JPH0399010A - Pharmaceutical composition - Google Patents

Abstract

PURPOSE:To obtain a pharmacentical composition having remarkably improved aging stability of the active component by compounding a polyglycerol fatty acid ester to a composition containing chlorhexidine hydrochloride or chlorhexidine gluconate. CONSTITUTION:A polyglycerol fatty acid ester is compounded to a composition containing chlorhexidine hydrochloride or chlorhexidine gluconate as active component. The chlorhexidine hydrochloride, etc., are widely used in various pharmaceuticals as a fungicide having high safety. The polyglycerol of the polyglycerol fatty acid ester is a condensate of 6-12 glycerols and the fatty acid is lauric acid, myristic acid, palmitic acid, etc. The amount of the active component such as chlorhexidine hydrochloride is 0.01-1.0wt.% and that of the polyglycerol fatty acid ester is usually 0.1-10wt.%.

Description

DETAILED DESCRIPTION OF THE INVENTION Field of the Invention The present invention relates to pharmaceutical compositions in which chlorhexidine hydrochloride or chlorhexidine gluconate is stabilized.

BACKGROUND OF THE INVENTION Chlorhexidine hydrochloride and chlorhexidine gluconate are highly safe as bactericidal agents and are therefore widely used in various pharmaceutical products. When formulating these pharmaceuticals, for example, in the case of liquid formulations such as veterinary drugs, oil-soluble ingredients such as fragrances, flavoring agents, and cooling agents are dissolved in water or uniformly dispersed to improve the usability. For this purpose, surfactants are added. Surfactants are also included as essential ingredients in external preparations such as creams and lotions in order to emulsify oil components in water. In this case, the surfactant used is a polyoxyethylene surfactant, which is a type of nonionic surfactant (for example, polyoxyethylene hydrogenated castor oil, polyoxyethylene sorbitan monosaccharide, polyoxyethylene hydrogenated monostearate, etc.)
was common.

Problems to be Solved by the Invention However, chlorhexidine hydrochloride and chlorhexidine gluconate become extremely unstable when mixed with polyethylene surfactants, making it difficult to provide consumers with long-term stable products. ．． Means for Solving the Problems As a result of intensive research in order to solve the above-mentioned problems, the present inventors found that Oyaki was used as a nonionic surfactant to be incorporated into preparations containing chlorhexidine hydrochloride or chlorhexidine gluconate. The inventors have discovered that by using polyglycerin as a base, the decomposition of chlorhexidine hydrochloride or chlorhexidine gluconate over time in the preparation is extremely low, and a stable preparation can be obtained, and the present invention has been completed.

That is, the present invention is a pharmaceutical composition in which a polyglycerol fatty acid ester is blended into a composition containing chlorhexidine hydrochloride or chlorhexidine gluconate.

In the present invention, polyglycerin fatty acid esters include polyglycerin condensed with 6 to 12 glycerins, such as lauric acid, myristic acid, palmitic acid,
Esters of fatty acids such as stearic acid, linoleic acid, ricinoleic acid, isostearic acid, and oleic acid can be used. The amount of chlorhexidine hydrochloride or chlorhexidine gluconate is 0.01 to 1.0% by weight. The amount of bonoglycerin fatty acid ester blended varies depending on the amount of oil component blended and whether it is used for emulsification or solubilization, but is usually 0.1 to 10% by weight. In addition, disinfectants (e.g., hinokichi silica, thymol, etc.), sequestrants (e.g., ethylenediaminetetraacetic acid, polyphosphate, etc.), antioxidants (e.g., butylated hydroxyanisole, cyphthylhydroxytoluene, tocopherol, etc.) may be added as necessary. ), anti-inflammatory agents (e.g. glycyrrhetinic acid, dipotassium glycyrrhizinate, etc.), blood circulation promoters (e.g. vitamin E acetate, etc.), anionic surfactants (e.g. sodium lauryl sulfate, N-lauroyl glutamate, etc.), cooling agents. (petrol oil, menthol, etc.), preservatives (ethyl para-benzoate, proyl pro-xybenzoate, etc.), gelling agents (e.g. carboxyvinyl polymers, etc.), oil components (e.g. liquid paraffin, stearic acid). , cetanol, stearyl alcohol, etc.), flavoring agents (e.g., Igenol, Borneoil, etc.), neutralizing agents (e.g., diisobrobanolamine, etc.), polymeric compounds (e.g., sodium anolegate, canolepoxymethinoresenolose sodium) ), electrolytes (e.g., citric acid, nongoic acid, lactic acid, and their salts), solvents (e.g., propylene glycol, ethyl alcohol, purified water, etc.), etc. can be blended within a range that does not impair the effects of the present invention. .

The pharmaceutical composition of the present invention can be prepared by a commonly used method (for example,
It is prepared into various internal and external preparations such as liquids, creams, and gels according to the methods prescribed in the 11th revised Japanese Pharmacopoeia.

Effects of the invention [7J1! 1m, it has become possible to provide a pharmaceutical composition in which the stability of chlorhexidine hydrochloride or chlorhexidine gluconate over time is significantly improved compared to formulations containing conventional polyethylene-based surfactants.

EXAMPLES Hereinafter, the present invention will be explained in more detail with reference to Examples and Test Examples.

Example 1 (Liquid) Precepts Ingredients Chlorhexidine gluconate 1.0g Peppermint oil
1.0g year old Igenol
0.3g party-menthol
0.5g Borneo Il 0
．． 5g decaglycerin monolaurate 10. 0
g Ethyl alcohol 25. 0
g citric acid 0. 05
gPurified water total 1001IL
Echinoreanolenoleminah? A clear solution of gargle was prepared by dissolving chlorhexidine gnoreconate, chlorhexidine, menthol, decaglycerin monolaurate, and citric acid, and adding purified water to the solution.

Example 2 (cream) Ingredients Amount Chlorhexidine hydrochloride 0.1g Liquid paraffin
to. o g stearic acid
4.0g cetanol
3.0g stearyl alcohol
4.0g decaglycerin monomyristate 5.0g propylene glycol to. o Ethyl para-oxybenzoate o. os g brovyl xybenzoate 0. 05 g nongoic acid o. os g purified water total 100g chlorhexidine hydrochloride, liquid paraffin, stearic acid, cetanol,
Stearyl alcohol and decaglycerin monomyristate were heated and dissolved with stirring.

Probylene glycol, ethyl parabenzoate, probil parabenzoate, malic acid and purified water are heated, stirred and dissolved.The solution is added to the heated solution, stirred and mixed to prepare a cream for the skin. Prepared.

Example 3 (Gel) Ingredients Amount Chlorhexidine gluconate 0.1g Vitamin E acetate 0.5 Thymol 0.2 Glycyrrhetinic acid 0.1 Hinokichi Saichiru
0.1 Hexaglycerin monolaurate 5.0 Ethyl alcohol
35.0 Kanole boxy vinyl olevolimer 0
．． 7 Diisopropanolamine 0.7 Purified water Total 100-ethyl alcohol, hexaglycerin monolaurate, hinokichi saichiru, glycyrrhetinic acid, thymol and vitamin E acetate were dissolved with stirring, and purified water, chlorhexidine gluconate and Carboxyvinyl polymer was added and dissolved with stirring. Diisopropanolamine was added to this solution and mixed with stirring to prepare a transparent gel.

Test Example [Preparation of Test Samples Samples and control samples were prepared according to the formulations shown in Table 1. The preparation method is to add polyglycerol fatty acid ester (
In the control sample, 5 parts by weight of polyoxyethylene surfactant), 20 parts by weight of ethyl alcohol, and 0.05 parts by weight of citric acid were added, and the mixture was adjusted to a total of 100 parts by weight with purified water. The obtained formulation was stored in a constant temperature room at 50°C.

[Method for quantifying chlorhexidine hydrochloride or chlorhexidine gluconate] Quantifying chlorhexidine hydrochloride or chlorhexidine gluconate in each sample by liquid chromatography [length 150 mm,
A column with a diameter of 4 mm, IGK-Gel LS410 (trade name, manufactured by Toyo Soda Co., Ltd.) was used, and the column temperature was 50°C.
The mobile phase contained methanol: purified water: sodium launol sulfate: phosphoric acid = 82: 18: 0.5: o. A mixed solution of t was used. UV absorption at 260 nm was measured using a method to determine the remaining amount of chlorhexidine hydrochloride or chlorhexidine gluconate. The results are shown in terms of survival rate.
It is summarized in the table.

Claims (1)

[Claims] (1) A pharmaceutical composition in which a polyglycerol fatty acid ester is blended into a composition containing chlorhexidine hydrochloride or chlorhexidine gluconate.