JPH04202121A - Cetylpyridinium chloride-containing antimicrobial composition for oral cavity - Google Patents

Abstract

PURPOSE:To obtain a composition for the oral cavity having good properties by stably blending a specific polyoxyethylene.polyoxypropylene block copolymer in the composition. CONSTITUTION:A composition for the oral cavity is obtained by blending a polyoxyethylene.polyoxypropylene block copolymer having <=0.3 incorporation coefficient of micelles in cetylpyridinium chloride, i.e., the block copolymer having 950-2250 molecular weight and the ratio of the polyoxyethylene occupied in the whole molecular weight within the range of 70-80wt.% in an amount in the composition of 0.01-15wt.%, preferably 0.05-13wt.%. The amount of the cetylpyridinium chloride in the aforementioned composition is within the range of 0.001-5wt.%, preferably 0.01-0.5wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION The present invention relates to an oral composition, and more particularly to an oral composition containing cetylpyridinium chloride, a cationic bactericide, as an active ingredient.

BACKGROUND OF THE INVENTION Cetylpyry/nium chloride is a cationic bactericide that is effective in inhibiting plaque formation, and its inclusion in oral compositions has been proposed. However, since cetylpyridinium chloride is cationic, when combined with anionic components in oral compositions, it may cause electrical reactions and impair antibacterial activity.

Furthermore, in order to prevent such electrical inactivation of antibacterial activity, it has been proposed to use a combination with a nonionic surfactant, for example. However, whether there is any electrical inactivation in such a combination, as reported in the Journal of the American Pharmaceutical Association (Journa),
l of the American Pharmace
utical As5ocation), Volume 49, N
There is a problem in that nonionic surfactants such as polyoxyethylene sorbitan fatty acid esters combine with cetylpyridinium chloride, which is accompanied by a decrease in antibacterial activity, as disclosed in U.S. Pat. No. 0,7 (+960).

The present inventors have further investigated how to solve this problem and maintain the antibacterial activity of cetylpyridinium chloride in the composition stably, and by blending a specific polyoxyethylene/polyoxypropylene block copolymer, the objective The present inventors have discovered that this can be achieved, and have completed the present invention.

As a means for solving the problem, the present invention provides cetylpyridinium chloride, which is characterized in that it contains a polyoxyethylene polyoxypropylene block copolymer having a micelle uptake coefficient of cetylpyridinium chloride of 03 or less. The present invention provides an antibacterial oral composition containing Nium/Nium.

The polyoxyethylene/polyoxypropylene/mbro, wolfberry copolymer surfactant used in the present invention is a well-known surfactant consisting of polyoxy/ethylene/polyoxypropylene glycol, and is manufactured by BASF Corporation in the United States as "PLURONIC". )j.This surfactant is generally
It is chemically defined by the weight percent of the polyethylene propylene aqueous portion and polyethylene ethylene hydrophilic portion in the total molecular weight. In the present invention, in particular, the micelle has an uptake coefficient of cetylpyrinnium chloride of 0.3 or less, that is, the amount of water groups (polyoxypropylene) is 950 to 2250, The proportion of hydrophilic groups (polyoxy/ethylene) in the total molecular weight is 70-80
% by weight.

Here, the micelle uptake coefficient for cetylpyrinnium chloride (hereinafter sometimes abbreviated as OPC) is defined as follows. According to the method described below, the amount of free CPC (not incorporated into the active agent micelles) and the amount of bound CPC (incorporated into the active agent micelles) at various concentrations of cetylpyri chloride/:-ram was determined using a ≧16 permeable membrane. Measure free CI) C? #l! The horizontal axis is the reciprocal of degrees, and the bond C
When plotted on a graph with the reciprocal of the PC amount as the vertical axis, it becomes a straight line, and the following formula: % formula % [In the formula, Cbx is CPCffi taken into the micelles
g/activator g), C[ is C not incorporated into micelles.
The inverse Langmuir adsorption equation is applied to the PC concentration (g/K, where K refers to the distribution coefficient of CPC between the micelles and the aqueous phase). is called the incorporation coefficient.

In the present invention, such polyokine ethylene/polyokine propylene block Kobori? - 0.01 to 15% by weight of a surfactant in the composition, preferably about 0.05 to 1.0% by weight;
Blend at 3% by weight. The blending concentration of the surfactant is 0.0
If it is less than 1% by weight, desired solubilizing ability and foaming ability cannot be obtained.

On the other hand, if it is 15% by weight or more, the viscosity of the composition increases by 20%, making it impossible to obtain desired properties.

CPC used as an active ingredient of the present invention is usually 0.001 to 5% by weight, preferably about 0.001 to 5% by weight, based on the total amount of the composition.
It is blended in a proportion of 01 to 05% by weight.

If the amount is less than 0.001% by weight, sufficient sterilizing power will not be exhibited, and if it is more than 5% by weight, it will be irritating to the oral mucous membranes, causing problems in practical use.

The oral composition of the present invention can be made into a dosage form such as a mouthwash, pasta, or toothpaste according to a conventional method. and other medicinal agents may be appropriately incorporated within the range that does not impair the effects of the present invention.

EXAMPLES The present invention will be explained in more detail by the following experiments and examples.

The uptake coefficient for CPC was determined for various polyoxyethylene/polyoxypropylene bronocopolymer surfactants, and its influence on CI) C antibacterial activity was investigated using the method shown below.

[Determination of uptake coefficient for CPC The concentration of free CI (co-active agent, not incorporated into micelles) was determined by equilibrium membrane dialysis. This method uses pertyl and phos(
Patel & Foss). The dialysis cell consists of two Pyrex glass chambers (1, , R), each with a cavity of 60 ffC capacity. The dialysis crotch to be used is one that is permeable to CI') C molecules or non-permeable to active agent micelles (dialysis cello tube, manufactured by Hirai, fractionated molecules). ff18000), which was installed between two chambers with cavities facing each other.

Each chamber was securely fixed to each other at three locations with stainless steel Pol I and wing nuts.

An aqueous solution of each surfactant (3%) in Table 1 containing CPC (40, 100, 200 ppm) was injected into chamber R, and distilled water was injected into chamber L. The injection port of each chamber was plugged, stirred with a stirrer in a constant temperature bath at 25 °C, and after 3 days, each chamber (1:) CP C
a degree has reached equilibrium. Then, samples were taken from chambers L and R, respectively, and the spectrophotometer was 258% at t1.
The free CPC concentration and bound CPC amount were determined by measuring the absorbance at m.

That is, the free CPC concentration represents the concentration in chamber L, and the degree of bound CPC7j is defined as the concentration in chamber R minus the mustard concentration. The obtained data are then plotted as the reciprocal of the degree of bound CPCa (1/Cbx) on the vertical axis and the total free CP (reciprocal of 44 degrees (1/CI') on the horizontal axis (Fig. 1). Ngmuir adsorption etc.i! The uptake coefficient of each surfactant to CPC was determined using Equation 171. The results are shown in Table 1.

[Bactericidal power test] Various surfactants were weighed so that the concentration was 3%, 0.02%, 0.01%, 0008%, 0.006%.
, 0.004%, 0.002%, 0.001%, 0.0
0.005% and 0.0002% CPC aqueous solution to prepare a sample solution.

On the other hand, CPC was dissolved in distilled water, 0.001% and 0.001%, respectively.
．． MB with concentrations of 0.0005% and 0.0002%
It was used as a standard for C measurements.

Using the usual agar dilution method, the MBC (minimum bactericidal concentration) of each sample solution was examined for Streptococcus mutans + Fo13955 strain, which is a type of plaque-forming bacteria. The results are shown in Table 1.

As is clear from Table 1, the smaller the hydrophobic molecular weight of the polyoxyethylene/polyoxypropylene block copolymer surfactant, and the larger the proportion of hydrophilic groups in the total molecular weight, the higher the uptake coefficient for CI)C. small,
It has been found that those with an uptake coefficient of 0.3 or less do not particularly impair the antibacterial activity of CPC.

Example 1 [Mouthwash] A δL oral preparation was prepared according to a conventional method using the following formulation.

Ingredients Amount (wt%) Cetylpyrinnium chloride 01 Pluronic F-68
1,2 Average degree of polymerization: ethylene oxide 150 propylene oxide 30 CI) C uptake coefficient 0073 Ethanol 10.0 Concentrated glycerin 70 Sodium saccharin 0.1 Flavor
The composition of Example 1 prepared at 02 Purified Water 100 showed good antibacterial activity.

Example 2 [Toothpaste] A toothpaste was prepared according to a conventional method using the following formulation.

Ingredients Amount (wt%) Cetylpyridinium chloride 02 Pluronic F-77
10.0 Average degree of polymerization: ethylene oxide 104 propylene oxide 35 CPC uptake coefficient: O, I50 carbonic acid 35.0 sorbitol 30.0 saccharin sodium 02 hydroxyethyl cellulose
1.5 Fragrance Purified Water 100 The composition of Example 2 also showed good antibacterial activity.

Effects of the Invention According to the present invention, a single-lumen composition having good properties in which cetylpyridinium chloride is stably blended can be obtained.

[Brief explanation of the drawing]

FIG. 1 is a graph showing the relationship between the reciprocal of the free 14 CPC concentration and the reciprocal of the bound CPC amount of various polyoxyethylene/polyquine propylene block copolymer surfactants.

Claims (1)

[Claims] (1) An antibacterial oral cavity composition containing cetylpyridinium chloride, which contains a polyoxyethylene/polyoxypropylene block copolymer having a micelle uptake coefficient of cetylpyridinium chloride of 0.3 or less.