11 | 1985-10-24 | Hoechst Ag, 6230 Frankfurt | Implantierbare zubereitungen von regulatorischen peptiden mit gesteuerter freisetzung und verfahren zu ihrer herstellung |
| DE3428372A1 (de) * | 1984-08-01 | 1986-02-13 | Hoechst Ag, 6230 Frankfurt | Mikrokapseln von regulatorischen peptiden mit kontrollierter freisetzung, verfahren zu ihrer herstellung und injektionszubereitungen |
| GB8500209D0 (en) | 1985-01-04 | 1985-02-13 | Ceskoslovenska Akademie Ved | Synthetic polymeric drugs |
| US4863735A (en) * | 1985-02-19 | 1989-09-05 | Massachusetts Institute Of Technology | Biodegradable polymeric drug delivery system with adjuvant activity |
| US4897444A (en) | 1985-05-31 | 1990-01-30 | The Research Foundation Of The State University Of New York | Immobilized fluorogenic substrates for enzymes; and processes for their preparation |
| US4871716A (en) * | 1986-02-04 | 1989-10-03 | University Of Florida | Magnetically responsive, hydrophilic microspheres for incorporation of therapeutic substances and methods of preparation thereof |
| US4741872A (en) * | 1986-05-16 | 1988-05-03 | The University Of Kentucky Research Foundation | Preparation of biodegradable microspheres useful as carriers for macromolecules |
| US4962091A (en) * | 1986-05-23 | 1990-10-09 | Syntex (U.S.A.) Inc. | Controlled release of macromolecular polypeptides |
| NZ221411A (en) | 1986-08-11 | 1989-10-27 | Innovata Biomed Ltd | Pharmaceutical compositions containing microcapsules and a surfactant |
| US4911928A (en) | 1987-03-13 | 1990-03-27 | Micro-Pak, Inc. | Paucilamellar lipid vesicles |
| WO1988009664A1 (en) * | 1987-06-10 | 1988-12-15 | Massachusetts Institute Of Technology | Polyphosphazene matrix erosion and diffusion release systems |
| GB8714378D0 (en) | 1987-06-19 | 1987-07-22 | Hunchplan Ltd | Parenteral delivery of drugs |
| US4857311A (en) * | 1987-07-31 | 1989-08-15 | Massachusetts Institute Of Technology | Polyanhydrides with improved hydrolytic degradation properties |
| PT88490B (pt) * | 1987-09-14 | 1992-11-30 | Novo Nordisk As | Processo para a preparacao de composicoes farmaceuticas para libertacao nao-enterica trans-mucosa contendo monossacaridos ou oligossacaridos |
| GB2209937B (en) * | 1987-09-21 | 1991-07-03 | Depiopharm S A | Water insoluble polypeptides |
| JP2670680B2 (ja) * | 1988-02-24 | 1997-10-29 | 株式会社ビーエムジー | 生理活性物質含有ポリ乳酸系微小球およびその製造法 |
| EP0354714A3 (en) | 1988-08-12 | 1991-04-10 | Hadassah Medical Organization | Pharmaceutical compositions containing polyaromatic compounds |
| US5008116A (en) * | 1988-11-14 | 1991-04-16 | Frederick Cahn | Immunostimulatory microsphere |
| US5019400A (en) * | 1989-05-01 | 1991-05-28 | Enzytech, Inc. | Very low temperature casting of controlled release microspheres |
| CA2071840C (en) * | 1989-11-06 | 1997-02-04 | Edith Mathiowitz | Method for producing protein microspheres |
-
1991
- 1991-07-11 CA CA002046830A patent/CA2046830C/en not_active Expired - Fee Related
- 1991-07-12 NZ NZ238951A patent/NZ238951A/en not_active IP Right Cessation
- 1991-07-15 NO NO912769A patent/NO304411B1/no unknown
- 1991-07-16 AU AU80466/91A patent/AU656897B2/en not_active Ceased
- 1991-07-17 MX MX9100249A patent/MX9100249A/es not_active IP Right Cessation
- 1991-07-17 FI FI913455A patent/FI104954B/fi not_active IP Right Cessation
- 1991-07-17 ZA ZA915584A patent/ZA915584B/xx unknown
- 1991-07-19 CS CS912248A patent/CS224891A3/cs unknown
- 1991-07-19 DE DE69131677T patent/DE69131677T2/de not_active Expired - Fee Related
- 1991-07-19 DK DK91112118T patent/DK0467389T3/da active
- 1991-07-19 PT PT98397A patent/PT98397B/pt active IP Right Revival
- 1991-07-19 JP JP3179588A patent/JPH05103838A/ja active Pending
- 1991-07-19 EP EP91112118A patent/EP0467389B1/en not_active Expired - Lifetime
- 1991-07-19 ES ES91112118T patent/ES2138584T3/es not_active Expired - Lifetime
- 1991-07-19 AT AT91112118T patent/ATE185269T1/de not_active IP Right Cessation
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1995
- 1995-06-07 US US08/481,155 patent/US6306406B1/en not_active Expired - Fee Related
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1999
- 1999-12-07 GR GR990403145T patent/GR3032056T3/el unknown
-
2001
- 2001-09-04 US US09/944,369 patent/US20020051808A1/en not_active Abandoned
Also Published As
| Publication number | Publication date |
|---|---|
| NO912769D0 (no) | 1991-07-15 |
| CA2046830A1 (en) | 1992-01-20 |
| PT98397A (pt) | 1992-05-29 |
| FI913455A0 (fi) | 1991-07-17 |
| NZ238951A (en) | 1994-12-22 |
| JPH05103838A (ja) | 1993-04-27 |
| ATE185269T1 (de) | 1999-10-15 |
| DE69131677D1 (de) | 1999-11-11 |
| FI913455L (fi) | 1992-01-20 |
| FI104954B (fi) | 2000-05-15 |
| DE69131677T2 (de) | 2000-02-24 |
| ZA915584B (en) | 1992-04-29 |
| EP0467389A2 (en) | 1992-01-22 |
| EP0467389B1 (en) | 1999-10-06 |
| CS224891A3 (en) | 1992-03-18 |
| ES2138584T3 (es) | 2000-01-16 |
| AU8046691A (en) | 1992-01-23 |
| US20020051808A1 (en) | 2002-05-02 |
| NO912769L (no) | 1992-01-20 |
| GR3032056T3 (en) | 2000-03-31 |
| NO304411B1 (no) | 1998-12-14 |
| DK0467389T3 (da) | 2000-02-28 |
| AU656897B2 (en) | 1995-02-23 |
| CA2046830C (en) | 1999-12-14 |
| EP0467389A3 (https=) | 1994-02-02 |
| MX9100249A (es) | 1992-02-28 |
| US6306406B1 (en) | 2001-10-23 |
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