JP7079598B2 - Oral composition and collagen synthesis promoter - Google Patents

Description

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

Periodontal disease is an inflammatory disease that occurs in the periodontal tissues (ginger, cement, periodontal ligament, and alveolar bone) that support the teeth due to bacterial infection in the oral cavity. The main symptoms of periodontal disease include gingival inflammation and periodontitis, as well as destruction of gingival collagen (particularly types I and III).

Oral compositions such as dentifrices and troches containing ascorbic acid phosphate salts have been reported in anticipation of preventive / ameliorating effects on gingival inflammation and periodontitis (see, for example, Patent Document 1). ..
In addition, ascorbic acid phosphate is known to promote collagen synthesis in the gingiva (see, for example, Non-Patent Document 1).

Japanese Unexamined Patent Publication No. 2-292221

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

According to the dental disease fact-finding survey, it has been pointed out that the number of affected people with periodontal disease is as high as 80% of the population, and it is desired to develop an oral composition that can further improve the effect of preventing periodontal disease. ..
An object of the present invention is to provide an oral composition capable of promoting collagen synthesis of gingiva, particularly type I collagen synthesis.

As a result of diligent studies on the above-mentioned problems, the present inventors have found that the above-mentioned problems can be solved by using catechin in combination with an ascorbic acid phosphate ester or a salt thereof, and have completed the present invention.
That is, the present inventors provide the following [1] to [6].
[1] An oral composition containing (A) component: ascorbic acid phosphate ester or a salt thereof, and (B) component: catechin.
[2] The oral composition according to the above [1], wherein the content ratio ((A) / (B)) of the component (A) and the component (B) is 0.2 to 60.
[3] The oral composition according to the above [1] or [2], wherein the content of the component (A) is 0.001 to 5% by mass.
[4] The oral composition according to any one of the above [1] to [3], wherein the content of the component (B) is 0.0005 to 5% by mass.
[5] The oral composition according to any one of [1] to [4] above, wherein the component (B) is derived from a tea extract.
[6] A collagen synthesis promoter containing (A) component: ascorbic acid phosphate ester or a salt thereof, and (B) component: catechin.

According to the present invention, it is possible to provide an oral composition capable of promoting collagen synthesis of gingiva, particularly type I collagen synthesis.

Hereinafter, the present invention will be described in detail according to the preferred embodiment thereof.
Unless otherwise specified in the present specification, the content of each component is the amount of each component used in the preparation of the composition.

[1. Oral composition]
The oral composition of the present invention contains (A) component: ascorbic acid phosphate ester or a salt thereof, and (B) component: catechin. Since the oral composition of the present invention contains the component (A), it can generate collagen synthetic activity. Moreover, since the oral composition of the present invention contains the component (B), it can promote collagen synthesis activity.
Hereinafter, each component will be described.

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

As the component (A), a commercially available product may be used. As commercial products, for example, ascorbic acid-2-phosphate ester magnesium manufactured by Showa Denko Co., Ltd., Wako Pure Chemical Industries, Ltd., Ascorbin manufactured by Wako Pure Chemical Industries, Ltd., DSM Nutrition Japan Co., Ltd., BASF Japan Co., Ltd., etc. Acid-2-phosphate ester sodium can be mentioned.

In the oral composition of the present invention, the lower limit of the content of the component (A) is preferably 0.001% by mass or more, more preferably 0.03% by mass or more. The upper limit thereof is preferably 5% by mass or less, more preferably 4% by mass or less. 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 pharmaceutical product can be ensured.
One embodiment of the content of the component (A) is preferably 0.001 to 5% by mass, more preferably 0.03 to 4% by mass.

[1-2. (B) component]
The component (B) is catechin. Catechin is a general term for a type of flavonoid ( _{C15 H 14 O 6} ) and its derivatives. Examples of catechins include catechin, epicatechin, gallocatechin, epigallocatechin, epicatechin gallate, gallocatechin gallate, epigallocatechin gallate and the like.
The catechin may be one of these alone or in combination of two or more.

The origin of catechin is not particularly limited, and it may be derived from a plant (for example, tea or the like) or an artificial synthetic product. Among them, the catechin is preferably a plant-derived catechin, more preferably a tea extract-derived product, and even more preferably a green tea extract-derived product.

In the case of a tea extract-derived product, the method for extracting catechin from tea is not particularly limited. For example, one prepared by crushing tea leaves and extracting with a solvent by 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 the catechin, the solvent extract can be used as it is, but the concentrate obtained by distilling off the solvent and concentrating it may be used. A powder obtained by removing the solvent by drying (for example, freeze-drying) the solvent extract or concentrate may be used, or an excipient or the like may be added. Further, a powder such as a freeze-dried product may be redissolved in a solvent and adjusted to an appropriate concentration.
In addition, catechin may be used as an isolated component or may be used as a mixture with other components.

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

In the oral composition of the present invention, the lower limit of the content of the component (B) is preferably 0.0005% by mass or more, more preferably 0.001% by mass or more. The upper limit thereof is preferably 5% by mass or less, more preferably 1% by mass or less. When the content is 0.0005% by mass or more, the effect of promoting collagen synthesis can be exerted. On the other hand, when the content is 5% by mass or less, the stability of the pharmaceutical product such as prevention of coloring (yellow) can be ensured while suppressing bitterness.
In one embodiment of the content of the component (B), 0.0005 to 5% by mass is preferable, and 0.001 to 1% by mass is more preferable.

[1-3. Content ratio]
In the oral composition of the present invention, the lower limit of the content ratio ((A) / (B)) of the component (A) and the component (B) is preferably 0.2 or more, more preferably 3 or more, and 5 or more. Is even more preferable. The upper limit is preferably 60 or less, more preferably 50 or less, and even more preferably 30 or less.
One embodiment of the content ratio of the component (A) and the component (B) ((A) / (B)) is preferably 0.2 to 60, more preferably 3 to 50, and even more preferably 5 to 30.

[1-4. Optional ingredient]
In addition to the above components (A) and (B), the oral composition of the present invention may contain any components necessary for the composition. Examples of the optional component include a color inhibitor, an abrasive, a surfactant, a binder, a wetting agent (viscosing agent), a sweetening agent, a preservative, a fragrance, a medicinal component, and a solvent such as water. The content of the optional component may be blended within a range that does not impair the stability of the component (A) and the component (B), the collagen synthesis promoting effect, the extrudability in toothpaste, and the like.
The optional components are illustrated below. When the same component is listed as a different arbitrary component, these are used to distinguish the expressions for use. That is, when one component is described as a different optional component, it can be used for a plurality of uses.

[Color inhibitor]
Examples of the type of color inhibitor include silica and polyphosphate. It is preferable that the oral composition of the present invention contains a coloring inhibitor because it can prevent coloring of the composition by the components (A) and (B).

Examples of silica include precipitated silica, silica gel, titanium silicate, zirconium-bonded silicate, germanium-bonded silicate, and other substances in which Al, Mg, Cu, Zn and the like are bonded to anhydrous silicic acid.
When the oral composition of the present invention contains silica, the content thereof is preferably 1 to 30% by mass, more preferably 5 to 25% by mass.

Examples of the polyphosphate include a linear water-soluble polyphosphate represented by the following general formula (1).
General 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 having a degree of polymerization of n = 2, potassium pyrophosphate, sodium tripolyphosphate having n = 3, and the like can be used. Of these, sodium tripolyphosphate is more preferable. Commercially available products may be used as the polyphosphate. Examples of commercially available products of sodium tripolyphosphate include commercially available products manufactured by Taihei Kagaku Sangyo Co., Ltd.
When the oral composition of the present invention contains a polyphosphate, the content thereof is preferably 0.01 to 5% by mass, more preferably 0.1 to 3% by mass.

[Abrasive]
Types of abrasives include, for example, titanium oxide, silicic acid anhydride (hereinafter, silicic acid anhydride as an abrasive is also referred to as "polishable silica" or "silicic acid anhydride (polishable)"), crystalline silica, and non-polishing agent. Silica-based abrasives such as crystalline silica, silica gel, and aluminosilicate, zeolite, calcium hydrogen phosphate anhydrous, calcium hydrogen phosphate dihydrate, calcium pyrophosphate, calcium carbonate, aluminum hydroxide, alumina, magnesium carbonate, and so on. Examples thereof include magnesium triphosphate, zirconium silicate, calcium tertiary phosphate, hydroxyapatite, calcium tetraphosphate, and synthetic resin-based abrasives.

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

The abrasive can be used alone or in combination of two or more. When the abrasive is contained, the content thereof is preferably 2 to 40% by mass, more preferably 5 to 25% by mass, based on the whole composition.

[Surfactant]
Examples of the surfactant include anionic surfactants, nonionic surfactants, amphoteric surfactants and the like.
Examples of the anionic surfactant include alkyl sulfates such as sodium lauryl sulfate and sodium myristyl sulfate, N-acylamino acid salts, α-olefin sulfonates, N-acylsulfonates, sulfates of glycerin fatty acid esters and the like. Can be mentioned.
Examples of the nonionic surfactant include polyoxyethylene alkyl ether, polyoxyethylene hydrogenated castor oil, polyoxyethylene ether of glycerin ester, sucrose fatty acid ester, polyoxyethylene-polyoxypropylene block copolymer, and alkylolamide. And so on.
Examples of the amphoteric surfactant include betaine acetate types such as alkyldimethylaminoacetic acid betaine and betaine fatty acid amide propyldimethylaminoacetic acid betaine, and imidazoline types such as N-fatty acid acyl-N-carboxymethyl-N-hydroxyethylethylenediamine salt.
The surfactant may be used alone or in combination of two or more.

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

[Binder]
Examples of the binder include an organic binder and an inorganic binder. The binder may be used alone or in combination of two or more.

Examples of the organic binder include cellulose binders such as carboxymethyl cellulose, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose, hydroxypropyl cellulose and hydroxypropyl methyl cellulose; carrageenan, xanthan gum, Arabic gum, guar gum, locust bean gum and the like. Gum; Organic binders such as polyvinyl alcohol, polyvinylpyrrolidone, sodium alginate, sodium polyacrylic acid, propylene glycol alginate, carboxyvinyl polymer; purulan, gelatin and the like.
Examples of the inorganic caking agent include anhydrous silicic acid such as gelling silica and gelling aluminum silica (hereinafter, anhydrous silicic acid as a binder is referred to as "thickening silica" or "anhydrous silicic acid (thickening). ) ”) And bentnite. Of these, silicic anhydride is preferable.

The liquid absorption amount of the viscous silica is preferably 2.1 mL / g or more, and more preferably 2.1 to 5 mL / g.

The organic binder and the inorganic binder may be one kind or a combination of two or more kinds, respectively. Further, the binder may be a combination of an organic binder and an inorganic binder.

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

[Wetting agent]
Examples of the wetting agent (viscosing agent) include sugar alcohols such as sorbitol (Solbit), xylitol, erythritol, and reduced starch saccharified product; ethylene glycol, propylene glycol, butylene glycol, pentylene glycol, hexylene glycol, and octylene glycol. , Glycerin, polyhydric alcohols such as polyethylene glycol having an average molecular weight of 200 to 6,000 (average molecular weight described in the standard for raw materials for non-pharmaceutical products) and the like.
The wetting agent may be used alone or in combination of two or more.

When the oral composition contains a viscous agent, the content thereof can be determined within a range that does not interfere with the effects of the present invention. For example, it is usually 1 to 60% by mass, preferably 2 to 45% by mass, based on the total amount of the oral composition.

[Sweetness]
Examples of the sweetener include sodium saccharin, stebioside, neohesperidin hydrochalcone, glycyrrhizin, perillartine, p-methoxycinnamic aldehyde, thaumatin, palatinose, maltitol, xylitol, arabitol, erythritol and the like.
The sweetener may be used alone or in combination of two or more.

When the oral composition contains a sweetening agent, the content thereof can be appropriately determined as long as the effect of the present invention is not impaired.

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

When the oral composition contains a preservative, the content thereof can be appropriately determined as long as the effect of the present invention is not impaired.

[Fragrance]
Examples of the fragrance include mint-based (peppermint-based, spearmint-based), fruit-based, herbal-based, spice-based, tea-based, and mixed flavors thereof. Preferred flavors are tea-based flavors, or tea-based and other mixed flavors. The fragrance component is not particularly limited, and is, for example, menthol, anetol, carboxylic, eugenol, limonene, n-decyl alcohol, citronellol, α-terpineol, citronellyl acetate, cineole, linalol, ethyllinalol, varnish, timole, and sparemint oil. , Peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, katsura oil, pimento oil, katsura leaf oil, perilla oil, winter green oil, chopstick oil, eucalyptus oil and other fragrances for oral compositions. It can be used alone or in combination of two or more.

The form of the fragrance is not limited, and it may be an essential oil, an extract, a solid substance, or a powder obtained by spray-drying any of these.
When the oral composition contains a fragrance, the content thereof is preferably 0.000001 to 1% by mass with respect to the total amount of the oral composition. When a perfume for perfume using the above perfume is contained, the content thereof is preferably 0.1 to 2.0% by mass with respect to the total amount of the oral composition.

[Medicinal ingredient]
Examples of the medicinal ingredient include caries preventive agents such as fluoride (for example, sodium fluoride, sodium monofluorophosphate, stannous fluoride); isopropylmethylphenol, triclosan, cetylpyridinium chloride, chlorohexidine, zinc gluconate. , Nonionic or cationic bactericidal or antibacterial agents such as zinc citrate; Toothstone preventive agents such as condensed phosphate, ethanehydroxydiphosphonate; Anti-inflammatory agents such as; Enzyme agents such as dextranase and mutanase; Coating agents such as hydroxyethyl cellulose dimethyldiallyl ammonium chloride; Convergents; examples include hypersensitivity inhibitors such as strontium chloride, potassium nitrate, aluminum lactate and the like.

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

[solvent]
Examples of the solvent include water and alcohol (for example, lower monohydric alcohol such as ethanol), and water is preferable.
When the oral composition contains water, the content thereof is usually 60% by mass or more with respect to the total amount of the composition. When the oral composition contains a lower monohydric alcohol, the content thereof is usually 30% by mass or less, preferably 20% by mass or less.

[1-5. Dosage form]
The dosage form and shape of the oral composition are not particularly limited. For example, liquids (solutions, emulsions, suspensions, syrups, etc.), semi-solids (gels, creams, pastes, etc.), solids (tablets, particulate agents, capsules, film agents, kneaded products, molten solids, waxy solids, etc.) , Elastic solids, soft capsules, etc.). It is preferably a liquid or a semi-solid.
Examples of solid dosage forms of oral compositions include troches, gummies, gums, tablets, candy and toothpaste. Examples of the semi-solid dosage form oral composition include dentifrices and gel-like dentifrices. Examples of the oral composition in the form of a liquid include a mouthwash, a liquid dentifrice, and a mouthwash (spray, etc.). Of these, dentifrices and mouthwashes are preferred from the standpoint of efficacy and stability.

[PH]
The pH of the oral composition is usually 5-9, preferably 7-9. This can maintain effectiveness and stability.
Immediately after preparing the oral composition, the pH can be measured at 25 ° C. after 3 minutes using a pH meter (model number Hm-30S) manufactured by Toa Denpa Kogyo Co., Ltd.

If necessary, the oral composition may contain a pH regulator. Examples of the pH adjuster include phosphoric acid and a salt thereof (for example, sodium phosphate, disodium monohydrogen phosphate, monosodium dihydrogen phosphate), citric acid and a salt thereof (for example, sodium citrate), and malic acid. And their salts, gluconic acid and its salts, maleic acid and its salts, succinic acid and its salts, glutamic acid and its salts, lactic acid and its salts, hydrochloric acid, acetic acid, nitric acid, sodium hydroxide and potassium hydroxide.
When the oral composition contains a pH adjuster, the content thereof may be appropriately determined as necessary (for example, within a range that does not impair the effects of the present invention).

[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 those described in the above oral composition.

Hereinafter, the present invention will be described in detail with reference to Examples. The following examples are for the purpose of suitably explaining the present invention, and do not limit the present invention.

After culturing gingival fibroblasts according to a conventional method, the cells were seeded on a 6-well plate so as to have 3 × 10 ⁵ / well, and the components shown in Table 1 were added and stimulated for 48 hours.
After stimulation, the culture supernatant was collected, and the amount of type I collagen produced 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 the component (A) and the component (B) are used in combination, it can be seen that the amount of collagen synthesis activity of the component (A) alone is improved (Comparative Example 1 and Example 1, Comparative Example 2 and Example). 2-5, see Comparative Example 3 and Example 6). Moreover, when ascorbic acid was used instead of the component (A), cell death occurred and it could not be evaluated (see Comparative Example 7).
Therefore, by using the component (B), which has almost no collagen synthesis activity, in combination with the component (A), the collagen synthesis promoting effect of the component (A) can be recognized.

Hereinafter, a prescription example using the oral composition of the present invention will be shown. The L-ascorbyl magnesium phosphate and tea catechin are the same as the above products.

Prescription Example 1: Toothpaste L-Ascorbyl Magnesium 0.3%
Tea catechin 0.05%
Xanthan gum 0.8%
Sorbitol liquid (70%) 40%
Silicic acid anhydride 12%
Saccharin sodium 0.2%
Viscous silica 6%
Titanium oxide 0.5%
Propylene glycol 3%
Citric acid 0.1%
Sodium hydroxide 0.1%
Sodium lauryl sulfate 1.5%
Fragrance 0.8%
Purified water balance

Prescription example 2: Mouthwash L-ascorbyl magnesium 0.3%
Tea catechin 0.05%
Xanthan gum 0.1%
Propylene glycol 3%
Glycerin (85%) 6%
Xylitol 3%
Ethanol 2%
Citric acid 0.015%
Sodium citrate 0.12%
Disodium monohydrogen phosphate 0.1%
Fragrance 0.2%
Purified water balance

Prescription example 3: Oral agent L-ascorbyl magnesium phosphate 0.3%
Tea catechin 0.05%
Concentrated glycerin 10%
Propylene glycol 2%
Ethanol 15%
Xylitol 2%
Cetylpyridinium chloride 0.05%
Citric acid 0.05%
Sodium citrate 3.95%
Fragrance 0.10%
Purified water balance

Claims (5)

(A) Ingredients: Ascorbic acid phosphate magnesium and
(B) Ingredients: Contains catechin and
The content of the component (A) is 0.001 to 5% by mass, and the content is 0.001 to 5% by mass.
The content of the component (B) is 0.0005 to 5% by mass, and the content is 0.0005 to 5% by mass.
An oral composition for promoting collagen synthesis, wherein the content ratio ((A) / (B)) of the component (A) and the component (B) is 5 to 60 . The oral composition according to claim 1, wherein the content ratio ((A) / (B)) of the component (A) and the component (B) is 5 to 30 . The oral composition according to claim 1 or 2, wherein the content of the component (A) is 0.03 to 4 % by mass. The oral composition according to any one of claims 1 to 3, wherein the content of the component (B) is 0.001 to 1 % by mass. The oral composition according to any one of claims 1 to 4, wherein the component (B) is derived from a tea extract.