WO2001097832A1 - Preparations pharmaceutiques contenant des cylosporines et des huiles neutres - Google Patents

Preparations pharmaceutiques contenant des cylosporines et des huiles neutres Download PDF

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Publication number
WO2001097832A1
WO2001097832A1 PCT/EP2001/007037 EP0107037W WO0197832A1 WO 2001097832 A1 WO2001097832 A1 WO 2001097832A1 EP 0107037 W EP0107037 W EP 0107037W WO 0197832 A1 WO0197832 A1 WO 0197832A1
Authority
WO
WIPO (PCT)
Prior art keywords
acid
pharmaceutical composition
composition according
neutral oil
ester
Prior art date
Application number
PCT/EP2001/007037
Other languages
German (de)
English (en)
Inventor
Norbert KLÖCKER
Original Assignee
Audit Institute For Medical Services And Quality Assurance Gmbh
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
Priority claimed from DE2000130378 external-priority patent/DE10030378A1/de
Priority claimed from DE2001101529 external-priority patent/DE10101529A1/de
Application filed by Audit Institute For Medical Services And Quality Assurance Gmbh filed Critical Audit Institute For Medical Services And Quality Assurance Gmbh
Priority to AU66087/01A priority Critical patent/AU6608701A/en
Publication of WO2001097832A1 publication Critical patent/WO2001097832A1/fr

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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
    • 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
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/14—Esters of carboxylic acids, e.g. fatty acid monoglycerides, medium-chain triglycerides, parabens or PEG fatty acid esters
    • 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

Definitions

  • the invention relates to a pharmaceutical composition consisting of a water-insoluble or sparingly water-soluble active ingredient and neutral oil, it being possible to dispense with the use of solubilizers, additional components, and with alcohols and heating.
  • the invention relates to pharmaceutical compositions consisting of a cyclosporin and neutral oil.
  • compositions known hitherto for the use of cyclosporins contain alcoholic solutions or oily solutions.
  • Known oily solutions of cyclosporins are based on the use of paraffin oil, corn oil, fish oil, sesame oil, peanut oil, castor oil, etc. These have the disadvantage of a very high viscosity, which often makes sterile filtration impossible, or only by adding further components and / or by heating. This is lengthy and expensive. In addition, cleaning the filling system and validating the cleaning process during production is lengthy and costly. In addition, the known oily solutions are often unable to dissolve cyclosporin in therapeutically necessary concentrations, or only by adding solubilizers and / or further components and / or heating.
  • the object of the invention is to provide a pharmaceutical composition for the use of cyclosporins in the form of a solution, it being possible to dispense with the use of solubilizers and / or further components and / or heating, the composition being sterile filterable and stable.
  • the object is achieved according to the invention and unexpectedly by a pharmaceutical composition which contains at least one cyclosporin dissolved in a neutral oil.
  • the composition is essentially anhydrous.
  • Essentially water-free is understood here to mean a water content in the composition which can result from water of hydration, water of crystallization and / or residual moisture in the neutral oil, the active ingredients and / or the auxiliaries.
  • the composition is easy to filter, so that sterile filtration (0.2 ⁇ m pore size) can be used to produce a sterile solution without great effort.
  • the stability is very high.
  • the tolerance of the oil solution according to the invention is very good.
  • the production is simple and inexpensive, since no further additives are necessary and the neutral oil as a carrier is cheap.
  • neutral oil means medium-chain triglycerides. These can be achieved by esterifying medium-chain fatty acids such as Capronic acid, capric acid, caprylic acid, lauric acid, myristic acid, linoleic acid and succinic acid, in particular capric acid, caprylic acid, linoleic acid and succinic acid can be obtained with glycerol and / or propylene glycol (Miglyol 810, 812, 818, 840).
  • the viscosity of the neutral oils used is 1-40 mPa s, in particular 5-20 mPa s, a viscosity of 8-15 mPa s is preferred.
  • the preferred neutral oil according to the invention is Miglyol 840 and / or neutral oil according to DAB and Miglyol 812.
  • compositions according to the invention include formulations for topical application, for example on the eye, and for oral, rectal and parenteral application.
  • the pharmaceutical composition according to the invention can contain, for example, cyclosporin A, B, C, D and G, dihydrocyclosporins, isocyclosporins and / or their derivatives, in particular cyclosporin A, as an active ingredient component from the group of immunosuppressants.
  • the pharmaceutical composition according to the invention can have an active ingredient content of 0.01-20% by weight, in particular 0.05-15% by weight, preferably 0.1-10% by weight. The percentages relate to the total amount of the pharmaceutical composition.
  • the pharmaceutical composition according to the invention can optionally also contain antioxidants and / or sorption promoters such as, for example, tocopherol, ⁇ -tocopherol ester, ascorbic acid, ascorbic acid ester (myristate, palmitate and stearate), ⁇ -carotene, cysteine, acetylcysteine, folic acid (vitamin B 2 - Group), phytic acid, ice and / or trans-urocanoic acid, carnosine (N-ß-alanine-L-histidine), histidine, flavones, flavonoids, lycopene, tyrosine, glutathione, glutanate esters, ⁇ -lipoic acid, ubiquinone, nordihydroguaiaretic acid (NDGA ), Gallic acid esters (ethyl, propyl, octyl, dodecyl gallate), phosphoric acid derivatives (monophosphates, polyphosphates
  • the content of the optionally added antioxidants and / or sorption promoters can be 0.001-2% by weight, based on the total amount of the pharmaceutical composition.
  • the pharmaceutical composition according to the invention can contain water-insoluble or poorly water-soluble corticoids, androgens, estrogens, progestogens, sympatholytics / sympathomimetics, cholinergics / anticholinergics, weaning agents, immunosuppressants, virustatics, anal gels as possible active ingredient components.
  • Further active ingredients to be used according to the invention are from the group of corticoids, for example beclomethasone dipropionate, budesonide base, dexamethasone, hydrocortisone, flunisolide, prednisone, triamcinolone acetonide, methylprednisolone, Fluticasone, betamethasone, deflazacort, cortisone, cortisone acetate, prednilyden, cloprednol, fluocortolone-21-hexanoate and / or their derivatives, in particular prednisone, dexamethasone, beclomethasone dipropionate and / or budesonide base, from the group of androgens and testosterone and testosteronone, eg testonone and testosterone, for example testosterone and testosterone their derivatives, in particular testosterone, from the group of estrogens, for example estradiol, estradiol benzoate, estradiol valerate, estradi
  • composition for soft gelatin capsules Composition for soft gelatin capsules
  • composition for hard gelatin capsules Composition for hard gelatin capsules
  • composition for injection concentrate Composition for injection concentrate

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

Abstract

L'invention concerne une préparation pharmaceutique contenant en particulier une cyclosporine et de l'huile neutre, l'utilisation d'agents de solubilisation, de constituants additionnels et d'alcools, ainsi que le chauffage étant superflus.
PCT/EP2001/007037 2000-06-21 2001-06-21 Preparations pharmaceutiques contenant des cylosporines et des huiles neutres WO2001097832A1 (fr)

Priority Applications (1)

Application Number Priority Date Filing Date Title
AU66087/01A AU6608701A (en) 2000-06-21 2001-06-21 Pharmaceutical preparations containing cyclosporines and neutral oils

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
DE2000130378 DE10030378A1 (de) 2000-06-21 2000-06-21 Neue pharmazeutische Zusammensetzung zur topischen Anwendung von wasserunlöslichen und/oder schwer wasserlöslichen Wirkstoffen
DE10030378.1 2000-06-21
DE2001101529 DE10101529A1 (de) 2001-01-15 2001-01-15 Neue pharmazeutische Zusammensetzung
DE10101529.1 2001-01-15

Publications (1)

Publication Number Publication Date
WO2001097832A1 true WO2001097832A1 (fr) 2001-12-27

Family

ID=26006159

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2001/007037 WO2001097832A1 (fr) 2000-06-21 2001-06-21 Preparations pharmaceutiques contenant des cylosporines et des huiles neutres

Country Status (2)

Country Link
AU (1) AU6608701A (fr)
WO (1) WO2001097832A1 (fr)

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003055480A1 (fr) * 2001-12-21 2003-07-10 Pharmaconsult Oy Produits a utiliser dans une therapie immunosuppressive et renfermant de l'acide lipoique et un inhibiteur de la calcineurine
WO2004006890A1 (fr) * 2002-07-15 2004-01-22 Alcon, Inc. Compositions d'implants pharmaceutiques lipophiles non-polymeres pour utilisation intra-oculaire
US20120238536A1 (en) * 2009-11-19 2012-09-20 Novagali Pharma Sa Method for Treating Retinal Conditions Using an Intraocular Tamponade

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4388307A (en) * 1978-03-07 1983-06-14 Sandoz Ltd. Galenical compositions
WO1995024893A1 (fr) * 1994-03-16 1995-09-21 R.P. Scherer Limited Systemes d'administration s'appliquant a des medicaments hydrophobes
US5589455A (en) * 1994-12-28 1996-12-31 Hanmi Pharm. Ind. Co., Ltd. Cyclosporin-containing soft capsule compositions
US5639724A (en) * 1984-07-24 1997-06-17 Sandoz Ltd. Cyclosporin galenic forms
WO1997036610A1 (fr) * 1996-07-26 1997-10-09 Chong Kun Dang Corp. Composition pharmaceutique contenant une cyclosporine
WO1998040051A1 (fr) * 1997-03-12 1998-09-17 Abbott Laboratories Systemes lipophiles binaires permettant l'administration de composes lipophiles

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4388307A (en) * 1978-03-07 1983-06-14 Sandoz Ltd. Galenical compositions
US5639724A (en) * 1984-07-24 1997-06-17 Sandoz Ltd. Cyclosporin galenic forms
WO1995024893A1 (fr) * 1994-03-16 1995-09-21 R.P. Scherer Limited Systemes d'administration s'appliquant a des medicaments hydrophobes
US5589455A (en) * 1994-12-28 1996-12-31 Hanmi Pharm. Ind. Co., Ltd. Cyclosporin-containing soft capsule compositions
WO1997036610A1 (fr) * 1996-07-26 1997-10-09 Chong Kun Dang Corp. Composition pharmaceutique contenant une cyclosporine
WO1998040051A1 (fr) * 1997-03-12 1998-09-17 Abbott Laboratories Systemes lipophiles binaires permettant l'administration de composes lipophiles

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003055480A1 (fr) * 2001-12-21 2003-07-10 Pharmaconsult Oy Produits a utiliser dans une therapie immunosuppressive et renfermant de l'acide lipoique et un inhibiteur de la calcineurine
WO2004006890A1 (fr) * 2002-07-15 2004-01-22 Alcon, Inc. Compositions d'implants pharmaceutiques lipophiles non-polymeres pour utilisation intra-oculaire
CN100355455C (zh) * 2002-07-15 2007-12-19 爱尔康公司 用于眼内使用的非聚合亲脂性药物植入组合物
US7678827B2 (en) 2002-07-15 2010-03-16 Alcon, Inc. Non-polymeric lipophilic pharmaceutical implant compositions for intraocular use
US8178576B2 (en) 2002-07-15 2012-05-15 Novartis Ag Non-polymeric lipophilic pharmaceutical implant compositions for intraocular use
US20120238536A1 (en) * 2009-11-19 2012-09-20 Novagali Pharma Sa Method for Treating Retinal Conditions Using an Intraocular Tamponade
US9616016B2 (en) 2009-11-19 2017-04-11 Santen Sas Method for treating retinal conditions using an intraocular tamponade

Also Published As

Publication number Publication date
AU6608701A (en) 2002-01-02

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