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WO2010026375A1 - Préparation pharmaceutique comprenant une cathécine - Google Patents

Préparation pharmaceutique comprenant une cathécine Download PDF

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Publication number
WO2010026375A1
WO2010026375A1 PCT/GB2009/002113 GB2009002113W WO2010026375A1 WO 2010026375 A1 WO2010026375 A1 WO 2010026375A1 GB 2009002113 W GB2009002113 W GB 2009002113W WO 2010026375 A1 WO2010026375 A1 WO 2010026375A1
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WO
WIPO (PCT)
Prior art keywords
metabolite
catechin
composition
apocynin
paeonol
Prior art date
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Ceased
Application number
PCT/GB2009/002113
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English (en)
Inventor
Nicholas John Larkins
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Individual
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Individual
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Filing date
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Publication of WO2010026375A1 publication Critical patent/WO2010026375A1/fr
Anticipated expiration legal-status Critical
Ceased legal-status Critical Current

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/12—Ketones
    • 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
    • A61K31/11—Aldehydes
    • 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
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • A61K31/353—3,4-Dihydrobenzopyrans, e.g. chroman, catechin
    • 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
    • A61K36/16—Ginkgophyta, e.g. Ginkgoaceae (Ginkgo family)
    • 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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • 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)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/82—Theaceae (Tea family), e.g. camellia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A61P11/06—Antiasthmatics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P29/00—Non-central analgesic, antipyretic or antiinflammatory agents, e.g. antirheumatic agents; Non-steroidal antiinflammatory drugs [NSAID]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P35/00—Antineoplastic agents

Definitions

  • the present invention relates to compositions, for example, pharmaceutical compositions, for the treatment of disease.
  • Apocyri ⁇ n,(4-hydroxy-3-methoxyacetophenone, acetovanillone) is a methoxy- catechol. It is a natural organic compound which has been isolated from a variety of plant sources. Apocynin is an efficient inhibitor of the multienzyme complex NADPH oxidase. Compositions for the treatment of disease which use apocynin as active agent are known.
  • compositions for the treatment of disease which have, for example, improved bioavailability (e.g. increased oral bioavailability) and/or pharmacokinetic profile.
  • compositions for the treatment of disease which have more readily available (or cheaper) active agents.
  • composition for example a pharmaceutical composition
  • a composition comprising:
  • R 1 or R 2 is H and the other of R 1 or R 2 is Ci to C 6 branched or straight chain alkyl; and (ii) a ginkgolide or metabolite thereof, a paeonol or metabolite thereof, or 2- hydroxy-4-methoxybenzaldehyde or metabolite thereof.
  • the first component may comprise a compound according to formula [I] wherein R 1 is CH 3 and R 2 is H, wherein the first component comprises 4-hydroxy-3- methoxybenzaldehyde, also known as vanillin.
  • the first component may comprise a metabolite of a compound according to formula [I] wherein R 1 is CH 3 and R 2 is H, wherein the first component comprises a metabolite of vanillin.
  • the metabolite of vanillin may be, for example, vanillyl alcohol, vanillic acid, vanilloyl glycine, catechol, 4-methylcatechol, guaiacol or A- methylguaiacol.
  • the first component may comprise a compound according to formula [I] wherein R 1 is H and R 2 is CH 3 , wherein the first component comprises 3-hydroxy-4- methoxy-benzaldehyde, also known as isovanillin.
  • the first component may comprise a metabolite of isovanillin.
  • the metabolite of isovanillin may be, for example, isovanillyl alcohol, isovanillic acid, vanillic acid, isovanilloyl glycine, catechol or 4-methylcatechol.
  • the first component may comprise the compound of formula [I] or a metabolite thereof which is present as part of an unresolved mixture of compounds in the form of an unpurified plant or root extract (that is as a direct extract from a plant).
  • a compound according to formula [I] or metabolite thereof in the natural form” or a “natural compound” (e.g. "natural vanillin”, “natural isovanillin”, “natural vanillic acid” etc.).
  • the compound according to formula [I] is vanillin which is present in the composition as an extract of the vanilla bean or "vanilla extract” (which is a mixture of several hundred different compounds in addition to vanillin) this may be referred to as "natural vanillin”.
  • the first component may comprise a compound according to formula [I] in a purified or synthetic form, and this may be referred to as "isolated” compound according to formula [I].
  • the first component comprises a compound according to formula [I] which is in the form of synthetic vanillin, this compound may be referred to as isolated vanillin.
  • Synthetic vanillin may be made by methods well known in the art, e.g. from guaiacol or lignin.
  • compositions according to the invention which include a compound of formula (I) or metabolite thereof may show similar or improved effect when compared to a composition which includes apocynin. Further, compositions which include vanillin may show improved toxicity (e.g. reduced side effects at high doses) and/or may be less expensive to produce (because of the wide availability of vanillin as vanilla extract).
  • a composition for example, a pharmaceutical composition
  • a catechin for example, a pharmaceutical composition
  • a ginkgolide or metabolite thereof for example, a paeonol or metabolite thereof; or 2-hydroxy-4-methoxybenzaldehyde or metabolite thereof.
  • catechin means a polyphenol ⁇ antioxidant plant metabolite which belongs to the family of flavonoids (flavan-3-ols).
  • catechin includes catechin, epicatechin, gallocatechin, epigallocatechin, and the gallates.
  • the catechin is epicatechin.
  • a preferred epicatechin is (-)-epicatechin.
  • the catechin (e.g. epicatechin) may be present as part of an unresolved mixture of compounds in the form of an unpurified plant or root extract. If this is the case, it may be referred to as catechin [or epicatechin] "in the natural form” or "natural catechin” (e.g. "natural epicatechin", “natural (-)-epicatechin” etc.).
  • the catechin may be natural catechin in the form of an extract of Camellia sinenisis or Theobroma cacao.
  • the catechin may be present as an extract from, for example, white tea, green tea, black tea, Oolon tea.
  • the catechin (e.g. epicatechin) may be used in the composition or preparation in a purified or synthetic form, and this may be referred to as "isolated catechin” or "isolated epicatechin”.
  • compositions which include catechins may show improved toxicity (e.g. reduced side effects at high doses) and/or may be less expensive to produce (because of the wide availability of e.g. natural catechins in certain teas etc.).
  • the catechin is (-)-epicatechin, either in the isolated form, the natural form, or both.
  • the (-)- epicatechin may provide improved bioavailability over [and/or reduce side effects of], for example, natural forms of apocynin (e.g. Picrorhiza kurroa) because it is believed to act as a "prodrug" of apocynin-like metabolites, being metabolised in the liver to form these active species.
  • a composition for example, a pharmaceutical composition
  • a composition comprising: a derivative or metabolite of apocynin; and one or more of a gingkolide or metabolite thereof; a paeonol or metabolite thereof; or 2-hydroxy-4-methoxybenzaldehyde or metabolite thereof.
  • the metabolite of apocynin may be, for example, demethylated apocynin; a three ring-hydroxylated metabolite of apocynin; the para-methoxy derivative (acetoisovanillone); the dimethoxy-hydroxy derivative; a 1-phenylethanol derivative formed by ketone reduction of aceteovanillone; and a 1-phenylethanol derivative formed by ketone reduction of 3,4- dihydroxyacetophenone.
  • the derivative of apocynin may be, for example, a 4- nitroguaiacol (2-methoxy-4-nitrophenol) or 4-cyanoguaiacol.
  • compositions according to the invention which include: a compound of formula (I) or metabolite thereof; a catechin; or a derivative or metabolite of apocynin; may show similar or improved effect when compared to a composition which includes a (pharmaceutically) equivalent amount of apocynin.
  • At least 0.05% by weight of the composition may be the compound of formula (I) or metabolite thereof; the catechin
  • compositions of the invention may comprise a ginkgolide or metabolite thereof.
  • ginkgolide is understood all of the natural ginkgolides obtained from the Ginkgo biloba tree, as well as synthetic ginkgolides and their derivatives.
  • the ginkgolide may be present as part of an unresolved mixture of compounds in the form of an unpurified plant or root extract. If this is the case, it may be referred to as ginkgolide "in the natural form" or "natural ginkgolide".
  • the ginkgolide may be a natural ginkgolide in the form of ginkgo biloba; or extract or component thereof.
  • the ginkgo biloba may be in concentrated standard form, such as is well known in the art.
  • the ginkgo biloba may be a concentrated extract which is equivalent to four times the concentration of ginkgo biloba in the natural form, such as ginkgo biloba tablets sold by MediHerb of Australia (500 mg tablets containing ginkgo biloba concentrated extract equivalent to 2.Og dry leaf ginkgo biloba standardised to contain 22-26% ginkgo flavone glycosides).
  • the component of ginkgo biloba may be, for example, one of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J or ginkgolide M.
  • the ginkgolide may be used in the composition or preparation in a purified or synthetic form, and this may be referred to as "isolated ginkgolide".
  • isolated ginkgolide may be, for example, one (or more) of ginkgolide A, ginkgolide B, ginkgolide C, ginkgolide J or ginkgolide M.
  • the composition may include ginkgolide (e..g ginkgolide A, ginkgo biloba; or extract or component thereof) in an amount which is at least 1% by weight of the total composition.
  • ginkgolide e.g ginkgolide A, ginkgo biloba; or extract or component thereof
  • at least 5% by weight of the composition may be ginkgolide, for example, at least 10%, 15%, 20%, 25% or 30% by weight of the composition may be ginkgolide.
  • compositions according to the invention may comprise paeonol or metabolite thereof.
  • Paeonol is 2-hydroxy-4-methoxy-acetophenone and is shown by the following formula:
  • paeonol may be found in Paeonia suffruticosa, Paeonia lactiflora, Paeonia veitchii, Paeonia obovata, Glycyrrhiza glabra, Cynanchum paniculatum, Picrorrhiza kurroa, Picrorrhiza scrophulariiflora, Rheum palmatum (rhizome) and Scutellaria baicalensis (root).
  • compositions and preparations of the invention may include "isolated" paeonol, that is paeonol which has been synthesised or paeonol which has been extracted from plants and purified.
  • paeonol may be present in preparations according to the invention as direct extracts from plants
  • paeonol in the natural form
  • natural paeonol paeonol present in preparations according to the invention in the form of Paeonia suffruticosa or extract thereof
  • paeonol present in preparations according to the invention in the form of Paeonia suffruticosa or extract thereof
  • paeonol present in preparations according to the invention in the form of Paeonia suffruticosa or extract thereof
  • the terms paeonol "in the natural form” or “natural paeonol” include glycosides of paeonol such as those found in the plant species in which paeonol is found. Such glycosides include paeonin, paeonolide and paeonoside, for example.
  • compositions according to the invention may comprise paeonol metabolites. These include compounds which are formed by the metabolism of paeonol. Paeonol metabolites include 2, 4-dihydroxyacetophenone-5-0-sulfate, resacetophenone-2-O-sulfate, 2-hydroxy-4-methoxyacetophenone-5-O-sulfate, paeonol-2-O-sulfate, and resacetophenone.
  • the composition may include paeonol or metabolite thereof (e..g paeonol, Paeonia suffruticosa or extract thereof) in an amount which is at least 1% by weight of the total composition.
  • paeonol or metabolite thereof e.g paeonol, Paeonia suffruticosa or extract thereof
  • at least 5% by weight of the composition may be paeonol or metabolite thereof, for example, at least 10%, 15%, 20%, 25% or 30% by weight of the composition may be paeonol or metabolite thereof.
  • a preferred composition comprises a compound of formula (I) or metabolite thereof; a catechin; or a derivative or metabolite of apocynin; and paeonol (or metabolite thereof) wherein the ratio (by weight) of the compound of formula (I) or metabolite thereof; the catechin; or the derivative or metabolite of apocynin; to the paeonol is between about 1 to 100 and about 100 to 1 , preferably between about 1 to 10 and 1 to 30, more preferably between about 1 to 1 and 1 to 20, more preferably between about 1 to 2 and 1 to 10.
  • composition may further comprise Picrorrhiza kurroa.
  • composition may further comprise a gingerol (e.g. 6-gingerol), or a natural source of gingerols such as Zingiber Officinale or extract thereof.
  • a gingerol e.g. 6-gingerol
  • a natural source of gingerols such as Zingiber Officinale or extract thereof.
  • composition according to the invention further may further comprise L- glutamine.
  • composition according to the invention further comprises a filler.
  • Preferred fillers include at least one flavonoid, preferably a mixture of one or more flavonoids.
  • compositions may be used as pharmaceutical compositions, for the treatment of disease in humans, or veterinary compositions, for the treatment of non-human animals.
  • compositions may further comprise additional components such as pharmaceutically conventional carriers, diluents, flavourings, emulsifiers and stabilisers. They may comprise additional components (for example carriers or diluents) which are "conventional" in herbal remedies.
  • the pharmaceutical or veterinary composition may further comprise, for example, one or more of the following: [1] an agent to enhance the immune system, for example lactoferrin which has antiviral antibacterial and antioxidant effects; [2] a natural source of vitamins such as bee pollen; [3] a source, for example a natural source, of vitamins, minerals and amino acids, for example chlorella; [4] a source of trace elements, for example, chromium and/or vanadium and/or copper and/or zinc and/or manganese; and/or [5] taste masking agents, for example yoghurt, fruit juice, honey and syrup.
  • an agent to enhance the immune system for example lactoferrin which has antiviral antibacterial and antioxidant effects
  • a natural source of vitamins such as bee pollen
  • [3] a source, for example a natural source, of vitamins, minerals and amino acids, for example chlorella for example, chromium and/or vanadium and/or copper and/or zinc and/or manganese
  • compositions according to the invention may be useful for treatment of arthritis (including osteoarthritis, rheumatoid arthritis), bowel disease, asthma, COPD (congestive obstructive pulmonary disease), atherosclerosis, inflammation, hypertension, or cancer, or for lowering cholesterol.
  • arthritis including osteoarthritis, rheumatoid arthritis
  • bowel disease including asthma, COPD (congestive obstructive pulmonary disease), atherosclerosis, inflammation, hypertension, or cancer, or for lowering cholesterol.
  • COPD congestive obstructive pulmonary disease
  • atherosclerosis inflammation
  • hypertension or cancer
  • cancer or for lowering cholesterol.
  • compositions may be suitable for oral administration.
  • the methods of formulation of the compositions for oral administration are well known in the art.
  • the composition for administration may be prepared using a pharmaceutically acceptable carrier in a form suitable for administration.
  • a carrier can be prepared as a tablet, a pill, a sugar-coated agent, a capsule, a liquid, a gel, a syrup, a slurry, a suspension, etc.
  • the carrier may be a herbal binder such as Glycyrrhiza glabra or one or more pharmaceutically acceptable carriers such as liposomes, lactose, trehalose, sucrose, mannitol, xylitol, crystalline cellulose, chitosan, calcium carbonate, talc, titanium oxide, or silica (silicon oxide) or the like.
  • a herbal binder such as Glycyrrhiza glabra
  • pharmaceutically acceptable carriers such as liposomes, lactose, trehalose, sucrose, mannitol, xylitol, crystalline cellulose, chitosan, calcium carbonate, talc, titanium oxide, or silica (silicon oxide) or the like.
  • the composition may be obtained, for example, by combining the active ingredients with a solid excipient, pulverizing the mixture (if necessary) and inserting into a capsule, for example, a soft sealed capsule consisting of a gelatin capsule, gelatin and coating (e.g., glycerol or sorbitol) or a capsule composition suitable for vegetarians.
  • a capsule for example, a soft sealed capsule consisting of a gelatin capsule, gelatin and coating (e.g., glycerol or sorbitol) or a capsule composition suitable for vegetarians.
  • the composition may be dissolved or suspended in an appropriate liquid, such as a fatty oil, liquid paraffin or liquid polyethylene glycol, with or without a stabilizer.
  • the formulation may also be in the form of a standardised liquid extract.
  • Standardised liquid extracts may in some circumstances have advantages when compared to the solid dose forms (tablets and hard shell capsules). They may involve minimal processing during manufacture during manufacture and may reflect the true spectrum of the original herb (or plant etc.), in a compact and convenient form. There is also the possibility of superior bioavailability as the preparation is already in the liquid form.
  • the prescribed dose may then be easily diluted (water, fruit juice, adding ice etc.) so as to minimise the experience of any unpleasant taste thus increasing the likelihood of patient compliance.
  • preparations are suitable for other means of administration, for example mucosal delivery routes (for example rectal, nasal, vaginal) and also topical administration.
  • mucosal delivery routes for example rectal, nasal, vaginal
  • topical administration for example topical administration.
  • the methods of formulation of the compositions for use in these methods are well known in the art.
  • a method of treatment of arthritis including osteoarthritis, rheumatoid arthritis), bowel disease, asthma, COPD (congestive obstructive pulmonary disease), atherosclerosis, inflammation, hypertension, or cancer, or a method of lowering cholesterol in a patient, in need thereof, comprising a step of administering to the patient a composition (for example a pharmaceutical composition) comprising: (i) a first component selected from (a) a compound according to formula [I] or metabolite thereof:
  • R 1 or R 2 is H and the other of R 1 or R 2 is C 1 to C 6 branched or straight chain alkyl; (b) a catechin; or (c) a derivative or metabolite of apocynin; and; a second component comprising a ginkgolide or metabolite thereof, a paeonol or metabolite thereof; or 2-hydroxy-4-methoxybenzaldehyde or metabolite thereof.
  • composition for the treatment of cancer, osteoporosis or hypertension comprising: a first component selected from (a) a compound according to formula [I] or metabolite thereof:
  • R 1 or R 2 is H and the other of R 1 or R 2 is C 1 to C 6 branched or straight chain alkyl; (b) a catechin; (c) a derivative or metabolite of apocynin; or (d) apocynin; and a second component comprising a ginkgolide or metabolite thereof, a paeonol or metabolite thereof; or 2-hydroxy-4-methoxybenzaldehyde or metabolite thereof.
  • the present invention in a further aspect also provides compositions as disclosed and defined herein for use in the manufacture of medicaments for the treatment of disease.
  • the following preparation is suitable for the treatment of inflammation in adult humans.
  • This mix packs into a type 'O' capsule (650mg in total) and is taken (based on a human of body weight 60 to 80kg) at a rate of two such capsules twice per day: am and pm.
  • the dose may be increased at the beginning of treatment, (e.g. doubled for the first 1 to 3 days).
  • the following preparation is suitable for the treatment of inflammation in adult humans.
  • This mix packs into a type 'O' capsule (650mg in total) and is taken (based on a human of body weight 60 to 80kg) at a rate of two such capsules twice per day: am and pm.
  • the dose may be increased at the beginning of treatment, (e.g. doubled for the first 1 to 3 days).
  • the dose of the following Examples 3, 4, 5 and 6 for adults and mature children for the the treatment of asthma or reduction of excessive mucous production is 1 ,000 mg (two 500 mg capsules) in the morning and 1 ,000 mg (two 500 mg capsules) in the evening.
  • Example 3 The mixture of Example 3 was divided and prepared in a form suitable for dosing, for example, in a capsule form for oral dose.
  • Example 4 The mixture of Example 4 was divided and prepared in a form suitable for dosing, for example, in a capsule form for oral dose.
  • the mixture of Examples 5 was divided and prepared in a form suitable for dosing, for example, in a capsule form for oral dose.
  • the mixture of Examples 6 was divided and prepared in a form suitable for dosing, for example, in a capsule form for oral dose.
  • Inflammatory cytokines play a major role in osteoclastogenesis, leading to the bone resorption that is frequently associated with osteoporosis.
  • the applicants have shown that paeonol inhibits matrix metalloproteinase enzymes (MMP) activity and IL-1 ⁇ production.
  • MMP matrix metalloproteinase enzymes
  • NADPH oxidase assembly inhibitors inhibit the onset of the inflammatory cascade. This indicates that compositions according to the invention may find use in the treatment of osteoporosis.
  • NADPH oxidase might be a potential target for the treatment of pancreatic fibrosis. This indicates that compositions according to the invention may find use in the treatment of cancer.
  • NADPH oxidases have recently been shown to contribute to the pathogenesis of hypertension.
  • Paeonol inhibits MMP activity and IL-1 ⁇ production.
  • Paeonol upregulates the anti-inflammatory cytokine IL-10.
  • compositions according to the invention which include paeonol plus NADPH inhibitor (e.g. vanillin) may find use in the treatment of hypertension.
  • NADPH inhibitor e.g. vanillin

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  • Health & Medical Sciences (AREA)
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  • Bioinformatics & Cheminformatics (AREA)
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Abstract

La présente invention concerne une composition comprenant une cathécine; un ou des gingkolide(s) ou un métabolite de celui-ci; un paeonol ou un métabolite de celui-ci; ou 2-hydroxy-4- méthoxybenzaldéhyde ou un métabolite de celui-ci.
PCT/GB2009/002113 2008-09-02 2009-09-02 Préparation pharmaceutique comprenant une cathécine Ceased WO2010026375A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
GB0815972A GB2463080A (en) 2008-09-02 2008-09-02 Pharmaceutical preparation
GB0815972.5 2008-09-02

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WO2010026375A1 true WO2010026375A1 (fr) 2010-03-11

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Cited By (4)

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CN102079703A (zh) * 2010-12-16 2011-06-01 苏州大学 一种新型非甾体抗炎药制备方法及其抗炎镇痛作用
CN103342670A (zh) * 2013-07-18 2013-10-09 山东方明药业集团股份有限公司 丹皮酚磺酸钠的纯化方法
CN109045024A (zh) * 2018-09-05 2018-12-21 江苏康缘药业股份有限公司 一种治疗胰纤维化的中药组合物
CN114272237A (zh) * 2022-01-21 2022-04-05 苏州大学附属第一医院 一种用于治疗骨性关节炎的银杏提取物

Families Citing this family (5)

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Publication number Priority date Publication date Assignee Title
WO2012074183A1 (fr) 2010-12-03 2012-06-07 Sinil Pharmaceutical Co., Ltd. Composition pharmaceutique pour prévenir ou traiter des maladies inflammatoires comprenant un extrait de trachelospermi caulis et un extrait de paeonia suffruticosa andrews, et son procédé de préparation
EP2561767A1 (fr) 2011-08-24 2013-02-27 Nestec S.A. Epicatéchine pour soulager les symptômes d'allergie
WO2016046375A1 (fr) * 2014-09-25 2016-03-31 Institut National De La Sante Et De La Recherche Medicale (Inserm) Extrait de theobroma cacao pour son utilisation dans le traitement ou la prévention de troubles associés aux récepteurs tyrosine kinases
GB2547241A (en) * 2016-02-11 2017-08-16 Akl Res & Dev Ltd Anti-inflammatory formulation
GB2568698A (en) * 2017-11-23 2019-05-29 Akl Res & Development Ltd Formulation

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0303277A1 (fr) * 1987-08-12 1989-02-15 Oxo Chemie Ag Utilisation d'extraits de ginkgo biloba pour combattre les processus inflammatoires
WO2002004003A2 (fr) * 2000-07-10 2002-01-17 N.V. Nutricia Composition conçue pour le traitement de l'osteoarthrite
WO2002032435A2 (fr) * 2000-10-19 2002-04-25 Akl Technologies Limited Preparation de soulagement d'une maladie
WO2006106350A1 (fr) * 2005-04-08 2006-10-12 Akl Inflammatory Limited Formulation anti-inflammatoire
CN1899329A (zh) * 2006-07-27 2007-01-24 任长秋 具有降血脂功效的药物组合物
WO2007104985A1 (fr) * 2006-03-16 2007-09-20 Nicholas John Larkins Compositions comprenant de l'apocynine, du ginkgo et du gingembre et leurs utilisations

Family Cites Families (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FI20000004A0 (fi) * 2000-01-03 2000-01-03 Slk Foundation Flavonoidilääke...
US6821536B2 (en) * 2002-11-22 2004-11-23 Quercegen Holdings Llc Antioxidative compositions

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP0303277A1 (fr) * 1987-08-12 1989-02-15 Oxo Chemie Ag Utilisation d'extraits de ginkgo biloba pour combattre les processus inflammatoires
WO2002004003A2 (fr) * 2000-07-10 2002-01-17 N.V. Nutricia Composition conçue pour le traitement de l'osteoarthrite
WO2002032435A2 (fr) * 2000-10-19 2002-04-25 Akl Technologies Limited Preparation de soulagement d'une maladie
WO2006106350A1 (fr) * 2005-04-08 2006-10-12 Akl Inflammatory Limited Formulation anti-inflammatoire
WO2007104985A1 (fr) * 2006-03-16 2007-09-20 Nicholas John Larkins Compositions comprenant de l'apocynine, du ginkgo et du gingembre et leurs utilisations
CN1899329A (zh) * 2006-07-27 2007-01-24 任长秋 具有降血脂功效的药物组合物

Non-Patent Citations (11)

* Cited by examiner, † Cited by third party
Title
CELLULAR AND MOLECULAR TARGETS IN ALLERGY AND CLINICAL IMMUNOLOGY, PROCEEDINGS OF THE SYMPOSIUM OF THE COLLEGIUM INTERNATIONAL ALLERGOLOGICUM, 26TH, ST. JULIAN'S, MALTA, MAY 5-6, 2006 , MEETING DATE 2006, 332-335. EDITOR(S): HOLGATE, STEPHEN; MARONE, 2007 *
CHOI, YONG HWAN ET AL: "Effects of the constituents of Paeonia lactiflora root on arachidonate and NO metabolism", JOURNAL OF APPLIED PHARMACOLOGY , 14(4), 216-219 CODEN: JOAPA6; ISSN: 1225-6110, 2006, XP007910245 *
COOPER KAREN A ET AL: "Cocoa and health: a decade of research", BRITISH JOURNAL OF NUTRITION, vol. 99, no. 1, January 2008 (2008-01-01), pages 1 - 11, XP007910485, ISSN: 0007-1145 *
DATABASE CA [online] CHEMICAL ABSTRACTS SERVICE, COLUMBUS, OHIO, US; SUZUKI, Y. ET AL: "Epigallocatechine -3- gallate reduces allergic lung inflammation in guinea pig asthma -like reaction", XP002555184, retrieved from STN Database accession no. 2008:1016205 *
DATABASE WPI Week 200740, Derwent World Patents Index; AN 2007-413786, XP002555185 *
HIGDON JANE V ET AL: "Tea catechins and polyphenols: Health effects, metabolism, and antioxidant functions.", CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION, vol. 43, no. 1, January 2003 (2003-01-01), pages 89 - 143, XP007910471, ISSN: 1040-8398 *
MUKHTAR H ET AL: "Tea polyphenols: prevention of cancer and optimizing health.", THE AMERICAN JOURNAL OF CLINICAL NUTRITION JUN 2000, vol. 71, no. 6 Suppl, June 2000 (2000-06-01), pages 1698S - 702S ; di, XP007910470, ISSN: 0002-9165 *
PARK W-H ET AL: "Inhibitory effect of GBH on platelet aggregation through inhibition of intracellular Ca<2+> mobilization in activated human platelets", LIFE SCIENCES, PERGAMON PRESS, OXFORD, GB, vol. 75, no. 25, 5 November 2004 (2004-11-05), pages 3063 - 3076, XP004594892, ISSN: 0024-3205 *
PIETTA P ET AL: "Trolox equivalent antioxidant capacity (TEAC) of Ginkgo biloba flavonol and Camellia sinensis catechin metabolites", JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, NEW YORK, NY, US, vol. 23, 1 January 2000 (2000-01-01), pages 223 - 226, XP007910469, ISSN: 0731-7085 *
RAMIRO EMMA ET AL: "Flavonoids from theobroma cacao down-regulate inflammatory mediators", JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY, AMERICAN CHEMICAL SOCIETY, WASHINGTON, US, vol. 53, no. 22, 2 November 2005 (2005-11-02), pages 8506 - 8511, XP002495801, ISSN: 0021-8561, [retrieved on 20050930] *
WANG H-K: "THE THERAPEUTIC POTENTIAL OF FLAVONOIDS", EXPERT OPINION ON INVESTIGATIONAL DRUGS, ASHLEY PUBLICATIONS LTD., LONDON, GB, 1 September 2000 (2000-09-01), pages 2103 - 2119, XP001031837, ISSN: 1354-3784 *

Cited By (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN102079703A (zh) * 2010-12-16 2011-06-01 苏州大学 一种新型非甾体抗炎药制备方法及其抗炎镇痛作用
CN103342670A (zh) * 2013-07-18 2013-10-09 山东方明药业集团股份有限公司 丹皮酚磺酸钠的纯化方法
CN109045024A (zh) * 2018-09-05 2018-12-21 江苏康缘药业股份有限公司 一种治疗胰纤维化的中药组合物
CN114272237A (zh) * 2022-01-21 2022-04-05 苏州大学附属第一医院 一种用于治疗骨性关节炎的银杏提取物

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