JPS6043325B2 - Oral composition - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention is applicable to toothpastes, mouthwashes (liquids, tablets, powder forms, gel forms), chewing tablets, oral bands, topical applications (liquids, pastes), cavity sealants, super Regarding an oral composition that is used as a sonic treatment agent, an iontophoresis treatment agent, a profilaxis paste, a dental floss, a desensitizer, etc., and is particularly suitable as a toothpaste and a fluoride gel, more specifically, it is a fluoride gel. The present invention relates to an oral composition containing stannous, water-soluble fluoride, and a phytate compound, which can improve the acid resistance of tooth substance by application thereof and is effective in preventing dental caries.

Conventionally, various substances have been proposed as active ingredients for caries prevention.

In particular, it is known that when fluorine compounds are applied to the tooth surface, the fluoride is incorporated into the tooth enamel and strengthens the tooth structure, giving a good effect in preventing caries. Sodium phosphate, sodium fluoride, and stannous fluoride are most widely used, but it is difficult to say that each has a sufficient caries-inhibiting effect. In this case, fluorine compounds containing stannous ions, such as stannous fluoride, are more effective in improving the acid resistance of tooth structure than fluorine compounds that do not contain stannous ions, such as sodium fluoride. However, it is still difficult to say that it is sufficient, and even if a certain degree of tooth acid resistance is achieved after treatment, it does not improve the self-cleaning effect of saliva, brushing, and chewing of food. However, there is a problem that the effect is relatively easily lost. Furthermore, in addition to fluorine compounds, various compounds that have a caries-inhibiting effect have been studied, for example, using sodium phytate or calcium phytate to reduce the solubility of hydroxyapatite in acids. However, the evaluation is not consistent.

Furthermore, as an example of using this phytic acid, an oral composition containing a divalent metal salt of phytic acid such as calcium phytate together with a monofluorophosphate (British Patent No. 138
No. 4375), and further separates two phases: a phase containing a water-soluble calcium salt and a phase obtained by adding a water-soluble organic or inorganic phosphoric acid compound such as phytic acid, and optionally a water-soluble fluorine compound to this. Oral compositions (British Patent No. 14089n) have also been proposed, but their effects have not yet been widely recognized. In view of the above circumstances, the present inventors have developed an oral composition that is highly effective in improving tooth acid resistance, is suitable for caries prevention, and exhibits excellent effects even under weakly acidic (PH4-7) conditions. As a result of intensive studies, we found that the content of water-soluble fluoride such as sodium fluoride in stannous fluoride is 3.5 moles or less of fluorine per mole of tin,
In particular, if the phytic acid compound is added in an amount of 2.2 to 3.2 mol, and the phytic acid compound is added in an amount of 2 mol or less, especially 0.3 to 1.5 mol, per 1 mol of stannous tin, the pH of
7 shows a very high effect of improving tooth acid resistance, and also has excellent acid resistance even under low fluorine concentration conditions with a total fluorine content of around 1000 ppm or less, and therefore under conditions where the stannous ion concentration is also low. The present invention was based on the discovery that it can provide an improving effect and can therefore be effectively used as a toothpaste.

The present invention will be explained in detail below.

The oral composition according to the present invention contains stannous fluoride, a water-soluble fluoride, and a phytic acid compound, and the water-soluble fluoride includes sodium fluoride, potassium fluoride,
Water-soluble inorganic fluorides such as lithium fluoride, ammonium fluoride, sodium monofluorophosphate, potassium monofluorophosphate, ammonium monofluorophosphate, hexylamine hydrofluoride, laurylamine hydrofluoride, cetylamine hydrofluoride One or more water-soluble organic fluorides such as , glycine hydrofluoride, lysine hydrofluoride, and alanine hydrofluoride can be used, but especially sodium fluoride, potassium fluoride, ammonium fluoride, and monofluoroline. sodium acid, potassium monofluorophosphate,
Cetylamine hydrofluoride is preferably used.

In addition, phytic acid compounds include phytic acid, sodium salts, potassium salts, lithium salts, and ammonium salts of phytic acid in which some or all of the hydrogen atoms of the phosphoric acid groups at positions 1 to 6 of phytic acid are replaced with alkali metal groups. One or more salts or alkali earth metal salts such as magnesium salts of phytic acid are used,
Particularly preferred are phytic acid, and sodium, potassium, lithium, and ammonium salts of phytic acid. In the present invention, the water-soluble fluoride is
Adding fluorine in an amount of 3.5 moles or less, more preferably in the range of 2.2 to 3.2 moles, and
The phytic acid compound is the 11th! It is added in an amount of 2 mol or less, more preferably 0.3 to 1.5 mol, per 1 mol of A.

As a result, when the pH of the oral composition is between 4 and 7, an excellent effect of improving tooth acid resistance is provided. On the other hand, when the molar ratio of fluorine and the molar ratio of the phytic acid compound to stannous tin deviates from the above-mentioned ranges, especially when these molar ratios are higher than that, the effect of the composition PH4 to 7 decreases, and the present invention The purpose of the invention cannot be achieved. In this case, the blending amount of L-tin fluoride is preferably 0.03 to 4% by weight. In particular, when manufacturing toothpaste, the total fluorine content is 100 to 1000 ppm, the stannous content is 190 ppm,
The amount of phytic acid equivalent of the phytic acid compound is preferably 380 to 28,000 ppm. In this case, sodium fluoride can be suitably used as the water-soluble fluoride. In addition, in the present invention, there is no problem even if the stannous fluoride is blended in an amount exceeding the saturated solubility amount.
Also, depending on the amount of phytic acid compound blended with L-tin fluoride (particularly when the amount of phytic acid compound is small relative to the stannous fluoride), precipitation may occur; Regardless of the presence or absence of precipitation, as long as the molar ratio of the phytic acid compound and the molar ratio of water-soluble fluoride to the amount of stannous fluoride are within the ranges mentioned above, the tooth acid resistance effect can be achieved. It's expensive.

Other ingredients of the present invention include the type of oral composition;
Known ingredients are used depending on the purpose and dosage form, and the desired known ingredients are mixed with water to which stannous fluoride, water-soluble fluoride, and phytic acid compounds are added. Producing a composition.

That is, the oral composition according to the present invention can be used as a mouthwash (liquid, tablet, powder, paste), chewable tablet, oral band, topical liniment (liquid, paste), cavity sealant, ultrasonic It is used as a treatment agent, iontophoresis treatment agent, profilaxis paste, toothpaste, dental floss, desensitizer, etc., but for example, when manufacturing liquid mouthwashes, topical application agents, etc. Add stannous fluoride, water-soluble fluoride, and phytic acid compounds to distilled water, ion-exchanged water, ethanol, etc., and add sweeteners such as saccharin, peppermint oil, spearmint oil, anise oil, etc. as necessary. Manufactured by adding a small amount of flavoring agent. In addition, when producing gel-like mouthwashes, topical coatings, etc., a humectant such as glycerin, sorbitol, propylene glycol, polyethylene glycol, etc. is added to the liquid material (compounding amount: usually 5 to 7% by saliva). In addition, binders such as xanthan gum, guar gum, carrageenan, and sodium carboxymethylcellulose (compounding amount usually 0.3 to 10% by weight), and a small amount of preservatives such as ethyl roseoxybenzoate and butyl roseoxybenzoate are added. Manufactured by Furthermore, tablets and powder granules can be prepared using known tablet and powder granule ingredients, such as excipients such as lactose and mannitol, disintegrants such as corn starch and carboxymethyl cellulose, and binders, according to conventional methods. Oral bands can be manufactured using stannous fluoride, water-soluble fluorides, phytic acid compounds, adhesive polymeric substances that dissolve in water or gel with water, polyhydric alcohols, surfactants, etc. It is produced by dissolving or dispersing the ingredients in water, freeze-drying the solution, and cutting it into a desired shape. In addition, in the case of toothpaste, calcium pyrophosphate,
Insoluble alkali metal metaphosphate (e.g. insoluble sodium metaphosphate), titanium dioxide, resin, aluminum hydroxide, silicic anhydride, abrasive such as alumina silicate (compounding amount usually 20-6%), xanthan gum, guar gum, carrageenan , hydroxyethyl cellulose, sodium carboxymethyl cellulose, etc. (0.
5-5%), humectants such as glycerin, sorbitol, and other polyhydric alcohols (20-25%), water-soluble alkyl sulfates such as sodium lauryl sulfate, and other foaming agents (0.5-3%). It is manufactured using flavoring agents, sweeteners, preservatives, and active ingredients such as chlorhexidine. In addition, the pH of the oral composition according to the present invention is 4.
~7, but in this case, the pH adjustment is done using citric acid, tartaric acid, lactic acid, malonic acid, malic acid, L-ascorbic acid,
The desired pH may be adjusted by adding an organic acid such as succinic acid or an alkali metal/metal salt thereof, or an inorganic acid or an alkali such as sodium hydroxide.

The oral composition of the present invention is used in a conventional manner depending on its type, dosage form, etc. For example, in the case of a mouthwash, if it is a liquid, it can be applied as it is or diluted with water, and it can be applied as a tablet,
If it is in the form of powder or gel, it can be applied by dissolving or dispersing it in water.

In addition, oral bands are used by applying them to the teeth.
When applied, the adhesive polymer, which is the main component of this band, gels due to the action of saliva, becomes sticky and is held tightly against the teeth, and the active ingredients in the band (stannic fluoride,
Water-soluble fluoride, phytic acid compounds) act on teeth. Furthermore, in the case of a liniment, it may be applied by applying it to the tooth surface, as appropriate.
As described above, these oral compositions are applied as is or after being adjusted to a state suitable for oral application, such as by diluting, dissolving, or dispersing with water. Stannous fluoride, water-soluble fluoride, and phytic acid compounds contained in a specific molar ratio range have a pH of 4 to 7.
They act synergistically on tooth enamel and significantly increase the acid resistance of teeth.

Further, the oral composition of the present invention has a total fluorine concentration of 1000p.
Low fluorine concentration around pm or below (therefore,
Even when the concentration of stannous is low due to the molar ratio of tin and fluorine, it provides an excellent effect of improving acid resistance, and is suitably used as a toothpaste. Furthermore, the oral composition of the present invention is highly effective in improving the acid resistance of enamel even when treated at temperatures ranging from room temperature to about 30°C, and the effect is highly durable (for example, after treating enamel, The acid resistance of enamel is maintained at a very high level even after rinsing under running tap water for 2 hours), and it exhibits an excellent effect in suppressing caries. In addition, it has high storage stability, and there is almost no decrease in effectiveness even if it is stored at 40° C. for 2 months, for example.

Next, the effect of improving tooth acid resistance in the present invention will be specifically explained with reference to experimental examples.

In addition, in the following experimental examples, all percentages indicate weight percent. Experimental Example 1 Add 1.2% of stannous fluoride, sodium fluoride, and pentasodium phytate [formula (1) below] to water in a predetermined ratio, and add hydrochloric acid or an aqueous sodium hydroxide solution to adjust the pH. By adjusting the molar ratio of fluorine to stannous, the molar ratio of phytic acid compound to stannous, and the pH, test solutions were prepared.

Next, a specimen made from bovine front teeth was added to these test solutions. After immersing NamelProk at 30°C for 3 minutes, it was brushed with a toothbrush 10 times horizontally and vertically, for a total of 20 times, and then left in tap water for 2ctf at 37°C as a rinse to confirm the retention of the effect. .

Next, the treated tooth is treated with a demineralizing solution (a). 1M acetate buffer,
PH4.5). The hardness of the enamel surface after demineralization was measured using a Vickers hardness meter, and the effect of each test solution on improving acid resistance of enamel was evaluated based on the measured value. did. The results are shown in Tables 1-3.

Note that the above demineralization conditions and hardness measurement evaluation method for tooth acid resistance employ extremely harsh conditions and evaluation methods in which samples treated with an 8% SrlF2 aqueous solution are almost completely demineralized with the demineralization solution. This is what I did.

Therefore, those with a hardness value of 150 or more, especially 200 or more, exhibit very excellent acid resistance, and when incorporated as an active ingredient in an oral composition, provide an extremely high caries preventive effect. Experimental Example 2 Stannous fluoride 0.27% and sodium fluoride 0.07%
4% (total fluorine amount 1000 ppm 1F/Sn (■) = 3
．． 0 mol) and pentasodium phytate in water,
By adding hydrochloric acid or an aqueous sodium hydroxide solution to adjust the pH, test solutions were prepared in which the molar ratio of the phytic acid compound to stannous and the pH were varied.

Hereinafter, the same operation as in Experimental Example 1 was carried out to evaluate the effect of each test liquid on improving the acid resistance of enamel, and the results shown in Table 4 were obtained.

Experimental example 3 L tin fluoride and sodium fluoride were mixed with F/Sn(■)2
．． Total fluorine amount 1000p in the range of 2 to 3.5 moles
After adding pentasodium phytate to this, the pH was adjusted to 4.5, and test solutions were prepared with various molar ratios of phytate compound to stannous tin. The test solution was operated in the same manner as in Experimental Example 1 to evaluate the effect of improving enamel acid resistance, and the results shown in the drawings were obtained.

From the results of Experimental Examples 1 to 3, in a system containing stannous fluoride, sodium fluoride, and a phytic acid compound, the molar ratio of fluorine to stannous is 3.5 or less, particularly 2.2 to 3.2.
, when the molar ratio of the phytic acid compound to stannous tin is 2.0 or less, especially in the range of 0.3 to 1.5, weak acidity, especially P
It has been found that a very excellent acid resistance improving effect is exhibited at H4 or higher.

In particular, within the above conditions, the total fluorine amount is 1000pp.
The effect of improving the acid resistance of the tooth substance is excellent even at the permissible amount of m, which is commonly used in tooth brushing, and therefore, the formulation of the present invention was recognized to be very effective for tooth brushing as well. In addition, pentasodium phytate 1.0 is added to 0.76% sodium monofluorophosphate (total fluorine amount 1000 ppm), which has been conventionally blended into toothpaste as a fluorine source.
% and dissolved in water (PH5), the same experiment as above was conducted, but no effect was observed (Vickers hardness after demineralization: 50 or less).

Further, no effect was observed when 2.0% sodium fluoride and 1.0% sodium phytate were used together (PH5) (Vickers hardness after deashing was 50 or less). Examples are shown below.

In addition, in the following examples, all percentages indicate weight percent. In addition, the oral compositions according to each example were adjusted to the indicated pH using sodium hydroxide or hydrochloric acid. Example 5,
6

[Brief explanation of the drawing]

The drawing shows the molar ratio of phytate compound to stannous tin and Vickers hardness after enamel demineralization when enamel blocks were decalcified after being treated with test solutions with different molar ratios of phytate compound to stannous tin. It is a graph showing the relationship between

Claims (1)

[Claims] 1 Contains stannous fluoride, a water-soluble fluoride, and a phytic acid compound, and the mole of fluorine relative to the stannous is 3.
．． 5 or less, the molar ratio of the phytic acid compound to stannous tin is 2 or less, and the composition has a pH of 4 to 7. 2 The molar ratio of fluorine to stannous tin is 2.2 to 3.2, and the molar ratio of phytic acid compound to stannous tin is 0.2 to 3.2.
3 to 1.5, the oral composition according to claim 1. 3 The blending amount of stannous fluoride is 0.03 to 4% by weight of the total
The oral composition according to claim 1 or 2. 4. Claims 1 to 4, wherein the water-soluble fluoride is selected from sodium fluoride, potassium fluoride, ammonium fluoride, sodium monofluorophosphate, potassium monofluorophosphate, and cetylamine hydrofluoride. Oral composition according to any one of Item 3. 5. Stannous fluoride, sodium fluoride, and a phytic acid compound are used in toothpaste at a ratio of total fluorine of 100 to 1,000 ppm, stannous amount of 190 to 2,800 ppm, and phytic acid equivalent of the phytic acid compound of 380 to 28,000 ppm. An oral composition according to claim 1 or 2, which is formulated with the following.