WO2001005819A1 - Nouveaux composes conjugues a base de cyclosporine hydrosoluble - Google Patents

Nouveaux composes conjugues a base de cyclosporine hydrosoluble Download PDF

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Publication number
WO2001005819A1
WO2001005819A1 PCT/KR1999/000379 KR9900379W WO0105819A1 WO 2001005819 A1 WO2001005819 A1 WO 2001005819A1 KR 9900379 W KR9900379 W KR 9900379W WO 0105819 A1 WO0105819 A1 WO 0105819A1
Authority
WO
WIPO (PCT)
Prior art keywords
och
conjugated compound
mammal
cyclosporine
formula
Prior art date
Application number
PCT/KR1999/000379
Other languages
English (en)
Inventor
Hyuk-Koo Lee
Jang-Sik Choi
Jong-Bae Yoon
Original Assignee
Kuhnil Pharm. Co., Ltd.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Kuhnil Pharm. Co., Ltd. filed Critical Kuhnil Pharm. Co., Ltd.
Priority to AU49342/99A priority Critical patent/AU4934299A/en
Priority to PCT/KR1999/000379 priority patent/WO2001005819A1/fr
Priority to PCT/KR2000/000775 priority patent/WO2001005818A1/fr
Priority to AU57135/00A priority patent/AU5713500A/en
Publication of WO2001005819A1 publication Critical patent/WO2001005819A1/fr

Links

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
    • C07K7/64—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
    • 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
    • A61K47/60—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 the organic macromolecular compound being a polyoxyalkylene oligomer, polymer or dendrimer, e.g. PEG, PPG, PEO or polyglycerol
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K38/00—Medicinal preparations containing peptides

Definitions

  • Cyclosporine is a peptide compound having a unique structure consisting of 11 poly-N-methylated amino acids and has been known to have useful pharmacological activities. Especially, immunosuppressive properties of systematically administered cyclosporine are used in therapy or during organ transplants or bone marrow transplants. It is also applicable to the treatment of broad range of autoimmune diseases of inflammatory etiology and also to the antiparasitic treatment.
  • Cyclosporine is used, for example, for the treatment of rheumatic diseases (rheumatoid polyarthritis), hematological disease (aplastic anemia, idiopathic thrombocytopenia), gastric disorders (ulcerating colitis, crons disease), dermatic disease (psoriasis, sclerodermia) and eye diseases (uveitis). Also topical applications have been tested, for example, in treatment of psoriasis, uveitis and alopecia.
  • rheumatic diseases rheumatoid polyarthritis
  • hematological disease aplastic anemia, idiopathic thrombocytopenia
  • gastric disorders ulcerating colitis, crons disease
  • dermatic disease psoriasis, sclerodermia
  • eye diseases uveitis
  • Cyclosporine has a low bioavailability and tissue-availability and thus, should be administered in an excessive amount. Therefore, the administeration of excess cyclosporine may frequently has undesirable side effects such as nephrotoxicity, hypertension, hyperkalemia, hyperurikemia, hepatotoxicity, anemia, gastrointestinal intolerance, tremor and parestesia. The most frequent side effect is usually renal dysfunction. Acute cyclosporine nephrotoxicity is dose-dependent. There is a correlation with the blood level and a decrease in the dose or discontinuation of cyclosporine therapy leads to an improvement. However, progressive and irreversible damage of kidneys was reported in patients with transplants.
  • the present inventors have developed a novel water-soluble polymer-cyclosporine conjugated compound which is formed by chemically combining cyclosporine to a water-soluble carrier.
  • the compounds of this invention are water soluble prodrugs of cyclosporine which are useful as immunosuppressant, antiinflammatory, antifungal and antiproliferative agents.
  • the conjugated compounds of the present invention When administered for the treatment or inhibition of the above disease state, the conjugated compounds of the present invention can be administered orally, parenterally, intranasally, transdermally, topically, intravaginally or rectally.
  • the conjugated compounds of the present invention are particularly advantageous as immunosuppressive, antiinflammatory, antifungal, and antiproliferative agents because of their water solubility.

Landscapes

  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Genetics & Genomics (AREA)
  • Biophysics (AREA)
  • Proteomics, Peptides & Aminoacids (AREA)
  • Biochemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

Cette invention, qui a trait à un composé conjugué cyclosporine-polymère hydrosoluble, concerne, plus précisément, l'administration d'un médicament à base de cyclosporine. Dans le cadre de cette invention, le médicament possède une liaison chimique à un excipient polymère ou macromoléculaire hydrosoluble rendant ce médicament hydrosoluble et lui conférant une meilleure biodisponibilité.
PCT/KR1999/000379 1999-07-15 1999-07-15 Nouveaux composes conjugues a base de cyclosporine hydrosoluble WO2001005819A1 (fr)

Priority Applications (4)

Application Number Priority Date Filing Date Title
AU49342/99A AU4934299A (en) 1999-07-15 1999-07-15 Novel water soluble-cyclosporine conjugated compounds
PCT/KR1999/000379 WO2001005819A1 (fr) 1999-07-15 1999-07-15 Nouveaux composes conjugues a base de cyclosporine hydrosoluble
PCT/KR2000/000775 WO2001005818A1 (fr) 1999-07-15 2000-07-15 Nouveaux composes conjugues polymere-cyclosporinehydrosolubles
AU57135/00A AU5713500A (en) 1999-07-15 2000-07-15 Novel water soluble-cyclosporin conjugated compounds

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
PCT/KR1999/000379 WO2001005819A1 (fr) 1999-07-15 1999-07-15 Nouveaux composes conjugues a base de cyclosporine hydrosoluble

Publications (1)

Publication Number Publication Date
WO2001005819A1 true WO2001005819A1 (fr) 2001-01-25

Family

ID=19570922

Family Applications (2)

Application Number Title Priority Date Filing Date
PCT/KR1999/000379 WO2001005819A1 (fr) 1999-07-15 1999-07-15 Nouveaux composes conjugues a base de cyclosporine hydrosoluble
PCT/KR2000/000775 WO2001005818A1 (fr) 1999-07-15 2000-07-15 Nouveaux composes conjugues polymere-cyclosporinehydrosolubles

Family Applications After (1)

Application Number Title Priority Date Filing Date
PCT/KR2000/000775 WO2001005818A1 (fr) 1999-07-15 2000-07-15 Nouveaux composes conjugues polymere-cyclosporinehydrosolubles

Country Status (2)

Country Link
AU (2) AU4934299A (fr)
WO (2) WO2001005819A1 (fr)

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2002085928A2 (fr) * 2001-04-20 2002-10-31 Debiopharm S.A. Cyclosporine modifiee utilisable en tant que pro-drogue et son utilisation
WO2004026862A1 (fr) * 2002-09-20 2004-04-01 Sankyo Company, Limited Compose hydrosoluble de triazole
US7230023B2 (en) 2001-02-22 2007-06-12 Sankyo Company, Limited Water-soluble triazole fungicide
US7696165B2 (en) 2006-03-28 2010-04-13 Albany Molecular Research, Inc. Use of cyclosporin alkyne analogues for preventing or treating viral-induced disorders
US7696166B2 (en) 2006-03-28 2010-04-13 Albany Molecular Research, Inc. Use of cyclosporin alkyne/alkene analogues for preventing or treating viral-induced disorders
US9402913B2 (en) 2013-03-08 2016-08-02 Allergan, Inc. Cyclosporine A steroid conjugates
US9402912B2 (en) 2013-03-08 2016-08-02 Allergan, Inc. Antibiotic conjugates directly linked with steroid drugs
CN112888452A (zh) * 2018-08-22 2021-06-01 贝凯恩生物医疗技术有限公司 环孢菌素组合物及使用方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB0316294D0 (en) * 2003-07-11 2003-08-13 Polytherics Ltd Conjugated biological molecules and their preparation

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1995033490A1 (fr) * 1994-06-02 1995-12-14 Enzon, Inc. Procede de solubilisation de substances pratiquement insolubles dans l'eau
US5614549A (en) * 1992-08-21 1997-03-25 Enzon, Inc. High molecular weight polymer-based prodrugs
WO1998007713A1 (fr) * 1996-08-20 1998-02-26 Enzon, Inc. Promedicaments a base de polymere a poids moleculaire eleve

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5595732A (en) * 1991-03-25 1997-01-21 Hoffmann-La Roche Inc. Polyethylene-protein conjugates
AU4406793A (en) * 1992-06-04 1993-12-30 Clover Consolidated, Limited Water-soluble polymeric carriers for drug delivery
US5382657A (en) * 1992-08-26 1995-01-17 Hoffmann-La Roche Inc. Peg-interferon conjugates
US5880131A (en) * 1993-10-20 1999-03-09 Enzon, Inc. High molecular weight polymer-based prodrugs

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5614549A (en) * 1992-08-21 1997-03-25 Enzon, Inc. High molecular weight polymer-based prodrugs
WO1995033490A1 (fr) * 1994-06-02 1995-12-14 Enzon, Inc. Procede de solubilisation de substances pratiquement insolubles dans l'eau
WO1998007713A1 (fr) * 1996-08-20 1998-02-26 Enzon, Inc. Promedicaments a base de polymere a poids moleculaire eleve

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
PAPRICA ET AL.: "Preparation of novel cyclosporin A derivatives", BIOCONJUGATE CHEM., vol. 3, no. 1, pages 32 - 36, XP000261482, DOI: doi:10.1021/bc00013a005 *

Cited By (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7230023B2 (en) 2001-02-22 2007-06-12 Sankyo Company, Limited Water-soluble triazole fungicide
WO2002085928A2 (fr) * 2001-04-20 2002-10-31 Debiopharm S.A. Cyclosporine modifiee utilisable en tant que pro-drogue et son utilisation
WO2002085928A3 (fr) * 2001-04-20 2003-04-17 Debiopharm Sa Cyclosporine modifiee utilisable en tant que pro-drogue et son utilisation
US6995139B2 (en) * 2001-04-20 2006-02-07 Debiopharm S.A. Cyclic undecapeptide pro-drugs and uses thereof
KR100932859B1 (ko) * 2001-04-20 2009-12-23 오프탈모파르마 에이쥐 프로드럭으로서 사용가능한 개질된 사이클로스포린 및이의 용도
WO2004026862A1 (fr) * 2002-09-20 2004-04-01 Sankyo Company, Limited Compose hydrosoluble de triazole
US7696165B2 (en) 2006-03-28 2010-04-13 Albany Molecular Research, Inc. Use of cyclosporin alkyne analogues for preventing or treating viral-induced disorders
US7696166B2 (en) 2006-03-28 2010-04-13 Albany Molecular Research, Inc. Use of cyclosporin alkyne/alkene analogues for preventing or treating viral-induced disorders
US9402913B2 (en) 2013-03-08 2016-08-02 Allergan, Inc. Cyclosporine A steroid conjugates
US9402912B2 (en) 2013-03-08 2016-08-02 Allergan, Inc. Antibiotic conjugates directly linked with steroid drugs
CN112888452A (zh) * 2018-08-22 2021-06-01 贝凯恩生物医疗技术有限公司 环孢菌素组合物及使用方法
EP3840769A4 (fr) * 2018-08-22 2022-06-22 Bacainn Biotherapeutics, Ltd. Compositions de cyclosporine et méthodes d'utilisation

Also Published As

Publication number Publication date
AU4934299A (en) 2001-02-05
AU5713500A (en) 2001-02-05
WO2001005818A1 (fr) 2001-01-25

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