JP2006241122A - Recalcification-promoting composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a composition enabling teeth recalcification to be promoted. <P>SOLUTION: The recalcification-promoting composition comprises glucosamine and/or chitosan oligosaccharide and a fluorine ion-releasing substance. <P>COPYRIGHT: (C)2006,JPO&NCIPI

Description

  The present invention relates to a composition capable of promoting remineralization on the tooth surface.

  Conventionally, the mechanism of caries has been well studied, and a decrease in pH on the tooth surface due to growth of Streptococcus mutans present in the mouth is considered to trigger caries. That is, when food is ingested, sugars contained in the food are metabolized by Streptococcus mutans or the like present on the tooth surface to become acids, which lowers the pH of the tooth surface. And the hydroxyapatite which is the main component of the enamel constituting the tooth surface is dissolved and eluted as calcium ions and phosphate ions. This phenomenon is called decalcification, and as a result, initial caries called a subsurface demineralization state is formed.

  In response to this decalcification, the crystallization of calcium ions and phosphate ions on the tooth surface and inside is called remineralization. These remineralization and demineralization have a relationship of physicochemical equilibrium reaction, and whether this equilibrium reaction proceeds in the remineralization direction or demineralization direction depends on the ions involved in the reaction according to the principle of chemical equilibrium. Determined by the solubility product of Moreover, this reaction is influenced not only by an equilibrium reaction but also by the diffusion rate of chemical species such as calcium ions. Here, since saliva can be seen as a solvent for this reaction, the concentration of chemical species in the saliva and the presence of compounds that control its diffusion greatly affect the equilibrium reaction between remineralization and decalcification.

  In other words, the gap between the decalcification and remineralization of the teeth is repeated every time you eat, but the balance is increased by the increase in bacteria that cause caries and the residual food. When broken, it develops into caries.

  Considering the caries mechanism, the possibility of caries can be reduced by promoting remineralization. The degree of remineralization is affected by the oral environment of the individual, but it is also possible to promote remineralization by external factors. For example, it has long been known that fluorine ions promote remineralization.

  Fluorine ions are effective in preventing dental caries from the viewpoint of promoting remineralization and suppressing decalcification. In other words, a decrease in oral pH following food intake is an unavoidable event, but if there is a low concentration (several ppm level) of fluoride ions in the oral cavity, this coats the tooth surface and forms the tooth surface. And the elution of calcium from the crystal is suppressed (see Non-Patent Document 1). Furthermore, the recent health consciousness demands a technique for preventing caries such as promoting remineralization more easily, safely and effectively.

  In addition to fluorine ions, compounds having anti-cariogenic activity are known. For example, Patent Document 1 describes that a polymer saccharide, chitin or chitosan, having a low molecular weight and water-soluble inhibits the adsorption of Streptococcus mutans to teeth.

  Patent Document 2 discloses a composition containing fluoride ions and a non-metabolizable analog of caries (caries) -inducing hydrocarbon for reducing the expression of dental caries and the like. ing. As this non-metabolic analogue, 2-deoxy-D-glucose is mainly used, but glucosamine is also exemplified, and it has been experimentally shown that these suppress the decrease in pH due to Streptococcus mutans. Has been. However, the effect demonstrated in Patent Document 2 is only suppression of pH reduction, and there is no description regarding remineralization.

  An oral composition containing a nonionic surfactant and a quaternary ammonium salt together with a fluoride is known as a technique related to fluorine ions that show an effect of promoting remineralization (Patent Document 3). This Patent Document 3 discloses experimental data showing that the amount of fluorine taken into the tooth surface by the composition is increased. Therefore, according to the said technique, it is thought that the fluorine ion in a composition can be utilized effectively.

More recently, a combination of xylitol, calcium phosphate and seaweed extract (trade name: xylitol +2), a combination of casein phosphopeptide-amorphous calcium phosphate complex (trade name: licardent gum), phosphorylated oligo A product containing sugar calcium (trade name: Poscum Gum) has been approved by the Ministry of Health, Labor and Welfare for food for specified health use and is sold with the effect of making teeth healthy and durable. It is widely accepted and forms a large market.
JP-A-61-151112 ([Claims], [Experimental Examples]) JP-A-57-131714 ([Claims], FIG. 4 and explanation thereof) JP-A-6-9355 ([Claims], [Example]) Featherstone, Dent Oral Epidemiol, Vol. 27, Volume 1, Pages 31-40 (1999)

  As described above, it is considered that caries can be prevented by promoting remineralization and suppressing decalcification, and various techniques aiming at remineralization are also known. However, due to the recent health boom, better technology has been demanded.

  Then, the problem which this invention should solve is providing the composition which can accelerate | stimulate the remineralization of a tooth | gear.

  In order to solve the above-mentioned problems, the present inventors proceeded with investigations on suitable components by directly testing the remineralization effect of the fluorine-containing composition. As a result, it was found that glucosamine and its oligo body most enhanced the remineralization effect of fluorine ions, and the present invention was completed.

  That is, the remineralization promoting composition of the present invention is characterized in that it contains glucosamine and / or chitosan oligosaccharide, and a fluoride ion releasing substance.

  As the above composition, a glucosamine and / or chitosan oligosaccharide having an amount of 0.5 times mol or more with respect to the amount of fluoride ion contained in the fluoride ion free substance is highly effective. More preferably, it is 10 times mole or more. This is because a composition containing glucosamine or the like in a large excess with respect to fluorine ions has a particularly high promoting effect on remineralization.

  The amount of fluorine ions contained in the fluorine ion-free substance is preferably 0.1 to 2000 ppm with respect to the entire composition. It is because a side effect can be suppressed, exhibiting the caries prevention effect by mix | blending a fluorine in the quantity according to the form of the composition within such a range. Moreover, More preferably, it is 0.1-10 ppm. In particular, when it is used as a food or drink, if a large amount of fluoride ion is ingested, there is a risk that the living body will be adversely affected, and therefore it should be kept within this range. Moreover, according to the composition of the present invention, a good remineralization action can be exerted even with a slight fluorine ion concentration. Therefore, the requirement is meaningful to clarify the difference between the effects of the present invention and the prior art. There is also.

  The fluorine ion-free substance is one or more selected from the group consisting of sodium fluoride, sodium monofluorophosphate, tin fluoride, silver fluorinated diamine, tea and its extract, and seaweed and its extract. Is preferred. These are conventionally used as oral compositions and foods, and tea and seaweed are particularly suitable as foods containing fluoride ions.

  The remineralization promoting composition of the present invention can remarkably promote tooth remineralization by a combination of a fluoride ion free substance and glucosamine. As a result, remineralization can be promoted even at a fluorine ion concentration level suitable for food. Therefore, the onset of caries can be effectively prevented by the remineralization promoting composition of the present invention.

  The remineralization promoting composition of the present invention has a gist in that it contains glucosamine and / or chitosan oligosaccharide (hereinafter sometimes referred to as “glucosamine and the like”) and a fluoride ion releasing substance.

  Glucosamine is formally called 2-amino-2-deoxy-D-glucose. In the present invention, a commercially available free form or hydrochloride is used, or commercially available N-acetyl-D-glucosamine is removed. Acetylated ones can be used.

  Chitosan oligosaccharide refers to D-glucosamine linked with β-1,4, that is, deacetylated chitin. In the present invention, chitosan oligosaccharide which is an oligomer in which 2 to 10 D-glucosamines are bonded is used. As such chitosan oligosaccharide, a commercially available product or a product obtained by hydrolyzing a commercially available chitosan can be used.

  In the present invention, glucosamine or chitosan oligosaccharide can be used alone or in combination.

  The fluoride ion-releasing substance refers to a fluoride ion salt itself or a substance containing such a salt and having the property of releasing fluoride ions in the oral cavity due to the presence of moisture. The type is not particularly limited as long as it is used as an oral composition or food. For example, sodium fluoride, sodium monofluorophosphate, tin fluoride, silver fluorinated diamine, tea and its An extract, and seaweed and its extract can be mentioned, From this, 1 or 2 or more may be selected. In particular, natural fluorine-containing products used as food such as tea and seaweed are suitable when the composition of the present invention is used as food.

  The addition amount of the fluoride ion-free substance in the present invention is not particularly limited as long as the effect of promoting remineralization is exhibited and does not harm the living body, but a suitable addition amount according to the form of the composition should be adopted. is there. For example, when the composition for oral cavity is used mainly in the oral cavity without swallowing, the amount of fluoride ions contained in the fluoride ion free substance can be 0.1 to 2000 ppm with respect to the whole composition. In the case of food and drink, it can be 0.1 to 100 ppm. In the case of an oral composition or the like, 10 ppm or more is more preferable, and 200 ppm or more is more preferable. On the other hand, the upper limit is more preferably 1500 ppm or less. In the case of food and drink, 0.5 ppm or more is more preferable, and 1 ppm or more is more preferable. The upper limit is more preferably 100 ppm or less, but a sufficient effect can be obtained even in the range of about 30 ppm or less.

  The addition amount of glucosamine and the like in the present invention is not particularly limited as long as a synergistic effect is obtained together with the fluorine ions contained in the composition. For example, in terms of the number of moles, it can be 0.5 times mole or more with respect to the amount of fluorine ions contained in the fluorine ion free substance. In particular, when used as a food or drink, it is preferable to make a large excess with respect to the fluorine ions contained in the fluorine ion free substance, such as 2.5 times mole or more. More preferably, it is 5 times mol or more, and especially 10 times mol or more is suitable. It is because the composition containing glucosamine or the like within such a range has been demonstrated by Examples to be described later to exhibit a high remineralization promoting effect.

  In addition, the prescription | regulation of the said number of moles at the time of mix | blending chitosan oligosaccharide by this invention shall be based on the number of moles of D-glucosamine which comprises chitosan. That is, since chitosan oligosaccharide is D-glucosamine having a β-1,4 bond, when glucosamine dimer is used as chitosan oligosaccharide, the number of moles of the mixed chitosan oligosaccharide is multiplied by 2 and the above range. It shall be judged whether it is contained in. When a mixture of oligomers is blended as chitosan oligosaccharide, the average number of polymerizations may be multiplied.

  The dosage form of the remineralization promoting composition according to the present invention is not particularly limited as long as it contains a fluoride ion releasing substance and glucosamine. For example, foods such as candy, gum, tablet, jelly, etc .; Beverages such as soft drinks and energy drinks; toothpaste preparations (including pastes, liquids, liquids and powders), mouthwashes (including oral rinses, oral cleansers, oral deodorants), mouthwashes, etc. Mention may be made of oral compositions. Among these dosage forms, foods or beverages are preferable, and foods are particularly preferable.

You may mix | blend the additive component matched with the dosage form with this invention composition. As an additive component, for example, reduced maltose starch syrup, sucralose, xylitol, maltitol, saccharin, paratinite, acesulfame potassium, sorbitol and other sweeteners; acidulant; Antioxidants such as ascorbic acid; Preservatives; Solvents such as purified water, distilled water and ethanol; Abrasives such as dicalcium phosphate, calcium pyrophosphate and silica; Wetting agents such as glycerol and propylene glycol; Anions such as sodium lauryl sulfate Nonionic surfactants such as polyoxyethylene hydrogenated castor oil, sucrose ester, stearic acid monoglyceride; medicinal components such as chlorhexidine hydrochloride and cetylpyridinium chloride.
Hereinafter, the present invention will be described more specifically by way of examples. However, the present invention is not limited by the following examples, but may be appropriately modified within a range that can meet the purpose described above and below. It is also possible to implement, and they are all included in the technical scope of the present invention.

Production Example 1
In order to test the synergistic effect on remineralization by coexistence of fluoride ion-free substance and glucosamine or chitosan oligosaccharide, powdered tea leaves (produced in Shizuoka Prefecture) were added to an 8% paratinite (reduced palatinose) aqueous solution at the concentrations shown in Table 1. , Fluorine content: 100 to 300 ppm) and a treatment liquid to which D-glucosamine or chitosan oligosaccharide (5 to 8 mer of D-glucosamine) was added was prepared. The fluorine concentration in Table 1 is obtained by calculating the fluorine concentration contained in the treatment liquid from the actual measurement value of the fluorine concentration contained in the powdered tea leaves. Moreover, the density | concentration of glucosamine and chitosan oligosaccharide is the mass%.

Test Example 1 Remineralization Test A 3 × 4 mm enamel block was cut out from the extracted bovine teeth and the surface was polished. In addition to the processing solution described above Production Example 1, first decalcifying liquid (0.1M lactic /0.2% Carbopol / 50% HAP saturated solution), remineralization solution (1.5mM CaCl _{2/0. 9mM KH 2 PO 4, pH =} 7.0), was second decalcifying liquid _{(1.5mM CaCl 2 /0.9mM KH 2 PO} 4 / 50mM acetate, the pH = 5.0) was prepared.

  The enamel block was immersed in the first decalcification liquid at 37 ° C. for 72 hours, and then sufficiently washed with distilled water to obtain a sample block. Subsequently, it was similarly immersed in the remineralization liquid for 1 hour and washed with distilled water. After immersing this in the treatment liquids A to H for 2 hours, the remineralization liquid is 1 hour, the second demineralization liquid is 3 hours, the remineralization liquid is 1 hour, and each treatment liquid is again recalcified for 2 hours. It was immersed in the liquid for 15 hours. With this as one cycle, 10 cycles of treatment were performed.

  Next, in order to test the promoting action of remineralization by each treatment liquid, a thin slice was cut out from the surface of the bovine tooth block, polished to a thickness of about 100 μm, and used as a measurement sample. This section was photographed by microradiography (manufactured by HITEX, HB-50), and the remineralization rate was obtained as the tooth density using an image processing apparatus. The obtained results are shown in FIG. 1 as the relative remineralization rate when the remineralization rate is 100 when only powdered tea leaves are used (treatment liquid A).

  As shown in the results, the treatment liquid containing fluorine ions and glucosamine is clearly superior to the remineralization effect than the fluorine ion alone (A) and the fluorine ion and lysine combined (H). Proved. Moreover, this inventor has confirmed separately that the remineralization effect is not acquired only by glucosamine. Therefore, it is clear that the improvement effect of the remineralization rate obtained by the result is not additive but synergistic.

  In particular, in the treatment liquids B, C, and E to G, the improvement effect of the remineralization rate exceeds 1.5 times that of the fluorine ion alone (A). These treatment liquids have a molar ratio of glucosamine or the like to fluorine ions of 10 times or more. Therefore, in order to remarkably improve the remineralization rate, it has become clear that it is important to adjust the content ratio of fluorine ions and glucosamine in combination.

  Further, when the treatment liquids F and G are compared, the remineralization rate is not increased although G has a higher content of glucosamine. From this, depending on the blending amount and blending ratio of fluorine and glucosamine or the like, there may be a region where the proportional relationship between the blending amount and the remineralization rate is not observed.

Formulation Example 1 Candy Tea extract 5% by mass
Glucosamine 1% by mass
Reduced maltose starch syrup 10% by mass
Sucralose 0.2% by mass
Green tea fragrance 0.2% by mass
Reducing paratinit

Formulation Example 2 Gum Tea Extract 5% by mass
Chitosan oligosaccharide 0.5% by mass
Xylitol 35% by mass
Maltitol 25% by mass
Acesulfame potassium 0.05% by mass
Acidulant 0.2% by mass
Green tea fragrance 0.2% by mass
The rest of the gum base

Formulation Example 3 Tablet 10% by weight of green tea powder
1% tea extract
Glucosamine 1% by mass
Sucralose 0.2% by mass
Green tea powder fragrance 0.5% by mass
Sorbitol remaining

Formulation Example 4 Paste Sodium monofluorophosphate 0.7% by mass
Glucosamine 0.5% by mass
Sorbit 50% by mass
Calcium phosphate 15% by mass
Carboxymethylcellulose 1% by mass
1% polyoxyethylene hydrogenated castor oil
Saccharin 0.2% by mass
Fragrance 1% by mass
Purified water balance

Formulation Example 5 Paste Sodium fluoride 0.2% by mass
Glucosamine 3% by mass
Sorbit 30% by mass
Polyethylene glycol 2% by mass
Silica anhydride 20% by mass
Carboxymethylcellulose 1% by mass
Sodium lauryl sulfate 1.5% by mass
Saccharin 0.2% by mass
Fragrance 1% by mass
Purified water balance

Formulation Example 6 Mouthwash ethanol 15% by mass
Glycerin 10% by mass
Ascorbic acid 0.03% by mass
Saccharin sodium 0.05% by mass
1% polyoxyethylene hydrogenated castor oil
Sodium fluoride 0.05% by mass
Glucosamine 0.2% by mass
Purified water remainder (The above mixture is adjusted to pH = 6.5 with a citrate buffer system)

Formulation Example 7 Liquid dentifrice Sodium fluoride 0.05% by mass
Glucosamine 0.6% by mass
Ethanol 3% by mass
Glycerin 12% by mass
Saccharin sodium 0.1% by mass
Polyoxyethylene sorbitan fatty acid ester 0.5% by mass
Sodium monohydrogen phosphate 0.05% by mass
Sodium dihydrogen phosphate 0.05% by mass
Purified water balance

Formulation Example 8 Green Tea Beverage Powdered Tea Leaves 1g
(Shizuoka Prefecture, fluorine content: 100-300ppm)
Glucosamine 0.25g
250g of water
The mixture of the powdered tea leaves and glucosamine may be dissolved in water at the time of drinking.

Formulation Example 9 Green Tea Beverage Green Tea Extract 1000g
(Extracted for 5 minutes at 75 ° C using 30g tea leaves per kg water)
Glucosamine 1g
L-ascorbic acid 450ppm
(The above mixture is adjusted to pH 6.5 with sodium bicarbonate)

It is a figure which shows the remineralization promotion effect | action by the remineralization promotion composition of this invention.

Claims (6)

  A remineralization accelerating composition comprising glucosamine and / or chitosan oligosaccharide and a fluoride ion-releasing substance.   The composition for promoting remineralization according to claim 1, wherein the amount of glucosamine and / or chitosan oligosaccharide is 0.5 times mol or more with respect to the amount of fluoride ion contained in the fluoride ion-free substance.   The remineralization promoting composition according to claim 1, wherein the amount of glucosamine and / or chitosan oligosaccharide is 10 times mol or more with respect to the amount of fluoride ion contained in the fluoride ion-free substance.   The remineralization promoting composition according to any one of claims 1 to 3, wherein the amount of fluorine ions contained in the fluorine ion-free substance is 0.1 to 2000 ppm with respect to the entire composition.   The remineralization promoting composition according to any one of claims 1 to 3, wherein the amount of fluorine ions contained in the fluorine ion-free substance is 0.1 to 10 ppm with respect to the entire composition. The fluoride ion releasing substance is one or more selected from the group consisting of sodium fluoride, sodium monofluorophosphate, tin fluoride, silver fluorinated diamine, tea and its extract, and seaweed and its extract The remineralization acceleration | stimulation composition in any one of Claims 1-5.

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