TW200533333A - Human beta-defensin production accelerator - Google Patents

Abstract

Provided is a beta-defensin production accelerator capable of accelerating the expression of human beta-defensin. As an active ingredient of human beta-defensin production accelerator, use is made of at least one component selected from the group consisting of an aloe vera extract, a gentian extract, a Rehmannias radix extract, a meadowsweet extract, an arnica extract, a gardenia extract, a peony extract, a carrot extract, an orange extract, a peach extract, a seaweed extract, a fermented soybean extract, levan, inulin, poly-D-glutamic acid, soybean fermentation bacteria, a fermentation product from rice extract, a wheat embryo extract, a wheat hydrolyzate, a soybean hydrolyzate, glycine, L-methionine, L-alanine, L-citrulline, propolis, polyphenol, a purine nucleic acid associated substance, lactoprotein, casein, a casein hydrolyzate, whey protein, a whey protein hydrolyzate, lactoperoxidase, lysozyme and lactoferrin. This human beta-defensin production accelerator is provided as an external drug, cosmetic, food, internal drug, bath agent, etc.

Description

200533333 IX. Description of the invention: [Technical field to which the invention belongs] The present invention relates to a human defensin production promoter that can promote the production of human defensins. In addition, the present invention relates to a method for promoting the production of human anti-purpurin. [Prior technology] It has been known from the past that in plants, insects, amphibians, mammals, etc., there are antibacterial substances in the living body, especially antibacterial peptides. As the anti-purple mechanism of living organisms, these are called natural immunity. , Responsible for preventing purple infection in local areas. Antibacterial peptides in 10 humans are collectively called defensins, and defensins have antibacterial activity against bacteria, fungi, etc., and are associated with various living defense mechanisms in the body. Defensins appearing in the mucous epithelium of the skin, lungs, trachea, kidneys, genitals, etc., are known as defensins. At present, there are 6 human defensins (human / 5 defensin-1, human defensin-2, human defensin-3, human / 3 defensin-4, human / 3 defensin-5, and Human defensin_6) has been isolated and its structure has been determined. In particular, human defensin_2 has been clearly known to be particularly strong in mucosal tissues and skin such as the oral cavity, lungs, trachea, eyes, nose, and digestive organs, as well as in the skin. This feature is derived from the following manifestations (for example, refer to Non-Patent Document i), and it has been shown to be closely related to tracheal infection or inflammation such as pneumonia. In recent years, there have been reports that yj defensin is not only related to local infection defense, but is also related to acquired nature by chemotaxis of epithelial tissue repair, or dendritic cells, T lymphocytes, monocytes and other cells. Immunity is related (for example, non-patent documents 2 to 5). In addition, it has been reported that it has a tumor-derived 5 200533333 immunity to exert anti-tumor effects or inhibit proliferation in cancer cells (for example, refer to Non-Patent Documents 6 and 7). Here, "if it can promote the production of human defensins that control infection defense in vivo", it will not only strengthen the direct antibacterial effect, but also mobilize 5 immune-responsible cells at the infection site, which should further strengthen the living defense mechanism. However, the production mechanism of human yS defensins is still not very clear. [Non-Patent Document 1] Tada Chita, etc., "Defensins as Living Defense Mechanisms", Journal of the Japanese Geriatrics Association, 2001; 38 (4): 440 [Non-Patent Document 2] Yang D, Chertov 0, Bykovskaia, SN et al · 10 β -Defensins: linking innate and Adaptive immunity through dendritic and T cell CCR6. Science 1999; 286: 525 [Non-Patent Document 3] Territo MC, Ganz T, Sellsted ME et al,

Monocyto-chemotactic activity of defensins from human neutrophils. J Clin Invest 1989; 84; 2017 15

[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 1999, 96 651 [Non-Patent Document 5] Nagaoka Gong, etc., The role of Defensin in infection defense and immune 20 response ", Clinical Immunity 2000; 33: 577) [Non-Patent Document 6] Nagaoka Gong et al." Defensin matures and activates dendritic cells to exert antitumor effects-adjuvant Effect on B-cell malignancies- ", Clinical Immunology 2003; 40 (4): 424) [Non-Patent Document 7] Byragyn A, Surenhu M, Yang D et al. 6 200533333

Mediators of innate immunity that target immature, but not mature, dendritic cells induce antitumor immunity when genetically fused with immunogenic tumor antigens. J Immunol 2001; 167: 6644 [Summary of the invention] 'The object of the present invention is to provide a human defensin Appear and produce / 3 defensin production promoter. Another object of the present invention is to provide a human point defensin production promoter which can be prepared into 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 point defensins. The present inventors intensively studied in order to solve the above-mentioned problems. As a result, they found that (heart 10 15 specific plant extracts, (b) seaweed extracts, (c) fine 5-^ i, iy ,,, Menli, natto, Natto extract, (d) fermented product of rice extract, (e) wheat germ extract, wheat hydrolysate, (g) soybean hydrolysate, various kinds of lysine, glutamate, (j) specific amines Base acid, (k) propolis, (1) polyphenols, (claw) purine-based nucleic acid-related substances, U) milk proteins, (.) Road proteins, road protein hydrolysates,: :) Contains lactoperoxidase, lactoferrin Protein, lysozyme whey protein, whey protein pyrolysate, (q) lactoperoxidase, (r) lysozyme, and (s) lactoferrin T, which can promote the development and production of human / 3 defensins enhancement. This translation is based on the discovery, and iterative review and development. In addition to the 20 agents, the present invention provides the following human defensin production-promoting 1 · -type human ys defensin production-promoting agents, which are selected from the group consisting of Dong Cang cuttings, gentian extracts, and digitalis extracts. Extract, extract from rusty chrysanthemum " extract from food truck net, extract, extract from seaweed, extract from natto, levans, extract from chrysanthemum, extract from peony, carrot extract, orange extract 、 Pochi-Polyyl 7 200533333 =, Γ bacteria, fermented rice extract, wheat germ extract, wheat water acid, bee cut, glycine 'W thioic acid, L • alanine, L- Citrullinol, purine-based nucleic acid-related substances, milk protein, casein 5 II: Hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme ^ ferritin formed at least- As the active ingredient. It is transcribed from the person of item Z1_anti-material production promoter, where the active ingredient =: from glycine, M thioic acid, L acetic acid, l_citrulline, bee win, Tα shellfish: protein, protein The hydrolysate, whey protein, and whey protein were hydrolyzed by 10 minutes. It is recognized that at least one of the group 1 formed by Weimei, lysozyme and lactoferrin is a human Lufenin production promoter, which is selected from the group consisting of lactoprotein, A 〒 忒 active ingredient M white h protein hydrolysate. , Whey protein, milk > moon protein hydrolysate, milk peroxidation peak, lysozyme, and milk gift. From the formed group of 15 4 · The person of item 1_defensin production promoter is selected from the group consisting of milk protein, whey protein, whey protein hydrolysate, active ingredient enzyme, lysozyme and lactoferrin The formation of at least five substances-milk peroxidation promoters of human defensins, is :::. 20 items, gentian extract, radix rehmanniae extract, rusty thread extract ^ extract from Lu Hui extract gardenia extract, peony extract, carrot extract ^ cornflower extract, extract, sea rat extract 'natto extract Substance, levans = extract, peach surface acid, natto bacteria, rice fermentation extract, wheat germ; ^, poly-D-poly-based soybean hydrolysate, glycanic acid, L-methionine, L-propylamine Jealousy, wheat hydrolysate, gum, dolphin. Nucleic acid-related substances, milk protein / L, citrulline, bee shell, casein, casein 8 200533333 5

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20 Hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme and lactoferrin in the group formed by at least two components as active ingredients. 6. The human / 5 defensin production promoter according to item 5, which contains (A) selected from the group consisting of a nucleic acid-related substance, milk protein, whey protein, whey protein hydrolysate, lactoferrin, and lysozyme At least one component of the group and (B) lactoperoxidase are effective ingredients. 7. The human point defensin production promoter according to item 5, which contains lactoferrin and lysozyme as active ingredients. 8. The human cold defensin production promoter according to any one of items 1 to 7, whose production promotion target is human defensin-2. 9. The human / 5 defensin production promoter according to any one of items 1 to 8, which is an internal medicine. 10. The human / 3 defensin production promoter according to item 9, wherein the active ingredient is contained in a proportion of 0.001 to 50% by weight relative to the total weight of the agent. 11. The human / 3 defensin production promoter according to any one of items 1 to 8, which is a food. 12. The human cold defensin production promoter according to item 11 is a food for promoting the production of human cold defensins. 13. The human / 3 defensin production promoter according to item 11, wherein the active ingredient is contained in the proportion of 0.001 to 50% by weight relative to the total weight of the agent. 14. The human cold defensin production promoter according to any one of items 1 to 8 is a topical medicine or cosmetic. 15. The human stone defensin production promoter according to item 14, which contains the aforementioned active ingredient in a proportion of 0.001 to 50% by weight relative to the total weight of the agent. 9 200533333 16. The ethnographic bath preparation according to any one of items 1 to 8. The cold defensin production promoter is 17. The concentration of the aforementioned active ingredient of human stone defensin as described in item 16 is 0.01 to 10 () mg /: L, and the method of using it is that the present invention is Provide the following disclosed persons _ Wan defensin production promoter 18. A kind of human cold defensin production promoter ^ extract, gentian extract, digitalis extract, will be selected from aloe vera 10 20 extracts, vibrator extracts, peony extracts, caraway extracts, cornflower extracts peach extracts, seaweed extracts, natto extract extracts, glutamic acid, natto bacteria, fermented extracts of rice extracts, L-Sugar, Inulin, Polybasic Hydrolysate, Soy Hydrolysate, Glycine, L Malamine Extract, Wheat Hydrate, Propolis, Polyphenols, Purine-Based Nucleic Acid Related Substances-Alanine, Citrullin Casein Hydrolysate, whey protein, whey protein protein, casein, 15 bacterial enzymes and lactoferrin, at least one pyrolysate, lactoperoxidase, soluble or externally used as appropriate, Prevention == Effectiveness' Within 19. As the human being in item 18 orders to produce Jinfang: entrants. By the method of glycine, L-sulfuric acid, and propylamine, the method is selected from the group consisting of sulfonium, sulfa, cinnamic acid, bee dolphin, i △ shellfish, casein, casein hydrolysate, Whey egg beer, beer protein peroxizine, lysate and lactoferrin / U egg self-hydrolysate, milk for internal or external use are appropriately used for the desired 'v tooth weight component, as described in section 2.0. Person of 18 items _ defense Xin ^ anti-purpurin production promoter. Production method from milk protein to μ, transmitted by Jiang, Deng, Li protein shellfish, casein, casein hydrolysis, and selected from the group consisting of solution surface oxidase, lysate and lactoferrin, and lysoprotein The freshness of at least one kind of 10 200533333 ingredients, suitable for internal or external use, is expected to promote human / 5 defensin production promoters.

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20 21. The method for promoting human / 3 defensin production according to item 18, which is selected from the group consisting of milk protein, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and lactoferrin. At least one component of the group is suitably used internally or externally for a human / 5 defensin production promoter. 22. The method for promoting the production of human defensins according to item 18, which is selected from the group consisting of extracts from aloe, extracts from gentian, extracts from rehmannia glutinosa, extracts from rusty clover, extracts from coneflower, and extract from gardenia. Extract, peony extract, carrot extract, orange extract, peach extract, seaweed extract, natto extract, levans, inulin, polyglycolic acid, natto bacteria, rice fermentation extract, wheat germ extract , Wheat hydrolysate, soybean hydrolysate, glycine, L-methionine, L-alanine, L-citrulline, propolis, polyphenols, purine-based nucleic acid-related substances, milk protein, casein, casein Hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and lactoferrin, at least two components of the group, suitable for internal or external use for human / 3 defensin production promoters. 23. The human cold defensin production promotion method according to item 22, wherein (A) is selected from the group consisting of a nucleic acid-related substance, milk protein, whey protein, whey protein hydrolysate, lactoferrin, and lysozyme At least one component of the group and (B) lactoperoxidase are suitably used internally or externally for those who want a human / 3 defensin production promoter. 24. The method for promoting human / 3 defensin production according to item 22, which uses human / 3 defensin production promoters containing lactoferrin and lysozyme for internal or external use as appropriate for the desired human / 3 defensin Generate promoters. 11 200533333 25. The human cold defensin production and promotion method according to items 18 to 24 ψ /, the production promotion object is ㈣m 26. If the person from item 18 comes to g ^ 5

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20. The method for promoting human defensin production is to use the anti-purpurin production promoters from the first to the third and the middle, and to use it appropriately for internal or external use as a promoter of light human performance production. Furthermore, the present invention provides use of the following aspects: 27.-uses selected from the group consisting of extracts from aloe, extracts from gentian, extracts from radix rehmanniae, extracts from rustworm, extracts from coneflower, Sophora extract, peony extract, caraway extract, orange extract, peach extract, seaweed extract, natto extract, levans, inulin, polyglycolic acid, natto bacteria, rice extract, etc. Fermented product, wheat material extract, wheat hydrolysate, soy hydrolysate, glycine, L-methionine, U alanine, L_citrulline, propolis, dophan, throat nucleic acid related substances, Milk protein, road protein, road protein hydrolysate, whey protein, polite egg hydrolysate, lactoperoxidase, lysozyme, and lactoferrin at least the H phase of the group formed in the production of human auxin production promoters . 28 · A use 'is selected from the group consisting of glycine, L-sulfuric acid, L-alanine, L-citrulline, propolis, milk protein, road protein, road protein hydrolysate, whey protein, At least one component of the group formed by whey protein hydrolysate, lactoperoxidase, lysin and lactoferrin is used to produce human production promoters. 29.-Uses selected from the group consisting of milk protein, road protein, road protein hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and lactoferrin Life promoter. This ingredient is used for the production of human stone defensin, whey protein, whey egg 30 · —uses selected from the group consisting of milk protein 12 200533333 hydrolysate, ritual peroxidase, lysozyme and lactoferrin At least one of the formed groups is used to make human stone defensin production promoters. A variety of uses are selected from aloe extract, gentian extract, ground 5 10 15 20 extract, rust thread extract, chrysanthemum extract, gardenia extract, peony carrot extract, Orange extract, peach extract, seaweed extract bean extract, levulinan, inulin, polybasic acid, natto, fermented rice], wheat germ extract, wheat hydrolysate, soybean hydrolysate, glycine , L-methycinuronic acid, L-alanine, L-citrulline, propolis, polyphenols, lysin-based nucleic acids, protein, complex protein, protein hydrolysate, whey protein, milk / month protein At least one component of the group formed by the hydrolysate, lactoperoxidase, lysozyme, and lactoferrin is used to produce a human defensin production promoter. The uses are selected from (A) at least one component selected from the group consisting of a nucleic acid-related substance, milk protein II, gifted albumin, whey protein hydrolysate, lactoferrin, and lysozyme, and (B ) Lactoperoxidase is used in the manufacture of human fosmin production promoters. Ding is used to produce lactoferrin and lysobacteria for the production of human anti-violin production promoters. [Embodiment] The present invention will be described in detail below. L Human stone defensin production promoter This human% defensin production promoter includes human_defensin-1, human / 3 antipurin_2, human Dot-flocculant-3, human defensin_4, human stone anti-flavin_5, and human tritium deflocculant-6. Among them, human defensin_2 can effectively promote production by using the above-mentioned reduction of 13 200533333 points, and is therefore the most suitable production promotion object. The active ingredients used in the production-promoting plant of the present invention include (a) specific plant extracts, (b) seaweed extracts, (c) natto bacteria, natto 'natto extract, and (d) fermented product of rice extract. , (E) wheat germ extract, (f) 5 wheat hydrolysate, (g) soybean hydrolysate, (h) specific polysaccharides, (丨) polyglutamic acid, (j) specific amino acids, ( k) propolis, (1) polyphenols, (m) purine-based nucleic acid-related substances, (η) milk protein, (0) casein, casein hydrolysate, (P) whey protein, whey protein hydrolysate, ( q) lactoperoxidase, (r) lysozyme, and (s) lactoferrin. Hereinafter, these active ingredients will be described. 10 U) Plant extract: The plant extract used as the active ingredient of the Lufen defensin production promoter of the present invention may be aloe extract, gentian extract, digitalis extract, rust wire extract, golden car Li extract, vibrator extract, peony extract, carrot extract, orange extract and peach extract. 15 The above aloe extract can be obtained from the aloe of the family Liliaceae (Aloe ferox, Aloe barbadiensis. Aloe arborescent or the leaves or juice of its close plants as the raw material, which can be obtained by extracting the solvent. The above gentian extract The gentian gentian (Gentiana lutea 厶) or its roots and rhizomes can be used as raw materials, and the solvent can be extracted to obtain 20. Yellow (Rehmannia ^ lutinosa Libosohitz var. Purpurea Makino), Rehmannia ^ lutinosa Uhosc-hitz. Forma hueichin 殳 ensis Hsiao, or the roots of related plants were used as raw materials, which were obtained by solvent extraction. 14 200533333 The extract of the rusty chrysanthemum can be obtained by extracting the inflorescence of Rosaceae mineral line chrysanthemum (Spiraea japonica L. /// ·) or its related plants with a solvent. The chrysanthemum extract can be obtained by extracting the flower of asteraceae (Centrum chrysanthemum (Arnica 5 montana) Z >.) or its related plants with a solvent. The vibrator extract can be Section vibrator flower (Shanhuang locust (Gardemia jasminoside)) or fruits of related plants as raw material, and the extraction solvent

10 The peony extract can be obtained by extracting the solvent from the rhizome of the peony (Paeonia suffruticosa Andrews) or its related plants as a raw material. The carrot extract can be obtained by extracting a carrot rhizome with a solvent. 15

The above-mentioned orange extract can be obtained by extracting the orange fruit with a solvent. The peach extract can be obtained by extracting a 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 above-mentioned plant extract can be produced by a method generally used to extract a plant extract generally used. Specifically, the above-mentioned plant extracts are those that have been dried, finely cut, crushed, pressed or boiled directly or as necessary with cold water, hot water or organic solvents, or water and organic solvents. The mixture is extracted and extracted to obtain it. The organic solvent used in this extraction can be, for example, methanol, ethanol, isopropanol, propylene glycol, 1,3-butanediol, acetone, ethyl acetate, trichloropyrene, toluene, pentyl, and hexane. Burn, Geng :): complete alone or a combination of 2 or more. 5 The above plant extracts can be used alone or in combination of two or more. (b) Algae extract

The seaweed extract used as an active ingredient in the present invention may be whole algae of seaweeds belonging to brown algae (C Laminaria) or red thin ceramium (Ceramium) 10 as raw materials and extracted with water. And get. The algae extract may be liquid or may be a dry powder. The production of the seaweed extract can be carried out by using the above-mentioned seaweed as a raw material in the same manner as the method for producing the plant extract. (c) Natto bacteria, natto, natto extract 15 20 The natto bacteria () used as an active ingredient in the present invention may be used in a bacterial state or may be dried. The natto used in the present invention may be natto used in common foods, that is, natto added to soybeans and fermented, or dried. Moreover, in this invention, the extract of the said natto can be used as an active ingredient. The natto extract may be liquid or may be a dry powder. The production of the natto extract can be carried out in the same way as the aforementioned method for producing a plant extract using natto as a raw material. (d) Fermented product of rice extract 16 200533333 The fermented product of rice extract used as an active ingredient in the present invention can use rice as a raw material to prepare the rice extract by the same method as the method for manufacturing the plant extract, and It is obtained by fermenting fungus, yeast or lactic acid bacteria. (e) Wheat germ extract 5 The wheat germ extract used as an active ingredient in the present invention can use the wheat germ portion used in common foods as a raw material, using the same method as the above-mentioned plant extract extract production method Method to obtain the extraction process. (f) Wheat hydrolysate Φ The wheat hydrolysate used as an active ingredient in the present invention can be obtained by hydrolyzing wheat used in general foods 10. The wheat hydrolysate may be a hydrolyzed polysaccharide in wheat, a hydrolyzed protein in wheat, or a mixture of the two. Wheat hydrolysates whose protein is hydrolyzed are more preferred. The wheat hydrolysate can be prepared by any one of acid decomposition, alkaline decomposition, or enzymatic decomposition, and the preparation method can be a method generally used in the technical field. 15 (g) Soy hydrolysate The soybean hydrolysate used as an active ingredient in the present invention can be obtained by hydrolyzing the soybean used in general food ®. The soy hydrolysate may be a hydrolyzed polysaccharide in soybean, a hydrolyzed protein in soybean, or a mixture of the two. Anyone may exist. Soy protein hydrolysate is preferably the hydrolysate of soybean protein. 20 The soybean hydrolysate can be prepared by any of acid decomposition, alkaline decomposition, and enzymatic decomposition, and the preparation method can be a method generally used in the technical field. (h) Specific polysaccharides The polysaccharides used as the active ingredient of the / 3 defensin production promoter of the present invention include levans and inulins. 17 200533333 The source of the levans used in the present invention is not particularly limited. For example, levans obtained by culturing sugar-producing microorganisms by culturing Bacillus subtilis, Baciu megatherium, streptococcus salivarius, and the like can be used. 5 The inulin used in the present invention is not particularly limited in molecular weight or source. The inulin can be obtained from the roots of compositae plants such as dahlia, chrysanthemum, inflorescences, and thistles, or from the roots of amphibians, and is obtained by a commonly used extraction method. These polysaccharides can be used alone or in combination of two or more. 10 (i) Polyglutamic acid The polyglycolic acid used as an active ingredient in the present invention is not particularly limited, and examples thereof include poly-D-polyglutamic acid, poly-L-polyglutamic acid, and r-polypolyglutamic acid (typically D-polyglutamic acid and L-polyglutamic acid are present in a ratio of about 8: 2, and polypolyglutamic acid is preferred. Specific examples of polyglutamic acid can be exemplified by a known method of cultivating B. subtilis (Bgcmus 15) , Bacillus anthracis (private anthracis), licheniformis (bacillus licheniformis), giant bacilli (& c /// ⑽ evasion / _), natto bacteria (Bacillus nano), etc. Or it can be obtained from natto by a known extraction method. The molecular weight of polybasic acid used in the present invention is not particularly limited, and a molecular weight of 20 2000 to 5000 can be taken as an example. (J) Amino acid For the / 3 defensin production promoter, an amino acid selected from the group consisting of glycine, L-methionine, L-alanine, and L-citrulline can be used as an active ingredient. The source of the amino acid used in the present invention And the manufacturing method is not particularly limited. Glycine 18 200533333 5

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20 The production methods of acid, L-sulfuric acid and L-alanine are taken as examples. A method of cultivating a microorganism having high amino acid production ability; a method of decomposing natural protein and recovering the above amino acid; A method for producing the above-mentioned amino acid enzyme and the like. In addition, the method for producing L-citrulline can be a method of extracting from the seeds of cucurbitaceae; a method for cultivating microorganisms having a high ability to produce L-citrulline; or making arginine in arginine Methods of dehydration (arginine deiminase) and so on. These amino acids may be used singly or in any combination of two or more. (k) Propolis The so-called propolis refers to the viscous resin-like substance produced by bees collected from the resin components or pollen collected by bees from tree buds or flower buds, and mixed with hormones called salivary hormones secreted by bees from the pharyngeal glands. . The propolis to be used as an active ingredient in the present invention is not particularly limited as long as it is acceptable in pharmacy or food hygiene. The propolis of the present invention can be propolis extract taken from the hive itself, or extracted by conventional methods such as ethanol extraction, water extraction, water and ethanol mixed liquid extraction, and supercritical carbon dioxide extraction. The origin of the propolis used in the present invention is not particularly limited, and examples thereof include Japan, East Asia, Southeast Asia, Europe, North and South America, and Africa. (l) Poly-S content The source or type of polyphenols used as an active ingredient in the present invention is not particularly limited as long as it is pharmacologically or food-hygienicly acceptable. An example of the source of this polyphenol is pine bark or grape seed. Examples of the polyphenols include proanthocyanidins, catechins, epicatechins, catechins, epigallocatechins, epicatechin gallic acid S, epigallocatechin Vegetarian gallate, quercetin, myricetin, procyanidin, etc. Among them, anthocyanins, catechins, epicatechins, catechins, 19 200533333 epigallocatechin, epicatechin gallate and epigallocatechin gallate are preferred. . (m) Purine-based nucleic acid-related substances

In the present invention, a purine-based nucleic acid-related substance can be used as an active ingredient of a cold defensin 5 promoter. Here, the purine-based nucleic acid-related substance refers to various derivatives and salts thereof having a purine or purine core as a skeleton. Purine-based nucleic acid-related substances include adenine, adenosine, and adenosine phosphate [for example, adenosine 2'-monophosphate, adenosine 3'-monophosphate, adenosine 5'-monophosphate, and adenosine 5 ' -Diphosphate, adenosine 5'-triphosphate, adenosine cyclic phosphate, adenosylsuccinate, nicotinamide adenine 10 single dinucleotide (NMN), nicotinamide adenine dinuclear Nitrate (NAD), Nicotinamide Adenine Dinucleotide Phosphate (NADP), Flavin Adenine Nucleotide (FAD), etc.], metabolites of these adenines, adenosine or adenosine phosphate esters [eg Hypoxanthine, carnitine, carnitine, etc.], and adenine-based nucleic acid-related substances such as these salts; guanine, guanosine, and guanine phosphate [guanine 3'-monophosphate, guanine 5 ' -15 monophosphate, guanine 5'-diphosphate, guanine 5'-triphosphate, etc.], and the metabolites of guanine, guanosine, or guanine σ that hinder acid _ [such as yellow σ ticket Yin Acids, yellow sigma, etc.], and guanine-based nucleic acid-related substances such as these salts. Among them, suitable adenine-based nucleic acid-related substances include the above-mentioned disclosed adenine-based nucleic acid-related substances. Among them, adenosine phosphate, its metabolites and salts are preferred, and adenosine phosphate and its salts are more preferred. Here, as the phosphoric acid ester of adenosine, adenosine-monophosphate, especially adenosine 5'-phosphate (AMP) is suitable. Examples of the salt include alkali metal salts such as sodium or potassium salts; alkaline earth metal salts such as calcium, magnesium, and barium salts; basic amino salts such as glutamic acid and lysine; ammonium salts or tricyclic rings Hexyl ammonium salt and other ammonium salts; monoethanolamine salt, diethanolamine salt, triethanolamine salt, monoisopropanolamine 20 200533333 salt, diisopropanolamine salt and triisopropanolamine salt, etc. Metal salts are preferred. Secret metal carcass can be glandular »Uranium monophosphate U and adenosine monophosphate disodium. , Isarate Sodium, (η) Milk Protein 5

10 The milk protein used as an active ingredient in the present invention may be

Si, β re-dried pores, fermented milk such as processed inflammable milk, etc. are used as raw materials, and are obtained by recycling the conventional methods contained therein. (3) White matter: (0) casein and casein hydrolysate. Specific examples of casein used as an active ingredient in the present invention include casein salts such as sodium casein, potassium casein, and calcium casein, or lactate casein,酸 Casein and other acid casein. In the present invention, the hydrolysate of casein may be used as an effective effect. The casein hydrolysate can be withdrawn by any of acid decomposition, alkaline decomposition, and enzymatic decomposition. In terms of simplicity and safety, casein hydrolysate adjusted by enzyme decomposition is preferred. The enzyme used in the casein hydrolysis may be, for example,

Trypsin_, chymotrypsin, pepsin, trypsin, carboxypeptidase, papaya, phoenix 4 azalea, protease, endprotease, exopeptidase, etc. Various conditions for the hydrolysis of the casein can be appropriately set by a general method. An example of the average molecular weight of the casein hydrolysate is 200 Da to 12,000 Da, and more preferably 20 300 to 20 OODa. (P) Whey protein, whey protein hydrolysate The whey protein used as an active ingredient in the present invention can be obtained by isolating it from human milk or the milk of a mammal such as a cow by a general method. In addition, in the present invention, the hydrolysate of the whey protein is used as an effective ingredient. The method for preparing the whey protein hydrolysate can be performed by the same method as the method for preparing the aforementioned protein hydrolysate. An example of the molecular weight of the whey protein hydrolysate is 300 to 20,000 Da, and preferably 10,000 to 20,000 Da: more preferably 2,000 to 15,000 Da. 5 (q) Lactoperoxidase The source and production method of the milk peroxidation peak used in the present invention are not limited. In the present invention, conventional methods such as ion exchange chromatography can be used to extract milk from human milk and human milk. , Goat milk, goat milk and other mammalian milk, or skimmed milk or whey, etc. from milk processed products. Lactoperoxidase is also present in secretions such as saliva, tears, nasal fluid, bronchial fluid, and intestinal endocrine fluid. Lactoperoxidase derived from these secretions can also be used. (0 Lysozyme The lysozyme used as an active ingredient in the present invention can usually be obtained from egg protein as a raw material by isolation and purification by ordinary methods. The lysozyme used in the present invention 15 can also be a salt. Type (such as chlorinated lysozyme, etc.) Lysozyme also exists in secretions such as saliva, tears, nasal fluid, bronchial fluid, and intestinal endocrine fluid, and lysozyme derived from the above-mentioned secretion fluid can also be used. (S) Lactoferrin Protein The lactoferrin used as an active ingredient in the present invention can be made from the milk of mammals such as cow's milk, human 20 milk, goat's milk, and goat's milk, and can be obtained by knife refining and refining by common methods. Lactoferrin also exists in Lactoferrin derived from the above-mentioned secretion fluid can also be used in secretions such as saliva, tear fluid, nasal fluid, branchhole fluid, and intestinal endocrine fluid. The above effective knife can be obtained commercially and can be easily used in the market. 22 200533333 Among the above active ingredients, based on the effect of promoting the production of better human anthocyanin, for example, glycine, L-sulfuric acid, alanine, citrulline, bee , Polyphenols, purine-based nucleic acid-related substances, milk proteins, lectins, 5 casein hydrolysates, whey proteins, whey protein hydrolysates, lactoperoxidase, lysozyme, and lactoferrin are preferred, and more preferred The active ingredients include milk protein, road protein, road protein hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and lactoferrin ', and particularly suitable active ingredients include milk protein, Whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and milk 10 ferritin are preferred. Any one of the active ingredients of the human iS defense of the present invention is used above. Among the hormone-promoting agents, they can be used alone One of these can be used in combination with any of the above active ingredients. In particular, the human / 3 anti-stolen too much 15 20 π hormone production promoter of the present invention can be used by combining two or more of the above active ingredients. The human / 5 defensin production promotion effect is enhanced in a specific ratio, so the human / 3 defensin production promotion agent should contain more than two kinds of effective knife-forming combinations described above. It can make people _ .. An example of a combination of active ingredients that is enhanced in equal proportions. ^ "Bovine" (A) is selected from the group consisting of nucleic acid-associated substances, ritual protein, whey protein, lactobacillus Tv ^ .. hydrolysate, lactoferrin, and lysozyme At least one component A of the formed group is hereinafter referred to as (A) component), and (B) a combination of pores and insects. In addition, the combination of appropriate and effective ingredients may be a combination of lactoferrin and lysozyme. Thousands of combinations of two or more ingredients are used to adjust the type of ingredients used, etc. 4: The mixing ratio of the wide ingredients can be adjusted according to the field. For example, using the above (A) as 23 200533333 ^ ratio) ^ ㈣, the above (A) 0: (B) lactoperoxidase (weight =-again ~ ~ two-day peroxidase and lysozyme, milk can be lifted Peroxidase: lysozyme (Zhongli-the ratio of i · 0.01 ~ M. However, the above example of the mixing ratio of lactoperoxidase ^ is suitable for the use of lactoperoxidase with a green activity of 136 her.

When Tian uses lactoperoxidase having an activity different from that described above, the mixing ratio can be appropriately set according to the activity of the milky rail and the above-mentioned mixing ratio at the same time. Here, the "milk peroxidation peak unit" refers to "when it is acted in ABTS (2,2 10 azino-bis (3-ethylbenzothiazoline) -6'sulfonate) at lmM under the conditions of pH 5, 37 ° C" The amount of enzyme required to oxidize 1 // mol of ABTS in the first minute of the reaction ". In addition to the above effective ingredients, the human / 3 defensin production promoter of the present invention may contain other ingredients such as bases, carriers, or additives that are tolerable in food hygiene, pharmacy, or cosmetics. 15 The human / 5 defensin production promoter of the present invention can promote the production of human / 5 defensins regardless of whether it is used internally or externally. Therefore, the human defensin production promoter of the present invention can be prepared as a food or an internal medicine or the like, and can also be prepared as an external medicine or a cosmetic. Furthermore, the human defensin production promoter of the present invention can be prepared as a bath agent. In addition, among the above-mentioned internal medicines, 20 includes external medicines for internal medicine. In addition, the above-mentioned external medicines include external medicine department external medicines. [External medicines and cosmetics] By preparing the human cold defensin production promoter of the present invention as external medicines or cosmetics, it is possible to provide human tritium defensin production promotion external medicine 24 200533333 5

10 15

20 products and cosmetics for human / 3 defensin production promotion. When the human defensin production-promoting agent of the present invention is prepared into a topical medicine or a cosmetic, the above-mentioned active ingredient can be mixed with a base or carrier that is pharmaceutically or cosmetically acceptable to prepare a desired form. . In addition, various surfactants, pigments (dyestuffs, pigments), perfumes, preservatives, bactericides (antibacterial agents), thickeners, antioxidants, metal blocking agents, and cooling agents can be mixed within the range that does not impair the effects of the present invention. , Deodorant, pH adjuster and other additives. In addition, humectants, ultraviolet absorbers, ultraviolet diffusers, vitamins, plant extracts, skin astringents, anti-inflammatory agents (anti-inflammatory agents), whitening agents, cell activating agents, vasodilators, Hematology promoters, skin function anti-advancing agents, and other well-known medicinal ingredients that can be mixed with external agents. The external medicines or cosmetics are not particularly limited as long as they can be applied to the skin or mucous membranes. For example, they can be liquid, emulsion, powder, solid, suspension, cream, ointment, or muses. Shape, granule shape, pastille shape, jelly shape, paste-like shape, paste-like shape, health-like shape, spray-like shape, coin-like shape, thickener, facial mask, etc. In addition, the above-mentioned external medicines or cosmetics can be adjusted into wound healing agents, mouth patches, tooth brushes, mouthwashes, mouth cooling agents, eye drops, eye wash, nasal drops, nasal wash, and intestines Preparations, suppositories, mouthwashes, oral and throat preparations, inhalants, light wipes, detergents (such as wash pigments, facial cleansers, body cleansers, etc.), basic cosmetics (such as lotions, creams, lotions) , Cosmetic liquid, oil and mask, etc.). When the human stone defensin production promoter of the present invention is prepared into a pharmaceutical or cosmetic for external use, the mixing ratio of the above active ingredients in the composition may be 25 200533333.

10 15

20 It is appropriately set according to the form of the external medicine or cosmetic, the type of active ingredient, the age or sex of the subject, and the expected effect. For example, relative to the total weight of the external pharmaceutical or cosmetic material, the proportion of the active ingredient may be 0.001 to 50% by weight, more preferably 0.05 to 20% by weight, and more preferably 0.01 to 10% by weight. . However, when the active ingredient is lactoperoxidase, the above examples of mixing ratios are suitable for use when lactoperoxidase having an enzyme activity of 136 units / mg is used. Therefore, when a lactoperoxidase having an activity different from the above is used, its mixing ratio can be appropriately set according to the activity of the lactoperoxidase used and the above-mentioned mixing ratio when the activity is 136 units / mg. The human defensin-promoting agent prepared as a medicine or cosmetic for external use can promote the defensin-promoting effect by using it on the skin or mucous membrane. Regarding the amount and number of times that the human point defensin production promoter is used, the effective amount can be adjusted from 1 to 3 times a day according to the type or concentration of the active ingredient, the age or sex of the user, the form of use, and the degree of expectation. To the extent it applies to the skin or mucous membranes. [Food] By preparing the human yS defensin production promoter of the present invention into a food, a human / 3 defensin production promotion food can be provided. When the human stone defensin production promoter of the present invention is prepared into a food, the above-mentioned active ingredient may be used as one of the ingredients, and it may be mixed with food or beverage. In addition, the human / 3 defensin production promoter may be appropriately added with, for example, sweeteners, colorants, preservatives, thickeners, stabilizers, gelatinizers, pastes, antioxidants, colorants, Bleaching agent, antifungal agent (antifungal agent), instant food, gum 26 200533333 base (gumbase), flavor, sour flavor, seasoning, coagulant for tofu, emulsifier, pH adjuster, sweet water, bulking agent, nutrition fortification Food additives, such as food additives, which are hygienic.

Examples of the food include foods for specific health care, nutritional supplements, and foods for patients. More specifically, beverages (carbonated drinks, refreshing beverages, milk beverages, alcoholic beverages, fruit drinks, teas, nutritional beverages, etc.), powdered beverages (powdered juice, powdered soup, etc.), snacks (gum, candy, etc.) , Biscuit, gum dessert, senbei, biscuit, fruit bed, lemon sugar, bubble gum, edible sheet, edible flakes, throat lozenge, etc., mouth cooling agent (gum, #, gum 10 quality dessert, Edible sheets, edible flakes, lozenges, etc.), dairy products (cheese, yogurt, etc.), breads, noodles, quinces, seasonings (sauces, sauces, etc.), etc. Chewing gum, gummies, bubble gum, candy, edible sheets and edible flakes. When the human / 3 defensin production promoter is prepared as a food, the mixing ratio of the above active ingredients in the 15 foods can be appropriately set according to the type of the active ingredient, the age, sex, and expected effect of the subject . For example, relative to the total weight of the food, the proportion of the active ingredient may be 0.001 to 50% by weight, more preferably 0.005 to 20% by weight, and still more preferably 0.01 to 10% by weight. However, if the active ingredient is lactoperoxidase, the above-mentioned mixing ratio example 20 is suitable for the use of lactoperoxidase having an enzyme activity of 136 units / mg. Therefore, when using a lactoperoxidase having an activity different from the above, the mixing ratio can be appropriately set according to the activity of the lactoperoxidase used and the above-mentioned mixing ratio when the activity is 136 units / mg. Each of the above-mentioned human / 3 defensin production promoters prepared as food is 27 200533333. Ingestion can be based on the view or concentration of the active ingredient, the age or sex of the person, the form of the food, and the expected effect. Appropriate adjustment. [Internal medicine]

Furthermore, by preparing the human anti-purpurin production-promoting agent of the present invention as an internal-use pharmaceutical product, it is possible to provide human internal anti-purpurin-production-promoting pharmaceutical product for internal use. In the case of preparing the human 3 axoflavin-promoting agent of Ben Maoming as an internal medicine, in addition to the above-mentioned active ingredients, a pharmaceutically acceptable base or carrier may be further mixed to prepare a desired form. In addition, pharmacologically acceptable additives such as a binding agent, a disintegrating agent, a lubricating agent, a wetting agent, a buffering agent, a preservative, and a fragrance can be arbitrarily blended as required. There is no particular limitation on the form of the above-mentioned domestic medicine. For example, tablets, V tablets, throat tablets, powders, lozenges, granules, capsules, syrups, liquids, and the like can be mentioned. Among them, flakes, chewable tablets and laryngeal tablets are more suitable. When the human tritium defensin production-promoting agent of the present invention is prepared into an internal medicine 15, the mixing ratio of the above-mentioned effective ingredients in the internal medicine can be adjusted according to the type of the active ingredient, the form of the composition, and the target person. The age, sex, desired effect, and the like are appropriately set. For example, with respect to the total weight of the above-mentioned internal-use pharmaceutical products, the proportion of the active ingredient is 0.00U0% by weight, more preferably 0.005-20% by weight, and still more preferably 0.01-10% by weight. 20 However, if the above active ingredient is lactoperoxidase, the above examples of mixing ratios are suitable for the use of lactoperoxidase with an enzyme activity of 136 units / mg. Therefore, when using a lactoperoxidase having an activity different from the above, the mixing ratio can be appropriately set according to the activity of the lactoperoxidase used and the above-mentioned mixing ratio when the activity is 136 units / mg. 28 200533333 The above-mentioned human yS defensin production promoter, which is prepared as an internal medicine, can be administered at a ratio of 1 to 5 times a day. In addition, the ingestion amount of the human /? Defensin production promoter can be determined according to the type or concentration of the active ingredient, the age or sex of the user, the shape of the composition, the method of administration, and the degree of expectation. Suitable for 5 adjustments.

10 15

[Bath agent] By preparing the human / 5 defensin production promoter of the present invention as a bath agent, a bath agent for human / 5 defensin production promotion can be provided. When the human / 5 defensin production promoter of the present invention is prepared into a bath preparation, the above-mentioned effective ingredients and components commonly used in the bath preparation can be added to adjust to a desired form such as a liquid state and a solid state. When the human cold defensin production promoter of the present invention is prepared as a bath agent, the mixing ratio of the above-mentioned effective ingredients can be appropriately set according to the type of the active ingredient, the form of the bath agent, the expected effect, and the like. For example, when the bath preparation is used, the proportion of the above-mentioned active ingredient is 0.01 to 100 mg / L in total, and a concentration of 0.05 to 50 mg / L is more preferable. The human / 3 defensin production promoter of the present invention can promote the production of / 5 defensins in vivo. yS defensins have a wide range of antibacterial activity against bacteria or fungi. Therefore, by promoting the production of the cold defensins in vivo, the defense ability of bacterial infections or the ability to eliminate bacteria can be improved. Therefore, the human yS defensin production promoter of the present invention is effective in preventing or alleviating symptoms caused by bacterial, fungal, viral, and protozoal infections. Specifically, the human / 5 defensin production promoter of the present invention can be effectively used to prevent secondary infections of atopic dermatitis, prevent facial acne, prevent bad breath, prevent foot odor, prevent shaving and hair removal. Second sense 29 200533333 5

10 15

20 Staining, prevention of secondary infections in diaper treatment, prevention of secondary infections in gardenia, prevention of secondary infections in scalds, prevention of susceptibility due to the use of steroids, skin care for rough skin, dry skin, rich hands, etc. It is also effective on ringworm. In addition, it is known that / 3 defensin is related to acquired immunity by dendritic cells or memory T lymphocytes (chemotaxis), that is, mobilizing immune-responsible cells. Therefore, by promoting the production of / 3 defensin, it can be enhanced Immune effect, improve defense mechanism in vivo. Therefore, the use of the above-mentioned effective ingredients to promote the production of human /? Defensin can enhance the immune effect. Therefore, the human / 3 defensin production promoter of the present invention can also be used as an immune booster. In addition, the human / 3 defensin production promoter of the present invention exhibits an epithelial tissue repair promoting effect on eyes, nose, oral cavity, trachea, esophagus, other digestive organs, genitals, and skin, and therefore, it can cause infection, inflammation, or other damage Recovery is also useful. 2. Human cold defensin production promotion method As mentioned above, among the active ingredients of the human yS defensin production promoter mentioned above, it has the effect of promoting / 3 defensin production by appropriate use internally or externally. Therefore, the present invention further provides a human / 3 defensin production promotion method, which uses the effective amount of the active ingredient of the above-mentioned human stone defensin production enhancer internally or externally for those who wish to produce a human / 3 defensin. In the production promotion method, the types of the active ingredients of the human / 3 defensin production promoter, the appropriate effective use amount thereof, and the appropriate daily use frequency are the same as those of the aforementioned human defensin production promoter. Documented in the project. The proper production method of the production promotion method can be implemented by appropriately using the aforementioned human / 5 defensin production enhancer in accordance with the type of the agent for the human yS defensin producer. 30 200533333 Examples Hereinafter, the present invention will be described using test examples and examples, but the present invention is not limited to these examples. Example 1 Toner Ingredient Name Aloe Extract 1,3-Butanediol Concentrated Glycerol Monolaurate Polyhydroxyethylene Sorbitol Anhydride (20E.O.) Ethanol Preservative pH Adjusting Agent Refined Water Total Mixing Amount (Weight %) 0.1 2.0 2.0 1.0 5.0 Right amount Residual 100

5 Example 2 Ingredient name of beauty liquid Seaweed extract Orange tangerine extract Dipropylene glycol Concentrated glycerol Sodium hyaluronate Polyhydroxyethylene fluorenyl polysiloxane Copolymer methoxyethanol Maleic anhydride copolymer Ethanol pH adjustment Example 3 Total amount of refined water of the agent Emulsion% Weight and weight. 0.5.0.0.1.2.2.0 Weight and balance 00 {10.3.2.0.0.0.3 Appropriate Residual 1 Volume Blend Ingredient Name Lactoperoxidase Monostearate Decapropyl Triol ester Monostearate Glycerol monostearate Lignostearate Tris 2-ethylhexanoate glycerol Squalane Mixing amount (% by weight) 0.1 2.0 1.0 3.0 2.0 5.0 2.0 31 200533333 Decamethylcyclopentasil Oxylan acetate dl-α-tocopherol concentrated glycerol 1,3-butanediol acrylic methacrylate copolymer preservative pH adjuster total refining water Example 4 Cream Ingredient Name Lactoferrin Co-denatured Shixadecylcyclopentasiloxane Flowing stone weir Concentrated glycerol Polyethylene glycol 1000 Ethanol Preservative pH adjuster Refined water Total 0.1.0.0 1 amount remaining 0. Appropriate residual mixing amount (weight %) 0.1 2.0 18.0 4.0 3.0 4.0 5.0 Appropriate amount Appropriate amount Residual 100 Example 5 Bath preparation ingredient Adenosine 5 ' -Total disodium phosphate, sodium bicarbonate, sodium bicarbonate, sodium carbonate, succinic acid, flavor, total amount (% by weight) 5.0 48.0 15.0 4.0 28.0 Appropriate amount 100 Example 6 Ingredient name Sodium protein Sodium gum Xylitol maltitol reduction water Glycerol flavor chewing gum Mixing amount (% by weight) 0.2 28.0 32.0 25.58 6.0 0.3 2.0 32 200533333 End of juice 6.12 Total 100 Example 7 Cooling tablets in the mouth (liquid) Ingredient name Lactoperoxidase 1 -Menthol ethanol Glycerol Monolaurate Decatriol Total blended amount of refined alcohol refined water (% by weight) 0.2 1.0 40.0 20.0 0.5 0.1 Residual amount 100

Example 8 Coolant in the mouth (liquid) Component name Chlorolysozyme 1 -Menthol Alcohol Glycerol Monolaurate Decatriol Flavor Purified water Total Mixing amount (% by weight) 0.2 1.0 40.0 20.0 0.5 0.1 Residual amount 100

Example 9 Eye Drop Ingredient Name Sodium Chloride Potassium Chloride Flavin Adenodinucleotide Sodium Hyaluronate pH Adjusting Agent Refined Water Total Mixing Amount (wt%) 0.5 0.1 0.05 0.1 Moderate Residue 100 Example 10 Nasal Ingredient Name Adenosine 5'-Phosphate Disodium Concentrated Glycerol Polyethylene Diluted Ramie Oil Hydroxypropyl Methyl Cellulose Chloramine pH Adjuster Mixing Amount (wt%) 0.5 2.5 0.2 2.0 0.005 Amount 33 200533333 Total amount of purified water remaining 100 Bubble gum mixed amount (% by weight) 7.5 7.5 40.0 30.0 15.0 100 Human yS defensin-2 production promotion confirmation test-1

Example 11 Component name Citric acid Sodium bicarbonate Xylitol Maltitol Corn starch Total Test Example 1 In order to evaluate the promotion of human Θ defensin-2 of various components shown in Table 1, the following test was performed. < Add the test sample to normal human epidermal keratinocytes and cell recovery> (1) Seed the cells (NHEK (F): normal human neonatal foreskin epidermal keratinocytes, Kurashiki) in a 10ml liquid medium (HuMedia_KG2; Normal human epidermal keratinocyte proliferation with serum-free liquid culture medium, Kurashiki) in a 10cm dish, make! 50,000cells / dish. 10 (2) Add the test sample to the cell culture solution under the condition of 80 ~ pooled, so that the final concentration is as shown in Tables 1 and 2, and incubate at 37 ° C in a 5% CO2 incubator. 4 days. The positive control was the addition of bacterial cells (107 cells / ml) that had been heat-treated with Escherichia coli ATCC 8739 at 100 ° C for 30 minutes under the same conditions. In addition, those who did not add the test 15 samples were cultured under the same conditions for comparison. In addition, each culture line was performed with n = 3. (3) The cell culture solution is recovered after 4 days of culture, and freeze-dried. The dried sample was dissolved in 10% Calf serum / RIA Buffer (0.1% Bovine Serum Albumin in PBS (-)), and the sample was separated at 300 rpm for 10 minutes. The clear solution is the measurement sample. < Evaluation of the promotion effect of human / 3defensin-2 > The concentration of human / 3defensin-2 in the sample was measured by ELISA method, and the amount of free human / 3defensin-2 in each medium was determined. . Let the amount of free human / 3 defensin-2 in the culture medium without the addition of the test sample be 1 and calculate the amount of free human point defensin-2 in the culture solution recovered 4 days after the addition of each test sample. The amount-relative value, to evaluate the promotion effect of each test sample. < Results > The results obtained in Φ are shown in Table 1. 10 From Table 1, it can be known and confirmed that the production of human / 5 defensin_2 in cells can be increased by adding various ingredients used as effective ingredients of the present invention to the culture medium. In particular, glycine, L-sulfuric acid, L · alanine, L-citrulline, propolis, lactoperoxidase, lysozyme, and lactoferrin, even at low concentrations, can achieve excellent human / Since 3 defensin-2 has a promoting effect, it has been confirmed that it is particularly useful as a 15 human / 3 defensin-2 production promoter.

35 200533333 Table 1

Test sample (brand name) Concentration in culture medium (% by weight) Production amount of human / 3 defensin-2 (relative value) No addition — 1 Escherichia coli ATCC 8739 Heat-dead bacteria 1 8 Glycine (Wako Pure Chemical Industries) 5 46 L-Aminothioic acid (Wako Pure Chemical Industries) 0.1 4 L-Alanine (Wako Pure Chemical Industries) 0.1 2 L-Citrulamic acid (Wako Pure Chemical Industries) 0.1 2 Propolis (Linwon Corporation) 0.05 3 Milk peroxidation Enzyme (DMV INTERNATIONAL) 0.2 5 Aloe extract (brand name "Aloe Extract GB-50", Xiangrong Industrial) 0.5 15 Gentian extract (brand name "Gentian Extract", Maruzen Pharmaceutical) 0.2 3 Rehmannia extract (Trade name "Rehmannia glutinosa extract", Xiang Rong Xingye) 0.2 3 Extract of rust thread (Trade name "Centrum quinquefolium extract", Xiang Rong industry) 0.2 2 Extract of Golden chrysanthemum (Trade name "Chrysanthemum Essence ", Xiang Rong Industrial Co., Ltd. 0.2 6 Huaizi Extract (trade name" Vibrator Extract ", Xiang Rong Industrial Co., Ltd.) 0.1 2 Peony Extract (trade name" Falco Rex Peony E ", Ichimaru Falco Division) 0.1 4 carrot extract (brand name Hormones Phlox Carrot ", Xiang Rong Xingye) 0.1 4 Orange Extract (Trade Name: Hormon Phlox Orange Mandarin), Xiang Rong Xingye 0.1 2 Peach Extract (Trade Name" Hermon Phlox "Peach ”, Xiang Rong Xingye) 0.1 2 Seaweed extract (trade name“ Seaweed Extract K ”, Xiang Rong Xingye) 0.2 2 Natto extract (trade name“ Soy Polymer F ”, Yimaru Falcos) 1 4 Bacillus natto force Fermentation of 14-meter extract of oral dead bacteria (trade name "GMT-SOD-5L", forest industry) 0.1 3 Wheat germ extract (trade name "HP wheat germ tooth extract", Yamamoto spice) 0.1 3 Sugar (Wako Pure Chemical Industries) 0.01 6 Inulin (Wako Pure Chemical Industries) 1 2 Poly-D-polyglutamic acid (Wako Pure Chemical Industries) 0.1 2 36 200533333 Test Example 2 Human yS defensin-2 production promotion confirmation test The various human defensins_2 production promotion shown in Tables 2 and 3 were evaluated, and the following tests were performed. < Add test sample to normal human epidermal keratinocytes and cell recovery > 5 (1) Seed the cells (NHEK (F); normal human neonatal foreskin epidermal keratinocytes, Kurashiki) in a 10 ml liquid medium ( HuMedia-KG2; Serum-free liquid culture medium, Kurashiki) for normal human epidermal keratinocyte proliferation in a 10cm dish, 1800 ~ 2400 cells / 2. (2) When the cells become pooled, add the test sample to the cell culture medium 10 so that the final concentration is as shown in Tables 3 and 4, and incubate at 37 ° C for 3 days in a 5% CO2 incubator. . As a positive control, coliform powder (Escherichia coli KI2, Lyophilized cells (SIGMA)) was added to 0.001% by weight 'and cultured under the same conditions. In addition, the test samples were also cultured under the same conditions for comparison without comparison. In addition, each of the culture lines 15 was performed at n = 1 to 3. (3) Collect the cell culture solution after 3 days of culture and freeze-dry it. The dried sample has a proper amount of 10% Calf serum / RIA Buffer (〇 1%

Bovine Serum Albumin in PBS (-)) was dissolved and centrifuged at 5000 rpm for 15 minutes. The upper clear solution was used as a measurement sample. In addition, 1% lysozyme was not freeze-dried, and the culture supernatant liquid was used as a measurement sample. < Evaluation of the effect of promoting the production of human yS defensin-2> The human cold defensin concentration in the aforementioned measurement sample was measured by ELISA method, and the amount of human 0 defensin_2 free in each medium was determined. Let the amount of free human 0 defensin_2 in the medium without added test samples be 丨, and calculate the amount of free human yS defensin-2 in the culture fluid recovered on the 3rd day after adding 37 200533333 after adding each test sample. Relative value to evaluate the promotion effect of each test sample. < Results > The results obtained are shown in Tables 2 and 3 together. From Tables 2 and 3, it is known and confirmed that the production of human yS defensin-2 in cells can be increased by adding various components used as the effective components of the present invention to the culture medium. Table 2

Test sample (trade name and supply company) Concentration in culture medium (% by weight) Production amount of human / 3 defensin-2 (relative value) No addition — 1 AMP2Na (trade name "5'-adenosine disodium", flax Soy sauce) 0.1 5 Concentrated milk protein (trade name "MPC80", DMV INTERNATIONAL) 1 132 Soy protein hydrolysate (trade name "SE70M", DMV INTERNATIONAL) 1 9 Wheat protein hydrolysate glutamate peptide (trade name "WGE80GPN" DMV INTERNATIONAL) 1 3 Whey Protein Hydrolysate (average molecular weight 570D) (trade name "WE80BG", DMV INTERNATIONAL) 1 6 Whey Protein Hydrolysate (average molecular weight 11532D) (trade name "WE80FG" DMV INTERNATIONAL) 1 95 Casein Magnesium (Trade name "MAGNECIUM CACEINATE S", DMV INTERNATIONAL) 1 39 Casein hydrolysate (average molecular weight 640D) (Trade name "CE90GMM", DMV INTERNATIONAL) 1 17 Dopan (Trade name "Sang Fu La Bang", Sun Chemical ) 1 2 Grape seed variety (brand name "Gravinol", Biochemicals Division) 1 2 38 200533333 Table 3 Concentration in test sample medium (% by weight) human / 3 Production of defensin-2 (relative value) No added — 1 coliform powder (from St.K-12) 0.001 121 Lactoferrin (DMV INTERNATIONAL) 0.01 3 0.1 4 1 12 Lactoperoxidase (DMV INTERNATIONAL) 0.01 1 0.1 7 1 170 Lysozyme (trade name "Lysozyme, Chicken Egg White", CALBIOCHEM) 0.01 2 0.1 62 1 1484 Test example 3 Human / 3 defensin-2 production promotion confirmation test-3

The promotion effect of human / 3 defensin-2 achieved by combining the components shown in Tables 4 and 5 was evaluated by the same method as in Test Example 2 described above. 5 The results obtained are shown in Tables 4 and 5. From Tables 4 and 5, it can be known and confirmed that the various ingredients used as the active ingredients of the present invention have a human / 3 defensin-2 promoting effect even when used alone. In addition, the combined use of two or more ingredients as the effective ingredients of the present invention can increase the amount of human cold defensin-2 produced in proportion to the case where it is used alone. 10 Table 4 Concentrations in test sample culture medium (% by weight) Production of human / 3 defensin-2 (relative value) No added — 1 lactoferrin 0.2 4 lactoperoxidase 0.2 26 lysozyme 0.2 62 lactoferrin + milk Peroxidase 0.2 9 each lactoperoxidase + lysozyme 0.2 66 each lactoferrin + lysozyme 0.2 453 each lactoferrin + lysozyme + lactoperoxidase 0.2 each 158 39 200533333 Table 5 Test samples (trade name and supply Company) Concentration in culture medium (% by weight) Production of human / 3 defensin-2 (relative value) No addition — 1 lactoperoxidase ("Lactoperoxidase", DMV INTERNATIONAL) 0.2 64 AMP2Na (trade name "5'-gland Disodium glycoside ”, flax soy sauce) 0.1 5 Concentrated milk protein (trade name“ MPC80 ”, DMV INTERNATIONAL) 1 132 Whey protein hydrolysate (average molecular weight 570D) (trade name“ WE80BG ”, DMV INTERNATIONAL) 1 6 Milk Albumin hydrolysate (average molecular weight 11532D) (trade name "WE80FG" manufactured by DMV INTERNATIONAL) 1 95 lactoperoxidase + AMP2Na 0.2 0.1 245 lactoperoxidase + concentrated milk protein 0.2 1.0 498 Enzyme + whey protein hydrolyzate (average molecular weight of 570D) 0.2 1.0 144 lactoperoxidase + whey protein hydrolyzate (average molecular weight of 11532D) 0.2 1.0 365

Industrial Applicability It is currently known that human point defensins have the following excellent characteristics: (a) because it has antibacterial properties, it can exert antibacterial effects in a short time; (b) because it is derived in vivo, it is effective for Xi It is known that antibacterial agents have difficulty in using external or internal forms to administer drugs, and can also exhibit excellent antibacterial effects; (c) chemotactic dendritic cells or memory T lymphocytes (that is, mobilize immune-responsible cells to Immune-related), and (d) has an epithelial tissue repair promoting effect. The human yS defensin-derived promoter of the present invention can promote the derivation of / 3 defensins in vivo, especially the derivation of human / 3 defensins-2. Therefore, the human stone defensin production promoter of the present invention can promote the / 3 defensin derivation, enhance the antibacterial effect, anti-inflammatory effect or immune effect in the living body, and improve the infection defense mechanism of the living body. In addition, there are reports that / 3 defensin can be derived from epithelial tissue repair and tumor immunity, and exerts wound healing or antitumor effects. Therefore, it is estimated that the comprehensive defense mechanism in vivo can be further strengthened.

Therefore, the human / 5 defensin production promoter of the present invention can effectively prevent or alleviate symptoms caused by bacterial, fungal, viral, and protozoal infections, such as 5 to prevent secondary infections of atopic dermatitis, and to prevent facial blistering. Acne, prevent periodontal disease, prevent bad breath, prevent foot odor, prevent secondary infections after shaving and epilation, prevent secondary infections of diaper rash, prevent secondary infections of gardenia, prevent secondary infections due to burns, prevent causes The susceptibility caused by the use of steroids is also effective for skin care such as rough skin, dry skin, rich hands, and prevention of athlete's foot. 10 Moreover, the human point defensin production promoter of the present invention can be expected to have a pharmacological effect based on the human cold defensin production promotion effect. Therefore, the human point defensin production promoter of the present invention can prevent or treat viral conjunctivitis, bacterial conjunctivitis, stye, corneal injury, etc. when administered into the eye; when administered into the nasal cavity or throat, it can prevent or treat Colds, influenza, etc .; When administered in the nasal cavity, it can prevent or treat rhinitis, purulent rhinorrhea, paranasal inflammation, etc .; When it is used in the mouth, it can prevent or treat periodontal disease, intraoral inflammation, tooth decay, bad breath When used on the lips, it can prevent or treat simple herpes. When used on the skin, it can prevent or treat athlete's foot, herpes, warts, infectious soft swelling, chicken pox, sexual organ vesicle virus infection, Candidiasis, vesicular therapy, bubble therapy alone, facial blisters, 20 atopic dermatitis, trauma treatment, etc .; when used in other parts, it can be used as pneumonia, gastritis, tumors, acquired immunodeficiency, trypanosomiasis Preventive or therapeutic agents for diseases. Among these diseases, they are particularly useful as preventive or therapeutic agents for diseases related to bacteria, fungi, viruses, and protozoa. In addition, the human of the present invention; 5 defensin production promoter, exhibits the promotion effect of epithelial tissue repair on the eyes, nose, oral cavity, trachea, esophagus, other digestive organs, 41 200533333 genitals and skin, so it has an effect on infection, inflammation or Recovery from other injuries is also useful. In particular, the human / 3 defensin production promoter of the present invention can exert excellent defensin production promotion effects in mucosal tissues such as the eyes, nose, anus, trachea, esophagus, and oral cavity, and can therefore be used in preparations for mucosa. Among them, the human / 5 defensin production-promoting agent of the present invention can be effectively used as a preventive or therapeutic agent for periodontal disease, intrastomatitis, tooth decay, bad breath, eye infections, corneal damage, rhinitis, and the like. Therefore, the human defensin production promoter of the present invention can be used as an oral care product, an eye care product, and a nasal care product to maintain a healthy environment of the mouth, eyes, or nose. 10 [Schematic description] None [Description of main component symbols] None 42

Claims (1)

200533333 10. Scope of patent application: 5 10 15 20 1. A human / 3 defensin production promoting agent selected from the group consisting of extracts from aloe, extracts from gentian, extracts from rehmannia glutinosa, extracts from rust, extracts from coneflower, extracts from gardenia, Peony extract, carrot extract, orange extract, peach extract, seaweed extract, natto extract, levans, inulin, dodecyl acid, natto bacteria, rice extract and other fermented products, wheat germ Extracts, wheat hydrolysates, soy hydrolysates, glycine, L-methionine, L-alanine, L-citrulline, propolis, polyphenols, throat nucleic acid-related substances, milk proteins, casein , Casein hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and at least one component of a group formed by lactoferrin as an active ingredient. 2. For example, the human / 3 defensin production promoter in the scope of the patent application, wherein the active ingredient is selected from the group consisting of glycine, L-methionine, L-alanine, L-citrulline, Propolis, milk protein, casein, casein hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme and lactoferrin. 3. The human point defensin production promoter according to item 1 of the patent application scope, wherein the active ingredient is selected from the group consisting of milk protein, casein, casein hydrolysate, whey protein, whey protein hydrolysate, and milk. At least one component of a group formed by oxidase, lysozyme, and lactoferrin. 4. A human pupal defensin production promoting agent selected from the group consisting of extracts from aloe, extracts from gentian, extracts from radix rehmanniae, extracts from rusty clover, extracts from rudbeckia, extracts from gardenia, and extracts from peony. Extract, carrot extract, orange extract, peach extract, seaweed extract, natto extract, levan, 43 200533333 5 10 15 . 20 inulin, polyglycolic acid, natto bacteria, rice fermentation extract, wheat germ extract, wheat hydrolysate, soybean hydrolysate, glycine, L-methionine, L-alanine, L-citrulline Groups of acids, propolis, polyphenols, purine-based nucleic acid-related substances, milk proteins, casein, casein hydrolysates, whey proteins, whey protein hydrolysates, lactoperoxidase, lysozyme, and lactoferrin Those with at least two ingredients as active ingredients. 5. If the human cold defensin production promoter of item 1 of the scope of patent application is applied, its production promotion object is human 0 defensin-2. 6. For example, the human / 3 defensin production promoter in the scope of patent application is an internal medicine. 7. The human cold defensin production enhancer as claimed in item 1 of the patent application is a food. 8. If the human / 3 defensin production promoter in the scope of the patent application is applied, it is an external medicine or cosmetic. 9. If the human / 3 defensin production promoter in the scope of patent application is No. 1, it is a bathing agent. 10. A method for promoting the production of human / 3 defensins, which is selected from the group consisting of extracts from aloe, extracts from gentian, extracts from rehmannia glutinosa, extracts from rusty clover, extracts from coneflower, and extracts from gardenia. , Peony extract, carrot extract, orange extract, peach extract, seaweed extract, natto extract, levans, inulin, dodecyl acid, natto bacteria, rice extract and other fermented products, wheat Germ extract, wheat hydrolysate, soy hydrolysate, glycine, L-sulfuric acid, L-alanine, L-citrulline, propolis, polyphenols, purine-based nucleic acid related substances, milk protein, casein , Casein hydrolysate, whey protein, milk 44 200533333 albumin hydrolysate, lactoperoxidase, lysozyme and lactoferrin, an effective amount of at least one component of the group, suitable for internal or external use Hope the human / 3 defensin production promoter. 11. If the method for promoting the production of human stone defensins in item 10 of the scope of the patent application is applied, the human yS defensin production promoter in any of the scope of applications 1 to 9 of the patent application shall be used appropriately for internal or external use. Yu hopes that human yS defensin production promoters. 10 15 12. —Uses selected from aloe extract, gentian extract, rehmannia extract, clematis extract, coneflower extract, vibrator extract, peony extract, carrot extract, Orange extract, peach extract, seaweed extract, natto extract, fermented substances such as levans, inulin, polyquinic acid, natto bacteria, rice extract, wheat germ extract, wheat hydrolysate, soybean Hydrolysates, glycine, L-methionine, L-alanine, L-citrulline, propolis, polyscore, sigmoidin-based nucleic acid-related substances, milk protein, cool protein, brewed protein hydrolysate, At least one component of a group formed by whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and lactoferrin is used to produce a human / 3 defensin production promoter. 13. A use selected from the group consisting of milk protein, casein, casein hydrolysate, whey protein, whey protein hydrolysate, lactoperoxidase, lysozyme, and lactoferrin A promoter for the production of human / 3 defensins. 45 200533333 VII. Designated Representative Map: (1) The designated representative map in this case is: (none) map. (2) Brief description of the representative symbols of the components in this representative map: 8. If there is a chemical formula in this case, please disclose the chemical formula that best shows the characteristics of the invention: