JP7448137B2 - actin polymerization promoter - Google Patents

Description

The present invention relates to an actin polymerization promoter.

Actin is present in almost all eukaryotic cells and forms the main cytoskeleton. Actin is also the most abundant protein in many non-muscle cells.
Actin plays important roles in muscle contraction, cell division, and cell movement.

By the way, when a human body is injured, cells must migrate and occlude the wound site in order for the wound site to recover. It is known that actin protein polymerization and fibrillation play important roles in this cell migration.
For this reason, substances that control actin polymerization are being developed (Patent Documents 1 and 2).

Special Publication No. 11-514865 Japanese Patent Application Publication No. 2013-6775

However, with conventional substances, it has been difficult to sufficiently control actin polymerization.
Therefore, an object of the present invention is to provide an actin polymerization promoter that can sufficiently control (promote) actin polymerization.

The actin polymerization promoter according to the present invention is characterized by containing allantoin chlorhydroxyaluminum and carrot extract .
Further, the actin polymerization promoter according to the present invention is preferably an actin polymerization promoter of gingival fibroblasts .
Further, in the actin polymerization promoter according to the present invention, when the content of the allantoin chlorohydroxyaluminum is 1 part by mass, the content of the carrot extract may be 1/300,000 parts by mass or more and 100,000 parts by mass or less. preferable.

According to the present invention, it is possible to provide an actin polymerization promoter that can sufficiently control (promote) actin polymerization.

Hereinafter, preferred embodiments of the actin polymerization promoter of the present invention will be described in detail.
The actin polymerization promoter of the present invention is characterized in that it contains allantoins.
Allantoin, represented by allantoin, is a component that is expected to have effects such as promoting wound healing and suppressing skin roughness due to its anti-inflammatory effect.

The present invention is based on the new finding that allantoins have the effect of promoting actin polymerization.
By using an actin polymerization promoter containing allantoins, it is possible to promote actin polymerization and enhance the expression of fibrillar actin in cells.

Allantoins include, but are not particularly limited to, allantoin, allantoin aluminum salt (a condensate of allantoin and aluminum), and the like. Examples of the allantoin aluminum salt include allantoin hydroxyaluminum, allantoin dihydroxyaluminum, allantoin chlorohydroxyaluminum, and the like, and among these, it is particularly preferable to use allantoin chlorohydroxyaluminum.

The content of allantoins in the actin polymerization promoter is preferably 0.00001% by mass or more and 3% by mass or less, more preferably 0.0001% by mass or more and 0.5% by mass or less, and 0.0001% by mass or more and 3% by mass or less, more preferably 0.0001% by mass or more and 0.5% by mass or less. More preferably, the content is 0.003% by mass or more and 0.01% by mass or less.
When the content of allantoins is within the above range, the expression of fibrillar actin in cells can be more effectively improved.

The content of carrot extract in the actin polymerization promoter is preferably 0.00001% by mass or more and 1% by mass or less, more preferably 0.00005% by mass or more and 0.5% by mass or less, and 0.00001% by mass or more and 1% by mass or less, more preferably 0.00005% by mass or more and 0.5% by mass or less. More preferably, the content is 0001% by mass or more and 0.01% by mass or less.
When the content of carrot extract is within the above range, the expression of fibrillar actin in cells can be more effectively improved.

Further, the actin polymerization promoter preferably contains carrot extract in addition to allantoins.
Carrot extract is a component that has the effect of promoting metabolism.
By using such a carrot extract in combination, the expression of filamentous actin in cells can be further enhanced.

The content of carrot extract is not particularly limited, but when the content of allantoin is 1 part by mass, it is preferably 1/300,000 parts by mass or more and 100,000 parts by mass or less, and 1/10,000 parts by mass or more and 5,000 parts by mass. It is more preferably the following, and even more preferably 0.01 parts by mass or more and 40% parts by mass or less. Thereby, the expression of filamentous actin within cells can be more effectively enhanced.

As the extraction solvent for obtaining the carrot extract, for example, various inorganic solvents and various organic solvents can be used. More specifically, water; monohydric alcohols such as methanol, ethanol, propyl alcohol, isopropyl alcohol, butanol, isobutanol, octanol, and phenol; propylene glycol, 1,3-butylene glycol, 1,2-butylene glycol, 1, 4-butylene glycol, 1,5-pentanediol, 1,2-pentanediol, 1,3-pentanediol, 1,4-pentanediol, 1,3,5-pentanediol, glycerin, polyethylene glycol (molecular weight 100~ 100,000); Ketones such as acetone and methyl ethyl ketone; Esters such as ethyl acetate and methyl acetate; Ethers such as diethyl ether, dimethyl ether, ethyl methyl ether, and dioxane; Nitriles such as acetonitrile; Chloroform, Examples include halides such as carbon tetrachloride; aliphatic hydrocarbons such as hexane, octane, and cyclohexane; aromatic hydrocarbons such as xylene, toluene, and benzene, and one or more selected from these may be used in combination. Can be used. In addition, the extraction solvent may be an acid (e.g., hydrochloric acid, sulfuric acid, nitric acid, phosphoric acid, formic acid, acetic acid, etc.) or an alkali (e.g., sodium hydroxide, potassium hydroxide, calcium hydroxide, ammonia, etc.) whose normality has been adjusted appropriately. etc.) may be used.

Among them, it is preferable to use 1,3-butylene glycol as the extraction solvent for obtaining carrot extract. Thereby, the above-mentioned effects can be more prominently exhibited.

In the oral composition, the carrot extract may be contained in any form, for example, it may be contained in powder or granule form, it may be contained as an oily component, or it may be contained in a solution dissolved in other components. It may be included in the state.

In addition to the above-mentioned components, the actin polymerization promoter of the present invention includes, for example, abrasives, wetting agents, solvents, binders, fragrances, excipients, sweeteners, pH adjusters, preservatives, emulsifiers, and solubilizers. , a foaming agent, a lubricant, a surfactant, an oil, a pigment, an antioxidant, and other chemicals may be appropriately added. These additives are commonly used in the design of pharmaceutical compositions, oral compositions, or food formulations, and can be appropriately selected within a range that does not impair the effects of the present invention, and can be blended in appropriate amounts. can. Examples of such additives include the following.

Examples of abrasives include silica-based abrasives such as silica gel, precipitated silica, igneous silica, hydrated silicic acid, anhydrous silicic acid, zeolite, aluminosilicate, and zirconosilicate, dibasic calcium phosphate dihydrate, and dibasic calcium phosphate. Calcium hydrogen phosphate for toothpaste such as anhydrate, calcium pyrophosphate, tribasic magnesium phosphate, tribasic calcium phosphate, aluminum hydroxide, alumina, light calcium carbonate, heavy calcium carbonate, magnesium carbonate, zirconium silicate, synthetic resin type Examples include abrasives, among which one type or two or more types can be used in combination.

Wetting agents include glycerin, diglycerin, polyglycerin, 1,3-butylene glycol, polyethylene glycol, 1,2-pentanediol, 1,3-hexanediol, propylene glycol, dipropylene glycol, isopropylene glycol, polypropylene glycol. , ethylene glycol, diethylene glycol, triethylene glycol, maltitol, reduced starch syrup, lactitol, palatinit, erythritol, sorbitol, mannitol, xylitol, xylose, trehalose, glucose, lactose, mannose, maltose, fructose, inositol, pentaerythritol, maltotriose , starch decomposition sugar, starch decomposition sugar reduced alcohol, and other polyhydric alcohols, among which one type or a combination of two or more types can be used.

The solvent is preferably an organic solvent such as alcohol or water, and examples thereof include ethanol, propyl alcohol, isopropyl alcohol, and the like. These solvents may be used alone or in combination of two or more.

As a binder, alginates and their derivatives such as carrageenan (ι, λ, κ), alginic acid, sodium alginate, propylene glycol alginate, calcium-containing sodium alginate, potassium alginate, calcium alginate, ammonium alginate, xanthan gum, guar gum, Examples include agar, sodium carboxymethyl cellulose, hydroxyethyl cellulose, and sodium polyacrylate, and one or more of these can be used in combination.

Examples of fragrances include l-menthol, anethole, menthone, cineole, limonene, carvone, methyl salicylate, ethyl butyrate, eugenol, thymol, cinnamic aldehyde, trans-2-hexenal, and one or two of these. More than one species can be used in combination. These components may be blended singly, but essential oils containing them may also be blended. In addition to the above-mentioned fragrance ingredients, fragrance ingredients such as aliphatic alcohols and their esters, terpene hydrocarbons, phenol ethers, aldehydes, ketones, and lactones, and essential oils may also be blended within a range that does not impede the effects of the present invention.

Examples of excipients include sucrose, lactose, starch, glucose, crystalline cellulose, mantu, sorbitol, xylitol, erythritol, palatinit, palatinose, maltitol, trehalose, lactitol, lactulose, reduced starch sugar, reduced isomaltooligosaccharide, Coupling sugar, gum base, gum arabic, gelatin, cetyl methylcellulose, light silicic anhydride, magnesium aluminate, calcium aluminate metasilicate, sodium bicarbonate, calcium phosphate, and the like.

Examples of sweeteners include saccharin sodium, aspartame, trehalose, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perillartin, etc., and one or more of these can be used in combination. can.

Examples of pH adjusting agents include citric acid, phosphoric acid, pantothenic acid, malic acid, pyrophosphoric acid, lactic acid, tartaric acid, glycerophosphoric acid, acetic acid, nitric acid, or chemically available compounds such as disodium hydrogen phosphate. Examples include salts and sodium hydroxide, and these can be used alone or in combination of two or more so that the pH of the composition is within an appropriate range.

Examples of the preservative include paraoxybenzoic acid esters, benzoic acid and its salts, salic acid and its salts, sorbic acid and its salts, phenoxyethanol, alkyldiaminoethylglycine hydrochloride, etc. One or two of these More than one species can be used in combination.

Examples of emulsifiers include polyoxyethylene alkyl ether, polyoxyethylene fatty acid ester, polyoxyethylene sorbitan fatty acid ester, sorbitan fatty acid ester, glycerin fatty acid ester, polyglycerin fatty acid ester, polyoxyethylene hydrogenated castor oil, sodium stearoyl lactate, Examples include soybean phospholipids and alkyltrimethylammonium chloride.
Examples of the solubilizing agent include esters, polyethylene glycol derivatives, polyoxyethylene hydrogenated castor oil, fatty acid esters of sorbitan, and sulfated fatty alcohols.

Foaming agents include sodium lauryl sulfate, sodium lauroyl sarcosine, sodium alkyl sulfosuccinate, sodium coconut oil fatty acid monoglycerol sulfonate, sodium α-olefin sulfonate, N-acylamino acid salts such as N-acylglutamate, 2-alkyl- N-carboxymethyl-N-hydroxyethylimidazolinium betaine, maltitol fatty acid ester, sucrose fatty acid ester, polyglycerin fatty acid ester, fatty acid diethanolamide, polyoxyethylene sorbitan monostearate, polyoxyethylene hydrogenated castor oil, polyoxy Examples include ethylene fatty acid esters, among which one type or two or more types can be used in combination.
Examples of the lubricant include magnesium stearate, sucrose fatty acid ester, talc, and hydrogenated oil.
Examples of the oil include oils other than the essential oils used as antibacterial ingredients and the oils used as fragrances, such as coconut oil, olive oil, sesame oil, peanut oil, parsley oil, parsley seed oil, and safflower oil.

Examples of surfactants include sodium lauryl sulfate, sodium α-olefin sulfonate, sodium dodecylbenzenesulfonate, sodium lauryl sulfoacetate, sodium N-lauroyl sarcosinate, N-acyl glutamate, sucrose fatty acid ester, polyoxy Ethylene hydrogenated castor oil, polyoxyethylene polyoxypropylene block copolymer, alkyl glycosides, sorbitan fatty acid ester, polyoxyethylene sorbitan fatty acid ester, alkyl dimethyl amine oxide, lauryl ethanolamide, sodium cocoyl sarcosinate, N-lauroyl methyl taurine Examples include sodium solutions.

In addition to the above-mentioned components, for example, dyes such as Blue No. 1, pigments such as titanium oxide, antioxidants such as dibutylhydroxytoluene, chelating agents such as edetate, flavoring agents such as tea extract and tea carbonization liquid, etc. It may also contain agents.

The actin polymerization promoter of the present invention, which is a combination of the above-mentioned components, can be produced according to a conventional method.

Although the actin polymerization promoter of the present invention has been described above, the present invention is not limited thereto. For example, the actin polymerization promoter of the present invention may contain a component having any desired function in addition to the components described above.

Next, specific examples of the present invention will be described.
(experimental method)
Gingival fibroblasts were cultured using Fibrolife S2 Comp kit (Kurabo Industries, Ltd.) in a CO2 incubator at 37°C until confluent, and then seeded onto a collagen-coated glass bottom 24-well plate. After 6 hours, the medium was replaced with L-glutamine-containing FibroLife BM medium (Kurabo Industries).
The next day, each component was added to the L-glutamine-containing FibroLife BM medium to which TGF-β had been added to a final concentration of 0.1 ng/mL at the concentrations shown in each example in Table 1 below, and the mixture was incubated for another 2 days. Cultured. After culturing, the cells were fixed, membrane permeabilized, stained for F-actin (filamentous actin) with Phalloidin-iFluor 594 Conjugate (Cayman Chemical), observed under a fluorescence microscope, and the F-actin fiber area was quantified. The relative areas are shown in Table 1 when the F-actin fiber area of the control to which the components of Comparative Example 1 were not added was taken as 100%.

In addition, the following carrot extract was used.
・Carrot extract (lyophilized powder): Manufactured by Maruzen Pharmaceutical Co., Ltd., product name: Carrot extract

Table 1 shows that the expression of filamentous actin in cells is enhanced in the present invention. In particular, it can be seen that when allantoin chlorhydroxyaluminum is used, the effect of promoting actin polymerization is high even at a low concentration. It is also understood that when used in combination with carrot extract, a further polymerization promoting effect is expressed.

Claims (3)

An actin polymerization promoter characterized by containing allantoin chlorhydroxyaluminum and carrot extract . The actin polymerization promoter according to claim 1, which is an actin polymerization promoter for gingival fibroblasts . The actin polymerization promoter according to claim 1 or 2, wherein the content of the carrot extract is 1/300000 parts by mass or more and 100000 parts by mass or less when the content of the allantoin chlorhydroxyaluminum is 1 part by mass.