JPS6234012B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an oral composition stably containing dextranase. Conventionally, it has been known that dextranase is incorporated into oral compositions to prevent the formation of dental plaque as an active ingredient for caries prevention (Patent No. 782154).
issue). However, dextranase has the problem of being easily deactivated due to the influence of moisture, anionic activators, etc. in oral compositions, and for this reason, conventional methods for stably blending dextranase into oral compositions have been developed. Various proposals have been made (Patent No. 802787, Patent No. 924229)
However, the stabilization of dextranase is still insufficient, especially when stored at high temperatures, and therefore, a method that can further stabilize dextranase in oral compositions is desired. It is rare. The present inventors conducted various studies on stabilizing the formulation of dextranase into oral compositions, and found that
Together with dextranase, the following formula (1) NH ₂ -CH ₂ -R-COOH ... (1) (where R is a cyclohexane ring or n-C ₄ H ₈
When omega amino acids represented by the following groups or their alkyl esters or aryl ester derivatives, particularly tranexamic acid and epsilon aminocaproic acid, are incorporated, dextranase is stabilized in oral compositions, and oral compositions can be prepared at high temperatures of 40°C. The residual rate of dextranase is high even after long-term storage of the composition, and the effect of dextranase is effectively exhibited. The present invention was based on the discovery that the effectiveness of oral compositions is enhanced by the combination with omega amino acids and their derivatives, and the caries preventive effect and alveolar pyorrhea preventive effect are synergistically enhanced. . The present invention will be explained in detail below. The oral composition according to the present invention is used as a dentifrice such as a toothpaste, a moisturized toothpaste, a liquid toothpaste, a mouthwash, a troche, a chewing gum, a gingival massage cream, etc. One or more of the indicated omega amino acids or their alkyl esters or aryl ester derivatives are blended. In this case, the amount of dextranase blended is usually 100 to 100,000 units per gram of toothpaste (u/g of dentifrice), particularly preferably 1,000 to 50,000 u/g of dentifrice. Here, 1 unit refers to the amount of enzyme that produces free reducing sugars equivalent to 1 μg of glucose per minute when the reaction is performed using dextran as a substrate. Further, as the omega amino acid, tranexamic acid in which R in the above formula (1) is a cyclohexane ring, and epsilon aminocaproic acid in which R is an n-C ₄ H ₈ group can be used, and as their alkyl ester or aryl ester derivative, epsilon Aminocaproic acid hexyl ester, epsilon aminocaproic acid heptyl ester, tranexamic acid hexyl ester, tranexamic acid phenyl ester, etc. can be used, but tranexamic acid and epsilon aminocaproic acid are particularly preferably used from the viewpoint of preventing alveolar pyorrhea. The amounts of the above omega amino acids and their derivatives are:
From the viewpoint of the stabilizing ability of dextranase, it is preferably 0.01% (by weight, the same hereinafter) or more, and from the viewpoint of the usability and stability of the oral composition, it is preferably 3% or less, and within this range, dextranase In addition to the stabilizing effect, the caries prevention and alveolar pyorrhea prevention effects are also well exhibited, and the usability is also good. In addition, the more preferable blending amount of omega amino acids and their derivatives is 0.03 to 1%. In the present invention, appropriate commonly used components may be blended depending on the type of oral composition. For example, in the case of toothpaste, dibasic calcium phosphate dihydrate and anhydride, calcium carbonate, calcium pyrophosphate, aluminum oxide compounds,
One or more of silica, aluminum silicate, insoluble sodium metaphosphate, tertiary magnesium phosphate, magnesium carbonate, calcium sulfate, synthetic resin, etc. may be blended (the amount usually ranges from 20% to 90%).
%, 20% to 60% in case of toothpaste). In _particular , _among these, _aluminum oxide compounds (alumina,
Alumina hydrate) is preferably used, and by using this aluminum oxide compound as the main polishing agent, stabilization of dextranase can be achieved more reliably. In this case, the aluminum oxide compound is preferably α-alumina or α-alumina hydrate. As alumina hydrate, gypsite, bayerite, boehmite, diaspore, etc. can be suitably used, and trihydrate is particularly excellent as a mild abrasive, but among these, gypsite is preferably used in terms of supplyability etc. It will be done. In addition, in the case of toothpaste, binders include cellulose derivatives such as carrageenan and sodium carboxymethylcellulose, alkali metal alginates such as sodium alginate, gums such as vegum and xanthan gum, synthetic binders such as polyvinyl alcohol, silica gel, and aluminum. One or more types of inorganic binders such as silica gel may be blended (the blending amount is usually 0.3 to 5%). In particular, when blending an alkali metal monofluorophosphate as an active ingredient, it is preferable to use carrageenan and an alginate alkali metal salt in combination from the viewpoint of stability and usability of the dentifrice composition. In this case, Katsupa-carrageenan is more effective in preventing skin roughness in dentifrice compositions than ordinary carrageenan (Katsupa/iota mixed system), so Katsupa-carrageenan can be used as carrageenan in terms of stability of dentifrice compositions. Preference is given to using carrageenan. Furthermore, in the production of dentifrices, one or more of sorbitol, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, xylit, malt, lactic, etc. may be blended as a viscosity agent ( (Usually 10-70%). In this case, it is desirable to use 1 to 5% propylene glycol as the binder dispersion, but if a large amount is blended, the residual rate of dextranase during storage will decrease, so sorbitol is blended as the main thickener, and propylene glycol 1 - 5% is used. It is desirable to use 6 to 60 parts by weight of sorbitol in combination with 6 to 60 parts by weight of sorbitol. Furthermore, when manufacturing toothpastes, water-soluble salts of higher alkyl sulfuric acid whose alkyl group has 8 to 18 carbon atoms such as sodium lauryl sulfate and sodium myristyl sulfate, sodium lauryl monoglyceride sulfonate, and sodium coconut monoglyceride sulfonate are used. The number of carbon atoms in the fatty acid group is 10.
Water-soluble salt of higher fatty acid monoglyceride sulfonate which is ~18, higher fatty acid sodium monoglyceride monosulfate, sodium-N-methyl-N-palmitoyltauride, sodium-N-
The number of carbon atoms in the fatty acid group is 12, such as lauroyl sarcosinate and sodium-N-lauroyl-β-alanine.
Anion activators such as salts of amides of higher fatty acids and lower aliphatic amino acids with a carbon number of 12 to 18, fatty acid diethanolamides such as lauric acid diethanolamide, stearyl monoglyceride, sucrose mono- and dilaurate, etc. ~18
Sucrose fatty acid ester, lactose fatty acid ester, lactitol fatty acid ester, maltitol fatty acid ester, ethylene glycol approx.
Nonionic surfactants such as sorbitan monostearate condensates with moles added, polymers of ethylene oxide and propylene oxide, derivatives such as polyoxyethylene polyoxypropylene monolauryl ester, amphoteric surfactants such as betaine type, amino acid type, etc. One or more surfactants (compounding amount usually 0.5 to 7%) may be blended. As fragrances, essential oils such as peppermint and spearmint, l-
Flavoring materials such as menthol, carvone, eugenol, anethole, etc. may be blended alone or in combination in an amount of about 0.1 to 5% of the total. Satucalin sodium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perilartin,
Sweeteners such as p-methoxycinnamic aldehyde, p-hydroxymethylbenzoic acid,
Preservatives such as p-hydroxybutylbenzoic acid and other ingredients may be added. For example, in the case of toothpaste, the above-mentioned desired ingredients may be mixed with an appropriate amount of water. Furthermore, when producing mouthwashes, troches, chewing gums, gingival pine surge creams, etc., they can be produced in accordance with conventional methods using appropriate commonly used ingredients. In addition, in the present invention, in addition to dextranase and omega amino acids, enzymes such as amylase, protease, mutanase, lysozyme, and litetsuenzyme, sodium monofluorophosphate, and potassium monofluorophosphate are used as active ingredients. Alkali metal monofluorophosphates such as sodium fluoride, fluorides such as stannous fluoride, chlorhexidine salts, aluminum chlorohydroxylalantoin, dihydrocholesterol, glycyrrhizin salts, glycerophosphate, sodium chloride, water-soluble inorganic phosphoric acid compounds One or more types of active ingredients such as the following may be blended. In particular, when an alkali metal monofluorophosphate such as sodium monofluorophosphate is used in combination with dextranase, it stabilizes dextranase and maintains a high residual rate of dextranase in the dentifrice composition after long-term storage. It is desirable because it can be done. In this case, the blending amount of alkali metal monofluorophosphate is 0.1 to 1
It is preferable to set it as weight%. In addition, when dextranase and mutanase are combined, a synergistic effect occurs to dissolve plaque and prevent re-deposition, and the combination of dextranase and Litetsuque enzyme has benefits such as strengthening the efficacy of Liteque enzyme. be. Note that the water-soluble inorganic phosphoric acid compound includes potassium salts or sodium salts of orthophosphoric acid, pyrophosphoric acid, and polyphosphoric acid, and potassium salts are preferred. In the oral composition according to the present invention, dextranase is stabilized by using one or more of omega amino acids or its alkyl ester or aryl ester derivative in combination with dextranase. The removal effect remains high for a long period of time, and by increasing the plaque removal effect, the effect not only of caries prevention but also of alveolar pyorrhea is enhanced. When used in combination with omega amino acids such as omega amino acids and their derivatives, higher caries preventive effects and alveolar pyorrhea preventive effects are exhibited. Next, experimental examples will be shown to specifically explain the effects of the present invention. Experimental example The following formulation: Dibasic calcium phosphate 50% Sorbiturate 15 Propylene glycol 3 Sodium lauryl sulfate 1.5 Lauric acid diethanolamide 1.2 Carrageenan 0.5 Sodium alginate 0.5 Gelatin 0.4 Sodium saccharin 0.1 Flavoring 1.0 Sodium monofluorophosphate 0.76 Dextranase 2000u /g toothpaste water remaining 100.0% toothpaste (comparison toothpaste 1), and this comparison toothpaste 1
In the formulation, toothpaste containing 0.1% tranexamic acid (invention toothpaste 1), toothpaste containing 0.1% epsilon aminocaproic acid (invention toothpaste 2), and toothpaste containing 0.1% glycine (comparison toothpaste 2) were prepared. The amount of dextranase was measured immediately after preparation and after storage at 40°C for one month, and the residual rate of dextranase was investigated. The results are shown in the table below. The survival rate is indicated by the dextranase activity immediately after preparation and after storage at 40°C for one month.

[Table] From the above results, it was found that dextranase was stabilized by the addition of tranexamic acid and epsilon aminocaproic acid, and there was little deactivation of dextranase even after long-term storage at relatively high temperatures. Examples are shown below. Example 1 Toothpaste alumina hydrate (gypsite, average particle size 10μ)
50% Propylene glycol 2% Sorbit 20 Sodium lauryl sulfate 1.5 Lauric acid diethanolamide 1.0 Carrageenan 1.0 Saccharin sodium 0.1 Fragrance 1.0 Tranexamic acid 0.05 Dextranase 2000u/g Toothpaste water Remaining 100.0% Example 2 Toothpaste dibasic calcium phosphate 45% Sorbit 25 Sodium lauryl sulfate 1.5 Lauric acid diethanolamide 0.5 Carrageenan 0.3 Sodium alginate 0.7 Sodium monofluorophosphate 0.76 Sodium saccharin 0.1 Fragrance 1.0% Tranexamic acid 0.2 Dextranase 1000u/g toothpaste water Remaining 100.0% Implementation Example 3 Junsei toothpaste calcium carbonate 70% Glycerin 10 Sodium lauroyl sarcosinate 0.5 Lactitol monolaurate 1.5 Gelatin 0.3 Satucharin sodium 0.2 Fragrance 1.0 Sodium chloride 5.0 Epsilon aminocaproic acid 0.04 Dextranase 10000u/g Toothpaste water Remaining 100.0% Example 4 Liquid toothpaste glycerin 35% Sodium polyacrylate 5% Sodium lauryl sulfate 1 Satucalin sodium 0.2 Fragrance 3 Tranexamic acid 3 Dextranase 30000u/g Toothpaste water Remaining 100.0% Example 5 Mouthwash ethanol (90%) %) 20% Satucalin sodium 0.3 Polyoxyethylene (80 mol) Sorbitan monolaurate 0.5 Flavor 3 Tranexamic acid 1 Dextranase 5000u/ml Mouse dew water Remaining 100.0% Example 6 Lozenge gum arabic 6% Glucose 92 Flavor 1 % Epsilon aminocaproic acid 1 Dextranase 2500u/g Lozenge water Remaining 100.0% Example 7 Chewing gum gum base 20 parts by weight Calcium carbonate 2 Starch syrup 15 Powdered sugar 60 Flavoring 1 Tranexamic acid 0.1 Dextranase 1000u /g gum The oral compositions of Examples 1 to 7 all have high storage stability of dextranase.

Claims (1)

[Claims] 1 Together with dextranase, the following formula NH ₂ -CH ₂ -R-COOH (wherein R is a cyclohexane ring or n-C ₄ H ₈
An oral composition characterized in that one or more of the following omega amino acids or their alkyl ester or aryl ester derivatives are used in combination. 2 Claim 1 in which the omega amino acid is tranexamic acid or epsilon aminocaproic acid
Oral composition as described in . 3. Omega amino acid content is 0.01-3% of the total
The oral composition according to claim 1 or 2.