JP2002068971A - Gingivitis improving composition - Google Patents

Abstract

(57) [Problem] To provide a gingivitis-improving composition in which a bactericide for the purpose of preventing gingivitis is sufficiently exerted to effectively reach the gingival sulcus. SOLUTION: This gingivitis-improving composition is obtained by using a long-chain glyceryl ether represented by the following general formula (I) in combination with a nonionic fungicide. R ¹ OCH ₂ CH (OH) CH ₂ OH (I) (wherein, R ¹ represents a saturated or unsaturated aliphatic group having 8 to 16 carbon atoms)

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a gingivitis-improving composition having a high permeability to a gingival sulcus and having excellent bactericidal properties against bacteria in the sulcus. The gingivitis-improving composition of the present invention can provide a gingivitis-improving product such as an interdental film composition, dental cream, or a liquid preparation for mucosal administration for the purpose of preventing gingivitis.

[0002]

2. Description of the Related Art Conventionally, various medicinal components such as a bactericide and a cell activator have been incorporated into periodontal pocket osmotic preparations, dentifrices and mouthwashes for the purpose of preventing gingivitis. The target site for these drugs is the gingival margin, which is the first site of periodontal disease, especially in the opening of the sulcus, and it is known that ensuring the penetration of the drug into the gingival sulcus is the key to preventing gingivitis. Have been. However, the gingival sulcus is always filled with gingival sulcus exudate, and moreover, seepage from the inside of the living body to the oral cavity occurs. For this reason, it has been difficult to allow a sufficient amount of the medicine in a normal dentifrice or mouthwash to reach the inside of the gingival sulcus.

[0003]

SUMMARY OF THE INVENTION It is an object of the present invention to provide a gingivitis-improving composition which can sufficiently exhibit the effect of effectively allowing a bactericide to prevent gingivitis to reach the gingival sulcus. I do.

[0004]

Means for Solving the Problems The present inventors have made intensive studies to solve the above-mentioned problems, and as a result, the following general formula (I)
In combination with a long-chain glyceryl ether represented by the formula (1) and a nonionic fungicide, especially triclosan and / or biosol, the penetration of the fungicide into the gingival sulcus is increased, and a sufficient bactericidal effect against bacteria in the gingival sulcus can be exhibited. The present inventors have found that a composition for oral cavity osmotic permeability can be obtained, and have accomplished the present invention. That is, the present invention provides a gingivitis-improving composition comprising a combination of a long-chain glyceryl ether represented by the following general formula (I) and a nonionic fungicide. R ¹ OCH ₂ CH (OH) CH ₂ OH (I) (wherein, R ¹ represents a saturated or unsaturated aliphatic group having 8 to 16 carbon atoms)

[0005]

BEST MODE FOR CARRYING OUT THE INVENTION The present invention will now be described in more detail. The composition for improving gingivitis of the present invention (hereinafter also simply referred to as "composition") comprises an interdental film, a dental cream, and a liquid preparation for mucosal administration. It can be prepared as a gum massage agent or the like, and contains the long-chain glyceryl ether represented by the general formula (I) and a nonionic fungicide.

The long-chain glyceryl ether used in the present invention is
In the above general formula (I), R ¹Is saturated or unsaturated
An aliphatic group having 8 to 16, preferably 10 to 14 carbon atoms
Show. In this case, the aliphatic group includes an alkyl group and an alkyl group.
Nyl groups are included.

In the general formula (I), the long-chain alkyl (or alkenyl) glyceryl ether is obtained, for example, by subjecting the corresponding glycidyl ether to ring-opening hydrolysis of an epoxy ring using an acid catalyst in the presence of acetone and water. (JP-A-9-124532) and a method of reacting a long-chain aliphatic sulfate with a dioxolane derivative of glycerin in the presence of a basic catalyst (JP-A-9-295994).
Publication), a method of reacting glycerin carbonate with an alcohol, and the like.

Specific examples of the long-chain alkyl (or alkenyl) glyceryl ether include, for example, methyl glyceryl ether, ethyl glyceryl ether, propyl glyceryl ether, isopropyl glyceryl ether, butyl glyceryl ether, isobutyl glyceryl ether, pentyl glyceryl ether, Hexyl glyceryl ether, heptyl glyceryl ether, octyl glyceryl ether, nonyl glyceryl ether, decyl glyceryl ether, dodecyl glyceryl ether, tetradecyl glyceryl ether, hexadecyl glyceryl ether, octadecyl glyceryl ether,
Oleyl glyceryl ether, octadecyl trioxy glyceryl ether, icosyl glyceryl ether, docosyl glyceryl ether and the like can be mentioned.

In the present invention, triclosan and / or biosol are preferably selected as the nonionic fungicide to be used in combination with the long-chain glyceryl ether, but carvacrol such as thymol, cresol, biosol, hinokitiol and the like are preferred. There can be. In general, any nonionic germicide can be used in combination without being limited to the above germicides.

In the present invention, the mixing ratio of the nonionic fungicide to the long-chain glyceryl ether is from 1/2 to 1 by mass.
/ 200, preferably 1/10 to 1/5
It is in the range of 0.

The amount of the nonionic fungicide used in the present invention is preferably 0.005 to 1%, particularly preferably 0.01 to 0.5%. If the content is more than 1%, a peculiar off-odor and off-flavor may occur, and if less than 0.005%, sufficient bactericidal activity is not produced.

The composition of the present invention is applied in a dosage form such as an interdental insertion film, a dental cream, a liquid preparation for mucosal administration, a gum massage agent, etc., depending on the dosage form, in addition to the above essential components. Various additives can be blended as optional components.

In the case of an interdental insertion film, specific examples of the water-soluble polymer used as the film base include:
For example, non-ionic water-soluble polymers such as methylcellulose, hydroxypropylcellulose, cellulose lower alkyl ether compounds such as hydroxypropylmethylcellulose, polyvinylpyrrolidone, vinyl compounds such as polyvinyl alcohol, pullulan, polysaccharides such as starch and derivatives thereof, polyacrylamide , Polyethylene oxide, polyoxyethylenes such as high-molecular-weight polyethylene glycol; anionic water-soluble polymers such as carboxypinyl polymer, salts such as carboxymethylcellulose and carboxymethylcellulose calcium, salts such as polyacrylic acid and sodium polyacrylate, and alginic acid , Sodium alginate, ammonium alginate,
Salts such as triethanolamine alginate, copolymers obtained by copolymerizing tragacanth, methacrylic acid, styrene or vinyl-type ethanol monomers with acrylic acid, and salts thereof; polypeptides such as gelatin, guar gum, and gum arabic as other water-soluble polymers , Chitin and chitosan.

When controlling the pH of the composition of the present invention, the pH adjuster may be a pharmaceutically acceptable acid or acid.
Any basic substance can be used without any particular limitation. Such substances include, for example, hydrochloric acid, citric acid, acetic acid, tartaric acid, lactic acid, boric acid, sulfuric acid, carbonate, phosphate, ammonia water, sodium hydroxide, ethanolamine, diethanolamine, triethanolamine, sodium chloride Are used.

Further, the composition of the present invention may further contain various additives as required. Examples of these are as follows.

Examples of the plasticizer include polyethylene glycol (molecular weight: 200 to 6000), sorbitol, glycerin, propylene glycol, xylit, 1,3-butylene glycol, ethylene oxide-propylene oxide copolymer, diethyl phthalate, dibutyl phthalate, butyl phthalate. Rubutyl glycolate, ethylene glycol, dipropylene glycol, triacetin and the like.

Examples of the coloring agent include tar dyes such as Blue No. 1 and Red No. 104.

As flavoring agents, natural or synthetic flavors, saccharin, citric acid, fumaric acid, menthol,
Mentha oil, tartaric acid, aspartame and the like.

Examples of the dissolution regulator include higher fatty acids such as shellac, stearic acid and palmitic acid, water-soluble polymers such as ethyl cellulose, and p-types such as Eudragit E, L and S.
Examples thereof include H-sensitive polymers, higher alcohols such as cetanol, and inorganic powders such as titanium oxide.

As the polymer crosslinking agent, magnesium,
Calcium, barium, zinc, copper, iron, aluminum,
Inorganic or organic metal salts having two or more valences such as tin are exemplified.

The shape of the composition of the present invention is appropriately determined depending on the application site. For example, when inserted into a periodontal pocket, the shape is preferably a film, sheet, or rod.

[0022]

Industrial Applicability The gingivitis-improving composition of the present invention is one in which the permeability of a nonionic fungicide into the gingival sulcus is improved, and a sufficient bactericidal power can be exhibited.

[0023]

EXAMPLES Hereinafter, the present invention will be described in detail with reference to experimental examples and examples, but the present invention is not limited to the following examples.

Experimental Example 1 An interdental insertion film-like composition was prepared as follows, and an appropriate amount (about 0.5 g) was inserted into the interdental region by 20 subjects. In this case, the test composition includes a composition having the following composition 1, composition, excluding C ₁₂ alkyl glyceryl ether from the composition of the composition 1 (Composition 2) was prepared, subject 2
0 subjects were randomly assigned according to a random assignment table. The fungicide concentration in the gingival sulcus was measured as follows. Table 1 shows the measurement results. Composition 1: C ₁₂ alkyl glyceryl ether 1.5 (%) triclosan 0.3 polyvinyl pyrrolidone 48 sodium polyacrylate 7 polyacrylic acid 7 propylene glycol 7 perfume 1.0 water balance

(1) Preparation of Composition Each component was added to water and dissolved by stirring. Leave it overnight,
After defoaming, the mixture was cast on a normal glass plate, made uniform in thickness using a doctor knife, air-dried, and then forcibly dried at 40 ° C. to prepare a film-shaped periodontal pocket insertion composition having a thickness of 300 μm.

(2) Measurement of the concentration of the fungicide in the gingival sulcus Thirty minutes after the use of the periodontal pocket insertion composition, periopaper was inserted into the gingival sulcus for 10 seconds to collect gingival sulcus. The amount of the sampled liquid was calculated from the periotron value from a standard curve created in advance. 0.3% methanol on the same perio paper
ml of the solution was added dropwise to extract triclosan, and the triclosan was measured by high performance liquid chromatography under the following conditions. (Analysis conditions) Column: (TSK / gelODS / 80Ts4.6φ)
× 150 mm) Detection wavelength: 280 nm Flow rate: 0.9 ml / min Column temperature: 40 degrees Mobile phase: methanol: water: phosphoric acid (700: 300:
1) (Result of measurement) The concentration of triclosan in the gingival sulcus after 30 minutes is shown below.

[0027]

[Table 1]

[0028] As apparent from Table 1, the composition 1 of the present compositions formulated with C ₁₂ alkyl glyceryl ether and triclosan, whereas triclosan has reached a sufficient amount in the gingival sulcus, for comparison It became clear that a sufficient amount of triclosan did not reach the composition of composition 2.

EXPERIMENTAL EXAMPLE 2 An interdental film composition of composition 1 shown in Experimental Example 1
And its composition 1 to C ₁₂Alkyl glyceryl ether
Prepare the interdental insertion film-like composition, and remove gingivitis.
30 subjects were asked to follow the randomization table
Assigned to random. Use the above composition twice daily in the morning and evening
For one month. The degree of gingivitis is determined by GI (Gi
evaluation). Table below shows the results
Shown in

[0030]

[Table 2]

[0031] As apparent from Table 2, the C ₁₂ alkyl glyceryl ether and composition of composition 1 triclosan was blended, while gingivitis is improved significantly in the composition of the composition 2 for comparison It became clear that sufficient improvement effect was not obtained.

Specific examples of the formulation of the composition of the present invention are shown below. Example 1 (gullet insert film composition) C ₁₂ alkyl glyceryl ether 1.2 (%) Triclosan 0.1 Polyvinyl alcohol 48 Sodium carboxymethyl cellulose 20 cellulose 20 Propylene glycol 9.6 Magnesium chloride 0.4 Perfume 0.2 Water

Example 2 (interdental film composition) C ₁₄ alkyl glyceryl ether 1.5 (%) biosol 0.05 polyvinyl alcohol 45 sodium carboxymethyl cellulose 15 methyl cellulose 18 propylene glycol 10 ascorbic acid 0.4 perfume 2 water remainder

Example 3 (Dental Cream) C ₁₀ Alkyl Glycerin Ether 1.0 (%) Triclosan 0.3 Glycerin 30 Xanthan Gum 1.5 Poly (Na acrylate) 0.9 Saccharin Sodium 0.1 Propylene Glycol 3.0 Fragrance 0. 1 water balance

Example 4 (Dental cream) C ₁₆ alkyl glyceryl ether 0.5 (%) Biosol 0.1 Sorbit (70%) 30 Sodium lauryl sulfate 1.5 CMCNa 2.0 Saccharin sodium 0.1 Propylene glycol 3 Tranexamic acid 0.05 Perfume 1.4 Water balance

Example 5 (Liquid mucosal preparation) C ₁₄ alkyl glyceryl ether 1.2 (%) Triclosan 0.1 Glycerin 5 Denatured alcohol 5 Xylitol 5 Citric acid 0.04 Sodium citrate 0.3 Saccharin sodium 0.1 Methyl paraben 0 .01 Perfume 0.4 Water balance

 ──────────────────────────────────────────────────の Continuing on the front page (72) Inventor Haruki Honjo 1-3-7 Honjo, Sumida-ku, Tokyo Inside Lion Corporation (72) Inventor Toru Yoshii 1-3-7 Honjo, Sumida-ku, Tokyo No. Lion Corporation (72) Inventor Tsuyoshi Terabayashi 1-3-7 Honjo, Sumida-ku, Tokyo F-Term within Lion Corporation (reference) 4C076 AA06 AA09 AA11 AA71 BB23 CC31 DD05 DD23 DD38 DD39 DD41 DD61 EE06 EE09 EE30 EE32 FF34 4C206 AA01 AA02 CA17 CA28 MA02 MA03 MA05 MA77 NA05 ZA67

Claims (2)

[Claims] 1. A gingivitis improving composition comprising a combination of a long-chain glyceryl ether represented by the following general formula (I) and a nonionic fungicide. R ¹ OCH ₂ CH (OH) CH ₂ OH (I) (wherein, R ¹ represents a saturated or unsaturated aliphatic group having 8 to 16 carbon atoms) 2. The gingivitis-improving composition according to claim 1, wherein the nonionic bactericide comprises one or two selected from triclosan and biosol.