JPH0260658B2 - - Google Patents

Description

[Detailed description of the invention]

<Industrial Application Field> The present invention relates to a method for stabilizing highly biologically active carpronium halide, particularly carpronium chloride. <Prior art> The present inventor and his family have conducted numerous studies on the pharmacological effects of carpronium chloride.
Clinical application has actually been attempted, and it is now on the market under trade names such as actinamine and flozin. Regarding the method for stabilizing the liquid property, there is Japanese Patent Application Laid-Open No. 143616/1983. <Problems to be Solved by the Invention> However, this method not only has many shortcomings, but also generally has many unresolved problems in stabilizing carpronium chloride. <Means for solving the problems> The present invention contemplates the application of carpronium chloride as a treatment for skin diseases, cosmetics, etc., and in connection with this, a thorough study has been carried out on methods for stabilizing the substance,
We succeeded in discovering individual stabilizers and further promoting stabilization by combining them. The discovery of a large number of stabilizers and the promotion of stabilization through their combinations will help solve the seemingly contradictory but difficult problems of improving the quality of cosmetics such as tonics, emulsions, and creams, and stabilizing the main ingredients. It is something that cannot be done. <Example> Example 1 (comparative example) PH-rate profile of carpronium chloride (hereinafter abbreviated as CC) The relationship between the decomposition of CC and PH at a temperature of 95°C for 1 hour was determined, and the PH-rate profile was calculated as in the pattern. The optimum pH for stability was determined. The maximum stability of CC is approximately within the range of PH4.5 to 5.5. Example 2 (comparative example) Method for stabilizing CC with alcohols Alcohols were added at various concentrations to an aqueous solution of 1 to 5% CC at a temperature of 50°C, and the effects on the decomposition of CC were investigated. It was discovered that alcohol slows down the hydrolysis rate of CC. In particular,
Ethyl alcohol and methyl alcohol were found to have the effect of preventing the decomposition of CC in proportion to their concentration (Table 1). Propylene glycol and polyethylene glycol 400 both showed significant effects at 30%. This material is also used as a cream base material, and is used as a cream base material.
It can be an important stabilizer as a base material when containing CC.

【table】

[Table] 1 at 50℃ for various organic acids and their salts.
The influence on hydrolysis in ~5% CC aqueous solution was investigated. It was discovered that lactic acid, glutamic acid, etc. particularly prevent the hydrolysis of CC and contribute to its stability. Table 2 lists the main ones. Although the CC stabilizing effect of these acids is remarkable,
The higher the concentration, the better the effect is not necessarily, but the stabilizing effect is particularly good at a concentration of M/10 to M/20.

[Table] (Example) Promotion of CC stabilizing effect by blending organic acid and alcohol Tables 3 and 4 show the results of stabilizing a 1-5% CC solution by blending organic acid and ethyl alcohol. Table 5 summarizes the stabilization by blending citric acid buffer and various alcohols, and blending sodium glutamate and propylene glycol.

【table】

【table】

[Table] Example 6 (Example) Method for stabilizing CC contained in cream. The method for stabilizing the CC contained in the cream is the same as the stabilization of water-containing CC, but it is an acidic cream, and this acidity is caused by the presence of organic compounds such as citric acid, glutamic acid, and lactic acid, which have a strong CC stabilizing effect. We are forced to adopt new principles such as being an acid and restricting the use of alcohols with strong CC effects such as ethanol. In particular, the use of organic acids often leads to destabilization of emulsions, and the combination of organic acids and other components such as emulsifiers poses problems. Table 6 shows prescription examples of CC-containing creams.
Cream with this formulation has t ₁₀ % = 50℃
It was 5 months old. Table 6 Formulation example of CC-containing acidic cream A Oil-based component Beeswaxetanol flow Para ◎ Propylene glycol Lipophilic nonionic surfactant B Water-based component Amisoft 〇 Borax 〇 Boric acid or other acids 〇 Glutamic acid (M/20) (+ pantothenyl ethyl ether 2%) or succinic acid M/20 〇PEG400 Preservative Adjust to pH 4.9 After emulsification, cool at 50℃ and add CC0.1-1.0% and fragrance. Note: The circle mark indicates a component added to stabilize CC. Pantothenyl ethyl ether may or may not be added.

Claims (1)

[Claims] 1. For hydrous administration type carpronium chloride, an organic acid selected from lactic acid, glutamic acid, citric acid, and salts of these acids, and an alcohol selected from ethyl alcohol, glycerin, ethylene glycol, propylene glycol, and polyethylene glycol. 1. A method for stabilizing water-containing administration type carpronium chloride, which comprises preventing hydrolysis of carpronium chloride by incorporating.