WO2008006582A1 - Compositions comprenant du magnolol ou de l'honokiol et d'autres agents actifs pour le traitement de maladies inflammatoires - Google Patents

Compositions comprenant du magnolol ou de l'honokiol et d'autres agents actifs pour le traitement de maladies inflammatoires Download PDF

Info

Publication number
WO2008006582A1
WO2008006582A1 PCT/EP2007/006189 EP2007006189W WO2008006582A1 WO 2008006582 A1 WO2008006582 A1 WO 2008006582A1 EP 2007006189 W EP2007006189 W EP 2007006189W WO 2008006582 A1 WO2008006582 A1 WO 2008006582A1
Authority
WO
WIPO (PCT)
Prior art keywords
hydroxy
composition
acid
butenyl
methoxy
Prior art date
Application number
PCT/EP2007/006189
Other languages
English (en)
Inventor
Daniel Raederstorff
Joseph Schwager
Karin Wertz
Original Assignee
Dsm Ip Assets B.V.
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Dsm Ip Assets B.V. filed Critical Dsm Ip Assets B.V.
Publication of WO2008006582A1 publication Critical patent/WO2008006582A1/fr

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • 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
    • A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
    • A61K31/05—Phenols
    • 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
    • A61K31/365—Lactones
    • 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)
    • A61K36/57—Magnoliaceae (Magnolia family)
    • A61K36/575—Magnolia
    • 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
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/34—Alcohols
    • A61K8/347—Phenols
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
    • A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
    • A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/02—Drugs for skeletal disorders for joint disorders, e.g. arthritis, arthrosis
    • 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]

Definitions

  • the present invention relates to novel compositions comprising magnolol and/ or honokiol and at least one additional component selected from the group of ligustilide, oleuropein (I), oleuropein aglycone (II), tyrosol, hydroxytyrosol, rosehip, genistein, resveratrol, EGCG, glucosamine, methylsulfonylmethane, SAMe, collagen hydrolysate, collagen, ascorbyl phosphate, lycopene, lutein, zeaxanthin, ⁇ -cryptoxanthin, Devil's Claw, milk protein concentrate, solubilized keratin, celery seed extract, cetylated fatty acids, carnitine, thymoquinone, 2-hydroxy-4-methoxy-3-(2- hydroxy-3-methyl-3-butenyl)-6-(2-phenylethyl)-benzoic acid (III), Amorf
  • Inflammatory disorders are one of the most important health problems in the world. Inflammation is in general a localized protective response of the body tissues to invasion of the host by foreign material or injurious stimuli.
  • the causes of inflammation can be infectious agents such as bacteria, viruses, and parasites; or physical agents such as burns or radiation; or chemicals like toxins, drugs or industrial agents; or immunological reactions such as allergies and autoimmune responses or conditions associated with oxidative stress.
  • Inflammation is characterized by pain, redness, swelling, heat, and eventual loss of function of the affected area. These symptoms are the results of a complex series of interactions mainly taking place between the cells of the immune system. The response of the cells results in an interacting network of several groups of inflammatory mediators: Proteins (e.g. cytokines, enzymes [e.g..proteases, peroxydase], major basic protein, adhesion molecules [ICAM, VCAM]), lipid mediators (e.g.,eicosanoids, prostaglandins, leukotrienes, platelet activating factor [PAF]), reactive oxygen species (e.g..hydroperoxides, superoxyde anion O 2 " , nitric oxide [NO] etc).
  • proteins e.g. cytokines, enzymes [e.g..proteases, peroxydase], major basic protein, adhesion molecules [ICAM, VCAM]
  • lipid mediators e.g.,eicosanoids
  • Acute and chronic inflammation resulting from an excessive biosynthesis of inflammatory mediators is involved in numerous inflammatory disorders such as arthritis (e.g. osteoarthritis, rheumatoid arthritis), asthma, inflammatory bowel diseases, inflammatory diseases of the skin (e.g. contact dermatitis [particularly diaper area dermatitis], atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, acne, thermal and radiation burns such as sunburn,) and chronic inflammatory disorders, such as atherosclerosis, heart diseases, metabolic syndrome X, cancer, Alzheimer's disease and pre-stages thereof such as mild cognitive impairment or photoageing which is associated with chronic skin inflammation.
  • arthritis e.g. osteoarthritis, rheumatoid arthritis
  • asthma e.g. contact dermatitis [particularly diaper area dermatitis], atopic dermatitis, xerosis, eczema,
  • Rheumatoid arthritis is a chronic inflammatory disease of the joints and is one of many different forms of arthritis.
  • arthritis includes rheumatoid arthritis, spondyloarthopathies, gouty arthritis, osteoarthritis, systemic lupus erythematosus and juvenile arthritis.
  • rheumatoid arthritis is characterized at the molecular level by chronically unbalanced expression of cytokines, chemokines, kinins and their receptors, adhesion molecules and their respective receptors, as well as inflammatory enzymes.
  • Psoriasis is one of the most common skin problems, affecting 1-3% of the human population.
  • Inflammatory bowel disease is a general term used to describe gastrointestinal tract diseases and includes disorders such as ulcerative colitis and Crohn's disease.
  • Atherosclerosis results from vascular injury which triggers inflammation.
  • Activated macrophages, T-lymphocytes, and eventually smooth muscle cells are present in atherosclerotic plaques.
  • Monocyte/macrophage and lymphocyte activation leads to the release of eicosanoids, cytokines and matrix metalloproteinases (MMPs) which are implicated in endothelial damage, as well as in the formation and eventually the rupture of atherosclerotic plaques.
  • MMPs matrix metalloproteinases
  • CRP C-reactive protein
  • fibrinogen fibrinogen
  • interleukins circulating inflammatory markers
  • CRP C-reactive protein
  • CAD coronary artery diseases
  • Inflammatory processes are also associated with the pathophysiology of Alzheimer's disease. There is evidence of inflammation in the brain of patients with Alzheimer's disease, as it is characterized by increased levels of cytokines and activated microglial cells. Thus, inflammation is not only involved in the classical inflammatory disorders (e.g., arthritis, asthma, bowel diseases) but is also associated with many chronic inflammatory disorders (e.g., atherosclerosis, heart diseases, metabolic syndrome X, cancer, Alzheimer disease).
  • classical inflammatory disorders e.g., arthritis, asthma, bowel diseases
  • chronic inflammatory disorders e.g., atherosclerosis, heart diseases, metabolic syndrome X, cancer, Alzheimer disease.
  • Inflammatory events are also associated with the pathophysiology of different types of cancers (e.g. gastric and intestinal cancers, melanomas). Increased levels of inflammatory mediators such as prostaglandins have been found in cancers of breast, colon, lung and pancreas in humans.
  • cancers e.g. gastric and intestinal cancers, melanomas.
  • Increased levels of inflammatory mediators such as prostaglandins have been found in cancers of breast, colon, lung and pancreas in humans.
  • NSAIDs nonsteroidal anti-inflammatory drugs
  • corticosteroids provide essentially symptomatic relief.
  • Use of corticosteroids has declined due to a growing concern about the serious side effects of prolonged use.
  • NSAIDs are among the most widely used drugs, primarily for the treatment of pain and inflammatory disorders, in particular for the treatment of arthritis (i.e. pain relief).
  • Epidemiological studies have suggested that patients taking NSAIDs have a lower risk of developing Alzheimer's disease than those not taking NSAIDs.
  • a protective effect of NSAIDs suggests that the cyclooxygenases might be involved in the neurodegenerative process.
  • Epidemiological studies showed a significant reduction in the risk of colorectal, gastric, esophageal, and breast cancers among people who take NSAIDs compared with those not taking NSAIDs. In animal models, NSAIDs significantly reduced tumor development.
  • the invention relates to a composition
  • a composition comprising magnolol and/ or honokiol and at least one additional component selected from the group of ligustilide, oleuropein (I), oleuropein aglycone (II), tyrosol, hydroxytyrosol, rosehip, genistein, resveratrol, EGCG, methylsulfonylmethane, SAMe, collagen hydrolysate, collagen, ascorbyl phosphate, lycopene, lutein, zeaxanthin, ⁇ - cryptoxanthin, Devil's Claw, milk protein concentrate, solubilized keratin, celery seed extract, cetylated fatty acids, carnitine, thymoquinone, 2-hydroxy-4-methoxy-3-(2-hydroxy-3-methyl-3- butenyl)-6-(2-phenylethyl)-benzoic acid (III), Amorfrutin B (
  • the invention relates to a composition
  • a composition comprising magnolol and/ or honokiol and at least one additional component selected from the group of ligustilide, oleuropein (I), oleuropein aglycone (II), hydroxytyrosol, rosehip, genistein, resveratrol, EGCG, cashew fruit extract and Glycyrrhiza foetida.
  • the invention relates to a composition comprising magnolol and/ or honokiol and at least one additional component selected from the group of ligustilide, hydroxytyrosol, rosehip, genistein, resveratrol, EGCG, cashew fruit extract and Glycyrrhiza foetida.
  • the invention relates to a composition comprising magnolol and/ or honokiol and at least one additional component selected from the group of ligustilide, rosehip, hydroxytyrosol, genistein, resveratrol and EGCG.
  • the invention relates to a composition
  • a composition comprising magnolol and/ or honokiol and ligustilide.
  • the invention relates to a composition comprising magnolol and/ or honokiol rosehip.
  • the invention relates to a composition
  • a composition comprising magnolol and/ or honokiol and an olive derivable (poly)phenol such as oleuropein (I), oleuropein aglycone (II), tyrosol or hydroxytyrosol, in particular hydroxytyrosol.
  • an olive derivable (poly)phenol such as oleuropein (I), oleuropein aglycone (II), tyrosol or hydroxytyrosol, in particular hydroxytyrosol.
  • the invention relates to a composition
  • a composition comprising magnolol and/ or honokiol and genistein.
  • the invention relates to a composition
  • a composition comprising magnolol and/ or honokiol and resveratrol.
  • the invention relates to a composition
  • a composition comprising magnolol and/ or honokiol and EGCG.
  • composition of the present invention function synergistically in their anti-inflammatory activity.
  • composition of the present invention may be especially useful in the treatment, co-treatment and prevention of inflammatory disorders, such as heart disease, multiple sclerosis, osteo- and rheumatoid arthritis, atherosclerosis, and osteoporosis.
  • composition of the present invention is especially suitable for the treatment, co-treatment and prevention of different forms of arthritis, in particular osteoarthritis and rheumatoid arthritis.
  • compositions of the present invention are suitable as an agent for treatment, co- treatment and prevention of joint disorders in particular for reduction of joint inflammation, maintenance and/or increase of joint health, prevention of joint stiffness, increase of joint mobility, providing supple and/or flexible joints, lubrication of the joints, relief of pain associated with joint inflammation, decrease of joint swelling, lessening joint problems, and providing joint care.
  • the invention also relates to the use of a composition according to the invention as an agent for the treatment, co-treatment or prevention of inflammatory disorders as well as joint disorders.
  • the invention relates to the use of a composition of the invention as an agent for the treatment, co-treatment or prevention of inflammatory disorders more preferably of arthritis or skin inflammation, most preferably of osteoarthritis or sunburn.
  • the invention also relates to the composition of the invention for use as a medicament.
  • the invention relates to the use of a composition according to the invention for the manufacture of a nutraceutical, pharmaceutical, cosmetic or dermatological preparation suitable for the treatment, co-treatment or prevention of inflammatory disorders, more preferably of arthritis or skin inflammation, most preferably of osteoarthritis or sunburn.
  • the invention relates to a method for treatment, co-treatment and prevention of inflammatory disorders, in particular of arthritis, more in particular of osteoarthritis or rheumatoid arthritis, in animals including humans said method comprising the step of administering 'an effective amount of the composition according to the invention' to animals including humans, which are in need thereof.
  • the inflammatory disorder is arthritis, most preferably osteoarthritis.
  • an effective amount of the composition according to the invention' refers to an amount necessary to obtain a physiological effect.
  • the physiological effect may be achieved by one single dose or by repeated doses.
  • the dosage administered may, of course, vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired and can be adjusted by a person skilled in the art.
  • the invention relates to a nutraceutical composition
  • a nutraceutical composition comprising the composition according to the invention and a nutraceutically acceptable carrier.
  • nutraceutical composition as used herein include food product, foodstuff, dietary supplement, nutritional supplement or a supplement composition for a food product or a foodstuff.
  • the present invention relates to a nutraceutical wherein the nutraceutical is a food product, foodstuff, dietary supplement, nutritional supplement or a supplement composition for a food product or a foodstuff.
  • the term food product refers to any food or feed suitable for consumption by humans or animals.
  • the food product may be a prepared and packaged food (e.g., mayonnaise, salad dressing, bread, or cheese food) or an animal feed (e.g., extruded and pelleted animal feed, coarse mixed feed or pet food composition).
  • foodstuff refers to any substance fit for human or animal consumption.
  • dietary supplement refers to a small amount of a compound for supplementation of a human or animal diet packaged in single or multiple dose units. Dietary supplements do not generally provide significant amounts of calories but may contain other micronutrients (e.g., vitamins or minerals).
  • the term nutritional supplement refers to a composition comprising a dietary supplement in combination with a source of calories.
  • nutritional supplements are meal replacements or supplements (e.g., nutrient or energy bars or nutrient beverages or concentrates).
  • Food products or foodstuffs are for example beverages such as non-alcoholic and alcoholic drinks as well as liquid preparation to be added to drinking water and liquid food
  • non-alcoholic drinks are for instance soft drinks, sport drinks, fruit juices, such as for example orange juice, apple juice and grapefruit juice; lemonades, teas, near-water drinks and milk and other dairy drinks such as for example yoghurt drinks, and diet drinks.
  • food products or foodstuffs refer to solid or semi-solid foods comprising the composition according to the invention.
  • These forms can include, but are not limited to baked goods such as cakes and cookies, puddings, dairy products, confections, snack foods, or frozen confections or novelties (e.g., ice cream, milk shakes), prepared frozen meals, candy, snack products (e.g., chips), liquid food such as soups, spreads, sauces, salad dressings, prepared meat products, cheese, yogurt and any other fat or oil containing foods, and food ingredients (e.g., wheat flour).
  • food products or foodstuffs also includes functional foods and prepared food products, the latter referring to any pre-packaged food approved for human consumption.
  • Animal feed including pet food compositions advantageously include food intended to supply necessary dietary requirements, as well as treats (e.g., dog biscuits) or other food supplements.
  • the animal feed comprising the composition according to the invention may be in the form of a dry composition (for example, kibble), semi-moist composition, wet composition, or any mixture thereof.
  • the animal feed is a supplement, such as a gravy, drinking water, yogurt, powder, suspension, chew, treat (e.g., biscuits) or any other delivery form.
  • Dietary supplements of the present invention may be delivered in any suitable format.
  • dietary supplements are formulated for oral delivery.
  • the ingredients of the dietary supplement of this invention are contained in acceptable excipients and/or carriers for oral consumption.
  • the actual form of the carrier, and thus, the dietary supplement itself, is not critical.
  • the carrier may be a liquid, gel, gelcap, capsule, powder, solid tablet (coated or non- coated), tea, or the like.
  • the dietary supplement is preferably in the form of a tablet or capsule and most preferably in the form of a hard (shell) gelatin capsule.
  • Suitable excipient and/or carriers include maltodextrin, calcium carbonate, dicalcium phosphate, tricalcium phosphate, microcrystalline cellulose, dextrose, rice flour, magnesium stearate, stearic acid, croscarmellose sodium, sodium starch glycolate, crospovidone, sucrose, vegetable gums, lactose, methylcellulose, povidone, carboxymethylcellulose, corn starch, and the like (including mixtures thereof).
  • Preferred carriers include calcium carbonate, magnesium stearate, maltodextrin, and mixtures thereof.
  • the various ingredients and the excipient and/or carrier are mixed and formed into the desired form using conventional techniques.
  • the tablet or capsule of the present invention may be coated with an enteric coating that dissolves at a pH of about 6.0 to 7.0.
  • a suitable enteric coating that dissolves in the small intestine but not in the stomach is cellulose acetate phthalate. Further details on techniques for formulation for and administration may be found in the latest edition of Remington's Pharmaceutical Sciences (Maack Publishing Co., Easton, PA).
  • the dietary supplement is provided as a powder or liquid suitable for adding by the consumer to a food or beverage.
  • the dietary supplement can be administered to an individual in the form of a powder, for instance to be used by mixing into a beverage, or by stirring into a semi-solid food such as a pudding, topping, sauce, puree, cooked cereal, or salad dressing, for instance, or by otherwise adding to a food e.g. enclosed in caps of food or beverage container for release immediately before consumption.
  • the dietary supplement may comprise one or more inert ingredients, especially if it is desirable to limit the number of calories added to the diet by the dietary supplement
  • the dietary supplement of the present invention may also contain optional ingredients including, for example, herbs, vitamins, minerals, enhancers, colorants, sweeteners, flavorants, inert ingredients, and the
  • the dietary supplements further comp ⁇ se vitamins and minerals including, but not limited to, calcium phosphate or acetate, t ⁇ basic, potassium phosphate, dibasic, magnesium sulfate or oxide, salt (sodium chlo ⁇ de), potassium chlo ⁇ de or acetate, ascorbic acid, ferric orthophosphate, niacinamide, zinc sulfate or oxide, calcium pantothenate, copper gluconate, riboflavin, beta-carotene, py ⁇ doxine hydrochlo ⁇ de, thiamin mononitrate, folic acid, biotin, chromium chlo ⁇ de or picolonate, potassium iodide, sodium selenate, sodium molybdate, phylloquinone, vitamin D3, cyanocobalamin, sodium selemte, copper sulfate, vitamin A, vitamin C, inositol, potassium iodide Suitable dosage
  • the present invention provides nutritional supplements (e g , energy bars or meal replacement bars or beverages) comp ⁇ sing the composition according to the invention
  • the nut ⁇ tional supplement may serve as meal or snack replacement and generally provide nutrient calories
  • the nut ⁇ tional supplements provide carbohydrates, proteins, and fats in balanced amounts
  • the nut ⁇ tional supplement can further comprise carbohydrate, simple, medium chain length, or polysaccharides, or a combination thereof
  • a simple sugar can be chosen for desirable organoleptic properties
  • Uncooked cornstarch is one example of a complex carbohydrate If it is desired that it should maintain its high molecular weight structure, it should be included only in food formulations or portions thereof which are not cooked or heat processed since the heat will break down the complex carbohydrate into simple carbohydrates, wherein simple carbohydrates are mono- or disaccha ⁇ des
  • the nutritional supplement contains, in one embodiment, combinations of sources of carbohydrate of three levels of chain length (simple, medium and complex, e g , sucrose, maltodext ⁇ ns, and
  • the nutritional supplement can also contain other ingredients, such as one or a combination of other vitamins, minerals, antioxidants, fiber and other dietary supplements (e.g., protein, amino acids, choline, lecithin). Selection of one or several of these ingredients is a matter of formulation, design, consumer preference and end- user.
  • the amounts of these ingredients added to the dietary supplements of this invention are readily known to the skilled artisan. Guidance to such amounts can be provided by the U.S. RDA doses for children and adults.
  • vitamins and minerals that can be added include, but are not limited to, calcium phosphate or acetate, tribasic; potassium phosphate, dibasic; magnesium sulfate or oxide; salt (sodium chloride); potassium chloride or acetate; ascorbic acid; ferric orthophosphate; niacinamide; zinc sulfate or oxide; calcium pantothenate; copper gluconate; riboflavin; beta-carotene; pyridoxine hydrochloride; thiamin mononitrate; folic acid; biotin; chromium chloride or picolonate; potassium iodide; sodium selenate; sodium molybdate; phylloquinone; vitamin D3 ; cyanocobalamin; sodium selenite; copper sulfate; vitamin A; vitamin C; inositol; potassium iodide.
  • the nutritional supplement can be provided in a variety of forms, and by a variety of production methods.
  • the liquid ingredients are cooked; the dry ingredients are added with the liquid ingredients in a mixer and mixed until the dough phase is reached; the dough is put into an extruder, and extruded; the extruded dough is cut into appropriate lengths; and the product is cooled.
  • the bars may contain other nutrients and fillers to enhance taste, in addition to the ingredients specifically listed herein. It is understood by those of skill in the art that other ingredients can be added to those described herein, for example, fillers, emulsifiers, preservatives, etc. for the processing or manufacture of a nutritional supplement.
  • flavors, coloring agents, spices, nuts and the like may be incorporated into the nutraceutical composition.
  • Flavorings can be in the form of flavored extracts, volatile oils, chocolate flavorings, peanut butter flavoring, cookie crumbs, crisp rice, vanilla or any commercially available flavoring.
  • useful flavoring include, but are not limited to, pure anise extract, imitation banana extract, imitation cherry extract, chocolate extract, pure lemon extract, pure orange extract, pure peppermint extract, imitation pineapple extract, imitation rum extract, imitation strawberry extract, or pure vanilla extract; or volatile oils, such as balm oil, bay oil, bergamot oil, cedarwood oil, walnut oil, cherry oil, cinnamon oil, clove oil, or peppermint oil; peanut butter, chocolate flavoring, vanilla cookie crumb, butterscotch or toffee.
  • the dietary supplement contains cocoa or chocolate.
  • Emulsifiers may be added for stability of the nutraceutical compositions.
  • suitable emulsifiers include, but are not limited to, lecithin (e.g., from egg or soy), and/or mono- and di- glycerides.
  • Other emulsifiers are readily apparent to the skilled artisan and selection of suitable emulsifier(s) will depend, in part, upon the formulation and final product.
  • Preservatives may also be added to the nutritional supplement to extend product shelf life.
  • preservatives such as potassium sorbate, sodium sorbate, potassium benzoate, sodium benzoate or calcium disodium EDTA are used.
  • the nutraceutical composition can contain natural or artificial (preferably low calorie) sweeteners, e.g., saccharides, cyclamates, aspartamine, aspartame, acesulfame K, and/or sorbitol.
  • natural or artificial sweeteners e.g., saccharides, cyclamates, aspartamine, aspartame, acesulfame K, and/or sorbitol.
  • artificial sweeteners can be desirable if the nutritional supplement is intended to be consumed by an overweight or obese individual, or an individual with type II diabetes who is prone to hyperglycemia.
  • a multi-vitamin and mineral supplement may be added to the nutraceutical compositions of the present invention to obtain an adequate amount of an essential nutrient, which is missing in some diets.
  • the multi-vitamin and mineral supplement may also be useful for disease prevention and protection against nutritional losses and deficiencies due to lifestyle patterns.
  • the dosage and ratios of magnolol and/ or honokiol and the at least one additional component administered via a nutraceutical will, of course, vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired which can be determined by the expert in the field with normal trials, or with the usual considerations regarding the formulation of a nutraceutical composition.
  • the nutraceutical comprises per serving an amount of 0.01 to Ig, more preferably 0.2 mg to 500 mg of magnolol and/ or honokiol preferably in the form of a magnolia bark extract and at least one component selected from • Ligustilide: 0.5 to 500 mg and/ or • Hydroxytyrosol: 0.2 mg to 500 mg of each, and/ or • Rosehip: 0.1 to 1Og based on the weight of dried rosehip concentrate and/ or
  • Resveratrol 0.2-500 mg, and/ or
  • Glycyrrhiza foetida or one or several compounds selected from formula (III) to (XI): 0.5 - 1000 mg of each, preferably in the form of a Glycyrrhiza foetida extract in the indicated amounts.
  • the invention in another aspect, relates to a pharmaceutical comprising the composition according to the invention and a pharmaceutically acceptable carrier.
  • Suitable pharmaceutical carriers are e.g. described in Remington's Pharmaceutical Sciences, supra, a standard reference text in this field.
  • examples of such pharmaceutically acceptable carriers are both inorganic and organic carrier materials, suitable for oral/parenteral/injectable administration and include water, gelatin, gum arabic, lactose, starch, magnesium stearate, talc, vegetable oils, and the like.
  • the pharmaceutical composition may further comprise conventional pharmaceutical additives and adjuvants, excipients or diluents, including, but not limited to, water, gelatin of any origin, vegetable gums, ligninsulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.
  • conventional pharmaceutical additives and adjuvants, excipients or diluents including, but not limited to, water, gelatin of any origin, vegetable gums, ligninsulfonate, talc, sugars, starch, gum arabic, vegetable oils, polyalkylene glycols, flavoring agents, preservatives, stabilizers, emulsifying agents, buffers, lubricants, colorants, wetting agents, fillers, and the like.
  • the pharmaceutical is in the form of a powder, tablet, capsule, gel, liquid or solid embodiment.
  • the dosages and ratios of the individual components in a pharmaceutical composition can be determined by the expert in the field with normal preclinical and clinical trials, or with the usual considerations regarding the formulation of pharmaceutical composition.
  • magnolol and/ or honokiol is administered via a pharmaceutical composition either in the form of a single dose or by multiple doses in an amount of at least 0.01 mg/ kg bodyweight/ day, preferably in an amount of 0.1-50 mg/ kg body weight/ day, most preferably in an amount of 0.3-15 mg/ kg body weight / day.
  • the nutraceutical and pharmaceutical according to the present invention may be in any galenic form that is suitable for administering to the animal body including the human body, more in particular in any form that is conventional for oral administration, e.g. in solid form, for example as (additives/supplements for) food or feed, food or feed premixes, fortified food or feed, tablets, pills, granules, dragees, capsules, and effervescent formulations such as powders and tablets, or in liquid form, for instance in the form of solutions, emulsions or suspensions, for example as beverages, pastes and oily suspensions.
  • the pastes may be filled into hard or soft shell capsules.
  • nutraceutical and pharmaceutical may be in the form of controlled (delayed) release formulation.
  • pharmaceuticals also include compositions suitable for topical application such as cremes, gels, sprays, dry sticks, powders etc.
  • magnolol as used herein comprises the pure compound also known as 5,5'-Diallyl- 2,2'-biphenyldiol or 5,5'-di-2-propenyl-[l,l'-Biphenyl]-2,2'-diol (CAS [528-43-8]) and plant extracts containing the same.
  • magnolol also comprises etherified or esterified hydroxy derivatives from 5,5'-Diallyl-2,2'-biphenyldiol or 5,5'-di-2-propenyl-[l,l'-Biphenyl]-2,2'-diol.
  • the ester or ether groups may for example be derived from straight or branched alkyl groups having 1 to 26 carbon atoms or from substituted or unsubstituted straight or branched aliphatic, araliphatic or aromatic carboxylic acids having 1 to 26 carbon atoms.
  • etherified hydroxy groups further include glycoside groups.
  • esterified hydroxy group further include glucuronide or sulfate groups.
  • magnolol as used herein is 5,5'-Diallyl-2,2'-biphenyldiol or 5,5'-di-2-propenyl-[l,l'-Biphenyl]-2,2'-diol.
  • honokiol as used herein comprises the pure compound also known as 3',5-Diallyl- 2,4'-biphenyldiol or 3',5-di-2-propenyl-[l ,l'-Biphenyl]-2,4'-diol (CAS [35354-74-6]) and plant extracts containing the same.
  • honokiol also comprises etherified or esterified hydroxy derivatives from 3',5-Diallyl- 2,4'-biphenyldiol or 3',5-di-2-propenyl-[l,l'-Biphenyl]-2,4'-diol.
  • the ester or ether groups may for example be derived from straight or branched alkyl groups having 1 to 26 carbon atoms or from substituted or unsubstituted straight or branched aliphatic, araliphatic or aromatic carboxylic acids having 1 to 26 carbon atoms.
  • etherified hydroxy groups further include glycoside groups.
  • esterified hydroxy group further include glucuronide or sulfate groups.
  • "honokiol" as used herein is 3',5-Diallyl-2,4'-biphenyldiol or 3',5-di-2- propenyl-[ 1 , 1 '-Biphenyl]-2,4'-diol.
  • Magnolol and/ or honokiol may be obtained either by chemical synthesis or by isolation from plant material or by mixtures thereof.
  • magnolol and/ or honokiol may be used in the form of a composition comprising the magnolol and/ or honokiol such as a plant extract.
  • the term magnolol and/ or honokiol encompasses both "natural” (isolated) and "synthetic" (manufactured).
  • magnolol and/ or honokiol also includes any plant material or extract comprising at least one of magnolol or honokiol.
  • the amount of magnolol and/ or honokiol in a plant material or extract is not critical. Preferably an amount of at least 1 wt.% of at least one of magnolol or honokiol based on the total weight of the plant material or extract is present. More preferably an amount of at least 50 wt.%, even more preferably an amount of at least 90 wt. % based on the total weight of the plant material or extract is present.
  • magnolol and/ or honokiol are used in the form of a plant extract derived from the bark of Magnolia officinalis obtainable e.g. by stripping the bark from stems, branches, and roots.
  • the plant extract comprising the biphenyl derivatives may be prepared, for example, by processing a natural source of Magnolia bark such that at least one of magnolol or honokiol has been selectively removed, retained, or enriched.
  • purified magnolol and/ or honokiol can be used to make such compositions.
  • Such a composition can also be prepared, for example, by adding an amount of at least one of magnolol and/ or honokiol to a natural source or processed form of a natural source comprising the magnolol and/ or honokiol.
  • a Magnolia Bark Extract in particular an extract derived from the bark of Magnolia officinalis comprising magnolol as well as honokiol is used in all embodiments of the invention.
  • Plant extracts containing the magnolol and/ or honokiol include extracts from Magnolia officinalis, Magnolia obovata, Magnolia rostrata, Magnolia bilboa, Magnolia biondii, Magnolia quinquepeta, Magnolia sprengeri, Manglietia insignis, Manglietia szechuanica, Manglietia yuyuanensis, Cercidiphyllum japonicum, Machilus thunbergii and others.
  • Magnolol and/ or honokiol are preferably derived from Magnolia bark that may be obtained from conventional and commercially available sources.
  • the Magnolia bark derived magnolol and/ or honokiol are obtainable via a number of methods known in the art.
  • the magnolia bark may be processed by any suitable means to obtain magnolol and/ or honokiol'.
  • Plant extracts containing at least one of magnolol and/ or honokiol may be obtained by conventional extraction of Magnolia bark (optionally in dried or grinded form) with solvents like ethanol, dichloromethane at reflux temperature or at lower temperature.
  • magnolia bark extract may be subjected to further processing steps to enrich the content of magnolol and/ or honokiol. Extraction and/ or purification processes are e.g. described in Journal of Separation Science (2006), 29(3), 351-357 or Journal of Chromatography, A (2004), 1036(2), 171-175 without being limited thereto. If desirable, the extract or the pure isolated compounds may be further derivatized by methods known by a person skilled in the art e.g. using alkylating or acetylating agents in order to obtain the desired derivatives.
  • the plant extract comprising magnolol and/ or honokiol is obtained by supercritical carbon dioxide extraction of Magnolia bark.
  • the magnolol and/ or honokiol may alternatively be obtained by chemical synthesis.
  • Honokiol may e.g. be synthesized starting from 5-bromosalicylic acid and p-hydroxybenzoic acid by utilizing a Pd-catalyzed Suzuki-Miyaura coupling reaction as a key step as described in Bioorganic & Medicinal Chemistry Letters (2004), 14(10), 2621-2625.
  • a synthesis of magnolol is e.g. described in JP 2004292392.
  • magnolol and/ or honokiol are used in the form of an extract from the bark of Magnolia officinalis in compositions according to the invention.
  • Magnolol and/ or honokiol used in compositions according to the invention are preferably employed in a concentration so that at least 0.005 mg/ kg bodyweight/ day are administered to an animal including humans.
  • the daily consumption by an animal including human is in the range of 0.01 to 50 mg/ kg bodyweight/ day, most preferably in an amount of 0.1 to 15 mg/ kg bodyweight / day based on the weight of the pure magnolol and/ or honokiol.
  • a nutraceutical preferably comprises 2mg to 500 mg of magnolol and/ or honokiol per serving.
  • a pharmaceutical may for example comprise magnolol and/ or honokiol in an amount from 1 mg to 500 mg per dosage unit, e.g. per capsule or tablet, of from 5 mg daily dose to 2000 mg per daily dose of a liquid formulation.
  • Ligustilide may be isolated by methods known in the art [see, e.g., Beck J.J. and Stermitz F.R., J. Natural Products, Vol. 58, No. 7, pp. 1047-1055, 1995] from various plants such as Angelica glauca, Angelica acutiloba, Angelica sinensis, Angelicae dahuricae, Ligusticum acutilobum, Ligusticum officinale, Ligusticum sinense, Ligusticum wallichii, Cnidium officinale, Rhizoma Chuanxiong, Pleurospermum hookeri, Trachyspermum roxburghianum, Meum athamanticum, Lomatium torreyi, Scutellaria baicalensis, Opopanax chironium, Cenolophium denudatum, Coriandrum sativuum, Silaum silaus, but may also be synthesized by methods known in the art.
  • ligustilide is used in form of a purified plant extract, e.g., from Ligusticum species, especially L. wallichii, comprising at least 50 wt.-% of ligustilide, and no more than 10 wt.-% of fatty acids and triglycerides as obtainable by the process disclosed in European patent application No. 05 002333.2, the contents of which are incorporated herein by reference.
  • ligustilide is used in an effective dose of 0.01 to 50 mg/kg body weight/day, more preferably 0.1 to 5 mg/kg body weight/day.
  • a nutraceutical preferably comprises 0.5 mg to 500 mg of ligustilide per serving. If the composition is a pharmaceutical, such composition may preferably comprise ligustilide in an amount from 1 mg to 500 mg per dosage unit, e.g., per capsule or tablet, or from 1 mg per daily dose to 2000 mg per daily dose of a liquid formulation.
  • Magnolol and/ or Honokiol is preferably combined with an olive derivable (polyphenol such as oleuropein (I), oleuropein aglycone (II), tyrosol, hydroxytyrosol (in the following referred to as 'phenolic compounds'), or mixtures thereof, more preferably with hydroxytyrosol.
  • an olive derivable polyphenol such as oleuropein (I), oleuropein aglycone (II), tyrosol, hydroxytyrosol (in the following referred to as 'phenolic compounds'), or mixtures thereof, more preferably with hydroxytyrosol.
  • the phenolic compounds may either be of synthetic origin or may be obtained from natural sources such as from products and by-products derived from the olive tree by extraction and/or purification.
  • Products and by products of olive trees encompass olives, olive tree leafs, olive pulps, olive oil, olive-derived vegetation water and olive oil dregs without being limited thereto. Based on the extraction procedure the amount, respectively the ratio of the phenolic compounds can be easily adjusted by a person skilled in the art.
  • the phenolic compounds are derived from olives that may be obtained from conventional and commercially available sources such as growers.
  • hydroxytyrosol has a purity of at least 90%, more preferably a purity of at least 91%, even more preferably a purity of at least 92%, even more preferably a purity of at least 93%, even more preferably a purity of at least 94%, even more in particular a purity of at least 95%, in particular a purity of at least 96%, more in particular a purity of at least 97%, even more in particular a purity of at least 98%, most in particular a purity of at least 99%.
  • the purity of hydroxytyrosol can be determined by methods known to a person skilled in the art such as e.g. by HPLC, or LC-MS.
  • the olive-derived phenolic compounds employed herein can be prepared by a number of methods known in the art.
  • the olives may be processed by any suitable means to obtain the compositions described.
  • the olives and/or olive leaves may be pressed to obtain a mixture including olive oil, vegetation water and solid byproducts.
  • the phenolic compounds may be obtained directly from the mixture or the mixture may be fractionated and/or purified to obtain the phenolic compounds.
  • the compositions may be fractionated and/or purified by a number of methods known to the person skilled in the art. Examples of fractionating methods include partitioning with an organic solvent, chromatography, for example high pressure liquid chromatography (HPLC) or the use of supercritical fluids.
  • HPLC high pressure liquid chromatography
  • references that deal with the extraction of oleuropein and/or hydroxytyrosol from olive leaves are WO02/18310 Al, US 2002/0198415 Al, WO2004/005228 Al , US 6,416,808 and US 2002/0058078 Al which disclose a method for acidic hydrolysis of olive vegetation water for 2 to 12 months until at least 90% of the present oleuropein has been converted.
  • a method of extraction of phenolic compounds from olives, olive pulps, olive oil and oil mill waste water is described by Usana Inc. patents US 6,361,803 and WOO 1/45514 Al and in US 2002/0004077 Al .
  • EP 1 582 512 Al describes an extraction of hydroxytyrosol from olive leaves.
  • a method for obtaining hydroxytyrosol and/or oleuropein from the vegetation water of de-pitted olives is disclosed in US 2004/0039066 Al in paragraphs [0080]-[0O91].
  • hydroxytyrosol containing olive extracts which may be used in combination with rosehip according to the invention include e.g. extracts from olive fruits such as
  • EP 1582512 olive leaf extract, rich in oleuropein, such as available from Furfural and/or HIDROX ® from CreAgri.
  • HIDROX ® from CreAg ⁇
  • HIDROX ® 2% spray dried powder HIDROX ® Gold freeze d ⁇ ed powder (9%) and/ or HIDROX ® 6% freeze dried powder organic olive juice extract
  • hydroxytyrosol may be prepared with a purity > 90%
  • the hydrogenation may be carried out in the presence of a precious metal catalyst such as Pd and Rh, separately or in mixtures, in a manner known per se
  • a precious metal catalyst such as Pd and Rh
  • carriers such as activated carbon, alumina or kieselguhr
  • Pd/C precious metal catalyst
  • the hydrogenation is earned out in the presence of a lower alkanol, i e a Ci i 0 -alkanol, such as methanol, ethanol, propanol, isopropanol, butanol, preferably in methanol or ethanol, preferably in the presence of a strong acid, preferably hydrochloric acid, preferably at a temperature from ambient temperature to 100 0 C or higher, preferably from 40-65 0 C, preferably at a hydrogen pressure at least higher than the vapor pressure of the solvent at the hydrogenation temperature
  • the pressure can be from normal, i e atmospheric pressure, to 100 bar or higher
  • the reaction which is preferably carried out as a through process can be accomplished in two separate steps, i e , a first step wherein an ester of 3,4-dihydroxymandehc acid is built by este ⁇ fication of the acid and a second step wherein the 3,4-dihydroxymandehc acid lower alkyl ester is hydrogenated
  • the reduction of the (3,4-dihydroxyphenyl)-acetic acid Ci io-alkyl ester to give hydroxytyrosol can be achieved in a known manner
  • the preferred reduction agents are complex hyd ⁇ ds of aluminum and boron, such as LiAlH 4 and NaBH 4
  • the starting material, 3,4- dihydroxymandehc acid is well-known and can be prepared in accordance with methods described in the literature, e g , by condensation of catechol with glyoxyhc acid
  • the phenolic compound is preferably used in a concentration so that the daily consumption by an animal including humans (e g weighing about 70 kg) is in the range of from 1 mg/day to 2000 mg/day, more preferably from 5 mg/day to 500 mg/day
  • a nutraceutical composition preferably comprises 0.5 mg to 1000 mg of phenolic compound per serving. If the composition is a pharmaceutical composition such composition may for example comprise a phenolic compound in an amount from 1 mg to 2000 mg per dosage unit, e.g., per capsule or tablet, or from 1 mg per daily dose to 3000 mg per daily dose of a liquid formulation.
  • rosehip examples include dried rosehip concentrate, a lipophilic extract of rosehip (including rosehip oil, rosehip seed oil or a fractionated lipophilic extract) or a hydrophilic extract of rosehips (a rosehip extract comprising water-soluble parts of rosehips, such as for instance polysaccharides).
  • Rosehip extract may be obtained from rosehip, the fruit, petals and/or seeds from wild rose bushes, such as Rosa canina ("dog rose-hip"), Rosa gallica, Rosa condita, Rosa rugosa, Rosa hugonis, Rosa nitida, Rosa pendulina, Rosa pimpinellifolia, and Rosa sericea.
  • Rosa canina dog rose-hip
  • Rosa gallica Rosa condita
  • Rosa rugosa Rosa hugonis
  • Rosa nitida Rosa pendulina
  • Rosa pimpinellifolia Rosa sericea
  • rosehip extract is prepared from the fruit ⁇ i.e. the rosehip).
  • Rosehip is a natural product and hence its composition may vary somewhat.
  • the hydrophilic extract e.g. has a high vitamin C content which might be in the range of 0.6 and 1.5 mg per g and contains as well other vitamins and minerals.
  • An example of a rosehip extract is that produced in accordance with the description in US 6,024,960. Of course, the quantities of the specific vitamins and minerals may vary by species or through use of different extraction/concentration methods.
  • An exemplary rosehip extract is shown in Table I (page 4 and 5) of WO 02/342274, however the invention is not limited thereto.
  • Dried rosehip concentrate can be obtained from dried and milled rosehips that are reduced to powder.
  • a rosehip concentrate may for example be obtained in the following method: Rosehips are harvested in a generally known manner when the hips are fully ripe. Rosehip can be obtained from any of the multiple species of plants that belong to the Rosa family, for example from rosehips from wild rose bushes, such as Rosa canina ("dog rose-hip"), Rosa gallica, Rosa condita, Rosa rugosa, Rosa hugonis, Rosa nitida, Rosa pendulina, Rosa pimpinellifolia, and Rosa sericea, more preferably hips of the Rosa canina are used.. After the hips are harvested, the hips are chopped into pieces.
  • the hips may be frozen for storage.
  • the next step is to dry the chopped rosehips to a water content of about at most 5% by weight.
  • the drying is conducted in such a way that the vitamin content of the rosehips is preserved, for example by drying the rosehips at a temperature below 50°C with air and by avoiding sunlight.
  • the dried and chopped rosehips may then be passed through a separation step in which extraneous matter, for instance nuts, hairs etc., that may have accompanied the rosehips during harvesting is removed.
  • the remaining fruit flesh is then crushed in a grinding mill.
  • the obtained material has a particle size of below 1 mm, more preferably between 0.1 and 0.5 mm.
  • a process for obtaining a dried and milled rosehip concentrate may comprise the following steps: a) harvesting rosehips when the hips are fully ripe b) chopping the harvested rosehips into pieces c) drying the chopped rosehips to a water content of at most 5% by weight d) optionally passing the dried and chopped rosehips through a separation step in which extraneous matter is removed e) optionally the fruit flesh and the seeds may be separated and extracted separately f) crushing the remaining material in a grinding mill to a particle size of below 1 mm.
  • the extract (fraction) comprises at least cyanidin-3-o-glucoside, cyanidin-3-o- rutinoside or glycosides of diacylglycerol such as 3-beta-D-galactopyranosyloxy-2-(octadeca- 9Z, 12Z, 15Z-trienoyloxy)propanyl octadeca-9Z, 12Z, 15Z-trienoate (GOPO), in particular at least GOPO.
  • diacylglycerol such as 3-beta-D-galactopyranosyloxy-2-(octadeca- 9Z, 12Z, 15Z-trienoyloxy)propanyl octadeca-9Z, 12Z, 15Z-trienoate (GOPO), in particular at least GOPO.
  • the rosehip is in the form of a dried rosehip concentrate.
  • Rosehip is preferably used in an amount sufficient to administer to animals including humans (e.g. weighing about 70 kg) a dosage of at least 0.02 g/day based on the weight of dried rosehip concentrate.
  • a dosage of at least 0.02 g/day based on the weight of dried rosehip concentrate Preferably an amount of 0.1 g/day to 30 g/day based on the weight of dried rosehip concentrate, more preferably from 2 g/day to 10 g/day based on the weight of dried rosehip concentrate is used.
  • the daily dosage based on the weight of dried rosehip concentrate is at least 0.3 mg/kg body weight, preferably an average dosage of 1-450 mg/kg body weight, most preferable of 3-140 mg/kg of bodyweight is used.
  • the amount of a dried rosehip concentrate comprised therein is preferably in the range from about 0.1 g to about 10 g, and even more preferably between 0.5 and 2.0 g per serving.
  • the composition is a pharmaceutical composition such composition may for example comprise from 20 mg to 1 g per solid dosage unit, e.g., per capsule or tablet, or for example from 500 mg per daily dose to 6000 mg per daily dose of a liquid formulation.
  • the amount used may be derived from the amount of dried rosehip concentrate and finding the optimal dosage is a matter of routine experimentation for the person skilled in the art.
  • genistein as used herein comprises the aglycone (4', 5, 7-trihydroxyisoflavone) and derivatives thereof, e.g., genistein glycosides, genistein sulfates, genistein glucuronides.
  • Genistein is preferably used in a concentration so that the daily consumption by an animal including humans ⁇ e.g. weighing about 70 kg) is in the range of from 0.5 mg/day to 2000 mg/day.
  • a nutraceutical preferably comprises for example 0.2 mg to 500 mg of genistein per serving.
  • a pharmaceutical composition may for example comprise a genistein in an amount from 0.5 mg to 500 mg per dosage unit, e.g., per capsule or tablet, or from 0.5 mg per daily dose to 2000 mg per daily dose of a liquid formulation.
  • resveratrol as used herein comprises a derivative, metabolite or analogue thereof.
  • the carbon-carbon double bond may be trans or cis and includes cis/trans mixtures.
  • Etherif ⁇ ed or esterified hydroxy groups may be derived from unsubstituted or substituted, straight or branched chain alkyl groups having 1 to 26 carbon atoms or from unsubstituted or substituted, straight or branched chain aliphatic, araliphatic or aromatic carboxylic acids having 1 to 26 carbon atoms.
  • Etherified hydroxy groups may further be glycoside groups and esterified hydroxy groups may further be glucuronide or sulfate groups.
  • Of primary interest for the purposes of the invention is (trans)-res veratrol .
  • Resveratrol is preferably used in amount sufficient to administer to an animal including humans (e.g. weighing about 70 kg) a dosage from 0.5 mg/day to 2000 mg/day, more preferably from 5 mg/day to 500 mg/day.
  • a nutraceutical composition the amount of a resveratrol comprised therein is preferably in the range from 0.2 mg to 500 mg per serving.
  • the composition is a pharmaceutical composition such composition may preferably comprise from 0.5 mg to 500 mg per solid dosage unit, e.g., per capsule or tablet, or from 0.5 mg per daily dose to 2000 mg per daily dose of a liquid formulation.
  • EGCG comprises (-)-epigallocatechin gallate (EGCG in the narrower sense) and/or one or more derivatives (esterified forms, glycosides, sulphates) thereof, or other catechins found in green tea such as (-) epigallocatechin (EGC), (-) epicatechin-3-gallate (ECG), (-) epicatechin (EC), (+) gallocatechin, and (+) catechin and derivatives thereof.
  • ECG epigallocatechin
  • ECG epicatechin-3-gallate
  • EC epicatechin
  • (+) gallocatechin (+) catechin and derivatives thereof.
  • catechin and derivatives thereof Of primary interest for use in the present invention is (-)-epigallocatechin gallate.
  • EGCG is preferably used in a concentration so that the daily consumption by an animal including humans (e.g. weighing about 70 kg) is in the range of from 5 mg/day to 2000 mg/day, preferably from 20 mg/day to 300 mg/day.
  • a nutraceutical composition preferably comprises for 2 mg to 500 mg of EGCG per serving. If the composition is a pharmaceutical composition such composition may comprise EGCG for example in an amount from 5 mg to 500 mg per dosage unit, for example per capsule or tablet, or from 10 mg per daily dose to 2000 mg per daily dose of a liquid formulation.
  • boswellic acid encompasses pure boswellic acid and derivatives thereof as well as extracts comprising boswellic acid.
  • Boswellic extract comprising e.g. 3-O-acetyl-l l-keto-beta- boswellic acid, are known to the person skilled in the art. For instance, it is available on the market in a dietary supplement called 5-LOXIN ® (company PL Thomas). The extract itself it available as WokVel ® from Geni Herbs. It may be extracted from Boswellia serrata.
  • the daily intake by a human adult (weighing approximately 70kg) of boswellic acid (extracts) is preferably between 5 and 1000 mg per day, preferably between 100 and 500 mg per day.
  • a nutraceutical composition preferably comprises between 5 mg and 500 mg of boswellic acid or boswellic acid extract per serving. If the composition is a pharmaceutical composition such composition may preferably comprise boswellic acid or boswellic acid extract in an amount from 50 mg to 500 mg per dosage unit, e.g., per capsule or tablet, or from 50 mg per daily dose to 1000 mg per daily dose of a liquid formulation.
  • Methylsulfonylmethane may be synthesized by methods known to the person skilled in the art.
  • Daily intake of methylsulfonylmethane by a human adult is preferably between 100 and 7000 mg per day, more preferably between 500 and 2000 mg/day, most preferably between 250 and 750 mg per day.
  • a nutraceutical preferably comprises 5 mg to 3000 mg of MSM per serving.
  • a pharmaceutical may preferably comprise MSM in an amount from 10 mg to 1000 mg per dosage unit, e.g., per capsule or tablet, or from 250 mg per daily dose to 750mg per daily dose of a liquid formulation.
  • SAMe is defined as S-adenosylmethionine.
  • SAMe is commercially available and is preferably dosed between 50 and 3000 mg/day. Examples of amounts used in commercially available products are: 200 mg SAMe (from 400 mg of SAMe- tosylate disulfate); 400 mg S-adenosyl L-methionine (from SAMe); 200mg S-adenosyl methionine; 400 mg SAMe (as S-adenosylmethionine 1, 4-butanedisulfonate).
  • a nutraceutical preferably comprises 5 mg to 1000 mg of SAMe per serving.
  • a pharmaceutical may preferably comprise SAMe in an amount from 10 mg to 1000 mg per dosage unit, e.g., per capsule or tablet, or from 10 mg per daily dose to 3000 mg per daily dose of a liquid formulation.
  • Collagen hydrolysate is a protein mixture which may be extracted from animal cartilage. It is commercially available from many supplement companies. Collagen hydrolysate and collagen are commercially available and the daily intake thereof by a human adult (weighing approximately 70kg) is preferably between 500 and 10000 mg per day, preferably between 2000 and 8000 mg per day.
  • Unhydrolyzed or undenatured collagen herein referred to as 'collagen' may be isolated from chicken sternum by methods known to the person skilled in the art.
  • a nutraceutical preferably comprises between 5 mg and 5000 mg of collagen or collagen hydrolysate per serving.
  • a pharmaceutical composition may preferably comprise collagen in an amount from 10 mg to 1000 mg per dosage unit, e.g., per capsule or tablet, or from 10 mg per daily dose to 5000 mg per daily dose of a liquid formulation.
  • corbyl phosphate denotes metal salts of mono- and poly- phosphoric acid esters of ascorbic acid wherein the phosphorylated hydroxy group of the ascorbic acid molecule features one or more phosphoric acid (phosphate) units, and metal cations, e.g. sodium and/or magnesium or calcium ions, are also present.
  • poly generally denotes 2 - 10, preferably 2 - 4, phosphate units.
  • the ascorbyl phosphates may also be referred to in general as
  • ascorbyl (polyphosphates) to embrace both mono- and polyphosphates.
  • Typical ascorbyl phosphates for use in the present invention are L-ascorbic acid phosphate ester salts such as sodium ascorbyl phosphate, potassium ascorbyl phosphate, magnesium ascorbyl phosphate, calcium ascorbyl phosphate and sodium magnesium L-ascorbyl-2-monophosphate.
  • ascorbyl phosphates comprise trisodium L-ascorbyl-2-monophosphate which is available as STAY-C ® 50 from DSM Nutritional Products AG, (4303 Kaiseraugst, Switzerland) and magnesium L-ascorbyl phosphate available from Showa Denko) and sodium magnesium L- ascorbyl-2-monophosphate and L-ascorbic acid-monophosphate which is available as ROVIMIX ® STAY-C ® 35 from DSM Nutritional Products AG, (4303 Kaiseraugst, Switzerland).
  • the preferred ascorbyl phosphate for the purposes of the present invention is trisodium L- ascorbyl-2-monophosphate.
  • the ascorbyl phosphate may be incorporated into the nutraceutical, pharmaceutical, cosmetic or dermatological preparations in many dosage amounts as known to the person skilled in the art.
  • Lycopene ( ⁇ , ⁇ carotene; C 40 H 56 ; CAS-number: 502-65-8) belongs to the carotenoid family and contains 1 1 conjugated double-bonds and an additional two non-conjugated carbon-carbon double-bonds. Lycopene is one of the major dietary carotenoids and is found in various fruits and vegetables, especially in tomatoes and tomato products. It also occurs e.g. in water melon, pink grapefruit, guava.
  • Lycopene is preferably used in a concentration so that the daily consumption by an animal including humans (e.g. weighing about 70 kg) is in the range of from 0.05 mg/day to 50 mg/day, more preferably from 0.5 mg/day to 30 mg/day.
  • a nutraceutical composition preferably comprises 0.05 mg to 50 mg of lycopene per serving. If the composition is a pharmaceutical composition such composition may preferably comprise Lycopene in an amount from 0.5 mg to 50 mg per dosage unit, e.g., per capsule or tablet, or a liquid formulation.
  • cardol diene (XII) is used in the composition of the present invention.
  • Cardol diene (XII) and/ or cardol triene (XIII) is preferably used in a concentration so that the daily consumption by an animal including humans (e.g. weighing about 70 kg) is in the range of from 1 mg/day to 2000 mg/day, preferably from 5 mg/day to 500 mg/day.
  • a nutraceutical composition preferably comprises between 0.2 mg and 1000 mg of cardol diene (XII) and/ or cardol triene (XIII) per serving.
  • the amount of cardol diene (XII) and/ or cardol triene (XIII) may be selected from 0.5 mg and 2000 mg per dosage unit, e.g., per capsule or tablet, or between 1 mg per daily dose and 3000 mg per daily dose of a liquid formulation.
  • Cardol diene (XII) and/ or cardol triene (XIII) may also be used in the form of an extract for instance an - preferably organic phase or supercritical fluid - extract of the cashew plant (Anacardium occidentale)) or a part of the cashew plant, for example in the form of an extract of cashew fruit.
  • Cardol diene (XII) and/ or cardol triene (XIII) may be synthesized or extracted and/or purified by methods known to the person skilled in the art.
  • Cardol diene (XII) and/ or cardol triene (X ⁇ II) are preferably derived from the cashew plant that may be obtained from conventional and commercially available sources such as growers.
  • a number of phenolic compounds are found in Anacardium occidentale, the cashew nut, the cashew nut shell, the cashew apple, and from various Toxicodendron species like T. radicans, T. diversilobum, also from Rhus verniciflua, and Melanorrhoea usitata.
  • Cardol diene (XII) and/ or cardol triene (XIII) as employed herein may be prepared by a number of methods known in the art.
  • the mentioned plants may be processed by any suitable means to obtain the compositions described.
  • cashew apple may be extracted to obtain a mixture.
  • Cardol diene (XII) and/ or cardol triene (XIII) may be obtained directly from the mixture or the mixture may be fractionated and/or purified to obtain cardol diene (XII) and/ or cardol triene (XIII).
  • the compositions may be fractionated and/or purified by a number of methods known to the person skilled in the art. Examples of fractionating methods include partitioning with an organic solvent, chromatography, for example high pressure liquid chromatography (HPLC) or the use of supercritical fluids.
  • HPLC high pressure liquid chromatography
  • Cardol diene (XII) and/ or cardol triene (XIH) can for example be obtained by extraction of dried plant material of Anacardium occidentale with methanol: methyl tert butyl ether (9: 1) and by subsequent fractionation of the thus obtained crude extract by preparative HPLC in a buffered solvent system.
  • Cashew fruit extract is preferably used in such an amount that the amount of cardol diene (XII) and/ or cardol triene (XIII) is as described above.
  • Magnolol and/ or honokiol may also be combined with Glycyrrhiza foetida.
  • the term 1 Glycyrrhiza foetida' encompasses all parts of the plants derived from Glycyrrhiza foetida as well as extracts derived thereof.
  • Magnolol and/ or honokiol may also be combined with compounds isolated from Glycyrrhiza foetida such as 2-hydroxy-4-methoxy-3-(2-hydroxy-3-methyl-3-butenyl)-6-(2-phenylethyl)- benzoic acid (III), Amorfrutin B (IV), Amorfrutin A (V), 2-hydroxy-4-methoxy-3-(3-methyl-2- butenyl)-6-pentyl -benzoic acid (VI), Cannabigerolic acid monomethyl ether (VII), 2-hydroxy-4- methoxy-3-(2-hydroxy-3-methyl-3-butenyl)-6-pentyl-benzoic acid (VIII), 3-methoxy-2-(3- methyl-2-butenyl)-5-(2-phenylethyl)-phenol (IX), the compound of formula (X) and 2-hydroxy-4- methoxy-5-(2-hydroxy-3-methyl-3-butenyl)-6-(2-phen
  • Glycyrrhiza foetida as a whole or parts thereof such as the seedlings, the young plants, the leaves, the flowers (optionally in dried or ground form) or seeds may be used in dried and grinded form or may be extracted conventionally with solvents like ethanol, dichloromethane at reflux temperature or at lower temperature. Alternatively, it may be extracted with supercritical fluids like SF carbondioxyde or by steam distillation of the plant with water followed by sampling of the distilled organic part. Sampling may for example be done by extraction with an organic solvent like dichloromethane, ethylacetate etc. Subsequent removal of the solvent gives the desired Glycyrrhiza foetida extract.
  • the thus obtained Glycyrrhiza foetida extract may be subjected to further processing steps to enrich the content of specific compounds to give an extract of Glycyrrhiza foetida e.g. enriched in 2-hydroxy-4-methoxy-3-(2-hydroxy-3-methyl-3-butenyl)-6-(2-phenylethyl)-benzoic acid (III), Amorfrutin B (IV), Amorfrutin A (V), 2-hydroxy-4-methoxy-3-(3-methyl-2-butenyl)-6- pentyl-benzoic acid (VI), Cannabigerolic acid monomethyl ether (VII), 2-hydroxy-4-methoxy-3- (2-hydroxy-3-methyl-3-butenyl)-6-pentyl-benzoic acid (VIII), 3-methoxy-2-(3-methyl-2- butenyl)-5-(2-phenylethyl)-phenol (IX), the compound of formula (X) and 2-hydroxy-4-
  • All compounds (III) -(XI) can e.g. be obtained by extraction of dried plant material of Glycyrrhiza foetida with methanol: methyl tert butyl ether (MTB) (9: 1) and by subsequent fractionation of the thus obtained crude extract by preparative HPLC, for example in a buffered solvent system or can be synthesized.
  • fractionating methods include partitioning with an organic solvent, chromatography, for example high pressure liquid chromatography (HPLC) or the use of supercritical fluids.
  • HPLC high pressure liquid chromatography
  • the compounds of (III) -(XI) may also be accessible via chemical synthesis)
  • compounds (III) to (XI) are used in the form of an extract derived from Glycyrrhiza foetida.
  • the Glycyrrhiza foetida extract and/or the compounds contained therein are preferably derived from Glycyrrhiza foetida that may be obtained from conventional and commercially available sources such as growers.
  • the Glycyrrhiza foetida as well as the extracts derived thereof are preferably used so that the daily consumption by an animal including humans ⁇ e.g. weighing about 70 kg) is in the range of from 0.5 mg/day to 2000 mg/day, preferably from 5 mg/day to 500 mg/day.
  • a nutraceutical composition preferably comprises 0.5 mg to 1000 mg of a Glycyrrhiza foetida extract. If the composition is a pharmaceutical composition such composition may comprise the Glycyrrhiza foetida extract in an amount from preferably 1 mg to 2000 mg per dosage unit, e.g., per capsule or tablet, or from 1 mg per daily dose to 3000 mg per daily dose of a liquid formulation.
  • the individual compounds isolated from the Glycyrrhiza foetida are preferably used in a concentration so that the daily consumption by an animal including humans (e.g. weighing about 70 kg) is in the range of from 0.5 mg/day to 2000 mg/day, preferably from 5 mg/day to 500 mg/day.
  • a nutraceutical composition preferably comprises 0.5 mg to 1000 mg of such a compound. If the composition is a pharmaceutical composition such composition may comprise one or more of the compounds contained in Glycyrrhiza foetida in an amount from preferably 1 mg to 2000 mg per dosage unit, e.g., per capsule or tablet, or from 1 mg per daily dose to 3000 mg per daily dose of a liquid formulation.
  • the extract is preferably used in such an amount that the amount of individual compound(s) is as described above.
  • Extracts of of Harpagophytum procumbens are on the market.
  • the active ingredient in Devil's Claw is a glycoside called harpagoside.
  • Other constituents of Devil's Claw include beta-sitosterol, harpagide, procumbine, sugars, gum resin and bitter ingredients.
  • Devil's Claw's dosage can easily be determined by the person skilled in the art and is preferably within the same range as on the market.
  • Milk protein concentrate includes milk protein hydrolysates and is commercially available for example as MicroLactinTM from Brandenburg nutrition or as Peptopro from DSM Food Specialities. It's dosage can easily be determined by the person skilled in the art and is preferably within the same range as on the market.
  • Horse chestnut extract refers to an extract obtained from Aesculus hippocastanum comprising a mixture of saponins.
  • the invention relates to a cosmetic or dermatological preparation (the latter preparation are a specific type of a pharmaceutical) comprising an effective amount of the composition of the invention and a cosmetically or dermatologically acceptable carrier.
  • the cosmetic or dermatological composition may further comprise conventional cosmetic respectively dermatological adjuvants and/or additives and/or additional active ingredients.
  • the cosmetic or dermatological preparations are skin care formulations for the treatment, co-treatment or prevention of inflammation of the skin, in particular of sunburn caused by UV-radiation, of contact dermatitis (particularly diaper area dermatitis), atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, thermal burns, photoageing or for the treatment, co-treatment or prevention of impure skin.
  • impure skin include pimples, acne and other skin impurities with an inflammatory aspect.
  • the term "effective amount” means preferably at least 0.001% of each active agents as listed above based on the total weight of the cosmetic or dermatological composition.
  • the cosmetic or dermatological preparations comprise the active agents selected from the list above in an amount between 0.01 wt.-% and 20 wt.-%, more preferably between 0.05 and 10 wt.-%, still more preferably between 0.1 and 5 wt.-%.
  • the amount of the cosmetic or dermatological preparation which is to be applied to the skin depends on the concentration of the active ingredients in the preparation and the desired cosmetic or pharmaceutical effect.
  • the application can be such that a creme is applied to the skin.
  • a creme is usually applied in an amount of about 1 to 2 mg creme/cm 2 skin.
  • the amount of the composition which is applied to the skin is, however, not critical, and if with a certain amount of applied composition the desired effect cannot be achieved, a higher concentration of the active preparations which contain more active ingredient might be employed.
  • the invention also relates to the use of the cosmetic preparation for the cosmetic treatment, co- treatment or prevention of inflammation of the skin, in particular for the cosmetic treatment, co- treatment or prevention of sunburn, contact dermatitis (particularly diaper area dermatitis), atopic dermatitis, xerosis, eczema, rosacea, seborrhea, psoriasis, neurodermitis, thermal burns or photoageing.
  • the invention relates to a method for the treatment, co-treatment or prevention of inflammation of the skin, in particular of sunburn in humans, of impure skin such as for example acne or of photoageing which is associated with chronic skin inflammation, said method comprising the step of administering an effective amount of the dermatological composition according to the invention to humans, which are in need thereof.
  • the invention relates to a method for cosmetic treatment, co-treatment or prevention of inflammation of the skin, in particular of sunburn or of impure skin by a cosmetic preparation according to the invention. Sunburn prevention is preferably achieved with topical application comprising the composition of the invention preferably in combination with suitable light screening agents.
  • the cosmetic or dermatological preparations according to the invention may be in the form of a suspension or dispersion in solvents or fatty substances, or alternatively in the form of an emulsion or micro emulsion (in particular of O/W or W/O type, 0/W/O or W/O/W-type, wherein O stands for oil phase and wherein W stands for water phase), such as a cream, a paste, a lotion, a thickened lotion or a milk, a vesicular dispersion in the form of an ointment, a gel, a solid tube stick or an aerosol mousse, and may be provided in the form of a mousse, foam or a spray foams, sprays, sticks or aerosols or wipes.
  • an emulsion or micro emulsion in particular of O/W or W/O type, 0/W/O or W/O/W-type, wherein O stands for oil phase and wherein W stands for water phase
  • cosmetic or dermatological preparations are skin care preparations, in particular, body oils, body lotions, body gels, treatment creams, skin protection ointments, moisturizing gels, moisturizing sprays, revitalizing body sprays, after sun preparations or sunscreen formulations.
  • the cosmetic or dermatological composition for the treatment, co-treatment or prevention of inflammation of the skin may be in a form that is conventional for oral administration, examples of which are described above and also include beauty foods and supplements.
  • the cosmetic or dermatological preparations of the invention for instance as sunscreen formulations or after sun preparations may further comprise the usual cosmetic respectively dermatological adjuvants and/or additives such as preservatives/ antioxidants, fatty substances/ oils, water, organic solvents, silicones, thickeners, softeners, emulsifiers, additional light screening agents, antifoaming agents, moisturizers, fragrances, surfactants, fillers, sequestering agents, anionic, cationic, nonionic or amphoteric polymers or mixtures thereof, propellants, acidifying or basifying agents, dyes, colorants, pigments or nanopigments, light stabilizers, insect repellants, skin tanning agents, skin whitening agents, antibacterial agents, preservatives active ingredients or any other ingredients usually formulated into cosmetics.
  • preservatives/ antioxidants such as preservatives/ antioxidants, fatty substances/ oils, water, organic solvents, silicones, thickeners, softeners, emulsifiers, additional light screening agents, antif
  • Light screening agents which may be incorporated into cosmetic or dermatological preparations of the invention for instance sunscreen formulations are advantageously selected from IR, UV-A,
  • UV-B, UV-C and/ or broadband filters examples of UV-B or broad spectrum screening agents, i.e. substances having absorption maximums between about 290 and 340 nm may be organic or inorganic compounds.
  • Organic UV-B or broadband screening agents are e.g. acrylates such as 2- ethylhexyl 2-cyano-3,3-diphenylacrylate (octocrylene, PARSOL ® 340), ethyl 2-cyano-3,3- diphenylacrylate and the like; camphor derivatives such as 4-methyl benzylidene camphor
  • Examples of broad spectrum or UV A screening agents 1 e substances having absorption maxima between about 320 and 400 nm may be organic or inorganic compounds e g dibenzoylmethane derivatives such as 4-tert butyl-4'-methoxydibenzoyl-methane (PARSOL® 1789), dimethoxydibenzoylmethane, isopropyl dibenzoylmethane and the like, benzot ⁇ azole derivatives such as 2,2'-methylene-bis-(6-(2H-benzot ⁇ azole-2-yl)-4-(l,l,3,3,-tetramethylbutyl)-phenol (TINOSORB M) and the like, bis-ethylhexyloxyphenol methoxyphenyl t ⁇ azine (Tinosorb S) and the like, phenylene-l,4-bis-benzimidazolsulfonic acids or salts such as 2,2-(l,4-phenylene)bis-
  • microparticulated refers to a particle size from about 5 nm to about 200 nm, particularly from about 15 nm to about 100 nm.
  • the particles may also be coated by other metal oxides such as e.g. aluminum or zirconium oxides or by organic coatings such as e.g. polyols, methicone, aluminum stearate, alkyl silane. Such coatings are well known in the art.
  • conventional UV-A screening agent also refers to dibenzoylmethane derivatives such as e.g. PARSOL ® 1789 stabilized by, e.g. 3,3-
  • Active ingredients which may be included in the cosmetic or dermatological preparations of the invention are for example vitamins and derivatives thereof, for example tocopherol, tocopherol acetate, ascorbic acid, ascorbyl phosphate, vitamin Q, D, and K, retinol, retinal, retinoic acid, retinol acetate, retinol palmitate, biotin, carotenoid derivatives such as beta-carotene, lycopene, asthaxanthin, vegetable extracts, antibacterial ingredients, instable amino acids comprising dipeptides, oligopeptides and polypeptides such as methionine, cysteine, cystine, tryptophan, phenylalanine, tyrosine, phenols, polyphenols or flavanoids, bisabolol, allantoin, phytantriol, panthenol, AHA acids, ubiquinones such as coenzyme Q 10, ceramides, pseudoceramides, essential oils, plant extract
  • the necessary amounts of the cosmetic and dermatological adjuvants, additives and/or additional active ingredients can, based on the desired product, easily be chosen by a person skilled in the art and will be illustrated in the examples, without being limited hereto.
  • the invention relates to the use of magnolol and/ or honokiol for enhancing the anti -inflammatory activity of one or several compounds selected from the group of ligustilide, oleuropein (I), oleuropein aglycone (H), tyrosol, hydroxytyrosol, rosehip, genistein, resveratrol, EGCG, methylsulfonylmethane, SAMe, collagen hydrolysate, collagen, ascorbyl phosphate, lycopene, lutein, zeaxanthin, ⁇ -cryptoxanthin, Devil's Claw, milk protein concentrate, solubilized keratin, celery seed extract, cetylated fatty acids, carnitine, thymoquinone, 2-hydroxy- 4-methoxy-3-(2-hydroxy-3-methyl-3-butenyl)-6-(2-phenylethyl)-benzoic acid (III), Amor
  • the invention relates to the use of magnolol and/ or honokiol for enhancing the anti -inflammatory activity of one or several compounds selected from the group of from the group of ligustilide, rosehip, hydroxytyrosol, genistein, resveratrol and/ or EGCG.
  • the invention relates to the use of magnolol and/ or honokiol for enhancing the anti- inflammatory activity of ligustilide.
  • the invention relates to the use of magnolol and/ or honokiol for enhancing the anti -inflammatory activity of rosehip.
  • inventions relate to the use of magnolol and/ or honokiol for enhancing the anti -inflammatory activity of an olive derivable (polyphenol such as oleuropein (I), oleuropein aglycone (II), tyrosol or hydroxytyrosol, in particular hydroxytyrosol.
  • an olive derivable polyphenol such as oleuropein (I), oleuropein aglycone (II), tyrosol or hydroxytyrosol, in particular hydroxytyrosol.
  • the invention relates to the use magnolol and/ or honokiol for enhancing the anti-inflammatory activity of genistein.
  • the invention relates to use of magnolol and/ or honokiol for enhancing the anti-inflammatory activity of resveratrol.
  • the invention relates to use of magnolol and/ or honokiol for enhancing the anti-inflammatory activity of EGCG.
  • the invention also relates to a method of enhancing the efficacy of magnolol and/ or honokiol which comprises adding to a composition containing magnolol and/ or honokiol an effective amount of one or several components selected from the group of ligustilide, oleuropein (I), oleuropein aglycone (II), tyrosol, hydroxytyrosol, rosehip, genistein, resveratrol, EGCG, methylsulfonylmethane, SAMe, collagen hydrolysate, collagen, ascorbyl phosphate, lycopene, lutein, zeaxanthin, ⁇ -cryptoxanthin, Devil's Claw, milk protein concentrate, solubilized keratin, celery seed extract, cetylated fatty acids, carnitine, thymoquinone, 2-hydroxy-4-methoxy-3-(2- hydroxy-3-methyl-3-but
  • an effective amount' refers to an amount necessary to obtain a synergistic effect.
  • the dosage may, of course, vary depending upon known factors, such as the physiological characteristics of the particular composition and its mode and route of administration; the age, health and weight of the recipient; the nature and extent of the symptoms; the kind of concurrent treatment; the frequency of treatment; and the effect desired and can be adjusted by a person skilled in the art.
  • the invention relates to a method of enhancing the efficacy of magnolol and/ or honokiol which comprises adding to a composition containing magnolol and/ or honokiol an effective amount of ligustilide.
  • the invention in another preferred embodiment relates to a method of enhancing the efficacy of magnolol and/ or honokiol which comprises adding to a composition containing magnolol and/ or honokiol an effective amount of rosehip.
  • invention relates to a method of enhancing the efficacy of magnolol and/ or honokiol which comprises adding to a composition containing magnolol and/ or honokiol an effective amount of an olive derivable (poly)phenol such as oleuropein (I), oleuropein aglycone (II), tyrosol or hydroxytyrosol, in particular hydroxytyrosol.
  • the invention relates to a method of enhancing the efficacy of magnolol and/ or honokiol which comprises adding to a composition containing magnolol and/ or honokiol an effective amount of genistein.
  • the invention relates to a method of enhancing the efficacy of magnolol and/ or honokiol which comprises adding to a composition containing magnolol and/ or honokiol an effective amount of resveratrol.
  • the invention relates to a method of enhancing the efficacy of magnolol and/ or honokiol which comprises adding to a composition containing magnolol and/ or honokiol an effective amount of EGCG.
  • compositions according to the invention are also suitable for the treatment, co-treatment or prevention of another joint disorder namely cartilage degradation or cartilage damage in joints and as such for treatment of the cartilage degradation component of joint disorders, for example degenerative joints disorders such as osteoarthritis; or sport injuries.
  • Cartilage degradation is defined within the framework of the invention as a metabolic disorder of joint cartilage characterized by increased production of cartilage-degrading enzymes such as matrix metalloproteases.
  • Osteoarthritis is a chronic degenerative disease of the joint of non-inflammatory origin, which develops by wear and tear of the joints during aging and results in pain and diminished joint function. Symptoms of osteoarthritis include pain, stiffness and loss of mobility in one or more joints. Excessive joint loading increases the risk of osteoarthritis, hence osteoarthritis mostly affects the weight-bearing joints such as spine, knees and hips, but thumb and finger joints may also be affected. Joint disorders can also results from injury, i.e. microdamage or blunt trauma, fractures, damage to tendons, menisci or ligaments or can be the result of excessive mechanical stress or other biomechanical instability resulting from for example an injury or obesity.
  • Joint disorders due to cartilage degradation are leading causes of disability and dysfunction in the elderly; almost 80% of people over age 60 show some evidence of these disorders.
  • Age, genetic factors, muscle disuse and weakness, trauma, obesity and anatomical abnormalities contribute to the development of the disorder. Joint disorders are difficult to treat.
  • treatment was largely limited to addressing the symptoms mainly with non-steroidal anti-inflammatory drugs.
  • the drugs are given to control the pain and to restrain swelling, but do not prevent or treat damage to the cartilage.
  • the patients experiencing severe cartilage damage frequently require surgery, including joint replacement surgery. Therefore, there was a great need for agents that treat or prevent cartilage loss and damage, which need has been solved by the present invention.
  • compositions of the present invention may have one or more of the following properties: it maintains and/or improves joint health, it prevents joint stiffness, it promotes joint mobility, it provides supple and/or flexible joints, it lubricates the joints, it relieves arthritis pain, it lessens joint problems, it provides joint care, it treats or prevents joint degradation, it provides joint integrity, it retards or prevents the progression of joint damage, it supports joint function, it promotes joint health and function, it naturally supports joint health and mobility for active individuals, it maintains the active flexibility of joints, it promotes joint flexibility and promotes joint mobility.
  • further objects of the present invention are: it maintains and/or improves joint health, it prevents joint stiffness, it promotes joint mobility, it provides supple and/or flexible joints, it lubricates the joints, it relieves arthritis pain, it lessens joint problems, it provides joint care, it treats or prevents joint degradation, it provides joint integrity, it retards or prevents the progression of joint damage, it supports joint function, it promotes joint health and function
  • composition according to the invention as cartilage-regenerating and - maintaining agents.
  • a method for the regeneration and/or maintenance of (articular) cartilage in a mammal which comprises administering to a mammal in need of such regeneration and/or maintenance an effective amount of a composition according to the invention.
  • Group (A) is defined as the following group of compounds: ligustilide, oleuropein (I), oleuropein aglycone (II), tyrosol, hydroxytyrosol, rosehip, genistein, resveratrol, EGCG, methylsulfonylmethane, SAMe, collagen hydrolysate, collagen, ascorbyl phosphate, lycopene, lutein, zeaxanthin, ⁇ -cryptoxanthin, Devil's Claw, milk protein concentrate, solubilized keratin, celery seed extract, cetylated fatty acids, carnitine, thymoquinone, 2-hydroxy- 4-methoxy-3-(2-hydroxy-3-methyl-3-butenyl)-6-(2-phenylethyl)-benzoic acid (III), Amorfrutin B (IV), Amorfrutin A (V), 2-hydroxy-4-methoxy-3-
  • Example 1 Synergistic effect The anti-inflammatory effects of combinations of magnolia bark extracts [MBE] (or its main constituents honokiol and magnolol) and representatives of other groups of natural substances such as resveratrol, EGCG, ligustilide and hydroxytyrosol were evaluated in activated macrophages by determining the inhibition of the synthesis of nitric oxide and/or proinflammatory prostaglandins (PG).
  • PGE 2 plays a critical role in the inflammation process, while nitric oxide (NO) is a hallmark of inflammation in various chronic inflammatory diseases including various forms of arthritis, gastro-intestinal diseases and metabolic syndrome.
  • NO nitric oxide
  • Resveratrol, ligustilide, EGCG and genistein was synthesized by DSM Nutritional Products. Hydroxytyrosol was from Cayman Chemicals or synthesized by DSM Nutritional Products. Magnolol and Honokiol were from Apin Chemicals Ltd, UK. Magnolia Bark extract was from Novanat Bioresources Co. Ltd. China and contained according to the specification > 80% Magnolol and Honokiol.
  • the anti inflammatory effect of compounds was tested in cellular assays using a murine macrophage indicator cell line, RAW267.7, which were purchased from American Type Culture Collection (ATCC) and cultured in DMEM Cells ( ⁇ 50'000/well) were seeded into flat-bottomed microtiter plates and cultured for one day. Cells were then starved in complete medium containing 0.25% FCS (D-025). After overnight culture, medium was removed and replaced by 100 ⁇ L of D-025 containing the test compounds at twice the final concentration. Subsequently, 100 ⁇ L of D-025 containing 2 ⁇ g/ml lipopolysaccaride (LPS) was added ⁇ i.e.
  • APC American Type Culture Collection
  • magnolia bark extract when combined with resveratrol, ligustilide, EGCG or hydroxytyrosol (OH-Tyrosol), synergistically inhibits nitric oxide production.
  • a positive value for ⁇ means that the two substances out-perform the inhibitory power of the two individual components of the mixture. With 'observed' is meant the actual observed inhibition. With 'additive' is meant the theoretical sum of the inhibition of the two compounds.
  • magnolia bark when combined with EGCG, resveratrol or genistein synergistically inhibit PGE 2 production.
  • Additive ⁇ (compound A (e.g. MB) + compound B (e.g. RES/ LIG etc.))
  • Additive ⁇ (compound A (e.g. MB) + compound B (e.g. RES etc.))
  • Soft gelatin capsules are prepared by conventional procedures providing a dose of magnolol and/ or honokiol of 100 mg and at least one compound selected from the group of Group (A) as defined above of 50 mg (e.g. EGCG).
  • a suitable daily dose is 1 to 8 capsules.
  • Other ingredients glycerol. Water, gelatine, vegetable oil
  • Example 3 Hard gelatin capsules are prepared by conventional procedures providing a dose of magnolol and/ or honokiol of 75 mg and at least one component selected from the group of Group (A) as defined above of 100 mg (EGCG). A suitable daily dose is 1 to 5 capsules.
  • Tablets are prepared by conventional procedures providing as active ingredient 50 mg of magnolol and/ or honokiol per tablet and at least one component selected from the group of Group (A) as defined above of 50 mg Ligustilide, and as excipients microcrystalline cellulose, silicone dioxide (SiO 2 ), magnesium stearate, crospovidone NF (which is a disintegration agent) ad 500 mg.
  • Group (A) as defined above of 50 mg Ligustilide
  • Example 5 soft drink An orange juice drink coloured with beta-Carotene 10% CWS and with magnolol and/ or honokiol and at least one component selected from the group of Group (A) as defined above e.g. Genistein may be prepared as follows: Ingredients FgI
  • Lemon Juice Concentrate 45°Brix 173.3 Oily orange flavour 5.0 beta-Carotene 10% C WS as 10% stock solution 10.0
  • Example 6 Preparation of a dermatological composition comprising magnolol and/ or honokiol (treatment cream) which may be used for (cosmetic) treatment of inflammation of the skin caused by sunburn.
  • a treatment cream may be prepared with the following ingredients, in the following amounts:
  • Example 10 Anti pimple skin-tonic
  • Example 11 Anti-acne treatment with Stav-C 50
  • Example 13 Dry dog feed comprising magnolol and/ or honokiol and genistein
  • Commercial dry dog food Hill's Science diet "Canine Maintenance dry” for dogs as supplied by Hill's Pet Nutrition GmbH, Liebigstrasse 2-20, D- 221 13
  • a suspension of magnolol and/ or honokiol and genistein in an amount sufficient to administer to a subject a daily dose of 0.5 mg to 1 mg of magnolol and/ or honokiol and 0.1 mg to 3 mg genistein per kg body weight.
  • Vitamin C and E and beta-carotene are incorporated in an amount sufficient to provide 30 mg vitamin C/kg, and 300 IU vitamin E/kg and 280 mg beta-carotene/kg in the final food composition before extruding the entire blend.
  • the food composition is dried to contain dry matter of about 90 % by weight.
  • Example 14 Wet cat food comprising magnolol and/ or honokiol and sodium ascorbyl phosphate
  • Commercial wet cat food Hill's Science diet "Feline Maintenance wet” for cats as supplied by Hill's Pet Nutrition GmbH, Liebigstrasse 2-20, D- 22113
  • magnolol and/ or honokiol in an amount sufficient to administer to a subject a daily dose of 1 mg to 5 mg magnolol and/ or honokiol.
  • ROVIMIX ® STAY-C ® 35 available from DSM Nutritional Products AG, Vitamin E and beta-carotene are incorporated in an amount sufficient to provide 30 mg ROVIMIX ® STAY-C ® 35/kg, and 300 IU vitamin E/kg and 280 mg beta-carotene/kg in the final food composition before cooking the entire blend.
  • the food composition is dried to contain a dry matter of about 90 % by weight.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Birds (AREA)
  • Chemical & Material Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Rheumatology (AREA)
  • Dermatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Emergency Medicine (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Medical Informatics (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Immunology (AREA)
  • Pain & Pain Management (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)

Abstract

La présente invention concerne de nouvelles compositions comprenant du magnolol et/ou de l'honokiol et au moins un autre composant, choisi p. ex. parmi le ligustilide, l'oleuropéine (I), l'oleuropéine aglycone (II), l'hydroxytyrosol, le cynorrhodon, la génistéine, le resvératrol, l'EGCG, l'extrait de fruit de cajou et Glycyrrhiza foetida, ainsi que l'utilisation de ces compositions comme médicament, en particulier pour traiter, cotraiter ou prévenir des troubles inflammatoires.
PCT/EP2007/006189 2006-07-14 2007-07-12 Compositions comprenant du magnolol ou de l'honokiol et d'autres agents actifs pour le traitement de maladies inflammatoires WO2008006582A1 (fr)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
EP06014644 2006-07-14
EP06014644.6 2006-07-14

Publications (1)

Publication Number Publication Date
WO2008006582A1 true WO2008006582A1 (fr) 2008-01-17

Family

ID=37309747

Family Applications (1)

Application Number Title Priority Date Filing Date
PCT/EP2007/006189 WO2008006582A1 (fr) 2006-07-14 2007-07-12 Compositions comprenant du magnolol ou de l'honokiol et d'autres agents actifs pour le traitement de maladies inflammatoires

Country Status (1)

Country Link
WO (1) WO2008006582A1 (fr)

Cited By (29)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008130752A2 (fr) * 2007-04-19 2008-10-30 Mary Kay Inc. Compositions contenant un extrait de magnolia
EP2070523A1 (fr) * 2007-12-11 2009-06-17 DSM IP Assets B.V. Composition comprenant Magnolol et Honokiol en quantités synergiques
EP2070524A1 (fr) * 2007-12-11 2009-06-17 DSM IP Assets B.V. Nouvelles compositions comprenant Magnolol et/ou Honokiol et Glucosamine et leur utilisation pour le traitement, le cotraitement ou la prévention de maladies inflammatoires
EP2070525A1 (fr) * 2007-12-11 2009-06-17 DSM IP Assets B.V. Nouvelles compositions comprenant Magnolol et/ou Honokiol et chondroïtine et leur utilisation pour le traitement, le cotraitement ou la prévention de maladies inflammatoires
WO2009131470A1 (fr) * 2008-04-24 2009-10-29 Fonterra Co-Operative Group Limited Compositions et procédés pour le maintien de la santé des os ou pour la réduction de la perte osseuse
FR2933300A1 (fr) * 2008-07-02 2010-01-08 Europ Finances Compositions comprenant au moins une lignane et/ou neolignane en association avec un compose actif contre l'acne
WO2010018458A3 (fr) * 2008-08-12 2010-04-08 Crystalgenomics, Inc. Dérivés de phénol et leurs procédés d'utilisation
DE102009048044A1 (de) * 2009-10-02 2011-04-21 Beiersdorf Ag Verwendung von Magnolol oder Honokiol als antibakterielle, antimycotische, antiparasitäre oder antivirale Wirkstoffe
DE102010015793A1 (de) * 2010-04-20 2011-10-20 Beiersdorf Ag Wirkstoffkombination aus Magnolienrindenextrakt und einem oder mehreren grenz- oder oberflächenaktiven Phosphorsäureestern
DE102010015792A1 (de) * 2010-04-20 2011-10-20 Beiersdorf Ag Wirkstoffkombinationen aus Magnolienrindenextrakt und oberflächenaktiven Agentien
US20120128737A1 (en) * 2009-06-22 2012-05-24 Gelita Ag Compositions for treating degenerative joint diseases
CN102520112A (zh) * 2011-12-16 2012-06-27 重庆天生药业有限公司 一种厚朴精制饮片的质量控制方法
US20120294812A1 (en) * 2010-02-24 2012-11-22 Colgate-Palmolive Company Oral care compositions
WO2012033646A3 (fr) * 2010-09-10 2013-04-25 Mary Kay Inc. Formulations topiques de soin de la peau contenant de la pulpe de jaboticaba et de noix de cajou et des extraits de ceux-ci
WO2014005597A1 (fr) * 2012-07-06 2014-01-09 Axellus A/S Composition de cynorrhodon, procédé pour la fabrication de la composition de cynorrhodon et ladite composition destinée à être utilisée dans un procédé pour l'entretien d'articulations souples et d'une inflammation réduite
CN103553888A (zh) * 2013-11-07 2014-02-05 蚌埠医学院 和厚朴酚衍生物及其制备方法和在制备抗肿瘤药物中的应用
CN103585135A (zh) * 2012-08-14 2014-02-19 赖媛淑 厚朴酚在制备治疗恶病质及癌症的药物中的应用
WO2015006651A1 (fr) * 2013-07-11 2015-01-15 Specialty Nutrition Group, Inc. Compositions comprenant un hydroxytyrosol, un resvératrol, un lycopène, des flavanols, et/ou des flavonoïdes et leur utilisation
CN104667045A (zh) * 2014-01-24 2015-06-03 潍坊医学院 治疗顽固性痤疮的药物
US20180042962A1 (en) * 2016-08-15 2018-02-15 Summit Innovation Labs LLC Vascular Calcification Prevention and Treatment
CN109498617A (zh) * 2018-12-26 2019-03-22 南京中医药大学 藁本内酯在制备防治骨质疏松症药品中的应用
US10342802B2 (en) * 2016-10-04 2019-07-09 Nutramax Laboratories, Inc. Compositions comprising hydroxytyrosol and boswellic acid
US10932480B2 (en) 2016-01-29 2021-03-02 Klaus Neufeld Animal feed additive containing diurnosid and/or cestrumosid
WO2021225756A1 (fr) * 2020-05-07 2021-11-11 Innophos, Llc Compositions et méthodes pour des articulations saines
CN113717683A (zh) * 2021-09-27 2021-11-30 武汉纺织大学 一种光固化水下生物基抗菌胶粘剂及其制备方法
US11357250B2 (en) 2016-08-15 2022-06-14 Summit Innovation Labs LLC Treatment and prevention of diabetes and obesity
WO2022238388A1 (fr) * 2021-05-10 2022-11-17 Tomcat International Limited Composition cosmétique anti-vieillissement à base de resvératrol et de magnolia
CN117731710A (zh) * 2023-12-20 2024-03-22 南开大学 一种具有晒后皮肤舒缓和镇痛功效的组合物及其应用
US11980624B2 (en) 2016-10-04 2024-05-14 Nutramax Laboratories, Inc. Methods for administering compositions comprising hydroxytyrosol and boswellic acid

Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5922756A (en) * 1998-02-14 1999-07-13 Chan; Marion Man-Ying Method of inhibiting nitric oxide synthase
WO1999059561A2 (fr) * 1998-05-18 1999-11-25 Hensley, Kenneth, L. Inhibition de myeloperoxydase par du resveratrol
US6024960A (en) * 1998-04-17 2000-02-15 Otto Torbjorn Hansen And Marianne Hansen Rose-hip formulations as anti-inflammatory natural medicine for alleviating/reducing symptoms associated with inflammation and arthritis
WO2001076579A1 (fr) * 2000-04-06 2001-10-18 Perricone Nicholas V Traitement des lesions cutanees a l'aide des polyphenols de l'huile d'olive
US20030152657A1 (en) * 2001-12-17 2003-08-14 The Chinese University Of Hong Kong Active compounds of Bao-Ji-Wan for anti-diarrhea and relieving gastrointestinal symptoms
US20060018975A1 (en) * 2004-07-20 2006-01-26 Talbott Shawn M Methods and compositions for weight management and mood enhancement
US20060110415A1 (en) * 2004-11-22 2006-05-25 Bioderm Research Topical Delivery System for Cosmetic and Pharmaceutical Agents
US20060134024A1 (en) * 2004-12-22 2006-06-22 Colgate-Palmolive Company Antibacterial and anti-inflammatory oral care composition
US20060140885A1 (en) * 2004-12-29 2006-06-29 Abdul Gaffar Method of reducing oral tissue inflammation using magnolia extract
WO2006125651A2 (fr) * 2005-05-24 2006-11-30 Dsm Ip Assets B.V. Nouvelle utilisation de composes organiques

Patent Citations (10)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5922756A (en) * 1998-02-14 1999-07-13 Chan; Marion Man-Ying Method of inhibiting nitric oxide synthase
US6024960A (en) * 1998-04-17 2000-02-15 Otto Torbjorn Hansen And Marianne Hansen Rose-hip formulations as anti-inflammatory natural medicine for alleviating/reducing symptoms associated with inflammation and arthritis
WO1999059561A2 (fr) * 1998-05-18 1999-11-25 Hensley, Kenneth, L. Inhibition de myeloperoxydase par du resveratrol
WO2001076579A1 (fr) * 2000-04-06 2001-10-18 Perricone Nicholas V Traitement des lesions cutanees a l'aide des polyphenols de l'huile d'olive
US20030152657A1 (en) * 2001-12-17 2003-08-14 The Chinese University Of Hong Kong Active compounds of Bao-Ji-Wan for anti-diarrhea and relieving gastrointestinal symptoms
US20060018975A1 (en) * 2004-07-20 2006-01-26 Talbott Shawn M Methods and compositions for weight management and mood enhancement
US20060110415A1 (en) * 2004-11-22 2006-05-25 Bioderm Research Topical Delivery System for Cosmetic and Pharmaceutical Agents
US20060134024A1 (en) * 2004-12-22 2006-06-22 Colgate-Palmolive Company Antibacterial and anti-inflammatory oral care composition
US20060140885A1 (en) * 2004-12-29 2006-06-29 Abdul Gaffar Method of reducing oral tissue inflammation using magnolia extract
WO2006125651A2 (fr) * 2005-05-24 2006-11-30 Dsm Ip Assets B.V. Nouvelle utilisation de composes organiques

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
FRETLAND D J ET AL: "INHIBITION OF NITRIC OXIDE SYNTHASE AND PROSPECTS FOR THERAPY IN INFLAMMATORY DISEASES", CHEMICAL ABSTRACTS + INDEXES, AMERICAN CHEMICAL SOCIETY. COLUMBUS, US, vol. 128, no. 7, 1998, pages 3, XP002942380, ISSN: 0009-2258 *
TZENG S-C ET AL: "Peroxidase-catalyzed synthesis of neolignan and its anti-inflammatory activity", JOURNAL OF MOLECULAR CATALYSIS. B, ENZYMATIC, ELSEVIER, AMSTERDAM,, NL, vol. 32, no. 1-2, 22 December 2004 (2004-12-22), pages 7 - 13, XP004654609, ISSN: 1381-1177 *
VERDRENGH M ET AL: "Genistein as an anti-inflammatory agent.", INFLAMMATION RESEARCH : OFFICIAL JOURNAL OF THE EUROPEAN HISTAMINE RESEARCH SOCIETY ... [ET AL.] AUG 2003, vol. 52, no. 8, August 2003 (2003-08-01), pages 341 - 346, XP002459442, ISSN: 1023-3830 *

Cited By (53)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US9844503B2 (en) 2007-04-19 2017-12-19 Mary Kay Inc. Magnolia extract containing compositions
US9101555B1 (en) 2007-04-19 2015-08-11 Mary Kay Inc. Magnolia extract containing compositions
US10434056B2 (en) 2007-04-19 2019-10-08 Mary Kay Inc. Magnolia extract containing compositions
US9622965B2 (en) 2007-04-19 2017-04-18 Mary Kay Inc. Magnolia extract containing compositions
WO2008130752A2 (fr) * 2007-04-19 2008-10-30 Mary Kay Inc. Compositions contenant un extrait de magnolia
US11660259B2 (en) 2007-04-19 2023-05-30 Mary Kay Inc. Magnolia extract containing compositions
WO2008130752A3 (fr) * 2007-04-19 2009-03-19 Mary Kay Inc Compositions contenant un extrait de magnolia
US11045403B2 (en) 2007-04-19 2021-06-29 Belaj Innovations Llc Magnolia extract containing compositions
EA016247B1 (ru) * 2007-04-19 2012-03-30 Мэри Кэй Инк. Топическая композиция для уменьшения темных кругов, отечности и отвисания кожи в области глаз человека и способ ее применения
US9668964B1 (en) 2007-04-19 2017-06-06 Mary Kay Inc. Magnolia extract containing compositions
EP2070525A1 (fr) * 2007-12-11 2009-06-17 DSM IP Assets B.V. Nouvelles compositions comprenant Magnolol et/ou Honokiol et chondroïtine et leur utilisation pour le traitement, le cotraitement ou la prévention de maladies inflammatoires
EP2070524A1 (fr) * 2007-12-11 2009-06-17 DSM IP Assets B.V. Nouvelles compositions comprenant Magnolol et/ou Honokiol et Glucosamine et leur utilisation pour le traitement, le cotraitement ou la prévention de maladies inflammatoires
EP2070523A1 (fr) * 2007-12-11 2009-06-17 DSM IP Assets B.V. Composition comprenant Magnolol et Honokiol en quantités synergiques
WO2009131470A1 (fr) * 2008-04-24 2009-10-29 Fonterra Co-Operative Group Limited Compositions et procédés pour le maintien de la santé des os ou pour la réduction de la perte osseuse
FR2933300A1 (fr) * 2008-07-02 2010-01-08 Europ Finances Compositions comprenant au moins une lignane et/ou neolignane en association avec un compose actif contre l'acne
WO2010018458A3 (fr) * 2008-08-12 2010-04-08 Crystalgenomics, Inc. Dérivés de phénol et leurs procédés d'utilisation
US8778422B2 (en) * 2009-06-22 2014-07-15 Gelita Ag Compositions for treating degenerative joint diseases
US20120128737A1 (en) * 2009-06-22 2012-05-24 Gelita Ag Compositions for treating degenerative joint diseases
DE102009048044A1 (de) * 2009-10-02 2011-04-21 Beiersdorf Ag Verwendung von Magnolol oder Honokiol als antibakterielle, antimycotische, antiparasitäre oder antivirale Wirkstoffe
US20120294812A1 (en) * 2010-02-24 2012-11-22 Colgate-Palmolive Company Oral care compositions
US9801940B2 (en) * 2010-02-24 2017-10-31 Colgate-Palmolive Company Oral care compositions
DE102010015792A1 (de) * 2010-04-20 2011-10-20 Beiersdorf Ag Wirkstoffkombinationen aus Magnolienrindenextrakt und oberflächenaktiven Agentien
DE102010015793A1 (de) * 2010-04-20 2011-10-20 Beiersdorf Ag Wirkstoffkombination aus Magnolienrindenextrakt und einem oder mehreren grenz- oder oberflächenaktiven Phosphorsäureestern
CN103442691A (zh) * 2010-09-10 2013-12-11 玫琳凯有限公司 包含拟爱神木和腰果树果肉及其提取物的局部护肤制剂
WO2012033646A3 (fr) * 2010-09-10 2013-04-25 Mary Kay Inc. Formulations topiques de soin de la peau contenant de la pulpe de jaboticaba et de noix de cajou et des extraits de ceux-ci
KR101910482B1 (ko) 2010-09-10 2018-10-22 마리 케이 인코포레이티드 자보티카바 및 캐슈 과육 및 이들의 추출물을 포함하는 국소 피부 케어 제형
US8747927B2 (en) 2010-09-10 2014-06-10 Mary Kay Inc. Topical skin care formulations comprising jaboticaba and cashew fruit pulps and extracts thereof
US9028892B2 (en) 2010-09-10 2015-05-12 Mary Kay Inc. Topical skin care formulations comprising jaboticaba and cashew fruit pulps and extracts thereof
US9333168B2 (en) 2010-09-10 2016-05-10 Mary Kay Inc. Topical skin care formulations comprising jaboticaba and cashew fruit pulps and extracts thereof
CN102520112B (zh) * 2011-12-16 2016-01-20 重庆天生药业有限公司 一种厚朴精制饮片的质量控制方法
CN102520112A (zh) * 2011-12-16 2012-06-27 重庆天生药业有限公司 一种厚朴精制饮片的质量控制方法
WO2014005597A1 (fr) * 2012-07-06 2014-01-09 Axellus A/S Composition de cynorrhodon, procédé pour la fabrication de la composition de cynorrhodon et ladite composition destinée à être utilisée dans un procédé pour l'entretien d'articulations souples et d'une inflammation réduite
CN103585135B (zh) * 2012-08-14 2015-10-28 赖媛淑 厚朴酚在制备治疗恶病质及癌症的药物中的应用
CN103585135A (zh) * 2012-08-14 2014-02-19 赖媛淑 厚朴酚在制备治疗恶病质及癌症的药物中的应用
WO2015006651A1 (fr) * 2013-07-11 2015-01-15 Specialty Nutrition Group, Inc. Compositions comprenant un hydroxytyrosol, un resvératrol, un lycopène, des flavanols, et/ou des flavonoïdes et leur utilisation
CN103553888A (zh) * 2013-11-07 2014-02-05 蚌埠医学院 和厚朴酚衍生物及其制备方法和在制备抗肿瘤药物中的应用
CN103553888B (zh) * 2013-11-07 2016-06-08 蚌埠医学院 厚朴酚衍生物及其制备方法和在制备抗肿瘤药物中的应用
CN104667045A (zh) * 2014-01-24 2015-06-03 潍坊医学院 治疗顽固性痤疮的药物
US10932480B2 (en) 2016-01-29 2021-03-02 Klaus Neufeld Animal feed additive containing diurnosid and/or cestrumosid
AU2017312737B2 (en) * 2016-08-15 2022-12-22 Summit Innovation Labs, LLC Vascular calcification and cardiovascular/associated diseases prevention and treatment
CN109641183A (zh) * 2016-08-15 2019-04-16 顶峰创新实验室有限公司 血管钙化以及心血管/相关疾病的预防和治疗
US11344575B2 (en) 2016-08-15 2022-05-31 Summit Innovation Labs, LLC Vascular calcification prevention and treatment
US11357250B2 (en) 2016-08-15 2022-06-14 Summit Innovation Labs LLC Treatment and prevention of diabetes and obesity
CN109641183B (zh) * 2016-08-15 2022-07-12 顶峰创新实验室有限公司 血管钙化以及心血管/相关疾病的预防和治疗
US20180042962A1 (en) * 2016-08-15 2018-02-15 Summit Innovation Labs LLC Vascular Calcification Prevention and Treatment
US10342802B2 (en) * 2016-10-04 2019-07-09 Nutramax Laboratories, Inc. Compositions comprising hydroxytyrosol and boswellic acid
US11980624B2 (en) 2016-10-04 2024-05-14 Nutramax Laboratories, Inc. Methods for administering compositions comprising hydroxytyrosol and boswellic acid
CN109498617A (zh) * 2018-12-26 2019-03-22 南京中医药大学 藁本内酯在制备防治骨质疏松症药品中的应用
WO2021225756A1 (fr) * 2020-05-07 2021-11-11 Innophos, Llc Compositions et méthodes pour des articulations saines
CN115484835A (zh) * 2020-05-07 2022-12-16 伊诺弗斯有限责任公司 用于关节健康的组合物和方法
WO2022238388A1 (fr) * 2021-05-10 2022-11-17 Tomcat International Limited Composition cosmétique anti-vieillissement à base de resvératrol et de magnolia
CN113717683A (zh) * 2021-09-27 2021-11-30 武汉纺织大学 一种光固化水下生物基抗菌胶粘剂及其制备方法
CN117731710A (zh) * 2023-12-20 2024-03-22 南开大学 一种具有晒后皮肤舒缓和镇痛功效的组合物及其应用

Similar Documents

Publication Publication Date Title
US8841264B2 (en) Compositions
JP5170577B2 (ja) 炎症障害の治療のためにバラの実および他の活性剤を含んでなる組成物
WO2008006582A1 (fr) Compositions comprenant du magnolol ou de l'honokiol et d'autres agents actifs pour le traitement de maladies inflammatoires
JP5633856B2 (ja) 炎症性障害および／または関節障害の治療、共治療または予防のための三環式ジテルペンおよびそれらの誘導体の使用
US20140162976A1 (en) Compositions comprising hydroxytyrosol and chondroitin and use thereof for the treatment, co-treatment or prevention of inflammatory disorders
US20110300240A1 (en) Cajanus extracts and glucosamine for inflammatory disorders
US8158681B2 (en) Nutraceutical and pharmaceutical compositions and use thereof for the treatment, co-treatment or prevention of inflammatory disorders
EP2070525A1 (fr) Nouvelles compositions comprenant Magnolol et/ou Honokiol et chondroïtine et leur utilisation pour le traitement, le cotraitement ou la prévention de maladies inflammatoires
EP2070524A1 (fr) Nouvelles compositions comprenant Magnolol et/ou Honokiol et Glucosamine et leur utilisation pour le traitement, le cotraitement ou la prévention de maladies inflammatoires

Legal Events

Date Code Title Description
121 Ep: the epo has been informed by wipo that ep was designated in this application

Ref document number: 07786021

Country of ref document: EP

Kind code of ref document: A1

NENP Non-entry into the national phase

Ref country code: DE

NENP Non-entry into the national phase

Ref country code: RU

122 Ep: pct application non-entry in european phase

Ref document number: 07786021

Country of ref document: EP

Kind code of ref document: A1