JPH0629177B2 - Oral composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an oral composition containing a cationic and / or zwitterionic bactericide, and more specifically, a nonionic surfactant of the cationic and / or zwitterionic bactericide. The present invention relates to a composition for oral cavity, which is prevented from being deactivated by an agent.

Conventionally, cationic compositions such as chlorhexidine and cetylpyridinium chloride, and zwitterionic compositions such as N-lauryldiaminoethylglycine have been compounded as active ingredients in oral compositions such as toothpaste, and teeth have strong bactericidal action. It is known to prevent and treat periodontal diseases, and it is also known to add these fungicides to an oral composition containing a nonionic surfactant such as sucrose fatty acid ester.

However, as a result of the study by the present inventors, when a cationic bactericide or a zwitterionic bactericide is used in combination with a nonionic surfactant, the cationic bactericide is significantly deactivated, and its effect is sufficiently exerted. It was discovered that it will not be done.

Therefore, the present inventors have stably added a cationic and / or zwitterionic bactericidal agent to an oral composition containing a nonionic surfactant to obtain a strong cationic or zwitterionic bactericidal agent. As a result of earnest studies on how to effectively exhibit the bactericidal effect, the following general formula (1) was applied to the oral composition containing a cationic and / or zwitterionic bactericide and a nonionic surfactant in combination. (In the formula, R ₁ is a group represented by — (CH ₂ ) _m — or —CH═CH—, R ₂ is an alkyl group having 1 to 8 carbon atoms, a hydroxy-substituted alkyl group or alkenyl group, and n is 1 ~ 3
And m is an integer of 0 to 2, and —R ₁ —COOR ₂ is located at the ortho position or meta position with respect to the OH group when n is 1) and the following general formula (2). (Wherein R ₃ is an alkyl group having 1 to ₃ carbon atoms, R ₄ is an alkyl group having 1 to 3 carbon atoms, a propenyl group or an acetyl group, and n is an integer of 1 to 3) The present invention has been made based on the finding that the inactivation of these germicides can be effectively prevented and that the above-mentioned object can be achieved by blending one or more of the above.

Hereinafter, the present invention will be described in detail.

The composition for oral cavity according to the present invention comprises a cationic and / or zwitterionic bactericide, a nonionic surfactant, and (1) above.
A compound containing at least one compound selected from the group consisting of the compound of formula and the compound of formula (2), toothpaste such as toothpaste, moisturizing toothpaste, mouthwash, gum massage cream, liquid or paste Topical application,
It is used as a troche or chewing gum.

In the present invention, as the cationic bactericide, chlorhexidine hydrochloride: chlorhexidine gluconate: chlorhexidine acetate: 1,6-bis- (2-ethylhexyl biguanide hexane) dihydrochloride: 1,6-di (N ₁ , N ₁ ′) - phenyl jig biguanide -N _5, N ₅ ') hexane tetrahydrochloride: 1,6 (N _1,
N ₁ ′ -phenyl-N ₁ , N ₁ ′ -methyldiguanide-
N ₅ , N ₅ ′) Hexanedihydrochloride): 1,6
- di (N _1, N ₁ '-o- chlorophenyl jig biguanide -N
₅ , N ₅ ′) Hexanedihydrochloride: 1,6-di (N ₁ , N ₁ ′ -2,6-dichlorophenyldiguanide-
N ₅ , N ₅ ′) Hexanedihydrochloride: 1,6-
Di [N ₁ , N ₁ ′ -β- (p-methoxyphenyl) diguanide-N ₅ , N ₅ ′] hexanedihydrochloride:
1,6 (N _1, N ₁ '-α- methyl -β- phenyl jig biguanide -N _5, N _5') hexane dihydrochloride: 1,6 (N _1, N ₁ '-p - nitrophenyl jig biguanide -N _5, N ₅ ') hexane dihydrochloride:
ω, ω′-di (N ₁ , N ₁ ′ -phenyldiguanide-
N _5, N ₅ ') - di -n- propyl ether dihydrochloride: omega, omega .'- di (N _1, N _1' -p- chlorophenyl jig biguanide -N _5, N ₅ ') - di -n -Propyl ether tetrahydrochloride: 1,6-di (N ₁ ,
N ₁ '-2,4-dichlorophenyl jig biguanide -N _5, N
₅ ′) Hexanetetrahydrochloride: 1,6-di (N ₁ , N ₁ ′ -p-methylphenyldiguanide-N ₅ ,
N ₅ ') hexane dihydrochloride: 1,6 (N _1, N _1' -2,4,5- trichlorophenyl jig biguanide -N _5, N ₅ ') hexane tetrahydrochloride: 1,6 di _{[N 1, N 1 '-α-} (p- chlorophenyl) Echirujiguanido -N _5, N _5'] hexane dihydrochloride: omega, omega .'- di (N _1, N ₁ '-p- chlorophenyl jig biguanide -N _5, N ₅ ') -m- xylylene hydrochloride: 1,12 (N _1, N _{1'-p-chlorophenyl} jig biguanide -N _5, N ₅ ') dodecane dihydrochloride: 1, 10- di (N _1, N ₁ '- phenyl - Jiguanido -N _5, N _5') decane tetrahydrochloride: 1,12 (N _1, N ₁ '- phenyl jig biguanide -N _5, N ₅ ′) Decane tetrahydrochloride:
1,12-di (N ₁ , N ₁ ′ -phenyldiguanide-
N ₅ , N ₅ ′) Dodecane tetrahydrochloride: 1,
6- di (N _1, N ₁ '-o- chlorophenyl jig biguanide -
N ₅ , N ₅ ′) Hexanedihydrochloride: 1,6-
Di (N ₁ , N ₁ ′ -p-chlorophenyldiguanide-
N ₅ , N ₅ ′) hexane tetrahydrochloride: ethylene bis (1-tolyl biguanide): ethylene bis (p
-Tolylbiguanide): ethylenebis (3,5-dimethylphenylbiguanide): ethylenebis (p-tolylbiguanide): ethylenebis (3,5-dimethylphenylbiguanide): ethylenebis (p-tertiary-amylphenylbiguanide) : Ethylene bis (nonylphenyl biguanide): ethylene bis (phenyl biguanide): ethylene bis (N-butylphenyl biguanide): ethylene bis (2,4-dimethylphenyl biguanide): ethylene bis (o-diphenyl biguanide): ethylene bis ( Mixed amylnaphthyl biguanide): N-butylethylene bis (phenyl biguanide): trimethylene bis (o-tolyl biguanide): N-butyl trimethylene bis (phenyl biguanide): tetramethylene bis (1-tolyl biguanide): and Salts of serial compound, such as acetate;
Gluconate; Hydrochloride; Hydrobromide; Citrate; Bisulfite; Fluoride; Polymaleate; N-coconut alkyl sarcosinate;
Phosphite; perfluorooctanoate; silicate; sorbate; salicylate; maleate; tartrate; fumarate; ethylenediaminetetraacetate; iminodiacetate; cinnamate; thiocyanate; alginate; pyromellitate; tetracarboxybutyrate; benzoate; glutarate; monofluorophosphate Fate; perfluoropropionate; and a salt formed by the reaction of a bis-biguanide compound with the following salt: ethane-1-hydroxy-1,1-diphosphonate disodium; ethane-1,2-dicarboxy-
1,2-Diphosphonic acid disodium salt; ethane-
1,2-dicarboxy-1,2-dihydroxy-1,2
-Dipotassium salt of diphosphonic acid; ethene-1,2-
Dicarboxy-1,2-diphosphonic acid monocalcium salt; Ethyne-1,2-dicarboxy-1-hydroxy 1,1-diphosphonic acid monomagnesium salt; Ethane-1,2-dicarboxy-1,2- Diphosphonic acid di (triethanolammonium salt); ethane-
1,2-Dicarboxy-1,2-diphosphonic acid disodium salt; ethane-1,2-dicarboxy-1,2
Diammonium salt of diphosphonic acid; ethane-1,
2-dicarboxy-1,2-dihydroxy-1,2-diphosphonic acid monocalcium salt; ethane-1,2-dicarboxy-1-hydroxy-1,2-diphosphonic acid distannous salt; ethene-1 , 2-dicarboxy-1
An indium salt of phosphonic acid; a triammonium salt of ethane-1,2-dicarboxy-1,2-dihydroxy-1,2-diphosphonic acid; a triammonium salt of ethene-1,2-dicarboxy-1-phosphonic acid. Sodium salt; ethane-1,2-dicarboxy-1,2-diphosphonic acid distannous salt; cyclotetraphosphonic acid hexasodium salt; methanecyclohexylhydromexidiphosphonic acid trisodium salt; methanecyclobutyl Hydroxydiphosphonic acid diammonium salt; Methanecyclopentylhydroxydiphosphonic acid monocalcium salt; Methanecycloheptylhydroxydiphosphonic acid distannous salt; Methanecyclooctylhydroxydiphosphonic acid indium salt; Methanecyclononylhydroxy Triammonium salt of phosphonic acid; Trisodium salt of methanecyclodecylhydroxydiphosphonic acid; Distannous salt of methanecyclohexylhydroxydiphosphonic acid; Methanecycloalkylhydroxydiphosphonic acid; Tris (1-phosphonoethyl) amine Tris (2-phosphono-2-propyl) amine tetrasodium salt; bis (phosphonomethyl) -1-phosphonoethylamine dipotassium salt; bis (phosphonomethyl) -2-phosphono-2-propylamine mono Calcium salt; bis (1
-Phosphonoethyl) monomagnesium salt of phosphonomethylamine; biguanide fungicides such as chlorhexidis such as distannous salt of bis (2-phosphono-2-propyl) phosphonomethylamine, and further cetylpyridinium chloride, One or more kinds of quaternary ammonium salt-based fungicides such as benzalkonium chloride, benzenium chloride and decalinium chloride may be used. Examples of the zwitterionic germicide include N-alkyldiaminoethylglycine such as N-lauryldiaminoethylglycine and N-myristyldiaminoethylglycine. The compounding amount of these bactericides is not particularly limited, but is usually 0.001 to 0.5% (% by weight, the same applies hereinafter) of the entire oral composition.

As the nonionic surfactant, a fatty acid ester of sugar or sugar alcohol, for example, a fatty acid residue having 12 to 18 carbon atoms and an average esterification degree of 1.1 to 2.
5, more preferably 1.2 to 1.9 sucrose fatty acid ester, maltose fatty acid ester, maltitol fatty acid ester, maltotriitol fatty acid ester, maltotetriitol fatty acid ester, maltopentitol fatty acid ester, maltohexayl ester Tall fatty acid ester, maltoheptaitol fatty acid ester, sorbitan fatty acid ester, lactose fatty acid ester, lactitol fatty acid ester, and polyoxyethylene sorbitan monostearate, and polyoxyethylene sorbitan fatty acid ester such as polyoxyethylene sorbitan monostearate. Polyoxyethylene fatty acid ester, for example, polyoxyethylene hydrogenated castor oil, is preferably used, and fatty acid ester such as lauric acid mono- or diethanolamide is used. Ruamido, fatty acid monoglyceride, polyoxyethylene higher alcohol ethers, polyoxyethylene polyoxypropylene copolymers, polyoxyethylene polyoxypropylene fatty acid esters may also be used.

These nonionic surfactants may be used alone or in combination of two or more. Moreover, the compounding quantity of a nonionic surfactant is usually 0.01-5 of the whole.
%, More preferably 0.05 to 3%.

In the present invention, at least one compound represented by the above formulas (1) and (2) is added to a system containing the above-mentioned cationic and / or zwitterionic bactericide and a nonionic surfactant. This makes it possible to prevent deactivation of the cationic bactericide and the zwitterionic bactericide by the nonionic surfactant as much as possible.

In this case, as the compound of the formula (1), specifically, salicylic acid which is o-hydroxybenzoic acid, methyl, ethyl and propyl of m-hydroxybenzoic acid (tert-, sec
-, N-) butyl, pentyl, 2-hydroxyethyl,
Examples thereof include esterified products such as (2- or 3-) hydroxypropyl and hydroxybutyl, and esterified products such as o-, m-hydroxyphenylacetic acid, and methyl, ethyl and propyl gallates. Of these compounds,
In the formula (1), a compound in which m is O, R ₂ is an alkyl group having 1 to 3 carbon atoms or a hydroxyalkyl group, and n is 1 is preferable, and among these, methyl salicylate, ethyl salicylate, and propyl salicylate are particularly preferable. Also, (2)
Specific examples of the compound of the formula include eugenol, isoeugenol, banitrove, 4-ethylguaiacol,
2-tert-butyl-4-hydroxyanisole, acetovanillin, paeonol and the like are exemplified. Among these compounds, compounds in which R ₃ is an alkyl group having 1 to ₃ carbon atoms, R ₄ is 1- or 2-propenyl group, and n-is 1 in the formula (2) are preferable, and among them, eugenol and iso- Eugenol is particularly preferred. Although the compounding amount of these compounds can be arbitrarily determined, it is usually 0.0005 to 3%, preferably 0.001 to 1% of the total composition.

In addition to the above-mentioned components, the oral composition of the present invention may further contain appropriate components depending on the purpose, type of composition, and the like.

For example, in the case of toothpaste, dibasic calcium phosphate-2
Hydrates and anhydrides, monobasic calcium phosphate, tribasic calcium phosphate, calcium carbonate, calcium pyrophosphate,
Aluminum hydroxide, alumina, silicic acid anhydride, silica gel, aluminum silicate, insoluble sodium metaphosphate, tribasic magnesium phosphate, magnesium carbonate, calcium sulfate, synthetic resin such as polymethylmethacrylate, bentonite, zirconium silicate and the like 1 One kind or two or more kinds may be mixed (the compounding amount is usually 20 to 90%, and in the case of toothpaste, 20 to 60%).

In the case of a paste composition such as toothpaste, carrageenan, sodium carboxymethyl cellulose, methyl cellulose, hydroxyethyl cellulose as a binder,
Cellulose derivatives such as sodium carboxymethyl hydroxyethyl cellulose, alkali metal alginates such as sodium alginate, propylene glycol alginate, xanthan gum, tragacanth gum, gums such as karaya gum and arabic gum, polyvinyl alcohol, sodium polyacrylate, carboxyvinyl polymer, polyvinylpyrrolidone, etc. Synthetic binder, silica gel, aluminum silica gel, veegum,
One kind or two or more kinds of inorganic binders such as laponite may be blended (the blending amount is usually 0.3 to 5%).

Furthermore, in the production of paste or liquid oral compositions such as toothpaste, as a viscous agent, sorbit, glycerin, ethylene glycol, propylene glycol, 1,3-butylene glycol, polyethylene glycol, polypropylene glycol, xylit, maltite, lactit. 1 type or 2 types or more of the same can be blended (the blending amount is usually 10
70%).

The oral composition of the present invention further includes menthol, carvone, anethole, limonene, ocimene, n-decyl alcohol, citronellol, α-terpineol, methyl acetate, citronellyl acetate, methyl eugenol, cineol, 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, winter green oil, clove oil,
Fragrances such as eucalyptus oil alone or in combination 0-1
In addition to 0%, preferably 0.5 to 5%, saccharin sodium, stevioside, neohesperidyl dihydrochalcone, glycyrrhizin, perillartin,
A sweetener (0 to 1%, preferably 0.01 to 0.5%) such as thaumatin, aspartyl phenylalanine methyl ester and p-methoxycinnamic aldehyde may be added.

In the present invention, as an active ingredient, in addition to the above-mentioned cationic and zwitterionic fungicides, enzymes such as dextranase, amylase, protease, mutanase, lysozyme, lytic enzyme (lytic enzyme), monofluoroline Sodium acid salts, alkali metal monofluorophosphates such as potassium monofluorophosphate, sodium fluoride, fluorides such as stannous fluoride, tranexamic acid and epsilon aminocaproic acid, aluminum chlorohydroxyallantoin, dihydrocholesterol, glycyrrhizin salts, glycyrrhetinic acid , Glycerophosphate, chlorophyll, sodium chloride, caropeptide, water-soluble inorganic phosphate compound, etc. may be used alone or in combination of two or more.

Next, the effects of the present invention will be specifically described with reference to experimental examples.

[Experimental Example] An aqueous solution containing 0.1% of chlorhexidine hydrochloride (CHX), 1.0% of the surfactant shown in Table 1 and 0.5% of the drug, respectively, was made 5-fold with a phosphate buffer of pH 7.0. Prepare the sample solution by diluting it, and the final concentration of the bacteria is 2.5 x in this sample solution.
E. coli suspension was added to 10 ⁸ CFU / m 2,
After adding the bacterium, the sterilization reaction was carried out for 1 minute in a 35 ° C warm bath. Then, it is diluted with a diluent (physiological saline) containing 1% of polyoxyethylene sorbitan monooleate and 0.2% of lecithin, and a certain amount of SCDLP containing polyoxyethylene sorbitan monooleate and lecithin.
(Fifth Nutrient Chemistry Co., Ltd.) The plate was cultured on an agar plate at 37 ° C. overnight, and the number of surviving bacteria was determined. The results are shown in Table 1.

As the surfactant, the constituent fatty acid was palmitic acid: stearic acid about 70:30, and the monoester 7
Sucrose fatty acid ester (P-1670 manufactured by Ryoto Co., Ltd.) and polyoxyethylene sorbitan monostearate (TS-10 manufactured by Nikko Chemical Industry Co., Ltd.) of 5% and 25% or more of diester were used.

Examples will be shown below.

[Example 1] Mouthwash Ethanol 10% by weight Glycerin 10P. O. E. (60) Hydrogenated castor oil 5 Fragrance 1.6 Sodium saccharin 0.5 Chlorhexidine gluconate (20% solution) 0.5 Methyl salicylate 0.4 Water Residual 100.0 wt% [Example 2] Mouthwash Cetylpyridinium chloride 0.1. 1% by weight glycyrrhetinic acid diammonium salt 0.2 lauryl monoglyceride 0.05 P.I. O. E. (60) Sorbitan 0.01 Monostearate Fragrance (l-menthol, anethole) 1.0 Ethanol 3.0 Eugenol 0.2 Water residue
100.0% by weight [Example 3] Mouthwash Lauryldiaminoethylglycine 0.01% by weight Sodium lauryl sulfate 0.05 Sucrose monolaurate 1 Isoeugenol 0.1 Sodium fluoride 0.5 Sorbit 15 Ethanol 0.1 Fragrance (carvone, anethole) 0.5 Sodium saccharin 0.1 Water 100.0% by weight remaining [Example 4] Oral spray Chlorhexidine gluconate 0.5% by weight P.I. O. E (40) Sorbitan monostearate 0.5 Ethyl salicylate 0.5 Ethanol 30 Sodium saccharin 0.1 Perfume 1.2 Water residue (used in pump type dispenser) 100.0% by weight [Example 5] Oral troche Lactose 99.5% by weight Chlorhexidine gluconate 0.05 P.I. O. E (60) Monostearate 0.2 Methyl salicylate 0.01 Stevia extract 0.2 Perfume 0.01 Hydroxyethyl cellulose 0.03 100.0 wt% [Example 6] Oral pasta Liquid paraffin 15 wt% Cetanol 10 Glycerin 20 sorbitan monopalmitate 0.6 P.I. O. E (40) Sorbitan monostearate 5.0 Chlorhexidine gluconate 0.1 Perfume 0.5 2-Hydroxyethyl salicylate 0.2 Water 100.0% by weight [Example 7] Toothpaste silica (Zeo49) 25% by weight Hydroxy Ethyl cellulose 0.7 Hydroxypropyl cellulose 0.5 Glycerin 15.0 Sorbit 17.0 Sucrose monolaurate (esterification degree 1.4) 2.0 Fragrance 1.0 Sodium saccharin 0.2 m Ethyl hydroxybenzoate 0. 05 Sodium monofluorophosphate 0.75 Chlorhexidine hydrochloride 0.05 Water Residual 100.0% by weight or more In any of the above compositions, the compounded bactericide is stably retained.

Claims (8)

[Claims] 1. An oral composition comprising a combination of at least one bactericide selected from cationic bactericides and zwitterionic bactericides and a nonionic surfactant, wherein the following general formula (1) (In the formula, R ₁ is a group represented by — (CH ₂ ) _m — or —CH═CH—, R ₂ is an alkyl group having 1 to 8 carbon atoms, a hydroxy-substituted alkyl group or alkenyl group, and n is 1 ~ 3
, M is an integer of 0 to 2, and —R ₁ —COOR ₂ is located at the ortho position or meta position relative to the OH group when n is 1) and the following general formula (2). (Wherein R ₃ is an alkyl group having 1 to ₃ carbon atoms, R ₄ is an alkyl group having 1 to 3 carbon atoms, a propenyl group or an acetyl group, and n is an integer of 1 to 3) An oral composition comprising one or more of the above. 2. The oral composition according to claim 1, wherein the compounding amount of the compounds represented by the formulas (1) and (2) is 0.001 to 1% by weight based on the whole composition. 3. The oral composition according to claim 1 or 2, wherein the cationic bactericide is a biguanide bactericide. 4. The oral composition according to claim 3, wherein the biguanide fungicide is a chlorhexidine. 5. The oral composition according to claim 1, wherein the cationic bactericide is a quaternary ammonium salt. 6. The zwitterionic bactericide is N-alkyldiaminoethylglycine as claimed in claim 1 or 2.
The oral composition according to the item. 7. The oral composition according to any one of claims 1 to 6, wherein the nonionic surfactant is a fatty acid ester of sugar or sugar alcohol. 8. The nonionic surfactant is a polyoxyethylene fatty acid ester and claims 1 to 6.
The composition for oral cavity according to any one of items.