HK1092057B - HUMAN β-DEFENSIN SECRETION PROMOTER - Google Patents
HUMAN β-DEFENSIN SECRETION PROMOTER Download PDFInfo
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- HK1092057B HK1092057B HK06112727.9A HK06112727A HK1092057B HK 1092057 B HK1092057 B HK 1092057B HK 06112727 A HK06112727 A HK 06112727A HK 1092057 B HK1092057 B HK 1092057B
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Description
Technical Field
The present invention relates to a beta defensin secretion promoter capable of promoting the secretion of beta defensin. Furthermore, the present invention relates to a method for promoting secretion of beta defensin.
Background
It is known that plants, insects, amphibians, mammals and the like have an antibacterial substance (antibacterial peptide) as an inherent defense mechanism in the body. This is called innate immunity and bears the defense against local infections. Defensins, which are one of the antibacterial peptides in the human body, are known to have antibacterial activity against bacteria, fungi, protozoa, viruses, and the like, and to participate in various body defense mechanisms in the body.
Beta defensins are known as defensins appearing on mucosal epithelia such as skin, lung, trachea, kidney, and genitals. Now, the structures of 6 kinds of human beta defensins (human beta defensin-1, human beta defensin-2, human beta defensin-3, human beta defensin-4, human beta defensin-5, and human beta defensin-6) have been isolated and determined. In particular, beta-defensin-2 has been found to be particularly strongly expressed in the skin, lung, trachea and oral mucosa, and is characterized by induction of bacterial infection and inflammatory cytokine-stimulated expression (refer to Futian philosophy, et al, "defensin as a defense mechanism of the body", journal of Japanese aged medical society, 2001, Vol. 38, No. 4, page 440-443), indicating that it is closely related to tracheal infection and inflammation such as pneumonia.
In recent years, it has been reported that β defensins not only protect against local infection, but also participate in acquired immunity by mobilizing stem cells, T lymphocytes, and monocytes. (see Yang, D., Chertov, 0., Bykovskaia, S.N.et. al., "β -defenses: linking in and Adaptive immune response through diagnostic and T cell CCR 6", Science, 1999, vol.286, p.525; Territo, M.C., Ganz, T., Selsted, M.E.et. et. al., "monoclonal-chemometric activity of defenses from microorganisms, J.Clin.vector., 1989, vol.84, p.2017; Lillard, J.W., Jr., Boyaka, P.N., Chertov.0. et. e., Mechnical for obtaining, Achilled, P.N., Cherton.0. et. e.7, immune response of Del. et. I., S.N.7, Nat. 7, S.7. et. 7. et. p.7. et. 7. et. in immune response to S.7. et. Nature, S.7. et. No. 7, Nature, S.7. et. No. 3. Immunity, S. 3, S. 7, et. No. 3, et. Immunity, et. No. 3, 2, Immunity, et al., Immunity, et.
Heretofore, inflammatory cytokines and lipopolysaccharides have been known to have an effect of promoting secretion of human beta defensins. However, the mechanism of production and secretion of human beta-defensins has not been fully understood. Methods for promoting the secretion of human beta-defensins other than the above-mentioned substances are not clear.
Disclosure of Invention
The purpose of the present invention is to provide a beta-defensin secretion promoter capable of promoting the secretion of human beta-defensin. It is another object of the present invention to provide a human beta-defensin secretion promoter which can be used in various forms such as an external preparation, an internal preparation, and a food.
It is another object of the present invention to provide a method for effectively promoting the secretion of human beta-defensin.
The present inventors have intensively studied to solve the above problems, and as a result, have found that an organic acid has an action of promoting the secretion of human beta defensin. The present invention has been developed based on such findings and further through repeated studies.
That is, the present invention is a human beta-defensin secretion promoter described below.
A human beta defensin secretion promoter characterized by comprising an organic acid as an active ingredient.
The human beta-defensin secretion promoter according to [1], wherein the organic acid is at least one selected from the group consisting of fumaric acid, malic acid, citric acid, ascorbic acid, lactic acid, acetic acid, adipic acid, tartaric acid, cinnamic acid, glutamic acid and succinic acid.
The human beta-defensin secretion promoter according to [1], wherein the organic acid is at least one selected from fumaric acid, malic acid, citric acid and tartaric acid.
The human beta-defensin secretion promoter according to [1], wherein the human beta-defensin to be secretion-promoted is human beta-defensin-2.
The human beta-defensin secretion promoter according to [1], which is used in the oral lip or the oral cavity.
A composition for external use for promoting secretion of human beta-defensin, comprising the human beta-defensin secretion promoter according to any one of [1] to [4 ].
An oral composition for promoting secretion of human beta-defensin, comprising the human beta-defensin secretion promoter according to any one of [1] to [4 ].
A food for promoting the secretion of human beta-defensin, comprising the human beta-defensin secretion promoter according to any one of [1] to [4 ].
The present invention also provides a method for promoting the secretion of human beta-defensin, which comprises:
a method of promoting the secretion of human beta defensin comprising administering or causing the ingestion thereof an effective amount of an organic acid.
The method for promoting secretion of human beta-defensin according to [9], wherein the organic acid is at least one selected from the group consisting of fumaric acid, malic acid, citric acid, ascorbic acid, lactic acid, acetic acid, adipic acid, tartaric acid, cinnamic acid, glutamic acid and succinic acid.
The method for promoting secretion of human beta-defensin according to [9], wherein the organic acid is at least one selected from the group consisting of fumaric acid, malic acid, citric acid and tartaric acid.
The method for promoting the secretion of human beta-defensin according to [9], wherein the human beta-defensin to be secretion-promoted is human beta-defensin-2.
The method for promoting secretion of human beta-defensin according to [9], wherein the secretion of human beta-defensin is promoted in the oral lip or the oral cavity.
The method for promoting secretion of human beta-defensin according to [9], wherein the human beta-defensin promoter according to any one of [1] to [5] is used as the organic acid.
The method for promoting secretion of human beta-defensin according to [9], which uses the composition for internal use according to [6] as an organic acid.
The method for promoting secretion of human beta-defensin according to [9], which comprises using the food according to [7] as an organic acid.
The method for promoting secretion of human beta-defensin according to [9], which comprises using the composition for external use according to [8] as an organic acid.
The present invention is also directed to the use of:
use of an organic acid for producing a secretion promoter for human beta-defensin.
Use of an organic acid for the manufacture of an oral composition for promoting the secretion of human beta defensin.
Use of an organic acid for the manufacture of a food product for promoting the secretion of human beta defensin.
Use of an organic acid for the manufacture of a topical composition for promoting the secretion of human beta defensin.
Use of an organic acid for promoting the secretion of human beta defensin.
Drawings
FIG. 1 is a graph showing the amount (ng/min) of human beta-defensin-2 promoting secretion in saliva when each organic acid was applied to the oral cavity in test example 1.
FIG. 2 is a graph showing the amount (ng/min) of human beta-defensin-2 promoting secretion in saliva when each organic acid was applied to the oral cavity in test example 2.
FIG. 3 is a graph showing the amount (ng/min) of human beta-defensin-2 promoting secretion in saliva when various amounts of malic acid were applied to the oral cavity in test example 3.
Detailed Description
(1) Human beta defensin secretion promoter
In the human beta-defensin secretion promoter of the present invention, the human beta-defensin to be secretion-promoted contains: human beta defensin-1, human beta defensin-2, human beta defensin-3, human beta defensin-4, human beta defensin-5 and human beta defensin-6. Among these substances, human beta-defensin-2 is the most suitable target for promoting secretion because it promotes secretion more efficiently.
The active ingredient of the beta defensin secretion promoter of the present invention is an organic acid. The organic acid used in the present invention is not particularly limited as long as it is pharmaceutically, cosmetically or food hygienically acceptable. Examples of the organic acid used in the present invention include: monocarboxylic acids such as formic acid, acetic acid, propionic acid, butyric acid, valeric acid, caproic acid, caprylic acid, capric acid, lauric acid, myristic acid, palmitic acid, stearic acid, acrylic acid, propionyl acid, cinnamic acid, and caffeic acid; dicarboxylic acids such as oxalic acid, malonic acid, succinic acid, n-glutaric acid, adipic acid, pimelic acid, fumaric acid, maleic acid, phthalic acid, isophthalic acid, and terephthalic acid; amino acids such as glutamic acid and aspartic acid; glycolic acid, malic acid, tartaric acid, isotartaric acid, citric acid, isocitric acid, lactic acid, hydroxyacrylic acid, α -hydroxybutyric acid, glyceric acid, hydroxymalonic acid, salicylic acid, gallic acid, tropic acid, ascorbic acid, gluconic acid, and the like; folic acid; pantothenic acid; nicotinic acid; and other organic acids such as sugar derivatives. Among these organic acids, fumaric acid, malic acid, citric acid, ascorbic acid, lactic acid, acetic acid, adipic acid, tartaric acid, cinnamic acid, glutamic acid and succinic acid are preferable. More preferred are fumaric acid, malic acid, citric acid and tartaric acid. These organic acids may be used alone, or 2 or more of them may be used in any combination. In the present invention, a salt of the organic acid may be used as an active ingredient in place of or in combination with the organic acid, as pharmaceutically, cosmetically or food hygienically acceptable.
The organic acid may not necessarily be a purified substance, and may be used as an active ingredient of the human beta-defensin secretion promoter of the present invention as long as it contains the organic acid as one of the components.
The human beta defensin secretion promoter of the present invention may be a substance composed of the above active ingredient, or a substance containing other ingredients such as a base, a carrier or an additive which are acceptable in food hygiene, pharmacy or cosmetics, in addition to the above active ingredient.
The target of application of the human beta-defensin secretion promoter of the present invention is not particularly limited, and may be any part or tissue of a living body. From the viewpoint of further excellent promotion of secretion of human beta-defensin, the nasal cavity, the anal region, the respiratory tract, the oral lip, the oral cavity, the pharynx, the eye, the genitalia, the skin, the digestive tract and the like are preferable subjects to be applied, and particularly, the mucosal transition region and the mucosal epithelium thereof are preferable subjects to be applied. Among them, the human β -defensin secretion promoting action is particularly excellent in the oral lip and the oral cavity, and the oral lip and the oral cavity are the most suitable application targets of the human β -defensin secretion promoting agent of the present invention.
The human beta-defensin secretion promoter of the present invention can be used as a food or an oral composition for promoting the secretion of human beta-defensin in combination with foods, oral drugs, external preparations, and the like. The human beta-defensin secretion promoter of the present invention may be used as an external composition for promoting secretion of human beta-defensin in combination with external drugs, external medical products for external use, cosmetics, external products (adhesive plasters), and the like.
When preparing the human beta-defensin secretion-promoting external composition containing the human beta-defensin secretion-promoting agent of the invention, a desired form can be prepared by adding a pharmaceutically or cosmetically acceptable base material or carrier to the above active ingredient. In addition, various additives such as various surfactants, pigments (dyes and pigments), perfumes, preservatives, bactericides (antibacterial agents), thickeners, antioxidants, metal sealants, cooling agents, deodorants, and pH adjusters may be blended in the composition for external use within a range not to impair the effects of the present invention. If necessary, the composition may further contain known pharmaceutical ingredients blended with external preparations such as a moisturizer, an ultraviolet absorber, an ultraviolet diffusing agent, vitamins, plant extracts, a skin astringent, an anti-inflammatory agent (anti-inflammatory agent), a whitening agent, a cell activator, a vasodilator, a blood circulation promoter, a skin function promoter, an antiallergic agent, an antihistamine, an antibiotic and the like.
The composition for external use is not particularly limited in shape, and can be applied to the skin and mucous membranes. Examples include: liquid, emulsion, powder, suspension, cream, ointment, mousse, gel, jelly, paste, thin shell, stick, aerosol, spray, liniment, filler, and patch. The shape of the composition for external use may be appropriately set according to the site to be administered.
The above-mentioned external composition is an external composition having an action other than the secretion-promoting action of human beta defensin, as long as the secretion-promoting action of human beta defensin is exerted, and specifically, may be in the form of a wound healing agent, a wiping agent, a cleansing agent (for example, a wash pigment, a cleanser, a body cleanser, etc.), a base cosmetic (for example, an emulsion, a cream, a lotion, an oil, a mask, etc.), a toothpaste, a mouth wash, a mouth freshener, an oral patch, etc. In particular, from the viewpoint of exerting the secretion promoting effect of human beta-defensin when applied in the oral cavity, the form of a stick, toothpaste, mouthwash or mouth freshener for oral use is preferable.
The composition for external use may be in the form of an enema, eye drops, nasal drops, or the like.
In addition, as long as the evaporation organic acid is used as an active ingredient of the human beta defensin secretion promoter, the active ingredient may be volatilized (evaporated) and inhaled to be applied to the inside of the nostril, the oral cavity or the bronchus. Examples of the method used in this form include: heating an aqueous solution containing an active ingredient, and inhaling the obtained vapor. The above-mentioned composition for external use may be prepared in a form in which the active ingredient is volatilized and used. When formulated in such a form, the external composition can be used as a fragrant liquid by containing a fragrant component as needed. Examples of the evaporative organic acids used as the active ingredient of the human beta-defensin secretion promoter include: acetic acid, propionic acid, formic acid, butyric acid, valeric acid, and the like.
The mixing ratio of the human β -defensin secretion promoter in the composition for external use for promoting β -defensin secretion may be appropriately set according to the form of the composition, the kind of the active ingredient, the age and sex of the subject to be used, the desired effect, and the like. For example, the proportion of the active ingredient of the human beta-defensin secretion promoter is 0.001 wt% or more, preferably 0.005 to 99 wt%, more preferably 0.01 to 99 wt% in total, based on the total weight of the external composition.
The human beta-defensin secretion promoter of the present invention can exert a beta-defensin secretion promoting effect by being applied to the skin or mucous membrane. The amount and frequency of application of the human beta-defensin secretion promoter are appropriately set according to the kind and concentration of the active ingredient, the age and sex of the user, the application form, and the desired degree. For example, 0.1mg or more, preferably 0.5 to 10000mg of the active ingredient of the human beta-defensin secretion promoter may be applied to the skin or mucous membrane 1 to 10 times a day.
In addition, when preparing a food for promoting secretion of human β -defensin, which contains the human β -defensin secretion promoter of the present invention, the food (including a beverage) may be blended with the above-mentioned active ingredient as one component in general food production. The food for promoting the secretion of human beta-defensin may contain various food additives that are acceptable in food hygiene.
Examples of the food include: specific health food, nutrition supplementary food, and food for patients. More specific examples are: beverages (carbonated beverages, refreshing beverages, milk-containing beverages, alcoholic beverages, fruit juice beverages, teas, nutritional beverages, etc.), powdered beverages (powdered fruit juices, powdered soup bases, etc.), cakes (chewing gums, candies, cookies, elaeagnus pungens, cookies, biscuits, jellies, caramels, lemon cakes, edible sheets, edible films, tablets, etc.), mouth refresheners (chewing gums, sugars, elaeagnus pungens, edible sheets, edible films, tablets, etc.), dairy products (cheeses, yogurt, etc.), bread, noodles, skewers, seasonings (dips, sauces, etc.), and the like. From the viewpoint of promoting the secretion of human beta-defensin in the oral cavity, among them, suitable are, for example: chewing gum, Elaeagnus pungens, cold beverage, candy, edible sheet and edible film.
The ratio of the human beta-defensin secretion promoter to be blended in the food for promoting the secretion of human beta-defensin can be appropriately set according to the kind of the active ingredient, age and sex of the subject to be used, desired effect, and the like. For example, the proportion of the active ingredient of the human beta-defensin secretion promoter is 0.01 wt% or more, preferably 0.02 to 100 wt%, and more preferably 0.05 to 100 wt% based on the total weight of the food.
The daily intake amount of the food for promoting secretion of human beta-defensin can be appropriately set to an effective amount necessary for promoting secretion of human beta-defensin according to the kind and concentration of the active ingredient, the age and sex of the user, the shape of the food, and the desired effect level. For example, the food is ingested in an amount of 0.1mg or more, preferably 0.5 to 10000mg, as an active ingredient for promoting the secretion of human beta-defensin per day.
In addition, when preparing an oral pharmaceutical composition or an oral pharmaceutical composition for promoting the secretion of human beta-defensin, which contains the human beta-defensin secretion promoter of the present invention, a pharmaceutically acceptable base material or carrier may be added to the above active ingredient to prepare a desired form. Further, pharmaceutically acceptable additives such as a binder, a disintegrant, a lubricant, a wetting agent, a buffer, a preservative, and a perfume may be optionally blended as required.
The form of the oral pharmaceutical composition or the external composition is not particularly limited, but is preferably soluble in mucous membranes, particularly in the oral cavity. For example, film preparations, tablets, chewable tablets, powders, lozenges, granules, capsules, syrup preparations and the like. Among them, from the viewpoint of being soluble in the oral cavity, film preparations, tablets and chewable tablets are preferable, for example.
The mixing ratio of the human beta-defensin secretion promoter in the oral pharmaceutical composition or the external pharmaceutical composition may be appropriately set according to the kind of the active ingredient, the form of the composition, the age and sex of the subject to be used, the desired effect, and the like. For example, the ratio of the active ingredient of the human beta-defensin secretion promoter to the total weight of the oral pharmaceutical composition or the external pharmaceutical composition is 0.01 wt% or more, preferably 0.02 to 99 wt%, and more preferably 0.05 to 99 wt%.
The daily dose of the oral pharmaceutical composition or the external pharmaceutical composition varies depending on the kind and concentration of the active ingredient, the age and sex of the user, the shape of the composition, the method of administration, the desired degree, and the like, and therefore cannot be determined uniformly, and is an effective amount for promoting the secretion of human beta-defensin. For example, the effective component for promoting secretion of human beta-defensin is administered in an amount of 0.1mg or more, preferably 0.5 to 10000mg per time, and the administration is performed about 1 to 10 times per day.
As described above, the organic acid has an effect of promoting secretion of human beta defensin. Thus, the present invention further provides the use of an organic acid for producing a human beta defensin secretion promoter. The present invention also provides the use of an organic acid for producing an external composition or an internal composition for promoting the secretion of human beta-defensin.
(2) Method for promoting secretion of human beta defensin
As described above, the organic acid can effectively promote the secretion of human beta defensin. Accordingly, the present invention provides a method for promoting the secretion of human beta defensin using an organic acid.
The method for promoting the secretion of human beta-defensin of the present invention can be performed by administering an organic acid in a form other than the drug to a body site intended for the promotion of the secretion of human beta-defensin. The method for promoting the secretion of human beta-defensin of the present invention may be performed by administering or ingesting an organic acid in an oral form. The method of the present invention is preferably carried out by using the human beta-defensin secretion promoter of the above (1), particularly an external composition, an internal composition or a food for promoting human beta-defensin secretion.
In the method of the present invention, the human beta-defensin whose secretion is promoted, the organic acid used, the amount and frequency of administration of the organic acid, the body part (or tissue) to be the secretion-promoting subject, and the like are as described in the above (1).
By using an organic acid, the secretion of human beta defensin can be effectively promoted. Thus, the present invention further provides the use of an organic acid for promoting the secretion of human beta defensin.
(3) Method for promoting secretion of human beta defensin-2
Further, the present inventors have found that secretion of human β defensin in the oral cavity can be promoted by temporarily changing the environment in the oral cavity to an acidic environment. Based on such findings, the present invention further provides a method for promoting the secretion of human beta-defensin in the oral cavity. When the secretion of human beta-defensin is promoted by such a method, the temporal acidity of the oral environment, specifically, the pH in the oral cavity is maintained at 7 or less, preferably 6.2 or less. In such a method, the time for maintaining the acidic environment in the oral cavity may be an effective retention time for promoting the secretion of human beta-defensin. In such a method, the organic acid may be administered, for example, in the oral cavity in order to make the oral environment acidic. In a preferred embodiment of such a method, for example, the human beta-defensin secretion promoter is administered orally. According to this method, since the oral health can be maintained, the method has a certain effect in preventing and alleviating periodontal disease, stomatitis, dental caries, halitosis, etc.
In the use of the human beta-defensin secretion promoter of the above (1) or the human beta-defensin secretion promoting method of the above (2), the pH conditions on the skin and mucous membrane are not particularly limited.
Examples
The present invention will be described below by way of examples and test examples, but the present invention is not limited to these examples. Hereinafter, the human beta defensin may be abbreviated as hBD-2.
Example 1 chewing gum
Chewing gum of the following formulation was manufactured according to a common method.
Compounding amount (% by weight)
Lime powder 5.0
(75 wt% citric acid in lime powder)
Gum base (main component: vinyl acetate) 22.0
Xylitol 35.0
Maltitol 27.0
Proper amount of perfume
Total 100% by weight
Example 2 lemon pastry
Lemon pastry of the following formulation was manufactured according to a common method.
Compounding amount (% by weight)
Malic acid 7.5
Sodium bicarbonate 7.5
Xylitol 40.0
Maltitol 30.0
Corn starch 15.0
Total 100% by weight
EXAMPLE 3 mouth freshener (liquid)
The mouth freshener (liquid) of the following formulation was produced according to a usual method.
Compounding amount (% by weight)
Lactose 0.2
1-menthol 1.0
Ethanol 40.0
Glycerol 20.0
Monolauric acid decaglycerol ester 0.5
Fragrance 0.1
Residual amount of pure water
Total 100% by weight
EXAMPLE 4 mouth Cooling agent (tablet)
The mouth coolants (tablets) of the following formulation were produced in accordance with a usual method.
Compounding amount (% by weight)
Tartaric acid 45
1-menthol 1
Sodium bicarbonate 24
Lactose 25
Sucrose fatty acid ester 3
Flavour enhancers 1
Sweetener 1
Total 100% by weight
EXAMPLE 5 food product (tablet)
The following formulation of the food (tablet) was prepared according to a usual method.
Compounding amount (% by weight)
Ascorbic acid 5.0
Lactose 85.5
Xylitol 5.0
Sucrose fatty acid ester 4.0
Flavor enhancer 0.5
Total 100% by weight
EXAMPLE 6 liquid toothpaste
The following prescription of liquid toothpaste was made according to a usual method.
Compounding amount (% by weight)
Fumaric acid 45
1-menthol 1
Sodium bicarbonate 24
Lactose 25
Sucrose fatty acid ester 3
Flavour enhancers 1
Sweetener 1
Total 100% by weight
Example 7 fragrance liquid
The following aromatic liquids were prepared according to a conventional method.
Compounding amount (% by weight)
Pure water 54
Anhydrous ethanol 40
Lemon extract 4
Grapefruit extract 1
Acetic acid 1
Proper amount of perfume
Total 100% by weight
EXAMPLE 8 nasal drops
The nasal drops of the following formulation were prepared according to a conventional method.
Ingredient name and mixing amount (% by weight)
Sodium chloride 0.9
Citric acid 1.0
proper amount of pH regulator
Residual amount of pure water
Total 100% by weight
Example 9 eye drops
The following eye drops were prepared according to a conventional method.
Ingredient name and mixing amount (% by weight)
Sodium chloride 0.9
Potassium chloride 0.1
Flavin adenine dinucleotide 0.05
Hyaluronic acid sodium salt 0.1
Citric acid 1.0
proper amount of pH regulator
Residual amount of pure water
Total 100% by weight
Test example 1Test 1 for confirming the promotion of secretion of beta defensin
In order to evaluate the effect of various organic acids on promoting the secretion of β defensin, the following test was performed with the healthy person 1 as the subject.
Saliva secreted by the test subjects in a resting state for 3 minutes was collected by a spitting method (hereinafter, this saliva was referred to as a control). Thereafter, 50mg of fumaric acid was placed in the oral cavity, and after keeping for 1 minute, it was collected together with the secreted saliva. The concentration of human beta-defensin-2 in the collected saliva was measured by ELISA method, and the amount of human beta-defensin-2 secreted by the organic acid within 1 minute was calculated according to the following calculation formula. The saliva amount (ml) in the following formula was calculated, and the saliva weight (g) was calculated from the saliva collected, assuming that the saliva weight (1 g) was 1 ml. The same tests as above were carried out using ascorbic acid, citric acid, malic acid, lactic acid, adipic acid, acetic acid and tartaric acid instead of fumaric acid. In the case of using lactic acid and acetic acid, the above test was performed by inhaling into the oral cavity an aqueous solution prepared by adding water to 50mg of the organic acid to a total amount of 1 g.
Calculation formula
[ amount of hBD-2 secreted in 1 minute (ng/min) ] -, i.e.
{ [ concentration of hBD-2 in saliva (ng/ml) ] × [ saliva amount (ml) ] }/[ saliva recovery time (min) ]
# saliva recovery time, 3 minutes in the case of control and 1 minute in the case after organic acid administration.
The results obtained are shown in FIG. 1. From this, it is found that the amount of human beta-defensin-2 secreted in saliva is increased by applying an organic acid to the oral cavity. From these results, it was confirmed that the organic acid had an effect of promoting the secretion of human beta-defensin-2 in vivo, and particularly, had an excellent effect of promoting the secretion of human beta-defensin-2 in the oral cavity.
Test example 2Test 2 for confirming the promotion of secretion of beta defensin
In order to evaluate the effect of various organic acids on promoting the secretion of β defensin, the following test was performed with 6 healthy persons as subjects. Citric acid, malic acid, fumaric acid, L-glutamic acid, trans-cinnamic acid, L (+) -ascorbic acid, succinic acid, DL-tartaric acid, adipic acid, L-lactic acid and acetic acid are used as organic acids.
Saliva secreted by the test subjects for 3 minutes in a resting state was collected by the spitting method (hereinafter, this saliva was referred to as a control). Thereafter, 50mg of the organic acid was placed in the oral cavity, and after keeping for 1 minute, the organic acid was recovered together with the secreted saliva. The concentration of human beta-defensin-2 in the collected saliva was measured by ELISA method, and the amount of human beta-defensin-2 secreted by the organic acid within 1 minute was calculated according to the following calculation formula. The saliva amount (ml) in the following formula was calculated, and the saliva weight (g) was calculated from the saliva collected, assuming that the saliva weight (1 g) was 1 ml. In the case of using lactic acid and acetic acid, the above test was performed by inhaling into the oral cavity an aqueous solution prepared by adding water to 50mg of the organic acid to a total amount of 1 g.
Calculation formula
[ amount of hBD-2 secreted in 1 minute (ng/min) ] -, i.e.
{ [ concentration of hBD-2 in saliva (ng/ml) ] × [ saliva amount (ml) ] }/[ saliva recovery time (min) ]
# saliva recovery time, 3 minutes in the case of control and 1 minute in the case after organic acid administration.
The results obtained are shown in FIG. 2. From these results, it was found that the amount of human beta-defensin-2 secreted from saliva was increased by applying an organic acid to the oral cavity, as in the case of the result of test 1.
Test example 3Test 3 (concentration dependence) for confirming the promotion of secretion of beta defensin
In order to evaluate the dependency of the concentration of the effect of promoting the secretion of β defensin by organic acid, healthy persons 3 were used as subjects, and the following test was performed.
Saliva secreted by the test subjects for 3 minutes in a resting state was collected by the spitting method (hereinafter, this saliva is referred to as a control liquid). Thereafter, 1ml of a 0.01 wt% aqueous solution of malic acid (malic acid intake 0.1mg) was placed in the oral cavity, and after keeping for 1 minute, the mixture was collected together with the secreted saliva. The concentration of human beta-defensin-2 in the recovered saliva was measured by ELISA method, and the amount of human beta-defensin-2 secreted by ingestion of 0.1mg of malic acid within 1 minute was calculated according to the following calculation formula. The saliva amount (ml) in the following formula was calculated, and the saliva weight (g) was calculated from the saliva collected, assuming that the saliva weight (1 g) was 1 ml. The same tests as described above were carried out using 0.05, 0.1, 0.2, 0.5 and 1 wt% aqueous solutions of malic acid (intake amounts 0.5, 1, 2, 5, 10 mg).
Calculation formula
[ amount of hBD-2 secreted in 1 minute (ng/min) ] -, i.e.
{ [ concentration of hBD-2 in saliva (ng/ml) ] × [ saliva amount (ml) ] }/[ saliva recovery time (min) ]
# saliva recovery time, 3 minutes in the case of control and 1 minute in the case after organic acid administration.
The results obtained are shown in FIG. 3. As can be seen from FIG. 3, the amount of human beta-defensin-2 secreted in saliva increased with increasing concentration of malic acid in water. From these results, it was confirmed that the effect of the organic acid in promoting the secretion of human beta-defensin-2 is concentration-dependent, and that the organic acid has an effect of inducing the secretion of human beta-defensin-2 even at a concentration of 0.01% (0.1 mg of the intake amount).
Industrial applicability
Human beta defensins are known to have the following excellent properties: (a) because of its own antibacterial properties, it can exert antibacterial action in a short time; (b) since it is secreted in the body, it can exert its excellent antibacterial action even on a site to which a conventional antibacterial agent is difficult to administer in a form for external use or internal use. (c) Allowing the rod cells and memory T lymphocytes to swim (i.e., mobilizing immunocompetent cells to participate in the acquired immunity).
The secretion promoter for human beta-defensin of the present invention can promote the secretion of beta-defensin, particularly human beta-defensin-2, at the site to which it is applied. This is because the beta-defensin secretion promoter of the present invention can enhance the antibacterial action and the immunological action in the body by promoting the secretion of beta-defensin, and thus can enhance the defensive action of the body defense mechanism. Thus, the beta-defensin secretion promoter of the present invention can effectively prevent and alleviate symptoms caused by bacterial, fungal, viral, and protozoal infections. In particular, it is effective for skin care such as prevention of secondary infection of atopic dermatitis, prevention of acne, prevention of halitosis, prevention of foot odor, prevention of secondary infection after shaving or depilation, prevention of secondary infection of diaper rash, prevention of secondary infection of miliaria, prevention of secondary infection of scald, and prevention of infection caused by use of steroid. In addition, it is effective for caring skin such as chapped skin, dry skin, chapped hand, etc. caused by bacteria, fungi, viruses, protozoa infection.
In addition, the human beta-defensin secretion promoter of the present invention is expected to have a pharmacological effect based on the secretion promoting action of human beta-defensin. Therefore, the human beta defensin secretion promoter of the present invention can be used for the prevention and treatment of viral conjunctivitis, bacterial conjunctivitis, hordeolum, etc., in the case of intraocular administration; in the case of nasal and intra-pharyngeal administration, can be used for the prevention and treatment of cold, influenza, etc.; in case of nasal administration, can be used for preventing and treating rhinitis, purulent nasal discharge, paranasal sinusitis, etc.; in case of oral administration, it can be used for preventing and treating periodontal disease, stomatitis, dental caries, etc.; can be used for preventing and treating herpes simplex, etc. when used on lips; in the case of skin use, it can be used for preventing and treating ringworm, impetigo, wart, molluscum contagiosum, chicken pox, genital herpes contagiosum, candidiasis, herpes zoster, herpes simplex, acne, atopic dermatitis, wound healing agent, etc.; when used in other parts, it can be used for preventing or treating pneumonia, gastritis, tumor, acquired immune deficiency syndrome, trypanosomiasis, etc. Among these diseases, the compound is particularly effective for the prevention and treatment of diseases involving bacteria, fungi, viruses, protozoa, and the like.
The human beta-defensin secretion promoter of the present invention can exert its more excellent human beta-defensin secretion promoting action in the oral cavity and the labia, and is therefore particularly effective as a drug for preventing and treating periodontal diseases, stomatitis, dental caries, halitosis, herpes simplex and the like. Therefore, the human beta-defensin secretion promoter of the present invention is suitable for an oral care preparation for maintaining a healthy oral environment.
Claims (6)
1. Use of at least one organic acid selected from fumaric acid, malic acid, citric acid and tartaric acid for the preparation of an oral care article for enhancing the immune function by promoting the secretion of beta defensins in humans, the oral care article being administered to the oral cavity of a healthy subject.
2. The use according to claim 1, wherein the human beta defensin is human beta defensin-2.
3. The use as claimed in claim 1, wherein secretion of human beta defensin is promoted in oral mucosa other than teeth.
4. Use according to claim 1, wherein the oral care product is applied for the prevention of oral diseases.
5. Use as claimed in claim 4 wherein the oral disease is selected from periodontal disease, stomatitis, dental caries and halitosis.
6. Use according to claim 1, wherein the oral care product is in the form of a mouth cooling agent.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP328704/2003 | 2003-09-19 | ||
| JP2003328704 | 2003-09-19 | ||
| PCT/JP2004/014024 WO2005027893A1 (en) | 2003-09-19 | 2004-09-17 | HUMAN β-DEFENSIN SECRETION PROMOTER |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| HK1092057A1 HK1092057A1 (en) | 2007-02-02 |
| HK1092057B true HK1092057B (en) | 2011-01-14 |
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