WO2005077349A1 - ヒトβディフェンシン産生促進剤 - Google Patents
ヒトβディフェンシン産生促進剤 Download PDFInfo
- Publication number
- WO2005077349A1 WO2005077349A1 PCT/JP2005/002308 JP2005002308W WO2005077349A1 WO 2005077349 A1 WO2005077349 A1 WO 2005077349A1 JP 2005002308 W JP2005002308 W JP 2005002308W WO 2005077349 A1 WO2005077349 A1 WO 2005077349A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- extract
- human
- defensin
- hydrolyzate
- casein
- Prior art date
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Definitions
- the present invention relates to a human ⁇ -defensin production promoter capable of promoting human ⁇ -defensin production.
- the present invention also relates to a method for promoting the production of human j8 defensin.
- antimicrobial substances In plants, insects, amphibians, mammals, and the like, the existence of antimicrobial substances, particularly antimicrobial peptides, in vivo has been known as an innate biological defense mechanism. These are called innate immunity and have been elucidated to be responsible for local infection protection. Antimicrobial peptides in humans are collectively referred to as defensins. Defensins have antibacterial activity against bacteria, fungi and the like, and are known to be involved in various biological defense mechanisms in vivo.
- ⁇ -defensin is known as a defensin expressed in mucosal epithelium such as skin, lung, trachea, kidney, and genital organs.
- mucosal epithelium such as skin, lung, trachea, kidney, and genital organs.
- human ⁇ -defensins human ⁇ -defensin 1, human 13-defensin 2, human 13-defensin 3, human 13-defensin-4, human ⁇ -defensin 5, and human ⁇ -defensin 6 have been isolated. It has been.
- human ⁇ -defensin-2 is particularly strongly expressed in mucous tissues and skin, such as the oral cavity, lungs, trachea, eyes, nose, and digestive organs, and is induced by bacterial infection and stimulation of inflammatory sites. It has been elucidated that there is such a characteristic (for example, see Non-Patent Document 1), and it is suggested that there is a close relationship with tracheal infections such as pneumonia and inflammation.
- ⁇ -defensin has also been involved in acquired immunity by migrating cells such as tissue repair dendritic cells, lymphocytes, monocytes, etc. of epithelial tissues, which are not only protected by local infection.
- migrating cells such as tissue repair dendritic cells, lymphocytes, monocytes, etc. of epithelial tissues, which are not only protected by local infection.
- it has been reported that it induces tumor immunity and exerts an antitumor effect, and has a growth inhibitory activity on cancer cells (for example, see Non-Patent Documents 6 and 7).
- Non-patent document 1 Tetsuji Tomita et al., "Defensin as a biological defense mechanism", Journal of Geriatrics Society of Japan 2001; 38 (4): 440
- Non-Patent Document 2 Yang D, Chertov O, Bykovskaia SN et al. ⁇ -Defensins: linking innate and Adaptive immunity through dendritic and T cell CCR6. Science
- Non-patent document 3 Territo MC, Ganz T, Selsted ME et al. Monocyte-chemotactic activity of defensins from human neutrophils. J Clin Invest 1989; 84; 2017
- Non-patent document 4 Lillard JW Jr, Boyaka PN, Chertov O et al . Mechanisms for induction of acquired host immunity by neutrophil peptide defensins. Proc Natl Acad Sci USA
- Non-Patent Document 5 Nagaoka Isaota, "role in protection against infection and immune response of Defe nS i n", clinical immunity 2000; 33: 577
- Non-Patent Document 6 Isao Nagaoka, "Defensin activates maturation of dendritic cells and exerts antitumor effect-Adjuvant effect on B-cell malignant tumor-", Clinical Immunity
- an object of the present invention is to provide a ⁇ -defensin production promoter capable of promoting the expression and production of human ⁇ -defensin.
- Another object of the present invention is to provide a human defensin production promoter prepared in various forms such as external preparations, internal preparations, and foods.
- another object of the present invention is to provide a method for promoting the production of human j8 defensin. Means for solving the problem
- the present inventors have conducted intensive studies to solve the above problems, and found that (a) a specific plant extract, (b) a seaweed extract, (c) natto fungus, natto, natto extract, (d) ) Fermented rice extract, (e) wheat germ extract, (D wheat hydrolysate, (g) soy hydrolysate, (h) various polysaccharides, (0 polyglutamic acid, G) specific amino acids, (K) propolis, (1) polyphenol, (m) purine nucleic acid-related substance, (n) milk protein, (0) casein, casein hydrolyzate, (p) lactoperoxidase, lactoferrin, lysozyme It has been found that whey protein, whey protein hydrolyzate, (q) lactoperoxidase, (r) lysozyme, and (s) ratatopherin containing the same have an effect of promoting the expression and production of human j8 defens
- the present invention provides the following human ⁇ -defensin production promoters:
- Item 1 Aloe extract, Gentian extract, Geo extract, Shimoke extract, Alniki extract, Gardenia extract, Button extract, Caralot extract, Orange extract, Peach extract, Seaweed extract, Natto Extract, Levan, Inulin, Poly-D-glutamic acid, Bacillus natto, Fermented rice extract, Wheat germ extract, Wheat hydrolyzate, Soy hydrolyzate, Glycine, L-methionine, L-alanine, L- At least one selected from the group consisting of citrulline, propolis, polyphenol, purine nucleic acid-related substance, milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme, and ratatopherin An agent for promoting human ⁇ -diffensin production, comprising a component as an active ingredient.
- the active ingredients are glycine, L-methionine, L-alanine, L-citrulline, propolis, milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme, and ratatoferin Item 3.
- the human ⁇ -defensin production promoter according to Item 1 which is at least one component selected from the group consisting of: Item 3.
- the active ingredient is at least one component selected from the group consisting of milk protein, casein, casein hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and ratatoferin. 2.
- Item 4 The human ⁇ -defensin production according to Item 1, wherein the active ingredient is at least one selected from the group consisting of milk protein, whey protein, whey protein hydrolyzate, ratatobar oxidase, lysozyme, and ratatoferin. Accelerator.
- Item 6 A group consisting of nucleic acid-related substances, milk protein, whey protein, whey protein hydrolyzate, ratatoferin and lysozyme as active ingredients, and at least one component selected from the group consisting of (ii) lactoperoxidase and (ii) lactoperoxidase Item 6.
- Item 7 The human ⁇ -defensin production promoter according to Item 5, comprising ratatoferin and lysozyme as active ingredients.
- Item 8 The human ⁇ -defensin production promoter according to any one of Items 1 to 7, wherein the production promotion target is human ⁇ -defensin 2.
- Item 9 The human ⁇ -defensin production promoter according to any one of Items 1 to 8, which is an internal medicine.
- Item 10 The human ⁇ -defensin production promoter according to item 9, comprising the active ingredient in a proportion of 0.001 to 50% by weight based on the total weight of the agent.
- Item 11 The human ⁇ -defensin production promoter according to any one of Items 1 to 8, which is a food.
- the human ⁇ -defensin production promoter according to Item 11 which is a food for promoting human ⁇ -defensin production.
- Item 13 The human ⁇ -defensin production promoter according to Item 11, comprising the active ingredient in a proportion of 0.001 to 50% by weight based on the total weight of the agent.
- Item 14 The human ⁇ -defensin production enhancer according to any one of Items 1 to 8, which is a topical drug or cosmetic.
- Item 15 The human ⁇ -defensin production enhancer according to Item 14, comprising the active ingredient in a proportion of 0.001 to 50% by weight based on the total weight of the agent.
- Item 16 The human ⁇ -defensin production promoter according to any one of Items 1 to 8, which is a bathing agent.
- Item 17 The human ⁇ -defensin production enhancer according to item 16, wherein the concentration of the active ingredient at the time of use is 0.01 to 100 mgZL.
- the present invention provides the following methods for promoting the production of human ⁇ -defensin: Item 18. Aloe extract, gentian extract, dio extract, simocke extract, al-force extract, gardenia extract, button Extracts, carrot extract, orange extract, peach extract, seaweed extract, natto extract, levan, inulin, polyglutamic acid, natto, fermented rice extract, wheat germ extract, wheat hydrolyzate , Soybean hydrolyzate, glycine, L-methionine, L-alanine, L-citrulline, propolis, polyphenol, purine nucleic acid-related substances, milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, The effective amount of at least one component selected from the group consisting of lactoperoxidase, lysozyme and ratatoferin is also selected. Characterized by internal use or external use applicable to those promoting production of human ⁇ defens,
- Item 19 Group strength composed of glycine, L-methionine, L-alanine, L-citrulline, propolis, milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme and ratatoferin Item 19.
- Item 20 Is the group consisting of milk protein, casein, casein hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme and ratatoferin
- Item 21 The method for promoting human ⁇ -defensin production according to Item 18, wherein the at least one component selected from the above is applied internally or externally to a person who wishes to promote human ⁇ -defensin production.
- Item 21 Milk protein, whey Item 18.
- a group consisting of protein, whey protein hydrolyzate, lactoperoxidase, lysozyme and ratatopherin At least one selected component is applied internally or externally to a person who desires to promote the production of human ⁇ -defensin.
- the method for promoting the production of human ⁇ -defensin according to the above.
- Item 22 Aloe extract, gentian extract, dio extract, simocke extract, alhi extract, gardenia extract, button extract, carrot extract, orange extract, peach extract, seaweed extract, Natto extract, levan, inulin, polyglutamic acid, natto, fermented rice extract, wheat germ extract, wheat hydrolyzate, soy hydrolyzate, glycine, L-methionine, L-aranan, L-citrulline, propolis, Polyphenol, purine nucleic acid-related substance, milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme, and at least two components selected from the group consisting of ratatopherin, Item 19, which is applied internally or externally to a person who wishes to promote the production of human ⁇ -defensin.
- G Method for promoting ⁇ -defensin production.
- Item 23 ( ⁇ ) A group consisting of nucleic acid-related substances, milk protein, whey protein, whey protein hydrolyzate, ratatoferin and lysozyme At least one component selected from the group consisting of ( ⁇ ) lactoperoxidase and human / Item 3.
- Item 24 The method for promoting human ⁇ -defensin production according to Item 22, which comprises ratatoferin and lysozyme, and is internally or externally applied to a person who desires to promote human ⁇ -defensin production.
- Item 25 The human ⁇ -defensin production promoter according to any one of Items 18 to 24, wherein the production promotion target is human ⁇ -defensin 2
- Item 26 The human ⁇ -defensin according to Item 18, wherein the human ⁇ -defensin production promoter according to any one of Items 1 to 17 is applied internally or externally to a person who wishes to promote human ⁇ -defensin production. Production promotion method. Further, the present invention provides the use of the following embodiments:
- Item 27 Aloe extract, gentian extract, dio extract, simocke extract, ar2 extract, gardenia extract, button extract, carrot extract, orange extract, peach extract, seaweed extract, Natto extract, levan, inulin, polyglutamic acid, fermented natto, rice extract, wheat germ extract, wheat hydrolyzate, soy hydrolyzate, glycine, L-methionine, L-aranan, L-citrulline, At least one component selected from the group consisting of propolis, polyphenol, purine nucleic acid-related substances, milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme, and ratatopherin. , For the production of a human ⁇ -defensin production promoter.
- Item 28 A group consisting of glycine, L-methionine, L-alanine, L-citrulline, propolis, milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme and ratatoferin Use of at least one component selected for the manufacture of a human ⁇ -defensin production enhancer.
- a human ⁇ -defensin production promoter comprising at least one component selected from the group consisting of milk protein, casein, casein hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and ratatoferin Use for the manufacture of.
- Item 30 Use of at least one component selected from the group consisting of milk protein, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme and ratatopherin for the production of a human ⁇ -defensin production promoter.
- Item 31 Aloe extract, Gentian extract, Zio extract, Shimoke extract, Al-force extract, Gardenia extract, Button extract, Caralot extract, Orange extract, Peach extract, Seaweed extract, Natto extract, levan, inulin, polyglutamic acid, natto fungus, fermented rice extract, wheat germ extract, wheat hydrolyzate, soy hydrolyzate, glycine, L-methionine, L-alanine, L-citrulline, propolis, Polyphenol, purine nucleic acid-related substance, milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme, and ratatopherin Use of at least two components selected for the manufacture of a human 13 defensin production enhancer.
- Item 32 (A) a group consisting of (A) a nucleic acid-related substance, milk protein, whey protein, whey protein hydrolyzate, ratatoferin and lysozyme, and at least one component selected from the group consisting of (B) lactoperoxidase, Use for the production of human / 3 defensin production enhancer.
- A a nucleic acid-related substance, milk protein, whey protein, whey protein hydrolyzate, ratatoferin and lysozyme, and at least one component selected from the group consisting of (B) lactoperoxidase, Use for the production of human / 3 defensin production enhancer.
- Item 33 Use of ratatoferin and lysozyme for producing a human / 3 defensin production enhancer.
- the human ⁇ -defensins whose production is to be promoted include human 13 defensin 1, human 13 defensin 2, human 13 defensin 13, human 13 defensin 4, human 13 defensin 5, and human 13 defensin 5. All of human 13 defensin 6 are included. Among these, human j8 defensin 2 is an optimal production promotion target because the above active ingredient promotes production more effectively.
- the active ingredients used in the ⁇ -defensin production promoter of the present invention include (a) a specific plant extract, (b) a seaweed extract, (c) natto fungus, natto, natto extract, (d) ) Fermented rice extract, (e) wheat germ extract, (D wheat hydrolysate, (g) soy hydrolysate, (h) specific polysaccharide, (0 polyglutamic acid, (j) specific amino acid , (K) propolis, (1) polyphenol, (m) purine-based nucleic acid-related substance, (n) milk protein, (0) casein, casein hydrolyzate, (p) whey protein, whey protein hydrolyzate, Examples of (q) lactoperoxidase, (r) lysozyme, and (s) ratatoferin are described below.
- Examples of the plant extract used as an active ingredient of the ⁇ -defensin production promoter of the present invention include aloe extract, gentian extract, dio extract, simocke extract, Alniki extract, gardenia extract, and button extract. Products, carot extract, orange extract and peach extract.
- the aloe extract can be obtained by using leaves or sap of Aloe (Aloe ferox. Aloe barbadiensis. Aloe arborescens) or a plant closely related thereto as a raw material and extracting it with a solvent.
- the gentian extract can be obtained by using a root and rhizome of Gentian lutea or its closely related plants as a raw material and extracting it with a solvent.
- the dio extract is prepared from acadiaz (RehmanniaglutinosaLibosc—hitz var. Purpurea).
- the above-mentioned Shimoke extract can be obtained by using the inflorescence of Rosaceae Shimoke (Spiraea iaponica L. fil.) Or an inflorescence of a closely related plant as a raw material and extracting the same with a solvent.
- the above al-force extract can be obtained by extracting a flower of an Asteraceae al-force (Arnica montana L.) or its edible plant as a raw material and extracting it with a solvent.
- the above-mentioned gardenia extract can be obtained by extracting a gardenia (Gardemia iasminoside) or a closely related plant fruit as a raw material and extracting it with a solvent.
- G. button extract can be obtained by extracting a rhizome of Paeonia sufiruticosa Andrews or a rhizome of a closely related plant with a solvent and extracting it with a solvent.
- the above-mentioned carot extract can be obtained by extracting a carrot rhizome as a raw material and extracting it with a solvent.
- the orange extract can be obtained by using orange fruit as a raw material and extracting it with a solvent.
- the peach extract can be obtained by extracting peach fruit as a raw material with a solvent.
- the shape of the plant extract is not particularly limited, and may be a liquid or a dry powder.
- the plant extract can be produced by a method generally used for extracting a commonly used plant extract. Specifically, the above-mentioned plant extract may be obtained by drying, shredding, crushing, squeezing or boiling the extract as it is or as necessary, using cold water, hot water or an organic solvent, or water and an organic solvent. By extracting with a mixture of Can be obtained.
- organic solvent used for this extraction examples include, but are not limited to, methanol, ethanol, isopropanol, propylene glycol, 1,3-butylene glycol, acetone, ethyl ether, ethyl acetate, chloroform, toluene, pentane, hexane, heptane and the like. Or a combination of two or more.
- the above plant extracts may be used alone or in any combination of two or more.
- the seaweed extract used as an active ingredient in the present invention is obtained by extracting all the seaweeds such as the genus Lambaria (Laminaria) belonging to the brown algae and the genus Aegis (Ceramium) belonging to the red algae as a raw material, and extracting this with water. Obtainable.
- the seaweed extract may be a liquid or a dry powder.
- the production of the seaweed extract can be carried out by using the above-mentioned seaweed as a raw material and in the same manner as the method for producing the plant extract.
- natto Bacillus Natto
- used as an active ingredient in the present invention may be used in the state of a living bacterium itself, or may be used after drying.
- the natto used in the present invention may be natto itself that is usually used in foods, that is, one obtained by fermenting soybeans with natto (Bacillus Natto). It may be a dried one.
- the above-mentioned natto extract can be used as an active ingredient.
- the natto extract may be liquid or dry powder.
- the production of natto extract can be carried out using natto as a raw material in the same manner as the above-mentioned method for producing a plant extract.
- a fermented product of a rice extract used as an active ingredient in the present invention is prepared by preparing a rice extract using rice as a raw material in the same manner as in the method for producing a plant extract described above, and adding a koji mold, yeast, or lactic acid bacterium thereto. By fermentation.
- the wheat germ extract used as an active ingredient in the present invention is usually used in foods. It can be obtained by performing an extraction treatment in the same manner as the above-mentioned method for producing a plant extract, using the wheat germ part as a raw material.
- the wheat hydrolyzate used as an active ingredient in the present invention can be obtained by hydrolyzing wheat usually used in foods.
- the wheat hydrolyzate may be one in which polysaccharide in wheat is hydrolyzed, one in which protein in wheat is hydrolyzed, or one in which these are mixed.
- it is a wheat hydrolyzate obtained by hydrolyzing proteins in wheat.
- the wheat hydrolyzate may be prepared by any of acid degradation, alkali degradation, or enzymatic degradation, and a method for preparing the same may be a method commonly used in the art. Can be adopted.
- the hydrolyzate of soybean used as an active ingredient in the present invention can be obtained by hydrolyzing soybean which is usually used in foods.
- the soybean hydrolyzate may be any of those obtained by hydrolyzing polysaccharides in soybean, those obtained by hydrolyzing proteins in soybean, and those in which these are mixed.
- it is a wheat hydrolyzate obtained by hydrolyzing proteins in soybeans.
- the soybean hydrolyzate may be prepared by any of acid decomposition, alkali decomposition, or enzymatic decomposition, and a method for preparing the same may be a method commonly used in the art. Can be adopted.
- Polysaccharides used as an active ingredient of the ⁇ -defensin production promoter of the present invention include levan and inulin.
- the origin of the levan used in the present invention is not particularly limited.
- levan obtained by cultivating Lenone-producing microorganisms such as Bacillus subtiiis and Bacillus megatherium ⁇ Streptococcus salivarius; can be used.
- the inulin used in the present invention is not particularly limited in molecular weight, origin, and the like.
- the inulin is used in rhizomes and chicory of Asteraceae plants such as Dariya, Jerusalem artichoke, Oguruma and Mazami.
- the root can be obtained as a raw material by a commonly used extraction means.
- the above polysaccharides may be used alone or in any combination of two or more.
- the polyglutamic acid used as an active ingredient in the present invention is not particularly limited. Examples include poly-D-glutamic acid, poly-L-glutamic acid, and ⁇ -polyglutamic acid (usually D-glutamic acid and L-glutamic acid are present in a ratio of about 8: 2). Among them, poly-D-glutamic acid is preferred. As specific examples of polyglutamic acid, Baciliussubtilis, Baciliusanthracis, Bacillus licheniformis, Bacillusmegaterium,
- Examples thereof include those obtained by culturing a polyglutamic acid-producing microorganism such as Eadil Mt ⁇ by a known method, and those obtained by a known extraction method using natto power.
- the molecular weight of the polyglutamic acid used in the present invention is not particularly limited, one having a molecular weight of 2000 to 5000 can be mentioned as an example.
- an amino acid selected from glycine, L-methionine, L-alanine and L-citrulliner can be used as an active ingredient of the ⁇ -defensin production promoter of the present invention.
- the origin and production method of the amino acid used in the present invention are not particularly limited.
- a method for producing glycine, L-methionine and L-alanine a method for culturing a microorganism having a high ability to produce the amino acid; a method for recovering the amino acid by decomposing a natural protein; or a method for producing the amino acid Examples of the method include production using an enzyme.
- L over citrulline for example, ⁇ seed force of Li Plants also a method of extracting; high production capability, the L over citrulline, a method for culturing a microorganism; or ⁇ arginine arginine di deiminase (argi n i ne deiminase ) Can be used.
- the above amino acids may be used alone or in any combination of two or more.
- Propolis is defined as a mixture of fat components and pollen collected by bees from buds, buds, etc. of the tree, and the bee itself, a hormone called barotin, which is secreted from the pharyngeal line. It is a viscous fatty substance made by In the present invention, propolis used as an active ingredient is not particularly limited as long as it is pharmaceutically or food sanitary acceptable. In the present invention, propolis itself may be used as the propolis, which may be used as a propolis itself, or it may be used in a known manner such as ethanol extraction, water extraction, water / ethanol mixture extraction, and supercritical diacid carbon extraction. Propolis extract obtained by the extraction treatment according to the above method may be used. In addition, the production place of the propolis used in the present invention is not particularly limited. For example, Japan, East Asia, Southeast Asia, Europe, North and South America, Africa and the like can be mentioned.
- the origin and type of polyphenol used as an active ingredient are not particularly limited as long as they are pharmaceutically or food sanitary acceptable.
- examples of the origin of the polyphenol include pine, bark and grape seeds.
- Examples of the porifenol include proanthocyanidin, catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, epigallocatechin gallate, quercetin, myricetin, and procyadine.
- a purine nucleic acid-related substance can be used as an active ingredient of the ⁇ -defensin production promoter of the present invention.
- the purine nucleic acid-related substances are various derivatives having a purine or purine nucleus skeleton and salts thereof.
- Purine nucleic acid-related substances include, in general, adenine, adenosine, adenosine phosphate (eg, adenosine 2'-phosphate, adenosine 3'-phosphate, adenosine 5'-phosphate, adenosine 5'-diphosphate, adenosine).
- guanine, guanosine, phosphate of guanosine [guanosine 3'-phosphate, guanosine 5'-phosphate, guanosine 5'-diphosphate, guanosine 5'-triphosphate, etc.], guanine, guanosine or Guanine-based nucleic acid-related substances such as metabolites of guanosine phosphate (eg, xanthylic acid, xanthin, etc.) and salts thereof can be mentioned.
- preferred examples of the purine nucleic acid-related substance include the adenine nucleic acid-related substances listed above.
- adenosine phosphates Preferred are adenosine phosphates, metabolites thereof and salts thereof, and more preferred are adenosine phosphates and salts thereof.
- adenosine phosphate adenosine monophosphate, particularly adenosine 5'-phosphate (AMP) can be preferably mentioned.
- AMP adenosine 5'-phosphate
- alkali metal salts such as sodium salt and potassium salt
- alkaline earth metal salts such as calcium salt, magnesium salt and barium salt
- basic amino acid salts such as arginine and lysine
- Ammonium salts such as ammonium salt and tricyclohexylammonium salt
- various salts such as monoethanolamine salt, diethanolamine salt, triethanolamine salt, monoisopropanolamine salt, diisopropanolamine salt and triisopropanolamine.
- Alkanolamine salts and the like can be mentioned.
- alkali metal salts such as sodium salts.
- Specific examples of such alkali metal salts include monosodium adenosine monophosphate and disodium adenosine monophosphate.
- the milk protein used as an active ingredient in the present invention is obtained by using a milk, processed milk, fermented milk such as chocolate as a raw material, and recovering the protein contained in the milk by a known method. Obtainable.
- casein used as an active ingredient in the present invention include casein salts such as casein sodium, casein potassium, casein canolesum, and casein such as seasoning acid casein and hydrochloric acid casein. be able to.
- a hydrolyzate of the above casein may be used as an active ingredient.
- the casein hydrolyzate can be prepared by any of acid decomposition, alkali decomposition or enzymatic decomposition. Forces prepared by enzymatic decomposition for ease and safety Zein hydrolyzate is preferred.
- the enzymes used for the hydrolysis of casein include trypsin, chymotrypsin, pepsin, pancreatin, canoleboxypeptidase, papain, bromelain, fusin, endoprotease, exopeptidase and the like.
- Various conditions for the above casein hydrolysis are appropriately set according to a conventional method.
- An example of the average molecular weight of the casein hydrolyzate is 200 Da to 12000 Da, preferably 300 to 2000 Da.
- whey protein used as an active ingredient can be obtained by separating it from milk of mammals such as human lung and the like according to a conventional method.
- a hydrolyzate of the whey protein may be used as an active ingredient.
- the method for preparing the whey protein hydrolyzate can be performed in the same manner as the method for preparing the casein hydrolyzate described above.
- As one row of the average molecular weight of the whey protein hydrolyzate it is possible to show 300 to 20000 Da, preferably 1000 to 20000 Da, and more preferably 2000 to 15000 Da.
- lactoperoxidase used in the present invention are not particularly limited. In the present invention, for example, it is separated from milk of mammals such as cow's milk, human milk, goat's milk, and sheep's milk, or skim milk whey, which is a processed product of these milks, by a known means such as ion-exchange chromatography.
- the lactoperoxidase obtained by the above can be used. Lactova oxidase is also contained in secretions such as saliva, tears, nasal secretion, bronchial fluid, and intestinal secretions, and it is better to use those derived from these secretions.
- the lysozyme used as an active ingredient in the present invention can be usually obtained by separating and purifying chicken egg white as a raw material by a general method.
- the lysozyme used in the present invention may be in the form of a salt (for example, lysozyme chloride or the like).
- the lysozyme is also contained in secretions such as saliva, tears, nasal secretion, bronchial fluid, and intestinal secretions, and those derived from these secretions can also be used.
- secretions such as saliva, tears, nasal secretion, bronchial fluid, and intestinal secretions, and those derived from these secretions can also be used.
- Ratatofurin used as an active ingredient in the present invention can be obtained by separating and purifying by a general method using mammalian milk such as cow's milk, human milk, goat's milk, and sheep's milk as a raw material. Ratatofurin is also contained in secretions such as saliva, tears, nasal discharge, bronchial fluid, intestinal secretions, and the like, and those derived from these secretions can be used.
- mammalian milk such as cow's milk, human milk, goat's milk, and sheep's milk
- secretions such as saliva, tears, nasal discharge, bronchial fluid, intestinal secretions, and the like, and those derived from these secretions can be used.
- active ingredients from the viewpoint of exhibiting a more excellent human ⁇ -defensin production promoting effect, glycine, L-methionine, L-alanine, L-citrulline, proboris, polyphenol, purine nucleic acid are preferable.
- milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme and ratatoferin can be mentioned.
- More preferred active ingredients include milk protein, casein, casein hydrolyzate, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme, and ratatopherin.
- Particularly preferred active ingredients include milk protein, whey protein, whey protein hydrolyzate, lactoperoxidase, lysozyme and ratatofurin.
- any one of the above active ingredients may be used alone, or two or more of the above active ingredients may be used in any combination. Is also good.
- the human ⁇ -defensin production promoter of the present invention by using two or more of the above-mentioned active ingredients in combination, the human ⁇ -defensin production promoting action may be synergistically enhanced.
- a human ⁇ -defensin production promoter containing two or more active ingredients in combination is preferable.
- combinations of active ingredients that can synergistically enhance human ⁇ -defensin production promoting activity include (ii) a group consisting of nucleic acid-related substances, milk protein, whey protein, whey protein hydrolyzate, ratatoferin, and lysozyme.
- a combination of at least one selected component (hereinafter, sometimes simply referred to as component (II) and sometimes (III)) and lactoperoxidase can be exemplified.
- a preferred combination of the active ingredients is a combination of ratatoferin and lysozyme.
- the mixing ratio of each component can be appropriately adjusted depending on the type of components used and the like.
- the above-mentioned component (A) when used in combination with (B) ratatopa oxidase, the above-mentioned (A) component: (B) lactovar oxidase (weight ratio) is 1: 0.01-100, preferably Is 1: 0.05-50.
- a ratio in which ratatoferrin: lysozyme (weight ratio) is 1: 0.01-50 can be mentioned.
- the above examples of the mixing ratio of ratatoperoxidase are applied when using lactoperoxidase having an enzyme activity of 136 units Zmg. Therefore, when using lactoperoxidase having an activity different from the above, the mixing ratio is appropriately set based on the activity of ratato peroxidase used and the above mixing ratio when the activity is 136 units Zmg. be able to.
- one lactate of lactoperoxidase is described as "ABTS (2,2,2) of ImM under conditions of pH5 and 37 ° C.
- azino-bis (3-ethylbenzothiazoline) -6-sulfonate) shows the amount of enzyme required to oxidize 1 ⁇ mol of ABTS in the first minute of the reaction.
- the human ⁇ -defensin production promoter of the present invention may further comprise, in addition to the above active ingredients, other ingredients such as a base, carrier, or additive that is pharmaceutically or cosmetically acceptable for food safety. Can be included.
- the human ⁇ -defensin production promoter of the present invention can promote the production of human j8 defensin even when it is applied in the form of internal / external use! Therefore, the human j8 defensin production promoter of the present invention may be prepared as a food, an internal medicine or the like, or may be prepared as an external medicine or a cosmetic preparation. Furthermore, the human ⁇ -defensin production promoter of the present invention can also be prepared as a bath agent.
- the above-mentioned medicine for internal use also includes quasi-drugs for internal use. In addition, the above external medicines also include quasi-drugs for external use.
- the human ⁇ -defensin production promoter of the present invention can be prepared as a topical drug or cosmetic.
- an external medicine for promoting human ⁇ -defensin production and a cosmetic for promoting human ⁇ -defensin production are provided.
- a pharmaceutically or cosmetically acceptable base or carrier is added to the above-mentioned active ingredient. They may be combined and prepared into a desired form. Furthermore, as long as the effects of the present invention are not impaired, various surfactants, dyes (dye and pigment), fragrances, preservatives, bactericides (antibacterial agents), thickeners, antioxidants, sequestering agents, Various additives such as a cooling agent, a deodorant, and a ⁇ adjuster may be added.
- moisturizers In addition, if necessary, moisturizers, ultraviolet absorbers, ultraviolet dispersants, vitamins, plant extracts, skin astringents, anti-inflammatory agents (anti-inflammatory agents), whitening agents, cell activators, vasodilators, blood circulation enhancers And a known medicinal component to be mixed with an external preparation such as a skin function enhancer.
- the form of the above external medicine or cosmetic is not particularly limited as long as it can be applied to skin and mucous membranes.
- Examples include liquids, emulsions, powders, solids, suspensions, creams, ointments, mousses, granules, tablets, gels, jellies, bases, jewels, aerosols, sprays Form, liniment, pack and the like.
- the above-mentioned external medicine or cosmetic includes a wound healing agent, an oral patch, a dentifrice, a mouthwash, a mouth freshener, an eye drop, an eye wash, a nasal drop, a nasal wash, an enema preparation, Suppositories, gargles, oropharyngeal agents, inhalants, wipes, detergents (eg, facial cleansers, cleansing, body cleansers, etc.), and basic cosmetics (eg, emulsions, creams, lotions, serums) , Oils and packs).
- a wound healing agent e.g, an oral patch, a dentifrice, a mouthwash, a mouth freshener, an eye drop, an eye wash, a nasal drop, a nasal wash, an enema preparation, Suppositories, gargles, oropharyngeal agents, inhalants, wipes, detergents (eg, facial cleansers, cleansing, body cleansers, etc.), and basic cosmetics (e
- the mixing ratio of the above-mentioned active ingredient in the composition depends on the form of the external medicine or cosmetic, It can be set appropriately according to the type, age and gender of the subject, expected effects, and the like.
- the total amount of the active ingredient is 0.001 to 50% by weight, preferably 0.05 to 20% by weight, and more preferably 0.01 to 10% by weight, based on the total weight of the topical drug or cosmetic. %.
- examples of the above mixing ratio are as follows. It is applied when using lactoperoxidase with a basic activity of 136 units Zmg. Therefore, when using a lactoperoxidase having an activity different from the above, the mixing ratio is appropriately determined based on the activity of the lactoperoxidase used and the above mixing ratio when the activity is 136 unitszmg. Can be set.
- the human ⁇ -defensin production promoter prepared as an external medicine or cosmetic can exert a j8 defensin production promotion effect by being applied to skin and mucous membranes through its use.
- the amount and frequency of application of the human ⁇ -defensin production promoter should be set to 1 per day, depending on the type and concentration of the active ingredient, the age and sex of the user, the form of application, the expected degree, etc. It may be applied to the skin or mucous membrane about once or three times.
- a food for promoting human ⁇ -defensin production is provided.
- the human ⁇ -defensin production promoter of the present invention may include, if necessary, for example, a sweetener, a coloring agent, a preservative, a thickener, a stabilizer, a gelling agent, a sizing agent, an antioxidant, a coloring agent, a bleaching agent.
- Food hygiene such as food additives, fungicides (antifungals), yeast foods, gum bases, fragrances, acidulants, seasonings, coagulants for tofu, emulsifiers, ⁇ regulators, sweeteners, swelling agents, nutrient enhancers, etc.
- Food additives to be added may be added as appropriate.
- Examples of the above-mentioned foods include foods for specified health use, dietary supplements, foods for the sick, and the like. More specifically, beverages (carbonated drinks, soft drinks, milk drinks, alcoholic drinks, fruit drinks, teas, nutritional drinks, etc.), powdered drinks (powder juice, powdered soup, etc.), confectionery (gum, candy, Cookie, gummy, rice cracker, biscuit, jelly, ramune confectionery, foaming agent, edible sheet, edible film, troche, etc., mouth freshener (gum, candy, gummy, edible sheet, edible film, troche, etc.) (Examples include dairy products (cheese, yogurt, etc.), breads, vegetables, cereals, seasonings (sources, dressings, etc.). Among them, gum, gummy, foaming agents, candy, edible Sheet and edible Films may be mentioned.
- the proportion of the above-mentioned active ingredient in the food depends on the type of the active ingredient, the age, sex, expected effect, etc. of the subject. Can be set appropriately according to the conditions.
- the total amount of the active ingredient is 0.001 to 50% by weight, preferably 0.05 to 20% by weight, and more preferably 0.01 to 10% by weight based on the total weight of the food. The ratio can be mentioned.
- the above-mentioned examples of the mixing ratio are applied when using lactoperoxidase having an enzyme activity of 136unitsZmg. Therefore, when using a lactoperoxidase having an activity different from the above, the mixing ratio is appropriately determined based on the activity of the lactoperoxidase used and the above mixing ratio when the activity is 136 unitszmg. Can be set.
- the daily intake of the human ⁇ -defensin production promoter prepared as food depends on the type and concentration of the active ingredient, the age and sex of the user, the shape of the food, the expected degree, and the like. It is adjusted appropriately.
- an internal medicine for promoting human ⁇ -defensin production is provided.
- a pharmaceutically acceptable base material and a carrier are blended in addition to the above-mentioned active ingredient to prepare a desired form. do it.
- pharmaceutically acceptable additives such as a binder, a disintegrant, a lubricant, a wetting agent, a buffer, a preservative, and a fragrance may be arbitrarily compounded.
- the form of the internal medicine is not particularly limited. Examples include films, chewable tablets, troches, powders, tablets, granules, capsules, syrups, solutions and the like. Preferred among these are film preparations, chewable tablets and troches.
- the mixing ratio of the above-mentioned active ingredient in the medicine for internal use depends on the kind of the active ingredient, the form of the composition, and the It can be set appropriately according to age, gender, expected effects, and the like.
- the total amount of the active ingredient is 0.001 to 50% by weight, preferably 0.005 to 20% by weight, more preferably 0.01 to 10% by weight based on the total weight of the internal medicine. Can be cited.
- the above-mentioned examples of the mixing ratio are applied when using lactoperoxidase having an enzyme activity of 136 units Zmg. Therefore, when using a lactoperoxidase having an activity different from the above, the mixing ratio is appropriately determined based on the activity of the lactoperoxidase to be used and the above mixing ratio when the activity is 136 unitszmg. Can be set.
- the above-mentioned human ⁇ -defensin production promoter prepared as an internal medicine can be administered at a rate of about 115 times a day.
- the daily dose of the human ⁇ -defensin production enhancer is appropriately adjusted according to the type and concentration of the active ingredient, the age and gender of the user, the shape of the composition, the administration method, the expected degree, etc. can do.
- a bath agent for promoting human ⁇ -defensin production can be provided.
- the mixing ratio of the above-mentioned active ingredients is appropriately determined according to the type of the active ingredient, the form of the bath agent, the expected effect, and the like. Can be set.
- the concentration of the above-mentioned active ingredient is 0.01 to 100 mg ZL, preferably 0.05 to 50 mg ZL.
- the human ⁇ -defensin production promoter of the present invention it is possible to promote ⁇ -defensin production in a living body. Since j8 defensin has a broad antibacterial spectrum against bacteria, fungi, and the like, by promoting the production of ⁇ -defensin in vivo, the ability to protect bacteria from infection and to eliminate bacteria can be increased. Therefore, the present invention Human beta-defensin production enhancers are effective in preventing or alleviating the symptoms caused by bacterial, fungal, viral, and protozoal infections.
- the human ⁇ -defensin production promoter of the present invention can be used to prevent secondary infection of atopic dermatitis, acne, periodontal disease, halitosis, foot odor, shaving and hair loss.
- Prevention of secondary infections prevention of secondary infections of slime, prevention of secondary infections of hot flashes, prevention of secondary infections of burns, prevention of infectiousness by using steroids, skin care for rough skin 'dry skin', rough hands, etc., prevention of athlete's foot It is effective for etc.
- ⁇ -defensin is known to chemoaxis ⁇ cells and memory ⁇ lymphocytes, ie, to mobilize immunocompetent cells and to participate in acquired immunity.
- ⁇ -defensin is known to chemoaxis ⁇ cells and memory ⁇ lymphocytes, ie, to mobilize immunocompetent cells and to participate in acquired immunity.
- the human defensin production promoter of the present invention can also be used as an immunopotentiator.
- the human ⁇ -defensin production promoter of the present invention exhibits an effect of promoting the repair of epithelial tissue in the eyes, nose, oral cavity, respiratory tract, esophagus, other digestive organs, genital organs, and skin, so that infection, inflammation or other injuries may occur. It is also useful for recovery.
- the active ingredient of the human j8 defensin production promoter has an action of promoting the production of human ⁇ -defensin when applied internally or externally. Therefore, the present invention further provides a human ⁇ -defensin characterized in that an effective amount of the active ingredient of the human ⁇ -defensin production promoter is applied internally or externally to a person who desires human ⁇ -defensin production.
- the types of effective components of the human ⁇ -defensin production promoter to be used, the effective amounts thereof, the number of applications per day, and the like are described in the aforementioned human j8 defensin production promotion. It is as described in the section of the agent.
- the production promotion method is preferably carried out by applying the human ⁇ -defensin production promoter to a person who desires the production of human j8 defensin according to the form of the agent.
- Component name Amount (% by weight) Lactoperoxidase 0.1 acid
- Component name Amount (% by weight) Sodium chloride 0.5 Potassium chloride 0.1 Flavin adenine dinucleotide 0.05 Sodium hyaluronate 0.1 pH adjuster Appropriate amount Purified water Residual Total 100
- NHEK normal human neonatal foreskin keratinocytes, Kurabo Industries
- liquid medium Human Media-KG2; serum-free liquid medium for normal human keratinocyte proliferation, Kurabo Industries
- test sample In the state of 80-90% confluence, add the test sample to the cell culture solution so that the final concentration becomes the concentration shown in Tables 1 and 2, and incubate for 4 days in a 5% CO incubator.
- the cells were cultured at 37 ° C.
- the concentration of human ⁇ -defensin 2 in the measurement sample was measured by ELISA, and the amount of human j8-defensin 2 released in each medium was determined. Assuming that the amount of ⁇ -defensin 2 released in the culture medium without the test sample is 1, the relative amount of human ⁇ -defensin 2 released in the culture medium obtained by collecting each test sample 4 days after addition is By calculating the value, the production promoting effect of each test sample was evaluated.
- Table 1 shows the obtained results.
- Table 1 shows the obtained results.
- Table 1 shows the obtained results.
- Table 1 it was confirmed that the addition of various components used as the active ingredient of the present invention to the medium increased the amount of ⁇ -diffinsin 2 produced by the cells.
- glycine, L-methionine, L-alanine, L-citrulline, propolis, lactoperoxidase, lysozyme, and ratatopherin have excellent human ⁇ -defensin 2 production promoting effects even at low concentrations. Two It was confirmed that it was particularly useful as a production promoter.
- Test Example 2 Human ⁇ -defensin 2 production promotion test 2 The following tests were conducted to evaluate the promotion of human ⁇ -defensin 2 production by the various components shown in Tables 2 and 3.
- NHEK normal human neonatal foreskin keratinocytes, Kurabo Industries
- liquid medium Human Media- KG2; serum-free liquid medium for normal human keratinocyte proliferation, Kurabo
- test sample With the cells in a confluent state, add the test sample to the cell culture so that the final concentration will be the concentration shown in Tables 3 and 4, and place it in a 5% CO incubator for 3 days.
- E. coli powder Escherichia coli K12. Lyophilized cells, SIGMA
- SIGMA SIGMA
- the concentration of human ⁇ -defensin 2 in the measurement sample was measured by ELISA, and the amount of human j8-defensin 2 released in each medium was determined. Assuming that the amount of ⁇ -defensin 2 released in the medium of the test sample-free casket is 1, the amount of human ⁇ -defensin 2 released in the culture solution obtained by collecting each test sample on day 3 after addition is The production promotion effect of each test sample was evaluated by calculating the relative value of the amount.
- Concentrated milk protein (Product name "MPC80”, DMV
- human defensin has the following excellent properties: ( a ) it can exert its antibacterial action in a short time because of its antibacterial properties; (b) In vivo (C) migration of ⁇ cells and memory T lymphocytes (c) which can exert excellent antibacterial effects even on sites where conventional antibacterial agents administered in external or internal form are difficult chemotaxis (ie, mobilizes immunocompetent cells to participate in acquired immunity) and (d) promotes epithelial tissue repair.
- the human ⁇ -defensin production promoter of the present invention can promote the induction of ⁇ -defensin in vivo, particularly the induction of human / 3-defensin 2. Therefore, according to the human j8 defensin induction promoter of the present invention,
- 8 defensin induction can be promoted, and the antibacterial action, anti-inflammatory action, and immunity action in the living body can be enhanced.
- the defense mechanism can be increased.
- j8 defensin exerts a wound healing effect and an antitumor effect by inducing tissue repair of epithelial tissue and tumor immunity. Therefore, the present invention is intended to further enhance the overall biological defense mechanism. It is useful to promote human ⁇ -defensin production.
- the human / 3 defensin production promoter of the present invention is useful for preventing or alleviating symptoms caused by bacterial, fungal, viral, or protozoal infections, for example, for preventing secondary infection of atopic dermatitis, Acne prevention, periodontal disease prevention, halitosis prevention, foot odor prevention, prevention of secondary infection after shaving and hair loss, prevention of secondary infection of umuk rash, prevention of secondary infection of hot flashes, prevention of secondary infection of burns, steroids It is effective for prevention of infectiousness due to use, skin care for rough skin and dry skin, and prevention of athlete's foot.
- the human / 3 defensin production promoter of the present invention is expected to have a pharmacological effect based on the human j8 defensin production promotion effect. Therefore, the human ⁇ -defensin production promoter of the present invention may be administered, for example, when administered intraocularly, to viral conjunctivitis, bacterial conjunctivitis, stye, corneal injury, etc .; Cold, influenza, etc .; rhinitis, purulent rhinorrhea, rhinosinusitis, etc.
- the human j8 defensin production promoter of the present invention has an effect of promoting epithelial tissue repair in the eyes, nose, oral cavity, respiratory tract, esophagus, other digestive organs, genital organs and skin, so that it can recover from infection, inflammation or other injuries. It is also useful for
- the human ⁇ -defensin production promoter of the present invention can exert an excellent ⁇ -defensin production promotion effect in mucosal tissues such as eyes, nose, anus, respiratory tract, esophagus, and oral cavity, and is therefore useful as a preparation for mucosal application.
- the human ⁇ -defensin production promoter of the present invention is effective as a prophylactic or therapeutic agent for periodontal disease, stomatitis, caries, bad breath, infection in eyes, corneal damage, rhinitis and the like. Therefore, the human
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Cited By (18)
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JP2007070292A (ja) * | 2005-09-07 | 2007-03-22 | Asahi Breweries Ltd | 植物病害抵抗性遺伝子活性化用組成物 |
WO2008105384A1 (ja) * | 2007-02-26 | 2008-09-04 | Kyowa Hakko Bio Co., Ltd. | シトルリン含有錠剤 |
WO2010037545A1 (en) * | 2008-10-02 | 2010-04-08 | Bayer Consumer Care Ag | Compositions for treating or alleviating skin diseases or disorders related to an enhanced level of anti-microbial peptides and proteins |
EP2218452A1 (en) | 2007-05-22 | 2010-08-18 | Galderma Research & Development | Combination comprising pyrrolidone-5-carboxylic acid and at least one compound from citrulline, arginine and asparagine, and use thereof in the treatment of atopic dermatitis |
JP2011032244A (ja) * | 2009-08-05 | 2011-02-17 | Akita Univ | 分子シャペロン誘導剤組成物及びこれを含む癌抑制剤組成物 |
WO2011077701A1 (ja) * | 2009-12-24 | 2011-06-30 | 株式会社ロッテ | 抗アンドロゲン剤、皮脂分泌抑制剤、養毛剤及び飲食品 |
JP2012140336A (ja) * | 2010-12-28 | 2012-07-26 | Rikomu:Kk | ヒトβディフェンシン2産生促進剤 |
WO2013120481A3 (de) * | 2012-02-13 | 2014-09-18 | Dr. Kurt Wolff Gmbh & Co. Kg | Verwendung eines mittels zur stimulation der gen-expression antimikrobieller peptide (amp) |
WO2015079016A1 (en) | 2013-11-29 | 2015-06-04 | Galderma Sa | Compound of the avermectin family or of the milbemycin family for the treatment and/or prevention of atopic dermatitis |
CN104970333A (zh) * | 2014-12-02 | 2015-10-14 | 铜陵梧桐树农业发展有限公司 | 一种含牡丹花蕊味精的制作工艺 |
CN105661507A (zh) * | 2016-01-15 | 2016-06-15 | 王军 | 一种固态发酵生产菊粉纳豆酵素粉的方法 |
WO2017001433A1 (en) | 2015-06-29 | 2017-01-05 | Galderma Research & Development | Cgrp receptor antagonist compounds for topical treatment of skin disorders |
WO2017033616A1 (ja) * | 2015-08-21 | 2017-03-02 | 森永乳業株式会社 | 上気道保護剤及び上気道保護用飲食品組成物 |
WO2018056600A1 (ko) * | 2016-09-23 | 2018-03-29 | 씨제이제일제당 (주) | 밀배아 발효물의 추출물을 유효성분으로 함유하는 피부진정 외용제 조성물 |
JP2018522031A (ja) * | 2015-08-04 | 2018-08-09 | ズートツッカー アーゲー | 副鼻腔炎に対するイヌリンの予防的使用 |
CN111135125A (zh) * | 2020-01-10 | 2020-05-12 | 广州贝玛生物科技有限公司 | 一种可改善妊娠纹的组合物、含有该组合物的产后修复润肤霜及其制备方法 |
KR20200102061A (ko) * | 2019-02-21 | 2020-08-31 | 주식회사 유진바이오텍 | 밀배아 추출물을 유효성분으로 함유하는 여드름 및 백선 개선용 조성물 |
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JP2007070292A (ja) * | 2005-09-07 | 2007-03-22 | Asahi Breweries Ltd | 植物病害抵抗性遺伝子活性化用組成物 |
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JPWO2008105384A1 (ja) * | 2007-02-26 | 2010-06-03 | 協和発酵バイオ株式会社 | シトルリン含有錠剤 |
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JP2015078226A (ja) * | 2008-10-02 | 2015-04-23 | バイエル・コンシューマー・ケア・アクチェンゲゼルシャフトBayer Consumer Care AG | 抗菌ペプチドおよびタンパク質のレベルの上昇に関連する皮膚の疾患または障害を処置または緩和するための組成物 |
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US9114115B2 (en) | 2008-10-02 | 2015-08-25 | Bayer Consumer Care Ag | Compositions for skin disease or disorders |
JP2012504564A (ja) * | 2008-10-02 | 2012-02-23 | バイエル・コンシューマー・ケア・アクチェンゲゼルシャフト | 抗菌ペプチドおよびタンパク質のレベルの上昇に関連する皮膚の疾患または障害を処置または緩和するための組成物 |
JP2011032244A (ja) * | 2009-08-05 | 2011-02-17 | Akita Univ | 分子シャペロン誘導剤組成物及びこれを含む癌抑制剤組成物 |
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