JP2775051B2 - Oral composition - Google Patents

Description

Description: TECHNICAL FIELD The present invention relates to an oral composition for supplying fluorine to teeth.

2. Description of the Related Art It is known that fluorine acts on teeth to improve the acid resistance of tooth enamel and suppress the occurrence of dental caries. For this reason, conventionally, as a fluorine source, various oral compositions such as sodium fluoride, stannous fluoride, sodium monofluorophosphate, etc., for example, dentifrices, mouthwashes, coating agents, etc. To prevent dental caries by acting on the tooth surface.

In addition, it has been recently reported that fluorine treatment in the initial stage of dental caries restores to healthy tooth material again, that is, promotes so-called remineralization.

However, when such fluorine compounds are used in dentifrices, mouthwashes and coatings, the operability is good, but the retention in the oral cavity is poor, and the amount of fluorine taken up into the teeth is short due to the short action time of fluorine. It is small and cannot expect a sufficient effect.

That is, in the case of a fluorine coating agent for preventing caries, all of the fluorine compounds used are water-soluble, and the dosage form is generally water-soluble, and the retention in the oral cavity is poor.

Therefore, in order to improve the retention in the mouth, methods such as thickening or gelling with a water-soluble polymer or dispersing a fluoride in a natural resin are also performed, but the method remains in the mouth for several hours. It's just not enough.

SUMMARY OF THE INVENTION The inventors of the present invention have conducted intensive studies in view of the above problems, and have found that a fluorine compound is blended in a solution of a copolymer obtained by copolymerizing a predetermined acrylic monomer at a specific ratio. As a result, the present inventors have found that extremely excellent adhesiveness to the tooth surface can be obtained, and that fluorine ions can act on the tooth surface for a long time, thereby completing the present invention.

That is, the present invention [Wherein, R ¹¹ is an alkyl group having 1 to 10 carbon atoms; R ¹² is a lower alkyl group; R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ and R ¹⁷ each independently represent hydrogen or a methyl group] And a structural unit represented by the formula Ia is 5 to 30% by weight, and a structural unit represented by the formula Ib is 20 to 6% by weight.
0% by weight, 20 to 60% by weight of the structural unit represented by the formula Ic,
A copolymer (I) containing 0.2 to 20% by weight of a structural unit represented by Id; and Wherein R ²¹ and R ²² each independently represent an alkyl group having 1 to 10 carbon atoms; R ²³ , R ²⁴ and R ²⁵ each independently represent hydrogen or a methyl group. 5 to 80% by weight of the structural unit represented by the formula IIa, and 10 to 80% by weight of the structural unit represented by the formula IIb.
A copolymer (II) containing 95% by weight and 0 to 85% by weight of a structural unit represented by the formula IIc; 5 to 40% by weight of one or more copolymers obtained from the group consisting of: An oral composition characterized by comprising 0.01 to 6% by weight of phosphoric acid and / or tartaric acid, a fluorine compound, and a volatile solvent.

According to the present invention, the acrylic copolymer (I) and / or (II) represented by the above formula is purified and dissolved in a solvent, and the solution is applied to the tooth surface so that the tooth surface is uniform and water-resistant. A film having an excellent and strong adhesive force is formed, and fluoride can act on the teeth for a long time. Further, fluoride can be stably compounded by mixing phosphoric acid and tartaric acid.

Next, the present invention will be described in detail.

The acrylic copolymer used in the composition of the present invention is the copolymer (I) or (II) or a mixture thereof.

First, the monomers used in the production of the acrylic copolymer (I) are acrylic acid or methacrylic acid represented as the monomer units in the formulas (Ia) to (Id); alkyl acrylate or alkyl methacrylate. Esters; hydroxyalkyl acrylate or hydroxyalkyl methacrylate; and acryloxypropyl trialkoxysilane or methacryloxypropyl trialkoxysilane.

Examples of the alkyl acrylate or alkyl methacrylate include methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, butyl methacrylate, 2-ethylhexyl acrylate, and 2-ethylhexyl methacrylate.

Examples of hydroxyalkyl acrylate or hydroxyalkyl methacrylate include hydroxyethyl acrylate, hydroxyethyl methacrylate, hydroxypropyl acrylate, hydroxypropyl methacrylate, and the like.

Further, as acryloxypropyl trialkoxysilane or methacryloxypropyl trialkoxysilane, acryloxypropyltrimethoxysilane, methacryloxypropyltrimethoxysilane, methacryloxypropyltriethoxysilane and the like are used.

The weight composition ratio of the monomers in the acrylic copolymer (I) is 5 to 30% by weight of acrylic acid or methacrylic acid, preferably 10 to 20% by weight, 20 to 60% by weight of acrylic acid alkyl ester or methacrylic acid alkyl ester. %, Preferably 25 to 40% by weight, hydroxyalkyl acrylate or hydroxyalkyl methacrylate 20 to 60% by weight, preferably 30 to 50% by weight, and acryloxypropyl trialkoxysilane or methacryloxypropyl trialkoxysilane 0.2 to 20%. % By weight, preferably 1 to 10% by weight.

The weight average molecular weight of the acrylic copolymer (I) is several thousand to
Hundreds of thousands.

On the other hand, examples of the monomer used in the production of the other acrylic copolymer (II) blended in the composition of the present invention include acrylic acid or methacrylic acid, and one or two of acrylic acid ester and methacrylic acid ester. Can be Examples of these acrylates or methacrylates include methyl acrylate, methyl methacrylate, ethyl acrylate, ethyl methacrylate, butyl methacrylate, 2-ethylhexyl acrylate, and methacrylic acid.
It is preferably used such as 2-ethylhexyl.

The weight composition ratio of the monomers in the acrylic copolymer (II) is 5 to 80% by weight, preferably 25 to 50% by weight of acrylic acid or methacrylic acid, and one or two alkyl acrylates or methacrylic acids are used. The acid alkyl ester content is 20 to 95% by weight, preferably 50 to 75% by weight.

The weight average molecular weight of the acrylic copolymer (II) is from several thousand to several hundred thousand.

The acrylic copolymers (I) and (II) used in the composition of the present invention can be produced by ordinary solution polymerization. That is, each monomer is dispersed and dissolved in a volatile solvent at a predetermined ratio.

Examples of such a polymerization solvent include methanol, ethanol, isopropanol, acetone, chloroform, ethyl acetate and the like, and it is most preferable to use ethanol in consideration of harmfulness in use in the oral cavity.

Examples of the polymerization catalyst used include known radical-forming compounds such as 2,2'-azobisisobutyronitrile, 2,2'-azobis (4-methoxy-2,4-dimethylvaleronitrile), dimethyl 2,2'-azobisisobutyrate, 2,2'-azobis (2,4-dimethylvaleronitrile), benzoyl peroxide, diisopropyl purge carbonate, t-butyl perisobutyrate and the like can be used. The amount of these polymerization catalysts added is based on the total weight of the monomers.
It is 0.05 to 2% by weight, preferably 0.1 to 0.5% by weight.

The polymerization reaction is preferably carried out at 50 to 100 ° C., and it is generally preferred to carry out the reaction at the boiling point of the volatile solvent.

Since the obtained copolymer solution does not contain unreacted monomers, it has no harmful effect because it is in the oral cavity and can be sufficiently used as the composition of the present invention without purification usually.

The amount of the copolymers (I) and (II) thus obtained is 5 to 40% by weight, preferably 10 to 30% by weight, based on the total weight of the composition. If the amount is more than 40%, it is difficult to form a uniform coating with high viscosity, which is unsuitable. Also, the usability is poor. On the other hand, if it is less than 5% by weight, sufficient adhesive strength cannot be obtained, and a good film cannot be obtained.

As the fluorine compound, any of the conventionally known compounds having the effect of strengthening the dentin may be used. Specifically, sodium fluoride, calcium fluoride, primary fluoride
Examples thereof include tin, zinc fluoride, strontium fluoride, and sodium monofluorophosphate. From the viewpoint of the effect of preventing dental caries, it is preferable to add 0.001 to 0.02% by weight based on the total amount of the composition.

Examples of the volatile solvent used in the composition of the present invention include methanol, ethanol, isopropanol, acetone, chloroform, ethyl acetate and the like, and ethanol is most preferably used in consideration of harmfulness in use in the oral cavity. New

Phosphoric acid and tartaric acid used in the present invention have a property of improving the solubility of fluoride which is conventionally hardly soluble in ethanol, and these may be used as a mixture. By blending phosphoric acid or tartaric acid into the composition, fluoride is solubilized and stable blending becomes possible. As phosphoric acid, orthophosphoric acid or orthophosphoric acid, as well as phosphorous acid, metaphosphoric acid, polyphosphoric acid and the like can be used. The compounding amount of phosphoric acid or tartaric acid is 6% by weight or less, preferably 0.01 to 1% by weight based on the total weight.

The stabilizing effect of phosphoric acid and tartaric acid upon blending the fluoride into the volatile solvent was examined by the following method. As an experimental method, 0.1% of phosphoric acid or tartaric acid
A large excess of sodium fluoride was added to a container containing 20 ml of a -10% ethanol solution, and the mixture was shaken at 30 ° C for 2 hours and further at 20 ° C. Subsequently, the excess sodium fluoride was filtered off, and the fluoride ion content of the filtrate was measured with a fluoride ion electrode.

 The results are shown in Table 1 below.

As is clear from Table 1, when tartaric acid or phosphoric acid is blended in an amount not exceeding 6%, the solubility of fluoride is improved. If the amount is more than 6%, the solubility of the fluoride becomes worse, and the solubility of the copolymer in the volatile solvent is hindered. That is, stable blending of fluoride is possible with blending of tartaric acid or phosphoric acid of 6% or less.

Thus, the composition of the present invention is produced by mixing and dissolving desired components according to a conventional method.

The oral composition of the present invention is further blended with a pigment, a preservative, and the like in order to clarify an applied portion, and is used as a caries preventive agent or a treatment for promoting remineralization by being applied to an initial carious surface. It can be used as an agent. In addition, it is only necessary to apply air to the tooth material with a small brush and then air-dry, and since a film is formed in a short time, it is simple and easy to use.

Examples Hereinafter, the present invention will be described in more detail with reference to Examples, Production Examples, and Test Examples. In these, all% means% by weight.

Production Example 1 25 g of methacrylic acid, 25 g of methyl methacrylate and 117 g of ethanol were charged into a four-necked flask equipped with a thermometer, a reflux condenser, a stirrer, and a nitrogen inlet tube, and stirred for 2 hours while introducing nitrogen to degas. did. Next, as a polymerization initiator 2,
Add 0.5 g of 2'-azobisisobutyronitrile, and add
Polymerized for 0 hours. Further, 0.2 g of a polymerization initiator was additionally added, and the mixture was refluxed for 4 hours to complete the polymerization.

Analysis of the polymerization solution by gel permeation chromatography (hereinafter abbreviated as GPC) confirmed that the total amount of remaining monomers was 0.05%. The polymerization solution was further diluted with ethanol to adjust the concentration to 20% to obtain a colorless and transparent polymer solution. (Copolymer A ₁ ) The weight average molecular weight of the obtained copolymer was 4.1 × 10 ^{4 as} measured by GPC. Solution viscosity (B-type rotational viscometer,
25 ° C.) was 125 centipoise. The copolymer solution was applied to a Teflon plate and air-dried, and the infrared absorption spectrum of the polymer film obtained was measured. IR (cm ^-1 ): 2950 (C
_{H 3, νCH), 1720 (} COO, νC = O), 1490 (CH 2, δC
H), 1160 (COO group, νC-OC).

Production Example 2 In the same four-necked flask as in Production Example 1, methacrylic acid 15
g, methyl methacrylate (20 g), butyl methacrylate (15 g) and ethanol (117 g) were charged and stirred for 2 hours while introducing nitrogen to degas. Next, 0.25 g of 70% t-butyl perisobutyrate was added as a polymerization initiator, and polymerization was performed at 70 ° C. for 20 hours. Further, 0.2 g of an initiator was added, and the mixture was refluxed for 4 hours to complete the polymerization.

As a result of analyzing the polymerization solution by GPC, it was confirmed that the total amount of the remaining monomers was 0.04%. The polymerization solution was further diluted with ethanol to adjust the concentration to 20% to obtain a colorless and transparent polymer solution. (Copolymer A ₂ ) The weight average molecular weight of the obtained copolymer was 7.5 × 10 ^{4 as} measured by GPC. Solution viscosity (B-type viscometer, 25
° C) was 80 centipoise. The copolymer was applied to a Teflon plate and air-dried, and the infrared absorption spectrum of the polymer film obtained was measured. IR (cm ^-1 ): 2960 (CH ₃ , νCH),
1725 (COO, νC = O), 1480 (CH ₂ , δCH), 970 (δC
Outside the H plane).

Production Example 3 In the same four-necked flask as in Production Example 1, methacrylic acid 5
g, 15 g of methyl methacrylate, 25 g of hydroxyethyl methacrylate, 5 g of γ-methacryloxypropyltrimethoxysilane, and 117 g of ethanol were stirred and degassed for 2 hours while introducing nitrogen. Next, as a polymerization initiator 2,
0.25 g of 2'-azobis (2,4-dimethylvaleronitrile)
Was added and polymerized at 70 ° C. for 20 hours. Further, 0.2 g of an initiator was added, and the mixture was refluxed for 4 hours to complete the polymerization.

As a result of analyzing the polymerization solution by GPC, it was confirmed that the total amount of the remaining monomers was 0.06%. The polymerization solution was further diluted with ethanol to a concentration of 20% to obtain a colorless and transparent polymer solution. (Copolymer B ₁ ) The weight average molecular weight of the obtained copolymer was 5.0 × 10 ^{4 as} measured by GPC. Solution viscosity (B-type viscometer, 25
C) was 30 centipoise. The obtained copolymer was applied to a Teflon plate and air-dried, and the infrared absorption spectrum of the polymer film obtained was measured. IR (cm ^-1 ): 3500 (OH,
νOH), 2960 (CH ₃ , νCH), 1725 (COO, νC = O),
1450 (CH ₃ , δCH), 1160 (COO, νC-OC).

Production Example 4 In the same four-necked flask as in Production Example 1, methacrylic acid 5
g, 24 g of ethyl methacrylate, 20 g of 2-hydroxyethyl acrylate, 1 g of γ-methacryloxypropyltrimethoxysilane and 117 g of ethanol, and the mixture was stirred and degassed for 2 hours while introducing nitrogen. Next, as a polymerization initiator
2,2'-azobis (2,4-dimethylvaleronitrile) 0.25
g was added and polymerized at 70 ° C. for 20 hours. Further, 0.2 g of an initiator was added, and the mixture was refluxed for 4 hours to complete the polymerization. GPC polymerization liquid
As a result, it was confirmed that the total amount of the remaining monomers was 0.02%. Dilute the polymerization solution further with ethanol
The concentration was adjusted to 20% to obtain a colorless and transparent polymer solution.
(Copolymer B ₂ ) The weight average molecular weight of the obtained copolymer was 7.6 × 10 ^{4 as} measured by GPC. Solution viscosity (B-type viscometer, 25
C) was 35 centipoise. The copolymer solution was applied to a Teflon plate and air-dried, and the infrared absorption spectrum of the polymer film obtained was measured. IR (cm ^-1 ): 3500 (OH, νO
H), 2950 (CH ₃ , νCH), 1720 (COO, νC = O), 149
0 (CH ₂ , δCH), 970 (out of δCH plane).

Production Example 5 In a flask similar to that of Production Example 1, 5 g of methacrylic acid, 24 g of butyl methacrylate, 20 g of 2-hydroxyethyl methacrylate, 1 g of γ-methacryloxypropyltrimethoxysilane and 117 g of ethanol were charged, and nitrogen was introduced. Degas by stirring for 2 hours. Next, t is used as a polymerization initiator.
-Butyl perisobutyrate (0.25 g) was added and polymerized at 70 ° C for 20 hours. Further, 0.2 g of an initiator was added, and the mixture was refluxed for 4 hours to complete the polymerization. As a result of analyzing the polymerization solution by GPC, it was confirmed that the total amount of the remaining monomers was 0.04%. The polymerization solution was further diluted with ethanol to adjust the concentration to 20% to obtain a colorless and transparent polymer solution. (Copolymer B ₃ ) The weight average molecular weight of the obtained copolymer was 20.2 × 10 ^{4 as} measured by GPC. The solution viscosity (B-type rotational viscometer, 25 ° C.) was 69 centipoise. The obtained copolymer was applied to a Teflon plate and air-dried, and the infrared absorption spectrum of the obtained polymer film was measured. IR (cm ^-1 ): 3
500 (OH, νOH), 2950 (CH ₃ , νCH), 1720 (COO, ν
C = O), 1490 (CH ₃ , δCH), 970 (out of δCH plane).

Example 1 Based on the formulation shown in Table 2 below, each component was mixed and dissolved according to a conventional method, and a transparent liquid oral composition (sample 1 to sample 1) was prepared.
7) was obtained. These have excellent adhesion to tooth material and supply fluorine for a long time.

Test Example 1 Bovine tooth enamel block (7 mm x 5 mm) was Ca5mM, P3m
It was immersed in a 0.1 M lactic acid solution containing M for 3 days to form an initial caries artificially. The composition (samples 1 and 2) obtained in Example 1 was applied to this block to form a transparent film.

Then, place the block in artificial saliva (pH 7.0) at 37 ° C for 2 hours.
After soaking for days, the composition was removed. Subsequently, the block was immersed in an acetate buffer at 37 ° C. for 6 hours, and the amount of Ca eluted from the dentin into the solution was measured. As a control, a block treated in exactly the same manner except that the oral composition was not applied was treated in the same manner. The results obtained are shown below.

From the results shown in Table 3, when the composition of the present invention (samples 1 and 2) was applied, the amount of Ca eluted from artificial caries was smaller and the acid resistance of the tooth material was lower than in the case of no treatment. Improve,
The tendency of caries to recover to healthy enamel was recognized, and the effect of strengthening the teeth was remarkable. That is, fluorine acts on the dentin from the composition of the present invention, and is effective in preventing caries.

Effect of the Invention The composition of the present invention has excellent adhesiveness and water resistance to tooth material, can be adhered for a long time, and furthermore, fluorine is stably compounded, so that the tooth surface Fluorine acts continuously on the tooth material from the film formed thereon. Therefore, by applying the composition of the present invention to the tooth, it is possible to suppress dental caries and improve the tooth quality.
In addition, since the fluoride is less likely to be washed away by the saliva, a large effect can be obtained with a fluoride having a lower concentration than the conventional one.

Further, the composition of the present invention is easily applied, can form a film in a short time, and is excellent in usability.

──────────────────────────────────────────────────続 き Continuing on the front page (72) Inventor Hiroshi Furuji 6-5 Meishincho, Takatsuki City, Osaka Prefecture (72) Inventor Takao Makishima 29-1-205 Yamada Minami, Suita City, Osaka Prefecture (72) Inventor Kiyoshi Maekawa Shiga 859-33, Sakamoto-cho, Otsu City, Prefecture (56) References JP-A-54-160752 (JP, A) JP-A-63-130524 (JP, A) (58) Fields investigated (Int. Cl. ⁶ , DB name) ) A61K 7/16-7/28

Claims (3)

(57) [Claims] (1) [Wherein, R ¹¹ is an alkyl group having 1 to 10 carbon atoms; R ¹² is a lower alkyl group; R ¹³ , R ¹⁴ , R ¹⁵ , R ¹⁶ and R ¹⁷ each independently represent hydrogen or a methyl group] And a structural unit represented by the formula Ia is 5 to 30% by weight, and a structural unit represented by the formula Ib is 20 to 6% by weight.
0% by weight, 20 to 60% by weight of the structural unit represented by the formula Ic,
A copolymer (I) containing 0.2 to 20% by weight of a structural unit represented by Id; and Wherein R ²¹ and R ²² each independently represent an alkyl group having 1 to 10 carbon atoms; R ²³ , R ²⁴ and R ²⁵ each independently represent hydrogen or a methyl group. 5 to 80% by weight of the structural unit represented by the formula IIa, and 10 to 80% by weight of the structural unit represented by the formula IIb.
A copolymer (II) containing 95% by weight and 0 to 85% by weight of a structural unit represented by the formula IIc; 5 to 40% by weight of one or more copolymers selected from the group consisting of: An oral composition comprising 0.01 to 6% by weight of phosphoric acid and / or tartaric acid, a fluorine compound, and a volatile solvent. 2. The composition according to claim 1, wherein the fluorine compound is sodium fluoride. 3. The composition according to claim 1, wherein the volatile non-aqueous solvent is ethanol.