JP2003221320A - Composition for oral use - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide composition for oral use which effectively exerts a bactericidal action of a cationic bactericide within the oral cavity, is extremely effective for preventing and improving tooth decay, peridontal diseases, stench, or the like, and exerts an excellent shelf stability at low temperatures. <P>SOLUTION: This composition for oral use is a sol-gel transition preparation containing a cationic bactericide and a temperature-sensitive polyoxyethylene/ polyoxypropylene block copolymer surfactant. Here, the polyoxyethylene/ polyoxypropylene block copolymer surfactant is a combined system of (A) a surfactant wherein the polyoxyethylene portion accounts for 75-85% of the total molecular weight and the polyoxypropylene portion has a molecular weight of 2,000-2,500 and (B) a surfactant wherein the polyoxyethylene portion accounts for 65-75% of the total molecular weight and the polyoxypropylene portion has a molecular weight of 3,400-4,300. The compounding ratio of (B) to (A) is 2-30%, and the total amount of surfactants (A) and (B) accounts for 10-25 wt.% of the composition for oral use. The sol-gel transition temperature is within the range of 20-45°C. <P>COPYRIGHT: (C)2003,JPO

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a sol-gel transition type oral composition containing a cationic bactericide. More specifically, the bactericidal action of the cationic bactericide is effectively exerted in the oral cavity, which is effective in preventing and improving caries, periodontal disease, halitosis, etc., and also has storage stability under low temperature conditions. It relates to a good sol-gel transition type oral composition.

[0002]

2. Description of the Related Art Conventionally, a cationic bactericide has been blended with oral compositions such as toothpaste and mouthwash. Typical examples of the cationic bactericide include cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride, etc., which prevent caries, periodontal diseases, halitosis, etc.
Formulated for improvement. In this type of cationic fungicide-containing oral composition, it is possible to easily spread the formulation to every corner of the oral cavity, and further, when considering prevention of oral diseases, the formulation that has penetrated to every corner remains for a long time. Therefore, it is necessary to exert a bactericidal effect. However, a medicinal component such as a cationic bactericide generally has a low retention property in the oral cavity, and particularly in a liquid dosage form such as a mouthwash, the drug is squeezed into the oral cavity by spitting or swallowing after the mouthwash. However, it is the current situation that improvement of the sustainability of drug efficacy is desired.

[0003] By the way, many methods have been proposed for improving the local retention of liquid preparations and enhancing the duration of drug effect. Among them, the technology of temperature-sensitive sol-gel transition preparation is well known. The temperature-sensitive sol-gel transition preparation is a reversible thermogelling preparation that gels when applied topically to mucous membranes, and is a technique applied to, for example, an oral ointment. Generally, a temperature-sensitive sol-gel transition preparation is prepared by blending an aqueous composition with a gelling agent such as a temperature-sensitive polymer compound. As a typical gelling agent, a temperature-sensitive polyoxyethylene / polyoxypropylene block copolymer-based surfactant is known. This product is preferred because of its excellent surface-active ability and safety.

On the other hand, however, it is known that the antibacterial activity of a cationic fungicide such as cetylpyridinium chloride and a nonionic surfactant are simultaneously reduced (Journal of the American Farr). Mathematical Association (Journal of
the American Pharmaceutical
al Association); Volume 49, No. 7
No., 1960). Polyoxyethylene / polyoxypropylene block copolymer-based surfactant is a typical nonionic surfactant, for example, cetylpyridinium chloride and polyoxyethylene / polyoxypropylene block copolymer-based surfactant In the sol-gel transition preparation combined with the name "Pluronic F-108" (manufactured by BASF), the antibacterial activity of cetylpyridinium chloride is impaired.
It is disclosed in Comparative Example 2 of Japanese Patent Publication No. 79. In the case of a sol-gel transition preparation using a polyoxyethylene / polyoxypropylene block copolymer-based surfactant, the active agent is precipitated when it is stored at a low temperature of about 5 ° C or lower or when the liquid agent is frozen at a low temperature. There was also a problem in terms of low temperature stability.

As described above, in the prior art, the sol-gel transition type oral composition containing a cationic bactericide and a temperature-sensitive polyoxyethylene / polyoxypropylene block copolymer surfactant is It was difficult to provide the antibacterial activity of the bactericide with good storage stability at low temperature.

[0006]

The present invention provides a sol-gel transfer agent type oral composition containing a cationic bactericide and a temperature-sensitive polyoxyethylene / polyoxypropylene block copolymer surfactant. It is an object of the present invention to provide an improved oral composition in which the activity of a cationic bactericide is exhibited and the low-temperature stability of the preparation is good.

[0007]

The present inventors have completed the present invention as a result of intensive studies to solve the above problems. According to the studies by the present inventors, the oral composition of the present invention is liquid at room temperature and becomes gel-like, that is, non-fluid (semi-solid) when heated to human body temperature, resulting in high oral cavity. Shows internal retention. Further, it spreads to every corner where the medicinal component is hard to penetrate, and exhibits local retention of the medicinal component. It also has excellent low temperature sound stability.

That is, according to the present invention, there is provided a sol-gel transition preparation containing a cationic bactericidal agent and a temperature-sensitive polyoxyethylene / polyoxypropylene block copolymer surfactant, which comprises the following (I) to ( An oral composition having the characteristics of II) is provided. (I) The polyoxyethylene / polyoxypropylene block copolymer-based surfactant is an interface in which the proportion of the polyoxyethylene portion in the total molecular weight is 75 to 85% and the molecular weight of the polyoxypropylene portion is 2,000 to 2,500. In the two-use combination system of the activator (A) and the surfactant (B) in which the proportion of the polyoxyethylene portion in the total molecular weight is 65 to 75% and the molecular weight of the polyoxypropylene portion is 3,400 to 4,300. Yes, the mixing ratio of (B) to (A) is 2 to
Within the range of 30%, and the surfactants (A) and (B)
Is 10 to 25% by weight of the oral composition. (II) The sol-gel transition temperature is in the range of 20 to 45 ° C.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION The oral composition of the present invention comprises a cationic bactericidal agent and two kinds of polyoxyethylene / polyoxypropylene block copolymer surfactants.
The composition has a gel transition temperature T (G) in the range of 20 to 45 ° C., shows a liquid state at a temperature lower than the T (G), and a gel at a temperature higher than the T (G). It shows the state.

Examples of the cationic bactericide used in the present invention include various kinds of cationic bactericides known in the field of oral drugs and oral cosmetics. Specifically, cetylpyridinium chloride, benzethonium chloride, benzalkonium chloride, chlorhexidine hydrochloride and gluconate, alkylbenzyldimethylammonium chloride having 8 to 18 carbon atoms in the alkyl group, and 8 to 8 carbon atoms in the alkyl group.
Alkyldimethylammonium chloride of 22 and the like can be mentioned. These 1 type can be used individually or in combination of 2 or more types. The amount of the cationic bactericide compounded is 0.005 to 5%, particularly 0.01 to 0.
It is preferably 5%.

The polyoxyethylene / polyoxypropylene block copolymer-based surfactant has a general formula: HO
(C2H4O) a- (C3H6O) b- (C2H4O)
It is expressed in cH. In the formula, a, b and c represent arbitrary integers. Of these, in the present invention, the temperature-sensitive polyoxyethylene / polyoxypropylene block copolymer surfactants (A) and (B) are used in combination.

The first surfactant (A) has a polyoxyethylene portion in the total molecular weight of 75 to 85% and a polyoxypropylene portion of 2,000 to 2,500.
Is a polyoxyethylene / polyoxypropylene block copolymer surfactant. A typical specific example thereof is polyoxyethylene (200) polyoxypropylene glycol (40), which is sold under the trade name of Pluronic F-88 or the like by BASF Japan and the like.

The second surfactant (B) has a polyoxyethylene portion in the total molecular weight of 65 to 75% and a polyoxypropylene portion of 3,400 to 4,300.
Is a polyoxyethylene / polyoxypropylene block copolymer surfactant. A typical example thereof is polyoxyethylene (200) polyoxypropylene glycol (70), and Pluronic F-12
7, trade names such as Lutrol F-127 and Poloxamer 407 are sold.

The mixing ratio of the surfactant (B) to the surfactant (A) is in the range of 2 to 30% (mass percentage, the same applies hereinafter). If it is less than 2%, problems such as the formation of precipitates will occur when stored at low temperature, and if it exceeds 30%, the effect of the cationic bactericide will be significantly impaired. next,
The total content of the surfactant (A) and the surfactant (B) is preferably 10 to 25% by weight of the total oral composition. If it is less than 10%, the composition does not show sol-gel transition, and if it exceeds 25%, the effect of the cationic bactericide is significantly reduced.

The oral composition of the present invention is a liquid preparation such as mouthwash, preparation for periodontal pocket, liquid dentifrice, mouth freshener,
In addition, it can be prepared as a detergent, an aqueous gel base for the oral cavity and the like.

The oral composition of the present invention comprises, in addition to the above essential components, optional components such as thickeners, binders, sweeteners, preservatives, fragrances, and colorings in a quantitative range that does not impair the effects of the present invention. Agent,
Additives such as surfactants and abrasives and other medicinal components can be added.

As the thickening agent, glycerin, sorbit, propylene glycol, polyethylene glycol,
Xylit, maltite, lactit, etc. may be blended.
Examples of the binder include sodium carboxymethyl cellulose, hydroxyethyl cellulose, carrageenan, sodium alginate, xanthan gum, garbopol,
Gua gum, montmorillonite, gelatin and the like may be added. As the sweetening agent, sodium saccharin, stevioside, stevia extract, paramethoxycinnamic aldehyde, neohesperidyl dihydrochalcone, perillartin and the like can be blended. As the preservative, paraoxybenzoic acid ester, sodium benzoate, etc. may be added.
As the fragrance, various fragrance components known in the fields of oral cosmetics and food can be blended. As a colorant, blue 1
No. 4, yellow No. 4, titanium dioxide, alumina oxide, etc. may be blended.

As the surface active agent, an anionic surface active agent, a cationic surface active agent, a nonionic surface active agent or the like may be blended, and specifically, sodium lauryl sulfate, α-
Sodium olefin sulfonate, N-acyl sarcosinate, N-acyl glutamate, 2-alkyl-N-
Carboxymethyl-N-hydroxyethylimidazolinium betaine, N-acyl taurate, sucrose fatty acid ester, alkyl amide, polyoxyethylene hydrogenated castor oil, polyglycerin fatty acid ester, polyoxyethylene sorbitan monostearate, etc. It may be blended.

As the medicinal component, sodium fluoride, potassium fluoride, ammonium fluoride, stannous fluoride,
Fluorides such as sodium monofluorophosphate, potassium salts of orthophosphoric acid, water-soluble phosphate compounds such as sodium salts, allantoinchlorohydroxyaluminum, lysozyme chloride, glycyrrhizic acid and its salts, sodium chloride, epsilon aminocaproic acid, α-Bisaborol, isopropylmethylphenol, azulene, water-soluble azulene, glycyrrhetinic acid, dipotassium glycyrrhizinate, copper chlorophyllin sodium, copper compounds such as copper gluconate, aluminum lactate, strontium chloride,
Potassium nitrate, berberine, hydroxamic acid and its derivatives, sodium tripolyphosphate, zeolite, dextranase, mutanase, amylase, methoxyethylene, maleic anhydride copolymer, polyvinylpyrrolidone, epidihydrocholesterine, dihydrocholesterol-
In addition, extracts such as red, trichlorocarbanilide, zinc citrate, soft extract of Toki, clove, rosemary, sardine, safflower and the like may be blended.

[0020]

INDUSTRIAL APPLICABILITY The sol-gel transition type oral composition of the present invention exhibits the bactericidal action of a cationic bactericide effectively in the oral cavity, and is effective in preventing and improving dental caries, periodontal disease, halitosis and the like. It is extremely effective. It also has excellent storage stability under low temperature conditions.

[0021]

EXAMPLES Next, the present invention will be described in more detail by way of examples.

[Examples 1 to 3 and Comparative Examples 1 to 5] Liquid formulations having the following compositions and containing the pluronic amount shown in Table 1 were prepared, and the sol-gel transition temperature was measured and the bactericidal activity was measured according to the following methods. Tests and low temperature stability evaluations were performed. The results are shown in Table 1.

[Composition] Pluronic Content in Table 1 Cetylpyridinium chloride 0.05% Ethanol 5.5% β-Glycyrrhetinic acid 0.025% Sorbitol 7.0% Glycerin 11.0% Sodium benzoate 0.3% Quen Acid 0.05% Sodium citrate 0.3% Perfume 0.6% Purified water Balance 100.0%

[Measurement of sol-gel transition temperature] 4 mL of each of the prepared liquid preparations was placed in a test tube with a stopper, and the temperature was gradually raised in the cornix. After standing for 10 minutes, the test tube was tilted to determine whether it gelled and did not flow. The temperature at which the sample did not flow was defined as the sol-gel transition temperature.
The judgment was based on the following criteria. ◯: Within transition temperature range of 20 to 45 ° C. ×: No transition temperature or transition temperature of 20 to 45
Out of range

[Bactericidal test] Each liquid preparation is diluted 1.5 times with phosphate buffer (pH 7.0) and kept at 37 ° C. Per 1 mL of this solution, Porphyromonas gingivali (Porphyromonas gingivali)
s) ATCC 33277 bacteria (hereinafter, P.G bacteria abbreviated) is a bacterial solution so that the ¹⁰ 8 CFU addition, 37 ° C., after kept for 5 minutes, Todd immediately added hemin, menadione
Hebit Broth (TODD HEWIT BROT
H, abbreviated as THB hereinafter) 10-fold serial dilution in liquid medium. 0.05 mL of each diluted solution is spread on a THB blood agar plate to which hemin and menadione are added. Each THB blood agar plate was cultured under anaerobic conditions at 37 ° C. (nitrogen gas / hydrogen gas / carbon dioxide = 80/10/10) for 6 days, and then the viable cell count was measured. The sterilizing power evaluation criteria are shown below. ○: viable cell number ¹⁰ 5 CFU / mL or less △: viable cell number ^{10 5 CFU / mL~10 7 CFU /} mL ×: viable cell number ¹⁰ 7 CFU / mL or more

[Evaluation of stability at low temperature] Each liquid preparation was tested at -10 ° C.
After storing for 1 week under the temperature conditions of
The low temperature stability was evaluated. The judgment was based on the following criteria. ○: No change ×: Precipitate

[0027]

[Table 1]

Preparations containing cetylpyridinium chloride having a Pluronic content of 25% or more, or F-
When the compounding amount of F-127 with respect to 88 was not within the range of 2 to 30%, good results were not obtained in either sterilizing power or low temperature stability. On the other hand, the amount of Pluronic compounded is in the range of 10 to 25%, and F to F-88 is
It was confirmed that the sol-gel transition preparation containing -127 in the range of 2 to 30% had good bactericidal activity and low-temperature stability. As the results of Comparative Example 1 show, the cetylpyridinium chloride aqueous solution has a high bactericidal activity.

[0029] This composition had a sol-gel transition temperature in the range of 25 to 45 ° C, and had good bactericidal activity and low-temperature stability.

[0030] This composition had a sol-gel transition temperature in the range of 25 to 45 ° C, and had good bactericidal activity and low-temperature stability.

[0031] This composition had a sol-gel transition temperature in the range of 25 to 45 ° C, and had good bactericidal activity and low-temperature stability.

[0032] This composition had a sol-gel transition temperature in the range of 25 to 45 ° C, and had good bactericidal activity and low-temperature stability.

[0033] This composition had a sol-gel transition temperature in the range of 25 to 45 ° C, and had good bactericidal activity and low-temperature stability.

[0034] This composition had a sol-gel transition temperature in the range of 25 to 45 ° C, and had good bactericidal activity and low-temperature stability.

Continued front page    F-term (reference) 4C083 AA112 AC102 AC122 AC132                       AC302 AC472 AC482 AC622                       AC691 AC692 AC741 AC742                       AC812 AC862 AD042 AD051                       AD532 AD552 BB41 BB48                       CC41 DD23 DD41 EE01 EE32                       EE33 EE34

Claims (2)

[Claims] 1. A sol-gel transition preparation containing a cationic bactericide and a temperature-sensitive polyoxyethylene / polyoxypropylene block copolymer-based surfactant, which has the following characteristics (I) to (II): Oral composition. (I) The polyoxyethylene / polyoxypropylene block copolymer-based surfactant is an interface in which the proportion of the polyoxyethylene portion in the total molecular weight is 75 to 85% and the molecular weight of the polyoxypropylene portion is 2,000 to 2,500. In the two-use combination system of the activator (A) and the surfactant (B) in which the proportion of the polyoxyethylene portion in the total molecular weight is 65 to 75% and the molecular weight of the polyoxypropylene portion is 3,400 to 4,300. Yes, the mixing ratio of (B) to (A) is 2 to
Within the range of 30%, and the surfactants (A) and (B)
Is 10 to 25% by weight of the oral composition. (II) The sol-gel transition temperature is in the range of 20 to 45 ° C. 2. The oral cavity according to claim 1, wherein the cationic bactericide is one or more selected from the group consisting of cetylpyridinium chloride, benzalkonium chloride, benzethonium chloride and chlorhexidine hydrochloride. Composition.