WO2002002124A1 - Compositions containing ascorbic acid phosphoric acid esters - Google Patents

Abstract

Compositions containing ascorbic acid phosphoric acid esters characterized by containing: (A) an ascorbic acid phosphoric acid ester or its salt; (B) an anionic surfactant; and (C) one or more sugar alcohols selected from among monosaccharide alcohols having 4 or more carbon atoms, oligosaccharide alcohols and reducing starch syrups; having less than 10% by weight, based on the whole composition, of calcium and aluminum ion sources, and showing a pH value of 8.0 or higher after storing at 25 °C for 1 month.

Description

 Detail

 Acid Phosphate-Containing Composition Technical Field

 The present invention relates to a composition for oral cavity and dermis containing ascorbic acid phosphates. Background art

 Ascorbic acid phosphate and salts thereof play an important role in the expression of various enzyme activities in living organisms, and are known to 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 bimin which eliminates excess active oxygen produced in the body and protects biological tissues from oxygen damage, and is known to have various physiological activities. .

 Conventionally, compositions containing ascorbic acid phosphate and its salts include cosmetics (JP-A-62-298508 and JP-A-3-63208), and whitening cosmetics (JP-A-63-243014). Gazettes, JP-A-1-305509, JP-A-3-133914), oral agents (JP-A-62-96408), bath agents (JP-A-62-96410), oral compositions ( JP-A-2-292210, JP-A-2-292211, JP-A-173173727), skin external preparations (JP-A-3-34908, JP-A-7-206632, JP-A-133951), etc. Stuff has been proposed.

 However, when ascorbic acid phosphate or a salt thereof is added to various compositions, the composition becomes unstable due to the influence of calcium, metal, microorganisms, pH, etc., and as a result, there is a problem that 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 antioxidants and chelating agents, and to make the composition powdery or granular in order to minimize contact with water (Japanese Patent Publication No. Hei 7-252127). Gazette). However, such ascorbic acid phosphates In a composition containing tellurium or a salt thereof, it is necessary not only to stably combine phosphoric acid esters of ascorbate, but also to express higher physiological activity when using the same. .

 In this regard, select dosage forms with excellent usability, such as pastes, liquids, and creams, and maintain appropriate foaming power and dispersibility. It is desired that the ester or its salt be absorbed by living organisms while maintaining the structure of the ester or its salt. In such a dosage form containing water, ascorbic acid phosphate and its salt are stably blended, and its effect is improved. It is hoped that technology that will effectively demonstrate the benefits will be developed. Disclosure of the invention

 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.

 As a result of intensive studies to achieve the above object, the present inventors have found that, in a composition containing ascorbic acid phosphate or a salt thereof, an anionic surfactant, a monosaccharide alcohol having 4 or more carbon atoms, an oligosaccharide, Selected from alcohol and reduced syrup

Combine one or more kinds and limit the content of calcium and aluminum ion sources to less than 10% (mass percentage, the same applies hereinafter) of the total composition. PH after storage for 1 month at 8.0 or more, particularly preferably 8.0.

By adjusting the initial pH so as to be 5 to 9.5, the stability over time of the composition containing the ascorbic acid phosphate or a salt thereof is improved, and the ascorbic acid phosphate is maintained even after long-term storage. Alternatively, it was found that a reduction in the residual ratio of the salt was effectively prevented, and the effect was effectively exhibited. In this case, many of the compositions containing the ascorbic acid phosphate or a salt thereof have an initial pH of 8.0 or more, particularly 8.5 to 9.5, even if adjusted to around room temperature after production. Even after storage, pH may change significantly within one month, and pH may be lower than 8.0.

If the pH after storage for one month falls below 8.0, stable combination of ascorbate phosphate ester and its salt will not be achieved, so that it will be stored at 25 ° C for one month. It has been found that the pH value of the composition after the preservation is important for incorporating the ascorbic acid phosphate and its salt in a stable and active state. BRIEF DESCRIPTION OF THE FIGURES

 〔Figure 1〕

 (A) is a state without gingivitis, (B) is a state with some gingivitis, and (C) is a state with considerable gingivitis. BEST MODE FOR CARRYING OUT THE INVENTION

 Hereinafter, the present invention will be described in more detail.

 The composition of the present invention comprises (A) ascorbic acid phosphate or a salt thereof, (B) anionic surfactant, (C) a monosaccharide alcohol having 4 or more carbon atoms, an oligosaccharide alcohol, and reduced starch syrup. One or more selected sugar alcohols are contained, the content of calcium and aluminum ion sources is less than 10% by mass of the whole composition, and after storage at 25 ° C for one month, pH is 8.0 or more.

 Here, ascorbic acid phosphoric acid ester is one in which one or more of the hydroxyl groups at any of the 2, 3, 5, and 6 positions of ascorbic acid has become an ester of a compound such as phosphoric acid or polyphosphoric acid. Examples thereof include ascorbic acid-2-phosphate, ascorbic acid-3-phosphate, ascorbic acid-6-phosphate, and ascorbic acid-12-polyphosphate. Examples of the salts include alkali metal salts such as sodium salt, potassium salt, calcium salt, and magnesium salt, and alkaline earth metal salts. Among them, particularly when used for the oral cavity, magnesium ascorbate phosphate sodium salt is preferably used from the viewpoint of the effect of preventing and improving periodontal disease.

The compounding amount is preferably 0.01 to 10%, particularly preferably 0.01 to 5% of the whole composition. If the amount is too small, the effect may not be sufficiently exhibited, and if the amount is too large, the usability may be reduced. Next, an anionic surfactant is blended for the purpose of imparting an appropriate foaming power or imparting dispersibility. In this case, it has been said that the anionic surfactant reduces the stability of the ascorbic acid phosphate or a salt thereof due to its combination. However, in the present invention, the composition is stored at 25 ° C for one month. By adjusting the pH to 8.0 or more, stabilization of ascorbic acid phosphate or a salt thereof was successfully achieved even when an anionic surfactant was added.

 Here, as the anionic surfactant, various kinds of conventionally known anionic surfactants, for example, alkyl sulfate, polyoxyethylene alkyl sulfate, α-sulfo fatty acid ester, << olefin sulfonate, alkyl Or hydroxyalkyl ether carboxylate, Ν-acylated taurine, Ν-acylated glycine, Ν-asinoleated aspartate, Ν-acylated sarcosine, Ν-acylated glutamate, monoalkyl phosphate ester salt , Alkyl amide ether sulfate, alkyl (poly) glyceryl ether sulfonate, alkyl (poly) dali seryl ether carboxylate, secondary amide-type amino acid salt, alkyl tartrate, alkyl amide malate , Quinic acid alkylamide, alkyl ( Li) glyceryl sulfonate, although monoglyceride succinate salts, and Ru and the like, alkyl sulfate salt is preferred among these.

 The compounding amount of the anionic surfactant is appropriately selected, but is preferably 0.1 to 10%, particularly preferably 0.5 to 3% of the whole composition.

 The composition of the present invention further contains one or more of monosaccharide alcohols having 4 or more carbon atoms, oligosaccharide alcohols, and reduced starch syrups. Specific examples of the monosaccharide alcohol having 4 or more carbon atoms include erythritol, xylitol, mannitol, sorbitol, galactitol, and iditol. Oligosaccharide alcohols include, for example, mulch! One example is 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%, particularly 5 to 60% of the whole composition, but is 0.5 as a weight ratio to the amount of water contained in the composition. As described above, it is more preferable that the compound is blended at a ratio of 0.5 to 2.0, and more preferably 0.75 to 1.5, whereby the effect of ascorbic acid phosphate ester or a salt thereof is reduced. It can be more effectively exerted.

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

 In the composition of the present invention, the content of a calcium ion source, an aluminum ion source, for example, a calcium-containing compound such as calcium hydrogen phosphate, tertiary calcium phosphate, or calcium pyrophosphate, or an aluminum-containing compound such as aluminum hydroxide is adjusted to the entire composition. Is less than 10%, preferably 1% or less, more preferably 0.1% or less, 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. Alternatively, the decomposition of a salt thereof is promoted, but these disadvantages can be prevented by limiting the content of the calcium-containing compound and the aluminum-containing compound to less than 10% of the whole composition.

 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. However, it may be prepared into a dosage form such as a paste, liquid, or 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, compositions for the oral cavity are prepared as dentifrices such as toothpastes and liquid dentifrices, gingival massage creams, topical coatings and mouthwashes. In the case of dentifrices, abrasives, binders and sweeteners are used. Agents, perfumes, various active ingredients, and the like can be added at ordinary doses.

In this case, the polishing agent is preferably a silica-based polishing agent such as silica gel, precipitated silica, aluminosilicate, zirconosilicate (titanium-binding silica), and other components such as magnesium carbonate, bentonite, and polymethyl methacrylate. Can be. Examples of the binder include carrageenan, cellulose derivatives such as carboxymethylcellulose sodium, methylcellulose and hydroxyethylcellulose; alginic acid derivatives such as sodium alginate and propylenedaricol alginate; xanthan gum, dielan gum, trangant gum, and karaya gum. One or two or more of gums such as poly (vinyl alcohol), sodium polyacrylate, synthetic binders such as propyloxypiryl polymer, and inorganic binders such as silica gel, veegum, and labonite .

 As the thickener, the above sugar alcohol is used, and if necessary, dariserin, propylene glycol, polyethylene glycol, or the like may be added. In addition to the above anionic surfactant, a surfactant such as decayl laurate is used. Nonionic surfactants such as glyceryl and myristic acid diethanolamide, and amphoteric surfactants such as betaine may be blended.

 The fragrance ingredients include menthol, anethol, carvone, eugenol, n-decyl alcohol, citronellol, α-terpineol, cineol, linamouth, ethyl linalool, peniline, thymol, peppermint oil, spearmint oil, wintergreen Flavors such as oil, t-shaped oil and eucalyptus oil can be used alone or in combination. Further, sweeteners such as saccharin sodium, perillartin, somatatin and the like may be added.

In addition, the present invention relates to cationic bactericides such as chlorhexidine, benzethonium chloride, benzalkonium chloride, cetylpyridinium chloride, decalinium chloride, and the like, such as tricoctane, hinokitiol, and biozol. Enzymes such as phenolic compounds, dextranase, mutanase, lysozyme, amylase, protease, lytic enzyme, and SOD; alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate; sodium fluoride; and stannous fluoride. Which fluoride, tranexamic acid, epsilon aminocaproic acid, allantoin, dihydrocholesthanol, glycyrrhizic acids, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, xylitol, zinc chloride, water Sex inorganic phosphoric acid compounds, vitamin A, vitamin B group, etc. vitamins 及 beauty their derivatives such as vitamin E, known active ingredients can be formulated alone or in combination. The composition of the present invention has an initial pH adjusted so 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. I do. 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 then stabilized. This is because it was found that the pH after storage at 25 C for one month was important.

 In this case, the pH fluctuation differs depending on the ingredients.For example, when silica gel is blended, the pH increases after storage at 25 ° C for 1 month compared to the initial pH, and conversely, when precipitated silica is combined. pH drops. Therefore, to adjust the initial pH to the required pH after storage at 25 ° C for one month, set the initial pH to 25 ° C and set the pH after storage for one month according to the formulation of the composition. Adjust to lower or higher. If necessary, a method of examining the relationship between the initial pH and the pH after storage at 25 ° C for one month through preliminary tests may be adopted. For pH adjustment, commonly used pH adjusters can be used, but sodium hydroxide and potassium hydroxide can be suitably used.Also, water-soluble citrate, phosphate, Carbonates, bicarbonates and the like can also be preferably used.

 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 effectively exerts its effects even after long-term storage.

 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. A one-week use test was performed using dentifrice for one to three months after adjustment, and the effect of improving gingivitis was observed. That is, 10 healthy volunteers used the following toothpastes A and B for one week, then stopped oral cleaning for two days, self-evaluated their gingival condition, and filled out a questionnaire. There was at least one week between each dentifrice use. In the questionnaire, the gingiva in the upper and lower jaw of the anterior teeth was observed and scored as shown below with reference to Figures 1 (A) to (C). Table 1 shows the results.

 0: No gingivitis, Fig. 1 (A)

1: Slight gingivitis, Fig. 1 (B) 2: Gingivitis present, Fig. 1 (C)

In the figures, X indicates teeth, Y indicates gingiva, and Z indicates gingivitis.

 Dentifrice A Dentifrice B

Magnesium L-ascorbic acid 2-phosphate ester 0.3% 0.3% Precipitated silica 5% 5% Propylene glycol 3 5% 3 5% Carboxymethylcellulose 5% 5% Butyl paraoxybenzoate 0 1% 0 1 %

 0 2% 0 2% Fragrance% 1% Sodium lauryl sulfate 5% 5% Titanium dioxide 0 5% 0 5% Cunic acid 0 1% 0 1%

70% sorbite liquid 50%

85% glycerin 40% sodium hydroxide 0.3% 0.35% purified water

 Total 100.0% 100.0% H (initial) 8.93 8.96 H (25Τ months later) 8.58 8.60 Water content of sugar alcohol (weight ratio) 0.706

 〔table 1〕

 (Example 15 and Comparative Example 14)

Dentifrices were prepared by blending the components shown in Table 2 (silica, sorbitol or glycerin) with the common composition below. The pH was measured immediately after preparation of these dentifrices and after storage at 25 ° C for 1 month, 6 months, and 18 months. Also, store in a 60 ° C thermostat for 1 month. After storage for 6 months in a 40 ° C thermostat, and after storage for 18 months at 25 ° C, the residual ratio of magnesium ascorbyl phosphate was measured. It was measured. Table 2 shows the results.

Common composition

 Magnesium L-ascorbic acid 2-phosphate ester 0.3% Propylene glycol 3.5

Carboxymethyl cellulose 1.5

Butyl paraoxybenzoate 0.1

Saccharin sodium 0.2

Fragrance 1

Sodium lauryl sulfate 1.5

Titanium dioxide 0.5

Cuic acid 0.1

Sodium hydroxide (appropriate amount) about 0.3 silica Table 2

Sorbit Table 2

Glycerin Table 2

Purified water _ residue

(Table 2)

Silica type A: Silica gel

 B: precipitated silica

 [Example 6] toothpaste

 Propylene glycol 5%

7 0% sorbit 5 0

 Kara Senichi Nan 1 2

 Saccharin sodium 0 2

 Sodium lauryl sulfate 2

 Ethyl paraoxybenzoate 0

 Ascorbic acid mono-phosphate magnesium salt 0 2

 Cuic acid monohydrate 0 2

 Zirconosilicate 1 8

 Gay anhydride (from Tokuyama) 3

 Perfume 0 9

 Sodium hydroxide

purified water Total 00%

Initial pH 9.28 25 ° C After 1M pH 8.80 [Example 7] Toothpaste

Polyethylene glycol 400 5% 70% sorbit 40

Xanthan gum 1,

Xylitol 10

Sodium lauryl sulfate 0 9 Myristic acid diethanolamide 0 9 Palmitic acid 0 5 Ascorbic acid monophosphate phosphate sodium salt

Quenoic acid monohydrate 0.5 Ethyl paraoxybenzoate 0.1 Aluminosilicate 20

Spice

purified water _

 Total 100%

Initial pH 8.71 25 ° Cli ^ pH 8.92 [Example 8] Toothpaste

Propylene glycol 400 4% Solpit liquid (60%) 40

Carboxymethyl cellulose 2

Saccharin sodium 0,15 Sodium lauryl sulfate 1

Lauroyl sarcosine: 0 2 Sodium benzoate 0, 5 Tranexamic acid 0 05 Ascorbic acid phosphate magnesium salt 0 05 Sodium tartrate 0 02 Titanium binding silica 20

Igneous silica 1

Spice

Sodium hydroxide

purified water

 Total 100%

Initial pH 9.05 25 ° C After 1M pH 8.61 [Example 9] Toothpaste

Propylene glycol 5% sorbite solution (60%) 60

Sodium alginate 3

Saccharin sodium 0.15 Sodium lauryl sulfate 1

Butyl para-oxybenzoate 0.5 Tric-mouth mouth 0.1 Ascorbic acid 2-sodium phosphate sodium salt 1

 Sodium tripolyphosphate 1

Sodium myristate 0.2 Silica gel 20

Fragrance 1

Sodium hydroxide suitable amount

Purified water residue

 Total 100%

Initial pH 7.91 25 ° C After 1M pH 8.58 Example 10 Toothpaste Sodium polyacrylate 0 5% Xanthan gum 0.5 Propylene glycol 5

 70% sorbite liquid 50

Saccharin sodium 0

Sodium benzoate 0 3 Sodium lauryl sulfate 5 Tranexamic acid 0,1 Ascorbic acid monophosphate 2-magnesium phosphate 0,5 Triethanolamine 2.5 Tartaric acid 2

d 1-a-Tocopherol 0 2 Ovarak extract 0 05

 0 2

 Ten

Precipitated silica 10

Fragrance 1

Carbonate:

purified water

 Total 00%

Initial; PH 8.71 25 ° C after 1M pH 8.68 [Example 11] Mouthwash

Ethanol 10% glycerin .5

Sorbit 5

Manni 1 ^ 3

Maltitol 3

Polyoxyethylene (60) hydrogenated castor oil 1 0 Sodium lauryl sulfate 0.1

Ascorbic acid monophosphate 2 magnesium salt 0.2

Tocopherol acetate 0.05 Fragrance 0.3 Total 00%

Initial PH 8.44 25 ° C after 1M ρΗ 8.49 [Example 12] Oral pasta

Cetanol 20% squalane 5

 P. 〇. Ε (40) Hardened castor oil 0.

Xylitol 8

Sorbitan monooleate 1

Lauryl sulfate: 0 2

Glycyrrhetinic acid 0

 0 6

Ascorbic acid phosphate sodium salt 0 3

Cuenoic acid 0 5

Caic anhydride 3

Fragrance 0 3

Potassium hydroxide

purified water _

 Total 100%

Initial PH 8.25

25 ° C after 1M ρΗ 8.38

Claims

The scope of the claims  1. (A) Ascorbic acid phosphate or a salt thereof, (B) Anionic surfactant, (C) One or two kinds selected from monosaccharide alcohols having 4 or more carbon atoms, oligosaccharide alcohols and reduced starch syrups Contain the above sugar alcohol, the content of calcium and aluminum ion sources is less than 10% by mass of the total composition, and the pH after storage at 25 ° C for 1 month is 8.0 or more A composition containing phosphate esters of ascorbic acid, characterized in that:  2. The composition according to claim 1, comprising a sugar alcohol in a weight ratio of 0.5 or more to the water content in the composition. 3. The composition according to claim 1, which is for oral use.