JP2019099486A - Oral composition and collagen synthesis promoter - Google Patents

Abstract

To provide an oral composition that can promote gum collagen synthesis, particularly type I collagen synthesis.SOLUTION: The present invention provides an oral composition containing (A) component: ascorbic acid phosphoric ester or a salt thereof, and (B) component: catechin.SELECTED DRAWING: None

Description

  The present invention relates to an oral composition and a collagen synthesis promoter.

  Periodontal disease is an inflammatory disease that occurs in periodontal tissues (gum, cementum, periodontal membrane, and alveolar bone) supporting teeth due to infection of bacteria in the oral cavity and the like. The main symptoms of periodontal disease include, in addition to gingivitis and periodontitis, the destruction of gingival collagen (especially types I and III).

A composition for oral cavity such as a toothpaste and a troche, which contains ascorbic acid phosphate ester salt, has been reported in expectation of a preventive and ameliorating effect on gingivitis and periodontitis (see, for example, Patent Document 1) .
In addition, ascorbic acid phosphate is known to promote collagen synthesis in gingiva (see, for example, Non-Patent Document 1).

Unexamined-Japanese-Patent No. 2-292211

Journal of Periodontal Research, 2012, 47, 263-271

According to the dental disease survey, it is pointed out that periodontal disease is as high as 80% of the population, and development of an oral composition that enables further improvement of the periodontal disease prevention effect is desired .
An object of the present invention is to provide an oral composition which can promote gingival collagen synthesis, particularly type I collagen synthesis.

MEANS TO SOLVE THE PROBLEM As a result of earnestly examining about the said subject, the present inventors find out that said subject can be solved by using ascorbic acid phosphate ester or its salt, and catechin together, and came to complete this invention.
That is, the present inventors provide the following [1] to [6].
[1] Component (A): a composition for oral cavity containing ascorbic acid phosphate or a salt thereof, and (B) component: catechin.
[2] The composition for oral cavity as described in [1] above, wherein the content ratio ((A) / (B)) of the component (A) to the component (B) is 0.2 to 60.
[3] The composition for oral cavity described in the above [1] or [2], wherein the content of the component (A) is 0.001 to 5% by mass.
[4] The composition for oral cavity according to any one of the above [1] to [3], wherein the content of the component (B) is from 0.0005 to 5% by mass.
[5] The composition for oral cavity according to any one of the above [1] to [4], wherein the component (B) is a tea extract-derived product.
[6] Component (A): A collagen synthesis promoter containing ascorbic acid phosphate or its salt, and (B) component: catechin.

  According to the present invention, it is possible to provide an oral composition which can promote gingival collagen synthesis, particularly type I collagen synthesis.

Hereinafter, the present invention will be described in detail in line with its preferred embodiments.
In the present specification, unless otherwise stated, the content of each component is the amount used of each component used for preparation of the composition.

[1. Oral Composition]
The composition for oral cavity of the present invention contains (A) component: ascorbic acid phosphate ester or a salt thereof, and (B) component: catechin. Since the composition for oral cavity of the present invention contains the component (A), it can produce collagen synthesis activity. Moreover, since the composition for oral cavity of this invention contains (B) component, it can accelerate | stimulate collagen synthetic activity.
Each component is described below.

[1-1. (A) component]
Component (A) is ascorbic acid phosphate or a salt thereof. Ascorbic acid phosphate ester is one in which one or two or more of hydroxyl groups at any one of positions 2, 3, 5 and 6 of ascorbic acid is an ester of a compound such as phosphoric acid or polyphosphoric acid. For example, ascorbic acid-2-phosphate, ascorbic acid-3-phosphate, ascorbic acid-6-phosphate, ascorbic acid-2-polyphosphate and the like can be mentioned.
Further, examples of the salts include alkali metal salts such as sodium salts, potassium salts, calcium salts and magnesium salts, and alkaline earth metal salts. In particular, they are used for oral cavity, and magnesium salts and sodium salts of ascorbic acid phosphate are preferably used from the viewpoint of the gingivitis preventing effect.

  A commercial item may be used as the component (A). Examples of commercially available products include, for example, ascorbic acid-2-phosphate magnesium ester, such as Showa Denko KK, Wako Pure Chemical Industries, Ltd., Wako Pure Chemical Industries, DSM Nutrition Japan, BASF Japan, etc. Acid 2-phosphate sodium ester may be mentioned.

0.001 mass% or more is preferable, and, as for the lower limit of content of (A) component in the composition for oral cavity of this invention, 0.03 mass% or more is more preferable. Moreover, 5 mass% or less is preferable, and, as for the upper limit, 4 mass% or less is more preferable. When the content is 0.001% by mass or more, the effect of collagen synthesis can be exhibited. On the other hand, when the content is 5% by mass or less, the stability of the preparation can be secured.
0.001-5 mass% is preferable, and, as for one embodiment of content of (A) component, 0.03-4 mass% is more preferable.

[1-2. (B) component]
The component (B) is catechin. Catechins are a generic term for flavonoid (C ₁₅ H ₁₄ O ₆ ) and its derivatives. Examples of catechin include catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, gallocatechin gallate, epigallocatechin gallate and the like.
These catechins may be used alone or in combination of two or more.

  The origin of catechin is not particularly limited, and may be derived from a plant (for example, tea etc.) or may be an artificially synthesized product. Among them, catechin is preferably catechin derived from a plant, more preferably a tea extract-derived product, and still more preferably a green tea extract-derived product.

  In the case of a tea extract-derived product, the method for extracting catechins from tea is not particularly limited. For example, one prepared by crushing tea leaves and extracting by solvent according to a known extraction method can be used. Examples of the solvent include water; lower monohydric alcohols such as methanol, ethanol and isopropanol; polyhydric alcohols such as ethylene glycol, polyethylene glycol, propylene glycol, polypropylene glycol and 1,3-butylene glycol; and mixtures thereof.

As catechin, although it is possible to use a solvent extract as it is, a concentrate obtained by evaporating and concentrating the solvent may be used. The powder obtained by removing the solvent by drying (for example, lyophilization) of the solvent extract or concentrate may be used, or an excipient may be added. Furthermore, it is possible to use a powder such as a freeze-dried product, which is redissolved in a solvent and adjusted to an appropriate concentration.
In addition, catechin may be used as an isolated component, and may be used as a mixture with other components.

  A commercial item may be used as catechin. For example, Sanphenon EGCG, Sanphenon 90S manufactured by Taiyo Kagaku Co., Ltd. can be used. Sanphenone EGCG is an extract product of green tea and is a white to light gray powder containing epigallocatechin gallate with high purity (the epigallocatechin gallate concentration in sanphenone EGCG is 95%). Sanphenon 90S is also a purified extract of green tea and is a pale yellow to reddish brown powder (the concentration of catechin in sanphenone 90S (the total concentration of various catechins) is 70%).

0.0005 mass% or more is preferable, and, as for the lower limit of content of (B) component in the composition for oral cavity of this invention, 0.001 mass% or more is more preferable. Moreover, 5 mass% or less is preferable, and, as for the upper limit, 1 mass% or less is more preferable. When the content is 0.0005% by mass or more, an effect of promoting collagen synthesis can be exhibited. On the other hand, stability of preparations, such as coloring (yellowing) prevention, can be secured, controlling bitterness as content is 5 mass% or less.
0.0005-5 mass% is preferable, and, as for one embodiment of content of (B) component, 0.001-1 mass% is more preferable.

[1-3. Content rate]
0.2 or more are preferable and, as for the lower limit of the content ratio ((A) / (B)) of (A) component and (B) component in the composition for oral cavity of this invention, 5 or more is more preferable. Is more preferred. Further, the upper limit thereof is preferably 60 or less, more preferably 50 or less, and still more preferably 30 or less.
0.2-60 are preferable, as for one embodiment of the content rate ((A) / (B)) of (A) component and (B) component, 3-50 are more preferable, and 5-30 are more preferable.

[1-4. Optional ingredients]
The composition for oral cavity of the present invention may contain optional components necessary for the composition, in addition to the above components (A) and (B). Examples of the optional components include solvents such as color inhibitors, abrasives, surfactants, binders, wetting agents (thickeners), sweeteners, preservatives, fragrances, medicinal ingredients, water and the like. The content of the optional component can be blended within a range that does not impair the stability of the component (A) and the component (B), the collagen synthesis promoting effect, and the extrudability upon toothpaste.
The optional components are exemplified below. In addition, when the same component is mentioned to a different arbitrary component, these distinguish the expression as a use. That is, when one component is described as a different optional component, it may be used as a plurality of applications.

[Coloring inhibitor]
Examples of types of color inhibitors include silica and polyphosphates. When the composition for oral cavity of the present invention contains a coloring inhibitor, it is preferable because the coloring of the composition by the components (A) and (B) can be prevented.

Examples of the silica include precipitated silica, silica gel, titanium silicate, zirconium-bonded silicate, germanium-bonded silicate, and those obtained by bonding Al, Mg, Cu, Zn and the like to anhydrous silicic acid.
When the composition for oral cavity of the present invention contains silica, its content is preferably 1 to 30% by mass, more preferably 5 to 25% by mass.

As a polyphosphate, the linear water-soluble polyphosphate represented by following General formula (1) is mentioned, for example.
Formula _{(1): M n + 2} P n O 3n + 1
(In the general formula (1), M represents a Na atom or a K atom, and n is an integer of 2 or 3.)

As the polyphosphate, sodium pyrophosphate or potassium pyrophosphate having a polymerization degree of n = 2, sodium tripolyphosphate of n = 3, or the like can be used. Among these, sodium tripolyphosphate is more preferable. The polyphosphate may be a commercially available product. Examples of commercial products of sodium tripolyphosphate include commercial products such as those manufactured by Taihei Kagaku Sangyo Co., Ltd.
When the composition for oral cavity of the present invention contains a polyphosphate, its content is preferably 0.01 to 5% by mass, more preferably 0.1 to 3% by mass.

[Abrasive]
As the type of the abrasive, for example, titanium oxide, anhydrous silicic acid (hereinafter, anhydrous silicic acid as the abrasive is also referred to as “abrasive silica” or “anhydrous silicic acid (abrasive)”), crystalline silica, non-silica Silica based abrasives such as crystalline silica, silica gel, aluminosilicate, zeolite, calcium hydrogen phosphate anhydrate, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, calcium carbonate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, Examples thereof include magnesium triphosphate, zirconium silicate, tribasic calcium phosphate, hydroxyapatite, tetrabasic calcium phosphate and synthetic resin abrasives.

The liquid absorption capacity of the abrasive silica is usually 0.5 to 2.0 mL / g, preferably 0.7 to 1.5 mL / g.
The liquid absorption amount is a value measured by the following method. That is, 1 g of a sample is weighed on a glass plate, and while a 42.5 mass% glycerin aqueous solution is dropped using a burette, mixing is performed so that the solution becomes uniform with a spatula. The amount of the aqueous glycerin solution required for 1.0 g of the sample is represented as the amount of liquid absorption (mL / g), where the sample is one lump and the end point is when the sample becomes cleanly separated from the glass plate with a spatula.

  The abrasives can be used singly or in combination of two or more. When it contains an abrasive | polishing agent, 2-40 mass% of the whole composition is preferable, and, as for the content, 5-25 mass% is more preferable.

[Surfactant]
As surfactant, an anionic surfactant, nonionic surfactant, an amphoteric surfactant etc. are mentioned, for example.
Examples of anionic surfactants include alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, N-acyl amino acid salts, α-olefin sulfonates, N-acyl sulfonates, sulfates of glycerin fatty acid esters, etc. It can be mentioned.
Examples of nonionic surfactants include polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene ether of glycerin ester, sucrose fatty acid ester, polyoxyethylene-polyoxypropylene block copolymer, alkylol amide Etc.
Examples of amphoteric surfactants include betaine acetate type such as alkyl dimethylamino acetic acid betaine and fatty acid amidopropyl dimethylamino acetic acid betaine, and imidazoline type such as N-fatty acid acyl-N-carboxymethyl-N-hydroxyethyl ethylenediamine salt.
The surfactant may be used alone or in combination of two or more.

  When the composition for oral cavity contains a surfactant, the content thereof is usually 0.2 to 15% by mass, preferably 0.5 to 10% by mass, with respect to the total amount of the composition for oral cavity.

[Baking agent]
Examples of the caking agent include organic caking agents and inorganic caking agents. In addition, a caking additive may be used individually by 1 type, and may use 2 or more types together.

Examples of organic binders include cellulose-based binders such as carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and hydroxypropyl methyl cellulose; carrageenan, xanthan gum, gum arabic, guar gum, locust bean gum, etc. Organic binders such as polyvinyl alcohol, polyvinyl pyrrolidone, sodium alginate, sodium polyacrylate, propylene glycol alginate, carboxyvinyl polymer and the like; pullulan, gelatin.
As the inorganic caking agent, for example, anhydrous silicic acid such as gelling silica, gelling aluminum silica (hereinafter referred to as "thickening silica" or "silicic anhydride (thickening silica as a caking agent)" Also referred to as ") and bentonite. Among these, anhydrous silicic acid is preferred.

  2.1 mL / g or more is preferable and, as for the liquid absorption amount of thickening silica, it is more preferable that it is 2.1-5 mL / g.

  Each of the organic binder and the inorganic binder may be of one type or a combination of two or more types. The caking agent may be a combination of an organic caking agent and an inorganic caking agent.

  When the composition for oral cavity contains a caking agent, the content thereof is usually 0.01 to 2% by mass of an organic caking agent, usually an inorganic caking, with respect to the total amount of the composition for oral cavity The agent is 0.1 to 10% by mass.

[Wetting agent]
As a wetting agent (thickening agent), for example, sugar alcohols such as sorbitol (sorbite), xylitol, erythritol, reduced starch saccharides, etc .; ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, octylene glycol And glycerin, and polyhydric alcohols such as polyethylene glycol having an average molecular weight of 200 to 6,000 (average molecular weight described in the quasi-drug raw material standard), and the like.
The wetting agent may be used alone or in combination of two or more.

  When the composition for oral cavity contains a thickener, the content thereof can be determined within a range that does not hinder the effects of the present invention. For example, it is usually 1 to 60% by mass, preferably 2 to 45% by mass, relative to the total amount of the composition for oral cavity.

[Sweetening agent]
As the sweetening agent, for example, saccharin sodium, stevioside, neohesperidin hydrochalcone, glycyrrhizin, perillaltin, p-methoxycinnamic aldehyde, thaumatin, palatinose, maltitol, xylitol, arabitol, erythritol and the like can be mentioned.
A sweetening agent may be used individually by 1 type, and may use 2 or more types together.

  When the composition for oral cavity contains a sweetening agent, the content thereof can be appropriately determined as long as the effects of the present invention are not impaired.

[Preservative]
Examples of the preservative include parahydroxybenzoic acid esters such as sodium benzoate, methylparaben, ethylparaben, butylparaben and the like.
The preservative may be used alone or in combination of two or more.

  When the composition for oral cavity contains a preservative, the content thereof can be appropriately determined as long as the effects of the present invention are not impaired.

[Perfuming]
As a flavor, for example, mint (peppermint type, spearmint type), fruit type, herb type, spice type, tea type, and mixed flavors thereof can be mentioned. Preferred flavors are tea based flavors, or tea based and other mixed flavors. The flavor component is not particularly limited, and, for example, menthol, anethole, carvone, ligenene, n-decyl alcohol, citronellol, alpha-terpineol, citronellyl acetate, cineole, linalool, ethyl linalool, crocodrine, thymol, spearmint oil , Perfume oils for oral compositions such as peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, cinnamon oil, perilla oil, winter green oil, chopped oil, eucalyptus oil etc. It can be used alone or in combination of two or more.

The form of the flavor is not limited, and may be any of an essential oil, an extract, a solid, and a powder obtained by spray-drying any of these.
When the composition for oral cavity contains a fragrance, the content thereof is preferably 0.000001 to 1% by mass with respect to the total amount of the composition for oral cavity. Moreover, when it contains the fragrance for perfuming which uses the said fragrance | flavor, as for the content, 0.1-2.0 mass% is preferable with respect to the composition for oral cavity whole.

[Medical active ingredient]
As a medicinal ingredient, for example, a caries preventive agent such as fluoride (for example, sodium fluoride, sodium monofluorophosphate, stannous fluoride), etc .; isopropylmethylphenol, triclosan, cetyl pyridinium chloride, chlorhexidine, zinc gluconate And nonionic or cationic bactericidal or antibacterial agents such as zinc citrate; tartarable preventive agents such as condensed phosphates and ethanehydroxy diphosphonates; tranexamic acid, glycyrrhizin dipotassium salt, ε-aminocaproic acid, oat extract Anti-inflammatory agents such as: dextranase, enzyme agents such as mutanase; coating agents such as hydroxyethyl cellulose dimethyl diallyl ammonium chloride; allantoin, allantoin chlorohydroxy aluminum, vitamin C, lysozyme chloride, glycyrrhizin acid and the like Salts, astringents such as sodium chloride; strontium chloride, potassium nitrate, and the hypersensitivity inhibitors such as aluminum lactate.

  When the composition for oral cavity contains a pharmaceutically active ingredient, the content thereof may be appropriately set within a pharmaceutically acceptable range for each pharmaceutically active ingredient.

[solvent]
Examples of the solvent include water and alcohols (for example, lower monohydric alcohols such as ethanol), preferably water.
When the composition for oral cavity contains water, the content thereof is usually 60% by mass or more based on the total amount of the composition. When the composition for oral cavity contains lower monohydric alcohol, its content is usually at most 30% by mass, preferably at most 20% by mass.

[1-5. Dosage form]
The dosage form and shape of the oral composition are not particularly limited. For example, liquid (solution, emulsion, suspension, syrup, etc.), semi-solid (gel, cream, paste etc.), solid (tablet, particulate agent, capsule, film agent, kneaded product, molten solid, waxy solid) , Elastic solid, soft capsule etc.). Preferably, the liquid is semisolid.
Oral compositions in solid dosage form include, for example, troches, gummies, gums, tablets, candies, tooth powders. Oral compositions in semi-solid dosage forms include, for example, toothpastes, gel-like dentifrices. As a composition for oral cavity of a liquid dosage form, a mouthwash, liquid dentifrice, mouth freshener (spray etc.) are mentioned, for example. Among these, dentifrices and mouthwashes are preferred from the viewpoint of efficacy and stability.

[PH]
The pH of the composition for oral cavity is usually 5 to 9, preferably 7 to 9. This may maintain efficacy and stability.
The pH can be measured 3 minutes later at 25 ° C. using a pH meter (type Hm-30S) manufactured by Toa Denpa Kogyo Co., immediately after preparation of the composition for oral cavity.

The composition for oral cavity may contain a pH adjuster as needed for pH adjustment. Examples of pH adjusters include phosphoric acid and salts thereof (eg, sodium phosphate, disodium monohydrogenphosphate, monosodium dihydrogenphosphate), citric acid and salts thereof (eg, sodium citrate), malic acid And salts thereof, gluconic acid and salts thereof, maleic acid and salts thereof, succinic acid and salts thereof, glutamic acid and salts thereof, lactic acid and salts thereof, hydrochloric acid, acetic acid, nitric acid, sodium hydroxide and potassium hydroxide.
When the composition for oral cavity contains a pH adjuster, the content thereof may be appropriately determined (eg, within the range that does not impair the effects of the present invention) as necessary.

[2. Collagen synthesis promoter]
The collagen synthesis promoter of the present invention contains (A) component: ascorbic acid phosphate ester or a salt thereof, and (B) component: catechin.
The details are the same as the contents described in the above composition for oral cavity.

  Hereinafter, the present invention will be described in detail by way of examples. The following examples are intended to illustrate the invention but not to limit it.

Gingival fibroblasts were cultured according to a standard method and then seeded in 6-well plates at 3 × 10 ⁵ / well, and the components described in Table 1 were added and stimulated for 48 hours.
After stimulation, the culture supernatant was collected, and the amount of type I collagen production was measured with an ELISA kit (manufactured by ACBio).
In Table 1, ascorbic acid phosphate was used for biochemistry manufactured by Wako Pure Chemical Industries, Ltd., and catechin was "Sanphenon 90S" manufactured by Taiyo Kagaku Co., Ltd.

As can be seen from Table 1, it can be seen that the component (A) has collagen synthesis activity (see Comparative Examples 1 to 3). However, almost no collagen synthesis activity is observed in the component (B) (see Comparative Examples 4 to 6). On the other hand, when (A) component and (B) component are used together, it turns out that the collagen synthetic activity amount in (A) component alone improves (comparative example 1 and example 1, comparative example 2 and example) 2-5, Comparative Example 3 and Example 6). When ascorbic acid was used instead of the component (A), cell death occurred and could not be evaluated (see Comparative Example 7).
Therefore, the collagen synthesis promoting effect of the component (A) can be recognized by using the component (B) in which the collagen synthesis activity is hardly recognized together with the component (A).

  Hereinafter, formulation examples using the composition for oral cavity of the present invention will be shown. L-ascorbyl magnesium phosphate and tea catechins are the same as the above-mentioned products.

Formulation example 1: Toothpaste L-Ascorbyl magnesium phosphate 0.3%
Tea catechins 0.05%
Xanthan gum 0.8%
Sorbit solution (70%) 40%
Silica 12%
Saccharin sodium 0.2%
Thickening silica 6%
Titanium oxide 0.5%
Propylene glycol 3%
Citric acid 0.1%
Sodium hydroxide 0.1%
Sodium lauryl sulfate 1.5%
Flavoring 0.8%
Purified water balance

Formulation example 2: mouth rinse L-ascorbyl magnesium phosphate 0.3%
Tea catechins 0.05%
Xanthan gum 0.1%
Propylene glycol 3%
Glycerin (85%) 6%
Xylitol 3%
Ethanol 2%
Citric acid 0.015%
Sodium citrate 0.12%
0.1% dihydrogen phosphate monobasic
Flavoring 0.2%
Purified water balance

Formulation example 3: Oral preparation L-ascorbyl magnesium phosphate 0.3%
Tea catechins 0.05%
10% concentrated glycerin
Propylene glycol 2%
Ethanol 15%
Xylitol 2%
Cetyl pyridinium chloride 0.05%
Citric acid 0.05%
Sodium citrate 3.95%
Flavoring 0.10%
Purified water balance

Claims (6)

Component (A): ascorbic acid phosphate or its salt,
(B) component: The composition for oral cavity containing catechin.   The composition for oral cavity according to claim 1, wherein the content ratio ((A) / (B)) of the component (A) to the component (B) is 0.2 to 60.   The composition for oral cavity according to claim 1 or 2, wherein the content of the component (A) is 0.001 to 5% by mass.   The composition for oral cavity according to any one of claims 1 to 3, wherein the content of the component (B) is from 0.0005 to 5% by mass.   The composition for oral cavity of any one of Claims 1-4 whose said (B) component is a tea extract origin. Component (A): ascorbic acid phosphate or its salt,
(B) Component: A collagen synthesis promoter containing catechin.