EP0977561A1 - Compositions de glucosamine et d'acide gras et leur utilisation - Google Patents

Compositions de glucosamine et d'acide gras et leur utilisation

Info

Publication number
EP0977561A1
EP0977561A1 EP98921639A EP98921639A EP0977561A1 EP 0977561 A1 EP0977561 A1 EP 0977561A1 EP 98921639 A EP98921639 A EP 98921639A EP 98921639 A EP98921639 A EP 98921639A EP 0977561 A1 EP0977561 A1 EP 0977561A1
Authority
EP
European Patent Office
Prior art keywords
glucosamine
fatty acid
acid
essential fatty
octadeca
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.)
Withdrawn
Application number
EP98921639A
Other languages
German (de)
English (en)
Inventor
David Frederick-Laxdale Limited HORROBIN
Mehar Singh-Scotia Pharmaceuticals MANKU
Austin-Scotia Pharmaceuticals McMORDIE
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.)
Scotia Holdings PLC
Original Assignee
Scotia Holdings PLC
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 Scotia Holdings PLC filed Critical Scotia Holdings PLC
Publication of EP0977561A1 publication Critical patent/EP0977561A1/fr
Withdrawn legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7004—Monosaccharides having only carbon, hydrogen and oxygen atoms

Definitions

  • the invention relates to the presentation and use of sugar amines.
  • N-methyl glucamine as an example of compounds broadly presented as N-alkyl polyhydroxy amines, is disclosed in the form of salts with polyunsaturated fatty acids.
  • the fatty acids are particularly the "6-desaturated" n-6 and n-3 essential fatty acids i.e. those beyond the 6-desaturation stage in bodily conversion of dietary linoleic and ⁇ -linolenic acids, and may be as such or in the form of their esters or amides with a bifunctional compound also having a salt-forming acidic function. Examples of such compounds are ascorbic acid, when the fatty acid is as a 6-ester, and salicylic acid.
  • the N-methyl glucamine salts are:-
  • the purpose is to present the fatty acids in water soluble form for their numerous therapeutic and other actions, allowing for example ready absorption from the gut into the hepatic portal system, or intravenous administration.
  • meglumine moiety lacking a carbonyl function, is only formally related to sugars and has no function other than as a carrier of the fatty acid.
  • EFAs essential fatty acids
  • the acids which in nature are of the all - cis configuration, are systematically named as derivatives of the corresponding octadecanoic, eicosanoic or docosanoic acids, e.g. z,z-octadeca - 9,12 - dienoic acid for LA or z,z,z,z,z,z - docosa- 4,7,10,13,16,19 - hexaenoic acid for DHA, but numerical designations based on the number of carbon atoms, the number of centres of unsaturation and the number of carbon atoms from the end of the chain to where the unsaturation begins, such as, correspondingly, 18:2 n-6 or 22:6 n-3, are convenient.
  • Drug treatments are many, but while analgesics (e.g paracetamol and codeine) and non-steroidal anti-inflammatory drugs (NSAIDs) are much used for relief of pain associated with osteoarthritis, rheumatoid arthritis and back problems, the NSAIDs are limited by their side effects and there is some evidence that they may actually impair cartilage metabolism.
  • Other pharmacological approaches include intra-articular steroid therapy, mechanical lubrication and chondroprotective agents including D-glucosamine sulphate, glycosaminoglycan-peptide complex and glycosaminoglycan polysulphate .
  • GLA fatty acids
  • ingestion of for example GLA elevates DGLA levels which results in an increase in production of anti-inflammatory 1 -series prostaglandins such as PGE1.
  • Ingested EPA e.g. from fish oil
  • the anti- inflammatory activity of both GLA and EPA in animal and human studies is well documented in prior patents of the applicants and in the general literature.
  • the amino-monosaccharide glucosamine is found in the matrix of articular cartilage where it is a component of various glycosaminoglycans. Synthesis of glycosaminoglycans requires sulphate ions as well as glucosamine. In vitro studies have long demonstrated that glucosamine stimulates the uptake of radioactively labelled sulphate ions by chondrocytes as a result of glycosaminoglycan synthesis. More recent in vitro studies have supported the conclusion that glucosamine stimulates synthesis of glycosaminoglycan and proteoglycans in general in chondrocytes.
  • glucosamine Additional properties include protection of articular cartilage from damage caused by some non-steroidal anti-inflammatory drugs as well as anti-inflammatory activity in models of acute and sub-acute inflammation not caused by inhibition of prostaglandin synthesis. Also, several clinical trials have demonstrated the efficacy of glucosamine in the control of symptoms of osteoarthritis. It has been concluded that oral glucosamine is as effective as a standard NSAID such as ibuprofen, in controlling symptoms with clinically evident signs of inflammation, while it is significantly better tolerated.
  • NSAID such as ibuprofen
  • the invention concentrates on glucosamine as a natural cartilage constituent and in chemical terms provides:
  • novel compositions of glucosamine and essential fatty acids especially the delta-6-desaturated n-6 and n-3 essential fatty acids such as GLA and EPA.
  • the fatty acids may be used in natural form e.g. as evening primrose oil, fish oil, fungal oil, algal oil or other assimilable forms, or alternatively they may for example be present as salts of the glucosamine itself.
  • the invention provides amide, ester or amide/ester derivatives of glucosamine wherein one or more of the amino and hydroxy functions carries a fatty acyl group derived from an n-6 or n-3 essential fatty acid, the fatty acid being linked to the amine or hydroxy function either directly or through a linking compound itself having a carboxylic acid function and in the latter case being replaceable by a corresponding fatty alcohol group esterified to a second carboxylic acid function of the linking compound.
  • Such a structure may be as set out below: -
  • R 1 to R 5 are independently H or a UFA-C • or UFA'-C/ group the same or different (but not all H) with the further possibility (when at least one of R 1 , R 3 , R 4 and R is such a group) that R is a to C 4 acyl group or other biocompatible derivatising function;
  • UFA is the carbon chain of an n-6 or n-3 preferably 6-desaturated essential fatty acid, and very preferably a fatty acid with anti-inflammatory activity such as GLA,
  • UFA 1 is the carbon chain of such a fatty acid, or of a corresponding fatty alcohol, covalently linked to a biocompatible bifunctional compound also having a free acidic group;
  • the compound may be in the form of the free base or as a salt with a pharmaceutically acceptable acid
  • the invention lies in application of compounds or compositions as above in the therapeutic or prophylactic treatment of disease or deterioration in bodily cartilaginous tissue.
  • the cartilaginous tissue may in particular be that of the joints including those of the vertebral column and the invention is particularly applicable in inflammatory joint conditions including osteoarthritis, other forms of arthritis and conditions leading to back pain.
  • the amounts of the fatty acids for daily administration are 10 mg to 10 g preferably 100 mg to 5 g and very preferably 300 mg to 3g and of the sugar amines 10 mg to 20 g, preferably 100 mg to 5 g and very preferably 300 mg to 3 g, preferably in corresponding molar amounts to the fatty acid where the two are not chemically combined.
  • the compounds may be applied by oral, enteral, parenteral or topical routes.
  • the compounds may be used directly in liquid form, or be formulated as emulsions, powders, tablets, or hard or soft gelatin capsules or in any other appropriate form known to those skilled in the art.
  • Example 2 In a similar manner to Example 1 but replacing z,z,z-octadeca-6,9,12-trienoyl chloride with z,z,z,z,z-eicosa-5,8,l l,14,17-pentaenoic acid was prepared N-(z,z,z,z,z-eicosa-5, 8, 11,14,17- pentaenoyl)-D-glucosamide as an off-white amorphous solid.
  • Examples 1 and 2 may be used without further purification in preparations for the purposes referred to herein, for example the treatment of osteoarthritis:-
  • Oral pharmaceutical preparations containing 100 mg to 1 g, in 5 ml, of the product.
  • Soft gelatin capsules conventional in themselves contain:- 295 mg evening primrose oil (8% GLA)
  • Part 1 preparation of l-(z,z,z-octadeca-6,9,12-trienoyloxy)-3-hydroxypropane
  • Part 2 preparation of butanedioic acid, monoester with l-(z,z,z-octadeca-6,9,12- trienoyloxy)-3 -hydroxypropane
  • Oxalyl chloride (3.9ml) was added to a solution of butanedioic acid, monoester with l-(z,z,z- octadeca-6,9,12-trienoyloxy)-3-hydroxypropane (13g) in methylene chloride (75ml). The mixture was stirred at room temperature under nitrogen for 2h and concentrated to dryness. Hexane (75ml) was added and the mixture concentrated to dryness. This process was repeated with two further portions of hexane to yield l-(3-(z,z,z-octadeca-6,9,12-trienoyloxy) propyl)oxycarbonyl-4-butanoyl chloride as a pale yellow oil.
  • Part 4 preparation of l-(3-(z,z,z-octadeca-6,9,12-trienoyloxy)propyl)oxycarbonyl-4-butanoic acid, N-hydroxysuccinimide ester
  • Example 5 In a similar manner to Example 5 but replacing l-(z,z,z-octadeca-6,9,12-trienoyloxy)-3- hydroxypropane in Part 2 with z,z,z-octadeca-6,9,12-trienol (prepared by reduction of z,z,z- octadeca-6,9,12-trienoic acid) was prepared l-(z,z,z-octadeca-6,9,12- trienyloxycarbonyl)-4- butanoyl-D-glucosamide as an off-white amorphous solid.
  • z,z,z-Octadeca-6,9,12-trienoic acid (2.78g) is added dropwise with stirring under nitrogen to a solution of D-glucosamine (1.79g) in water (50 ml). Stirring is continued at room temperature until a clear solution results. Lyophilisation yields glucosammonium z,z,z- octadeca-6,9, 12-trienoate.
  • Examples 5 to 7 may be used in the manner of Examples 3 and 4.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Molecular Biology (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

On décrit des compositions de glucosamine et d'un acide gras essentiel, en particulier un ou plusieurs des acides gras essentiels n-6 et n-3 'delta-6-désaturés', tels que GLA, DGLA, SA, EPA et DHA, mais différentes des compositions à base de sulphate de chondroïtine.
EP98921639A 1997-05-20 1998-05-18 Compositions de glucosamine et d'acide gras et leur utilisation Withdrawn EP0977561A1 (fr)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
GBGB9710351.9A GB9710351D0 (en) 1997-05-20 1997-05-20 Glucosamine fatty acids
GB9710351 1997-05-20
PCT/GB1998/001425 WO1998052556A1 (fr) 1997-05-20 1998-05-18 Compositions de glucosamine et d'acide gras et leur utilisation

Publications (1)

Publication Number Publication Date
EP0977561A1 true EP0977561A1 (fr) 2000-02-09

Family

ID=10812725

Family Applications (1)

Application Number Title Priority Date Filing Date
EP98921639A Withdrawn EP0977561A1 (fr) 1997-05-20 1998-05-18 Compositions de glucosamine et d'acide gras et leur utilisation

Country Status (6)

Country Link
EP (1) EP0977561A1 (fr)
AU (1) AU7442398A (fr)
CA (1) CA2290488A1 (fr)
GB (1) GB9710351D0 (fr)
WO (1) WO1998052556A1 (fr)
ZA (1) ZA984211B (fr)

Families Citing this family (61)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
DE60035227D1 (de) * 1999-11-02 2007-07-26 Shawn Paul Madere Oral zu verabreichende zubereitungen von nahrungsmittelzusätzen zur heilung von gelenkknorpeln
US7214666B1 (en) 1999-11-02 2007-05-08 Shawn Paul Madere Composition of orally administered nutritional supplements to repair articular cartilage
DE10019255A1 (de) * 2000-04-18 2001-10-31 Henkel Kgaa Glykosid-Ester und ihre Herstellung sowie Verwendung in Kosmetika, Pharmazeutika und Nahrungs- bzw. Futtermitteln
WO2004032824A2 (fr) * 2002-10-10 2004-04-22 Yeda Research And Development Co. Ltd. Esters de base d'alcools gras et leur utilisation comme agents anti-inflammatoires ou immunomodulateurs
CA2641510A1 (fr) * 2006-02-07 2007-08-16 Pal Rongved Omega 3
DE102007055344A1 (de) 2007-11-19 2009-05-20 K. D. Pharma Bexbach Gmbh Neue Verwendung von Omega-3-Fettsäure(n)
FR2940281B1 (fr) * 2008-12-22 2011-04-01 Fabre Pierre Dermo Cosmetique Ester de diol et d'acide gras polyinsature comme agent anti-acne
GB0907413D0 (en) 2009-04-29 2009-06-10 Equateq Ltd Novel methods
CN103384521A (zh) * 2010-12-21 2013-11-06 雀巢产品技术援助有限公司 用于预防和治疗骨关节炎的方法和组合物
US9303038B2 (en) 2011-09-06 2016-04-05 Cellix Bio Private Limited Compositions and methods for the treatment of epilepsy and neurological diseases
US8293790B2 (en) 2011-10-19 2012-10-23 Dignity Sciences Limited Pharmaceutical compositions comprising DGLA and benzoyl peroxide and methods of use thereof
WO2013167990A1 (fr) 2012-05-07 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement de la dépression
WO2013168021A1 (fr) 2012-05-07 2013-11-14 Mahesh Kandula Compositions et méthodes pour le traitement des troubles neuromusculaires et des troubles neurodégénératifs
SG11201407300VA (en) 2012-05-07 2014-12-30 Cellix Bio Private Ltd Compositions and methods for the treatment of neurological disorders
WO2013167993A1 (fr) 2012-05-08 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement de troubles neurologiques dégénératifs
US9266823B2 (en) 2012-05-08 2016-02-23 Cellix Bio Private Limited Compositions and methods for the treatment of parkinson's disease
US9309233B2 (en) 2012-05-08 2016-04-12 Cellix Bio Private Limited Compositions and methods for the treatment of blood clotting disorders
US20150148306A1 (en) * 2012-05-08 2015-05-28 Mahesh Kandula Compositions and methods for the treatment of inflammation
US9403826B2 (en) 2012-05-08 2016-08-02 Cellix Bio Private Limited Compositions and methods for the treatment of inflammatory disorders
US9522884B2 (en) 2012-05-08 2016-12-20 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic disorders
US9233161B2 (en) 2012-05-10 2016-01-12 Cellix Bio Private Limited Compositions and methods for the treatment of neurological conditions
US9242939B2 (en) 2012-05-10 2016-01-26 Cellix Bio Private Limited Compositions and methods for the treatment of respiratory disorders
US9573927B2 (en) 2012-05-10 2017-02-21 Cellix Bio Private Limited Compositions and methods for the treatment of severe pain
WO2013167999A2 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes de traitement d'affections neurologiques
WO2013168015A1 (fr) 2012-05-10 2013-11-14 Mahesh Kandula Compositions et méthodes pour le traitement de l'asthme et de l'allergie
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US9096537B1 (en) 2014-12-31 2015-08-04 Mahesh Kandula Compositions and methods for the treatment of mucositis
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US9173877B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Compositions and methods for the treatment of local pain
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US9175008B1 (en) 2014-11-05 2015-11-03 Cellix Bio Private Limited Prodrugs of anti-platelet agents
US9290486B1 (en) 2014-11-05 2016-03-22 Cellix Bio Private Limited Compositions and methods for the treatment of epilepsy
US9150557B1 (en) 2014-11-05 2015-10-06 Cellix Bio Private Limited Compositions and methods for the treatment of hyperglycemia
US9284287B1 (en) 2014-11-05 2016-03-15 Cellix Bio Private Limited Compositions and methods for the suppression of carbonic anhydrase activity
US9321716B1 (en) 2014-11-05 2016-04-26 Cellix Bio Private Limited Compositions and methods for the treatment of metabolic syndrome
WO2016088132A1 (fr) 2014-12-01 2016-06-09 Cellix Bio Private Limited Compositions et méthodes pour le traitement de la sclérose en plaques
US9206111B1 (en) 2014-12-17 2015-12-08 Cellix Bio Private Limited Compositions and methods for the treatment of neurological diseases
JP6679616B2 (ja) 2015-01-06 2020-04-22 セリックス バイオ プライヴェート リミテッドＣｅｌｌｉｘ Ｂｉｏ Ｐｒｉｖａｔｅ Ｌｉｍｉｔｅｄ 炎症及び疼痛の治療のための組成物及び方法
US20210315851A1 (en) 2020-04-03 2021-10-14 Afimmune Limited Compositions comprising 15-hepe and methods of treating or preventing hematologic disorders, and/or related diseases

Family Cites Families (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPS5939813A (ja) * 1982-08-26 1984-03-05 Shiseido Co Ltd 化粧料
JPH07507312A (ja) * 1992-05-26 1995-08-10 アルバータ　リサーチ　カウンスル 血液型決定基に関するオリゴ糖配糖体の時間依存性投与による炎症の低下
GB9413935D0 (en) * 1994-07-11 1994-08-31 Peptech Uk Ltd Use of maramyl peptide compounds
US5639787A (en) * 1995-02-28 1997-06-17 The Center For The Improvement Of Human Functioning Int'l, Inc. Therapeutic method for the treatment of cancer
GB9508023D0 (en) * 1995-04-20 1995-06-07 Scotia Holdings Plc Fatty acid derivatives
WO1997021434A1 (fr) * 1995-12-11 1997-06-19 Inholtra, Inc. Regime alimentaire a base de complements nutritionnels permettant de soulager les symptomes de l'arthrite

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
See references of WO9852556A1 *

Also Published As

Publication number Publication date
CA2290488A1 (fr) 1998-11-26
ZA984211B (en) 1998-11-20
AU7442398A (en) 1998-12-11
WO1998052556A1 (fr) 1998-11-26
GB9710351D0 (en) 1997-07-16

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