JP2005145952A - Caries-preventing composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To obtain a caries-preventing composition having an efficiently inhibiting effect on demineralization and accelerating re-calcification, and excellent in preservation stability for a long period. <P>SOLUTION: This caries-preventing composition characterized by being used by applying on the teeth is constituted with (a) 1-30 wt.% casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and/or casein phosphopeptide-amorphous calcium fluoride phosphate complex (CPP-ACFP), (b) 0.01-10 wt.% sodium carboxymethylcellulose having 0.7-1.0 etherification degree, (c) 0.5-40 wt.% thickening agent, (e) 0.01-5.0 wt.% at least 1 kind of fluorine compound selected from sodium fluoride, tin fluoride and monofluoro sodium phosphate, which may be blended as necessary, and (d) the balance of water. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

  The present invention relates to a composition for preventing caries having an effect of suppressing decalcification of teeth and promoting remineralization.

  Conventionally, a casein phosphopeptide-amorphous calcium phosphate complex (hereinafter referred to as CPP-ACP) is known as a dental caries prevention component. This CPP-ACP is a substance composed of a complex of milk protein (casein) -derived peptide and mineral (non-crystalline calcium phosphate), and it contains calcium and phosphorus, which are inorganic components of teeth, in its constituent elements. It is said that it affects the decalcification and remineralization of teeth (for example, see Non-Patent Documents 1 and 2).

  The prevention of dental caries by CPP-ACP can be thought of as two processes: remineralization of the tooth and anti-decalcification of the tooth. Tooth remineralization can be explained by the continuous supply of calcium and phosphorus ions into the subsurface demineralized lesion of enamel by CPP-ACP. The demineralization inhibitory action of the tooth is due to the fact that the concentration of these ions is kept supersaturated by calcium and phosphorus ions derived from CPP-ACP in the saliva on the surface of the enamel or inside the plaque. It is based on the logic that solubility is significantly reduced and teeth are less likely to melt.

  In addition, fluorine is known to have effects such as promoting remineralization, improving tooth acid resistance, antibacterial activity against plaque bacteria, and suppressing acid production. Casein phosphopeptides containing fluorine Amorphous calcium fluoride phosphate complex (hereinafter referred to as CPP-ACFP) is also effective in preventing dental caries.

  Disclosed are foods such as gums and candy, and oral care compositions such as dentifrices and mouthwashes that help prevent dental caries by containing CPP-ACP and CPP-ACFP having such actions. (For example, refer to Patent Documents 1 and 2.)

  However, in order to fully exert 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 is necessary to chew 3g) at the same time four times a day for 20 minutes as a guide for 2 weeks (Non-patent Document 3).

  Since it is difficult to apply it many times a day in consideration of the general lifestyle, so that the caries prevention effect of CPP-ACP can be exerted even once a day, A method of applying a paste-like or cream-like oral care composition containing CPP-ACP to a tooth has been studied.

  However, the conventional paste-like or cream-like oral care composition containing CPP-ACP has a problem that the state becomes non-uniform such as gelation or lumps when stored for a long period of time.

Special Table 2002-500626 Special Table 2002-540129 Reynolds EC et al. “Anticariogenicity of calcium phosphate complexes of tryptic casein phosphopeptides in the rat” J Dent Res. 1995 Jun; 74 (6): 1272-9. Reynolds EC “Remineralization of enamel subsurface lesions by casein phosphopeptide-stabilized calcium phosphate solutions.” J Dent Res. 1997 Sep; 76 (9): 1587-95. Shen P et al. “Remineralization of enamel subsurface lesions by sugar-free chewing gum containing casein phosphopeptide-amorphous calcium phosphate.” J Dent Res. 2001 Dec; 80 (12): 2066-70.

  Then, this invention makes it a subject to provide the composition for caries prevention which has the effect which suppresses demineralization efficiently and promotes remineralization, and was excellent in long-term storage stability.

  As a result of intensive studies to solve the above problems, the present inventors have found that (a) casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and / or casein phosphopeptide-amorphous calcium fluoride phosphate complex (CPP- ACFP), (b) sodium carboxymethylcellulose, (c) thickener, and (d) water, and (b) sodium carboxymethylcellulose having a specific degree of etherification as sodium carboxymethylcellulose. When used, the present invention was completed by investigating obtaining a composition for preventing caries having an effect of effectively suppressing demineralization and promoting remineralization and having excellent long-term storage stability. . It has also been found that it is more preferable to add a fluorine compound in order to give a more excellent remineralization effect.

That is, the present invention
(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) degree of etherification Carboxymethylcellulose sodium having a ratio of 0.7 to 1.0: 0.01 to 10% by weight, (c) a thickener: 0.5 to 40% by weight, and (d) water: the remainder, and teeth A composition for preventing dental caries, characterized by being applied 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, (b) degree of etherification Carboxymethyl cellulose sodium having a ratio of 0.7 to 1.0: 0.01 to 10% by weight, (c) a thickener: 0.5 to 40% by weight, and (e) a fluorine compound: 0.01 to 5 And (d) water: the remainder, and relates to a composition for preventing caries characterized by being applied to teeth and using fluorine in the latter composition for preventing caries The compound is preferably at least one selected from sodium fluoride, tin fluoride, and sodium monofluorophosphate.

Hereinafter, the composition for preventing caries according to the present invention will be described.
(a) Casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and / or casein phosphopeptide-amorphous calcium fluoride phosphate complex (CPP-ACFP) may be edible or dentally acceptable. There is no particular limitation, and for example, a phosphopeptide mixed with calcium, inorganic phosphoric acid, and optionally fluorine, and the mixture is filtered and dried (see JP 2002-500626 A) is used. It is preferable in terms of composition and crystallinity.

  Here, the blending amount of (a) casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and / or casein phosphopeptide-amorphous calcium fluoride phosphate complex (CPP-ACFP) is 1-30 of the entire composition. It is preferable that it is 1 to 10 weight% especially. 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, and if it exceeds 30% by weight, the viscosity of the composition becomes too high.

  (b) Sodium carboxymethyl cellulose having a degree of etherification of 0.7 to 1.0 is blended in order to obtain long-term storage stability, and the degree of etherification needs to be 0.7 to 1.0. In particular, 0.85 to 0.95 is preferable. The reason is that if the degree of etherification is less than 0.7, the effect of blending cannot be obtained, and if it exceeds 1.0, it is easily affected by calcium present in CPP-ACP and / or CPP-ACFP and is insoluble. This causes precipitation and gelation, resulting in poor storage stability.

  (b) The amount of sodium carboxymethylcellulose having a degree of etherification of 0.7 to 1.0 is 0.01 to 10% by weight, particularly preferably 1 to 5% by weight, based on the total composition. If it is less than 0.01% by weight, the viscosity of the composition is low, and when applied to the teeth, it will be easily washed away by saliva, so the effect of preventing caries cannot be obtained. When applied to teeth, the viscosity is high and the composition is difficult to spread, and the usability is also poor.

  The composition for preventing dental caries according to the present invention is applied to teeth and used in the composition (a) casein phosphopeptide-amorphous calcium phosphate complex (CPP-ACP) and / or casein phosphopeptide -It is necessary to use (c) a thickening agent in order to obtain a caries preventive effect due to retention of the amorphous calcium fluoride phosphate complex (CPP-ACFP) in the oral cavity. (c) As a thickener, natural products such as guar gum, kajib bean gum, tara gum, tamarind seed gum, gum arabic, tragacanth gum, caraya gum, carrageenan, xanthan gum, gellan gum, curdlan, chitin, chitosan, chitosamine, glycerin, propylene glycol, alginic acid Organic compounds such as sodium, propylene glycol alginate, sodium starch glycolate, sodium starch phosphate, sodium polyacrylate, polyvinylpyrrolidone, calcium carbonate, calcium silicate, silica fine powder, amorphous hydrous silica, hydrophobic Examples thereof include inorganic compounds such as silica.

  Considering the use method of applying directly to the teeth, the viscosity of the composition is suitably 1,000 to 500,000 cP at 25 ° C., and 20,000 to 200,000 cP is optimal. Accordingly, the blending amount of the (c) thickener is preferably 0.5 to 40% by weight, particularly 10 to 30% by weight, based on the entire composition.

  In order to impart a more excellent remineralization effect, the composition for preventing caries according to the present invention preferably contains 0.01 to 5.0% by weight of a fluorine compound, particularly preferably 0.05. ~ 0.2% by 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, at least one selected from sodium fluoride, tin fluoride, and sodium monofluorophosphate can be preferably used, and the compounding amount is 0.005 to 0.5% by weight in terms of the amount of fluorine atoms. In the case where only one fluorine compound is blended, sodium fluoride: 0.011 to 1.10% by weight, tin fluoride: 0.02 to 2.0%, sodium monofluorophosphate: 0.037 ˜3.7% by weight can be exemplified.

  Since the composition for preventing dental caries according to the present invention is applied directly to the teeth, it is preferable to adjust the pH within the range of 5.5 to 9.5, and the method for maintaining the pH within the range is not particularly limited. However, for example, it is preferable to adjust by adding an aqueous solution of phosphoric acid which is also a constituent of CPP-ACP or CPP-ACFP, or a salt thereof.

  It should be noted that the composition for preventing caries according to the present invention may be appropriately mixed with additives such as sweeteners, coloring agents, preservatives, antifungal agents, and fragrances used in ordinary compositions for preventing caries. Of course you can.

  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.

  Table 1 shows the composition of the compositions of Examples 1 to 10 when no fluorine compound is used, Table 2 shows the composition of the compositions of Examples 11 to 20 and Comparative Examples 1 to 4 when the fluorine compound is used. The pH and viscosity at 25 ° C. of the composition are summarized in Tables 3 and 4.

<Evaluation of storage stability>
The state after having stored the composition for caries prevention mix | blended with the composition shown in Table 1 and Table 2 in a 60 degreeC environment for 1 week was observed. The results are summarized in Table 3 and Table 4.

<Evaluation of remineralization effect>
Reynolds EC “Remineralization of enamel subsurface lesions by casein phosphopeptide-stabilized calcium phosphate solutions.” J Dent Res. 1997 Sep; 76 (9): 1587-95 went.
(1) Bovine teeth were embedded with dental resin, and an enamel test surface measuring 7 mm long × 1 mm wide was prepared. This was called an enamel block.
(2) The enamel block was immersed in 40 ml of decalcification liquid having the following composition in an atmosphere of 37 ° C. for 4 days to prepare an artificial caries.
Formulation of decalcification liquid (pH: 4.8) Lactic acid: 0.1 mol / L
Calcium chloride: 1.5m · mol / L
Potassium dihydrogen phosphate: 0.9m · mol / L
Sodium carboxymethyl cellulose (Serogen HE-1500F, manufactured by Daiichi Kogyo Seiyaku Co., Ltd.): 1% by weight
(3) In order to prevent remineralization from occurring in about a half of the surface of the enamel block on which the artificial caries was produced, enamel burnish was applied, and this enamel block was compared with Examples 1 to 20 and comparison. Examples 1 to 4 were immersed in a slurry solution diluted 5 times with distilled water for 10 days to perform remineralization treatment. In Examples 18, 19 and 20 in which sodium monofluorophosphate was blended, 0.025 units / mL of acid phosphatase (derived from wheat, SIGMA) was added to the slurry solution.
(4) A thin slice with a thickness of about 100 μm was prepared from the enamel block.
(5) Take an X-ray photograph of the thin section of (4), and calculate the amount of mineral in the decalcified and remineralized parts using an image analyzer from the distance from the surface and the brightness at that part. The remineralization rate was determined. The larger the value, the more remineralized. The results are summarized in Table 3 and Table 4.

<Evaluation of oral retention>
The composition for caries prevention blended with the composition shown in Table 1 and Table 2 was applied to the entire tooth surface with a toothbrush and evaluated by measuring the calcium ion concentration in saliva after 1 hour. The results are summarized in Table 3 and Table 4.

As is clear from Table 3, caries prevention composition containing CPP-ACP and / or CPP-ACFP can be cariesed by selecting and blending sodium carboxymethylcellulose specified at a specific degree of etherification. It has been confirmed that a composition for preventing caries can be obtained which is effective for prevention of caries and has excellent long-term storage stability.
Further, as is apparent from Table 4, a composition for preventing caries containing CPP-ACP and / or CPP-ACFP is selected and blended with sodium carboxymethyl cellulose specified with a specific degree of etherification, and further a fluorine compound It was confirmed that a composition for preventing caries can be obtained by blending with a composition that is more effective in preventing caries and superior in long-term storage stability than when no fluorine compound is blended.

Since the composition for caries prevention according to the present invention contains CPP-ACP and / or CPP-ACFP and contains sodium carboxymethylcellulose having a degree of etherification of 0.7 to 1.0, remineralization It is a composition for preventing dental caries that has an accelerating effect and has excellent long-term storage stability, and when it further contains a fluorine compound, it has a remineralization accelerating effect even more than when no fluorine compound is added. It is a composition for preventing dental caries that has excellent storage stability, and is very large in that it contributes to the improvement of dental and oral hygiene.

Claims (3)

(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) Degree of etherification Carboxymethylcellulose sodium having a ratio of 0.7 to 1.0: 0.01 to 10% by weight, (c) a thickener: 0.5 to 40% by weight, and (d) water: the remainder, and a tooth A composition for preventing dental caries, which is used by applying to the skin. (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) degree of etherification Carboxymethylcellulose sodium having a ratio of 0.7 to 1.0: 0.01 to 10% by weight; (c) a thickener: 0.5 to 40% by weight; and (e) a fluorine compound: 0.01 to 5 A composition for preventing dental caries, comprising 0.0% by weight and (d) water: the remainder, which is applied to teeth. (E) The composition for preventing caries according to claim 2, wherein the fluorine compound is at least one selected from sodium fluoride, tin fluoride, and sodium monofluorophosphate.