JP2010047494A - Composition for applying to tooth - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition for applying to teeth which maintains a caries-preventing effect such as a decalcification inhibition effect of CPP-ACP, a recalcification promoting effect for a long period. <P>SOLUTION: The composition for applying on teeth includes (a) 1-30 wt.% casein phosphopeptide-amorphous calcium phosphate composite (CPP-ACP) and/or casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP), (b) 1-50 wt.% film-forming polymer, (c) 5-70 wt.% alcohol, and (d) the balance water. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a composition for applying a tooth which forms a film by applying to a tooth and can obtain a caries prevention effect for a long period of time.

  A casein phosphopeptide-amorphous calcium phosphate complex (hereinafter referred to as CPP-ACP) is a substance composed of a complex of a protein derived from milk protein (casein) and an inorganic substance (non-crystalline calcium phosphate). Because it contains calcium and phosphorus, which are inorganic components of teeth, it has the effect of promoting tooth remineralization.

  There are two processes for preventing dental caries by CPP-ACP: a remineralization action of a tooth and a decalcification inhibitory action of the tooth. Tooth remineralization is caused by the continuous supply of calcium and phosphorus ions into the subsurface demineralized lesion of enamel by CPP-ACP. The decalcification-inhibiting action of the tooth is because the solubility of calcium phosphate in the surface layer of the tooth enamel is due to the fact that the concentration of these ions is kept supersaturated by the calcium and phosphorus ions derived from CPP-ACP in the saliva in the oral cavity This happens because the teeth are extremely lowered and the teeth are difficult to melt. Casein phosphopeptide-amorphous calcium fluoride phosphate complex (hereinafter referred to as CPP-ACFP) containing fluorine is also effective in preventing caries.

  CPP-ACP and CPP-ACFP are contained, and foods such as gums and candy for assisting the prevention of dental caries, oral care compositions such as dentifrices and mouthwashes, etc. are disclosed (for example, (See Patent Documents 1 and 2.) However, in order to fully exhibit the caries prevention effect of CPP-ACP in the oral cavity, it is necessary to stay CPP-ACP for a long time. For example, in the case of a gum containing CPP-ACP, 2 tablets ( It was necessary to continue 3g) at the same time, 4 times a day for 20 minutes as a guide for 2 weeks.

  Since it is difficult to apply many times a day in consideration of the general lifestyle, CPP-ACP intended to exert the caries prevention effect of CPP-ACP even if applied once a day There are also paste-like and cream-like compositions for preventing dental caries. (For example, refer to Patent Document 3).

  However, since this caries prevention composition is a paste-like composition rich in hydrophilicity, it dissolves in saliva etc. in the oral cavity, and when applied directly to the teeth, it is several tens of minutes, even if a tray is used. There was a problem of running down in about time. Therefore, there is a need in the market for a composition that once applied to a tooth, can be retained on the tooth for a long period of time and can continue to exert caries prevention effects such as decalcification suppression and remineralization of CPP-ACP. I came.

Special Table 2002-500626 Special Table 2002-540129 JP 2005-145952 A

  Then, this invention makes it a subject to provide the composition for tooth application which can maintain the caries prevention effects, such as the decalcification inhibitory effect which CPP-ACP has, and the remineralization promotion effect for a long period of time.

  The present invention relates to (a) casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and / or casein phosphopeptide-amorphous calcium fluoride phosphate complex (CPP-ACFP): 1 to 30% by weight; A composition for coating a tooth, comprising: 1) 50% by weight of a film-forming polymer; (c) an alcohol: 5 to 70% by weight; and (d) the remaining water. It is a thing.

  The composition for tooth application according to the present invention has an effect of suppressing decalcification that CPP-ACP has in the long term when applied to a tooth, and is capable of continuing to promote caries prevention effects such as a remineralization promoting effect. A composition for applying a tooth.

  Casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and / or casein phosphopeptide-amorphous calcium fluoride phosphate complex (CPP-ACFP) are particularly limited as long as they are edible or dentally acceptable. For example, the composition and crystallinity are obtained by using a method in which calcium, inorganic phosphoric acid, and optionally fluorine are mixed in a phosphopeptide, and the mixture is filtered and dried (see Patent Document 1). Is preferable.

  The amount of casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and / or casein phosphopeptide-amorphous calcium fluoride phosphate complex (CPP-ACFP) is 1 to 30% by weight of the total composition, especially It is preferably 1 to 15% by weight. If the amount is less than 1% by weight, the supply of calcium and phosphorus is insufficient and the effect of preventing dental caries cannot be obtained. If the amount exceeds 30% by weight, the viscosity of the composition becomes too high and the storage stability is deteriorated.

  The film-forming polymer forms a stable film containing CPP-ACP and / or CPP-ACFP on the tooth after applying the tooth coating composition to the tooth, and is held on the tooth as it is to prevent caries. It is a necessary ingredient to keep exerting various effects. (B) As a film-forming polymer, natural products such as shellac, rosin, pullulan, zein, carnauba wax, beeswax, hemirose, gelatin, polyethylene glycol, polypropylene glycol, polyethylene oxide, polyvinyl alcohol, alkyl acrylate polymer, methacrylic acid Examples thereof include organic compounds such as alkyl polymers, methoxymethylene / maleic anhydride copolymers, polyethylene glycol / methylene diisocyanatocyclohexane copolymers, polypropylene glycol / methylene diisocyanatocyclohexane copolymers. Of course, two or more kinds may be used in combination.

  The blending amount of the film-forming polymer is 1 to 50% by weight of the whole composition, and preferably 5 to 30% by weight. If the amount is less than 1% by weight, the film formed after coating is insufficient, causing inconvenience such as falling off immediately. If the amount exceeds 50% by weight, the storage stability of the prepared composition is lowered.

  The composition for tooth application of the present invention is applied to the tooth and then dried by natural drying or compressed air to form a film on the tooth surface. In order to satisfactorily apply, dry and form the film, it is necessary that (c) alcohol is contained as a volatile component.

  Examples of the alcohol include ethanol, methanol, propanol, isopropanol, butanol, isobutanol, pentanol, isopentanol, oleyl alcohol, methyl cellosolve, ethyl cellosolve, and butyl cellosolve, and any of them may be used. Absent. Two or more kinds of alcohols may be used in combination.

  The blending amount of the alcohol is 5 to 70% by weight of the whole composition, and particularly preferably 15 to 60% by weight. If it is less than 5% by weight, a sufficient volatilization effect for film formation cannot be obtained, and if it exceeds 70% by weight, CPP-ACP and / or CPP-ACFP in the composition is likely to be precipitated.

  Water is a component necessary for dissolving CPP-ACP and / or CPP-ACFP to form a stable tooth coating composition. The blending weight of (d) water is the balance of the entire composition, specifically about 5 to 80% by weight. In particular, 20 to 70% by weight is desirable.

  The composition for tooth application which concerns on this invention can also mix | blend a fluorine compound, in order to give the remineralization effect more. (E) It is preferable to mix | blend a fluorine compound 0.01 to 5.0 weight%, Especially preferably, it is 0.05 to 3.0 weight%. If it is less than 0.01% by weight, it is difficult to obtain a sufficient remineralization effect, and if it exceeds 5.0% by weight, it is not preferable in terms of safety to the human body. As the fluorine compound, one or two or more selected from sodium fluoride, tin fluoride, and sodium monofluorophosphate can be used.

  The composition for tooth application which concerns on this invention can also mix | blend an antibacterial agent in order to give a sterilization effect to a tooth surface by apply | coating to a tooth. (F) As an antibacterial agent, sodium azulenesulfonate, ε-aminocaproic acid, allantoin, allantoinchlorohydroxyaluminum, allantoindihydroxyaluminum, epidihydrocholesterin, dihydrocholesterol, glycyrrhizic acid, diammonium glycyrrhizinate, disodium glycyrrhizinate, Trisodium glycyrrhizinate, dipotassium glycyrrhizinate, monoammonium glycyrrhizinate, chlorhexidine gluconate, β-glycyrrhetinic acid, isopropylmethylphenol, cetylpyridinium chloride, decalinium chloride, benzalkonium chloride, benzalkonium chloride solution, benzethonium chloride, benzethonium chloride Solution, alkyldiaminoethylglycine hydrochloride, chlorhexidine hydrochloride, gluconic acid Lorhexidine, triclosan, pyridoxine hydrochloride, dl-α-tocopherol acetate, dl-α-tocopherol nicotinate, zeolite, methyl paraoxybenzoate, ethyl paraoxybenzoate, propyl paraoxybenzoate, butyl paraoxybenzoate, benzyl paraoxybenzoate, pyrroline Disodium dihydrogen acid, sodium pyrophosphate, anhydrous sodium pyrophosphate, sodium monohydrogen phosphate, trisodium phosphate, sodium polyphosphate, stearyldimethylbenzylammonium chloride, lauryldimethylbenzylammonium chloride, distearyldimethylammonium chloride, stearyl chloride Trimethylammonium, cetyltrimethylammonium chloride, lauryltrimethylammonium chloride, stearyltrimethylammonium bromide , Cetyltrimethylammonium bromide, benzalkonium chloride, benzethonium chloride, decalinium chloride, chlorhexidine chloride, chlorhexidine gluconate, chlorhexidine acetate, hexetidine, alkyldiaminoethylglycine hydrochloride, domifene bromide, lauroylcoraminoformylmethylpyridinium chloride, cetyltrimethyl Ammonium saccharin, triclosan, 2,2′-dihydroxy-5,5′-dibromo-diphenyl ether, 4 ′, 5-dibromosalicylanilide, 3,4 ′, 5-trichlorosalicylamide, 3,4 ′, 4-trichloro Carbanilide, 3-trifluoromethyl-4,4-dichlorocarboanilide, 2-isopropyl-5-methyl-phenol (thymol), 2-methoxy-4- (2-propenyl) -fur Examples include diol (eugenol), methyl-p-chlorophenol, ethyl-p-chlorophenol, hexyl resorcinol, methyl-resorcinol, methyl-resorcinol, dodecyl diaminoethyl glucin, benzoate, lauroyl sarcosine salt, lauryl sulfate, etc. Any one of them can be used. Two or more antibacterial agents may be used.

  (F) It is preferable to mix | blend an antibacterial agent in 0.001 to 3 weight%, Especially preferably, it is 0.01 to 0.5 weight%. If it is less than 0.001% by weight, a sufficient antibacterial effect is hardly obtained, and if it exceeds 3% by weight, it is not preferable in terms of safety to the human body.

  The composition for applying a tooth according to the present invention is preferably prepared in the range of 5.5 to 9.5 in order to be applied directly to teeth and from the viewpoint of the stability of CPP-ACP and CPP-ACFP. More preferably, the pH is in the range of 6.5 to 8.5. Specific methods for adjusting and maintaining the pH within the range include adjustment using an acid, a base, a buffer solution, and the like, and any of them may be used. More specifically, as the pH adjuster, there are phosphoric acid, citric acid, acetic acid, benzoic acid, hydrochloric acid, malic acid, fumaric acid, pyruvic acid and the like as acids, and sodium hydroxide, potassium hydroxide, There are ammonia water, sodium carbonate, monoethanolamine, morpholine, etc. Examples of the buffer solution include sodium citrate, benzoate, carbonate, bicarbonate, disodium hydrogen phosphate, sodium dihydrogen phosphate, and the like.

  The form of the tooth coating composition according to the present invention may be any of liquid, gel, paste, cream and the like. Moreover, as a method of applying to the teeth, a method of applying using a brush or a cotton swab, a method of spraying with a spray, and the like are conceivable, and any of these methods can be used.

  In relation to the foregoing, the composition for tooth application according to the present invention can be made into a gel or paste by increasing the viscosity of the composition by adding an appropriate thickener. As thickeners, aerosil, methylcellulose, carboxymethylcellulose, sodium carboxymethylcellulose, carboxymethylcellulose calcium, carboxymethylcellulose potassium, polyvinylpyrrolidone, acacia gum, gum arabic, guar gum, kajib bean gum, tara gum, tamarind seed gum, tragacanth gum, caraya gum, carrageenan, Examples include chitin, chitosan, chitosamine, xanthan gum, gellan gum, curdlan, sodium alginate, propylene glycol ester alginate, sodium starch glycolate, sodium starch phosphate, sodium polyacrylate, etc. Absent. Two or more thickeners may be used.

  In addition, generally used additives, such as a coloring agent, a flavoring agent, and a bleaching agent, can also be suitably mix | blended with the composition for tooth application | coating based on this invention.

  EXAMPLES Hereinafter, although an Example and a comparative example are shown and this invention is demonstrated concretely, this invention is not limited to the following Example.

  The composition of Examples 1 to 10 is shown in Table 1, the composition of Examples 11 to 20 and Comparative Examples 1 to 5 when a fluorine compound is used is shown in Table 2, and the pH and experimental results of the compositions are shown in Table 2. 3 and Table 4 collectively. The unit of numerical values in Tables 1 and 2 is parts by weight.

<Evaluation of tooth surface survivability-1 Long-term residence test>
(1) Embed bovine teeth with dental resin, and mirror-polish bovine enamel with water-resistant abrasive paper.
(2) To the mirror-polished bovine enamel, the tooth surface coating composition blended with the composition shown in Tables 1 and 2 was applied to the entire tooth surface with a brush, and dried with low-pressure compressed air. A film is formed on the tooth surface.
(3) After standing for 1 hour in an atmosphere with an air temperature of 37 ° C. and a humidity of 100%, it was immersed in distilled water and after 3 weeks at 37 ° C., the degree of film remaining on the tooth surface was confirmed.

<Evaluation of tooth surface survivability-2 abrasion test>
(1) Embed bovine teeth with dental resin, and mirror-polish bovine enamel with water-resistant abrasive paper.
(2) The tooth surface coating composition blended with the composition shown in Tables 1 and 2 on the mirror-polished bovine enamel is applied to the entire tooth surface with a brush, dried with low pressure air, and the tooth A film is formed on the surface.
(3) After being left for 1 hour at an air temperature of 37 ° C. and a humidity of 100%, a wear test was performed 500 times with a brush wear tester to confirm the remaining degree of the coating on the tooth surface.

<Evaluation of remineralization effect>
(1) The bovine teeth are cut at a thickness of 1 mm, and the bovine enamel side is polished with # 1500 water-resistant abrasive paper. Mask the test piece leaving about 2 mm on the enamel side.
(2) The test specimen was immersed in decalcified gel (lactic acid; 0.1 M, calcium chloride; 1.5 mM, potassium dihydrogen phosphate; 0.9 mM, CMC-Na; 1 wt%, pH 4.8) for 4 days. Create artificial caries.
(3) The demineralized specimen is observed by a transmission method using an X-ray CT apparatus, and the amount of mineral loss is obtained.
(4) On the artificial carious portion of the test body, the tooth surface coating composition blended with the composition shown in Tables 1 and 2 is applied and then dried to form a film.
(5) Each test specimen is immersed in artificial saliva for 2 weeks (artificial saliva is changed every day), and after 2 weeks, the specimen is again observed with a transmission method using an X-ray CT apparatus to determine the amount of mineral loss after remineralization.
(6) The remineralization rate (%) was determined by the following formula.
Remineralization rate (Rem%) = {(mineral loss amount at start-mineral loss amount after remineralization) / mineral loss amount at start} × 100
(The larger the value, the more remineralized.)
The results are summarized in Table 3 and Table 4.

<Evaluation of storage stability>
The state after having stored the caries prevention composition mix | blended with the composition shown in Table 1 and Table 2 in the environment of 60 degreeC temperature for 3 days was observed. The sample with no liquid separation, precipitation, or precipitation was defined as “good”. The results are summarized in Table 3 and Table 4.

  As is apparent from Tables 3 and 4, the tooth coating composition of the present invention forms a coating that is stable over the long term and resistant to wear, etc. when applied to the tooth and dried, and CPP-ACP , CPP-ACFP, and a fluorine compound, it was confirmed that the remineralization effect and the like were exhibited and the tooth surface coating composition had excellent properties.

Claims (4)

  (A) casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and / or casein phosphopeptide-amorphous calcium fluoride phosphate complex (CPP-ACFP): 1 to 30% by weight, (b) film formation height Molecule: 1 to 50% by weight, (c) Alcohol: 5 to 70% by weight, and (d) The remaining water, which is applied to teeth and used.   The tooth coating composition according to claim 1, further comprising (e) 0.01 to 5% by weight of a fluorine compound.   Furthermore, the composition for tooth application | coating of Claim 1 or 2 which contains 0.001 to 3 weight% of (f) antibacterial agents.   Film-forming polymer is shellac, rosin, pullulan, zein, carnauba wax, beeswax, hemirose, gelatin, polyethylene glycol, polypropylene glycol, polyethylene oxide, polyvinyl alcohol, alkyl acrylate polymer, alkyl methacrylate polymer, methoxymethylene / anhydrous 4. One or more combinations selected from a maleic acid copolymer, a polyethylene glycol / methylene diisocyanatocyclohexane copolymer, and a polypropylene glycol / methylene diisocyanatocyclohexane copolymer. The composition for tooth application as described in one term.