JPH0812571A - Disinfecting liquid for external use - Google Patents

Abstract

PURPOSE:To obtain a disinfecting liquid for external use containing an alkylbenzyldimethylammonium and a water-soluble negatively charged polymer as essential ingredients, excellent in humectant properties for preventing hands from roughening. CONSTITUTION:This disinfecting liquid for external use comprises (A) an alkylbenzyldimethylammonium or its salt (preferably, benzalkonium chloride or benzethonium chloride) and (B) a water-soluble negatively charge polymer and/or its salt (preferably, hyaluronic acid or its salt) as essential ingredients, and (C) 30-65wt./vol.% an aqueous solution of ethanol as a preferable solvent. The concentrations of the ingredients are preferably 0.05-0.5 (wt./vol.)% ingredient (A), 0.001-0.3 (wt./vol.)% ingredient (B) and 30-60 (wt./vol.)% ingredient (C). The disinfecting liquid for external use comprises, e.g. 40-60 (wt./vol.)% aqueous solution of ethanol containing 0.1-0.3 (wt./vol.)% benzalkonium chloride or benzethonium chloride, 0.002-0.05 (wt./vol.)% sodium hyaluronate or sodium hyaluronate and succinylated carboxymethylchitosan.

Description

Detailed Description of the Invention

[0001]

FIELD OF THE INVENTION The present invention relates to a disinfectant applied to human skin.

[0002]

2. Description of the Related Art In the field of medical treatment, bacteria, fungi, viruses, etc. that cause infectious diseases possessed by patients suffering from infectious diseases cause pollution of the medical environment and cause infectious diseases of other patients. It can be a serious problem. This bacterium,
Disinfection of patients and their hands and other medical personnel who may come into contact with patients is an effective means to prevent environmental pollution caused by fungi and viruses. As a method of this disinfection, there is dipping or cleaning of fingers with an antiseptic solution.In recent years, rubbing an alcoholic aqueous solution of a disinfectant containing benzalkonium chloride, chlorhexidine gluconate, etc. as an active ingredient, and drying as it is External topical agents are widely used. It has been shown that this method is simple to use and has immediate effect, and is also very useful for preventing disinfection solution exchange and cross contamination. Such disinfectants use about alcohol
It contains 66W / V% and makes good use of the effect of alcohol as its volatile property and disinfectant.

[0003]

However, since such a disinfectant needs to be used frequently by medical personnel in a day, it easily causes rough hands when alcohol is contained in a high concentration. In extreme cases, treatment of rough skin was necessary and continued use was sometimes impossible.

[0004]

The present inventors have arrived at the present invention as a result of intensive studies to solve the above-mentioned problems. The combination of benzalkonium chloride, which is useful as a disinfectant, and a water-soluble negatively charged polymer that has an excellent effect as a moisturizer and / or its salt, particularly hyaluronic acid, is widely known as a combination-incompatible combination that usually causes precipitation. However, the present inventors have found that a uniform solution can be obtained by devising the blending ratio and the solvent composition, and completed the present invention. That is, the present invention relates to a disinfecting solution for external use, which comprises a homogeneous solution containing alkylbenzyldimethylammonium or a salt thereof and a water-soluble negatively charged polymer and / or a salt thereof as essential components.

In the present invention, alkylbenzyldimethylammonium refers to benzalkonium, benzethonium, etc., and salts thereof include Cl, Br, I of these compounds.
And salt. In the present application, specifically, benzalkonium chloride and benzethonium chloride, which may be listed in the Japanese Pharmacopoeia and are used as sterilizing and disinfecting agents.

In the present invention, the water-soluble negatively charged polymer means a water-soluble polymer compound having an anionic dissociative group, for example, hyaluronic acid, chondroitin sulfate, carboxymethyl cellulose, carboxymethyl chitosan derivative or the like. The salts thereof are salts of these compounds such as sodium, potassium and calcium. More specifically, sodium hyaluronate, sodium chondroitin sulfate, carboxymethyl cellulose (CMC), sodium carboxymethyl cellulose (CMC-Na), succinylated carboxymethyl chitosan and the like can be mentioned. In the present invention, sodium hyaluronate, succinylated carboxymethyl chitosan Are preferred, and those containing hyaluronic acid or a salt thereof as an essential component are particularly preferred. The hyaluronic acid and / or its salt used in the present invention has an average molecular weight of 100,000 to 4,000,000. These may be used alone or in combination. As the succinylated carboxymethyl chitosan, for example, Chito Aqua (registered trademark) (manufactured by Hokkaido Soda Co., Ltd.) is used.

Benzalkonium chloride and benzethonium chloride are cationic surfactants in solution, have antibacterial properties, and are widely used as disinfectants or preservatives. On the other hand, the negatively charged polymer polysaccharide has viscosity-imparting, moisturizing and moisturizing effects, is used as a moisturizing and moisturizing agent, and is widely used in eye drops, cosmetics and the like.

[0008] However, when these components were blended in a solution, a precipitation was easily caused by an ionic bond, and the combination of these components was contraindicated to impair the characteristics of both. Various studies have been conducted to avoid this contraindication. For example, a method of adding cyclodextrin and its derivative as a third additive (Japanese Patent Laid-Open No. 64-1672).
8), a method of adding boric acid (JP-A-4-6934)
2), a method for specifying the length of the alkyl chain of benzalkonium chloride (JP-A-1-246227), a method for further blending a chelating agent (JP-A-2-164829) and the like are disclosed. All of these inventions relate to eye drops, and the concentration of benzalkonium chloride is as low as 0.01% or less when used as a preservative. On the other hand, when used as an external disinfectant, it is used at a concentration of 0.05% or higher.

On the other hand, the solvent composition of the conventional external disinfectant is used at a concentration of about 66 W / V% of disinfecting ethanol. If hyaluronic acid or a salt thereof is added to these, precipitation will occur and a uniform solution cannot be obtained. As a result of diligent examination of this formulation, the present inventors have determined that the ethanol concentration
When 30 to 65 W / V%, preferably 30 to 60 W / V%, both components are dissolved in a clear solution to form a uniform solution, and the bactericidal power is the same as that of the conventional benzalkonium chloride dissolved in disinfecting ethanol. I found that there is no.

According to the present invention, the concentration of alkylbenzyldimethylammonium or a salt thereof is in a range effective as an external disinfectant, for example, 0.05 to 0.5 W / V%, preferably 0.1.
A range of up to 0.3 W / V% is preferred. The concentration of the water-soluble negatively charged polymer or its salt is, for example, 0.001 to 0.3 W / V%, preferably
0.002-0.2 W / V% More preferably 0.002-0.05 W / V%. The composition of the solvent is ethanol 30 ~ 65 W / V% preferably 30
-60 W / V%, more preferably 40-60 W / V%. In addition to these component compositions, other additives such as polyhydric alcohols, for example, glycols such as 1,3-butylene glycol and propylene naglycol, glycerin and sorbitol may be added as wetting agents.

The preferable ratio of each component to the total external disinfecting solution of the present invention is shown below. Alkylbenzyldimethylammonium or a salt thereof;
0.05W / V% or more, preferably about 0.1W / V% or more and the upper limit is about 0.
5 W / V% Preferably about 0.3 W / V% Water-soluble negatively charged polymer and / or salt thereof; about 0.001 W / V%
Or more, preferably about 0.002 W / V% or more and the upper limit is about 0.3 W / V%
Preferably about 0.2 W / V%

Ethanol; about 30 W / V% or more, preferably about 40 W / V% or more and about 65 W / V% or less, preferably about 60
W / V% or less Other additives; 0 or more, preferably about 0.05 W / V%
Above about 5 W / V% or less, preferably about 3 W / V% or less, more preferably about 1 W / V% or less Water; balance

The preferred external disinfectant solution formulation in the present invention is as follows. 0.1 to 0, based on the entire antiseptic solution of the present invention.
3W / V% benzalkonium chloride or benzethonium chloride,
Disinfectant for external use consisting of 0.002 to 0.05 W / V% sodium hyaluronate or 40 to 60 W / V% ethanol aqueous solution containing sodium hyaluronate and succinylated carboxymethyl chitosan.

0.1 to 0.3 W based on the entire disinfectant solution of the present invention
/ V% benzalkonium chloride, 0.002 to 0.05 W / V% sodium hyaluronate or 40 to 60 W / V% ethanol aqueous solution containing sodium hyaluronate and succinylated carboxymethyl chitosan and 0.05 to 1 W / V% polyhydric alcohol Topical antiseptic solution.

As a result of the experiments by the present inventors, when the content of benzalkonium chloride in the whole preparation was 0.1 to 0.3 W / V% and the ethanol concentration was 50 W / V% or more and less than 70 W / V%, the ethanol concentration was A homogeneous solution is usually obtained when the concentration relationship of sodium hyaluronate satisfies the following relationship. In the following formula, X represents a numerical value of 0 to 5 and Y represents a numerical value of 0 to less than 10.

Ethanol concentration range Ethanol concentration (W / V%) Sodium hyaluronate concentration (W / V%) 50-55W / V% 50 + X 0.2-0.02X or less 55-60W / V% 55 + X 0.1-0.01 X or less 60 to less than 70 W / V% 60 + Y 0.05-0.005Y or less

In particular, in the above case, it is preferable that substantially no water-soluble ionic compound other than hyaluronic acid, such as an inorganic acid, an organic acid or a salt thereof, is contained, and even if it is contained, the solubility of hyaluronic acid is adversely affected. Limited to low concentration.

The effects of the present invention will be described below with reference to examples and experimental examples. Example 1: (Invention product 1) A solution is prepared so as to have the following composition. Benzalkonium chloride 0.2W / V% Sodium hyaluronate 0.2W / V% Ethanol 50.0W / V% Purified water Appropriate amount The prepared solution was viscous and clear.

Example 2: (Invention product 2) A solution is prepared so as to have the following composition. Benzalkonium chloride 0.2W / V% Sodium hyaluronate 0.1W / V% Ethanol 50.0W / V% Purified water Appropriate amount The prepared solution was viscous and clear solution.

Example 3: (Invention product 3) A solution is prepared so as to have the following composition. Benzalkonium chloride 0.2W / V% Sodium hyaluronate 0.02W / V% Ethanol 50.0W / V% Purified water Appropriate amount The prepared solution was a clear solution.

Example 4: (Invention product 4) A solution is prepared so as to have the following composition. Benzalkonium chloride 0.2W / V% Sodium hyaluronate 0.01W / V% 1,3-butylene glycol 0.5W / V% Ethanol 58.0W / V% Purified water Appropriate amount The prepared solution was a clear solution.

Example 5 (Invention product 5) A solution is prepared so as to have the following composition. Benzalkonium chloride 0.2 W / V% succinylated carboxymethyl chitosan 0.005 W / V% (Hokkaido Soda Co., Ltd.) Glycerin 0.5 W / V% Ethanol 58.0 W / V% Purified water Appropriate amount The prepared solution is a clear solution. became.

Example 6: (Invention product 6) A solution is prepared so as to have the following composition. Benzalkonium chloride 0.2W / V% Sodium hyaluronate 0.005W / V% Succinylated carboxymethylchitosan 0.002W / V% (Hokkaido Soda Co., Ltd.) 1,3-butylene glycol 0.2W / V% Ethanol 58.0W / V% purified water Appropriate amount The prepared liquid became a clear solution.

Comparative Control Example 1: (Welpass (registered trademark) -Maruishi Pharmaceutical Co., Ltd.) Benzalkonium chloride 0.2 W / V% Ethanol 83 V / V% (about 66 W / V%) Other amino acid surfactants, organic acid glycerides Including. Purified water Appropriate amount Comparative Control Example 2: Saline

Test Example 1 Sodium Hyaluronate Dissolution Test in Existing Disinfectant Sodium Hyaluronate 0.01 W / V% in Comparative Control Example 1
Was dissolved under the following blending conditions 1 and 2, but it was confirmed that both were insoluble. Blending condition 1; 10 mg of sodium hyaluronate was added to Control Example 1 (100 ml), and the mixture was stirred well. Blending condition 2; the solvent was distilled off from Control Example 1 (100 ml), and 83 ml (66 g) of ethanol was added to the residue to dissolve it. This is sodium hyaluronate 10m
17 ml of purified water is added to g and mixed with a solution in which it is uniformly dissolved.

The reason why sodium hyaluronate was insoluble in the existing disinfectants is considered to be that the amino acid type cationic surfactant was contained.

Test Example 2 Bactericidal activity of the product of the present invention and comparative control The bactericidal activity of the product of the present invention and a comparative control Escherichia coli (E. coli), Pseudomonas aeruginosa, Staphylococcus spp. aureus) and methicillin-resistant Staphylococcus aureus (MRSA), typical Candida albicans fungi and Aspergillus
llus fumigatus) was mixed with the test solution for about 10 ⁸ to 10 ⁹ cells / ml for a short time and then diluted with a medium in which the bacteria grow and cultured to test the bactericidal activity of the test solution. The results are shown in Tables 2 and 3.

Test Example 3 Feel of use of the product of the present invention About 3 ml of the product of the present invention was taken in the palm and rubbed with both hands to test the feel of use. As the concentration of sodium hyaluronate was higher, the product of the present invention was more viscous in the process of rubbing and drying, but after drying, the moisturizing effect of hyaluronic acid was recognized, and all were moist and good in use. Table 4 shows the results
It was shown to.

[0029]

[Table 2] Table 2. Bactericidal activity of the test solution (bacteria) Test solution Target bacteria Contact time with test solution (seconds) 10 20 30 60 Product 1 of the present invention Enterococcus ----- Pseudomonas aeruginosa ----- Staphylococcus aureus ----- Product 2 of the present invention --- --- Pseudomonas aeruginosa --- --- Staphylococcus aureus --- --- Product 3 of the present invention --- --- Pseudomonas aeruginosa --- --- Staphylococcus aureus --- --- MRSA − − − − Control product 1 E. coli − − − − Pseudomonas aeruginosa − − − − Staphylococcus aureus − − − − Control product 2 E. coli + + + + + Pseudomonas aeruginosa + + + + S. aureus + ++ + * Judgment −: No viable bacteria are recognized +: Viable bacteria are recognized

[0030]

[Table 3] Table 3. Bactericidal activity of test solution (fungus) Test solution Target bacteria Contact time with test solution (seconds) 15 30 45 Product of the present invention 1 Candida bacterium --- Aspergillus bacterium --- Control product 1 Candida bacterium --- Aspergillus bacterium --- -Control product 2 Candida ++ + + Aspergillus ++ + + * Judgment-: Viable bacterium is not recognized +: Viable bacterium is recognized

[0031]

[Table 4] Table 4. Usage test Test liquid Usage feeling Product 1 of the present invention: Viscous when rubbed, but fingers are moist after drying. Inventive product 2 It has a slight viscosity when rubbed, but the fingers are moist after drying. Inventive product 3 Rub and moisten with fingers after drying. Inventive product 4 Rub and moisten with fingers after drying. Inventive product 5 Rub and moisten with fingers after drying. In addition, the moist feeling continues after washing with water. The product of the present invention 6 Rub and moisten with fingers after drying. In addition, the moist feeling continues after washing with water.

The product of the present invention is a conventional benzalkonium chloride.
It is clear that it has the same bactericidal power as a 2% disinfecting ethanol solution.

[0033]

According to the present invention, it is possible to provide an external disinfectant having excellent moisturizing property for preventing rough hands.

Claims (8)

[Claims] 1. An external disinfectant solution comprising a homogeneous solution containing alkylbenzyldimethylammonium or a salt thereof and a water-soluble negatively charged polymer and / or a salt thereof as essential components. 2. The external disinfectant according to claim 1, wherein the solvent is a 30-65 W / V% ethanol aqueous solution. 3. The external disinfectant according to claim 1, wherein the alkylbenzyldimethylammonium or its salt is benzalkonium chloride or benzethonium chloride. 4. The external disinfectant according to claim 2, which contains hyaluronic acid or a salt thereof as an essential component as a water-soluble negatively charged polymer. 5. A 30-60 W / V% ethanol aqueous solution containing 0.05 to 0.5 W / V% alkylbenzyldimethylammonium or a salt thereof and 0.001 to 0.3 W / V% water-soluble negatively charged polymer and / or a salt thereof. Disinfectant for external use. 6. An aqueous solution of 0.1 to 0.3 W / V% benzalkonium chloride or benzethonium chloride, 0.002 to 0.05 W / V% sodium hyaluronate or 40 to 60 W / V% ethanol containing sodium hyaluronate and succinylated carboxymethyl chitosan. Disinfectant for external use consisting of. 7. The external disinfectant according to claim 5, further comprising 0.05 to 1 W / V% polyhydric alcohol. 8. A concentration of 0.1 to 0.3 W / V% of benzalkonium chloride, and a concentration of sodium hyaluronate and an ethanol concentration in the ethanol concentration range of 50 to less than 70 W / V% having the following relationship. Ethanol concentration range Ethanol concentration (W / V%) Sodium hyaluronate concentration (W / V%) 50 to 55W / V% 50 + X 0.2-0.02X or less 55-60W / V% 55 + X 0.1-0.01X or less 60 ~ 70W / V% or less 60 + Y 0.05-0.005Y or less [where X is a value from 0 to 5 and Y is a value from 0 to less than 10], an external disinfectant solution consisting of a uniform solution.