WO2009152917A4 - Stabilization of the composition of a mixture - Google Patents

Stabilization of the composition of a mixture Download PDF

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Publication number
WO2009152917A4
WO2009152917A4 PCT/EP2009/003666 EP2009003666W WO2009152917A4 WO 2009152917 A4 WO2009152917 A4 WO 2009152917A4 EP 2009003666 W EP2009003666 W EP 2009003666W WO 2009152917 A4 WO2009152917 A4 WO 2009152917A4
Authority
WO
WIPO (PCT)
Prior art keywords
petasin
extract
formula
carbon atoms
neopetasin
Prior art date
Application number
PCT/EP2009/003666
Other languages
French (fr)
Other versions
WO2009152917A3 (en
WO2009152917A2 (en
Inventor
Stephan Toff
Harun Parlar
Original Assignee
Max Zeller Söhne Ag
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 Max Zeller Söhne Ag filed Critical Max Zeller Söhne Ag
Priority to EP09765497A priority Critical patent/EP2285767A2/en
Publication of WO2009152917A2 publication Critical patent/WO2009152917A2/en
Publication of WO2009152917A3 publication Critical patent/WO2009152917A3/en
Publication of WO2009152917A4 publication Critical patent/WO2009152917A4/en

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Classifications

    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/205—Polysaccharides, e.g. alginate, gums; 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
    • A61K9/20—Pills, tablets, discs, rods
    • A61K9/2004—Excipients; Inactive ingredients
    • A61K9/2022—Organic macromolecular compounds
    • A61K9/2031—Organic macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyethylene glycol, polyethylene oxide, poloxamers
    • 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
    • A61P37/08—Antiallergic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C67/00—Preparation of carboxylic acid esters
    • C07C67/48—Separation; Purification; Stabilisation; Use of additives
    • C07C67/62—Use of additives, e.g. for stabilisation
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C2602/00—Systems containing two condensed rings
    • C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
    • C07C2602/14—All rings being cycloaliphatic
    • C07C2602/26—All rings being cycloaliphatic the ring system containing ten carbon atoms

Landscapes

  • Health & Medical Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Epidemiology (AREA)
  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Medicinal Preparation (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)

Abstract

Described is a method for slowing the speed of the isomerisation of petasin and neopetasin to isopetasin, and the isomerisation of S-petasin and neo-S-petasin to iso-S-petasin, especially in extracts from plants of the genus Petasites, preferably Petasites hybridus, by the addition of at least one suitable stabilizer and/or the removal of at least one destabilizing substance, e.g. a fatty acid.

Claims

AMENDED CLAIMS received by the International Bureau on 09 August 2010 (09.08.10)
1. Method for slowing the speed of the isomerisation of petasin and neopetasin to isopetasin, and the isomerisation of S-petasin and neo-S-petasin to iso-S-petasin in extracts from plants of Petasites hybridus, said extracts comprising petasin, neopetasin and isopetasin, by the addition of at least one suitable stabilizer and the removal of at least one destabilizing substance, wherein the stabilizer is selected from a) a compound of formula I
R1KCH2)H-OH (I) wherein n is 1, R1 represents alkyl having 2 to 30 carbon atoms wherein one or more non- adjacent carbon atoms may be replaced by oxygen; or R1 represents cycloalkyl, phenyl, or phenoxymethyl, each of which is unsubstituted or substituted in the cyclic moiety by Ci- Cγ-alkyl or Ci-C7-alkoxy, b) a glycol of the formula HO-[CHR2-CH2-O]m-H, wherein R2 is hydrogen or methyl and m is 1 to 500, or of the formula HO-[CH2-CH2-O]x-[CH2-CH(CH3)-0]y-[CH2-CH2-O]z-H wherein x is 50-125, y is 20-70 and z is 50-125, c) dibenzylether, and d) hydrogenated castor oil, and wherein the destabilizing substance is a fatty acid in free and/or bound form.
2. Pharmaceutical formulation comprising an extract from plants of Petasites hybridus, said extract comprising petasin, neopetasin and isopetasin, wherein the amount of fatty acids has been reduced below 50 % of the natural occurrence in the extract, together with a stabilizer selected from a) a compound of formula I
R1KCH2VOH (I) wherein n is 1, R1 represents alkyl having 2 to 30 carbon atoms wherein one or more non- adjacent carbon atoms may be replaced by oxygen; or R1 represents cycloalkyl, phenyl, or phenoxymethyl, each of which is unsubstituted or substituted in the cyclic moiety by Cj- C7-alkyl or Ci-C7-alkoxy, b) a glycol of the formula HO-[CHR2-CH2-O]m-H, wherein R is hydrogen or methyl and m is 1 to 500, or of the formula HO-[CH2-CH2-O]x-[CH2-CH(CH3)-O]y-[CH2-CH2-O]z-H wherein x is 50-125, y is 20-70 and z is 50-125, c) dibenzylether, and d) a hydrogenated plant oil, like hydrogenated castor oil, and a pharmaceutical excipient.
3. Pharmaceutical formulation according to claim 2, wherein the stabilizer is selected from a) a compound of formula I
R^(CH2)H-OH (I) wherein n is 1, R1 represents alkyl having 2 to 30 carbon atoms wherein one or more non- adjacent carbon atoms may be replaced by oxygen; or R1 represents cycloalkyl, phenyl, or phenoxymethyl, each of which is unsubstituted or substituted in the cyclic moiety by Q- Cyalkyl or Ci-C7-alkoxy, b) dibenzylether, and c) a hydrogenated plant oil, like hydrogenated castor oil.
4. Pharmaceutical formulation according to claim 2 substantially free from free fatty acids.
5. Pharmaceutical formulation according to any one of claims 2 -4 in a non- liquid form.
6. Pharmaceutical formulation according to any one of claims 2-4 wherein the amount by weight of the stabilizer is 3-6fold the amount by weight of the native extract.
7. Pharmaceutical formulation according to any one of claims 2-4 wherein the extract from plants of Petasites hybridus has been obtained by extraction with carbon dioxide.
8. Extract from plants of Petasites hybridus, said extract comprising petasin, neopetasin and isopetasin, wherein the amount of fatty acids has been reduced below 50 % of the natural occurrence in the extract, and further comprising a stabilizer slowing the speed of the isomerisation of petasin and neopetasin to isopetasin, and the isomerisation of S- petasin and neo-S-petasin to iso-S-petasin selected from a) a compound of formula I
R'-(CH2)n-OH (I) wherein n is 1, R1 represents alkyl having 2 to 30 carbon atoms wherein one or more non- adjacent carbon atoms may be replaced by oxygen; or R1 represents cycloalkyl, phenyl, or phenoxymethyl, each of which is unsubstituted or substituted in the cyclic moiety by C1- C7-alkyl or Ci-C7-alkoxy, b) a glycol of the formula HO-[CHR2-CH2-O]m-H, wherein R2 is hydrogen or methyl and m is 1 to 500, or of the formula HO-[CH2-CH2-O]x-[CH2-CH(CH3)-O]y-[CH2-CH2-O]z-H wherein x is 50-125, y is 20-70 and z is 50-125, c) dibenzylether, and d) hydrogenated castor oil.
9. Extract according to claim 8 which has been obtained by extraction with carbon dioxide.
10. Extract according to claim 8 substantially free from free fatty acids.
11. Process for the manufacture of an extract as claimed in any one of claims 8-10 by removing from an extract from plants of Petasites hybridus, said extract comprising petasin, neopetasin and isopetasin, fatty acids promoting the isomerisation of petasin and neopetasin to isopetasin by passing a solution comprising said extract through a suitable weakly alkaline ion exchanger or by neutralizing said fatty acid in said extract with a suitable base and extracting it with water followed by addition of a stabilizer as defined in claim 7.
12. Extract obtainable by the process according to claim 11.
13. Use of a stabilizer selected from a) a compound of formula I
R'-CCHΛ-OH (I) wherein n 1, R1 represents alkyl having 2 to 30 carbon atoms wherein one or more non- adjacent carbon atoms may be replaced by oxygen; or R1 represents cycloalkyl, phenyl, or phenoxymethyl, each of which is unsubstituted or substituted in the cyclic moiety by Cj- C7-alkyl or Ci-C7-alkoxy, b) a glycol of the formula HO-[CHR2-CH2-O]m-H, wherein R2 is hydrogen or methyl and m is 1 to 500, or of the formula HO-[CH2-CH2-O]x-[CH2-CH(CH3)-O]y-[CH2-CH2-O]z-H wherein x is 50-125, y is 20-70 and z is 50-125, c) dibenzylether, and d) hydrogenated castor oil, for slowing the speed of the isomerisation of petasin and neopetasin to isopetasin, and the isomerisation of S-petasin and neo-S-petasin to iso-S-petasin in an extract from plants of Petasites hybridus, wherein said extract comprises petasin, neopetasin and isopetasin, and wherein the amount of fatty acids has been reduced below 50 % of the natural occurrence in the extract.
PCT/EP2009/003666 2008-05-29 2009-05-23 Stabilization of the composition of a mixture WO2009152917A2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
EP09765497A EP2285767A2 (en) 2008-05-29 2009-05-23 Stabilization of the composition of a mixture

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP08009760 2008-05-29
EP08009760.3 2008-05-29

Publications (3)

Publication Number Publication Date
WO2009152917A2 WO2009152917A2 (en) 2009-12-23
WO2009152917A3 WO2009152917A3 (en) 2010-08-19
WO2009152917A4 true WO2009152917A4 (en) 2010-10-21

Family

ID=40010721

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2009/003666 WO2009152917A2 (en) 2008-05-29 2009-05-23 Stabilization of the composition of a mixture

Country Status (2)

Country Link
EP (1) EP2285767A2 (en)
WO (1) WO2009152917A2 (en)

Family Cites Families (17)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR8351M (en) * 1967-01-27 1971-02-08
CH537420A (en) * 1969-02-24 1973-05-31 Clausmann Otto Process for obtaining a stabilized, therapeutically highly active petasites extract with a content of 50 to 55% genuine petasin
CH660966A5 (en) * 1984-02-29 1987-06-30 Amo Pharm Ag Process for obtaining a petasites extract with high therapeutic activity from Petasites hybridus, with a content of from 60 to 75% petasin
RO90371A2 (en) * 1984-08-11 1986-09-30 Directia Sanitara A Judetului Neamt,Laboratorul"Plantavorel",Ro MEDICINAL PRODUCT PHYTOTHERAPY ANXIOLITIS TRANQUILIZING AND SPASMOLYTIC
JPS61206449A (en) * 1985-03-09 1986-09-12 松下電工株式会社 Deodorant
JPS62360A (en) * 1985-06-25 1987-01-06 松下電工株式会社 Deodorizing filter
ES2044848T3 (en) * 1987-03-12 1994-01-16 Plantamed Arzneimittel Gmbh USE OF PETASITE EXTRACTS TO PREPARE A MEDICATION FOR THE TREATMENT OF GASTROINTESTINAL DISEASES.
JPH02180267A (en) * 1988-12-30 1990-07-13 Matsushita Electric Works Ltd Deodorant
JP2804822B2 (en) * 1990-05-28 1998-09-30 松下電工株式会社 Deodorants
JPH0430855A (en) * 1990-05-28 1992-02-03 Matsushita Electric Works Ltd Mousse-like deodorant
JPH0693909B2 (en) * 1990-11-27 1994-11-24 松下電工株式会社 Deodorant for shaver
DE4208300C2 (en) * 1992-03-16 1994-01-13 Plantamed Arzneimittel Gmbh Use of oxopetasin as a component of medicines for the treatment of gastrointestinal diseases
DE19838848A1 (en) * 1998-08-26 2000-03-02 Weber & Weber Gmbh & Co Kg Composition containing pyrrolizidine alkaloid-free petasites
KR100438322B1 (en) * 2001-11-14 2004-07-02 한불화장품주식회사 A cosmetic composition containing an extract of petasites japonicus
KR100535655B1 (en) * 2003-03-14 2005-12-08 충남대학교산학협력단 Extract of Petasites japonicus having neuroprotective effect and antioxidant activity
JP2005179308A (en) * 2003-12-22 2005-07-07 Oriza Yuka Kk Antiallergy composition
DE102004039011A1 (en) * 2004-08-11 2006-03-30 Max Zeller Söhne Ag Extract, useful to prepare a medicament to treat e.g. gastrointestinal pain, cramps of urogenital tracts, asthma, cough and headache, comprises Petasites hybridus extract, that is free of pyrrolizidine alkaloid and furanoeremophilane

Also Published As

Publication number Publication date
WO2009152917A3 (en) 2010-08-19
WO2009152917A2 (en) 2009-12-23
EP2285767A2 (en) 2011-02-23

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