+

WO1990003793A1 - Compositions contenant des cyclosporines - Google Patents

Compositions contenant des cyclosporines Download PDF

Info

Publication number
WO1990003793A1
WO1990003793A1 PCT/GB1989/001183 GB8901183W WO9003793A1 WO 1990003793 A1 WO1990003793 A1 WO 1990003793A1 GB 8901183 W GB8901183 W GB 8901183W WO 9003793 A1 WO9003793 A1 WO 9003793A1
Authority
WO
WIPO (PCT)
Prior art keywords
cyclosporin
acid
gammalinoleic
composition according
immunosuppression
Prior art date
Application number
PCT/GB1989/001183
Other languages
English (en)
Inventor
Rajan Madhok
Original Assignee
Rajan Madhok
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 Rajan Madhok filed Critical Rajan Madhok
Publication of WO1990003793A1 publication Critical patent/WO1990003793A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • 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

Definitions

  • the invention is concerned with improvements in or relating to compositions containing pharmacologically active peptides, that is a selected cyclosporin, together with a carrier.
  • Cyclosporins are well known and are mentioned, for example, in GB 1491509 and GB 2015339. Cyclosporin -A and cyclosporin-G are commercially available.
  • the present invention provides a combination suitable for use in immunosuppression and/or the treatment of rheumatoid arthritis which combination comprises a pharmacologically active cyclosporin and gammalinoleic acid or a pharmaceutically acceptable functionally equivalent derivative thereof.
  • the gammalinoleic component may be used in a substantially pure form. Conveniently though it may be used in the form of a physiologically acceptable more or less readily obtainable oil mixture containing a substantial amount of gammalinoleic acid, such as evening primrose oil (EPO). Another suitable oil that may be mentioned is blackcurrant oil.
  • EPO evening primrose oil
  • the EPO is able to modify the body's immune system such that the production of those compounds against which cyclosporin is targetted is significantly reduced thereby enhancing the effectiveness of the cyclosporin.
  • EFA essential fatty acids
  • n-6 series there are two known main series of EFA, the so-called n-6 series and n-3 series, being references to the position of the first double bond in the carbon chain.
  • the parent molecule of the n-6 series is linoleic acid and of the n-3 series is alpha linoleic acid (or linolenic acid) .
  • Gammalinoleic acid ( 6,9,12-octadecatrienoic acid) has three double bonds and is a member of the n-6 series. Its abbreviation is 18:3,n-6.
  • linoleic acid (9,12- octadecadienoic acid 18:2,n-6) may be expected to be desaturated, by the appropriate enzyme, to gammalinoleic acid, but in many individuals this is an inefficient reaction and the required conversion rate may be inadequate.
  • oils such as evening primrose oil can bypass any metabolic block and supply the EFA as needed.
  • the EFA are the precursors for prostaglandins, specifically gammalinoleic acid is a precursor for the Series 1 (PGEi) series the presence of which act to reduce tissue impairment.
  • the expression “functionally equivalent derivative” indicates derivatives such as acids or esters which have been, or are converted in vivo into compounds, which have generally similar activity to that of gammalinoleic acid in the combination of the invention.
  • cyclosporin is conventionally used in the treatment of immune system related conditions, the dosages vary greatly according to purpose, to length of treatment period and to body weight of the recipient. It is suggested, however, that the highest acceptable dosage of cyclosporin has been considered to be in the region of 15mg/kg body weight and dosage at that level should continue for as short a time as possible. Nevertheless the risk of problems associated with renal vasoconstriction is high, and it may be that lOmg/kg is a more practical upper limit.
  • the level of the above mentioned practical doses may be reduced to 75% or 50% of the comparable figures giving similar effective desired beneficial results, but with correspondingly less risk.
  • cyclosporin and gammalinoleic acid components may be used in a wide range of relative proportions in the combinations of the invention. In general they are used in relative proportions of cyclosporin to gammalinoleic acid of from 10:1 to 1:100, preferably from 5:1 to 1:30.
  • the combination of the present invention may be used on its own, especially where the components are present in ratios at which the cyclosporin component is substantially solubilised by the gammalinoleic acid component, and the combination is to be administered as an oral draught or intramuscular injection or the like.
  • the combination is presented as a pharmaceutical composition including one or more other pharmaceutically acceptable carriers or excipients therefor.
  • a pharmaceutical formulation comprising the active combination together with a pharmaceutically acceptable carrier therefor.
  • the carrier must be "acceptable” in the sense of being compatible with the other ingredients of the formulation and not deleterious to the recipient thereof.
  • Such carriers are solid, liquid or gaseous materials recommended for the purpose of administering the medicament.
  • compositions may be administered orally or parenterally (including subcutaneous, intra ⁇ muscular and intravenous injection) or as a suppository or pessary. It is preferred that the compositions are administered orally or parenterally.
  • formulation and composition are used synonomously.
  • compositions may be presented as a draught in capsules, as an oleaginous solution or in suspension in a syrup, such suspensions optionally including suspending agents or as an oil-in-water or water-in-oil emulsion.
  • suspensions optionally including suspending agents or as an oil-in-water or water-in-oil emulsion.
  • desirable or necessary flavouring, sweetening, preserving, thickening or emulsifying agents may be included in the formulation.
  • the combination may be presented in an aqueous solution, if necessary with the presence of a surfactant.
  • Capsules and cachets may contain the active compound alone or in admixture with one or more accessory ingredients. Capsules may also contain the active combination in oleaginous solution, suspension or emulsion, optionally in association with accessory ingredients.
  • the active combination may be presented in admixture with a suitable carrier such as cocoa butter and other material commonly used in the art, the formulation conveniently being shaped by moulding.
  • the active combination is conveniently presented at 10 g to lOmg, desirably O.lmg to lOmg per tablet, capsule, suppository or pessary.
  • the active combination may be presented in sterile solutions or suspensions in oleaginous vehicles, which may also contain preservatives and material for rendering the solution or suspension isotonic with the blood of the intended recipient.
  • oleaginous vehicles which may also contain preservatives and material for rendering the solution or suspension isotonic with the blood of the intended recipient.
  • Such formulations may conveniently be presented in unit-dose or multi-dose sealed containers.
  • the active compounds may preferably be presented in solution or suspension or emulsion at a concentration of from 0.1 to 10%, more preferably 0.2 to 5% w/v in unit multi-dose form.
  • each dose-unit contains O.lmg to lOOmg, preferably lmg to lOmg of active compound.
  • All the above formulations are produced by processes which comprise bringing into association the active compounds and one or more carriers.
  • a process for producing a pharmaceutical formulation of a combination of the invention comprising bringing into association a combination of the invention and a pharmaceutically acceptable carrier therefor.
  • Combinations of the invention may be administered to human beings and to other animals for temporary immunosuppression.
  • the dosage administered obviously depends on the activity of the combinations and also on the speed with which it is absorbed into the body and on other well known pharmaceutical considerations.
  • the combination may be administered in the required dosages once or several times daily.
  • a pharmacologically active cyclosporin and gammalinoleic acid or a pharmaceutically acceptable functionally equivalent derivative thereof for use in the preparation of a medicament for immunosuppression and/or treatment or prophylaxis of rheumatoid arthritis.
  • the present invention provides: a method of immunosuppression comprising the administration of an effective dosage of the combination of the invention to a mammal; and a method of treatment or prophylaxis of rheumatoid arthritis comprising the administration of an effective dosage 'of the combination of the invention to a mammal.
  • a solution of cyclosporin is obtained by stirring 300mg thereof in 1.5ml of a mixture of 150mg a trans- esterification product of a vegetable oil triglyceride and a polyakylene polyol (LABRAFIL * M1944CS) and ethanol (in a ratio of 8:3 parts by weight). Evening primrose oil (0.6ml) was then added and the mixture filtered.
  • the solution obtained contains for every 10 parts by weight of LABRAFIL, 3 parts by weight cyclosporin, 3 parts by weight ethanol and 5 parts by weight EPO.
  • oils may be used in addition to EPO, for example certain fish oils rich in fatty acids.

Landscapes

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

Abstract

Les effets immunosuppressifs et antiarthritiques des cyclosporines sont potentialisés par la formulation avec un acide gammalinoléïque, un membre du groupe des acides gras non saturés des séries n-6, dans des proportions de poids variant entre 5:1 et 1:30. On peut ainsi réduire les doses de cyclosporine nécessaires, de sorte que les effets secondaires indésirables, tels que la vasoconstriction rénale, sont atténués.
PCT/GB1989/001183 1988-10-07 1989-10-06 Compositions contenant des cyclosporines WO1990003793A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB888823621A GB8823621D0 (en) 1988-10-07 1988-10-07 Compositions containing cyclosporins
GB8823621.1 1988-10-07

Publications (1)

Publication Number Publication Date
WO1990003793A1 true WO1990003793A1 (fr) 1990-04-19

Family

ID=10644893

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/GB1989/001183 WO1990003793A1 (fr) 1988-10-07 1989-10-06 Compositions contenant des cyclosporines

Country Status (3)

Country Link
AU (1) AU4346089A (fr)
GB (1) GB8823621D0 (fr)
WO (1) WO1990003793A1 (fr)

Cited By (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2218334B (en) * 1988-05-13 1991-10-02 Sandoz Ltd Cyclosprorin compositions for topical application
EP0784976A1 (fr) * 1996-01-17 1997-07-23 Senju Pharmaceutical Co., Ltd. Compositions potentialisant l'effet immunodépresseur contenant des diésters d'ascorbyl et tocophéryl de l'acide phosphorique
US5670478A (en) * 1992-09-07 1997-09-23 Galena, A.S. Pharmaceutical containing N-methylated cyclic undecapeptides
GB2327611A (en) * 1994-10-26 1999-02-03 Novartis Ag Stabilisation of Macrolide Compositions
US7060672B2 (en) 2001-10-19 2006-06-13 Isotechnika, Inc. Cyclosporin analog formulations

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB9113872D0 (en) * 1991-06-27 1991-08-14 Sandoz Ag Improvements in or relating to organic compounds

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1987006463A1 (fr) * 1986-05-02 1987-11-05 Brigham And Women's Hospital Composition a faible nephrotoxicite comprenant un composant contenant un acide gras et de la cyclocporine
EP0321128A1 (fr) * 1987-12-14 1989-06-21 Efamol Holdings Plc Compositions d'acide gras

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO1987006463A1 (fr) * 1986-05-02 1987-11-05 Brigham And Women's Hospital Composition a faible nephrotoxicite comprenant un composant contenant un acide gras et de la cyclocporine
EP0321128A1 (fr) * 1987-12-14 1989-06-21 Efamol Holdings Plc Compositions d'acide gras

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB2218334B (en) * 1988-05-13 1991-10-02 Sandoz Ltd Cyclosprorin compositions for topical application
US5670478A (en) * 1992-09-07 1997-09-23 Galena, A.S. Pharmaceutical containing N-methylated cyclic undecapeptides
GB2327611A (en) * 1994-10-26 1999-02-03 Novartis Ag Stabilisation of Macrolide Compositions
GB2327611B (en) * 1994-10-26 1999-06-02 Novartis Ag Macrolide compositions
EP0784976A1 (fr) * 1996-01-17 1997-07-23 Senju Pharmaceutical Co., Ltd. Compositions potentialisant l'effet immunodépresseur contenant des diésters d'ascorbyl et tocophéryl de l'acide phosphorique
US5861384A (en) * 1996-01-17 1999-01-19 Senju Pharmaceutical Co., Ltd. Immunosuppressive-activity potentiating compositions
US7060672B2 (en) 2001-10-19 2006-06-13 Isotechnika, Inc. Cyclosporin analog formulations
US7429562B2 (en) 2001-10-19 2008-09-30 Isotechnika Inc. Cyclosporin analog formulations

Also Published As

Publication number Publication date
AU4346089A (en) 1990-05-01
GB8823621D0 (en) 1988-11-16

Similar Documents

Publication Publication Date Title
US4970076A (en) Fatty acid composition
US5698594A (en) Treatment and prevention of risk factors for cardiovascular diseases
EP0003407B1 (fr) Composition pharmaceutique et diététique contenant des acides gamma-linoléniques
CN1230159C (zh) 必需脂肪酸在预防心血管疾病中的应用
JPS6296422A (ja) 子宮内膜増殖症予防または治療用組成物の製造方法およびその来成物を用いる前記増殖症の予防または治療方法
US4273763A (en) Pharmaceutical and dietary compositions
GB2148713A (en) Pharmaceutical composition and food product comprising higher fatty acids
EP0572159B1 (fr) Médicament pour le traitement de la dystrophie de la vulve ou de la sécheresse vaginale
WO1997039759A2 (fr) Acides gras omega 3 et phosphatidylcholine omega 3 utilises dans le traitement de troubles bipolaires
JPH0733655A (ja) 医薬組成物
KR20030016306A (ko) 지방산의 치료용 조합
EP0734723A1 (fr) Composition therapeutique utile pour traiter l'hyperparathyroidie d'un patient en dialyse artificielle
EP0087865B1 (fr) Composition pharmaceutique
JPH06511384A (ja) ヒトおよび動物用の栄養剤
EP0201159B1 (fr) Compositions pharmaceutiques et diététiques contenant des acides linoléniques pour le traitement de l'hypertrophie prostatique bénigne
WO1990003793A1 (fr) Compositions contenant des cyclosporines
EP0727989A1 (fr) Esters butyriques utilises comme agents pour induire une differentiation cellulaire
AU604547B2 (en) Antidiabetic composition comprising 7-thiaprostaglandin e1 or its derivative
JPS6216415A (ja) 月経前症候群治療用医薬組成物およびその治療方法
US3894153A (en) Method of medical treatment of asthma
JP2851704B2 (ja) 脳血栓症治療のための薬学的組成物
CA2504280A1 (fr) Acides gras essentiels pour la prevention ou le traitement de la depression chez les patients atteints d'une coronaropathie
JPS58210010A (ja) 抗腫瘍剤

Legal Events

Date Code Title Description
AK Designated states

Kind code of ref document: A1

Designated state(s): AU JP US

AL Designated countries for regional patents

Kind code of ref document: A1

Designated state(s): AT BE CH DE FR GB IT LU NL SE

点击 这是indexloc提供的php浏览器服务，不要输入任何密码和下载