IE62006B1 - "Orthorhombic ciclosporin crystal form, process for its production and pharmaceutical compositions containing it" - Google Patents
"Orthorhombic ciclosporin crystal form, process for its production and pharmaceutical compositions containing it"Info
- Publication number
- IE62006B1 IE62006B1 IE377988A IE377988A IE62006B1 IE 62006 B1 IE62006 B1 IE 62006B1 IE 377988 A IE377988 A IE 377988A IE 377988 A IE377988 A IE 377988A IE 62006 B1 IE62006 B1 IE 62006B1
- Authority
- IE
- Ireland
- Prior art keywords
- ciclosporin
- crystal form
- solvate
- cidosporin
- vith
- Prior art date
Links
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/04—Linear peptides containing only normal peptide links
- C07K7/06—Linear peptides containing only normal peptide links having 5 to 11 amino acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K7/00—Peptides having 5 to 20 amino acids in a fully defined sequence; Derivatives thereof
- C07K7/64—Cyclic peptides containing only normal peptide links
- C07K7/645—Cyclosporins; Related peptides
-
- 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
- A61K9/1682—Processes
- A61K9/1688—Processes resulting in pure drug agglomerate optionally containing up to 5% of excipient
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A61P17/06—Antipsoriatics
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P37/00—Drugs for immunological or allergic disorders
- A61P37/02—Immunomodulators
- A61P37/06—Immunosuppressants, e.g. drugs for graft rejection
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- General Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Veterinary Medicine (AREA)
- Public Health (AREA)
- Animal Behavior & Ethology (AREA)
- Pharmacology & Pharmacy (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Immunology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Biophysics (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biochemistry (AREA)
- Pain & Pain Management (AREA)
- Dermatology (AREA)
- Rheumatology (AREA)
- Transplantation (AREA)
- Epidemiology (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Medicinal Preparation (AREA)
- Peptides Or Proteins (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US13623087A | 1987-12-21 | 1987-12-21 | |
US17261388A | 1988-03-24 | 1988-03-24 | |
US21254888A | 1988-06-28 | 1988-06-28 |
Publications (2)
Publication Number | Publication Date |
---|---|
IE883779L IE883779L (en) | 1989-06-21 |
IE62006B1 true IE62006B1 (en) | 1994-12-14 |
Family
ID=27384838
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
IE377988A IE62006B1 (en) | 1987-12-21 | 1988-12-19 | "Orthorhombic ciclosporin crystal form, process for its production and pharmaceutical compositions containing it" |
Country Status (27)
Country | Link |
---|---|
JP (1) | JPH0791316B2 (xx) |
KR (1) | KR100188305B1 (xx) |
AT (1) | AT403163B (xx) |
AU (1) | AU626274B2 (xx) |
BE (1) | BE1002665A4 (xx) |
CA (1) | CA1341396C (xx) |
CH (1) | CH677926A5 (xx) |
CY (1) | CY1799A (xx) |
DE (1) | DE3843054C2 (xx) |
DK (1) | DK175220B1 (xx) |
ES (1) | ES2012580A6 (xx) |
FI (1) | FI89065C (xx) |
FR (1) | FR2624863B1 (xx) |
GB (1) | GB2211848B (xx) |
GR (1) | GR1002486B (xx) |
HK (1) | HK102894A (xx) |
HU (1) | HU203564B (xx) |
IE (1) | IE62006B1 (xx) |
IL (1) | IL88719A0 (xx) |
IT (1) | IT1235356B (xx) |
LU (1) | LU87409A1 (xx) |
MY (1) | MY103943A (xx) |
NL (1) | NL195096C (xx) |
NO (1) | NO177228C (xx) |
NZ (1) | NZ227384A (xx) |
SE (1) | SE503174C2 (xx) |
SG (1) | SG99494G (xx) |
Families Citing this family (25)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US5639724A (en) | 1984-07-24 | 1997-06-17 | Sandoz Ltd. | Cyclosporin galenic forms |
KR0148748B1 (ko) * | 1988-09-16 | 1998-08-17 | 장 크라메르, 한스 루돌프 하우스 | 사이클로스포린을 함유하는 약학조성물 |
US6007840A (en) * | 1988-09-16 | 1999-12-28 | Novartis Ag | Pharmaceutical compositions comprising cyclosporins |
US7081445B2 (en) | 1989-02-20 | 2006-07-25 | Novartis Ag | Cyclosporin galenic forms |
US5294604A (en) * | 1989-12-20 | 1994-03-15 | The Government Of The United States Of America As Represented By The Secretary Of The Department Of Health And Human Services | Method of treating ocular diseases by periocular administration of cyclosporine A or G |
GB9105705D0 (en) * | 1991-03-18 | 1991-05-01 | Sandoz Ltd | Improvements in or relating to organic compounds |
US6262022B1 (en) | 1992-06-25 | 2001-07-17 | Novartis Ag | Pharmaceutical compositions containing cyclosporin as the active agent |
WO1993023010A1 (en) * | 1992-05-13 | 1993-11-25 | Sandoz Ltd. | Ophthalmic compositions containing a cyclosporin |
ES2168271T3 (es) | 1992-09-25 | 2002-06-16 | Novartis Ag | Composiciones farmaceuticas que contienen ciclosporinas. |
EP0789580B1 (de) | 1994-11-03 | 2002-06-05 | Novartis AG | Neue zubereitungsformen des cyclosporins zur oralen applikation mit einfacher zusammensetzung und hoher bioverfügbarkeit und verfahren zu deren herstellung |
US5962019A (en) * | 1995-08-25 | 1999-10-05 | Sangstat Medical Corporation | Oral cyclosporin formulations |
US5766629A (en) | 1995-08-25 | 1998-06-16 | Sangstat Medical Corporation | Oral cyclosporin formulations |
DE19544507B4 (de) | 1995-11-29 | 2007-11-15 | Novartis Ag | Cyclosporin enthaltende Präparate |
US6262054B1 (en) | 1996-02-01 | 2001-07-17 | Sloan-Kettering Institute Of Cancer Research | Combination therapy method for treating breast cancer using edatrexate |
ES2229473T3 (es) | 1997-01-30 | 2005-04-16 | Novartis Ag | Composiciones farmaceuticas sin aceite que contienen ciclosporina a. |
TW581681B (en) | 1998-02-20 | 2004-04-01 | Nektar Therapeutics | Liquid crystal forms of cyclosporin |
US7732404B2 (en) | 1999-12-30 | 2010-06-08 | Dexcel Ltd | Pro-nanodispersion for the delivery of cyclosporin |
EP1706095B1 (en) | 2004-01-20 | 2008-12-24 | Allergan, Inc. | Compositions for localized therapy of the eye, comprising preferably triamcinolone acetonide and hyaluronic acid |
CN1763084B (zh) * | 2005-10-11 | 2010-04-21 | 山东新时代药业有限公司 | 高纯度环孢菌素a的制备方法 |
JP6163482B2 (ja) | 2011-05-27 | 2017-07-12 | アラーガン、インコーポレイテッドAllergan,Incorporated | シクロスポリンaの結晶形態、その調製方法、およびその使用のための方法 |
JP6204921B2 (ja) * | 2011-11-15 | 2017-09-27 | アラーガン、インコーポレイテッドAllergan,Incorporated | シクロスポリンaの形態2およびその作製方法 |
AU2012339701B8 (en) * | 2011-11-15 | 2017-11-16 | Allergan, Inc. | Autoclavable suspensions of cyclosporin A Form 2 |
EP3701939A1 (en) * | 2011-11-15 | 2020-09-02 | Allergan, Inc. | Suspensions of cyclosporin a form 2 |
CA2856044C (en) | 2011-11-15 | 2016-11-29 | Allergan, Inc. | Sustained action formulation of cyclosporin form 2 |
WO2024085235A1 (ja) * | 2022-10-20 | 2024-04-25 | 中外製薬株式会社 | 環状ペプチドの結晶の製造方法 |
Family Cites Families (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH614931A5 (xx) * | 1975-11-04 | 1979-12-28 | Sandoz Ag | |
CH640519A5 (en) * | 1976-04-09 | 1984-01-13 | Sandoz Ag | Process for preparing a modified form of the antibiotic S 7481/F-1 |
US4117118A (en) * | 1976-04-09 | 1978-09-26 | Sandoz Ltd. | Organic compounds |
DE2819094A1 (de) * | 1977-05-10 | 1978-11-23 | Sandoz Ag | Cyclosporin-derivate, ihre verwendung und herstellung |
CH637124A5 (en) * | 1978-10-18 | 1983-07-15 | Sandoz Ag | Antibiotic, its preparation and use |
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1988
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- 1988-12-19 DK DK198807054A patent/DK175220B1/da not_active IP Right Cessation
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- 1988-12-19 CH CH4687/88A patent/CH677926A5/de not_active IP Right Cessation
- 1988-12-19 AU AU27055/88A patent/AU626274B2/en not_active Expired
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- 1988-12-20 JP JP63321857A patent/JPH0791316B2/ja not_active Expired - Lifetime
- 1988-12-20 LU LU87409A patent/LU87409A1/fr unknown
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- 1988-12-21 CA CA000586611A patent/CA1341396C/en not_active Expired - Fee Related
- 1988-12-21 ES ES8803887A patent/ES2012580A6/es not_active Expired - Lifetime
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1994
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1995
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MK9A | Patent expired |