JPH08325128A - Long term sustainable base for oral cavity and composition using the same - Google Patents

Abstract

PURPOSE: To obtain a base dryable in a short time after applied to the both sift and hard tissues in the oral cavity, free from a sense of incompatibility of the film formed after applied to the oral cavity, and subject to stay in the oral cavity for a long time. CONSTITUTION: This long-term sustainable base for oral cavity is obtained by formulating a lower alcohol solution of an acrylic polymer with a fatty acid alcohol ester. The acrylic polymer accounts for 10-30wt.% of the final base, being e.g. an ethyl acrylate-methyl methacrylate-ethyl methacrylate trimethylammonium chloride copolymer. The fatty acid alcohol ester is e.g. triethyl citrate, accounting for 5-30wt.% of the final base. The lower alcohol (e.g. ethanol) accounts for 20-70wt.% of the final base. It is preferable that the weight ratio of the acrylic polymer to the fatty acid alcohol ester be (2:1) to (3:2). This base is a viscous liquid, forming a uniform film in a short time when applied to the oral cavity; the film is firmly adherable esp. to the dentin and retains its high adhesive force even in water or saliva.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The composition of the present invention relates to a long-term retention type base for the oral cavity. More specifically, a long-term retention type for the oral cavity, in which an oral preparation obtained by blending a fatty acid alcohol ester with a lower alcohol solution of an acrylic polymer is applied and retained in the oral cavity by forming a film on the oral cavity. Regarding the base.

[0002]

2. Description of the Related Art Conventionally, various compositions containing a polymer having a film-forming ability as a base for pharmaceutical preparations and cosmetics have been known. Use in the oral cavity is disclosed in JP-A-03-12831.
No. 6, JP-A-62-142112, and many others. However, these compositions take a long time to dry after administration, and the formed coating film is uncomfortable after application, and has a short residence time due to the complicated structure in the oral cavity, and easily peels off. There were drawbacks such as being lost.

[0003]

In view of these problems, the inventors of the present invention have applied the composition to the soft and hard tissues in the oral cavity and dried it in a short time so that the formed coating film does not feel uncomfortable and the oral cavity is for a long time. We have conducted intensive studies to obtain a long-term retention type base that stays in the mouth. As a result, it was newly found that the object can be achieved by combining an acrylic polymer, a fatty acid alcohol ester, and a lower alcohol.

As the acrylic polymer used in the present invention, those described in the compendials of the standards for pharmaceutical additives can be used, and it is soluble in lower alcohols, and a long-term oral retention base is applied. After that, since a film is formed and stays for a long time, methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, methacrylic acid / ethyl acrylate copolymer,
It is desirable to use a polymer selected from methacrylic acid / methyl methacrylate copolymer and ethyl acrylate / methyl methacrylate / trimethylammonium ethyl methacrylate acrylate copolymer, and more desirably, the water resistance of the formed film. Uses ethyl acrylate / methyl methacrylate / trimethylammonium methacrylate acrylate copolymer, which has the best properties and is hard to peel off. The blending amount of these acrylic polymers is preferably 10 to 30% by weight. Further, considering the feeling of use of the prepared composition, 20 to 25% by weight is more preferable.

As the fatty acid alcohol ester used in the present invention, those described in the compendial standard for pharmaceutical additives can be used. Among them, it is compatible with lower alcohols, and the prepared long-term retention type for oral cavity. It is preferable to use triacetin or triethyl citrate because the base film has flexibility and stays for a long time after application, and more preferably, triethyl citrate having excellent long-term stability is used.

The blending amount of the fatty acid alcohol ester is preferably 5 to 30% by weight in order to be flexible and to stay at the application site for a long time. Further, it is desirable that the blending ratio of the acrylic polymer and the fatty acid alcohol ester is acrylic polymer / fatty acid alcohol ester = 2/1 to 3/2.

The lower alcohol used in the present invention is
It is possible to use those described in the Japanese Pharmacopoeia, and it is preferable to use ethanol or isopropyl alcohol.

The lower alcohol content is preferably 20 to 70% by weight in order to dissolve the acrylic polymer and to dry immediately after application to form a film.
40-60% by weight is preferred.

The oral long-term retention type base of the present invention is manufactured by
For example, it can be performed as follows. First, the acrylic polymer is dissolved with a lower alcohol to obtain a viscous solution, and then a fatty acid alcohol ester and optionally a lower alcohol may be further added thereto to form a viscous solution. it can.

If desired, the oral long-term retention type base of the present invention further comprises a flavoring agent such as menthol, a sweetening agent such as sodium saccharin and stevioside, and an anti-inflammatory agent and / or a bactericide which can be generally used. It can be compounded as a drug to form an oral composition. Preferably, the composition for oral cavity for preventing dental caries can be prepared by incorporating fluorine.

[0011]

EXAMPLES The present invention will be described in more detail with reference to Examples and Test Examples. The present invention is not limited to these examples and test examples. Test Example 1: Drying property and film forming property test A film forming property test was conducted using the compositions obtained according to Examples 1 to 4 and Control Examples 1 to 7. An appropriate amount (2 to 4 mg) of each composition sample was applied to a slide glass under the conditions of a temperature of 25 ° C. and a relative humidity of 60%, and the drying time was measured every 30 seconds by finger contact. Further, the dried sample was sprayed with water using a spray, and it was visually observed whether or not it was a uniform continuous film and whether the film was clouded. The evaluation criteria for the coating are as follows. The results of the drying property and film forming property test are shown in Table 1. (Evaluation criteria) ++: Uniform film is formed +: Partial film is formed −: No film is formed

Example 1 Composition Blend amount (wt%) Ethyl acrylate / Methyl methacrylate / methacrylic acid Trimethylammonium ethyl chloride copolymer 25 Triethyl citrate 10 Ethanol 50 Water 15 Ethyl acrylate / Methyl methacrylate Dissolve the trimethylammonium methacrylic acid ethyl copolymer with 2 times the weight of lower alcohol to obtain a viscous solution. Next, triethyl citrate and water were further added to this, and the mixture was mixed and stirred until it became homogeneous to obtain a base for oral cavity.

Example 2 Component Content (wt%) Ethyl acrylate / Methyl methacrylic acid / methacrylic acid Trimethylammonium ethyl chloride copolymer 25 Triacetin 10 Ethanol 50 Water 15 Ethyl acrylate / Methyl methacrylic acid / methacrylic acid The trimethylammonium ethyl acid chloride copolymer is dissolved with twice the weight of the lower alcohol to give a viscous solution. Then add more triacetin and water,
The mixture was mixed and stirred until it became uniform to obtain an oral base.

Example 3 Component Blend Amount (% by Weight) Methyl Methacrylate / Butyl Methacrylate / Dimethylaminoethyl Methacrylate Copolymer 25 Triethyl Citrate 10 Ethanol 50 Water 15 Methyl Methacrylate / Butyl Methacrylate The dimethylaminoethyl methacrylate copolymer was dissolved in twice the weight of ethanol to give a viscous solution. Next, triethyl citrate and water were further added to this, and the mixture was mixed and stirred until it became homogeneous to obtain a base for oral cavity.

Example 4 Composition Blend amount (wt%) Ethyl acrylate / Methyl methacrylate / methacrylic acid Trimethylammonium ethyl chloride copolymer 25 Triethyl citrate 10 Ethanol 50 Strontium chloride 3 Water balance balance Ethyl acrylate methacrylic acid Methyl acid methacrylic acid trimethylammonium ethyl copolymer was dissolved in 2 volumes of ethanol containing strontium chloride to obtain a viscous solution. Next, triethyl citrate and water were further added to this, and the mixture was mixed and stirred until it became homogeneous to obtain a base for oral cavity.

Control Example 1 Composition Blend amount (wt%) Ethyl acrylate / Methyl methacrylic acid / methacrylic acid Trimethylammonium ethyl chloride copolymer 25 Polyethylene glycol 10 Ethanol 50 Water 15 Ethyl acrylate / Methyl methacrylic acid / meth The trimethylammonium ethyl acrylate copolymer was dissolved in twice the weight of ethanol to give a viscous solution. Next, polyethylene glycol and water were further added to this, and the mixture was mixed and stirred until it became uniform to obtain an oral base.

Control Example 2 Composition Blend amount (% by weight) Ethyl acrylate / Methyl methacrylate / Methacrylic acid Trimethylammonium ethyl chloride copolymer 15 Polyethylene glycol 30 Ethanol 40 Water 15 Ethyl acrylate / Methyl methacrylate / meta The trimethylammonium ethyl acrylate copolymer was dissolved in twice the weight of ethanol to give a viscous solution. Next, ethanol, polyethylene glycol, and water were further added to this, and the mixture was mixed and stirred until it became uniform to obtain an oral base.

Control Example 3 Component Blending Amount (wt%) Ethyl Cellulose 5 Triethyl Citrate 10 Ethanol 70 Water 15 Ethyl cellulose was dissolved in 3 times the weight of ethanol to obtain a viscous solution. Next, ethanol, triethyl citrate and water were further added thereto, and they were mixed and stirred until they were homogeneous to obtain a base for oral cavity.

Control Example 4 Composition Blend amount (% by weight) Methacrylic acid / methyl methacrylate copolymer 24.8 Sodium citrate 2.2 Ethanol 70.0 Strontium chloride 3.0 Methacrylic acid / Methyl methacrylate The copolymer was dissolved in twice the volume of ethanol containing strontium chloride to give a viscous solution. Then add ethanol,
Sodium citrate was further added, and the mixture was mixed and stirred until it became homogeneous to obtain an oral base.

Control Example 5 Composition Blend amount (% by weight) Ethyl acrylate / Methyl methacrylate / methacrylic acid Trimethylammonium ethyl chloride copolymer 24.8 Sodium citrate 2.2 Ethanol 70.0 Strontium chloride 3.0 A viscous solution was obtained by dissolving ethyl acrylate / methyl methacrylate / trimethylammonium ethyl methacrylate acrylate copolymer in twice the amount of ethanol containing strontium chloride. To this, ethanol,
Sodium citrate was further added, and the mixture was mixed and stirred until it became homogeneous to obtain a base for oral cavity.

Control Example 6 Composition Blend amount (% by weight) Ethyl cellulose (45 cp) 5.0 Gum rosin 25.0 Ethanol 53.0 Polyoxyethylene hydrogenated castor oil 60 12.0 Water balance Ethyl cellulose and gum rosin were dissolved in ethanol,
A viscous solution was obtained. Polyoxyethylene hydrogenated castor oil and water were further added to this, and the mixture was mixed and stirred until it became uniform to obtain an oral base.

Control Example 7 Composition Blend amount (% by weight) Ethyl cellulose (100 cp) 3.0 Gum rosin 15.0 Ethanol 73.0 Polyoxyethylene hydrogenated castor oil 60 3.0 Dibucaine hydrochloride 0.5 Water balance Ethyl cellulose and gum rosin Dissolve in ethanol,
A viscous solution was obtained. To this, dibucaine hydrochloride, polyoxyethylene hydrogenated castor oil, and water were further added, and the mixture was mixed and stirred until it became uniform to obtain an oral base.

[0023]

[Table 1]

As is clear from the results shown in Table 1, Example 1
It was confirmed that in Examples 4 to 4 and Comparative Examples 3, 5 and 7, a film having excellent film-forming property and a short drying time was obtained.

Test Example 2. Water immersion test A water immersion test was performed using the compositions obtained according to Examples 1 and 4 and Controls 4-7. An appropriate amount (5 to 10 mg) of each test composition sample was applied on a slide glass and dried at room temperature. This was immersed in a beaker containing distilled water, and the change in color of the coating after 8 hours and the strength of the coating at that time were observed. Table 2 shows the results.

[0026]

[Table 2] As is clear from the results in Table 2, it was confirmed that in Examples 1 and 4 and Comparative Example 6, a coating film having high strength upon immersion in water was obtained.

Test Example 3. Water Resistance Test A water resistance test was conducted using the compositions obtained according to Examples 1-3 and Control Examples 1-7. An appropriate amount (5 to 10 mg) of a sample of each test composition was applied onto a glass slide whose weight was measured in advance, and the sample was dried at room temperature and then weighed. This was immersed in distilled water stirred with a stirrer, the weight was measured after 2, 4, 8 and 24 hours, and the residual rate was calculated from the following formula 1. Table 3 shows the results of the water resistance test
Shown in

[0028]

## EQU1 ## L = W1-W3 / W2-W3 × 100 L = remaining rate (%) W1: total weight before immersion in water (g) W2: total weight after immersion in water (g) W3: weight of slide glass (G)

[0029]

[Table 3]

As is clear from the results shown in Table 3, Example 1
It was confirmed that a long-term retention type coating excellent in water resistance was obtained in Comparative Examples 1 to 3, and Comparative Examples 1, 4, 5, and 7.

Test Example 4. Flexibility test A flexibility test was performed using the compositions obtained according to Examples 1 to 4 and Controls 1 to 7. 1/2 of commercially available O-Band (fold width 100 mm x width 15 mm x thickness 1 mm)
To obtain a rubber band of 100 mm × 15 mm × 1 mm. As shown in FIG. 1, vinyl tape was attached to both ends of this rubber band, and a sample of each test composition was applied between both vinyl tapes. This was dried and pulled from the vinyl tape portion, the distance between the vinyl tapes when the sample cracked was measured, and the elongation rate was calculated from the following formula 2. The results of the flexibility test are shown in Table 4.

[0032]

[Equation 2] M = M1 / 5 cm × 100 M: Elongation (%) M1: Distance between vinyl tapes when sample cracks (cm)

[0033]

[Table 4]

As is clear from Table 4, in Examples 1 to 4, it was confirmed that coating films having high elongation and excellent flexibility were obtained. From the results of Test Examples 1 to 4, Examples 1 to 4
It was confirmed that a film having excellent film-forming property, short drying time, excellent water resistance, long-term retention, and excellent flexibility was obtained.

Test Example 5. Evaluation of Efficacy Against Hypersensitive Teeth The composition obtained according to Example 1 was used to evaluate the efficacy against hypersensitive teeth by the following method. The water of the hypersensitive tooth was lightly removed with a cotton swab, and then the test substance was applied. After air-drying for 15 to 20 seconds and confirming that a film was formed, the presence or absence of cold water pain, cold air pain and cold pain was confirmed. The test results are shown in Table 5. (Evaluation Criteria) 3: Remarkably Pain 2: Pain Pain 1: Slight Pain 0: No Pain

[0036]

[Table 5] As is clear from the results in Table 5, the composition of Example 1
It was confirmed that hyperesthesia can be effectively suppressed.

Test Example 6. Fluorine dissolution from fluorine-containing base
Ejection evaluation Using the composition obtained according to Example 5, a fluorine elution test was conducted. An appropriate amount (40 g) of the composition sample was applied on a plastic sheet whose weight was previously measured under the conditions of a temperature of 25 ° C. and a relative humidity of 60%, and the weight was measured after drying at room temperature. This was fixed to a plastic tube, 10 ml of distilled water was added, and the amount of fluorine in the eluate after 0.5, 1, 2, 4 and 8 hours was calculated using a fluorine ion electrode to calculate the elution rate of fluorine. The results of the dissolution test are shown in Table 6.

Example 5 Composition Blend amount (wt%) Ethyl acrylate / methyl methacrylate / methacrylic acid trimethylammonium ethyl chloride copolymer 25 Sodium fluoride 0.07 Triethyl citrate 10 Ethanol 50 Water 14.93 Acrylic A viscous solution is obtained by dissolving ethyl acetate / methyl methacrylate / methacrylic acid / trimethylammonium ethyl chloride copolymer with 2 times the weight of lower alcohol. Next, triethyl citrate and an aqueous solution of sodium fluoride were added thereto, and the mixture was stirred until it became uniform to obtain a sodium fluoride compounding agent.

[0039]

[Table 6] As is clear from the results in Table 6, the composition of Example 5 was
It was confirmed that the fluorine was gradually released. From this, it was found that it is effective in preventing dental caries.

Example 6 Ingredients Amount (wt%) Ethyl acrylate / Methyl methacrylate / methacrylic acid Trimethylammonium ethyl chloride copolymer 20 Triethyl citrate 10 Ethanol 55 Chlorhexidine 0.1 Saccharin sodium 0.1 l-ment -Le 0.1 Water balance

Example 7 Component Content (wt%) Methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, 10 triethyl citrate 5 isopropanol 70 cetylpyridinium chloride 0.1 saccharin atrium 0.1 l-menthol 0.1 water balance

Example 8 Ingredients Content (% by weight) Methacrylic acid / ethyl acrylate copolymer 20 Triethyl citrate 5 Ethanol 70 Chlorhexidine 0.1 Saccharin atrium 0.1 l-menthol 0.1 Water balance

[0043]

INDUSTRIAL APPLICABILITY By applying it in the oral cavity, a uniform film can be formed in a short time, and the formed film adheres extremely well to soft and hard tissues, especially dentin, and can be formed in water or saliva. Maintains high adhesion even inside. When it is used as a hypersensitivity suppressor, a uniform film is selected by drying the tooth surface and applying it with a brush, etc. It is more effective than the above film forming agents.

[Brief description of drawings]

FIG. 1 is a plan view schematically showing a rubber band to which a sample of a test composition is applied in a flexibility test.

─────────────────────────────────────────────────── ─── Continuation of the front page (51) Int.Cl. ⁶ Identification code Internal reference number FI Technical display area A61K 47/32 A61K 47/32 N

Claims (11)

[Claims] 1. A long-term retention type base for the oral cavity, which comprises an acrylic polymer soluble in a lower alcohol, a fatty acid alcohol ester and a lower alcohol. 2. The acrylic polymer is methyl methacrylate / butyl methacrylate / dimethylaminoethyl methacrylate copolymer, methacrylic acid / ethyl acrylate copolymer, methacrylic acid / methyl methacrylate copolymer, and The oral long-term retention type base according to claim 1, which is selected from ethyl acrylate / methyl methacrylate / trimethylammonium methacrylic acid ethyl acrylate copolymer. 3. The acrylic polymer is ethyl acrylate.
The long-term retention base for oral cavity according to claim 1, which is a methyl methacrylate / trimethylammonium methacrylic acid ethyl copolymer. 4. The amount of acrylic polymer compounded is 10 to 30.
The long-term retention type base for oral cavity according to claim 1, which is a weight%. 5. The long-term retention base for oral cavity according to claim 1, wherein the blending ratio of the acrylic polymer and the fatty acid alcohol ester is acrylic polymer / fatty acid alcohol ester = 2/1 to 3/2. 6. The long-term oral retention type base according to claim 1, wherein the fatty acid alcohol ester is selected from triethyl citrate and triacetin. 7. The long-term retention type base for oral cavity according to claim 1, wherein the blending amount of the lower alcohol is 20 to 70% by weight. 8. The long-term retention base for oral cavity according to claim 1, wherein the blending amount of the lower alcohol is 40 to 60% by weight. 9. The long-term retention base for oral cavity according to claim 1, wherein the lower alcohol is selected from ethanol and isopropanol. 10. A liquid form according to claim 1.
The long-term retention type base for the oral cavity described. 11. A composition for oral cavity for preventing dental caries, which comprises the base according to claim 1 and fluorine.