JP2002020292A - Composition containing ascorbic acid phosphoric esters - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain a composition containing an ascorbic acid phosphoric ester which is formulated with the ascorbic acid phosphoric ester or its salt in a stable and active state and effectively exhibits its effect even after long-term preservation. SOLUTION: This composition containing the ascorbic acid phosphoric ester is characterized in that the composition comprises (A) the ascorbic acid phosphoric ester or its salt, (B) an anionic surfactant and (C) one or more kinds of sugar alcohols selected from a >=4C monosaccharide alcohol, an oligosaccharide alcohol and a reducing starch syrup, has <10 mass % content of calcium and aluminum ion sources based on the whole composition and has pH>=8.0 after preservation at 25 deg.C for one month.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

[0001] The present invention relates to a composition for oral cavity and dermis containing a phosphoric acid ester of ascorbic acid.

[0002]

2. Description of the Related Art It is known that ascorbic acid phosphate and salts thereof play an important role in the expression of various enzyme activities in living organisms and have various physiological activities. . In particular, it acts as a coenzyme for prolyl and lysyl hydroxylase and is said to be essential for collagen synthesis. In recent years, it has also attracted attention as an antioxidant vitamin that eliminates excess active oxygen produced in the living body and protects living tissues from oxygen damage, and is known to have various physiological activities.

[0003] Conventionally, compositions containing ascorbic acid phosphate and salts thereof include cosmetics (JP-A-62
-298508, JP-A-3-63208), whitening cosmetics (JP-A-63-243014, JP-A-1
305,093 and 3-133914), oral agents (Japanese Patent Application Laid-Open No. 62-96408), bath agents (Japanese Patent Application Laid-Open No. 62-96410), and oral compositions (Japanese Patent Application Laid-Open No. 2-292210). 2-292221, 4-1
No. 73727), an external preparation for skin (JP-A-3-3490)
No. 8, No. 7-206632, and No. 8-133951).

However, when ascorbic acid phosphate or a salt thereof is blended in various compositions, the composition becomes unstable due to the influence of calcium, metal, microorganisms, pH and the like, and as a result, it is decomposed into ascorbic acid and phosphoric acid. Therefore, it was required to keep the composition stable.

In order to solve this problem, studies have been made to mix an antioxidant and a chelating agent, and to make the composition powdery or granular in order to minimize the contact with water (Japanese Patent Application Laid-Open No. Hei 7 (1994) -107). -252127). However, such a composition containing ascorbic acid phosphate or a salt thereof not only stably mixes ascorbic acid phosphates, but also exhibits a higher physiological activity when used. It is necessary to mix it.

[0006] In this respect, in particular, paste, liquid,
Select a dosage form with excellent usability, such as a cream, and apply it while maintaining appropriate foaming power and dispersibility and maintaining the structure of ascorbic acid phosphate or a salt thereof in these preparations. It is desired to be absorbed by a living body or the like, and in such a water-containing dosage form, it is desired to develop a technique for stably blending ascorbic acid phosphate and a salt thereof and effectively exhibiting its effect.

Accordingly, an object of the present invention is to provide a composition containing ascorbic acid phosphate and a salt thereof in a stable and active state.

[0008]

Means for Solving the Problems and Embodiments of the Invention As a result of intensive studies to achieve the above object, the present inventor has found that a composition containing ascorbic acid phosphate or a salt thereof has an anionic interface. An activator and one or more selected from monosaccharide alcohols having 4 or more carbon atoms, oligosaccharide alcohols, and reduced starch syrup are blended, and the content of calcium and aluminum ion sources is 10% of the total composition ( Mass percentage, hereinafter the same), and the pH of the composition after storage at 25 ° C. for 1 month.
Is adjusted to 8.0 or more, particularly preferably 8.5 to 9.5, whereby the stability with time of the composition containing ascorbic acid phosphate or a salt thereof is improved, It has been found that even after long-term storage, a decrease in the residual ratio of ascorbic acid phosphate or a salt thereof is effectively prevented, and the effect is effectively exhibited. In this case, most of the compositions containing the ascorbic acid phosphate or a salt thereof have an initial pH of 8.0 or more,
In particular, even if the pH is adjusted to 8.5 to 9.5, the pH greatly changes within one month even after storage at around room temperature after production, and the pH becomes 8.0.
If the pH after storage at 25 ° C. for one month is lower than 8.0, stable combination of the ascorbic acid phosphate and its salt cannot be achieved, and therefore, It has been found that the pH value of the composition after storage at 1 ° C. for one month is important for incorporating ascorbic acid phosphate and salts thereof in a stable and active state.

Hereinafter, the present invention will be described in more detail.
The composition of the present invention is selected from (A) ascorbic acid phosphate or a salt thereof, (B) an anionic surfactant, (C) a monosaccharide alcohol having 4 or more carbon atoms, an oligosaccharide alcohol, and reduced starch syrup. It contains one or more sugar alcohols, has a calcium and aluminum ion source content of less than 10% by mass of the whole composition, and has a pH of 8.0 after storage at 25 ° C. for one month. It is characterized by the above.

[0010] The ascorbic acid phosphoric acid ester is an ester of a compound such as phosphoric acid or polyphosphoric acid in which one or more of the hydroxyl groups at the 2,3,5,6-positions of ascorbic acid. And examples thereof include ascorbic acid-2-phosphate, ascorbic acid-3-phosphate, ascorbic acid-6-phosphate, and ascorbic acid-2-polyphosphate.
The salts include sodium salts, potassium salts,
Examples thereof include alkali metal salts such as calcium salts and magnesium salts, and alkaline earth metal salts. Among them, particularly when used for the oral cavity, magnesium or sodium ascorbic acid phosphate is preferably used from the viewpoint of the effect of preventing and improving periodontal disease.

The compounding amount is 0.001 to 0.001 of the whole composition.
It is preferably 10%, particularly preferably 0.01 to 5%. If the amount is too small, the effect is not sufficiently exhibited, and if it is too large, the feeling in use may be reduced.

Next, the anionic surfactant is blended for the purpose of imparting an appropriate foaming power or imparting dispersibility. In this case, the anionic surfactant is said to reduce the stability of the ascorbic acid phosphate or a salt thereof by its combination. However, in the present invention, the pH of the composition after storage at 25 ° C. for one month is adjusted. By setting it to 8.0 or more, even if an anionic surfactant is blended, stabilization blending of ascorbic acid phosphate or a salt thereof is successful.

As the anionic surfactant, various conventionally known anionic surfactants, for example, alkyl sulfate, polyoxyethylene alkyl sulfate, α-
Sulfo fatty acid ester salts, α-olefin sulfonates, alkyl or hydroxyalkyl ether carboxylates, N-acylated taurine, N-acylated glycine,
N-acylated aspartate, N-acylated sarcosine, N-acylated glutamate, monoalkyl phosphate, alkylamide ether sulfate,
Alkyl (poly) glyceryl ether sulfonate, alkyl (poly) glyceryl ether carboxylate, secondary amide type N-acyl amino acid salt, alkyltartaric acid, malic acid alkylamide, citric acid alkylamide, alkyl (poly) glyceryl sulfone Acid salts, monoglyceride succinate salts and the like, among which alkyl sulfate salts are preferred.

The amount of the anionic surfactant is appropriately selected, but may be 0.1 to 10%, preferably 0.5 to 10% of the whole composition.
Preferably, it is 3%.

The composition of the present invention further comprises a monosaccharide alcohol having 4 or more carbon atoms, an oligosaccharide alcohol, and reduced syrup.
Seeds or two or more kinds are blended. Specific examples of the monosaccharide alcohol having 4 or more carbon atoms include erythritol, xylitol, mannitol, sorbitol, galactitol, and iditol. Examples of the oligosaccharide alcohol include maltitol, lactitol, palatinit, maltotriitol, and isomalttriitol. Examples of the reduced syrup include reduced saccharified reduced syrup, highly saccharified reduced syrup, and reduced maltose syrup. These may be used alone or in combination of two or more.

The content of these sugar alcohols can be 1 to 80%, especially 5 to 60% of the whole composition, and is 0.5% by weight based on the amount of water contained in the composition. As described above, it is more preferable to mix at a ratio of 0.5 to 2.0, more preferably 0.75 to 1.5, whereby the effect of ascorbic acid phosphate or a salt thereof is more effective. Can be demonstrated.

Glycerin, which is a monosaccharide alcohol having 3 carbon atoms, has no such effect.

In the composition of the present invention, the contents of a calcium ion source, an aluminum ion source, for example, calcium-containing compounds such as calcium hydrogen phosphate, tribasic calcium phosphate and calcium pyrophosphate, and aluminum-containing compounds such as aluminum hydroxide are determined. The content is less than 10%, preferably 1% or less, more preferably 0.1% or less of the whole product, and it is particularly preferable not to mix these calcium-containing compounds and aluminum-containing compounds. When a large amount of a calcium-containing compound is present, the ascorbic acid phosphate or a salt thereof reacts with calcium to form an insoluble calcium salt, and when a large amount of an aluminum-containing compound is present, decomposition of the ascorbic acid phosphate or a salt thereof by aluminum is caused. Is promoted,
By limiting the contents of the calcium-containing compound and the aluminum-containing compound to less than 10% of the whole composition, these disadvantages can be prevented.

The composition of the present invention can be used for various uses such as for the oral cavity and for the outer skin, and its dosage form is variously selected, and is prepared into dosage forms such as paste, liquid and cream. Is preferred.

The composition of the present invention may contain known components in addition to the above components, depending on the use, dosage form and the like. For example, the oral composition is prepared as a toothpaste, a dentifrice such as a liquid dentifrice, a gingival massage cream, a topical application, and a mouthwash, but in the case of a dentifrice, an abrasive, a binder, and a sweetener. , Fragrance, various active ingredients and the like can be blended in a usual dose.

In this case, silica gel,
Silica-based abrasives such as sedimentable silica, aluminosilicate and zirconosilicate (titanium-binding silica) are preferable, and magnesium carbonate, bentonite, polymethyl methacrylate and the like can be added.

Examples of the binder include cellulose derivatives such as carrageenan, sodium carboxymethylcellulose, methylcellulose and hydroxyethylcellulose; alginic acid derivatives such as sodium alginate and propylene glycol alginate; gums such as xanthan gum, gellan gum, trangant gum and karaya gum. , Polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, and the like, and one or more kinds of inorganic binders such as silica gel, veegum, and laponite.

As the thickener, the above sugar alcohol is used, and if necessary, glycerin, propylene glycol, polyethylene glycol and the like can be blended.
As the surfactant, a nonionic surfactant such as decaglyceryl laurate and diethanolamide myristate, and an amphoteric surfactant such as betaine may be blended in addition to the anionic surfactant.

As the fragrance component, menthol, anethole, carvone, eugenol, n-decyl alcohol,
Flavors such as citronellol, α-terpineol, cineol, linalool, ethyl linalool, crocodile, thymol, peppermint oil, spearmint oil, wintergreen oil, clove oil, eucalyptus oil and the like can be used alone or in combination. Furthermore, sweeteners such as saccharin sodium, perillartin, thaumatin and the like can be added.

Also, the present invention provides a cationic fungicide such as chlorhexidine, benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, decalinium chloride, a phenolic compound such as triclosan, hinokitiol, biosol, etc., dextranase, mutanase, lysozyme. , Amylase, protease, lytic enzyme, SOD
Enzymes such as sodium monofluorophosphate and potassium monofluorophosphate, fluorides such as sodium fluoride and stannous fluoride, tranexamic acid, epsilon aminocaproic acid, allantoin, dihydrocholestanol Glycyrrhizic acids, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, xylitol, zinc chloride, water-soluble inorganic phosphate compounds, vitamins such as vitamin A, vitamin B group, vitamin E and derivatives thereof, and the like. One or more components can be blended.

The composition of the present invention has an initial pH such that the pH after storage at 25 ° C. for one month is 8.0 or more, preferably 8.0 to 9.5, particularly 8.5 to 9.5. To adjust. Here, the pH after storage for one month was used instead of the initial pH because, for many compositions, the pH greatly changed within one month after production even at around room temperature and was stabilized thereafter.
This is because it was found that the pH after storage at 5 ° C. for one month was important.

In this case, the pH fluctuation differs depending on the blending components. For example, when silica gel is blended, the pH after storage at 25 ° C. for one month increases with respect to the initial pH, and when precipitated silica is blended, reverse. The pH drops. Therefore, in order to adjust the initial pH to 25 ° C. and the pH after storage for one month to the required pH, the initial pH is adjusted to 2 according to the formulation of the composition.
Adjust so as to be lower or higher than the set pH after storage at 5 ° C for 1 month. If necessary, a preliminary test will
A method of examining the relationship between H and the pH after storage at 25 ° C. for one month may be employed. In addition, for pH adjustment, a commonly used pH adjuster can be used, but sodium hydroxide and potassium hydroxide can be suitably used, and water-soluble citrate, phosphate, Carbonates, bicarbonates and the like can also be preferably used.

[0028]

The ascorbic acid phosphate-containing composition of the present invention contains ascorbic acid phosphate or a salt thereof in a stable and active state, and its effects are effective even after long-term storage. Demonstrate.

[0029]

EXAMPLES Hereinafter, the present invention will be described in detail with reference to experimental examples, examples, and comparative examples, but the present invention is not limited to the following examples.

Experimental Example A dentifrice having the following formulation was prepared. Using a dentifrice for 1 to 3 months after the adjustment, a use test was carried out for one week, and the effect of improving gingivitis was observed. That is, ten healthy persons used the following toothpastes A and B for one week, and then stopped oral cleaning for two days, self-evaluated the gingival condition, and filled out a questionnaire. In addition, one week or more was left between each use of the dentifrice. In the questionnaire, the gums of the upper and lower jaw of the anterior teeth were observed and scored as follows with reference to FIGS. 1 (A) to 1 (C). Table 1 shows the results. 0: No gingivitis, FIG. 1 (A) 1: Slight gingivitis, FIG. 1 (B) 2: Gingivitis, FIG. 1 (C) In the figure, X indicates teeth, Y indicates gingiva, and Z indicates gingiva. Indicates a gingivitis part. Dentifrice A Dentifrice B L-ascorbic acid-2-phosphate magnesium salt 0.3% 0.3% Precipitable silica 15% 15% Propylene glycol 3.5% 3.5% Carboxymethylcellulose 1.5% 1 0.5% Butyl paraoxybenzoate 0.1% 0.1% Sodium saccharin 0.2% 0.2% Fragrance 1% 1% Sodium lauryl sulfate 1.5% 1.5% Titanium dioxide 0.5% 0.5% Citric acid 0.1% 0.1% 70% Sorbit solution 50% -85% glycerin-40% Sodium hydroxide 0.3% 0.35% Purified water Residue Total 100.0% 100.0% pH (initial 8.93 8.96 pH (1 month after 25 ° C.) 8.58 8.60 Water content (weight ratio) of sugar alcohol 0.760

[0031]

[Table 1]

Examples 1 to 5 and Comparative Examples 1 to 4 Dentifrices were prepared by blending the components shown in Table 2 (silica, sorbite or glycerin) with the following common composition. The pH was measured immediately after preparation of these dentifrices and after storage at 25 ° C. for 1, 6, and 18 months. Phosphorous ascorbate of a preserved product stored for 1 month in a 60 ° C constant temperature bath, a preserved product stored for 6 months in a 40 ° C constant temperature bath, and a preserved product stored for 18 months at 25 ° C The residual ratio of the acid ester magnesium salt was measured. Table 2 shows the results.

Common composition L-ascorbic acid-2-phosphate magnesium salt 0.3% propylene glycol 3.5 carboxymethylcellulose 1.5 butyl parahydroxybenzoate 0.1 sodium saccharin 0.2 fragrance 1 sodium lauryl sulfate 1.5 Titanium dioxide 0.5 Citric acid 0.1 Sodium hydroxide (appropriate amount) about 0.3 Silica Table 2 Sorbit Table 2 Glycerin Table 2 Purified water Balance 100.0%

[0034]

[Table 2]

Example 6 Toothpaste Propylene glycol 5% 70% Sorbite 50 Carrageenan 1.2 Sodium saccharin 0.2 Sodium lauryl sulfate 1.2 Ethyl parahydroxybenzoate 0.1 Ascorbic acid-2-phosphate magnesium salt 0 .2 citric acid monohydrate 0.2 zirconocene silicate 18 silicic anhydride (manufactured by Tokuyama Corp.) 3 perfume 0.9 sodium hydroxide qs purified water balance total 100% initial pH 9.28 25 ° C. 1M after pH 8 .80

Example 7 Toothpaste Polyethylene glycol 400 5% 70% Sorbite 40 Xanthan gum 1.1 Xylit 10 Sodium lauryl sulfate 0.9 Myristic acid diethanolamide 0.9 Palmitic acid 0.5 Ascorbic acid-2-phosphate sodium salt 1 citric acid monohydrate 0.5 ethyl parahydroxybenzoate 0.1 aluminosilicate 20 perfume 1 purified water balance total 100% initial pH 8.71 25 ° C. 1M after pH 8.92

Example 8 Toothpaste Propylene glycol 400 4% sorbite solution (60%) 40 Carboxymethylcellulose 2 Saccharin sodium 0.15 Sodium lauryl sulfate 1 Lauroyl sarcosine sodium 0.2 Sodium benzoate 0.5 Tranexamic acid 0.05 phosphoric acid ester magnesium salt 0.05 sodium tartrate ascorbate 0.02 titanium binding silica 20 pyrogenic silica 1 perfume 1 sodium hydroxide qs purified water balance total 100% initial pH 9.05 25 ° C. 1M after pH 8. 61

Example 9 Toothpaste Propylene glycol 5% Sorbite solution (60%) 60 Sodium alginate 3 Sodium saccharin 0.15 Sodium lauryl sulfate 1 Butyl paraoxybenzoate 0.5 Triclosan 0.1 Ascorbic acid-2-phosphate sodium salt 1 sodium tripolyphosphate 1 sodium myristate 0.2 silica gel 20 perfume 1 sodium qs purified water balance total 100% initial pH hydroxide 7.91 25 ° C. 1M after pH 8.58

Example 10 Toothpaste Sodium polyacrylate 0.5% Xanthan gum 0.5 Propylene glycol 5 70% sorbite solution 50 Saccharin sodium 0.1 Sodium benzoate 0.3 Sodium lauryl sulfate 1.5 Tranexamic acid 0. DESCRIPTION OF SYMBOLS 1 Ascorbic acid-2-phosphate ester magnesium salt 0.5 Triethanolamine 2.5 Tartaric acid 2 dl-α-tocopherol 0.2 Oak extract 0.05 Sodium fluoride 0.2 Silica gel 10 Precipitable silica 10 Perfume 1 Carbonate sodium qs purified water balance total 100% initial pH 8.71 25 ° C. 1M after pH 8.68

[Example 11] Mouthwash ethanol 10% glycerin 5 sorbitol 5 mannitol 3 maltitol 3 polyoxyethylene (60) hydrogenated castor oil 1.0 sodium lauryl sulfate 0.1 magnesium ascorbic acid-2-phosphate ester salt 0.2 tocopherol acetate 0.05 perfume 0.3 purified water balance total 100% initial pH 8.44 25 ° C. 1M after pH 8.49

Example 12 Oral Pasta Cetanol 20% Squalane 5P. O. E (40) Hardened castor oil 0.1 Xylitol 8 Sorbitan monooleate 1 Sodium lauryl sulfate 0.2 Glycyrrhetinic acid 0.1 Saccharin sodium 0.6 Ascorbic acid phosphate sodium salt 0.3 Citric acid 0.5 Silicic anhydride acid 3 perfume 0.3 potassium hydroxide qs purified water balance total 100% initial pH 8.25 25 ° C. 1M after pH 8.38

[Brief description of the drawings]

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a view for explaining a gingival state of an anterior tooth part.
Is a state without gingivitis, (B) is a state with some gingivitis,
(C) is a state in which gingivitis is considerably recognized.

[Explanation of symbols]

 X Teeth Y Gingiva Z Gingivitis

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI theme coat ゛ (Reference) A61P 1/02 A61P 1/02 F-term (Reference) 4C076 AA06 BB23 CC24 DD02 DD67Q EE30Q FF63 4C083 AA112 AB032 AB172 AB242 AB282 AB472 AC022 AC122 AC131 AC132 AC242 AC302 AC432 AC482 AC622 AC792 AC812 AC862 AD042 AD092 AD211 AD272 AD302 AD352 AD532 AD641 AD642 AD662 BB05 CC41 DD22 EE33 4C086 AA01 AA02 DA34

Claims (3)

[Claims] 1. One selected from (A) ascorbic acid phosphate or a salt thereof, (B) an anionic surfactant, (C) a monosaccharide alcohol having 4 or more carbon atoms, an oligosaccharide alcohol, and reduced starch syrup. Or containing two or more sugar alcohols and having a calcium and aluminum ion source content of less than 10% by mass of the total composition;
A composition containing ascorbic acid phosphates, which has a pH of 8.0 or more after storage at 5 ° C. for one month. 2. The composition according to claim 1, wherein the sugar alcohol is contained in a weight ratio of 0.5 or more with respect to the water content in the composition. 3. The composition according to claim 1, which is for oral use.