JPS60255717A - Composition for oral cavity - Google Patents

Abstract

PURPOSE:To obtain a composition for oral cavity, capable of preventing the inactivation of a germicide and exhibiting powerful germicidal effect, by incorporating a germicide selected from a cationic/amphoteric germicides with a nonionic surfactant in the presence of a specific compound. CONSTITUTION:A composition for oral cavity obtained by incorporating one or more germicides selected from a cationic germicide, e.g. chlorhexidine, and/or an amphoteric germicide, e.g. N-alkyldiaminoethylglycine, and a nonionic surfactant, e.g. sucrose ester of a fatty acid, with a compound expressed by formula I [R1 is -(CH2)m- or -CH=CH-; R2 is 1-8C alkyl, alkenyl, etc.; n is an integer 1-3; m is an integer 0-2], e.g. methyl salicylate, a compound expressed by formula II (R3 is 1-3C alkyl; R4 is 1-3C alkyl or propenyl, etc.), e.g. eugenol. The resultant composition is a composition capable of effectively preventing the inactivation of the germicide.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an oral composition containing a cationic and/or zwitterionic bactericide, and more specifically to a nonionic surfactant containing a cationic and/or zwitterionic bactericide. The present invention relates to an oral composition that prevents deactivation caused by agents.

Conventionally, cationic bactericidal agents such as chlorhexidine and cetylpyridinium chloride, and amphoteric ionic bactericidal agents such as N-lauryldiamino-l-tylglycine were combined as active ingredients in toothpaste and other 21-cavity compositions, and these have strong bactericidal effects. It is known that these bactericides can be used to prevent and treat periodontal diseases, and it is also known to incorporate these bactericides into oral compositions containing nonionic surfactants such as sucrose fatty acid esters.

However, as a result of studies conducted 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 inactivated and its effectiveness is not fully demonstrated. I found out that this is not the case.

For this reason, the present inventors have stably incorporated cationic and/or zwitterionic bactericides into oral compositions containing nonionic surfactants, and have attempted to eliminate the strong effects of cationic or zwitterionic bactericidal agents. As a result of intensive studies on how to effectively exhibit the bactericidal effect, we found that the following general formula (1) was used for oral compositions containing a combination of cationic and/or zwitterionic bactericides and nonionic surfactants. (In the formula, R1 is -(CN2)...- or -C)-1=c
A group represented by H-, R2 is an alkyl group having 1 to 8 carbon atoms,
hydroxy M-substituted alkyl or alkenyl group, n
is an integer of 1 to 3, and crow is an integer of 0 to 2) and the following general formula (2) (wherein, R3 is an alkyl group having 1 to 3 carbon atoms, R4 is an alkyl group having 1 to 3 carbon atoms, Propenyl group or acetyl group, n is an integer of 1 to 3)
The inventors have found that when 1II or more is added, the deactivation of these fungicides can be effectively prevented and the above object can be achieved, and this has led to the present invention.

The present invention will be explained in detail below.

The oral composition according to the present invention comprises a cationic and/or zwitterionic bactericide, a nonionic surfactant, and the above (1).
A compound containing at least 1 fI selected from the group consisting of a compound of formula (2) and a compound of formula (2),
m! It is used as toothpastes such as Ill1l brush and rIJ brush, mouthwash, gum pine surge cream, liquid or paste topical application, troche, chewing gum, etc.

In the present invention, the cationic fungicides include chlorhexidine hydrochloride: chlorhexidine gluconate: chlorhexidine acetate: 1,6-bis-(2-ethylhexylbiguanidohexane) dihydrochloride: 1,6-di(N+, N+'-phenyldiguanide-N5.N
5') Hexanetetrahydrochloride: 1,6-di(N+).

1,J,l-phenyl-N+,N+'-methyldiguanide-Ns,Ns')-hexanecibide[
lride): 1,6-di(N+,N+'-o-ri[
10 phenyl diquanide = Ns, Ns') hexane dihydrocolide: 1,6-di(N1°N+ '-2,
6-dichloro)1-nyldiguard-Ns, Ns') to 4
-Sandihydrochloride: 1,6-di[N+,I
'h'-β-(p-methoxyphenyl)diguanide-
N! l, N5'] to Kirin Sibide O Chloride: 1
,6-di(N+.

N+' -α-methyl-β-phenyldiguanide-Ns
, Ns') hexane dihydrochloride: 1.6-di(N+, N+' D-nido[1 phenyldiguanide-Ns, Ns') hexane dihydrochloride: ω,
ω'-di(N+, N-blind'-)■Nildiguanide Ns
, Ns')-ziloprobil ether dihydrochloride: ω, ω'-di(N+, N+' I)-riO
Lophenyldiguanide-Ns,Ns')-di-n-propylethertetrahydrotalide: 1,6-di(
N+.

N+'-2,4-dino D[:J phenyldiguanide-N
s, Ns') hexanetetrahydrochloride: 1,
6-di(N+,N+'+1-methylphenyldiguanide-Ns,Ns')hexane dino 1 hydrochloride:
1.6-di(N+,N+'2゜4.5-t-lichlorophenyldiguanide-Ns.

N5') Hexanetetrahydrochloride: 1゜6
-di[N+,N+' -α-(p-chloroO]l-nyl)■Tildiguanide N5. N5'] Hexane dihydrochloride: ω, ω'-di(N+.

N+'-1)'10lophenyldiguanide Ns.

Ns')-II-Pheasant Rangehide Mortar Chloride: 1.
12-di(N+,N+'l)-riOlophenyldiguanide-Ns,Ns')dodecanesibide Ochloride:
1,10-di(N+,N+'-7enyldiguanide Ns, Ns')decanedetrahydrochloride:1,12-di(N1゜N+'-phenyldiguanide-
Ns, Ns') Decanetetrahydride Oride: 1,
12-di(N+,N+'-phenyldiguanide N
-1N5') Dodecanetetrahyde O-D ride: 1
゜6-di(N+,N+'-o-o-lophenyldiguanide-Ns,Ns')hexane dihydrochloride: 1,6-di(N+,N1'l)-o-lophenyldiguanide -Ns, Ns') hexanetetrahydrochloride: ethylenebis(1-tolylbiguanide): ethylenebis(p-tolylbiguanide): ethylenebis(
3,5-dimethylphenylbiguanide): ethylene bis(pt-turbiguanide): ethylene bis(3,5-
dimethylphenyl biguanide): ethylene bis(p-3
-Amyl phenyl biguanide): Ethylene bis (nonylphenyl biguanide): Ethylene bis (phenyl biguanide): Ethylene bis (N-butylphenyl biguanide): 1-dilene his (2° 4-dimethylphenyl biguanide): Ethylene bis (0-diphenyl biguanide):
Ethylene bis(mixed amylnaphthyl biguanide)-N-
butylethylenebis()Jnylbiguanide) nitrimethylenebis(0-tolylbiguanide): N-butyltrimethylenebis(phenylbiguanide): tetramethylenebis(1-tolylbiguanide): and salts of the above compounds, such as acetate; 1 nate; hydrochloride; hydrobromide; citrate: bisulfite;
Fluoride: polymaleate; N-coconut alkyl sarcosinate; phosnonite; barfluorooctano]--to: silicate: sorbate; salicylate; Cinnamate; Thiocyanate; Alginate: Pyromellitate: Tetracarboxybutyrate; Benzoate;
glutarate; monofluorophosphate; perfluoropropionate; and salts formed by reaction of bis-biguanide compounds with the following salts: disodium ethane-1-hydroxy-1°1-diphosphonate; ethane-1°2 -Disodium salt of dicarboxy-1,2-cyphosphonic acid; ethane-1,2-dicarboxy-1,2
-dipotassium salt of dihydroxy-1,2-diphosphonic acid; monocalcium salt of etheno-1,2-dicarboxy-1,2-diphosphonic acid; ethyne-1,2-dicarboxy-1-hydroxy 1,1-cyphos 7 Monomagnesium salt of onic acid: ethane-1,2-dicarboxy-
1,2-diphosphonyl di(triethanolane D)
dilam 1): ethane-1,2-dicarboxy-1゜2
-Disodium salt of cyphous 7on; ethane-1,2
-diammonium salt of dicarboxy-1,2-diphosnotetraphosphoric acid; ethane-1,2-dicarboxy-1,2-dihydroxy-1,2-diphosphonic acid heptacalcium salt; ethane-1,2-diphosphonic acid diammonium salt; Carboxy-1-human 0xy-
Di-tin salt of 1,2-diphosphic acid: [ten-1
, 2-dicarboxy-1-indium salt of phosphonic acid: ethane-1,2-dicarboxy-1,2-dihyde [
Triammonium salt of 1x-1,2-dicarboxy-1-phosphonic acid; trisodium salt of etheno-1,2-dicarboxy-1-phosphonic acid; Hexasodium salt of dichlorotetraphosphinic acid: methanecyclohexylhydromexidiphosphin A)
L-lium salt: methanecycloptylhydroxydif A
Diane ■, nium salt of sulfonic acid: monocalcium salt of methanecyclopentylhydroxydiphosphonic acid; di-tin salt of methanecyclopentylhydroxydiphosphonic acid; Indium salt: Methanesic O nonyl human L1
triammonium salt of xydiphosphonic acid; trisodium salt of methanecyclodecylhydroxydiphosphonic acid; di-tin salt of methanecyclohexylhydroxydiphosphonic acid; methanecycloalkylhydroxydiphosulfonic acid; tris(1 -Phosphonoethyl)amine: Tetranalium salt of tris(2-phosphono-2-p[]bivirkamine; dipotassium salt of bis(phosphonomethyl)-1-phosph4nodelamine; bis(phosphonomethyl) -2-phosphono-2
- Monocalcium salt of propylamine: bis(1-)A
t-nondanesium salt of sulfomethylamine: bis(2-)A sulfin-2-propyl)
Paste such as di-tiny salt of phosphonomethylamine [1 type of biguanide fungicide such as 1-ruhexidi, and further 4 g/'n7nium salt-based fungicide such as sef-ruviridinium chloride, or Two or more types of l- are used (9).

Further, examples of the zwitterionic fungicides include N-alkyldiamino Y tylglycine such as N-lauryldiaminoethylglycine and N-myristyldiaminoethylglycine. The blend Φ of these bactericides is not particularly limited, but is usually 0.001 to 0.5% (
5%, hereinafter the same as F).

In addition, J1 ionic surfactant bamboo agents include fatty acid esters of sugars or sugar alcohols, for example, each fatty acid has a remaining carbon number of 12 to 18 and an average degree of esralization of 1.1 to 2.
, 5, more preferably 1.2 to 1.9 sugar fatty acid ester, maltitol fatty acid ester, maltitol fatty acid ester, maltotriitol fatty acid esral, maltoatoto, itol fat W11 ester, maltopentitol fatty acid ester , maltohex) nithol fatty acid - "ster, maltoheptitol fatty acid" Nisdel, sorbitan fatty acid ester, lactose fat ribs
esters, lactitol fatty acid esters, polyoxyethylene sorbitan fatty acid esters such as polyoxyethylene sorbitan monolaurate, polyoxyethylene turdotane monostearate, and polyoxyethylene fatty acid esters, such as polyoxyJ tylene hydrogenated castor In addition to oils, fatty acid ethanolamides such as lauric acid mono- or jetanolamide, fatty acid monoglycerides, polyoxyethylene higher alcohol ethers, polyoxyethylene polyoxypropylene small aggregates, polyA xyethylene polyoxypropylene Fatty acid esters, etc. may be used.

In addition, these No.1 Bamboo surfactants can be used alone or in combination of two or more.Also, the amount of nonionic surfactant blended is usually the same as the total amount. 0.0 of
1-5%, more preferably 0.05-3%.

The present invention is briefly described below: 1. : The above-mentioned (
1) At least b' of the compound represented by the formula 8 and (2)
The combination of I scale prevents as much as possible the deactivation of bamboo fungicides and zwitterionic bamboo fungicides caused by nonionic surfactants. There is also something r.

In this case, examples of the compound of formula (1) include salicylic acid which is 0-human O-oxybenzoic acid, m-hydro[l-oxybenzoic acid, methyl p-hydro-4-cybenzoic acid, -r-
1 each of ethyl, propyl, (tert-1sec-1n-)butyl, bempul, 2-hydro-1-tertyl, (2- or 3-)hydroxypropyl, hydroxybutyl, etc.
-esterification products, 0-1 steel- or p-hydroxydiphenylacetic acid, esterification products of gallic acid such as methyl, T-tyl, and propyl. The backside of these compounds
In the formula (1>, Ulll is O and R7 has 1 carbon number.
3 is an alkyl group or a do[]xyalkyl group, and a compound in which 0 is 1 is preferable, and even if <i, methyl salicylate,
1 Noripur pJ-del, especially propyl salicylate/l
It's so sad.

Specifically, the compound of the formula (2) includes eugenol, isoeugenol, vanyl-0-butyl, 4-1-tylgufino'kol, 2-terl-butyl-4-hydro''-dino? Examples include Nisole, j'human vanillin, BenAnor, and the like. Behind these compounds, the formula (2
), R3 is an alkyl group having 1 to 3 carbon atoms, R4 is 1
- or 2-probenyl group, preferably a compound in which 0 is 1,
Among these, eugenol and isoeugenol are particularly preferred. Although the amount of these compounds can be determined arbitrarily, 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 and requirements of the composition. Calcium phosphate dihydrate and anhydride, monocalcium phosphate, tertiary calcium phosphate, calcium carbonate, calcium birophosphate, aluminum hydroxide, alumina, silicic anhydride, silica gel, aluminum silicate, insoluble f [sodium metaphosphate, tertiary phosphate] Synthetic resins such as acid magnesium, magnesium carbonate, @fa) J lucium, polymethyl methacrylate, ben(-night), silicon resistant diluent, etc. or two or more types are blended (compounding amount is usually 20%).・~90%, when brushing teeth for 1s (to 120・6
0%).

In addition, in the case of paste-like silk products such as Ill Ill Polish, carrageenan, sodium carboxymethyl cellulose, methyl cellulose, human O-oxyethyl cellulose, carboxymethyl human cyedyl cell [-1
- cellulose derivatives such as sodium alginate, alkali metal alginates such as sodium alginate, propylene glycol alginate, gums such as xanthan gum, gum tragaganth, gum karare, gum arabic, polyvinyl alcohol, sodium polyacrylate,
Synthetic adhesives such as carboxyvinyl polymer, polyvinylpyrrolidone, silica gel, aluminum silica gel,
11I or two or more types of unmodified binders such as Veegum and Laponite may be blended (compounding ratio usually 0.3 to 5%).

Furthermore, in the production of pasty or liquid oral compositions such as toothpastes, sorbitol, glycerin, ethylene glycol, g[1-pyrene glycol, 1,3-butylene glycol, poly-1-ethylene glycol, polypropylene glycol] are used as thickening agents. , xylitol, malnut, luffit, etc. (J2f1 or more) may be blended (composition m is usually 10 to 70%).

The oral composition of the present invention further includes menthol, carvone, anethole, limonene, ocimene, n-decyl alcohol, 91-nerol, α-dervineol, methyl acetate-1-, citroneturu acetate, methyl eugenol, cineol, linalool, ■Dellinalool,
Vanillin, chilli, suberamine], oil, bepermin
~Fragrances such as oil, lemon oil, orange oil, sage oil, rosemary oil, cinnamon oil, vimento oil, mustard oil, perilla oil, wintergreen oil, clove oil, eucalyptus oil, etc. alone or in combination, total 0 ~10%, preferably about 0.5 to 5%, may be blended, as well as saccharin sodium, stevioside, NeA hesberidyl dihydrochalcone, glylruritin, berylardin, thaumatin, asparatylphenylalanine methyl 1 ster, p-methoxycinnamic. Eleven flavoring agents such as aldehydes (0-1%, preferably 0.01-0.5%)
) etc. and make 1.

In addition, in the present invention, in addition to the above-mentioned cationic and zwitterionic bactericides, the active ingredients include dex-1heranase, amylase, protease, 11-lyse, lysozyme, and lytic enzyme (lytic enzyme). enzymes such as
Alkali metal monofluorophosphates such as sodium monofluorophosphate and potassium monofluorophosphate; fluorides such as sodium fluoride and stannous fluoride; tranexamic acid and -epsilon aminohproic acid; Droxylalan-1-yne, dihydrocholestyrol, glycyrrhizin salts, glycyrrhetinic acid, glycerophosphate, chlorophyll, chloride
Contains one or two active ingredients such as Limium, Power L1 peptide, and water-soluble interstate phosphoric acid compounds! The above formulation () Next, the effects of the present invention will be specifically explained with reference to experimental examples.

[Experiment example] An aqueous solution containing 0.1% of chlorhexidine hydrochloride (CI-IX), 1.0% of the surfactant shown in Table 1, and 0.5% of the drug was mixed with a phosphorus buffer solution of pH 7.0 for 50 minutes. Prepare a sample solution by diluting it 2 times, and add the final concentration of the sample to 2 times.
．． An E. coli suspension was added to give a concentration of 5×10 EI CFU/y7, and after the bacteria were added, a sterilization reaction was carried out for 1 minute in a 35° C. bath.

Then, a diluted solution (physiological saline) containing 1% polyoxyethylene sorbitan monooleate and 0.2% lecithin
5CDLP containing polyoxyethylene sorbitan monooleate and lecithin (Daigo Nutrient Chemical Co., Ltd.) was diluted with Jfl* overnight at 37°C on an agar plate.
L. The number of viable bacteria was determined.

The results are shown in Table 1.

In addition, as a surfactant, the constituent fatty acids are about 70:30 of balmitic acid and nistearic acid, and Nananoste J
75% of diester, 25% of diester, cis]sugar fatty acid ester (P-1670 manufactured by Ryoto Co., Ltd.) and polyoxyethylene sorbitan monostearate (TS-10 manufactured by Nikko Chemical Industry Co., Ltd.) were used, respectively.

Table 1 Examples are shown below.

[Example 1] Mouthwash ethanol 10% by weight Glycerin 10 P, O, E, (60) [1 compound and mustard oil 5 Fragrance 1.
6 Satucalin sodium 0.5 O, chlorhexidine gluconate (20% solution) 0.5 Methyl salicylate 0.4 [Example 21 Mouthwash Chlorhexidine gluconate o, iiu% Diammonium glycyrrhetinate I O,2 lauryl monoglyceride 0. 05 P, O, E, (60) Sorbitan 0.01 Monostearate fragrance (J-menthol, anethole) 1.0 Ethanol 3.0 Eugenol 0.2 [Example 3] Mouthwash lauryl diaminoethylglycine 0. 011111%
Sodium lauryl acid 0.05 Sucrose monolaurate 1 Isoeugenol 0.1 Sodium fluoride 0.5 Sorbiturate 15 Ethanol 0.1 Flavor (carvone, anethole) 0.5 Zatukarin sodium o, i [Example 4 ] Oral spray chlorhexidine gluconate 0.5! Ht%P,O,
E (40) Sorbitan monostearate 0.5 Ethyl salicylate 0.5 Ethanol 30 Satucalin sodium 0.1 Flavoring 1.2 [Example 5] Lozenge lozenge Lactose 99.5% by weight Chlorhexidine gluconate 0. 05P, O, E (
60) Monostearate 0.2 Methyl salicylate 0
．． 01 Stevia extract 0.2 Flavor 0.01 [Example 6] Oral pasta liquid paraffin 15% by weight Setanol 10 Glycerin 20 Sorbitan monopalmitate 0.6 P, O, E (40) Sorbitan monostearate 5
．． 0 Chlorhexidine gluconate 0. 1 fragrance 0
．． 5 Salicyl 12-hydroxyethyl 0.2 [Example 7]
Toothpaste Silica (Zeo 49) 251! ffi% Hydroxyethylcellulose 0.7 Hydroxypropylcellulose 0.5 Glycerin 1
5.0 Sorbit 17.0 Sucrose monolaurate (esterified 11k1.4) 2
．． 0 fragrance 1.0 saccharin sodium 0.2 ethyl m-hydroxybenzoate 0.05 sodium monofluorophosphate 0.751! ! All compositions containing 0.05 to 100.0% by weight of chlorhexidine acid are those in which the bactericidal agent contained therein is stably retained.Applicant: Lion Lion Co., Ltd.1 Agent: Patent Attorney Kojima Kojima Procedures Correction il! (Voluntary) Manabu Shiga, Commissioner of the Japan Patent Office1, Indication of the case: Patent Application No. 111015 of 19822, Name of the invention: Oral composition3, Relationship with the person making the amendment Patent applicant's address: Tokyo 1-3-7 Honjo, Sumida-ku Name (6
76) Line A Line Co., Ltd. Representative Atsushi Kobayashi 4, Agent 104 Address 3rd floor, Medical Building, 4-13-18 Ginza, Chuo-ku, Tokyo Telephone (545) 6454 Name Patent attorney (793)
0) Takashi Kojima 6. Contents of amendment (1) Insert [, benzalkonium chloride, penzetonium chloride, dequalinium chloride] after "pyridinium chloride" on page 12, line 20 of the specification. .

(2) HT corrected ``r- (no CHX)'' in the drug column of Table 1 on page 22 to ``-'', and [
"Salicyl m (without CHX)" should be corrected to "υlycylic acid," and "Acetylsalicylic acid (without CHX)" should be corrected to "acetylsalicylic acid."

(3) In III, page 23, line 13, "chlorhexidine gluconate" is corrected to "cetylpyridinium chloride."

Less than ten

Claims (1)

[Claims] 1. An oral composition comprising a nonionic surfactant and a nonionic surfactant in combination with a fungicide selected from 1./J antibacterial agents and zwitterionic fungicides In the product, the following general formula (1
) (In the formula, R+(CH+)m - or L; is 10 H=
A group represented by 01-1-, R2 is an alkyl group having 1 to 8 carbon atoms, a hydroxy-substituted alkyl group, or an alkenyl group, n Lt is an integer of 1 to 3, m is an integer of 0 to 2, and the following General formula (2-4 (wherein, R3G is an alkyl group having 1 to 3 carbon atoms, R4 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 compounds represented by formula (1). 2. A patent claim in which the amount of the compound represented by formula (1) is o, ooi to 1% by weight of the entire composition. 3. The oral composition according to claim 1 or 2, wherein the cationic disinfectant is a biguanide disinfectant. 4. The oral composition according to claim 1, wherein the cationic disinfectant is a biguanide disinfectant. The composition for oral cavity according to claim 3, which is a chlorhexidine compound.5. 6. The oral composition according to claim 1 or 2, wherein the zwitterionic disinfectant is N-alkyldiamino]]purglycine. 7. The nonionic surfactant is a sugar or a saccharide. Claims 1 to 6 which are fatty 1Il11 esters of alcohol.
The composition for oral cavity according to any one of Items 1 to 3. 8. The oral composition according to any one of claims 1 to 6, wherein the nonionic surfactant is polyoxyethylene fatty acid Nisdel.