JPH10298045A - Composition for oral cavity - Google Patents

Abstract

PROBLEM TO BE SOLVED: To prepare a safe composition for an oral cavity, good in transmucosal absorptivity of taurine and effective in preventing and treating periodontal diseases by using the taurine with a specific surfactant in combination. SOLUTION: This composition for an oral cavity is prepared by formulating taurine with a taurine derivative type surfactant in combination. An N- lauroyltaurine salt, an N-lauroylmethyltaurine salt, an N-myristoylmethyltaurine salt and an N-palmitoylmethyltaurine salt are preferred as the taurine derivative type surfactant. The molar ratio of the taurine derivative type surfactant/taurine is >=0.01 and the amount of the formulated taurine derivative type surfactant is 0.01-10 wt.% based on the whole composition. The amount of the formulated taurine is 0.001-20 wt.% based on the whole composition.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a composition for oral cavity which has good transmucosal absorbability of taurine, which is an active ingredient for alveolar bone resorption, is safe, and is effective for prevention and treatment of periodontal diseases.

[0002]

BACKGROUND OF THE INVENTION Periodontal disease is a disease of the periodontal tissue caused by periodontopathic bacteria, and as its symptoms progress, the inflammation of the soft tissue in the periodontal tissue causes the alveolar bone. Is a disease that results in the absorption of bones and eventually leads to tooth loss.

[0003] Conventionally, flurbiprofen (J. Periodont. Res.,
23 , 166-169, 1988), indomethacin (J. Periodont. Res., 17 , 90-1).
00, 1982) have been reported to be effective, and further disclosed in JP-A-60-61524.
The publication describes that ibuprofen and flurbiprofen have an effect of inhibiting alveolar bone resorption.

However, there is a concern that prolonged use of these drugs may cause harmful effects on the oral mucosa. For prevention and prevention of alveolar bone resorption caused by periodontal disease which is a chronic disease, it is particularly desirable to use a drug which is safe even when used in the oral cavity for a long period of time. In addition, it was necessary to develop a drug having an excellent alveolar bone resorption inhibiting effect.

Therefore, Japanese Patent Application Laid-Open No. Hei 6-247834 describes the effect of taurine on alveolar bone resorption which is safe even when used in the oral cavity for a long period of time. Also, taurine is applied to the oral cavity by using a tooth glossing agent (JP-A-49-428).
No. 38), an oral composition for the prevention and treatment of periodontal disease (JP-A-63-132820, JP-A-8-132820)
No. 40858) is known.

[0006] However, for a drug applied to periodontal tissue, efficient drug delivery to a diseased part is required to further improve its efficacy. However, taurine is a water-soluble substance, and is generally used as a drug. Percutaneous absorption and transmucosal absorption of water-soluble drugs are by no means high. Therefore, when taurine is to be more effectively applied in the oral cavity which is constantly washed away with saliva, it is desired to develop a method and an additive for promoting its transmucosal absorbability.

The present invention has been made in view of the above circumstances, and can promote the transmucosal absorption of taurine, which is safe even when used in the oral cavity for a long period of time, and exhibits an excellent alveolar bone resorption inhibiting effect. It is an object of the present invention to provide a highly efficacious oral composition which is effective for prevention and treatment of periodontal disease.

[0008]

Means for Solving the Problems and Embodiments of the Invention The present inventors have made intensive studies in order to achieve the above-mentioned object, and as a result, by using taurine and a taurine derivative-type surfactant in combination, an experiment described later was carried out. As is clear from the examples, the transmucosal absorption of taurine is surprisingly lower than when taurine is used in combination with other surfactants other than taurine derivative types such as sodium lauryl sulfate, lauryl diethanolamide, and lauroyl sarcone sheet. Is very high and hence
The present inventors have found that a highly efficacious oral composition for preventing and treating periodontal diseases can be obtained, and have accomplished the present invention.

It has been known for a long time to incorporate a taurine derivative type surfactant into an oral composition, and JP-A-1-308219 and JP-A-7-48238 disclose suppression of plaque formation. What was aimed, JP-A-2-23
Japanese Patent Application Laid-Open No. 3607/2003 discloses a compound for stabilizing and compounding fluoride, Japanese Patent Application Laid-Open No. 3-38516 discloses a method for improving oral mucosal irritation, and Japanese Patent Application Laid-Open No. 3-200715 discloses a foaming property / stable with time. Japanese Patent Application Laid-open No.
Japanese Patent Application Laid-Open No. 59937/5937 aims to stabilize and mix caries and periodontal disease preventing antibodies, and Japanese Patent Application Laid-Open No. 5-201878 discloses a method intended for transparent stability of transparent toothpaste.
Japanese Patent Publication No. 175944/1999 reports a product aimed at improving low-temperature stability and usability after long-term storage. However, it is not known that the combined use of taurine and a taurine derivative-type surfactant promotes the transmucosal absorption of a specific drug taurine, which is a new finding of the present inventors.

[0010] Accordingly, the present invention provides an oral composition comprising taurine and a taurine derivative-type surfactant in combination.

Hereinafter, the present invention will be described in detail.
Oral composition of the present invention, toothpaste, liquid toothpaste, water toothpaste,
It can be prepared into various dosage forms such as mouth washes, and is characterized in that taurine and a taurine derivative are used in combination as active ingredients.

In this case, the amount of taurine is preferably 0.001 to 20% (% by weight, the same applies hereinafter), particularly 0.05 to 10% with respect to the whole composition. If it is less than 0.001%, a sufficient alveolar bone resorption inhibiting effect may not be obtained, and if it exceeds 20%, the feeling of use may be impaired.

Examples of the taurine derivative type surfactant used in the present invention include N-acyltaurine or a salt thereof, N-acylalkyltaurine or a salt thereof, taurine-conjugated bile acid or a salt thereof, and the like. Specifically, N-acyltaurine has 8 to 9 carbon atoms in the acyl group.
18, N-lauroyl taurine, N-myristoyl taurine, etc., and N-acylalkyltaurine is an acyl group having 8 to 18 carbon atoms of an acyl group and 1 to 3 carbon atoms of an alkyl group, for example, N-lauroylmethyl Taurine, N-myristoylmethyltaurine, N-coconut oil fatty acid methyltaurine and the like, as taurine-conjugated bile acids,
For example, taurocholic acid, tauroglycocholic acid and the like are exemplified. Examples of such salts include alkali metal salts such as sodium and potassium, alkaline earth metal salts, ammonium salts, and organic amine salts. In the present invention, among these, N-lauroyl taurine salt,
N-lauroylmethyltaurine salt, N-myristoylmethyltaurine salt, N-palmitoylmethyltaurine salt,
N-coconut fatty acid methyl taurate and taurocholate are preferred.

In the present invention, one or more of the above-mentioned taurine derivative-type surfactants are used, and the compounding amount thereof is such that the molar ratio of taurine derivative-type surfactant / taurine is 0.01 or more, particularly 0. The range of 0.05 to 2 is preferable, and the blending amount with respect to the total composition is preferably 0.01 to 10%, particularly preferably 0.1 to 3%. When the compounding amount of the taurine derivative type surfactant is less than 0.01 in the molar ratio with respect to taurine or the compounding amount with respect to the composition is less than 0.01%, a sufficient taurine absorption promoting effect cannot be obtained. When the amount is more than 10% based on the total composition, the feeling of use may be impaired.

The oral composition of the present invention contains taurine and a taurine derivative-type surfactant as essential components, and includes dentifrices such as toothpaste, liquid toothpaste, and dentifrice, oral paste, ointments, and the like. Mouthwash, periodontal pocket,
It can be prepared and applied to dosage forms such as patches and troches for the oral cavity.

The oral composition of the present invention may further contain, in addition to the above-mentioned components, appropriate components according to the type of the target composition.

For example, as the polymer, methylcellulose, hydroxylpropylcellulose, sodium carboxymethylcellulose, hydroxyethylcellulose, propylene glycol alginate, pullulan, tragacanth gum, xanthan gum, chitosan, polyethylene oxide, polyvinylpyrrolidone, polyacrylic acid and polymethacrylic acid or these Salts, gelatin, peptone, casein, collagen, albumin,
Carrageenan, gum arabic, gum karaya, carboxyvinyl polymer, Eudragit (E, L, SR, S,
NE), ethyl cellulose, cellulose acetate, polyvinyl acetal / dimethylaminoacetate, cellulose acetate / dibutylhydroxyl propyl ether, and the like.

As the oil, liquid paraffin, paraffin,
Higher alcohols such as cetyl alcohol and stearyl alcohol, and fatty acid esters such as oleic acid and isopropyl myristate can be blended.

As an excipient, aluminum hydroxide, second
Calcium phosphate dihydrate, dicalcium phosphate
Anhydrous, monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate, insoluble sodium metaphosphate, amorphous silica, crystalline silica, aluminosilicate, aluminum oxide, tribasic magnesium phosphate, magnesium carbonate, magnesium sulfate, Titanium oxide, crystalline cellulose and the like are blended.

As the alcohol, ethanol, propyl alcohol, isopropyl alcohol, butanol,
Lower alcohols such as isobutanol and ethylene glycol, diethylene glycol, propylene glycol,
Polyhydric alcohols such as dipropylene glycol, 1,3-butylene glycol, glycerin, 1,5-pentadiol, sorbite, and polyethylene glycol are blended.

Examples of the surfactant include nonionic surfactants such as sorbitan fatty acid ester, glycerin fatty acid ester, decaglycerin fatty acid ester, polyglycerin fatty acid ester, propylene glycol / pentaerythritol fatty acid ester, polyoxyethylene sorbitan fatty acid ester, and polyoxyethylene sorbitan fatty acid ester. Ethylene glycerin fatty acid ester, polyoxyethylene sorbite fatty acid ester, polyethylene glycol fatty acid ester, polyoxyethylene alkyl ether, polyoxyethylene polyoxypropylene alkyl ether, polyoxyethylene alkyl phenyl ether, polyoxyethylene castor oil / hardened castor oil, poly Oxyethylene lanolin, lanolin alcohol, beeswax derivative, polyoxyethylene alkylamine Fatty acid amides, polyoxyethylene alkylphenyl formaldehyde condensates, single chain length polyoxyethylene alkyl ethers, anionic alkyl sulfates, polyoxyethylene alkyl sulfates, N-
Acyl amino acids and salts thereof, polyoxyethylene alkyl ether acetate, alkyl sulfocarboxylate, α-
Olefin sulfonate, alkyl phosphate, polyoxyethylene alkyl ether phosphate, cationic surfactants are alkyl ammonium salts, alkyl benzyl ammonium salts, amphoteric surfactants are betaine acetate, imidazolinium betaine, lecithin Etc. can be blended.

As the sweetener, saccharin sodium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin, p-methoxycinamic aldehyde, aspartame and the like can be blended.

Essential oils such as peppermint and spearmint, l-menthol, carvone, eugenol,
Anethole and the like can be blended.

As the stabilizer, vitamin C, vitamin E, sodium sulfite, sodium pyrosulfite, sodium hydrogen sulfite, butylhydroxytoluene, propyl gallate, butylhydroxyanisole and the like can be blended.

The oral composition of the present invention may contain various medicinal ingredients, for example, antibacterial agents such as chlorhexidine, triclosan, cetylpyridinium chloride, hinokitiol, sodium fluoride, stannous fluoride, Gingivitis such as fluorine compounds such as sodium fluorophosphate, plaque formation inhibitors such as dextranase, mutanase, and protease; tranexamic acid, ε-aminocaproic acid, glycyrrhizic acid, glycyrrhetinic acids, azulene, allantoin, lysozyme chloride, and oak extract Preventive agents, tartar preventive agents such as polyphosphates, gum tightening agents such as sodium chloride, and various vitamins such as tocopherol acetate.

[0026]

The oral composition of the present invention can promote the transmucosal absorption of taurine, which is safe even when used in the oral cavity for a long period of time, and can exhibit an excellent alveolar bone resorption inhibiting effect. It can be prepared into various dosage forms and can be effectively used for prevention and treatment of periodontal disease.

[0027]

EXAMPLES Hereinafter, the effects of the present invention will be specifically described with reference to experimental examples and examples, but the present invention is not limited to the following examples. In the following examples, all percentages are by weight.

[Experimental Example] The transmucosal absorbability of a drug was compared and studied using a hamster teak pouch mucosa by the following method.

A teak pouch mucosa isolated from a Syrian hamster (male, 6 weeks old) was attached to a Franz cell,
After preincubation at 37 ° C., 100 μl of a sample solution containing taurine and various surfactants was added as shown in Table 1. After incubating at 37 ° C. for 5 minutes, the mucous membrane was removed from the cell, the surface was washed with water, the portion to which the sample was administered was cut out with a punch having an inner diameter of 7.5 mm, and homogenized with a 10% trichloroacetic acid solution. Centrifuge the mixture,
The supernatant was analyzed by high performance liquid chromatography, and the amount of taurine absorbed into the mucous membrane was measured (repeating number n = 5).
Table 1 shows the results.

From the results shown in Table 1, it was confirmed that the combined use of a taurine-type surfactant with taurine greatly promoted the transmucosal absorption of taurine as compared with the combination with other surfactants. Was.

[0031]

[Table 1]

Examples will be described below. [Example 1] Toothpaste Aluminum hydroxide 45.0% Gelling silica 5.0 Sorbit 25.0 Sodium carboxymethylcellulose 1.0 Sucrose monopalmitate 1.0 Sodium lauryl sulfate 1.2 Methyl paraoxybenzoate 0 .1 Butyl paraoxybenzoate 0.01 Sodium saccharin 0.05 Taurine 1.0 Sodium N-lauroylmethyltaurine 0.5 Perfume 0.8 Water Balance 100.00%

[Example 2] Toothpaste Precipitated silica 40.0% Sorbit 25.0 Glycerin 25.0 Polyvinylpyrrolidone 1.0 Lauroyl polyglycerin ester 1.0 Polyoxyethylene (60 mol) 0.5 Sorbitan monolau Rate Saccharin sodium 0.05 Ethyl parahydroxybenzoate 0.1 Tranexamic acid 0.1 Taurine 0.8 N-lauroyl taurine sodium 0.8 Perfume 0.8 Water Balance 100.00%

Example 3 Toothpaste Dibasic calcium phosphate 45.0% Carboxymethylcellulose 1.0 Carrageenan 1.0 Glycerin 15.0 Propylene glycol 2.0 Sodium lauryl sulfate 0.8 Lauryl diethanolamide 0.5 β- Dipotassium glycyrrhizinate 0.5 Calcium aspartate 0.8 Sodium saccharin 0.1 Triclosan 0.02 Taurine 1.0 Sodium N-myristoylmethyltaurine 0.6 Fragrance 1.0 Purified water Balance 100.00%

Example 4 Toothpaste Aluminum hydroxide 25.0% Sorbit 25.0 Glycerin 25.0 Polyvinylpyrrolidone 1.0 Lauroyl polyglycerin ester 1.0 Polyoxyethylene (60 mol) 0.5 Sorbitan monolau Rate Propyl parahydroxybenzoate 0.1 Sodium saccharin 0.2 Sodium fluoride 0.5 Taurine 1.0 Sodium taurocholate 1.0 Fragrance 0.8 Purified water Balance 100.00%

Example 5 Toothpaste Precipitable silica 20.0% Thickening silica 3.0 60% Sorbite solution 25.0 Polyethylene glycol # 400 4.0 Sodium carboxymethylcellulose 1.5 Sodium lauryl sulfate 1.2 Benzo Sodium citrate 0.5 Methyl paraoxybenzoate 0.15 Butyl paraoxybenzoate 0.01 Sodium saccharin 0.1 Chlorhexidine hydrochloride 0.1 Sodium hydroxide (50% aqueous solution) 0.3 Taurine 0.5 N-coconut oil fatty acid methyl Taurine sodium 0.5 Perfume 1.0 Purified water Balance 100.00%

Example 6 Toothpaste Dibasic calcium phosphate 45.0% Carboxymethylcellulose 1.5 Glycerin 15.0 Propylene glycol 2.0 Sodium lauryl sulfate 0.8 Imidazolinium betaine 0.5 Butyl paraoxybenzoate 12 sodium saccharin 0.1 hinokitiol 0.2 taurine 1.0 sodium N-coconut fatty acid methyltaurine 0.8 fragrance 1.0 purified water balance 100.00%

Example 7 Liquid Dentifrice Precipitable Silica 18.0% Propylene Glycol 2.0 60% Sorbitol 30.0 Glycerin 30.0 Sodium Polyacrylate 0.1 Xanthan Gum 0.2 Sodium Lauryl Sulfate 0.8 Polyglycerin fatty acid ester 1.6 Methyl parahydroxybenzoate 0.12 Butyl parahydroxybenzoate 0.01 Saccharin sodium 0.1 Vitamin C derivative 1.0 Taurine 1.0 N-lauroylmethyltaurine sodium 1.0 Fragrance 1.0 Purified water 100.00% remaining

Example 8 Toothpaste Precipitated Silica 25.0% Sorbit 25.0 Glycerin 25.0 Polyvinylpyrrolidone 1.0 Lauroyl Polyglycerin Ester 1.0 Polyoxyethylene (60 mol) 0.5 Sorbitan Monolau Rate Ethyl parahydroxybenzoate 0.1 Sodium saccharin 0.2 Vitamin E 0.6 Taurine 1.0 Sodium N-lauroylmethyltaurine 1.0 Fragrance 0.8 Purified water Balance 100.00%

Example 9 Toothpaste Precipitating silica 20.0% Thickening silica 3.0 60% Sorbitol 25.0 Polyethylene glycol # 400 4.0 Sodium carboxymethylcellulose 1.5 Sodium lauryl sulfate 1.5 Paraoxy Methyl benzoate 0.1 Propyl parahydroxybenzoate 0.02 Sodium saccharin 0.1 Chlorhexidine hydrochloride 0.1 Sodium hydroxide (50% aqueous solution) 0.3 Hinokitiol 0.2 Taurine 0.5 N-palmitoylmethyltaurine sodium 0. 5 Perfume 1.0 Purified water Balance 100.00%

Example 10 Mouthwash Sorbit 10.0% Ethanol 5.0 Sucrose Monopalmitate 0.2 Polyoxyethylene (60 mol) hydrogenated castor oil 0.1 Methyl parahydroxybenzoate 0.05 Saccharin sodium 0 .2 Taurine 1.0 Sodium taurocholate 1.0 Perfume 0.6 Purified water Balance 100.00%

Example 11 Mouthwash Sorbit 10.0% Ethanol 15.0 Polyoxyethylene (60 mol) 1.0 Sorbitan monolaurate Methyl parahydroxybenzoate 0.05 Saccharin sodium 0.1 Tin tin fluoride 0 1.1 Taurine 1.0 N-coconut oil fatty acid methyl taurine sodium 1.0 Fragrance 0.5 Purified water Balance 100.00%

Example 12 Oral Pasta Liquid Paraffin 15.0% Glycerin 15.0 Sodium Benzoate 0.1 Methylparaben 0.2 Cetanol 5.0 Microcrystalline Wain 10.0 Paraffin Wax 5.0 Sorbitan Monostearate 4.0 Taurine 1.5 N-lauroylmethyltaurine sodium 1.0 Fragrance 0.4 Purified water Balance 100.00%

Example 13 Ointment White petrolatum 10.0% Stearyl alcohol 10.0 Propylene glycol 2.0 Taurine 1.0 N-Myristoylmethyltaurine sodium 0.8 Calcium carbonate 0.2 Polyethylene glycol # 4000 0 Polyethylene glycol # 400 40.0 Ethanol Balance 100.00%

Claims (1)

[Claims] 1. An oral composition comprising taurine and a taurine derivative-type surfactant in combination.