WO2000051576A2 - Novel pharmaceuticals, dietary supplements and cosmetic compositions, and the use of certain mixtures for preparing a medicament or a dietary supplement for the treatment or prevention of inflammation, hypersensitivity reactions or pain - Google Patents

Novel pharmaceuticals, dietary supplements and cosmetic compositions, and the use of certain mixtures for preparing a medicament or a dietary supplement for the treatment or prevention of inflammation, hypersensitivity reactions or pain Download PDF

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Publication number
WO2000051576A2
WO2000051576A2 PCT/DK2000/000087 DK0000087W WO0051576A2 WO 2000051576 A2 WO2000051576 A2 WO 2000051576A2 DK 0000087 W DK0000087 W DK 0000087W WO 0051576 A2 WO0051576 A2 WO 0051576A2
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WIPO (PCT)
Prior art keywords
gingerol
shogaol
mixture
component
extract
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PCT/DK2000/000087
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French (fr)
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WO2000051576A3 (en
Inventor
Morten Sloth Weidner
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IDA ROYALTY APS
Astion Development AS
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IDA ROYALTY APS
Astion Development AS
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Priority to AT00907455T priority Critical patent/ATE249231T1/en
Priority to SI200030263T priority patent/SI1156814T1/en
Priority to DE60005152T priority patent/DE60005152T2/en
Priority to DK00907455T priority patent/DK1156814T3/en
Priority to AU29033/00A priority patent/AU2903300A/en
Priority to EP00907455A priority patent/EP1156814B1/en
Priority to CA002366318A priority patent/CA2366318A1/en
Priority to HK02103899.4A priority patent/HK1042240B/en
Application filed by IDA ROYALTY APS, Astion Development AS filed Critical IDA ROYALTY APS
Publication of WO2000051576A2 publication Critical patent/WO2000051576A2/en
Publication of WO2000051576A3 publication Critical patent/WO2000051576A3/en
Priority to US09/945,256 priority patent/US6482421B2/en
Anticipated expiration legal-status Critical
Priority to US10/266,470 priority patent/US6638525B2/en
Ceased legal-status Critical Current

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/906—Zingiberaceae (Ginger family)
    • A61K36/9068—Zingiber, e.g. garden ginger
    • 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

Definitions

  • the present invention relates to mixtures comprising at least one of the fatty acids eicosa- pentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3) and the plant Zingiber officinale Roscoe or parts thereof or an extract or a component thereof.
  • the invention relates to novel pharmaceuticals, dietary supplements or cosmetic compositions containing such mixtures, and to the use of such mixtures for preparing a medicament or a dietary supplement for the suppression of hypersensitivity and/or inflammatory reaction.
  • Hypersensitivity is defined as a state of altered reactivity in which the body reacts with an exaggerated immune response to a substance (antigen). Hypersensitivity may be caused by exogenous or endogenous antigens.
  • Hypersensitivity reactions underlie a large number of diseases. Among these, allergic and autoimmune conditions are of great importance. A classification of hypersensitivity dis- eases is given in the textbook Clinical Medicine (Kumar, P. and Clark, M.: “Clinical Medicine” , 3rd edition, p. 147-150, 1994, Bailliere Tindall, London).
  • Type I hypersensitivity reactions are caused by allergens (specific exogenous antigens), e.g. pollen, house dust, animal dandruff, moulds, etc. Aller- gic diseases in which type I reactions play a significant role include asthma, eczema (atopic dermatitis), urticaria, allergic rhinitis and anaphylaxis.
  • Type il hypersensitivity reactions are caused by cell surface or tissue bound antibodies (IgG and IgM) and play a significant role in the pathogenesis of myasthenia gravis, Good- pasture's syndrome and Addisonian pernicious anaemia.
  • IgG and IgM cell surface or tissue bound antibodies
  • Type III hypersensitivity reactions are caused by autoantigens or exogenous antigens, such as certain bacteria, fungi and parasites.
  • Diseases in which type III hypersensitivity reactions play a significant role include lupus erythematosus, rheumatoid arthritis and glomerulonephritis.
  • Type IV hypersensitivity reactions are caused by cell or tissue bound antigens. This type of hypersensitivity plays a significant role in a number of conditions, e.g. graft- versus-host disease, leprosy, contact dermatitis and reactions due to insect bites.
  • a number of drug classes are available for the treatment of hypersensitivity reactions. Some of these are applied systemically and some are applied topically.
  • corticosteroids are among the most widely used drugs for the treatment of hypersensitivity diseases. Corticosteroids primarily exert their pharmacological action by non- selectively inhibiting the function and proliferation of different classes of immune cells resulting in suppression of hypersensitivity reactions. Unfortunately the corticosteroids are associated with a number of serious side effects, e.g. immuno-suppression, osteoporosis and skin atrophy (when applied topically).
  • Zingiber officinale Roscoe (family Zingiberacea), commonly known as ginger, is an erect perennial herb with thick tuberous rhizomes (underground stems) from which the aerial stem grows about 1 m high.
  • Zingiber officinale Roscoe is native to Southern Asia and is extensively cultivated in the tropics, e.g. India, China, Jamaica, Haiti and Nigeria.
  • Ginger or ginger volatile oil is widely used as a flavour ingredient in the food industry.
  • the ginger rhizome contains a volatile oil which can be obtained by steam distillation.
  • the chemical composition of ginger oil depends on its geographic origin.
  • Ginger volatile oil generally contains the sesquiterpenes zingiberene and bisabolene as its major components.
  • Other sesquiterpenes and sesquiterpene alcohols present include ar-curcumene, ⁇ -sesquiphelandrene, sesquithujene, ⁇ -bisabolone, (E)- ⁇ -farnesene, zingiberol, zin- giberenol, cis-sesquisabinene hydrate, and cis- and trans-sesquiphellandrol.
  • Zingiber officinale Roscoe contains a number of phenolic compounds, most of which have a characteristic hydroxy-methoxy-phenyl moiety. These compounds are responsible for the pungency of ginger.
  • the quantitatively dominating group of these phenolic compounds are the gingerols.
  • the gingerols form a homologous series, 2-gingerol, 4-gingerol, 6- gingerol, 8-gingerol, 10-gingerol, 12-gingerol and 14-gingerol. The quantitatively dominating of these is 6-gingerol.
  • Another group are the shogaols which are dehydration products of gingerols.
  • the shogaols form a similar homologous series.
  • Other similar compounds present are zingerone, 6-gingerdiol, gingerdione, gingerenones A-C, isogingere- none B, etc.
  • Zingiber officinale Roscoe has been used in the traditional medicine in China and in the Indian subcontinent for more than 2500 years.
  • the Chinese prescribe fresh or dried ginger for the relief of a number of conditions, e.g. gastrointestinal disturbances, colds, in- flammations, headaches and as an antiemetic for the prevention of seasickness.
  • the arachidonic acid (AA) metabolism plays an essential role in hypersensitivity reactions because AA is converted by the enzyme cyclooxygenase into pro-inflammatory prosta- glandins and by the enzyme 5-lipoxygenase into proinflammatory leukotrienes.
  • the pros- taglandins and leukotrienes are commonly termed eicosanoids.
  • the modulation of the AA metabolism is a well established pharmacological strategy in relation to the treatment of hypersensitivity reactions.
  • Marine oils, especially fish oils contain relatively high concentrations of the fatty acids eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3).
  • fatty acids have been shown to reduce inflammatory reactions because they can replace AA in the AA metabolism.
  • the eicosanoids formed by the metabolism of eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3) have insignificant pro-inflammatory effects or even antiinflammatory effects.
  • Zingiber officinale Roscoe is derived from the ability of certain components to inhibit the generation of eicosanoids through a direct inhibition of cyclooxygenase and 5-lipoxygenase.
  • the therapeutic efficacy of Zingiber officinale Roscoe is limited strongly by the fact that its pharmacologically active components are only mild inhibitors of eicosanoid generation.
  • fatty acids eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) have a limited therapeutic efficacy, simply because they are only able to replace a limited fraction of the cellular pool of arachidonic acid after oral administration.
  • eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), and b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof; provides a synergistic effect in the treatment of hypersensitivity reactions, probably because both substances modulate the arachidonic acid metabolism, but at different levels.
  • eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) can be used in the form of free fatty acids or esters of any mono- or polyvalent alcohol.
  • the fatty acids may be used in the form of mono-, di- or triglycerides which can be derived from a number of natural sources, especially marine sources, such as fish in the form of fish oils.
  • Zingiber officinale Roscoe or parts thereof or an extract or component thereof may be used in any form, such as powdered plant material, extracts, concentrates or distillates or in the form of purified components of the plant, such as 2-gingerol, 4-gingerol, 6-gingerol, 8-gingerol, 10-gingerol, 12-gingerol, 14-gingerol, 2- shogaol, 4-shogaol, 6-shogaol, 8-shogaol, 10-shogaol, 12-shogaol, 14-shogaol, zingerone, 6-gingerdiol, gingerdione, gingerenones, isogingerenones, zingiberene, bis- abolene, ar-curcumene, ⁇ -sesquiphelandrene, sesquithujene, ⁇ -bisabolone, (E)- ⁇ - farnesene, zingiberol, zingiberenol,
  • Zingiber officinale Roscoe or parts thereof or an extract or compo- nent thereof is explained by the fact that the pharmacological effects of Zingiber officinale Roscoe is caused by a broad spectrum of pharmacologically active compounds, even though, of course, some substances are preferred.
  • the pharmaceutical compositions, dietary supplements and cosmetic compositions according to the present invention have the advantage of not being likely to be associated with any serious side effects, as eicosapentaenoic acid (20:5n3), docosahexaenoic acid (22:6n3), and Zingiber officinale Roscoe are non-toxic and well tolerated by the organism in the pharmacologically relevant doses.
  • compositions, dietary supplements and cosmetic compositions according to the invention can be employed for the following therapeutic applications:
  • the present invention provides a pharmaceutical, a dietary supplement or a cosmetic composition, comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically and/or cosmetically acceptable vehicle.
  • the present invention provides the use of a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; for preparing a medicament for immunomodulation, for the suppression of hypersensitivity reactions, such as IgE mediated allergic reac- tions and autoimmune reactions, and for the alleviation of pain.
  • a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; for preparing a medicament for immunomodulation, for the suppression of hypersensitivity reactions, such as IgE mediated allergic reac- tions and
  • a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; can be used in a method for the treatment or prevention of a hypersensitivity disease in an individual, said method comprising administering said mixture to said individual; and the invention comprises the use of said mixture for preparing a medicament for the treatment or prevention of hypersensitivity diseases.
  • a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; can be used in a method for the treatment or prevention of an autoimmune disorder in an individual, said method comprising administering said mixture to said individual; and the invention comprises the use of said mixture for preparing a medicament for the treatment or prevention of autoimmune disorders.
  • a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; can be used in a method for the treatment or prevention of an IgE mediated allergic reaction or condition in an individual, said method comprising administering said mixture to said individual; and the invention comprises the use of said mixture for preparing a medicament for the treatment or prevention of IgE mediated allergic reactions and conditions.
  • a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; can be used in a method for the alleviation of pain in an individual, said method comprising administering said mixture to said individual; and the invention comprises the use of said mixture for preparing a medicament for the alleviation of pain.
  • a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; exerts pharmacological actions relevant to the therapeutic treatment of conditions associated with hypersensitivity reactions and pain.
  • the present invention provides a pharmaceutical, a dietary supplement or a cosmetic composition, comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically and/or cosmetically acceptable vehicle.
  • the weight percentage (w/w) of eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) in the composition is typically at least 0.1%, such as at least 0.2%, e.g. at least 0.3%, at least 0.5%, at least 0.75%, at least 1.0%, at least 1.5%, such as at least 2.0%, e.g. at least 2.5%, at least 3.0%, at least 4.0%, at least 5.0%, at least 10.0%, such as at least 20.0%, e.g.
  • the weight percentage (w/w) of Zingiber officinale Roscoe or parts thereof or an extract or component thereof in the composition is typically at least 0.1%, such as at least 0.2%, e.g. at least 0.3%, at least 0.5%, at least 0.75%, at least 1.0%, at least 1.5%, such as at least 2.0%, e.g. at least 2.5%, at least 3.0%, at least 4.0%, at least 5.0%, at least 10.0%, such as at least 20.0%, e.g. at least 30.0%, at least 40.0%, at least 50.0%, at least 60.0%, at least 70.0%, at least 80.0%, at least 90.0%, such as at least 95.0%, e.g. at least 96.0%, at least 97.0%, at least 98.0%, at least 99.0%.
  • eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) can be used in the form of free fatty acids or esters of any mono- or polyvalent alcohol.
  • the fatty acids may be used in the form of mono-, di- or tri- glycerides which can be derived from a number of natural sources, especially marine sources, such as fish in the form of fish oils.
  • Zingiber officinale Roscoe or parts thereof or an extract or component thereof may be used in any form, such as powdered plant material, ex- tracts, concentrates or distillates or in the form of purified components of the plant, such as 2-gingerol, 4-gingerol, 6-gingerol, 8-gingerol, 10-gingerol, 12-gingerol, 14-gingerol, 2- shogaol, 4-shogaol, 6-shogaol, 8-shogaol, 10-shogaol, 12-shogaol, 14-shogaol, zingerone, 6-gingerdiol, gingerdione, gingerenones, isogingerenones, zingiberene, bis- abolene, ar-curcumene, ⁇ -sesquiphelandrene, sesquithujene, ⁇ -bisabolone, (E)- ⁇ - famesene, zingiberol, zingiberenol
  • the part of Zingiber officinale Roscoe is an extract.
  • Extracts according to the invention can i.a. be obtained by extraction or distillation (e.g. hydro, steam or vacuum distillation) of fresh or dried Zingiber officinale Roscoe or parts thereof, preferably the rhizome. Extraction may be performed with a number of different organic solvents, such as water miscible solvents, and mixtures thereof with water. The extraction can also be performed with water immiscible solvents, such as alkanes. The extraction can be performed hot or cold by the employment of any extraction technol- ogy e.g. maceration, percolation or supercritical extraction.
  • the preferred extraction solvents are pentane, hexane, heptane, acetone, methyl ethyl ketone, ethyl acetate, lower alkanols having 1 to 4 carbon atoms and mixtures thereof with water.
  • the preferred extraction temperature is close to the boiling point of the em- ployed solvent due to extraction efficacy, but lower temperatures are also applicable making necessary a longer period of extraction.
  • Supercritical extraction e.g. performed with C0 2
  • a “dietary supplement” is defined according to the U.S. Food and Drug Administration in the Dietary Supplement Health and Education Act of 1994 (DSHEA).
  • the DSHEA gives the following formal definition of a "dietary supplement”: "A dietary supplement:
  • • is a product (other than tobacco) that is intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by man to supplement the diet by increasing the total daily intake, or a concentrate, metabolite, constituent, extract, or combinations of these things. • is intended for ingestion in pill, capsule, tablet, or liquid form.”
  • a method for the treatment or prevention of hypersensitivity disease characterised by the administration of the above mentioned mixture.
  • the therapeutic action may be relevant to all known diseases associated with hypersensitivity reactions. Autoimmune disorders and IgE mediated allergic conditions are described below in more detail. Besides these specific therapeutic areas, the action of the above mentioned mixture is relevant to all known conditions and diseases associated with hypersensitivity reaction, and the following examples are not limiting with respect to this: infections (viral, bacterial, fungal, parasitic, etc.), cold and flu, contact dermatitis, insect bites, allergic vasculitis, postoperative reactions, transplantation rejection (graft-versus-host disease), etc.
  • the therapeutic action may be relevant to all known autoimmune disorders and the following examples are not limiting with respect to this: Autoimmune hepatitis, Primary biliary cirrhosis, Pri- mary sclerosing cholangitis, Autoimmune hemolytic anemias, Grave ' s disease, Myas- thenia gravis, Type 1 Diabetes Mellitus, Inflammatory myopathies, Multiple sclerosis, Hashimoto's thyreoiditis, Autoimmune adrenalitis, Crohn's Disease, Ulcerative Colitis, Glomerulonephritis, Progressive Systemic Sclerosis (Scleroderma), Sj ⁇ gren's Disease, Lupus Erythematosus, Primary vasculitis, Rheumatoid Arthritis,
  • the appli- cant puts forward the hypothesis that the therapeutic action is due to the suppressing effect on hypersensitivity reaction of the above mentioned mixture.
  • the therapeutic action may be relevant to all known IgE mediated allergic reactions and conditions, and the following examples are not limiting with respect to this: asthma, eczema (e.g. atopic dermatitis), urticaria, allergic rhinitis, anaphylaxis, etc.
  • the above mentioned mixture can be combined with any other active ingredient to potentiate the therapeutic action.
  • Vehicles other than water that can be used in compositions can include solids or liq- uids such as emollients, solvents, humectants, thickeners and powders. Examples of each of these types of vehicles, which can be used singly or as mixtures of one or more vehicles, are as follows:
  • Emollients such as stearyl alcohol, glyceryl monoricinoleate, glyceryl monostearate, propane-1 ,2-diol, butane-1 ,3-diol, cetyl alcohol, isopropyl isostearate, stearic acid, iso- butyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, cetyl palmitate, dimethylpolysiloxane, di-n-bu- tyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, castor oil, acetylated lanolin al- cohols, petroleum, mineral oil, buty
  • humectants or moistening agents such as glycerin, sorbitol, sodium 2-pyrrolidone-5- carboxylate, soluble collagen, dibutyl .phthalate, gelatin;
  • powders such as chalk, talc, kaolin, starch and derivatives thereof, gums, colloidal silicon dioxide, sodium polyacrylate, chemically modified magnesium aluminium silicate, hydrated aluminium silicate, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate;
  • gelling or swelling agents such as pectin, gelatin and derivatives thereof, cellulose de- rivatives such as methyl cellulose, carboxymethyl cellulose or oxidised cellulose, cellulose gum, guar gum, acacia gum, karaya gum, tragacanth gum, bentonite, agar, algi- nates, carbomer, gelatine, bladderwrack, ceratonia, dextran and derivatives thereof, ghatti gum, hectorite, ispaghula husk, xanthan gum;
  • polymers such as polylactic acid or polyglycolic acid polymers or copolymers thereof, paraffin, polyethylene, polyethylene oxide, polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone;
  • surfactants such as non-ionic surfactants, e.g. glycol and glycerol esters, macrogol ethers and esters, sugar ethers and esters, such as sorbitan esters, ionic surfactants, such as amine soaps, metallic soaps, sulfated fatty alcohols, alkyl ether sulfates, sul- fated oils, and ampholytic surfactants and lecitins;
  • non-ionic surfactants e.g. glycol and glycerol esters, macrogol ethers and esters, sugar ethers and esters, such as sorbitan esters
  • ionic surfactants such as amine soaps, metallic soaps, sulfated fatty alcohols, alkyl ether sulfates, sul- fated oils, and ampholytic surfactants and lecitins;
  • buffering agents such as sodium, potassium, aluminium, magnesium or calcium salts (such as the chloride, carbonate, bicarbonate, citrate, gluconate, lactate, acetate, glu- ceptate or tartrate).
  • the above mentioned mixture may be mixed with additives such as surfactants, solvents, thickeners, stabilisers, preservatives, antioxi- dants, flavours, etc. to obtain a desirable product formulation.
  • a pharmaceutical, dietary supplement or cosmetic composition according to the invention may further contain such additives.
  • the route of administration or dosage form of the formulation and the following examples are not limiting with respect to this: tablets, capsules, lozenges, chewing gum, fluids, granulates, gels, ointments, emulsions (e.g. creams and lotions), sprays (e.g.
  • the composition may also contain surfactants such as bile salts, polyoxyethylene-sorbitan-fatty acid esters or polyalcohol mixed chain-length fatty acid esters for improving dispersibility 5 of the composition in the digestive fluids leading to improved bioavailability or for obtaining the final dosage form of the composition.
  • surfactants such as bile salts, polyoxyethylene-sorbitan-fatty acid esters or polyalcohol mixed chain-length fatty acid esters for improving dispersibility 5 of the composition in the digestive fluids leading to improved bioavailability or for obtaining the final dosage form of the composition.
  • the described pharmaceutical, dietary supplement or cosmetic composition is used in mammals, such as a human.
  • a pharmaceutical composition or dietary supplement according to the invention was prepared as follows:
  • Roscoe 20 nale Roscoe were observed, such as gingerols, gingerdione, shogaols etc.
  • a cosmetic composition according to the invention was prepared according to the following recipe:
  • the preparation comprised a soft gelatine capsule containing: • 750 mg of a mixed fish oil derived from herring, salmon, sardine and sinker containing 18% eicosapentaenoic acid (20:5n3) and 12% docosahexaenoic acid (22:6n3). • 133 mg extract of Zingiber officinale Roscoe.
  • One patient male was 72 years old and had suffered from painful osteoarthritis of the right hand for four years.
  • the patient had in long periods been treated with non-steroidal- antiinflammatory drugs, but had given up the treatment because of unpleasant gastroin- testinal adverse effects.
  • the capsule according to the invention was administered twice daily and after four weeks a marked analgesic effect was observed and a significantly better quality of life was obtained. This level of efficacy was maintained for three months. No adverse effects were observed.
  • the other patient was 56 years old and had suffered from osteoarthritis of the knee for three years.
  • the patient was treated periodically with non-steroidal- antiinflammatory drugs, but did not obtain a sufficient analgesic effect with this class of drugs.
  • the capsule according to the invention was administered twice daily and after three weeks a marked analgesic effect was observed and this effect gradually improved during two months of treatment. After three months of treatment the same high level of efficacy was maintained with a significant improvement of quality of life. No adverse effects were observed.

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Abstract

The present invention relates to mixtures comprising at least one of the fatty acids eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3) and the plant Zingiber officinale Roscoe or parts thereof or an extract or a component thereof as novel pharmaceuticals, dietary supplements or cosmetic compositions containing such mixtures, and to the use of such mixtures for preparing a medicament or a dietary supplement for the suppression of hypersensitivity and/or inflammatory reaction.

Description

Novel pharmaceuticals, dietary supplements and cosmetic compositions, and the use of certain mixtures for preparing a medicament or a dietary supplement for the treatment or prevention of inflammation, hypersensitivity reactions or pain.
FIELD OF THE INVENTION The present invention relates to mixtures comprising at least one of the fatty acids eicosa- pentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3) and the plant Zingiber officinale Roscoe or parts thereof or an extract or a component thereof.
More specifically, the invention relates to novel pharmaceuticals, dietary supplements or cosmetic compositions containing such mixtures, and to the use of such mixtures for preparing a medicament or a dietary supplement for the suppression of hypersensitivity and/or inflammatory reaction.
BACKGROUND OF THE INVENTION
Hypersensitivity is defined as a state of altered reactivity in which the body reacts with an exaggerated immune response to a substance (antigen). Hypersensitivity may be caused by exogenous or endogenous antigens.
Hypersensitivity reactions underlie a large number of diseases. Among these, allergic and autoimmune conditions are of great importance. A classification of hypersensitivity dis- eases is given in the textbook Clinical Medicine (Kumar, P. and Clark, M.: "Clinical Medicine" , 3rd edition, p. 147-150, 1994, Bailliere Tindall, London).
Type I hypersensitivity reactions (IgE mediated allergic reactions) are caused by allergens (specific exogenous antigens), e.g. pollen, house dust, animal dandruff, moulds, etc. Aller- gic diseases in which type I reactions play a significant role include asthma, eczema (atopic dermatitis), urticaria, allergic rhinitis and anaphylaxis.
Type il hypersensitivity reactions are caused by cell surface or tissue bound antibodies (IgG and IgM) and play a significant role in the pathogenesis of myasthenia gravis, Good- pasture's syndrome and Addisonian pernicious anaemia.
Type III hypersensitivity reactions (immune complex) are caused by autoantigens or exogenous antigens, such as certain bacteria, fungi and parasites. Diseases in which type III hypersensitivity reactions play a significant role include lupus erythematosus, rheumatoid arthritis and glomerulonephritis.
Type IV hypersensitivity reactions (delayed) are caused by cell or tissue bound antigens. This type of hypersensitivity plays a significant role in a number of conditions, e.g. graft- versus-host disease, leprosy, contact dermatitis and reactions due to insect bites.
A number of drug classes are available for the treatment of hypersensitivity reactions. Some of these are applied systemically and some are applied topically.
The corticosteroids are among the most widely used drugs for the treatment of hypersensitivity diseases. Corticosteroids primarily exert their pharmacological action by non- selectively inhibiting the function and proliferation of different classes of immune cells resulting in suppression of hypersensitivity reactions. Unfortunately the corticosteroids are associated with a number of serious side effects, e.g. immuno-suppression, osteoporosis and skin atrophy (when applied topically).
Zingiber officinale Roscoe (family Zingiberacea), commonly known as ginger, is an erect perennial herb with thick tuberous rhizomes (underground stems) from which the aerial stem grows about 1 m high. Zingiber officinale Roscoe is native to Southern Asia and is extensively cultivated in the tropics, e.g. India, China, Jamaica, Haiti and Nigeria.
Ginger or ginger volatile oil is widely used as a flavour ingredient in the food industry.
Due to the extensive use of Zingiber officinale Roscoe in the food industry, it has been subject to some chemical investigations.
The ginger rhizome contains a volatile oil which can be obtained by steam distillation. The chemical composition of ginger oil depends on its geographic origin. Ginger volatile oil generally contains the sesquiterpenes zingiberene and bisabolene as its major components. Other sesquiterpenes and sesquiterpene alcohols present include ar-curcumene, β-sesquiphelandrene, sesquithujene, β-bisabolone, (E)-α-farnesene, zingiberol, zin- giberenol, cis-sesquisabinene hydrate, and cis- and trans-sesquiphellandrol. It also contains monoterpenes such as camphor, β-phellandrene, geranial, neral, linalool, camphene and d-bomeol. Zingiber officinale Roscoe contains a number of phenolic compounds, most of which have a characteristic hydroxy-methoxy-phenyl moiety. These compounds are responsible for the pungency of ginger. The quantitatively dominating group of these phenolic compounds are the gingerols. The gingerols form a homologous series, 2-gingerol, 4-gingerol, 6- gingerol, 8-gingerol, 10-gingerol, 12-gingerol and 14-gingerol. The quantitatively dominating of these is 6-gingerol. Another group are the shogaols which are dehydration products of gingerols. The shogaols form a similar homologous series. Other similar compounds present are zingerone, 6-gingerdiol, gingerdione, gingerenones A-C, isogingere- none B, etc.
Zingiber officinale Roscoe has been used in the traditional medicine in China and in the Indian subcontinent for more than 2500 years. The Chinese prescribe fresh or dried ginger for the relief of a number of conditions, e.g. gastrointestinal disturbances, colds, in- flammations, headaches and as an antiemetic for the prevention of seasickness.
The traditional use of Zingiber officinale Roscoe is limited to consumption of the ginger rhizome in a fresh or dried state. Obtaining an effect based on the traditional use requires high doses of the rhizome (Srivastava K C et al., Med. Hypotheses. 1989 May; 29(1): 25-8 and Shrivastava K C et al, Med. Hypothesis 1992 Dec; 39(4): 342-8).
An inhibiting effect on the formation of pro-inflammatory eicosanoids has been established in vitro for some components of Zingiber officinale Roscoe (Kiuchi F, et al, Chem. Pharm. Bull. Tokyo. 1992 Feb; 40(2): 387-91). Furthermore an inhibiting effect of ginger oil on ad- juvant arthritis in the rat has been established in vivo (Sharma J N et al, Pharmacology 1994; 49: 314-18). Despite these findings, the pharmacological effects of Zingiber officinale Roscoe upon administration to humans are mild and only of limited clinical relevance.
The arachidonic acid (AA) metabolism plays an essential role in hypersensitivity reactions because AA is converted by the enzyme cyclooxygenase into pro-inflammatory prosta- glandins and by the enzyme 5-lipoxygenase into proinflammatory leukotrienes. The pros- taglandins and leukotrienes are commonly termed eicosanoids. The modulation of the AA metabolism is a well established pharmacological strategy in relation to the treatment of hypersensitivity reactions. Marine oils, especially fish oils, contain relatively high concentrations of the fatty acids eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3). These fatty acids have been shown to reduce inflammatory reactions because they can replace AA in the AA metabolism. The eicosanoids formed by the metabolism of eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3) have insignificant pro-inflammatory effects or even antiinflammatory effects.
The drawback in relation to the therapeutic use of eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3) is that they are only mildly antiinflammatory and need to be administered for longer periods before a clinical effect can be observed.
SUMMARY OF THE INVENTION
It has been found by the present inventor that a combination of: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), and b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof;
significantly suppresses hypersensitivity reactions, and that such a combination is far superior to any of its components when they are used alone.
To the inventor's best knowledge, it is disclosed nowhere in the literature to use a combination of: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), and b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof; as active ingredients in pharmaceuticals, dietary supplements or cosmetics.
As mentioned above the therapeutic effect of Zingiber officinale Roscoe is derived from the ability of certain components to inhibit the generation of eicosanoids through a direct inhibition of cyclooxygenase and 5-lipoxygenase. The therapeutic efficacy of Zingiber officinale Roscoe is limited strongly by the fact that its pharmacologically active components are only mild inhibitors of eicosanoid generation.
Furthermore the fatty acids eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) have a limited therapeutic efficacy, simply because they are only able to replace a limited fraction of the cellular pool of arachidonic acid after oral administration.
Surprisingly the present inventor has found that a combination of: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), and b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof; provides a synergistic effect in the treatment of hypersensitivity reactions, probably because both substances modulate the arachidonic acid metabolism, but at different levels.
According to the present invention eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) can be used in the form of free fatty acids or esters of any mono- or polyvalent alcohol. Preferably the fatty acids may be used in the form of mono-, di- or triglycerides which can be derived from a number of natural sources, especially marine sources, such as fish in the form of fish oils.
According to the present invention Zingiber officinale Roscoe or parts thereof or an extract or component thereof may be used in any form, such as powdered plant material, extracts, concentrates or distillates or in the form of purified components of the plant, such as 2-gingerol, 4-gingerol, 6-gingerol, 8-gingerol, 10-gingerol, 12-gingerol, 14-gingerol, 2- shogaol, 4-shogaol, 6-shogaol, 8-shogaol, 10-shogaol, 12-shogaol, 14-shogaol, zingerone, 6-gingerdiol, gingerdione, gingerenones, isogingerenones, zingiberene, bis- abolene, ar-curcumene, β-sesquiphelandrene, sesquithujene, β-bisabolone, (E)-α- farnesene, zingiberol, zingiberenol, cis-sesquisabinene hydrate, cis-sesquiphellandrol, trans-sesquiphellandrol and β-phellandrene, or any mixture of any of these substances.
The broad definition of Zingiber officinale Roscoe or parts thereof or an extract or compo- nent thereof is explained by the fact that the pharmacological effects of Zingiber officinale Roscoe is caused by a broad spectrum of pharmacologically active compounds, even though, of course, some substances are preferred.
Compared to existing therapeutic agents, such as corticosteroids or non-steroidal-anti- inflammatory drugs, the pharmaceutical compositions, dietary supplements and cosmetic compositions according to the present invention have the advantage of not being likely to be associated with any serious side effects, as eicosapentaenoic acid (20:5n3), docosahexaenoic acid (22:6n3), and Zingiber officinale Roscoe are non-toxic and well tolerated by the organism in the pharmacologically relevant doses.
Due to the pharmacological effects mentioned above, probably caused by modulation of the arachidonic acid metabolism, the pharmaceutical compositions, dietary supplements and cosmetic compositions according to the invention can be employed for the following therapeutic applications:
Immunomodulation.
Treatment or prevention of hypersensitivity diseases.
Treatment or prevention of IgE mediated allergic reactions and conditions.
Treatment or prevention of autoimmune disorders.
Alleviation of pain.
Accordingly, the present invention provides a pharmaceutical, a dietary supplement or a cosmetic composition, comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically and/or cosmetically acceptable vehicle.
Furthermore, the present invention provides the use of a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; for preparing a medicament for immunomodulation, for the suppression of hypersensitivity reactions, such as IgE mediated allergic reac- tions and autoimmune reactions, and for the alleviation of pain.
Thus, according to the invention a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; can be used in a method for the treatment or prevention of a hypersensitivity disease in an individual, said method comprising administering said mixture to said individual; and the invention comprises the use of said mixture for preparing a medicament for the treatment or prevention of hypersensitivity diseases. Also, according to the invention a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; can be used in a method for the treatment or prevention of an autoimmune disorder in an individual, said method comprising administering said mixture to said individual; and the invention comprises the use of said mixture for preparing a medicament for the treatment or prevention of autoimmune disorders.
Further, according to the invention a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; can be used in a method for the treatment or prevention of an IgE mediated allergic reaction or condition in an individual, said method comprising administering said mixture to said individual; and the invention comprises the use of said mixture for preparing a medicament for the treatment or prevention of IgE mediated allergic reactions and conditions.
Also, according to the invention a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; can be used in a method for the alleviation of pain in an individual, said method comprising administering said mixture to said individual; and the invention comprises the use of said mixture for preparing a medicament for the alleviation of pain.
DETAILED DESCRIPTION OF THE INVENTION
Surprisingly it has been found that a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; exerts pharmacological actions relevant to the therapeutic treatment of conditions associated with hypersensitivity reactions and pain.
More specifically, the above mentioned mixtures provide the following pharmacological effects upon administration to the living organism: Immunomodulation.
Suppression of hypersensitivity reactions.
Suppression of IgE mediated allergic reactions.
Suppression of autoimmune reactions.
Reduction of pain.
The present invention provides a pharmaceutical, a dietary supplement or a cosmetic composition, comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically and/or cosmetically acceptable vehicle.
The weight percentage (w/w) of eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) in the composition is typically at least 0.1%, such as at least 0.2%, e.g. at least 0.3%, at least 0.5%, at least 0.75%, at least 1.0%, at least 1.5%, such as at least 2.0%, e.g. at least 2.5%, at least 3.0%, at least 4.0%, at least 5.0%, at least 10.0%, such as at least 20.0%, e.g. at least 30.0%, at least 40.0%, at least 50.0%, at least 60.0%, at least 70.0%, at least 80.0%, at least 90.0%, such as at least 95.0%, e.g. at least 96.0%, at least 97.0%, at least 98.0%, at least 99.0%.
The weight percentage (w/w) of Zingiber officinale Roscoe or parts thereof or an extract or component thereof in the composition is typically at least 0.1%, such as at least 0.2%, e.g. at least 0.3%, at least 0.5%, at least 0.75%, at least 1.0%, at least 1.5%, such as at least 2.0%, e.g. at least 2.5%, at least 3.0%, at least 4.0%, at least 5.0%, at least 10.0%, such as at least 20.0%, e.g. at least 30.0%, at least 40.0%, at least 50.0%, at least 60.0%, at least 70.0%, at least 80.0%, at least 90.0%, such as at least 95.0%, e.g. at least 96.0%, at least 97.0%, at least 98.0%, at least 99.0%.
According to the present invention eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) can be used in the form of free fatty acids or esters of any mono- or polyvalent alcohol. Preferably the fatty acids may be used in the form of mono-, di- or tri- glycerides which can be derived from a number of natural sources, especially marine sources, such as fish in the form of fish oils.
According to the present invention Zingiber officinale Roscoe or parts thereof or an extract or component thereof may be used in any form, such as powdered plant material, ex- tracts, concentrates or distillates or in the form of purified components of the plant, such as 2-gingerol, 4-gingerol, 6-gingerol, 8-gingerol, 10-gingerol, 12-gingerol, 14-gingerol, 2- shogaol, 4-shogaol, 6-shogaol, 8-shogaol, 10-shogaol, 12-shogaol, 14-shogaol, zingerone, 6-gingerdiol, gingerdione, gingerenones, isogingerenones, zingiberene, bis- abolene, ar-curcumene, β-sesquiphelandrene, sesquithujene, β-bisabolone, (E)-α- famesene, zingiberol, zingiberenol, cis-sesquisabinene hydrate, cis-sesquiphellandrol, trans-sesquiphellandrol and β-phellandrene.
In a preferred embodiment of the invention the part of Zingiber officinale Roscoe is an extract. Extracts according to the invention can i.a. be obtained by extraction or distillation (e.g. hydro, steam or vacuum distillation) of fresh or dried Zingiber officinale Roscoe or parts thereof, preferably the rhizome. Extraction may be performed with a number of different organic solvents, such as water miscible solvents, and mixtures thereof with water. The extraction can also be performed with water immiscible solvents, such as alkanes. The extraction can be performed hot or cold by the employment of any extraction technol- ogy e.g. maceration, percolation or supercritical extraction.
The preferred extraction solvents are pentane, hexane, heptane, acetone, methyl ethyl ketone, ethyl acetate, lower alkanols having 1 to 4 carbon atoms and mixtures thereof with water. The preferred extraction temperature is close to the boiling point of the em- ployed solvent due to extraction efficacy, but lower temperatures are also applicable making necessary a longer period of extraction. Supercritical extraction (e.g. performed with C02) is also a preferred mode of extraction.
A "dietary supplement" is defined according to the U.S. Food and Drug Administration in the Dietary Supplement Health and Education Act of 1994 (DSHEA).
The DSHEA gives the following formal definition of a "dietary supplement": "A dietary supplement:
• is a product (other than tobacco) that is intended to supplement the diet that bears or contains one or more of the following dietary ingredients: a vitamin, a mineral, an herb or other botanical, an amino acid, a dietary substance for use by man to supplement the diet by increasing the total daily intake, or a concentrate, metabolite, constituent, extract, or combinations of these things. • is intended for ingestion in pill, capsule, tablet, or liquid form."
Similar definitions exist in other parts of the world, e.g. in Europe; in the present context, the definition is as defined above. Different denominations concerning "dietary supplements" are used around the world, such as "food supplements", "neutraceuticals", "functional foods" or simply "foods". In the present context the term "dietary supplement" covers any such denomination or definition.
The above mentioned pharmacological actions provide part of the rationale for the following therapeutic applications of a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle:
• A method for the treatment or prevention of hypersensitivity disease characterised by the administration of the above mentioned mixture. The therapeutic action may be relevant to all known diseases associated with hypersensitivity reactions. Autoimmune disorders and IgE mediated allergic conditions are described below in more detail. Besides these specific therapeutic areas, the action of the above mentioned mixture is relevant to all known conditions and diseases associated with hypersensitivity reaction, and the following examples are not limiting with respect to this: infections (viral, bacterial, fungal, parasitic, etc.), cold and flu, contact dermatitis, insect bites, allergic vasculitis, postoperative reactions, transplantation rejection (graft-versus-host disease), etc.
• A method for the treatment or prevention of autoimmune disorders characterised by the administration of the above mentioned mixture. The applicant puts forward the hypothesis that the therapeutic action is due to the immunomodulating and suppressing effect on hypersensitivity reactions of the above mentioned mixture. The therapeutic action may be relevant to all known autoimmune disorders and the following examples are not limiting with respect to this: Autoimmune hepatitis, Primary biliary cirrhosis, Pri- mary sclerosing cholangitis, Autoimmune hemolytic anemias, Grave's disease, Myas- thenia gravis, Type 1 Diabetes Mellitus, Inflammatory myopathies, Multiple sclerosis, Hashimoto's thyreoiditis, Autoimmune adrenalitis, Crohn's Disease, Ulcerative Colitis, Glomerulonephritis, Progressive Systemic Sclerosis (Scleroderma), Sjόgren's Disease, Lupus Erythematosus, Primary vasculitis, Rheumatoid Arthritis, Juvenile Arthri- tis, Mixed Connective Tissue Disease, Psoriasis, Pemfigus, Pemfigoid, Dermatitis Herpetiformis, etc.
• A method for the treatment or prevention of an IgE mediated allergic reaction or condition characterised by the administration of the above mentioned mixture. The appli- cant puts forward the hypothesis that the therapeutic action is due to the suppressing effect on hypersensitivity reaction of the above mentioned mixture. The therapeutic action may be relevant to all known IgE mediated allergic reactions and conditions, and the following examples are not limiting with respect to this: asthma, eczema (e.g. atopic dermatitis), urticaria, allergic rhinitis, anaphylaxis, etc.
• A method for the treatment or prevention of any condition associated with pain characterised by the administration of the above mentioned mixture. The applicant puts forward the hypothesis that the therapeutic action is related to immunomodulation, possibly to a suppressing effect on hypersensitivity reactions.
According to the invention the above mentioned mixture can be combined with any other active ingredient to potentiate the therapeutic action.
Vehicles other than water that can be used in compositions can include solids or liq- uids such as emollients, solvents, humectants, thickeners and powders. Examples of each of these types of vehicles, which can be used singly or as mixtures of one or more vehicles, are as follows:
Emollients, such as stearyl alcohol, glyceryl monoricinoleate, glyceryl monostearate, propane-1 ,2-diol, butane-1 ,3-diol, cetyl alcohol, isopropyl isostearate, stearic acid, iso- butyl palmitate, isocetyl stearate, oleyl alcohol, isopropyl laurate, hexyl laurate, decyl oleate, octadecan-2-ol, isocetyl alcohol, cetyl palmitate, dimethylpolysiloxane, di-n-bu- tyl sebacate, isopropyl myristate, isopropyl palmitate, isopropyl stearate, butyl stearate, polyethylene glycol, triethylene glycol, lanolin, castor oil, acetylated lanolin al- cohols, petroleum, mineral oil, butyl myristate, isostearic acid, palmitic acid, isopropyl linoleate, lauryl lactate, myristyl lactate, decyl oleate, myristyl myristate; solvents, such as water, methylene chloride, isopropanol, castor oil, ethylene glycol monoethyl ether, diethylene glycol monobutyl ether, diethylene glycol monoethyl ether, dimethyl sulfoxide, tetrahydrofuran, vegetable and animal oils, glycerol, etha- nol, propanoi, propylene glycol, and other glycols or alcohols, fixed oils;
humectants or moistening agents, such as glycerin, sorbitol, sodium 2-pyrrolidone-5- carboxylate, soluble collagen, dibutyl .phthalate, gelatin;
powders, such as chalk, talc, kaolin, starch and derivatives thereof, gums, colloidal silicon dioxide, sodium polyacrylate, chemically modified magnesium aluminium silicate, hydrated aluminium silicate, carboxyvinyl polymer, sodium carboxymethyl cellulose, ethylene glycol monostearate;
gelling or swelling agents, such as pectin, gelatin and derivatives thereof, cellulose de- rivatives such as methyl cellulose, carboxymethyl cellulose or oxidised cellulose, cellulose gum, guar gum, acacia gum, karaya gum, tragacanth gum, bentonite, agar, algi- nates, carbomer, gelatine, bladderwrack, ceratonia, dextran and derivatives thereof, ghatti gum, hectorite, ispaghula husk, xanthan gum;
polymers, such as polylactic acid or polyglycolic acid polymers or copolymers thereof, paraffin, polyethylene, polyethylene oxide, polyethylene glycol, polypropylene glycol, polyvinylpyrrolidone;
surfactants, such as non-ionic surfactants, e.g. glycol and glycerol esters, macrogol ethers and esters, sugar ethers and esters, such as sorbitan esters, ionic surfactants, such as amine soaps, metallic soaps, sulfated fatty alcohols, alkyl ether sulfates, sul- fated oils, and ampholytic surfactants and lecitins;
buffering agents, such as sodium, potassium, aluminium, magnesium or calcium salts (such as the chloride, carbonate, bicarbonate, citrate, gluconate, lactate, acetate, glu- ceptate or tartrate).
Furthermore, it is obvious that in the use according to the invention for preparing medicaments, dietary supplements or cosmetics, the above mentioned mixture may be mixed with additives such as surfactants, solvents, thickeners, stabilisers, preservatives, antioxi- dants, flavours, etc. to obtain a desirable product formulation. Similarly, a pharmaceutical, dietary supplement or cosmetic composition according to the invention may further contain such additives. There are no limitations on the route of administration or dosage form of the formulation, and the following examples are not limiting with respect to this: tablets, capsules, lozenges, chewing gum, fluids, granulates, gels, ointments, emulsions (e.g. creams and lotions), sprays (e.g. aerosol), inhalants, eye drops, etc. Optionally, the composition may also contain surfactants such as bile salts, polyoxyethylene-sorbitan-fatty acid esters or polyalcohol mixed chain-length fatty acid esters for improving dispersibility 5 of the composition in the digestive fluids leading to improved bioavailability or for obtaining the final dosage form of the composition.
In preferred embodiments of the present invention the described pharmaceutical, dietary supplement or cosmetic composition is used in mammals, such as a human.
10 EXAMPLES
Example 1
A pharmaceutical composition or dietary supplement according to the invention was prepared as follows:
15 100 g of dried rhizome of Zingiber officinale Roscoe was percolated with 1000 ml of acetone for 24 hours. Thereafter the extract was filtered and evaporated to dryness under vacuum. Thus 4.7 g of concentrated liquid extract was obtained. The extract was subjected to high performance liquid chromatography (HPLC) with mass spectrometry and photodiode array detection. Several characteristic phenolic constituents of Zingiber offici-
20 nale Roscoe were observed, such as gingerols, gingerdione, shogaols etc.
3 g of the concentrated liquid extract of Zingiber officinale Roscoe was mixed with 7 g of cod liver oil containing eicosapentaenoic acid (20:5n3) and docosahexaenoic acid (22:6n3). Thus a homogeneous mixture was obtained suitable for encapsulation in soft 25 gelatine capsules.
Example 2
A cosmetic composition according to the invention was prepared according to the following recipe:
30 Cod liver oil, IDA A/S, Denmark 20.0%
Hydrogenated rapeseed oil, Cremeol PS-6, Aarhus Olie, Denmark 10.0%
Sodium stearoyl lactylate, Danisco Ingredients, Denmark 5.0%
Sorbitan monostearate, Danisco Ingredients, Denmark 3.0% Super Critical (C02) Extract of Zingiber officinale Roscoe 2.5%
Glyceryl monostearate, Danisco Ingredients, Denmark 2.0%
Methyl paraben, Unichem, Denmark 0.3%
Water, purified ad 100%
Example 3
In a small preliminary clinical investigation two persons administered an oral preparation according to the invention. The preparation comprised a soft gelatine capsule containing: • 750 mg of a mixed fish oil derived from herring, salmon, sardine and sinker containing 18% eicosapentaenoic acid (20:5n3) and 12% docosahexaenoic acid (22:6n3). • 133 mg extract of Zingiber officinale Roscoe.
One patient (male) was 72 years old and had suffered from painful osteoarthritis of the right hand for four years. The patient had in long periods been treated with non-steroidal- antiinflammatory drugs, but had given up the treatment because of unpleasant gastroin- testinal adverse effects. The capsule according to the invention was administered twice daily and after four weeks a marked analgesic effect was observed and a significantly better quality of life was obtained. This level of efficacy was maintained for three months. No adverse effects were observed.
The other patient (female) was 56 years old and had suffered from osteoarthritis of the knee for three years. The patient was treated periodically with non-steroidal- antiinflammatory drugs, but did not obtain a sufficient analgesic effect with this class of drugs. The capsule according to the invention was administered twice daily and after three weeks a marked analgesic effect was observed and this effect gradually improved during two months of treatment. After three months of treatment the same high level of efficacy was maintained with a significant improvement of quality of life. No adverse effects were observed.

Claims

1. A pharmaceutical, a dietary supplement or a cosmetic composition, comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically and/or cosmetically acceptable vehicle.
2. A pharmaceutical, a dietary supplement or a cosmetic composition according to claim 1 , wherein the component of Zingiber officinale Roscoe is selected from the group con- sisting of 2-gingerol, 4-gingerol, 6-gingerol, 8-gingerol, 10-gingerol, 12-gingerol, 14- gingerol, 2-shogaol, 4-shogaol, 6-shogaol, 8-shogaol, 10-shogaol, 12-shogaol, 14- shogaol, zingerone, 6-gingerdiol, gingerdione, gingerenones, isogingerenones, zingiber- ene, bisabolene, ar-curcumene, β-sesquiphelandrene, sesquithujene, β-bisabolone, (E)-α- farnesene, zingiberol, zingiberenol, cis-sesquisabinene hydrate, cis-sesquiphellandrol, trans-sesquiphellandrol and β-phellandrene.
3. A pharmaceutical, a dietary supplement or a cosmetic composition according to claim 1 or 2, wherein eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) is in the form of an ester or glyceride, such as an oil from a marine source.
4. The use of a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; for preparing a medicament or a dietary supple- ment.
5. The use of a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a cosmetically acceptable vehicle; for preparing a cosmetic product.
6. The use of a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; for preparing a medicament or a dietary supplement for immunomodulation.
7. The use of a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; for preparing a medicament or a dietary supplement for the suppression of hypersensitivity and/or inflammatory reaction.
8. The use according to claim 7 for preparing a medicament or a dietary supplement for the treatment or prevention of autoimmune disease and/or chronic inflammatory disease.
9. The use according to claim 8 for preparing a medicament or a dietary supplement for the treatment or prevention of Crohn's disease, ulcerative colitis, rheumatoid arthritis or osteoarthritis.
10. The use of a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically acceptable vehicle; for preparing a medicament or a dietary supplement for the alleviation of pain.
11. The use according to any one of claims 4 to 10, wherein the component of Zingiber officinale Roscoe is selected from the group consisting of 2-gingerol, 4-gingerol, 6-gingerol, 8-gingerol, 10-gingerol, 12-gingerol, 14-gingerol, 2-shogaol, 4-shogaol, 6-shogaol, 8-sho- gaol, 10-shogaol, 12-shogaol, 14-shogaol, zingerone, 6-gingerdiol, gingerdione, gingere- nones, isogingerenones, zingiberene, bisabolene, ar-curcumene, β-sesquiphelandrene, sesquithujene, β-bisabolone, (E)-α-famesene, zingiberol, zingiberenol, cis- sesquisabinene hydrate, cis-sesquiphellandrol, trans-sesquiphellandrol and β- phellandrene.
12. The use according to any one of claims 4 to 11 , wherein eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) is in the form of an ester or glyceride, such as an oil from a marine source.
13. A method for the treatment or prevention of hypersensitivity or inflammation in an individual, characterised by administering a mixture according to the invention to said individual, said mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), 5 b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically and/or cosmetically acceptable vehicle.
14. A method for the treatment or prevention of an autoimmune disorder and/or a chronic inflammatory disorder in an individual, characterised by administering a mixture according
10 to the invention to said individual, said mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically and/or cosmetically acceptable vehicle.
15 15. A method for the treatment or prevention of Crohn's disease, ulcerative colitis, rheumatoid arthritis and/or osteoarthritis in an individual, characterised by administering a mixture according to the invention to said individual, said mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and 20 c) a pharmaceutically and/or cosmetically acceptable vehicle.
16. A method for the treatment or prevention of pain in an individual, characterised by administering a mixture according to the invention to said individual, said mixture comprising:
25 a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a pharmaceutically and/or cosmetically acceptable vehicle.
17. A method according to any one of claims 13 to 16, wherein the component of Zingiber 30 officinale Roscoe is selected from the group consisting of 2-gingerol, 4-gingerol, 6- gingerol, 8-gingerol, 10-gingerol, 12-gingerol, 14-gingerol, 2-shogaol, 4-shogaol, 6- shogaol, 8-shogaol, 10-shogaol, 12-shogaol, 14-shogaol, zingerone, 6-gingerdiol, ginger- dione, gingerenones, isogingerenones, zingiberene, bisabolene, ar-curcumene, β- sesquiphelandrene, sesquithujene, β-bisabolone, (E)-α-famesene, zingiberol, zingibere- nol, cis-sesquisabinene hydrate, cis-sesquiphellandrol, trans-sesquiphellandrol and β- phellandrene.
18. A method according to any one of claims 13 to 17, wherein eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3) is in the form of an ester or glyceride, such as an oil from a marine source.
19. The cosmetic use of a mixture comprising: a) eicosapentaenoic acid (20:5n3) and/or docosahexaenoic acid (22:6n3), b) Zingiber officinale Roscoe or parts thereof or an extract or component thereof, and c) a cosmetically acceptable vehicle.
PCT/DK2000/000087 1999-03-03 2000-03-02 Novel pharmaceuticals, dietary supplements and cosmetic compositions, and the use of certain mixtures for preparing a medicament or a dietary supplement for the treatment or prevention of inflammation, hypersensitivity reactions or pain Ceased WO2000051576A2 (en)

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CA002366318A CA2366318A1 (en) 1999-03-03 2000-03-02 Novel pharmaceutical, dietary and cosmetic compositions comprising zinger officinale roscoe, eicosapentaenoic acid and/or docosahexaenoic acid
DE60005152T DE60005152T2 (en) 1999-03-03 2000-03-02 MEDICINAL PRODUCTS, FOOD ADDITIVES AND COSMETIC PREPARATION CONTAINING A FATTY ACID AND GINGER
DK00907455T DK1156814T3 (en) 1999-03-03 2000-03-02 Pharmaceuticals, supplements and cosmetic preparations comprising a fatty acid and ginger
AU29033/00A AU2903300A (en) 1999-03-03 2000-03-02 Novel pharmaceuticals, dietary supplements and cosmetic compositions, and the use of certain mixtures for preparing medicament or a dietary supplement for thetreatment or prevention of inflammation, hypersensitivity reactions or pain
EP00907455A EP1156814B1 (en) 1999-03-03 2000-03-02 Pharmaceuticals, dietary supplements and cosmetic compositions comprising a fatty acid and ginger
AT00907455T ATE249231T1 (en) 1999-03-03 2000-03-02 MEDICINAL PRODUCTS, FOOD SUPPLEMENTS AND COSMETIC PREPARATIONS CONTAINING A FATTY ACID AND GINGER
SI200030263T SI1156814T1 (en) 1999-03-03 2000-03-02 Pharmaceuticals, dietary supplements and cosmetic compositions comprising a fatty acid and ginger
HK02103899.4A HK1042240B (en) 1999-03-03 2000-03-02 Pharmaceuticals, dietary supplements and cosmetic compositions comprising a fatty acid and ginger
US09/945,256 US6482421B2 (en) 1999-03-03 2001-08-31 Pharmaceuticals, dietary supplements and cosmetic compositions, and the use of certain mixtures for preparing a medicament or a dietary supplement for the treatment or prevention of inflammation, hypersensitivity reactions or pain
US10/266,470 US6638525B2 (en) 1999-03-03 2002-10-08 Pharmaceuticals, dietary supplements and cosmetic compositions, and the use of certain mixtures for preparing a medicament or a dietary supplement for the treatment or prevention of inflammation, hypersensitivity reactions or pain

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US09/965,256 Continuation US6419830B2 (en) 1999-01-22 2001-09-27 Surface modified polymer beads

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Cited By (13)

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Publication number Priority date Publication date Assignee Title
WO2002034274A1 (en) * 2000-10-23 2002-05-02 HANSEN, Otto, Torbjørn A composition or rose hip and fish oil for alleviating joint pain and stiffness
WO2003030919A1 (en) * 2001-10-11 2003-04-17 Centro De Investigación Y Desarrollo De Medicamentos. Method of obtaining an extract of ginger
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WO2007066305A1 (en) * 2005-12-09 2007-06-14 Zelpy 2549 (Pty) Limited Compositions comprising sesquiterpene compounds for use in the prophylaxis or treatment of pain
WO2007071721A3 (en) * 2005-12-22 2007-09-07 Boehringer Ingelheim Int Ginger extract for inhibiting human drug transporters
WO2007071708A3 (en) * 2005-12-22 2007-09-07 Boehringer Ingelheim Int Ginger fraction for inhibiting human cyp enzymes
WO2007104985A1 (en) * 2006-03-16 2007-09-20 Nicholas John Larkins Compositions comprising apocynin , ginkgo and ginger and uses thereo
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WO2009150179A3 (en) * 2008-06-10 2010-02-04 Dsm Ip Assets B.V. Plant extract and pufa combinations
WO2012052848A1 (en) * 2010-10-21 2012-04-26 Innolipid, As Concentration of polyunsaturated fatty acids by distillation using removable isovolatile co-distilling agents
WO2021094268A1 (en) * 2019-11-11 2021-05-20 Firmenich Sa Gingerol compounds and their use as flavor modifiers
WO2024171115A1 (en) * 2023-02-15 2024-08-22 Evithe Limited Methods of preparation of zingerone, compositions comprising zingerone, and uses therefor

Families Citing this family (52)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US6469384B2 (en) * 2001-02-01 2002-10-22 Fairchild Semiconductor Corporation Unmolded package for a semiconductor device
US7025985B2 (en) * 2001-05-28 2006-04-11 Kanebo, Ltd. Dihydroxyphenyl compounds and glucoside compounds thereof
US6811796B2 (en) * 2002-04-22 2004-11-02 Matsuura Yakugyo Co., Ltd. Preventive or therapeutic agent for pollen allergy, allergic rhinitis, atopic dermatitis, asthma or urticaria, or health food for prevention or improvement or reduction of symptoms thereof
WO2005000332A2 (en) * 2003-06-27 2005-01-06 Astellas Pharma Inc. Therapeutic agent for soft tissue sarcoma
US8633246B2 (en) 2003-08-11 2014-01-21 Hill's Pet Nutrition, Inc. Omega-3 fatty acids for osteoarthritis
US8633247B2 (en) * 2003-08-11 2014-01-21 Hill's Pet Nutrition, Inc. Method for decreasing cartilage damage in dogs
US7338674B2 (en) * 2004-12-23 2008-03-04 Council Of Scientific And Industrial Research Anti-arthritic herbal composition and method thereof
KR100588469B1 (en) 2005-02-21 2006-11-23 한국생명공학연구원 Composition for the prevention and treatment of obesity, including shogaol isolated from ginger
US20060275516A1 (en) * 2005-06-02 2006-12-07 Ram A N S Compositions and methods for the treatment of allergic rhinitis
US8017162B2 (en) * 2005-10-26 2011-09-13 Oryza Oil & Fat Chemical Co., Ltd. Anti-inflammatory agent
EP1965820A4 (en) * 2005-11-16 2010-01-06 Natbio Pty Ltd Zingiber plant extract
JP5207341B2 (en) * 2006-10-26 2013-06-12 独立行政法人産業技術総合研究所 Inflammatory cytokine production inhibitor
PL2334295T3 (en) 2008-09-02 2017-12-29 Amarin Pharmaceuticals Ltd Pharmaceutical composition comprising eicosapentaenoic acid and nicotinic acid and methods of using same
SG10201912687WA (en) 2009-04-29 2020-02-27 Amarin Pharmaceuticals Ie Ltd Stable Pharmaceutical Composition And Methods Of Using Same
CN104042617A (en) 2009-04-29 2014-09-17 阿马里纳药物爱尔兰有限公司 Pharmaceutical Compositions Comprising Epa And A Cardiovascular Agent And Methods Of Using The Same
EP3698781A1 (en) 2009-06-15 2020-08-26 Amarin Pharmaceuticals Ireland Limited Compositions comprising eicosapentaenoic acid for treating myocardial infarction in a subject on concomitant statin therapy
CA2774542A1 (en) * 2009-09-18 2011-03-24 Phycoil Biotechnology International, Inc. Microalgae fermentation using controlled illumination
RU2758369C2 (en) 2009-09-23 2021-10-28 Амарин Фармасьютикалз Айрлэнд Лимитед Pharmaceutical composition containing omega-3 fatty acid and a statin hydroxy-derivative, and methods of using it
DE102009055917A1 (en) * 2009-11-27 2011-06-01 Beiersdorf Ag Use of Zingeron against aging skin
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NZ744990A (en) 2010-11-29 2019-10-25 Amarin Pharmaceuticals Ie Ltd Low eructation composition and methods for treating and/or preventing cardiovascular disease in a subject with fish allergy/hypersensitivity
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FR2973227B1 (en) * 2011-04-01 2014-08-08 Oreal COSMETIC COMPOSITION COMPRISING 4- (3-ETHOXY-4-HYDROXYPHENYL) BUTAN-2-ONE
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TWI468170B (en) 2011-07-18 2015-01-11 Univ Kaohsiung Medical Use of ginger compounds
WO2013070735A1 (en) 2011-11-07 2013-05-16 Amarin Pharmaceuticals Ireland Limited Methods of treating hypertriglyceridemia
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US20150265566A1 (en) 2012-11-06 2015-09-24 Amarin Pharmaceuticals Ireland Limited Compositions and Methods for Lowering Triglycerides without Raising LDL-C Levels in a Subject on Concomitant Statin Therapy
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US11058661B2 (en) 2018-03-02 2021-07-13 Amarin Pharmaceuticals Ireland Limited Compositions and methods for lowering triglycerides in a subject on concomitant statin therapy and having hsCRP levels of at least about 2 mg/L
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AU2022263358A1 (en) 2021-04-21 2023-11-30 Amarin Pharmaceuticals Ireland Limited Methods of reducing the risk of heart failure
KR102647997B1 (en) * 2021-06-15 2024-03-18 주식회사 제넨셀 Composition for preventing, improving, or treating degenerative arthritis comprising steamed ginger extract or 1-dehydro-6-gingerdione isolated therefrom as an active ingredient
CN116617249B (en) * 2023-06-16 2026-03-24 浙江省农业科学院 Application of Dendrobium officinale stem/leaf polysaccharides

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JPH01180822A (en) * 1988-01-12 1989-07-18 Dainippon Pharmaceut Co Ltd Anti-delayed type allergic agent
JPH07267856A (en) * 1994-02-09 1995-10-17 Green Cross Corp:The Oral immunosuppressant
GB9506837D0 (en) * 1995-04-03 1995-05-24 Scotia Holdings Plc Triglycerides
FR2752381B1 (en) * 1996-08-13 1998-11-06 Pierre Moreau AVIAN BIOTECHNOLOGY, BIOAVAILABLE MICRO NUTRIENTS. PREVENTION AND TREATMENT OF THE SPECIFIC PHYSIOPATHOLOGY OF DEGENESCENCE AND AGING DISEASES

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* Cited by examiner, † Cited by third party
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WO2003030919A1 (en) * 2001-10-11 2003-04-17 Centro De Investigación Y Desarrollo De Medicamentos. Method of obtaining an extract of ginger
WO2005046630A1 (en) * 2003-11-17 2005-05-26 Tsumura & Co. Hair restorer compositions and antipruritic agent
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JP2011523856A (en) * 2008-06-10 2011-08-25 ディーエスエム アイピー アセッツ ビー．ブイ． Combination of plant extract and PUFA
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WO2021094268A1 (en) * 2019-11-11 2021-05-20 Firmenich Sa Gingerol compounds and their use as flavor modifiers
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WO2000051576A3 (en) 2001-03-29
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AU2903300A (en) 2000-09-21
US20030035853A1 (en) 2003-02-20
ES2206195T3 (en) 2004-05-16
US20020051800A1 (en) 2002-05-02
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CA2366318A1 (en) 2000-09-08
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