CA2490735A1 - Liquid preparation comprising oligopeptides and etherified cyclodextrin - Google Patents

Liquid preparation comprising oligopeptides and etherified cyclodextrin Download PDF

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Publication number
CA2490735A1
CA2490735A1 CA002490735A CA2490735A CA2490735A1 CA 2490735 A1 CA2490735 A1 CA 2490735A1 CA 002490735 A CA002490735 A CA 002490735A CA 2490735 A CA2490735 A CA 2490735A CA 2490735 A1 CA2490735 A1 CA 2490735A1
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CA
Canada
Prior art keywords
pharmaceutical preparation
aqueous pharmaceutical
beta
preparation according
cyclodextrin
Prior art date
Legal status (The legal status 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 status listed.)
Granted
Application number
CA002490735A
Other languages
French (fr)
Other versions
CA2490735C (en
Inventor
Hiltrud Lindenblatt
Hans-Peter Zobel
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Merck Patent GmbH
Original Assignee
Hiltrud Lindenblatt
Hans-Peter Zobel
Merck Patent Gesellschaft Mit Beschraenkter Haftung
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 Hiltrud Lindenblatt, Hans-Peter Zobel, Merck Patent Gesellschaft Mit Beschraenkter Haftung filed Critical Hiltrud Lindenblatt
Publication of CA2490735A1 publication Critical patent/CA2490735A1/en
Application granted granted Critical
Publication of CA2490735C publication Critical patent/CA2490735C/en
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

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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
    • 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
    • A61K47/02—Inorganic compounds
    • 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
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • 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
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • 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
    • A61K47/26—Carbohydrates, e.g. sugar alcohols, amino sugars, nucleic acids, mono-, di- or oligo-saccharides; Derivatives thereof, e.g. polysorbates, sorbitan fatty acid esters or glycyrrhizin
    • 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
    • A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
    • A61K47/36—Polysaccharides; Derivatives thereof, e.g. gums, starch, alginate, dextrin, hyaluronic acid, chitosan, inulin, agar or pectin
    • A61K47/40—Cyclodextrins; Derivatives thereof
    • 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
    • A61K47/69—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit
    • A61K47/6949—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes
    • A61K47/6951—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 conjugate being characterised by physical or galenical forms, e.g. emulsion, particle, inclusion complex, stent or kit inclusion complexes, e.g. clathrates, cavitates or fullerenes using cyclodextrin
    • 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
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/08—Solutions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery

Abstract

The invention relates to an aqueous pharmaceutical preparation of oligopeptides containing an oligopeptide of formula I, cyclo-(n-Arg-nGly-nAs p- nD-nE) and a partially etherified -cyclodextrin whose solubility in water is greater than 1.8 mg / ml water. The invention also relates to the production of aqueous pharmaceutical preparations.

Claims (13)

1. Aqueous pharmaceutical preparation of oligopeptides, comprising an oligo-peptide of the formula I

cyclo-(n-Arg-nGly-nAsp-nD-nE) (I) in which D and E each, independently of one another, denote Gly, Ala, .beta.-Ala, Asn, Asp, Asp(OR), Arg, Cha, Cys, Gln, Glu, His, Ile, Leu, Lys, Lys(Ac), Lys(AcNH2), Lys(AcSH), Met, Nal, Nle, Orn, Phe, 4-Hal-Phe, homoPhe, Phg, Pro, Pya, Ser, Thr, Tia, Tic, Trp, Tyr or Val, where the said amino acid radicals may also be derivatised, R denotes alkyl having 1-18 C atoms, Hal denotes F, Cl, Br, I, Ac denotes alkanoyl having 1-10 C atoms, aroyl having 7-11 carbon atoms or aralkanoyl having 8-12 C atoms, n denotes a hydrogen atom or an alkyl radical R, benzyl or an aralkyl radical having 7-18 C atoms on the alpha-amino function of the corresponding amino acid radical, with the proviso that at least one amino acid radical has a substituent n, where n denotes R, and where, if they are radicals of optically active amino acids and amino acid derivatives, both the D and L forms are included, and physiologically acceptable salts thereof, and an etherified .beta.-cyclodextrin having a water solubility of greater than 1.8 mg/ml of water
2. Aqueous pharmaceutical preparation according to Claim 1, characterised in that the etherified .beta.-cyclodextrin present is partially etherified .beta.-cyclodextrin
3. Aqueous pharmaceutical preparation according to Claim 1 or 2, character-ised in that the ether substituents in the etherified .beta.-cyclodextrin are hydroxyethyl and/or hydroxypropyl groups
4. Aqueous pharmaceutical preparation according to one or more of Claims 1 to 3, characterised in that the etherified .beta.-cyclodextrin has a molar degree of substitution of between 0.2 and 10
5. Aqueous pharmaceutical preparation according to Claim 4, characterised in that the partially etherified .beta.-cyclodextrin has a molar degree of substitution of between 0.2 and 2, based on the ether substituents
6. Aqueous pharmaceutical preparation according to Claim 4, characterised in that the partially etherified .beta.-cyclodextrin has a molar degree of substitution of between 0.5 and 0.8, based on the ether substituents
7. Aqueous pharmaceutical preparation according to one or more of Claims 1 to 6, characterised in that the oligopeptide is cilengitide
8. Aqueous pharmaceutical preparation according to one or more of Claims 1 to 7, characterised in that an isotonicity agent is furthermore present in an amount necessary for establishing isotonicity
9. Aqueous pharmaceutical preparation according to one or more of Claims 1 to 8, characterised in that it has a pH of from 5 to 8, preferably a pH of from 5.6 to 7.4.
10. Aqueous pharmaceutical preparation according to Claim 9, characterised in that it has a pH of from 6 to 7.2
11. Aqueous pharmaceutical preparation according to one or more of Claims 1 to 10, characterised in that it comprises from 20 to 120 mg/ml of cilengitide and from 15 to 25 ~ by weight of hydroxypropyl-.beta.-cyclodextrin having a molar degree of substitution of from 0.5 to 0.8
12. Aqueous pharmaceutical preparation according to Claim 11, characterised in that it comprises about 80 mg/ml of cilengitide and about 20% by weight of hydroxypropyl-.beta.-cyclodextrin having a molar degree of substitution of about 0.58-0.73
13. Process for the preparation of an aqueous pharmaceutical preparation according to one or more of Claims 1 to 12, characterised in that firstly the .beta.-cyclodextrin ether ~ dissolved in water, and the active ingredient and any further adjuvants are subsequently added
CA2490735A 2002-06-24 2003-05-19 Liquid preparation comprising oligopeptides and etherified cyclodextrin Expired - Fee Related CA2490735C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
DE10228049.5 2002-06-24
DE10228049A DE10228049A1 (en) 2002-06-24 2002-06-24 Liquid preparation containing oligopeptides
PCT/EP2003/005224 WO2004000344A1 (en) 2002-06-24 2003-05-19 Aqueous preparation containing oligopeptides and etherified cyclodextrin

Publications (2)

Publication Number Publication Date
CA2490735A1 true CA2490735A1 (en) 2003-12-31
CA2490735C CA2490735C (en) 2012-11-20

Family

ID=29723395

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2490735A Expired - Fee Related CA2490735C (en) 2002-06-24 2003-05-19 Liquid preparation comprising oligopeptides and etherified cyclodextrin

Country Status (22)

Country Link
US (1) US7262165B2 (en)
EP (1) EP1515740B1 (en)
JP (1) JP5052750B2 (en)
KR (1) KR101024511B1 (en)
CN (1) CN100368013C (en)
AR (1) AR040444A1 (en)
AT (1) ATE337013T1 (en)
AU (1) AU2003240268B2 (en)
BR (1) BR0312157A (en)
CA (1) CA2490735C (en)
CY (1) CY1105706T1 (en)
DE (2) DE10228049A1 (en)
DK (1) DK1515740T3 (en)
ES (1) ES2270042T3 (en)
HK (1) HK1079430A1 (en)
MX (1) MXPA04012426A (en)
MY (1) MY135548A (en)
PL (1) PL205972B1 (en)
PT (1) PT1515740E (en)
RU (1) RU2322254C2 (en)
WO (1) WO2004000344A1 (en)
ZA (1) ZA200500585B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8183230B2 (en) 2004-01-30 2012-05-22 Pfizer Inc. Antimicrobial preservatives to achieve multi-dose formulation using beta-cyclodextrins for liquid dosage forms

Families Citing this family (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE102004011512B4 (en) 2004-03-08 2022-01-13 Boehringer Ingelheim Vetmedica Gmbh Pharmaceutical preparation containing pimobendan
US8980894B2 (en) 2004-03-25 2015-03-17 Boehringer Ingelheim Vetmedica Gmbh Use of PDE III inhibitors for the treatment of asymptomatic (occult) heart failure
EP1579862A1 (en) 2004-03-25 2005-09-28 Boehringer Ingelheim Vetmedica Gmbh Use of PDE III inhibitors for the reduction of heart size in mammals suffering from heart failure
RU2462261C2 (en) 2006-06-29 2012-09-27 Ариджен, Фармасьютикалз, Инк. Injectable antibiotic formulation and solution for its internal introduction
EP1920785A1 (en) 2006-11-07 2008-05-14 Boehringer Ingelheim Vetmedica Gmbh Liquid preparation comprising a complex of pimobendan and cyclodextrin
WO2008087025A2 (en) * 2007-01-18 2008-07-24 Merck Patent Gmbh Specific therapy and medicament using integrin ligands for treating cancer
WO2009110880A1 (en) * 2008-03-01 2009-09-11 Hewlett-Packard Development Company, L.P. Detecting colorants within carrier liquid
PE20120169A1 (en) * 2008-11-17 2012-02-29 Genentech Inc METHOD AND FORMULATION TO REDUCE THE AGGREGATION OF A MACROMOLECLE UNDER PHYSIOLOGICAL CONDITIONS
CN102223882B (en) 2008-11-25 2016-02-03 贝林格尔.英格海姆维特梅迪卡有限公司 Be used for the treatment of III type phosphodiesterase (PPE III) inhibitor or the Ca of hypertrophic cardiomyopathy 2+sensitizer
ES2742263T3 (en) * 2009-12-10 2020-02-13 Merck Patent Gmbh Pharmaceutical compositions comprising oligopeptides, preferably cilengitide
EP2825159B1 (en) 2012-03-15 2022-06-22 Boehringer Ingelheim Vetmedica GmbH Pharmaceutical tablet formulation for the veterinary medical sector, method of production and use thereof
CA2915445A1 (en) 2013-07-19 2015-01-22 Boehringer Ingelheim Vetmedica Gmbh Preserved etherified cyclodextrin derivatives containing liquid aqueous pharmaceutical composition
PL2925305T3 (en) 2013-12-04 2017-07-31 Boehringer Ingelheim Vetmedica Gmbh Improved pharmaceutical compositions of pimobendan
AU2016380988B2 (en) 2015-12-30 2022-07-21 Genentech, Inc. Formulations with reduced degradation of polysorbate
US10537570B2 (en) 2016-04-06 2020-01-21 Boehringer Ingelheim Vetmedica Gmbh Use of pimobendan for the reduction of heart size and/or the delay of onset of clinical symptoms in patients with asymptomatic heart failure due to mitral valve disease
US10975121B2 (en) 2017-06-24 2021-04-13 Cytogel Pharma, Llc Analgesic mu-opioid receptor binding peptide pharmaceutical formulations and uses thereof
JP7226830B2 (en) * 2017-11-30 2023-02-21 サイトジェル ファーマ リミテッド ライアビリティ カンパニー Novel analgesic drug formulations and their use

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE3346123A1 (en) * 1983-12-21 1985-06-27 Janssen Pharmaceutica, N.V., Beerse PHARMACEUTICAL PREPARATIONS OF SUBSTANCES MEDICAL OR UNSTABLE IN WATER AND METHOD FOR THE PRODUCTION THEREOF
GB9001987D0 (en) 1990-01-29 1990-03-28 Janssen Pharmaceutica Nv Improved cyclodextrin based erythropietin formulation
JP3934705B2 (en) * 1995-05-26 2007-06-20 ノバルティス ファーマ株式会社 Cyclodextrin composition
DE19534177A1 (en) 1995-09-15 1997-03-20 Merck Patent Gmbh Cyclic adhesion inhibitors
CN1360505A (en) 1999-04-15 2002-07-24 伊莱利利公司 Pseudomycin antifungal compositions and method for their use

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US8183230B2 (en) 2004-01-30 2012-05-22 Pfizer Inc. Antimicrobial preservatives to achieve multi-dose formulation using beta-cyclodextrins for liquid dosage forms

Also Published As

Publication number Publication date
US7262165B2 (en) 2007-08-28
CY1105706T1 (en) 2010-12-22
ATE337013T1 (en) 2006-09-15
MXPA04012426A (en) 2005-04-19
EP1515740A1 (en) 2005-03-23
DE50304763D1 (en) 2006-10-05
JP5052750B2 (en) 2012-10-17
ZA200500585B (en) 2005-11-30
AU2003240268B2 (en) 2008-10-23
CA2490735C (en) 2012-11-20
RU2322254C2 (en) 2008-04-20
AR040444A1 (en) 2005-04-06
PL205972B1 (en) 2010-06-30
RU2005101746A (en) 2005-08-27
HK1079430A1 (en) 2006-04-07
CN100368013C (en) 2008-02-13
WO2004000344A1 (en) 2003-12-31
KR101024511B1 (en) 2011-03-31
AU2003240268A1 (en) 2004-01-06
JP2005534671A (en) 2005-11-17
BR0312157A (en) 2005-03-29
ES2270042T3 (en) 2007-04-01
CN1662250A (en) 2005-08-31
KR20050013612A (en) 2005-02-04
PL372192A1 (en) 2005-07-11
PT1515740E (en) 2007-01-31
DE10228049A1 (en) 2004-01-15
DK1515740T3 (en) 2006-12-11
US20050239692A1 (en) 2005-10-27
EP1515740B1 (en) 2006-08-23
MY135548A (en) 2008-05-30

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Effective date: 20150519