JPH0343246B2 - - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an oral composition containing a cationic bactericide represented by a biguanide compound such as chlorhexidine. The present invention relates to an oral composition that is prevented from being deactivated by a surfactant. Traditionally, oral compositions such as toothpastes have been formulated with cationic bactericides represented by biguanide compounds such as chlorhexidine as active ingredients, and their strong bactericidal action has been used to prevent and treat periodontal diseases. It is also known to incorporate chlorhexidine and the like into oral compositions containing nonionic surfactants such as sucrose fatty acid esters. However, according to the results of the inventors' study,
It has been found that when a cationic fungicide such as chlorhexidine is used in combination with a nonionic surfactant, the cationic fungicide is significantly inactivated and its effectiveness is not fully exhibited. For this reason, the present inventors have made efforts to stably incorporate cationic bactericides such as chlorhexidine into oral compositions containing nonionic surfactants and to effectively exert their strong bactericidal effects. As a result of our investigation, we found that when a higher alcohol is added to an oral composition containing a combination of a cationic bactericide such as chlorhexidine and a nonionic surfactant, the cationic bactericide such as chlorhexidine is deactivated. The inventors have discovered that the above-mentioned problems can be effectively prevented and that the above objects can be achieved, leading to the present invention. The present invention will be explained in detail below. The oral composition according to the present invention contains a cationic bactericide, a nonionic surfactant, and a higher alcohol, and is suitable for use in dentifrices such as toothpaste and toothpaste, mouthwash, and gum tissue. It is used as a surge cream, liquid or paste topical preparation, etc. In the present invention, the cationic fungicide is
Chlorhexidine hydrochloride: Chlorhexidine glycolate: 1,6-bis-(2-ethylhexylbiguanidohexane) dihydrochloride: 1,6
-di-(N ₁ ,N′ ₁ -phenyldiguanide-N ₅ ,
N′ ₅ ) Hexanetetrahydrochloride: 1,
6-di( _N1 , _N'1 -phenyl- _N1 , _N'1 -methyldiguanide- _N5 , _N'5 )-hexane dihydrochloride: 1,6-di( _N1 , _N'1 - o- Chlorophenyl diguanide-N ₅ ,N' ₅ )hexane dihydrochloride: 1,6-di-(N ₁ ,N' ₁ -2,6
-dichlorophenyldiguanide-N ₅ , N′ ₅ )hexane dihydrochloride: 1,6-di[N ₁ ,
N'1 _- β-( p -methoxyphenyl)diguanide- _N5 , _N'5 ]-hexane dihydrochloride:
1,6-di(N ₁ ,N' ₁ -α-methyl-β-phenyldiguanide-N ₅ ,N' ₅ )hexane dihydrochloride: 1,6-di(N ₁ ,N' ₁ - p-Nitrophenyldiguanide- _N5 , _N'5 ) hexane dihydrochloride: ω,ω'-di( _N1 , _N'1 -phenyldiguanide- _N5 , _N'5 )-di -n-propyl ether dihydrochloride: ω, ω′-di(N ₁ ,
_N'1 - p -chlorophenyldiguanide- _N5 , _N'5 )
-di-n-propyl ether tetrahydrochloride: 1,6-di(N ₁ ,N' ₁₁ -2,4-dichlorophenyldiguanide-N ₅ ,N' ₅ )hexane tetrahydrochloride: 1,6 −di(N ₁ , N′ ₁
-p -methylphenyldiguanide- _N5 , _N'5 ) hexane dihydrochloride: 1,6-di( _N1 ,
N' ₁ -2,4,5-trichlorophenyldiguanide-N ₅ ,N' ₅ )hexanetetrahydrochloride: 1,6-di[N ₁ ,N' ₁ -α-( p -chlorophenyl)ethyldiguanide _-N5 , _N'5 ) hexane dihydro: ω,ω'-di( _N1 , _N'1 - p -chlorophenyldiguanide- _N5 , _N'5 ) -m -xylene dihydrochloride: 1 , 12−di(N ₁ ,N′ ₁ −
p-chlorophenyldiguanide-N ₅ , N′ ₅ ) dodecane dihydrochloride: 1,10-di(N ₁ ,
N′ ₁ -phenyl-diguanide-N ₅ , N′ ₅ )decanetetrahydrochloride: 1,12-di(N ₁ ,
N′ ₁ -phenyldiguanide-N ₅ , N′ ₅ )decanetetrahydrochloride: 1,12-di(N ₁ ,N′ ₁
-Phenyldiguanide- _N5 , _N'5 ) Dodecanetetrahydrochloride: 1,6-di( _N1 , _N'1-
o-chlorophenyldiguanide-N ₅ ,N′ ₅ )hexane dihydrochloride: 1,6-di(N ₁ ,
_N'1 - p -chlorophenyldiguanide- _N5 , _N'5 )
Hexanetetrahydrochloride: Ethylene bis(1-tolyl biguanide): Ethylene bis( p
-tolylbiguanide): ethylene bis(3,5-
dimethyl phenyl biguanide): ethylene bis( p -tolyl biguanide): ethylene bis(3,5
-dimethyl phenyl biguanide): Ethylene bis ( p -tertiary-amyl phenyl biguanide) - Ethylene bis (nonylphenyl biguanide): Ethylene bis (phenyl biguanide): Ethylene bis (N-butyl phenyl biguanide): Ethylene bis (2,4 dimethyl phenyl biguanide): Ethylene bis ( o -diphenyl biguanide): Ethylene bis (mixed amylnaphthyl biguanide): N-Butyl ethylene bis (phenyl biguanide): Trimethylene bis ( o -tolyl biguanide) ): N-butyltrimethylenebis(phenylbiguanide): Tetramethylenebis(1-tolylbiguanide): and salts of the above compounds, such as acetate: gluconate: hydrochloride: hydrobromide: citrate: bisulfite: fluoride: polymaleate: N - Coconut alkyl sarcosinate: phosphite: perfluorooctanoate: silicate: sorbate: salicylate: maleate: tartrate: fumarate:
Ethylenediaminetetraacetate: iminodiacetate: ginnamate: thiocyanate: alginate: pyromellitate: tetracarboxybutyrate: benzoate: glutarate: monofluorophosphate: perfluoropropionate: and for the reaction of bis-biguanide compounds with the following salts: The resulting salt: disodium ethane-1-hydroxy-1,1-diphosphonate:
Disodium salt of ethane-1,2-dicarboxy-1,2-diphosphonic acid: Dipotassium salt of ethane-1,2-dicarboxy-1,2-dihydroxy-1,2-diphosphonic acid: ethene-1,2
- Monocalcium salt of dicarboxy-1,2-diphosphonic acid: Monomagnesium salt of ethyne-1,2-dicarboxy-1-hydroxy-1,1-diphosphonic acid: ethane-1,2-dicarboxy-1, Di(triethanolammonium salt) of 2-diphosphonic acid: Disodium salt of ethane-1,2-dicarboxy-1,2-diphosphonic acid: ethane-1,2-dicarboxy-1,
Diammonium salt of 2-diphosphonic acid: Ethane-1,2-dicarboxy-1,2-dihydroxy-1,2-dihydroxy-1,2-diphosphonic acid monocalcium salt: Ethane-1,2-dicarboxy-1-hydroxy-1,2 - Distannic salt of diphosphonic acid: Indium salt of ethene-1,2-dicarboxy-1-phosphon: Triammonium of ethane-1,2-dicarboxy-1,2-dihydroxy-1,2-diphosphonic acid Salt: ethene-1,
2-dicarboxy-1-phosphonic acid trisodium salt: ethane-1,2-dicarboxy-
Distannous salt of 1,2-diphosphonic acid: Hexasodium salt of cyclotetraphosphonic acid:
Trisodium salt of methanecyclohexylhydroxydiphosphonic acid: Diammonium salt of methanecyclobutylhydroxydiphosphonic acid: Monocalcium salt of methanecyclopentylhydroxydiphosphonic acid: Distannic salt of methanecycloheptylhydroxydiphosphonic acid Salt: Indium salt of methanecyclooctylhydroxydiphosphonic acid: Triammonium salt of methanecyclononylhydroxydiphosphonic acid: Sodium salt of methanecyclodecylhydroxydiphosphonic acid: Di-1 salt of methanecyclohexylhydroxydiphosphonic acid Tin salt: Methanecycloalkylhydroxydiphosphonic acid: Tris(1-phosphonoethyl)amine: Tetrasodium salt of tris(2-phosphono-2-propyl)amine: Bis(phosphonomethyl)-1-phosphonoethylamine Dipotassium salt of: Monocalcium salt of bis(1-phosphonomethyl)-2-phosphono-2-propylamine: Monomagnesium salt of bis(1-phosphonoethyl)phosphonomethylamine: Bis(2-phosphono-2-
Examples include distannous salt of (propyl) phosphonomethylamine. In addition, as nonionic surfactants, higher fatty acid esters of sugars or sugar alcohols selected from sucrose, maltose, maltitol, and lactitol, especially those in which each fatty acid residue has 12 to 18 carbon atoms, are used.
with an average degree of esterification of 1.1 to 2.5, more preferably
Sucrose fatty acid esters of 1.2 to 1.9, lactose fatty acid esters, lactitol fatty acid esters, maltose fatty acid esters, and maltitol fatty acid esters are preferably used, and maltotriitol fatty acid esters, maltotetriitol fatty acid esters, and maltopentitol fatty acid esters are also preferably used. Esters, maltohexitol fatty acid esters, maltoheptitol fatty acid esters, and the like are also preferably used. The amount of the cationic fungicide is 0.001 to 0.5% (weight%, same below) of the entire composition.
The amount of nonionic surfactant is determined based on the total composition.
It is preferably 0.01 to 5%, particularly 0.05 to 3%. The present invention incorporates a higher alcohol into the system containing the above-mentioned cationic disinfectant and nonionic surfactant, thereby minimizing the deactivation of the cationic disinfectant by the nonionic surfactant. This could have been prevented. In this case, the higher alcohol has 10 carbon atoms.
~20 fatty acid alcohols (which may be saturated or unsaturated, linear or branched, and the alcohols may be monohydric or polyhydric), especially lauryl alcohol, myristyl alcohol, cetyl alcohol,
Stearyl alcohol is preferably used. The amount of these higher alcohols is 0.1 of the total composition.
It is preferable to set it to 10%. In addition to the above-mentioned components, the chloride oral composition can further contain appropriate components depending on the purpose, type of composition, etc. For example, in the case of toothpaste, dibasic calcium phosphate dihydrate and anhydride, dibasic calcium phosphate, dibasic calcium phosphate, calcium carbonate, calcium pyrophosphate, aluminum hydroxide, alumina, silicic anhydride, silica gel, aluminum silicate , insoluble sodium metaphosphate, tertiary magnesium phosphate, magnesium carbonate, calcium sulfate, polymethyl methacrylate, bentonite, zirconium silicate, synthetic resin, etc. (the amount usually ranges from 20% to 90% and 20% to 60% for toothpaste). In addition, in the case of pasty compositions such as toothpaste, binders include carrageenan, cellulose derivatives such as sodium carboxymethylcellulose, methylcellulose, hydroxyethylcellulose, and sodium carboxymethylhydroxyethylcellulose, alkali metal alginates such as sodium alginate, and propylene glycol alginate. Gums such as ester, xanthan gum, tragacanth gum, karaya gum, gum arabic, synthetic binders such as polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinylpyrrolidone, inorganic binders such as silica gel, aluminum silica gel, vegum, laponite, etc. One or more of these may be blended (compounding amount usually 0.3 to 5%). Furthermore, in the production of pasty or liquid oral compositions such as toothpastes, sorbitol, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylitol, malt, lactitol, etc. are used as thickeners. One or more of these may be blended (compounding amount usually 10 to 70%). The oral composition of the present invention further includes menthol,
Carvone, anethole, eugenol, methyl salicylate, limonene, ocimene, citronellol, α-terpineol, methyl acetate, citronellyl acetate, methyl eugenol, cineole, linalool, ethyl linalool, vanillin, thymol, spearmint oil, peppermint oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, pimento oil, cinnamon leaf oil, perilla oil,
Wintergreen oil, clove oil, eucalyptus oil as special fragrances alone or in combination, 0 to 10% of the total, preferably 0.5 to 5%
In addition, saccharin sodium,
Sweeteners (0 to 1%, preferably 0.01 to 0.5%) such as stepioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin, thaumatin, asparalphenylalanine methyl ester, and p-methoxycinnamic aldehyde may be blended. In addition, in the present invention, in addition to the above-mentioned cationic fungicide, dextranase,
Enzymes such as amylase, protease, mutanase, lysozyme, lytic enzyme (Lidetsu enzyme), alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate, sodium fluoride, fluoride 1
Contains active ingredients such as fluorides such as tin, tranexamic acid, epsilon aminocaproic acid, aluminum chlordohydroxyallantoin, dihydrocholesterol, glycyrrhetinic salts, glycyrrhetinic acid, glycerophosphate, chlorophyll, sodium chloride, calopeptide, and water-soluble inorganic phosphoric acid compounds. One type or two or more types may be blended. Next, the effects of the present invention will be specifically explained with reference to experimental examples. [Experiment example] Chlorhexidine hydrochloride 0.1%, surfactant 1.0%
Prepare a sample solution by diluting an aqueous solution containing a predetermined amount of additives and additives to 2 times (in the case of Figure 1) or 5 times (in the case of Figure 2) with a phosphate buffer solution of pH 7.0. A fixed amount of E. coli suspension was added to the sample solution, and after adding the bacteria, a sterilization reaction was carried out for 1 minute in a 35°C hot bath. After that, it was diluted with a diluent (physiological saline) containing 1% polyoxyethylene sorbitan monooleate and 0.2% lecithin, and a certain amount of it was diluted with SCDLP (Daigo Nutrition) containing polyoxyethylene sorbitan monooleate and lecithin. Kagaku Co., Ltd. on agar plate
The cells were cultured overnight at 37°C, and the number of viable bacteria was determined. The results are shown in FIGS. 1 and 2. In these results, the concentrations of chlorhexidine hydrochloride (indicated by CHX in the figure), surfactant, and additives are all shown as concentrations in the sample solution. Furthermore, the number of surviving bacteria when 0 to 0.05% of chlorhexidine hydrochloride was applied alone to the E. coli suspension was shown as CHX activity in comparison with the number of bacteria. Therefore, the residual activity of chlorhexidine hydrochloride in each sample solution becomes clear from the results for each sample solution. In addition, as a surfactant, the constituent fatty acids are palmitic acid and stearic acid at a ratio of about 70:30, 75% monoester, 25% diester or more, and sucrose fatty acid ester (P-1670 manufactured by Ryoto Co., Ltd.) and lauryl sulfate. Sodium (SDS) was used respectively. Examples are shown below. [Example 1] Mouthwash Ethanol 15% Glycerin 20 Sorbit (60% solution) 45 Polyoxyethylene (80 mol) Hydrogenated castor oil
0.05% Stearyl alcohol 0.1 Chlorhexidine hydrochloride 0.1 Satucalin sodium 0.1 Fragrance 3.0 Water Balance 100.0% [Example 2] Mouthwash ethanol 70% Polyoxyethylene sorbitan laurate
1.0 Sucrose monolaurate 0.5 Tranexamic acid 0.001 Sodium lauryl sulfate 0.05 Cetylpyridinium chloride 0.05 Satucalin sodium 0.03 Myristyl alcohol 0.5 Glycyrrhetinic acid 0.3 Fragrance 2.0 Water Remaining 100.0% [Example 9] Mouth freshener Chlorhexidine gluconate 0.07% Ethanol 30 Glycerin 10 Polyoxyethylene (40 mol) Hydrogenated Castor Oil
1.0 Sucrose monopalmitate 1.0 Sucrose dilaurate 1.0 Cetyl alcohol 0.5 Saccharin sodium 0.1 Flavor 2.5 Water Remaining 100.0% [Example 4] Mouth freshener ethanol 40% Sorbitto 30 Lactitol monolaurate 1.0 Maltitol monolaurate 1.0 Glycerin Monolaurate 0.5 Lauryl alcohol 0.1 Alexidine 0.05 Saccharin sodium 0.2% Fragrance 3.0 Water Balance 100.0% [Example 5] Oral pasta hinokitiol 0.1% Glycyrrhetinic acid 0.5 Epidihydroxycholestanol 0.1 Chlorhexidine acetate 0.2 Setanol 5.0 Microcrystalline wax 15.0 Sucrose dilaurate 3.0 Sucrose monopalmitate 1.0 Sorbitan monostearate 5.0 Sorbit (60% solution) 5.0 Flavoring 1.5 Water Balance 100.0% [Example 6] Toothpaste Al ₂ O ₃・3H ₂ O 45.0% Hydroxypropyl cellulose 1.0 % Sorbit (60%) 35.0 Polyethylene glycol 5.0 Maltitol monolaurate 1.0 Glycerin monooleate 1.0 Myristyl alcohol 0.5 Sodium monofluorophosphate 0.76 Dextranase 1.0 Alexidine (gluconate) 0.05 Satucalin sodium 0.1 Flavor 1.0 Water Remaining 100.0 % [Example 7] Toothpaste dicalcium phosphate 45.0% Carbopol 940 1.0 Ha ₂ HPO ₄ 0.5 Sorbit 35.0 Glycerin 5.0 Sucrose monolaurate 1.0 Polyoxyethylene (80 mol) Hydrogenated castor oil
0.01% Glycerin monooleate 0.1 Stearyl alcohol 0.3 Mutanase 0.1 Sodium fluoride 0.5 Chlorhexidine gluconate 0.01 Stevioside 1.2 Fragrance 1.0 Water Remaining 100.0%

[Brief explanation of drawings]

FIGS. 1 and 2 are graphs showing the residual activity (number of residual bacteria) of chlorhexidine hydrochloride when various additives are added to chlorhexidine hydrochloride and a surfactant, respectively.

Claims (1)

[Scope of Claims] 1. An oral composition comprising a combination of a cationic bactericide and a nonionic surfactant, characterized in that it contains a higher alcohol. 2. The oral composition according to claim 1, wherein the higher alcohol is lauryl alcohol, myristyl alcohol, cetyl alcohol, or stearyl alcohol. 3 The amount of higher alcohol is 0.1 of the total composition
~10% by weight in claim 1 or 2
Oral composition as described in . 4. The oral composition according to any one of claims 1 to 3, wherein the cationic fungicide is a biguanide fungicide. 5. The oral composition according to claim 4, wherein the biguanide fungicide is chlorhexidine. 6. The oral composition according to any one of claims 1 to 5, wherein the nonionic surfactant is a higher fatty acid ester of sugar or sugar alcohol selected from sucrose, maltose, maltitol, and lactitol.