JPS6328403B2 - - Google Patents

Description

[Detailed description of the invention]

Industrial Application Field The present invention relates to antimicrobial compositions, more specifically,
The present invention relates to various disinfectants that apply antimicrobial action based on the oxidation reaction of enediol compounds using copper ion catalysts, and compositions useful as preparations that require antifungal, antibacterial, and antiviral actions. Conventional technology When an enediol compound such as ascorbic acid is brought into contact with a small amount of copper compound in the presence of water, an oxidation reaction of the enediol compound occurs due to the action of a copper ion catalyst, resulting in antifungal and antibacterial effects. ,
It is known that antimicrobial effects such as antiviral effects occur (for example, U.S. Patent No.
No. 3065139). However, this reaction proceeds very rapidly, and its antimicrobial effect soon declines, making it extremely difficult to put this antimicrobial effect into practical use commercially. Therefore, in order to put this antimicrobial action into practical use commercially, various studies have been made regarding its stabilization and sustainability. For example, U.S. Pat.
No. 3,681,492 discloses an antimicrobial composition that uses an amine to suppress the rate of the oxidation reaction and maintains the antimicrobial effect. In addition, Japanese Patent Publication No. 5971/1989 discloses a method for sterilizing contact lenses using the antimicrobial action, in which an enediol compound and a copper compound are used together or individually.
Disinfectants are used that are formulated in a water-free dosage form and mixed with water at the time of use. Furthermore, it is stated that ammonium chloride or an amine for suppressing the reaction rate as in US Pat. No. 3,681,492 may be added to the disinfectant. Also, special public service in 1987
No. 52323 discloses a disinfectant that stabilizes the antimicrobial action in the form of an aerosol containing no free water, consisting of an enediol compound, a copper compound, and, optionally, a substance that suppresses the reaction rate as described above. Disclosed. Problems to be Solved by the Invention However, conventional measures for stabilizing and sustaining the antimicrobial action are not necessarily satisfactory. That is, even if the oxidation reaction rate is suppressed using amines or the like, it is almost impossible to sustain the antimicrobial effect to the extent that it can be put to practical use commercially. In addition, since this reaction is a radical reaction and proceeds even in the presence of a small amount of water, it is difficult to stabilize and sustain the antimicrobial effect unless this state is completely maintained, even if the dosage form does not contain water. On the other hand, it is extremely difficult to maintain a completely moisture-free state from a commercial practical standpoint. Furthermore, formulating enediol compounds and copper compounds in separate dosage forms is cumbersome and
There are problems such as limited application range. In view of these circumstances, the present invention aims to stabilize and sustain the antimicrobial action based on the oxidation reaction of an enediol compound using a copper ion catalyst so that it can be fully put into practical use commercially, and to achieve an excellent antimicrobial action. The present invention has been made to provide an antimicrobial composition having the following properties. Means for Solving the Problems The present inventors have conducted various studies on stabilizing and sustaining the antimicrobial action based on the oxidation reaction of enediol compounds using copper ion catalysts, and found that although the mechanism of action is not clear, , the coexistence of aliphatic dicarboxylic acids having 6 to 10 carbon atoms has a specific antimicrobial effect, regardless of the presence or absence of water, and even without formulating enediol compounds and copper compounds in separate dosage forms. It has been found that an excellent antimicrobial composition with stabilized and sustained action can be obtained. That is, the present invention provides enediol compounds selected from the group consisting of ascorbic acid, dihydroxymaleic acid, dihydroxyfumaric acid, reductinic acid, and derivatives thereof, cupric chloride, copper sulfate, hydrates thereof, and copper oleate. The present invention provides an antimicrobial composition comprising as essential components a copper compound selected from the group consisting of: and an aliphatic dicarboxylic acid having 6 to 10 carbon atoms. The enediol compound used is selected from the group consisting of ascorbic acid, dihydroxymaleic acid, dihydroxyfumaric acid, reductinic acid and derivatives thereof (eg, salts, ethers, ester derivatives). The amount of the enediol compound to be used can be selected as appropriate depending on the type of compound actually used, the dosage form of the composition, etc., but generally it is in the range of 0.01 to 10% (wt%, the same hereinafter) based on the total amount of the composition. That's enough. The copper compound used is a compound that generates copper ions that serve as a catalyst for the expression of the antimicrobial action, and is selected from the group consisting of cupric chloride, copper sulfate, hydrates thereof, and copper oleate. The amount of the copper compound to be used can be appropriately selected depending on the type of compound actually used, the dosage form of the composition, etc., but generally, a range of 0.0001 to 0.1% based on the total amount of the composition is sufficient. Aliphatic dicarboxylic acids having 6 to 10 carbon atoms, that is, adipic acid, pimelic acid, suberic acid, azelaic acid, or sebacic acid, are blended in an amount of 0.01 to 10% based on the total amount of the composition, and are generally used as enediol compounds. The same amount or less is sufficient. If the amount of aliphatic dicarboxylic acid is too small, no effect can be expected, and if it is too large, problems such as side effects caused by the aliphatic dicarboxylic acid may occur, and precipitation may occur because it is difficult to dissolve in water. . Thus, the compositions of the present invention can be formulated into solid dosage forms such as tablets, granules, or aqueous or non-aqueous solutions, dispersions, emulsions, lotions, pastes, gels, ointments, aerosols, etc. by conventional formulation techniques. It can be made into a dosage form, and other ingredients are not particularly limited. The solid composition of the present invention includes, for example,
When dissolved in water, it exhibits an antimicrobial effect; non-aqueous substances exhibit an antimicrobial effect when mixed with water, absorbed, or moistened. Water-based products produce antimicrobial effects when applied directly.
These compositions include, for example, contact lens cleaning disinfectants, gargling agents, denture cleaning disinfectants, toilet and bath cleaning disinfectants, antiperspirant sprays, foot sprays, disinfectants for tableware, etc., disinfectants for external use on the skin, It can be used as medicinal cosmetics in the form of hair preparations, ointments, creams, soaps, etc. Examples Next, the present invention will be explained in more detail with reference to examples. Example 1 Granules for gargling were manufactured according to the following formulation. Ingredients % Ascorbic acid 30.0 Pimelic acid 15.0 Sodium bicarbonate 30.0 Malic acid 23.0 Copper sulfate pentahydrate 0.2 Flavor 1.8 These ingredients were kneaded with ethanol and wet granulated according to a conventional method. The obtained granules are divided into packages of 1 g each, and when gargling, each package is dissolved in 30 to 100 ml of water before use. Example 2 Contact lens sterilization tablets were manufactured according to the following formulation. Ingredients % Ascorbic acid 30.0 Suberic acid 10.0 Sodium bicarbonate 14.0 Copper sulfate pentahydrate 0.2 Sodium chloride 0.6 Lubricating agent, neutralizing agent Appropriate amount Lactose Remaining amount One 100 mg tablet is directly compressed according to the conventional method. Tablets were manufactured. Dissolve one tablet in 10ml of water and use it to sterilize contact lenses. Example 3 An antiperspirant aerosol was manufactured using the following formulation. Ingredients % Dihydroxymaleic acid 0.5 Adipic acid 0.3 Cupric chloride dihydrate 0.005 Aluminum chlorohydrate 4.0 Freon 12 23.1 Freon 14 69.3 Starch fine powder Balance Fill into an aerosol container according to the usual method to create an antiperspirant aerosol was manufactured. Example 4 A germicidal agent for external use on the skin in the form of a gel was manufactured according to the following formulation. Ingredients % Carbopol 940 1.0 Ethanol 35.0 A Azelaic acid 1.0 Propylene glycol 15.0 Sodium ascorbate 1.0 B Fragrance Appropriate amount Water Balance Copper sulfate pentahydrate 0.01 Mix component A and component B according to the usual method, After dissolving, both solutions were combined, and copper sulfate was added and mixed while stirring to obtain a gel. Effects of the Invention In order to test the antimicrobial action stabilizing effect of various aliphatic dicarboxylic acids, various aliphatic dicarboxylic acids and ascorbic acids shown in Table 1 were
Copper sulfate 5
Dissolve the hydrate in a 20% alcohol aqueous solution to a concentration of 0.01%, adjust the pH to 6.0, and seal it for 40 minutes.
After being left at ℃ for 14 days, its antibacterial properties were measured. As controls, a solution without the addition of aliphatic dicarboxylic acid, a solution with the addition of ammonium chloride, which is known to inhibit the oxidation reaction rate of enediol compounds, instead of dicarboxylic acid, and a solution without addition of ascorbic acid were also used. Antibacterial properties were measured in the same manner. To measure antibacterial properties, Staphylococcus aureus cells were added to each solution at a final concentration of 1 x ¹⁰ cells/ml, and applied to an agar plate immediately after addition and after being left for 15 minutes. ,
After incubation at 37°C for 18 hours, the presence or absence of bacterial growth was determined using the following criteria. +...Many colonies formed, ±...Growth limit, -...No colonies. The results are shown in Table 1.

【table】

[Table] As shown in Table 1, aliphatic dicarboxylic acids having 6 to 10 carbon atoms specifically stabilize the antimicrobial action. Furthermore, it is clear that aliphatic dicarboxylic acid alone does not have an antimicrobial effect, and that microbial cells are viable immediately after addition to each solution. Note that aliphatic dicarboxylic acids having 11 or more carbon atoms are difficult to dissolve in water and are difficult to use.

Claims (1)

[Claims] 1. Ascorbic acid, dihydroxymaleic acid,
an enediol compound selected from the group consisting of dihydroxyfumaric acid, reductinic acid, and derivatives thereof; a copper compound selected from the group consisting of cupric chloride, copper sulfate, hydrates thereof; and copper oleate; An antimicrobial composition comprising 10 aliphatic dicarboxylic acids as essential components. 2. The composition according to item 1 above, containing 0.01 to 10% by weight of the enediol compound, 0.0001 to 0.1% by weight of the copper compound, and 0.01 to 10% by weight of the aliphatic dicarboxylic acid.