FR2866234A1 - Antiseptic disinfectant useful in cosmetic products, pharmaceutical products or foods comprises octopyrox and a 1,2-alkanediol - Google Patents

Abstract

Antiseptic disinfectant comprises octopyrox (1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone) and a 1,2-alkanediol (I). Antiseptic disinfectant comprises octopyrox (1-hydroxy-4-methyl-6-(2,4,4-trimethylpentyl)-2(1H)-pyridone) and a 1,2-alkanediol of formula (I): R-CH(OH)-CH 2OH (I) R : 3-8C alkyl. An independent claim is also included for a cosmetic product, pharmaceutical product or food containing the antiseptic disinfectant. ACTIVITY : Dermatological; Antibacterial; Fungicide. A 1:1 mixture of octopyrox and 1,2-octanediol had MIC values of 78 mu g/ml against Escherichia coli, Staphylococcus aureus, Candida albicans and Aspergillus niger. The same values were obtained with octopyrox alone. MECHANISM OF ACTION : None given.

Description

2866234 1

  The present invention relates to an antiseptic disinfectant and a cosmetic product, a pharmaceutical product and a food containing it. It is an object of the present invention to provide a disinfectant antiseptic containing a 1,2-alkanediol having 5 to 10 carbons and Octopyrox as active ingredients whose inherent antimicrobial potentials are synergistically enhanced by their combined use as well. a cosmetic product, a pharmaceutical product, and a food containing this antiseptic disinfectant.

  Cosmetic products (including quasi-drugs), pharmaceuticals and foods contain an antiseptic disinfectant such as paraben, benzoic acid or salicylic acid, and the like. However, conventional antiseptic disinfectants have a problem that their concentration range used is often limited because of their low level of safety, for example in terms of severe skin irritation. For example, the limiting concentrations of parabens and benzoate salts are 1% and those of benzoic acid and salicylic acid 0.2%. They have yet another problem: the stability of antiseptic bactericidal actions is significantly reduced because these antiseptic disinfectants are often affected by pH, and the antiseptic bactericidal action is sometimes significantly reduced by use in combination with another ingredient such as a surfactant. In addition, there has recently been a growing need for a cosmetic product, a pharmaceutical product and a food not containing or containing lower amounts of these antiseptic disinfectants, in a public orientation towards increased safety and increased number of people allergic to these antiseptic disinfectants.

  In these circumstances, Japanese Unexamined Patent Application Publication No. 53510 (1998) discloses an external preparation containing both 1,2-pentanediol and 2-phenoxyethanol and the publication of Unexamined Patent Application No. 310506 (1999) describes an antiseptic disinfectant containing 1,2-alkanediol and paraben as a way of reducing the amount of traditional antiseptic disinfectants used. However, these preparations were intended to improve the action of the antiseptic agent through the combined use of the conventional antiseptic agent and 1,2-alkanediol and thus not to eliminate the conventional antiseptic agent altogether or to enhance the action of the antiseptic agent. antimicrobial a 1,2-alkanediol.

  Japanese Unexamined Patent Application Publication No. 322591 (1999) discloses a disinfectant antiseptic containing a 1,2-alkanediol and Japanese Unexamined Patent Application Publication No. 48720 (2001) discloses a bacteriostatic moisturizer for cosmetic products. non-cleaning and cleaning agents containing 1,2-octanediol, and the like, for removing conventional antiseptic disinfectants. However, because an alkanediol such as 1,2-octanediol often has to be used in greater amounts to obtain a sufficient effect compared to when 1,2-alkanediol is used alone as an antiseptic disinfectant, and a 2-alkanediol has a characteristic odor, there is a need for a composition capable of exerting a sufficiently high antiseptic bactericidal action even at a lower content.

  On the other hand, Octopyrox is also known for its antibacterial action from the publication of Unexamined Patent Application No. 83322 (1990). However, Octopyrox is commonly used in cosmetic hair treatment products such as shampoos, especially dandruff shampoos, but no attempt has been made so far to improve the antibacterial action.

  The present invention has been made in view of the conventional art and one of its objects is therefore to provide an antiseptic disinfectant containing both 1,2-alkanediol and Octopyrox as active ingredients, synergistically exercising the actions antimicrobial agents in 1,2-alkanediol and Octopyrox on a wide range of microbial strains. Another object of the invention is a cosmetic product, a pharmaceutical product or a food containing this antiseptic disinfectant.

  For this purpose, the present invention provides an antiseptic disinfectant, characterized in that it contains Octopyrox and a 1,2-alkanediol represented by the formula (1): R CH (OH) CH 2 OH (1) in which R is an alkyl group having 3 to 8 carbons.

  Preferably, the 1,2-alkanediol is selected from 1,2-hexanediol, 1,2-octanediol and mixtures thereof.

  Most preferably 1,2-alkanediol is 1,2-octanediol. The invention also proposes a cosmetic product, a pharmaceutical product or a food containing the antiseptic disinfectant of the invention.

  The antiseptic disinfectant according to the present invention synergistically exerts the antimicrobial actions inherent to 1,2-alkanediol and Octopyrox over a wide range of microbial strains. In addition, cosmetics, pharmaceuticals and foods containing the antiseptic disinfectant of the invention do not need to contain a conventional antiseptic such as paraben, benzoic acid or salicylic acid; and the antiseptic disinfectant content per can be reduced to a lower amount because the antiseptic disinfectant subject of the present invention exhibits superior antibacterial action.

  The invention will be better understood and other features and advantages thereof will appear better on reading the detailed description which follows and which is made with reference to the figures in which: FIG. 1 is a two-dimensional diagram which illustrates the minimal inhibitory concentrations of E. coli obtained in EXAMPLE 1; FIG. 2 is a two-dimensional diagram illustrating the minimum inhibitory concentrations of Staphylococcus aureus obtained in EXAMPLE 1; FIG. 3 is a two-dimensional diagram which illustrates the minimum inhibitory concentrations of the microbe causing the oral candidiasis obtained in EXAMPLE 1; FIG. 4 is a two-dimensional diagram illustrating the minimum inhibitory concentrations of Aspergillus niger obtained in EXAMPLE 1; and FIG. 5 represents a curve illustrating a method for evaluating the combined action of two substances, having an antibacterial action when they are used together, from the two-dimensional curve illustrating the minimum inhibitory concentrations.

  The antiseptic disinfectant of the present invention contains 1,2-alkanediol and Octopyrox as active ingredients.

  The first ingredient of the present invention is 1,2-alkanediol. The 1,2-alkanediols used in the present invention include 1,2-alkanediols represented by the following formula (1): wherein R represents an alkyl group having from 3 to 8 carbons.

  Specific examples include 1,2-pentanediol, 1,2-hexanediol, 1,2-heptanediol, 1,2-octanediol, 1,2-nonanediol and 1,2-decanediol; among them 1,2-hexanediol and 1,2-octanediol are preferred and 1,2-octanediol is particularly preferred. In the present invention, these alkanediols can be used alone or in combination with two or more others.

  The second ingredient of the present invention is Octopyrox. The chemical name of Octopyrox is 1-hydroxy-4-methyl-6 (2,4,4-trimethylpentyl) -2 (1H) -pyridone and the compound is generally used in the form of its monoethanolamine salt.

  The contents of the first ingredient, a 1,2-alkanediol and the second ingredient, Octopyrox, in the antiseptic disinfectant according to the present invention are not particularly limited, but are added at a weight ratio of 0.1 1 to 10: 1, preferably 0.2: 1 to 5: 1. The addition of a 1,2-alkanediol in an amount 10 times greater, or less than one-tenth, with respect to Octopyron is not favorable, since the antimicrobial action may not be increased.

  The antiseptic disinfectant according to the present invention contains a 1,2-alkanediol as the first ingredient and Octopyrox as the second ingredient, and its antimicrobial action is significantly increased thanks to the synergistic effect of the first and second ingredients as shown in EXAMPLES below. For this reason, cosmetics, pharmaceuticals and foods containing the antiseptic disinfectant of the present invention require less or more of conventional antiseptic disinfectant such as paraben, benzoic acid or (1) 2866234 5 salicylic acid and that a much safer antiseptic disinfectant can be obtained.

  The antiseptic disinfectant according to the present invention can be used in cosmetics, pharmaceuticals, foods and the like because it is mixed. Specific examples include skin cosmetics, such as facial cleansers and facial lotions, emulsions, creams, foundations, mascara, nail polishes and lipsticks; hair cosmetics such as shampoo, hair treatments, hair growth stimulants, balms and hair lotions, hair foams and permanent products; medicated cosmetic products (quasi-drugs) for a specific purpose such as the treatment of stains and ephelides; pharmaceutical products such as pimples, gargles and cachets; foods such as chewing gum, sweets and drinking water, and the like.

  When producing a cosmetic product, a pharmaceutical product or a food using the antiseptic disinfectant according to the present invention other commonly used ingredients may be added as necessary to the cosmetic product, the pharmaceutical product or the foodstuff. a concentration not detrimental to the beneficial effects of the present invention. Examples of other ingredients used in cosmetics (including near-drugs) and in pharmaceuticals include fats and oils, waxes, higher fatty acids, lower alcohols, higher alcohols, sterols, fatty acid esters, moisturizers, surfactants, polymers, inorganic pigments, dyes, antioxidants, ultraviolet absorbers, vitamins, astringents, whiteners, plant and animal extracts, chelating agents, purified water, and the like. Examples of food additives include vegetable and animal oils, polysaccharides, sweeteners, dyes, gum bases, and the like.

  When the antiseptic disinfectant according to the present invention is added to a cosmetic product, a pharmaceutical product or a food, its mixed amount is not particularly limited but it is generally between 0.01 and 20% by weight, if possible. between 0.05 and 5% by weight, in the composition If the amount added is less than 0.01% by weight, the antimicrobial action decreases while if it exceeds 20% by weight no improvement in the antimicrobial action n ' appears.

EXAMPLES EXAMPLE 1

  (Microbes tests) Test microbes include gram-negative bacterium Escherichia coli IFO 3972, gram-positive bacterium Staphylococcus aureus IFO 013276, yeast Candida albicans IFO 1594 (the microbe causing oral candidiasis) and an Aspergillus niger fungus IFO 9455.

  (Preparation of microbial seeding suspensions) In the case of E. coli and Staphylococcus aureus, the microbial seed suspensions were prepared by culturing the microbes respectively on 35 C agar and then in a 35 C broth. after transfer and diluting the culture solution thus obtained with the broth to a concentration of about 108 cells / ml. Separately, a seed suspension of the microbe causing oral candidiasis at a concentration of about 10 cells / ml was prepared by culturing the microbe at 30 ° C and diluting the resulting culture solution in the same manner. while that of Aspergillus niger was prepared by adding physiological saline solution containing 2% Tween 80 (polyethylene sorbitan monooleate) (20) to the culture solution at 25 ° C, to obtain a spore suspension having a concentration. about 106 spores / ml.

  2866234 7 (Preparation of dilutions series of solutions of the test substance) 1,2-Octanediol solutions having a concentration of 5; 4; 3; 2.5; 2.25; 2; 1.75; 1.5; 1.25 and 1% w / v were prepared using a 20% w / w solution of ethyl cellusolve as a diluting solvent. Separately, a series of dilutions of Octopyrox solutions (manufactured by Clariant, Japan), and an equal mixture of 1,2-octanediol and Octopyrox, were prepared by diluting several times the 10% w / w solutions. volume.

  (Determination of Minimum Inhibitory Concentrations (MIC)) The microbial seed suspension was rubbed, about 1 cm in length, onto a 9 mL agar plate containing 1 mL of each of the solutions of the test substance. series of dilutions. E. coli and Staphylococcus aureus were cultured at 35 C and microbial growth was observed after two days. The microbe causing oral candidiasis and Aspergillus niger were cultured at 25 C and their growth was determined after three days. The minimum concentration at which microbial growth is no longer observed is called MIC. The results are summarized in TABLE 1.

[TABLE 1]

  Minimum Inhibitory Concentration (MIC) (ua / mL Substance Microbe test test _ E.Coli S.aureus C.albicans A.niger 1,2- 1250 2250 1500 _ Octanediol 1250 Octopyrox 78 78 78 78 Mixture of 78 78 78 78 2 ingredients above The antimicrobial action of each test substance can be evaluated by the MIC Test substance has no influence on the microorganism if the concentration of the test substance is lower, but it causes inhibition of growth if the concentration is increased, the degree of inhibition of growth depends on the concentration and the growth is totally inhibited at a certain concentration, at which time the concentration represents the MIC. concentration above the MIC.

  (Two-dimensional minimal inhibitory concentration) A curve of the two-dimensional minimal inhibitory concentration is obtained by plotting the MICs of 1,2-octanediol, Octopyrox and the mixture by weight of 1,2-octanediol and Octopyrox on a graph whose two axes, x and y, respectively represent the contents of 1, 2-octanediol and Octopyrox. The results are illustrated in Figures 1 to 4.

  The two-dimensional minimum inhibitory concentration curve makes it possible to determine the combined effect of a mixture of two substances both having an antibacterial action. More specifically, when two substances exerting an antibacterial action are mixed, the action of the mixture can be classified into three groups: synergistic, additive and antagonist. Synergistic action is a synergistic action by two substances and the antimicrobial action inherent to each substance is increased. Additive action is an action resulting from the sum of the antibacterial actions of each substance. The antagonistic action is an action in which one substance inhibits the antimicrobial action of another. The method for determining a combined action using the two-dimensional minimum inhibitory concentration curve is a method of determining the MICs of substances A and B by modifying the concentration, for example as shown in Figure 5. When the MIC of a pure substance A (point A) and the MIC of a pure substance B (point B) are connected by a line in the figure, if the MIC obtained by the combination of these substances is below the line ( point C), the antimicrobial action due to the combination is evaluated as a synergetic action; if it is on the line (point D) it is an additive action; and if it is above the line (point E) it is an antagonistic action which reduces one or both antimicrobial actions of the substances.

  2866234 9 (Evaluation of antimicrobial actions) The results of Figures 1 to 4 indicate that 1,2-octanediol and Octopyrox have synergistic antimicrobial action on a wide range of microbial strains when used together.

  Examples of cosmetics, pharmaceuticals and foods containing the antiseptic disinfectant according to the present invention are given below. In the examples which follow, the part indicates the part by weight.

  (Preparation Example 1: Moisturizer) 1.0 Monolaurate Decaglyceryl Polyoxyethylene (15) Glycerol Monosterate 1.0 Hydrogenated Soy Phospholipids 1.0 Stearic Acid 4.0 Cetanol 2.0 Behenyl Alcohol 2.0 Paraffin 3.0 Squalene 12.0 Jojoba oil 4.0 Methylpolysiloxane 0.2 1.3-Butylene glycol 3.0 L-Arginine 0.1 Xanthan gum 0.001 1,2-Octanediol 0.25 Octopyrox 0.1 Purified water qs

  Total 100.0 (Preparation example 2: hydrophilic ointment) Ascorbic acid 0.5 Polyoxyethylene cetyl ether 2.0 Sodium hydrogen phospholipids 1.0 Stearic acid 4.0 Glycerol monostearate 10.0 Liquid paraffin 10.0 Vaseline 4.0 Ketanol 5.0 Propylene glycol 5.0 1,2-Hexanediol 0.5 Octopyrox 0.2 Purified water qs

  Total 100.0 (Preparation example 3: drink) 0.5 Ascorbic acid Glucose syrup 33.0% grapefruit 64.0 1.2-Pentanediol 0.5 Octopyrox 0.1 Acidifier q.s.

  Total 100.0 The antiseptic disinfectant according to the present invention can be favorably used as an antiseptic disinfectant in cosmetics, pharmaceuticals, foods and the like, since 1,2-octanediol and Oxtopyrox exert an excellent antibacterial action. synergistic when used together and that they offer an increased degree of security.

Claims (1)

11 CLAIMS   1. An antiseptic disinfectant, characterized in that it contains Octopyrox and a 1,2-alkanediol represented by the formula (1): ## STR1 ## where R represents an alkyl group having from 3 to 8 carbons .   2. An antiseptic disinfectant according to claim 1, characterized in that the 1,2-alkanediol is selected from 1,2-hexanediol, 1,2-octanediol and mixtures thereof.   3. An antiseptic disinfectant according to claim 1, characterized in that the 1,2-alkanediol is 1,2-octanediol.   4. Cosmetic product, pharmaceutical product or food characterized in that it contains the antiseptic disinfectant according to one   any of claims 1 to 3. (1)