WO2008116391A1 - Promoteur de la prolifération de neuroblaste et promoteur de l'excroissance de neurite - Google Patents

Promoteur de la prolifération de neuroblaste et promoteur de l'excroissance de neurite Download PDF

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Publication number
WO2008116391A1
WO2008116391A1 PCT/CN2008/000600 CN2008000600W WO2008116391A1 WO 2008116391 A1 WO2008116391 A1 WO 2008116391A1 CN 2008000600 W CN2008000600 W CN 2008000600W WO 2008116391 A1 WO2008116391 A1 WO 2008116391A1
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WIPO (PCT)
Prior art keywords
extract
neuroblast
neurite
acid
glycoside compound
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PCT/CN2008/000600
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English (en)
Chinese (zh)
Inventor
Junji Tanaka
Hiroshi Shi-Moda
Hiromichi Murai
Original Assignee
Sinphar Tian-Li Pharmaceutical Co., Ltd. (Hangzhou)
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Application filed by Sinphar Tian-Li Pharmaceutical Co., Ltd. (Hangzhou) filed Critical Sinphar Tian-Li Pharmaceutical Co., Ltd. (Hangzhou)
Priority to CN200880009519.9A priority Critical patent/CN101657201B/zh
Publication of WO2008116391A1 publication Critical patent/WO2008116391A1/fr

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    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K50/00—Feeding-stuffs specially adapted for particular animals
    • A23K50/40—Feeding-stuffs specially adapted for particular animals for carnivorous animals, e.g. cats or dogs
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23C—DAIRY PRODUCTS, e.g. MILK, BUTTER OR CHEESE; MILK OR CHEESE SUBSTITUTES; MAKING THEREOF
    • A23C9/00—Milk preparations; Milk powder or milk powder preparations
    • A23C9/12—Fermented milk preparations; Treatment using microorganisms or enzymes
    • A23C9/13—Fermented milk preparations; Treatment using microorganisms or enzymes using additives
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/111—Aromatic compounds
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23K—FODDER
    • A23K20/00—Accessory food factors for animal feeding-stuffs
    • A23K20/10—Organic substances
    • A23K20/163—Sugars; Polysaccharides
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23L—FOODS, FOODSTUFFS, OR NON-ALCOHOLIC BEVERAGES, NOT COVERED BY SUBCLASSES A21D OR A23B-A23J; THEIR PREPARATION OR TREATMENT, e.g. COOKING, MODIFICATION OF NUTRITIVE QUALITIES, PHYSICAL TREATMENT; PRESERVATION OF FOODS OR FOODSTUFFS, IN GENERAL
    • A23L33/00—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof
    • A23L33/10—Modifying nutritive qualities of foods; Dietetic products; Preparation or treatment thereof using additives
    • A23L33/105—Plant extracts, their artificial duplicates or their derivatives
    • 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
    • A61K31/64—Sulfonylureas, e.g. glibenclamide, tolbutamide, chlorpropamide
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/70—Carbohydrates; Sugars; Derivatives thereof
    • A61K31/7028—Compounds having saccharide radicals attached to non-saccharide compounds by glycosidic linkages
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P17/00—Drugs for dermatological disorders
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A23—FOODS OR FOODSTUFFS; TREATMENT THEREOF, NOT COVERED BY OTHER CLASSES
    • A23V—INDEXING SCHEME RELATING TO FOODS, FOODSTUFFS OR NON-ALCOHOLIC BEVERAGES AND LACTIC OR PROPIONIC ACID BACTERIA USED IN FOODSTUFFS OR FOOD PREPARATION
    • A23V2002/00—Food compositions, function of food ingredients or processes for food or foodstuffs

Definitions

  • the present invention relates to a neuroblast (Neuroblast, also known as neuroblast) proliferation promoter and a neurite outgrowth using novel components.
  • the present invention can be widely applied to medicines for mammals, external preparations for skin, foods and the like including humans. Background technique
  • Cistanche tubulosa (Schrenk.) Wight, the parasitic plant of the family Denko, is the most cultivated of Cistanche.
  • Non-Patent Documents 1-3 A Japanese scholar has systematically studied the chemical constituents and pharmacological activities of Cistanche plants, and found that phenylethanoid glycosides are the main active components of these perennial herbaceous plants (for example, refer to Non-Patent Documents 1-3). . These active ingredients can be used as effective antioxidants, metabolism enhancers, memory improvers, libido enhancers, and the like. Many researchers have conducted in-depth studies on the medical properties of various phenylethanoid glycosides.
  • Patent Document 1 Japanese Patent Publication No. 2004-250449
  • Non-Patent Document 1 Sato T, et al. Yakugaku Zasshi, 1985, 105 (12): 1131
  • Non-Patent Document 2 Jimenez C., et al. Nat. Prod. Rep., 1994, 11 (6):
  • Non-Patent Document 3 Comet a F. , et al. Fitorick, 1993, 64 (3): 195
  • Non-Patent Document 4 Deng Min, et al. Pharmacoe Sin, 2004, 25 (10):
  • Patent Document 1 finds that brain function can be restored by administering a phenylethanoid compound in the case of a disorder of brain function, Patent Document 1 does not describe at all that phenylethanoid glycosides before brain disorders occur. Compounds can improve brain function. Further, in the above-mentioned Non-Patent Document 4, it is described that after the neuroblasts (Neuroblas, also called neuroblasts, neuroblasts) are impaired, the phenylephrase can be extended by the administration of the phenylethanoid glycoside to thereby function the brain.
  • Neuroblasts Neuroblasts
  • Non-Patent Document 4 In the state where the neuroblasts are not impaired, the buds can be proliferated by the addition of the phenylethanoid glycoside compound, and the nerve bud can be made. The neurites of the cells stretch. Under such a background, the present inventors have found out the following facts: extraction of phenylethanoid glycosides or phenoxyglucosides containing phenylethanoid glycosides in neuroblasts (SK-N-SH) without dysfunction After the substance, the proliferation of the nerve bud cells can be promoted, and the stretching of the neurites of the nerve bud cells can also be promoted, thereby completing the present invention.
  • the object of the present invention is to provide a novel neuroblast cell proliferation promoting agent and a neurite outgrowth agent, which can be used even in a state in which no abnormality occurs in the neuroblast cells.
  • the stretcher can also effectively prevent the reduction of nerve cells, thereby effectively preventing aging caused by the brain, and further improving the function of the brain.
  • the neuroblast growth promoting agent according to the first aspect of the invention is characterized in that the neuroblast growth promoting agent contains a phenylethanoid glycoside compound as an active ingredient. Further, preferably, the neuroblast growth promoting agent contains at least one of echinacoside and flavonoids as the phenylethanoid glycoside compound. More preferably, the neuroblast cell proliferation promoting agent contains both echinacoside and flavonoids as the phenylethanoid glycoside compound.
  • the neuroblast growth promoting agent according to the second aspect of the invention is characterized in that the neuroblast growth promoting agent is an extract of a plant of the genus Lepaceae as an active ingredient.
  • the extract contains a phenylethanoid glycoside compound as an active ingredient. Further, it is preferable that the extract contains at least one of echinacoside and flavonoids as the phenylethanoid glycoside compound. And more preferably, the extract contains both echinacoside and flavonoids as the phenylethanoid glycosidation Compound.
  • the neurite stretcher according to the third aspect of the invention is characterized in that the neurite stretcher is a phenylethanoid compound as an active ingredient. Further, it is preferable that the neurite stretcher contains at least one of echinacoside and flavonoids as the phenylethanoid glycoside compound.
  • the neurite outgrowth agent contains both echinacoside and flavonoids as the phenylethanoid glycoside compound.
  • the neurite stretcher according to the fourth aspect of the invention is characterized in that the neurite stretcher is an extract of a plant of the genus Lepaceae as an active ingredient. Further, it is preferable that the extract contains a phenylethanoid glycoside compound as an active ingredient. Further, it is preferable that the extract contains at least one of echinacoside and flavonoids as the phenylethanoid glycoside compound. More preferably, both of the extracts contain both echinacoside and flavonoids as the phenylethanoid glycoside compound.
  • the neuroblast cell proliferation promoting agent can promote the proliferation of the neuroblast cells even in the state where the neuroblast cells are not impaired, thereby promoting the neuroblast cells.
  • the neuroblast cell proliferation promoting agent can promote the proliferation of the neuroblast cells even in the state where the neuroblast cells are not impaired, thereby promoting the neuroblast cells.
  • By transforming into nerve cells it is possible to further improve functions such as memory, computational power, and judgment.
  • the function of the brain can be maintained by transforming the nerve bud cells into nerve cells. Therefore, it is possible to effectively prevent the occurrence of brain disorders such as aging or cognitive diseases in the brain.
  • the neurite stretcher of the third invention and the fourth aspect of the invention can promote the stretching of the neurites even in a state where the nerve bud cells are not obstructed. Therefore, for the normal brain, since the neurite stretcher can also construct many synapses, the function of the brain can be further improved. Further, even if the nerve cells are denatured due to aging or the like, since the neurite stretcher can rapidly construct a synapse for compensating for the function of the nerve cells, the function of the brain can be maintained. Therefore, it is possible to effectively prevent the occurrence of brain disorders such as aging or cognitive diseases in the brain.
  • the "nerve cell proliferation promoting agent and the neurite outgrowth agent (hereinafter also referred to simply as “neuroblast cell proliferation promoting agent”) in the present invention are characterized in that a phenylethanoid glycoside compound is used as an active ingredient.
  • a nerve cell proliferation promoting agent or the like means both a “nerve cell proliferation promoting agent” and a “neurite stretching agent”.
  • the "deuteroside glycoside compound” means a compound represented by the following chemical formula (1).
  • the phenylethanoid glycoside compound is not particularly limited, and examples thereof include echinacoside, phylloside, 2'-acetyl phylloside (2'-acetylacteoside;), and violet.
  • the neuroblast growth promoting agent or the like preferably contains at least one of echinacoside and flavonoid as a phenylethanoid glycoside compound. This is because it can have a higher neuroblast proliferation and neurite extension. Further preferably, at least the eosin stretching agent contains echinacein as an active ingredient. This is because it can have a more superior neurite extension.
  • the method for obtaining the phenylethanoid compound is not particularly limited and may be obtained by synthesis or may be obtained by extraction from plants.
  • the plant as a raw material is not particularly limited, and examples thereof include a crude drug of Rhizoma Polygonum, a plant of the family Labiatae, a fruit of the pepper family of the pepper family, a herb of the family Ledangaceae, and the like.
  • the phenylethanoid glycoside compound may be extracted using only one type of the plant, or two or more kinds of plants may be used in combination to extract the phenylethanoid glycoside compound.
  • plants of the family Leymanidae are most preferably used. This is because in the plants of the family Leucidaceae, as a phenylethanoid glycoside, in addition to echinacoside and flavonoids, it also contains 2'-acetyl leaf sinensis (2'-acetylacteoside; ), campneoside I, campneoside II, tube flower meat: ?
  • cistantubuloside A tuberculosis B., tube flower carotenoid ⁇ 2, tube flower meat ⁇ Cholesterol Cl, Cistanche C2, decaffeoylacteoside, isoacteoside, rhodiolaside, syringin A 3'-a ⁇ L-P Ratio 11 syringalide A 3'-aL-rhamnopyranoside, cyanine ⁇ 3'- ⁇ - L - p, 17 nyringalide A 3'--L-rhamnopyranoside and anthocyanin A ( Tubulos ide A), etc., has higher neuroblast cell proliferation and neurite outgrowth.
  • the Lista plant used as a raw material is not particularly limited, and, for example, the parasitic plant Ci Stanche tubulosa, Cistanche salsa, Aeginetia indica, grass ⁇ Rong (Boschniakia rossica), etc., but not limited to these plants. Further, these plants may be used alone or in combination of two or more. Among these plants, the parasitic plant Citrus tuan tubulosa is preferably used.
  • crenatoside is as shown in the following chemical formula (2).
  • the preparation contains substantially only a small amount or a small amount of other components than the echinacoside and the flavonoid in the above ingredients.
  • Cistanche glycosides C1/C2 H Rha Cf Glc OH (S/R) OH OH
  • the compounds shown in the above Table 1 were all confirmed by high performance liquid chromatography (HPLC). At this time, the conditions of the high performance liquid chromatography are as follows.
  • the stationary phase was C18 alkyl silane-bonded silica gel, and the mobile phase was acetonitrile-0.05 M phosphoric acid aqueous solution (elution gradient 4:96 ⁇ 15:85) with a flow rate of 1 liter/min and a detection wavelength of 330 nm.
  • the second neuroblast growth promoting agent or the like of the present invention is characterized in that an extract extracted from a plant of the genus Lepidoptera is used as an active ingredient.
  • the plant of the family Leucidaceae used as a raw material is not particularly limited, and for example, a whole parasitic plant tube flower can be cited: Cistanche tubulosa, Cistanche salsa, Aeginetia indica. , Boschniakia rossica, etc., but not limited to These plants. Further, these plants may be used alone or in combination of two or more. Further, among these plants, it is preferred to use the all-parasitic plant Cistanche tubulosa. ⁇
  • the "extract” contains a phenylethanoid glycoside compound.
  • the "phenylethanoid glycoside compound” is not particularly limited, and examples thereof include echinacoside, flavonoids, 2'-acetyl phylloside (2'-acetylacteoside), and purpura. Campneoside 1 , campneoside II , cistantubuloside A, cistanche B, tube Cistanche B2, Cistanche C, Piper Cistanche C2, crenatoside, decaff eoylacteoside, isoacteoside, rliodioloside, syringin A ⁇ -!
  • the extract may contain only one of the above components, or may contain a mixture of two or more components. Among them, it is particularly preferable to contain at least one of echinacoside and flavonoids.
  • the above extract is used as a neurite stretcher, it is preferred that at least the echinacoside is contained in the extract. This is because it can have a more excellent neurite extension.
  • the content of echinacoside is not particularly limited, and when the total shield amount of the extract of the plant (for example, the whole parasitic plant Cistanche tubulosa) is 100% by mass, Echinacea
  • the content of the glycoside is 10% by mass to 70% by mass, preferably 15% by mass to 50% by mass, and more preferably 20% by mass to 40% by mass. /. Further, it is preferably 23% by mass to 38% by mass.
  • the content of the flavonoids is not particularly limited, and when the total mass of the extract of the plant is 100% by mass, the content of the flavonoids is 1% by mass to 40% by mass, preferably 5 Shield%% to 30% by mass/», more preferably 7% by mass to 20% by mass, still more preferably 8% by mass to 10% by mass.
  • the extracted portion of the plant is not particularly limited, and leaves, roots, stems, and the like can be used as long as the desired effect can be achieved.
  • it is extracted from the stems of the plants of the family Levy, in particular fresh stems.
  • the method for obtaining the extract from the plant belonging to the genus Levodicaceae is not particularly limited, and examples thereof include a solvent extraction method, a supercritical extraction method, and the like.
  • the solvent to be used is not particularly limited, but a polar solvent is preferably used.
  • the polar solvent is not particularly limited, for example, Examples thereof include water, methanol, ethanol, isopropanol, acetone, 1, 3-butanediol, ethylene glycol, propylene glycol, glycerin, acetic acid, ethyl acetate, ether, and the like. These solvents may be used alone or in combination of two or more.
  • the treatment such as dilution, concentration, drying, purification, and the like is subsequently carried out because an extract containing a high concentration of the phenylethanoid glycoside compound can be obtained by such treatment.
  • the purification method include a method of activated carbon treatment, resin adsorption treatment, ion exchange resin, and liquid-liquid countercurrent distribution.
  • the method for producing the extract consists of two stages of extraction and purification.
  • the stem of the plant for example, the parasitic plant Cis tanche tubulosa
  • the fresh stem of the plant is sliced or pulverized into particles. Or powdery.
  • the sheet, or the fine particles or the powder thus obtained are immersed in water, a solvent such as a lower aliphatic alcohol such as methanol or ethanol, or a mixed solution thereof.
  • extraction was carried out at room temperature.
  • the mixed solution was filtered, and the filtrate was concentrated under reduced pressure or under vacuum to give an extract.
  • the extract is transferred to an adsorption column packed with a D-101 type or an AB-8 type macroporous adsorption resin. Purification was carried out.
  • the adsorption column is eluted by using water, methanol, ethanol, a mixed solution of water and decyl alcohol, or a mixed solution of water and ethanol as an elution solvent.
  • the elution solvent may be eluted as a solution of a certain concentration, or the elution solvent may be eluted according to a concentration gradient.
  • the eluate is collected, concentrated, and dried by a known drying method. After the eluate is dried, the above extract is obtained.
  • the extract thus obtained contains a phenylethanoid glycoside compound.
  • the neuroblast cell proliferation promoting agent or the like of the present invention can be used as a raw material for various drinking foods.
  • the drinkable food include edible oil (salad oil), snacks (chewing gum, candy, caramel, chocolate, biscuits, snacks, jelly, chewable tablets, small desserts, etc.), noodles (soba, Udon noodles, ramen noodles, etc., dairy products (milk, ice cream, yoghurt, etc.), seasonings (miso, miso, etc.), soups, drinks (juice, coffee, black tea, tea, carbonated drinks, sports drinks, etc.) General foods, or health foods (tablets, plastic bottles, etc.), nutritional supplements (nutritional drinks, etc.).
  • the neurotransmitter cell proliferation agent of the present invention or the like can be appropriately contained in these drinking foods.
  • various ingredients may be added thereto, for example, glucose, fructose, sucrose, maltose, sorbitol, stevioside ide, corn sugar may be used.
  • an auxiliary agent such as an antioxidant substance or a health food raw material may be added to the neuroblast growth promoter or the like of the present invention having a health-maintaining function, such as an antioxidant, reduced ascorbic acid (vitamin). C), vitamin E, reduced glutathione, tocotrienol, vitamin A derivative, lycopene, beta-zeaxanthin, astaxanthin, zeaxanthin, fucoidan, uric acid, ubiquinone, Coenzyme Q1G, folic acid, garlic extract, allicin, sesamin, lignin, catechin, isoflavones, chalcone, tannins, flavonoids, coumarins, isocoumarins, cranberry extract , arbutin, tannin, anthocyanin, apple polyphenol, grape seed extract, ellagic acid, kojic acid, sea buckthorn extract health food raw materials, V.
  • a health-maintaining function such as an antioxidant, reduced
  • vitamin A (vitamin) A, VB1, VB2, VB6, VB12, VC, VD, VE, VP, biliary, niacinamide, pantothenic acid, folic acid, EPA, oligosaccharides, dietary fiber, squalene, soy lecithin, taurine, Dunal iel la, protein Twenty-eight-pile alcohol, DHA, egg yolk lecithin, linoleic acid, lactoferrin, magnesium, zinc, chromium, selenium, potassium, heme, oyster meat extract, chitosan, chitin oligomerization Sugar, collagen, chondroitin, turmeric, licorice, hazelnut, cinnamon, hawthorn, ginger, ganoderma, mussel extract, squid, licorice, hazelnut, cinnamon, hawthorn, ginger, ganoderma, plantain, yellow flower Chrysanthemum, chamomile, d
  • the method of spray drying or freeze-drying can directly form the neuroblast growth promoter of the present invention (if the extract is used, the extract together with the dextrin) into powder, granules, and Tablets or solutions are thus easily included in foods (fast foods, etc.).
  • the neuroblast growth promoter or the like of the present invention may be mixed with a binder such as gum arabic to form a powder or granules, and then added to a solid food.
  • the extract may be directly added to the beverage, or the extract may be dispersed and dissolved in, for example, water, ethanol, glycerin or a mixture thereof, and then added to the beverage.
  • the neuroblast growth promoter of the present invention and the like can also be used as a raw material for pharmaceuticals (including pharmaceuticals and pharmaceutical products).
  • the drug can be produced by appropriately adding the neuroblast growth promoter of the present invention or the like to the raw material for pharmaceutical preparation.
  • the drug can be used for humans as well as mammals other than humans.
  • excipients for example, excipients (glucose, lactose, white sugar, sodium chloride, starch, carbonate 4, kaolin, crystalline cellulose, cocoa butter) can be mentioned.
  • the administration method of the neuroblast cell proliferation promoting agent or the like of the present invention can be orally administered in the form of a tablet, a pill, a soft gelatin, a hard gelatin, a microgranule, a powder, or a granule. .
  • the 7-soluble preparation may be administered orally or may be administered orally.
  • the neuroblast growth promoter or the like of the present invention may be dispersed in a suitable soluble reagent such as ethanol or water, followed by a cataplasm, a lotion, an ointment, an elixir, an emulsion, or the like. Formulations are used.
  • the water-soluble preparation such as the neuroblast growth promoter of the present invention may be used as it is, or a dispersing agent, a suspending agent, a stabilizer or the like may be added to the water-soluble preparation, and then a cataplasm, a lotion, an ointment may be added. Dosages such as agents, tinctures, and emulsions are used.
  • the dose to be administered may vary depending on the administration method, the condition, the age of the patient, etc., but in general, the active ingredient administered by the adult may be 5 mg-400 mg per day, and the active ingredient administered by the child according to 1 day is 0. A dose of about 5 mg to 200 mg is administered.
  • the ratio of its addition can be appropriately changed depending on the dosage form.
  • the ratio of the addition of a nerve cell growth promoter or the like may be about 0.01% by weight to 10% by weight, and the proliferation of the nerve cells is not carried out orally. 01 ⁇ % ⁇
  • the ratio of the addition agent may be from 0.01% by weight to about 20% by weight.
  • the pharmaceutical composition may contain other known compounds commonly used in the field of medicine, and may contain a compound which is required for molding in a form suitable for oral administration, in addition to the above-mentioned neuroblast growth promoter.
  • a compound which is required for molding in a form suitable for oral administration in addition to the above-mentioned neuroblast growth promoter.
  • Examples of such a compound include lactose, starch, hydroxypropylcellulose, kaolin, talc, calcium carbonate, and the like.
  • the feed for mammals may contain the neuroblast growth promoter of the present invention or the like.
  • the neuroblast growth promoter or the like of the present invention can be contained in the animal feed by the same method as the above-described drinking food.
  • the animal to which the animal feed can be used is not particularly limited.
  • the feed can be used for livestock animals such as cattle and pigs, accompanying animals such as dogs, cats, and hamsters (animals raised as pets).
  • livestock animals such as cattle and pigs
  • accompanying animals such as dogs, cats, and hamsters (animals raised as pets).
  • the companion animal For feed you can use flour, meat, and so on.
  • the flour for example, wheat flour, rice flour, rye flour, oat flour, buckwheat flour, millet flour, corn flour, soybean powder, or the like may be used, and these flours may be used in combination of two or more kinds.
  • the companion animal can be provided with nutrients such as carbohydrates.
  • wheat flour is most preferably used.
  • a strong powder, a medium-force powder, and a thin powder may be used singly or in an appropriate combination, and the wheat flour may be used in combination with other flours.
  • wheat flour may be used in combination with wheat bran, soybean protein or the like.
  • the network structure of the bran contained in the wheat flour forms a puffed structure after heat treatment, which contributes to the improvement of the mouthfeel.
  • the meat to be used in the present invention is not particularly limited, and chicken, pork, beef, lamb, goat meat, rabbit meat, turkey meat, horse meat, and the like can be used, and the best use of chicken meat is considered from the viewpoint of taste.
  • the edible meat can be obtained by slaughtering livestock animals by using a conventional method and dissecting.
  • the deterioration of the quality of the intermediate moisture product or the product in the low moisture state is mainly caused by the oxidation of the fat, so the edible meat to be used is preferably a lean fat or fat-removed lean meat.
  • the inclusion of meat in the feed not only provides the animal with an excellent animal protein, but also improves the hobby of the companion animal.
  • preferred methods include, for example, a method of preparing a mixed raw material mixture containing flour (preferably wheat flour) and edible meat (hereinafter referred to as "dough"" ), heat treatment after molding.
  • the composition of the flour and the meat in the dough is not particularly limited, and is generally formulated to be 5 ° /. - about 60%, preferably about 10% to 50%, of flour, about 5% to 80%, preferably 20°/. - About 50% of the meat and the necessary amount of moisture.
  • the amount of the Aw modifier added is about 5% to 30%, preferably about 10% to 20%.
  • the amount of water to be used may be appropriately adjusted depending on the mixing and kneading of the dough, the degree of formation, and the amount of flour, meat, Aw conditioner, and the like.
  • the method of preparing the dough is not particularly limited, and it is preferred that the meat is first made into a meat filling using a chopper, a chopper, or the like. At this time, in order to sufficiently contain air bubbles in the meat to be cooked, it is preferable to finely cut the meat. Then, flour, water, and, if necessary, an Aw conditioner or the like may be added to the meat-filled meat, and the mixture is sufficiently stirred to contain air bubbles, thereby preparing a dough containing bubbles.
  • a foaming agent may also be added, and particularly in the case where a flour other than wheat flour is used as the flour, a foaming agent is preferably used.
  • a foaming agent By adding a foaming agent, it is possible to uniformly contain fine bubbles in the dough.
  • various foaming agents can be used for the foaming agent, it is preferable to use a soy protein-based foaming agent and/or an enzyme-decomposed soy protein-based foaming agent from the viewpoint of stability of bubbles and the like.
  • the feed for the companion of the present invention is obtained.
  • the companion animal feed of the present invention may be formed into a suitable shape according to the ease with which the companion animal is eating, the ease of operation of the keeper, and the like, for example, the shape is a piece. Shape, rod shape, disc shape, ring shape, heart shape, etc.
  • the dough prepared from the same compounding component may be dyed with various dyes of different hues, or added to vegetables or fruits, etc., thereby preparing a plurality of doughs having different appearances, and the doughs are combined into a plurality of layers. Shape or concentric shape to shape.
  • the means for heating the dough after molding is not particularly limited.
  • the heating means may be oven heating, microwave heating or the like. These heating methods are well known and can be heat treated in accordance with a usual method.
  • the moisture content of the heat-treated feed is about 20% - 40%.
  • the dough is puffed due to evaporation of water and expansion of the bubbles, and the water is evaporated in a short time, so that Aw is lowered, and the preservability is improved.
  • the network structure of the bran contained in the wheat flour is fixed by heat treatment, thereby improving the mouthfeel.
  • the feed of the companion animal thus obtained is a feed having the characteristics of bread, and the feed is suitable for use as a companion for teeth such as puppies, aged dogs or cats because of its soft mouthfeel and suitable softness and elasticity.
  • Animal feed, snacks, etc. The animal feed described above is contained in a packaging container in an appropriate amount and sealed to form a product.
  • the packaging container it is preferred to use an oxygen-impermeable packaging material.
  • the shape of the package may, for example, be a vacuum package, a package filled with activated carbon, or the like, but a package filled with an oxygen scavenger (e.g., a sputum, etc.) and activated carbon is preferably used.
  • an oxygen scavenger e.g., a sputum, etc.
  • the neuroblast growth promoter of the present invention and the like can also be used as an external preparation for skin (including cosmetics, In the pharmaceuticals and the medical products, it is expected that the external preparation for skin has a neurite stretching action.
  • the external preparation for skin can be used for humans as well as other mammals other than humans.
  • an emulsion, a soap, a facial cleanser, a bathing agent, a skin cream, a lotion, a lotion, a toilet water, a shaving cream can be mentioned.
  • shaving lotion make-up oil
  • sunscreen lotion pressed powder, foundation, perfume, mask, nail polish, nail cream (enamel), nail polish lotion, eyebrow, blusher, eye cream, eye shadow, Mascara, eyeliner, lipstick, lipstick, shampoo, conditioner, hair dye, dispersion, detergent.
  • an ointment, an emulsion, an external solution or the like can be given as a form of a pharmaceutical product or a pharmaceutical external product which can be used in combination with the neuroblast growth promoting agent of the present invention.
  • the following substances may be added, and the substance may be added to the cosmetic.
  • Ingredients in skin external preparations such as pharmaceutical products, including oil components, higher alcohols, fatty acids, ultraviolet absorbers, powders, pigments, surfactants, polyols, sugars, polymers, physiologically active substances, solvents, Antioxidants, perfumes, preservatives, etc. Although examples of these substances are listed below, the present invention is not limited to these examples.
  • oil components of the esters are exemplified by: triethyl 2-ethylhexanoate, cetyl 2-ethylhexanoate, isopropyl myristate, butyl myristate , isopropyl palmitate, ethyl stearate, octyl palmitate, isohexadecanoyl isostearate, butyl stearate, butyl myristate, ethyl linoleate, isopropyl linoleate Ester, ethyl oleate, isohexadecanol myristate, isostearyl myristate, isostearyl palmitate, octyldodecan myristate, isohexadecane isostearate Ester, diethyl sebacate, diisopropyl adipate, isodecyl pentaeryth
  • hydrocarbon oil components are: squalene, liquid paraffin, ⁇ -olefin oligomer, isoparaffin, ceresin, paraffin, liquid isoparaffin, polybutene, microcrystalline wax, petrolatum and the like.
  • animal and vegetable oils and their hardened oils, as well as natural waxes are: tallow, hardened tallow, lard, hardened lard, horse oil, hardened horse oil, eucalyptus oil, only ⁇ 7 4 - a fish of the family , fish oil, hardened fish oil, egg butter and other animal oils and hardened oil thereof; avocado oil, almond oil, olive oil, cocoa butter, kiwi seed oil, almond oil, aloe vera oil, sesame oil, wheat germ oil, rice germ oil , black rice oil, safflower oil, shea butter, soybean oil, evening primrose oil, perilla oil, tea seed oil, camellia oil, corn oil, rapeseed oil, hardened rapeseed oil, palm kernel oil, hardened palm kernel oil, Peanut oil, hardened peanut oil, castor oil, hardened castor oil, hollyhock oil, grape seed oil, jojoba oil, hardened jojoba oil, macadamia nut oil, buck
  • siloxane-based oil components are: dimethylpolysiloxane, methylphenylpolysiloxane, fluorenylcyclosiloxane, octamethylpolysiloxane, decamethylpolysiloxane Alkane, dodecylpolysiloxane, methylhydrogenpolysiloxane, polyether modified organopolysiloxane, dimethylsiloxane, methylhexadecylhydroxysiloxane copolymer, two Methyl siloxane.
  • Examples of higher alcohols are: lauryl alcohol, myristyl alcohol, cetyl alcohol, stearyl alcohol, isostearyl alcohol, oleyl alcohol, behenyl alcohol, 2-ethylhexanol, hexadecane Alcohol, octyldodecanol, and the like.
  • fatty acids are: caprylic acid, capric acid, undecylenic acid, lauric acid, myristic acid, palmitic acid, palmitoleic acid, stearic acid, isostearic acid, oleic acid, linoleic acid, flax. Acid, arachidic acid, arachidonic acid, dodecanoic acid, sinapic acid, 2-ethylhexanoic acid, and the like.
  • UV absorbers are: p-aminobenzoic acid, amyl benzoic acid, ethyl dihydroxypropyl p-aminobenzoate, p-amino benzoate, ethyl p-aminobenzoate, p-amino Octyl benzoate, octyldidecyl p-aminobenzoate, ethylene glycol salicylate, octyl citrate, triethanolamine salicylate, phenyl salicylate, butyl phenyl salicylate, benzyl salicylate, Parylene salicylate, benzyl cinnamate, octyl p-methoxycinnamate, 2-ethylhexyl p-methoxycinnamate, di-p-methoxy cinnamic acid mono-2-ethylhexanoate, Isopropyl oxonium cinnamate
  • Examples of powders and pigments are: red 104, red 201, yellow 4, blue 1, black 401, etc.; yellow 4 AL precipitated color, yellow 203 BA precipitated pigment, etc. Pigment; nylon powder, silk powder, urethane powder, Teflon (registered trademark) powder, silicone powder, polymethyl methacrylate powder, cellulose powder, starch, silicone spherical elastomer powder, polyethylene Powder and other polymers; yellow iron oxide, red iron oxide, black iron oxide, chromium oxide, carbon black, ultramarine blue, dark blue and other colored pigments; zinc oxide, titanium oxide, cerium oxide and other white pigments; talcum powder, mica, white lead ore , kaolin, platy barium sulfate and other body pigments; mica titanium and other pearlescent pigments; barium sulfate, carbonic acid, magnesium carbonate, aluminum silicate, silicic acid and other metal salts; silicon, alumina and other inorganic powder; stearic acid Aluminum, magnesium stea
  • the shape (spherical shape, rod shape, needle shape, plate shape, amorphous shape, scaly shape, spindle shape, etc.) and particle diameter of these powders are not particularly limited.
  • known surface treatment methods eg, fluorine compound treatment method, silicone treatment method, silicone resin treatment method, suspension treatment method, silane coupling agent treatment method, titanium coupling agent treatment method, oil treatment
  • Method N-acylated resin treatment method, polyacrylic acid treatment method, metal soap treatment method, amino acid treatment method, lecithin treatment method, inorganic compound treatment method, plasma treatment method, mechanochemical treatment method, etc.
  • Anionic surfactants can be exemplified by: fatty acid soap, ⁇ -acyl sulfonate, alkyl sulfonate, alkyl allyl sulfonate, alkylnaphthalene sulfonate, alkane Sulfate, P0E alkyl ether sulfate, alkyl amino acid salt, alkyl brick salt, P0E alkyl acid salt, alkyl amino phosphate, alkanoyl alkyl taurate, hydrazine-acyl amino acid salt , P0E alkyl ether carboxylate, alkyl sulfosuccinate, sodium alkyl sulfoacetate, acylated hydrolyzed collagen peptide salt, perfluoroalkyl phosphate, and the like.
  • the cationic surfactant may, for example, be an alkyltrimethylammonium chloride, a stearyltrimethylammonium chloride, a stearyltrimethylammonium bromide or an octadecanoylhexadecanoyltrimethyl chloride.
  • Ammonium distearyl diammonium chloride, stearyl dimethyl benzyl ammonium chloride, dodecacarbonyl trimethyl ammonium bromide, chlorinated chlorhexidine, dioctanoate aminopropyl Mercaptohydroxypropyl ester ammonium chloride, diethylaminoacetamide stearate, dimethylaminopropionamide stearate, lanolin derivative quaternary ammonium salt, and the like.
  • amphoteric surfactant examples include a carboxybetaine type, an amidobetaine type, a sulfobetaine type, a hydroxysulfobetaine type, an amidosulfobetaine type, a phosphobetaine type, and an aminocarboxylate type. , imidazoline derivative type, amidoamine type, and the like.
  • nonionic surfactant examples include propylene glycol fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, sorbitan fatty acid ester, P0E sorbitan fatty acid ester, P0E sorbitol fatty acid ester, P0E.
  • Glycerol fatty acid ester ⁇ 0 alkyl ether, P0E fatty acid ester, P0E hardened castor oil, P0E.P0P copolymer, P0E.P0P alkyl ether, polyether modified silicone lauric acid alkyl alcohol amide, alkyl oxidation Amine, hydrogenated soybean egg fat and the like.
  • the natural surfactant include lecithin, saponin, and a saccharide surfactant.
  • polyhydric alcohol and the sugar examples include ethylene glycol, diethylene glycol, polyethylene glycol, propylene glycol, dipropylene glycol, polypropylene glycol, glycerin, diglycerin, polyglycerin, and 3-methyl-1. 3-butanediol, 1,3-butanediol, sorbitol, mannitol, raffinose, erythritol, glucose, sucrose, fructose, xylose, lactose, maltose, maltitol, trehalose, alkyl Fucose, mixed heterosexual sugar, sulfur Acidified trehalose, amylopectin, and the like. Further, chemical modifications thereof and the like can also be used.
  • Examples of the polymer are: acrylate/methacrylate copolymer (7° ⁇ X, manufactured by Mutual Chemical Co., Ltd.), vinyl acetate/crotonic acid copolymer (28-1310, manufactured by NSC Corporation) , vinyl acetate/crotonic acid/vinyl neodecanoate copolymer (28-2930, manufactured by NSC Forest Club), methyl vinyl ether maleic acid half ester (square, Bu' ES, ISP) Tert-butyl acrylate / ethyl acrylate / methacrylic acid copolymer ( ⁇ ' —, manufactured by BASF Co., Ltd.), vinyl pyrrolidone / vinyl acetate / vinyl propionate copolymer ( ⁇ ⁇ ' ⁇ t - VAP, BASF strain Co., Ltd.), Ethyl acetate/crotonic acid copolymer (t:, VII, Bu CA, BASF Co., Ltd.), Vinyl acetate/cro
  • VA manufactured by BASF Corporation , vinylpyrrolidone / dimethylaminoethyl methacrylate copolymer (: 2 water °!; - 937, ISP company), vinyl caprolactam / vinyl pyrrolidone / didecylaminoethyl methacrylate copolymer (! ; a VC71 3, manufactured by ISP), etc., such as nonionic polymer compounds.
  • the following natural polymer compounds are also suitable: cellulose and its derivatives, keratin and collagen or their derivatives, alginic acid, pullulan, agar, gelatin, tamarind seed polysaccharide, yellow Raw gum, carrageenan, high methoxyl pectin, low methoxyl pectin, guar gum, gum arabic, crystalline cellulose, arabinogalactan, karaya gum, tragacanth, alginic acid , albumin, casein, curdlan, gellan gum, glucoside Sugar and so on.
  • physiologically active ingredients those applied to the skin include those which can exert some physiological activity on the skin.
  • whitening ingredients immunostimulating agents, anti-aging agents, anti-UV agents, slimming agents, stretching agents, antioxidants, hair-increasing agents, hair growth agents, moisturizers, blood circulation-promoting agents, antibacterial agents, and fungicides can be cited.
  • desiccant cold sensitizer, warming agent, vitamins, amino acids, wound healing enhancers, irritant mitigators, analgesics, cell activating agents, enzyme components, and the like.
  • suitable components that are compatible with these physiological activities include, for example, backgrass extract, avocado extract, earthen mountain extract, hollyhock extract, arnica extract, aloe extract, apricot extract. , Apricot kernel extract, Ginkgo biloba extract, Fennel extract, Turmeric extract, Oolong tea extract, Camp extract, Echinacea extract, Astragalus extract, Astragalus extract, Coptis extract, Barley extract , forsythia extract, wild sesame extract, cardamom extract, orange extract, seawater dry matter, seaweed extract, hydrolyzed elastin, hydrolyzed wheat powder, hydrolyzed silk, chamomile extract, carrot extract, Artemisia argyi extract, licorice extract, hibiscus extract, Pyracantha extract, cinchona extract, cucumber extract, guanosine, hazelnut extract, mountain white bamboo extract, Sophora flavescens extract, walnut extract, grape Pomelo extract, Hydrangea vine extract, s
  • Hop extract pine extract, horse chestnut extract, water Plantain Extract, Sapindus Extract, Fragrant Bee Flower Extract, Peach Extract, Cornflower Extract, Eucalyptus Extract, Saxifrage Extract, Coix Seed Extract, Artemisia Extract, Lavender Extract, Apple extract, lettuce extract, lemon extract, milk vetch extract, rose extract, rosemary extract, Roman chamomile extract, royal jelly extract, etc.
  • biopolymers such as deoxyribonucleic acid, mucopolysaccharide, sodium hyaluronate, sodium chondroitin sulfate, collagen, elastin, chitin, chitosan, hydrolyzed eggshell membrane; , hydrolyzed peptides, sodium lactate, urea, sodium pyrrolidone carboxylate, betaine, whey, tridecyl glycine and other moisturizing ingredients; neurolipids, ceramides, phytosphingosine, cholesterol, cholesterol derivatives, phospholipids and other oily components; ⁇ -aminocaproic acid, glycyrrhizic acid, ⁇ -glycyrrhetinic acid, chlorinated lysozyme, guaiac blue hydrocarbon hydrocarbon, ⁇ ' mouth: 3- ⁇ f and other immunostimulating agents; vitamin A, vitamin B2, vitamin B6, Vitamin C, vitamin D, vitamin E
  • Whitening agent bellows glycosides, licorice extract, capsaicin, sterol, iodinated garlic extract, pyridoxine hydrochloride, DL- ⁇ -tocopherol, DL- ⁇ -tocopherol acetate, nicotinic acid, nicotinic acid derivative , pantothenic acid tetrahydro, D-panthenol, acetyl panthenyl ethyl ether, biotin, urinary steroid, isopropyl nonylphenol, estradiol, ethinyl estradiol, caprochloroammonium, benzalkonium chloride Ammonium, diphenhydramine hydrochloride, oxime, camphor, salicylic acid, vanillic acid amide, decanoic acid vanillyl amide, hydrazine. ⁇ ⁇ ;;, pentadecanoate, L-menthol, mononitroguaiacol, res
  • antioxidants include sodium hydrogen hydride, sodium sulfite, erythorbic acid, sodium erythorbate, dilauryl thiodipropionate, tocopherol, fluorenyl phenyl hydrazine, dehydroabioramic acid , p-hydroxyanisole, butyl hydroquinone, dibutyl hydroxy benzene, ascorbyl stearate, ascorbyl palmitate, octyl gallate, propyl gallate, carotenoids, flavonoids, enamel, A plant extract having an antioxidant effect, such as lignin, saponin, apple extract, and clove extract.
  • solvent examples include: purified water, ethanol, lower alcohol, ether, LPG, fluorocarbon, N-methylpyrrolidone, fluorine-substituted alcohol, volatile linear siloxane, secondary fluorid ⁇
  • Fig. 1 is a graph showing the proliferation of nerve bud cells of Cistanche tubulosa extract.
  • Fig. 2 is a graph showing the proliferation of neuroblasts of procyanidins and flavonoids.
  • Fig. 3 is a photograph showing the stretched state of neurites caused by Cistanche tubulosa extract.
  • Figure 4 is a photograph of the stretched state of neurites caused by echinacoside.
  • Fig. 5 is a photograph showing the stretched state of neurites caused by flavonoids. Best way to implement the invention
  • the content of echinacoside and flavonoids was determined by high performance liquid chromatography (HPLC). at this time,
  • the HPLC conditions were as follows: The stationary phase was C18 alkylsilane bonded silica gel, the mobile phase was methanol -0. 15% aqueous acetic acid (30:70), the flow rate was 1 ml/min, and the detection wavelength was 330 nm.
  • Example 1 pure echinacoside (manufactured by Xinghui Pharmaceutical Industry Co., Ltd.) was used, and in Example 3, pure flavonoids (manufactured by Xinghui Pharmaceutical Industry Co., Ltd.) was used.
  • Test Case 1 Evaluation of the proliferation of nerve bud cells - Method
  • Cistanche tubulosa extract showed a concentration-dependent proliferation of neuroblasts (Fig. 1).
  • concentration of Cistanche tubulosa extract was l O g/mL
  • the cell proliferation degree was 7%
  • the cell proliferation degree was 16% when the concentration of Cistanche tubulosa extract was 30 ⁇ g /mL. From this, it can be confirmed that even in the state where no abnormality occurs in the neuroblast cells Under N2008/000600, Cistanche tubulosa extract also has the effect of proliferating human neural bud cells (SK-N-SH). Further, as shown in Fig.
  • Cistanche tubulosa extract As shown in Fig. 3, although the control group showed cell proliferation, basically no neurite outgrowth was observed. In contrast, in the Cistanche tubulosa extract group, more neurite outgrowth was observed ( Refer to the case in Figure 3 for the actual coil). In particular, when the concentration of Cistanche tubulosa extract is 30 ⁇ g/mL, it can be found that neurites form a network with adjacent cells. From this, it was confirmed that the Cistanche tubulosa extract of the present Example also had a concentration-dependent neurite extension effect even in a state where no abnormality occurred in the neuroblast cells.
  • Fig. 4 and Fig. 5 although the control group exhibited a cell proliferation effect, substantially no neurite outgrowth was observed, and in contrast, the echinacoside group (Fig. 4) and the leaf type were observed. In the aspirin group (Fig. 5), more neurite outgrowth was observed (refer to the case of the dotted circle in Fig. 4 and Fig. 5). Further, in the echinacoside group, a network in which neurites and adjacent cells were formed was observed at a low concentration (refer to the case of the dotted circle in Fig. 5).
  • the phenylethanoid glycoside compound particularly the pine nut
  • the neuroblast growth promoter of the present invention is exemplified below as a formulation example of the neuroblast growth promoter of the present invention in a state in which no abnormality occurs in the neuroblast cells, but these formulation examples are not limited. this invention.
  • Fructose glucose sugar solution 30 30. 0% by weight
  • Lactose 54 0 weight ° /.
  • Neuroblast cell proliferation promoter etc. 1. 0 weight ° /.
  • Macadamia nut oil 2. 0% by weight
  • Tetra-oleic acid polyoxyethylene sorbitol 2.
  • Centella asiatica extract 1. 0
  • Propylene glycol 50 0% by weight Ethanol 20. 0 Sodium sulfate 5. 0 Neuroblast cell proliferation promoter, etc. 0. 5 Lanolin 0. 5 Avocado oil 0. 5 Pigment 1. 5 Spice 22. 0
  • the present invention can provide a novel neuroblast cell proliferation promoting agent and a neurite outgrowth agent, and the neuroblast cell proliferation promoting agent and the neurite outgrowth agent can be used even in a state where the neuroblast cells are not impaired.
  • the stretching agent can also effectively prevent the reduction of nerve cells, thereby effectively preventing the aging caused by the brain, and can also enter One step to improve the function of the brain.

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Abstract

La présente invention concerne un promoteur de la prolifération de neuroblaste comprenant des composés de glycoside de phényléthanol ou l'extrait de Cistanche, qui peut faciliter la prolifération de neuroblaste et l'excroissance de neurite du neuroblaste à la condition que le neuroblaste soit dépourvu de défauts. Le promoteur de la prolifération de neuroblaste peut être utilisé pour préparer des médicaments, la formule externe pour la peau, la nourriture à boire et les aliments pour les mammifères.
PCT/CN2008/000600 2007-03-26 2008-03-26 Promoteur de la prolifération de neuroblaste et promoteur de l'excroissance de neurite WO2008116391A1 (fr)

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CN106310010A (zh) * 2016-08-25 2017-01-11 广州暨南生物医药研究开发基地有限公司 一种治疗慢性湿疹的软膏剂及其制备方法
EP3181143A4 (fr) * 2014-07-03 2018-05-16 Sinphar Tian-li Pharmaceutical Co., Ltd. (Hangzhou) Applications de l'extrait de cistanche tubulosa dans la préparation d'un médicament ou produit de protection les cellules de l' il
US10905142B2 (en) 2016-03-01 2021-02-02 Kraft Foods Group Brands Llc Pelletized colorants comprising a pigment-protein complex and food products including the same

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JP5410683B2 (ja) * 2008-02-19 2014-02-05 学校法人近畿大学 カンカニクジュヨウから得られる肝保護剤及び抗ＴＮＦ−α作用剤
JP2009263279A (ja) * 2008-04-25 2009-11-12 Oriza Yuka Kk エラスターゼ阻害剤

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EP3181143A4 (fr) * 2014-07-03 2018-05-16 Sinphar Tian-li Pharmaceutical Co., Ltd. (Hangzhou) Applications de l'extrait de cistanche tubulosa dans la préparation d'un médicament ou produit de protection les cellules de l' il
US10967029B2 (en) 2014-07-03 2021-04-06 Sinphar Pharmaceutical Co., Ltd. Method of using Cistanche tubulosa extract to prevent, slow down, or treat an eye disease caused by oxidative stress
US10905142B2 (en) 2016-03-01 2021-02-02 Kraft Foods Group Brands Llc Pelletized colorants comprising a pigment-protein complex and food products including the same
US11659852B2 (en) 2016-03-01 2023-05-30 Kraft Foods Group Brands Llc Pelletized colorants comprising a pigment-protein complex and food products including the same
CN106310010A (zh) * 2016-08-25 2017-01-11 广州暨南生物医药研究开发基地有限公司 一种治疗慢性湿疹的软膏剂及其制备方法

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