SK285139B6 - Kompozícia vo forme mikroemulzného prekoncentrátuobsahujúca cyklosporín a jej použitie - Google Patents
Kompozícia vo forme mikroemulzného prekoncentrátuobsahujúca cyklosporín a jej použitie Download PDFInfo
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- SK285139B6 SK285139B6 SK1319-2000A SK13192000A SK285139B6 SK 285139 B6 SK285139 B6 SK 285139B6 SK 13192000 A SK13192000 A SK 13192000A SK 285139 B6 SK285139 B6 SK 285139B6
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Classifications
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- A61K9/1075—Microemulsions or submicron emulsions; Preconcentrates or solids thereof; Micelles, e.g. made of phospholipids or block copolymers
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/436—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a six-membered ring having oxygen as a ring hetero atom, e.g. rapamycin
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/12—Cyclic peptides, e.g. bacitracins; Polymyxins; Gramicidins S, C; Tyrocidins A, B or C
- A61K38/13—Cyclosporins
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- 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
- A61K9/4841—Filling excipients; Inactive ingredients
- A61K9/4858—Organic compounds
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
- A61P31/04—Antibacterial agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
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- A—HUMAN NECESSITIES
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- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
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- A—HUMAN NECESSITIES
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- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P41/00—Drugs used in surgical methods, e.g. surgery adjuvants for preventing adhesion or for vitreum substitution
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Public Health (AREA)
- General Health & Medical Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- General Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Epidemiology (AREA)
- Engineering & Computer Science (AREA)
- Dispersion Chemistry (AREA)
- Gastroenterology & Hepatology (AREA)
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- Pain & Pain Management (AREA)
- Oncology (AREA)
- Transplantation (AREA)
- Biophysics (AREA)
- Rheumatology (AREA)
- Molecular Biology (AREA)
- Surgery (AREA)
- Communicable Diseases (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Peptides Or Proteins (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB9804742.6A GB9804742D0 (en) | 1998-03-06 | 1998-03-06 | Organic compounds |
| GBGB9805104.8A GB9805104D0 (en) | 1998-03-10 | 1998-03-10 | Organic compounds |
| GBGB9805199.8A GB9805199D0 (en) | 1998-03-11 | 1998-03-11 | Organic compounds |
| PCT/EP1999/001415 WO1999044584A1 (en) | 1998-03-06 | 1999-03-04 | Emulsion preconcentrates containing cyclosporin or a macrolide |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| SK13192000A3 SK13192000A3 (sk) | 2001-02-12 |
| SK285139B6 true SK285139B6 (sk) | 2006-07-07 |
Family
ID=27269231
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| SK1319-2000A SK285139B6 (sk) | 1998-03-06 | 1999-03-04 | Kompozícia vo forme mikroemulzného prekoncentrátuobsahujúca cyklosporín a jej použitie |
Country Status (29)
Families Citing this family (45)
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| US5858401A (en) | 1996-01-22 | 1999-01-12 | Sidmak Laboratories, Inc. | Pharmaceutical composition for cyclosporines |
| JP2002531515A (ja) * | 1998-12-11 | 2002-09-24 | ファーマソリューションズ・インコーポレイテッド | 水に難溶性の薬剤のための自己乳化組成物 |
| DK1154759T3 (da) * | 1998-12-30 | 2008-12-08 | Dexcel Ltd | Dispergerbart koncentrat til indgift af cyclosporin |
| US6294192B1 (en) * | 1999-02-26 | 2001-09-25 | Lipocine, Inc. | Triglyceride-free compositions and methods for improved delivery of hydrophobic therapeutic agents |
| US6248363B1 (en) * | 1999-11-23 | 2001-06-19 | Lipocine, Inc. | Solid carriers for improved delivery of active ingredients in pharmaceutical compositions |
| US20070032853A1 (en) | 2002-03-27 | 2007-02-08 | Hossainy Syed F | 40-O-(2-hydroxy)ethyl-rapamycin coated stent |
| AU2127400A (en) * | 1999-11-02 | 2001-05-14 | Cipla Limited | A pharmaceutical composition for the administration of water-insoluble pharmaceutically active substances and process for preparation thereof |
| GB2362573A (en) * | 2000-05-25 | 2001-11-28 | Cipla Ltd | Cyclosporin formulation |
| AU1043201A (en) * | 1999-11-02 | 2001-05-14 | Cipla Limited | Cyclosporin formulation |
| GB0008785D0 (en) * | 2000-04-10 | 2000-05-31 | Novartis Ag | Organic compounds |
| DE10024451A1 (de) * | 2000-05-18 | 2001-11-29 | Asta Medica Ag | Pharmazeutische Darreichungsform für Peptide, Verfahren zu deren Herstellung und Verwendung |
| WO2003002095A1 (fr) * | 2001-06-28 | 2003-01-09 | Chugai Seiyaku Kabushiki Kaisha | Preparation d'une micro-emulsion de type huile-eau |
| US6960563B2 (en) | 2001-08-31 | 2005-11-01 | Morton Grove Pharmaceuticals, Inc. | Spontaneous emulsions containing cyclosporine |
| GB2391471B (en) * | 2002-08-02 | 2005-05-04 | Satishchandra Punambhai Patel | Pharmaceutical compositions |
| KR20040047056A (ko) * | 2002-11-29 | 2004-06-05 | 한미약품 주식회사 | 비페닐디메틸디카복실레이트의 경구용 마이크로에멀젼조성물 |
| US8802116B2 (en) | 2003-02-27 | 2014-08-12 | Novasel Australia Pty. Ltd. | Poloxamer emulsion preparations |
| KR20040084240A (ko) * | 2003-03-27 | 2004-10-06 | (주) 코스메디 | 고형지질나노입자, 이를 함유하는 활성성분 전달용약학조성물 및 이의 제조방법 |
| US20050118344A1 (en) | 2003-12-01 | 2005-06-02 | Pacetti Stephen D. | Temperature controlled crimping |
| JP2008518931A (ja) * | 2004-10-29 | 2008-06-05 | ノバルティス アクチエンゲゼルシャフト | 自発的に分散可能な医薬組成物 |
| MX2007011250A (es) * | 2005-03-21 | 2007-11-14 | Ivax Pharmaceuticals Sro | Inhibidor de la cristalizacion y su uso en capsulas de gelatina. |
| CN101032620B (zh) * | 2007-03-08 | 2010-05-19 | 上海凯昭医药科技有限公司 | 一种环孢素自乳化制剂及其制备方法 |
| US20090130198A1 (en) * | 2007-11-21 | 2009-05-21 | Innopharmax Inc. | Pharmaceutical composition with enhanced bioavailability |
| AU2009226019C1 (en) | 2008-03-20 | 2014-02-20 | Virun, Inc. | Emulsions including a PEG-derivative of tocopherol |
| CN102036661B (zh) | 2008-03-20 | 2016-12-28 | 维尔恩公司 | 维生素衍生物及其用途 |
| US11304960B2 (en) | 2009-01-08 | 2022-04-19 | Chandrashekar Giliyar | Steroidal compositions |
| JP5567909B2 (ja) * | 2010-06-17 | 2014-08-06 | 東洋カプセル株式会社 | タクロリムス含有カプセル剤 |
| US8741373B2 (en) | 2010-06-21 | 2014-06-03 | Virun, Inc. | Compositions containing non-polar compounds |
| US20180153904A1 (en) | 2010-11-30 | 2018-06-07 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9034858B2 (en) | 2010-11-30 | 2015-05-19 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US9358241B2 (en) | 2010-11-30 | 2016-06-07 | Lipocine Inc. | High-strength testosterone undecanoate compositions |
| US20120148675A1 (en) | 2010-12-10 | 2012-06-14 | Basawaraj Chickmath | Testosterone undecanoate compositions |
| JO3337B1 (ar) | 2010-12-13 | 2019-03-13 | Debiopharm Sa | تركيبات صيدلية تشمل أليسبوريفير |
| JP5717034B2 (ja) * | 2012-08-27 | 2015-05-13 | 丸和バイオケミカル株式会社 | マクロライド系化合物を含有する土壌線虫防除用薬剤 |
| US20150374835A1 (en) | 2012-12-31 | 2015-12-31 | Jrx Biotechnology, Inc. | Liquid topical pharmaceutical nano-emulsion formulations |
| KR101458466B1 (ko) * | 2013-06-24 | 2014-11-07 | 한국화학연구원 | 면역억제제가 봉입된 마이셀을 함유하는 경구제 |
| WO2016033556A1 (en) | 2014-08-28 | 2016-03-03 | Lipocine Inc. | BIOAVAILABLE SOLID STATE (17-β)-HYDROXY-4-ANDROSTEN-3-ONE ESTERS |
| US20170246187A1 (en) | 2014-08-28 | 2017-08-31 | Lipocine Inc. | (17-ß)-3-OXOANDROST-4-EN-17-YL TRIDECANOATE COMPOSITIONS AND METHODS OF THEIR PREPARATION AND USE |
| US20160361322A1 (en) | 2015-06-15 | 2016-12-15 | Lipocine Inc. | Composition and method for oral delivery of androgen prodrugs |
| CN108024914A (zh) | 2015-09-17 | 2018-05-11 | Jrx生物技术有限公司 | 改善皮肤的水合作用或润湿作用的方法 |
| WO2018098501A1 (en) | 2016-11-28 | 2018-05-31 | Lipocine Inc. | Oral testosterone undecanoate therapy |
| WO2020018974A1 (en) | 2018-07-20 | 2020-01-23 | Lipocine Inc. | Liver disease |
| SI3886813T1 (sl) * | 2018-11-26 | 2023-05-31 | Hepion Pharmaceuticals, Inc. | Farmacevtske formulacije analogov ciklosporina |
| WO2024014958A2 (en) * | 2022-07-15 | 2024-01-18 | Seranovo Holding B.V. | Lides formulation platform |
| WO2024014959A2 (en) * | 2022-07-15 | 2024-01-18 | Seranovo Holding B.V. | Micelle-generating formulations with improved hydrophobicity |
| CN117797093A (zh) * | 2024-02-29 | 2024-04-02 | 中国农业科学院农业环境与可持续发展研究所 | 一种以大环内酯类药物为活性成分的兽用口服纳米液体制剂 |
Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| GB8903804D0 (en) * | 1989-02-20 | 1989-04-05 | Sandoz Ltd | Improvements in or relating to organic compounds |
| US5639724A (en) * | 1984-07-24 | 1997-06-17 | Sandoz Ltd. | Cyclosporin galenic forms |
| JP2632010B2 (ja) * | 1988-01-29 | 1997-07-16 | 三共株式会社 | シクロスポリン製剤 |
| KR0148748B1 (ko) * | 1988-09-16 | 1998-08-17 | 장 크라메르, 한스 루돌프 하우스 | 사이클로스포린을 함유하는 약학조성물 |
| GB9113872D0 (en) * | 1991-06-27 | 1991-08-14 | Sandoz Ag | Improvements in or relating to organic compounds |
| EP1142568A1 (en) * | 1992-09-25 | 2001-10-10 | Novartis AG | Pharmaceutical compositions containing cyclosporins |
| GB2278780B (en) * | 1993-05-27 | 1998-10-14 | Sandoz Ltd | Macrolide formulations |
| DE4322826A1 (de) * | 1993-07-08 | 1995-01-12 | Galenik Labor Freiburg Gmbh | Pharmazeutisches Präparat |
| WO1995022343A1 (en) * | 1994-02-17 | 1995-08-24 | Shiseido Company, Ltd. | Cyclosporin-containing emulsion composition |
| JP3131112B2 (ja) * | 1994-02-17 | 2001-01-31 | 株式会社資生堂 | シクロスポリン含有乳化組成物 |
| DK0786986T3 (da) * | 1994-10-26 | 2002-04-29 | Novartis Ag | Anvendelse af en umættet fedtalkohol |
| IL129547A (en) * | 1994-10-26 | 2001-01-11 | Novartis Ag | Pharmaceutical compositions comprising a macrolide and an acid |
| HU215966B (hu) * | 1994-11-21 | 1999-07-28 | BIOGAL Gyógyszergyár Rt. | Orálisan alkalmazható, ciklosporint tartalmazó, összetett emulzió-előkoncentrátum |
| KR970064620A (ko) * | 1996-03-05 | 1997-10-13 | 임성기 | 사이클로스포린-함유 외용약제 조성물 |
| KR980008239A (ko) * | 1996-07-26 | 1998-04-30 | 김충환 | 사이클로스포린-함유 약학적 조성물 |
| US6063762A (en) * | 1997-12-05 | 2000-05-16 | Chong Kun Dang Corp. | Cyclosporin-containing microemulsion preconcentrate composition |
| DE69842121D1 (de) * | 1997-12-10 | 2011-03-17 | Cyclosporine Therapeutics Ltd | Omega-3 fettsäure enthaltende pharmazeutische zusammensetzungen |
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| Date | Code | Title | Description |
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| MM4A | Patent lapsed due to non-payment of maintenance fees |
Effective date: 20130304 |