JPH0580225B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to an antibacterial latex composition, and its purpose is to provide a latex composition suitable for producing latex molded products such as medical instruments, sanitary products, food manufacturing equipment, and fixtures having sustained antibacterial activity. An antibacterial latex composition is provided. Conventionally, various sterilizing disinfectants have been used in the medical, testing, and food fields to prevent contamination and infection from various types of bacteria, actinobacteria, fungi, slime molds, viruses, and the like. Among them, 1,6-di-(4-chlorophenyl biguanide)
Biguanide compounds, represented by hexane (also known as chlorhexidine), are the most widely used antibacterial agents today because they have strong bactericidal activity against a wide range of microorganisms and have low toxicity to the human body. It is one of the most popular disinfectants. Currently, these are usually provided as an aqueous solution (for example, an aqueous solution of chlorhexidine glyconate), and medical devices can be immersed in this aqueous solution or sprayed with this aqueous solution before use to achieve the intended purpose. has been achieved. However, when medical instruments are used for a long period of time, we often experience in our daily lives that the effectiveness of antibacterial agents gradually decreases or disappears if only the initial disinfection is performed, and there is a strong desire to improve this situation. The most effective countermeasure would be a system in which a constant amount of antibacterial agent at a minimum (growth) inhibitory concentration or higher is slowly released from the device during the use process. In order to realize such a system, it is necessary to obtain latex in which antibacterial agents are uniformly and stably dispersed.
It is necessary to mold this material into, for example, a medical device, etc., but the latex in which the biguanide compound is uniformly and stably dispersed can be
Haven't gotten it so far. First, polymer latexes in which hydrophobic natural rubber or synthetic polymer compounds are dispersed in an aqueous medium are used for a variety of useful purposes today, but these latexes usually contain a substance that stabilizes the latex particles. Contains various surfactants and protective colloids to aid in floating and dispersion. For example, in natural rubber latex, protein, which is an ampholyte contained in its components, is adsorbed onto the surface of rubber particles, thereby acting as a kind of protective colloid and helping to stabilize the dispersion of latex particles. In addition, natural rubber latex tends to generate acid and coagulate due to the action of enzymes and bacteria contained in it, so to prevent this, 0.5 to 1.0% ammonia is usually added to keep the liquid alkaline. ing. Therefore, since the rubber particles are basically negatively charged, they are stably suspended and dispersed without agglomeration due to the mutual electrostatic repulsion between the particles. Also, anionic and/or nonionic surfactants are added to synthetic polymer latexes before or after polymerization, and cationic surfactants are used in practice unless there are special circumstances. There are very few examples. On the other hand, as can be seen from its chemical structure, biguanide compounds as antibacterial agents belong to cationic fungicides that have a positive charge and a hydrophobic group in one molecule, and the biguanide group is one of the strongest organic bases. It has a high PKa value of about 12, and is almost 100% protonated in the physiological PH range. Therefore,
For example, adding soap, which is an anionic surfactant, to an aqueous solution of gluconate, which is a readily water-soluble salt of chlorhexidine, which is a commercially available product, causes the elimination or substitution of gluconic acid, forming a poorly water-soluble salt. However, as a result, it has been considered contraindicated in combination because it results in a decrease in bactericidal activity. This is explained in the 10th revised Japanese Pharmacy Law Explanation (Japan Official Publications Association, Hirokawa Shoten,
1981) C-677. Under the above technical background, for example, when an aqueous solution of chlorhexidine gluconate is added to natural rubber latex, the negative charge of latex particles is neutralized and destabilized, and as a result, the latex immediately becomes irreversible. To cause gelation,
Adding these chlorhexidine-based antibacterial agents to latex was conventionally considered to be nonsense, and no further serious consideration was given. The present inventors have conducted intensive studies on antibacterial latex compositions suitable for manufacturing medical devices, sanitary products, food manufacturing equipment, etc. made of latex with sustained antibacterial activity, and have surprisingly found that The present invention was achieved based on the discovery that a stable antibacterial latex composition can be obtained without causing gelation even when a poorly water-soluble biguanide compound or its salt is added to the latex. That is, the present invention is an antibacterial latex composition comprising a natural rubber latex or a synthetic polymer latex and a poorly water-soluble biguanide compound or its salt. The biguanide compound in the present invention is represented by the following general formula (I) or ().

[ka]

[Chemical formula] Here, R is an alkyl group, an aminoalkyl group, a phenyl group, an alkylphenyl group, a halogenated phenyl group, a hydroxyphenyl group, a methoxyphenyl group, a carboxyl phenyl group, a naphthyl group, or a nitrile group, R' is hydrogen or an alkyl group. n is a positive integer, preferably in the range of 2 to 10. Preferred specific examples of such biguanide compounds include 1,6-di-(4-chlorophenylbiguanide)hexane, diaminohexylbiguanide, and 1,6-di(aminohexylbiguanide)hexane. The salt of a biguanide compound in the present invention refers to a salt formed from a biguanide compound and an inorganic acid or an organic acid. Examples of inorganic or organic acids that form poorly water-soluble salts with biguanide compounds include hydrochloric acid, hydrobromic acid, nitric acid, sulfuric acid, carbonic acid, bicarbonate, citric acid, phosphoric acid, boric acid, formic acid, acetic acid, and benzoic acid. Examples include acid, tartaric acid, etc. In the present invention, poorly water-soluble means 100g at 20°C.
The solubility in distilled water is in the range of 0.001 to 3.0 g, preferably 0.005 to 2.0 g. If the solubility in water is less than 0.001 g, the efficacy as a bactericidal agent will be reduced, while if it exceeds 3.0 g, the latex will irreversibly gel when added to the latex, which is undesirable. The content of the poorly water-soluble biguanide compound or its salt in the antibacterial latex composition of the present invention varies depending on the purpose, but is usually preferably 0.01% of the solid content of the latex.
~30wt%, more preferably 0.1-10wt%.
If the content exceeds 30 wt%, the physical strength of the film of a molded product obtained from this latex composition tends to be poor, while if it is less than 0.01 wt%, it becomes difficult to exert its effectiveness as an antibacterial agent, so it is preferable. do not have. The natural rubber latex used in the present invention is
The dispersion medium is an aqueous solution containing various organic and inorganic substances that flows out when the bark of a rubber plant is cut, and the rubber component is used as the dispersoid. This refers to products that contain softeners, fillers, anti-aging agents, colorants, etc. Synthetic polymer latexes include, for example, homopolymers or copolymers of vinyl monomers such as ethylene, styrene, vinyl acetate, vinyl chloride, vinylidene chloride, acrylonitrile, (meth)acrylic acid esters, vinyl pyridine, and methyl vinyl ether. homopolymers of diene monomers such as butadiene, isoprene, 1,3-pentadiene, 1,5-hexadiene, 1,6-heptadiene, chloroprene, etc., or copolymers thereof; copolymers of the above vinyl monomers and diene monomers; Polymers and other functional groups such as epoxide groups, amino groups, carboxyl groups, acid anhydride groups, hydroxyl groups, amide groups, N-
The main component is a copolymer of a vinyl monomer having a methylolamide group, an isocyanate group, etc. and the various monomers mentioned above, and if necessary, a surfactant,
Examples include those containing crosslinking agents, fillers, softeners, etc. The method for preparing the antibacterial latex composition of the present invention is not particularly limited as long as each component is mixed uniformly, and various known methods can be used. For example, the antibacterial agent may be mixed in a ball mill. Preferably, a method is employed in which a homogeneous paste-like aqueous dispersion is obtained by grinding with a grinder, and natural rubber latex or synthetic polymer latex is added thereto and mixed with stirring. The antibacterial latex composition of the present invention can be suitably used for molding medical instruments, sanitary instruments, food manufacturing equipment or fixtures, etc., which have sustained antibacterial properties even during long-term use. Specific examples of molded products include various catheters including urinary catheters, fluid supply and drainage tubes, sponges, rubberized cloth, paper sizing agents, nonwoven fabric binders, paints, adhesives, and the like. These are molded by a conventionally known dipping method, casting method, electrodeposition method, or the like. To give a more specific application example, the antibacterial latex composition of the present invention can be used for urinary catheters, which frequently cause urethritis, cystitis, pyelitis, etc. due to bacteria that invade through the catheter when left in the body for a long period of time. The molded urinary catheter has the ability to release antibacterial agents in a sustained manner, and during its use, the antibacterial agents are continuously released through urine or body fluids, thereby preventing urinary tract infections from various bacteria. It is extremely effective. The present invention will be described in detail with reference to specific examples below. Note that "parts" in the examples mean "parts by weight." Example 1 0.3 parts of zinc dimethyldithiocarbamate, 1.5 parts of sulfur, 3 parts of zinc white, and 1.2 parts of stearic acid were added to 100 parts of a natural rubber latex solution (PH 10.7) with a solid content concentration of approximately 50 wt%, and the mixture was dispersed uniformly. A compounded latex containing natural rubber as the main component was obtained. This compounded latex contains 1,6-di-
(4-chlorophenyl biguanide) hexane hydrochloride (solubility in water at 20℃ is approximately 0.06wt
%) was uniformly dispersed in 12 parts of distilled water in the form of a paste, and added to the mixture while stirring, the latex did not aggregate and a latex composition in which the antibacterial agent was uniformly dispersed could be obtained. Ta. A film can be formed from the obtained composition, and about this film, Bacillus subtilis
When an antibacterial activity test was conducted using ATCC 6633 (medium NUTRIENT AGAR) as a test bacterium by the cylindrical plate method (disk method), an inhibition zone was produced, indicating that this composition had antibacterial properties. Comparative Example 1 When a 20 wt % aqueous solution of gluconate of 1,6-di-(4-chlorophenylbiguanide)hexane was added little by little to 100 parts of the same compounded latex used in Example 1 while stirring, the latex The viscosity gradually increased, and it completely gelled when approximately 3 ml was added. Example 2 1,6-di-(4-chlorophenylbiguanide)hexane (solubility in water is about 0.08 wt%) was added to 100 parts of the same compounded latex used in Example 1.
When 10 parts of the latex was preliminarily dispersed in 12 parts of distilled water to form a paste and added with stirring, the latex was uniformly dispersed without agglomeration. When the obtained composition was subjected to the same test as in Example 1, the film showed antibacterial properties. Example 3 To 100 parts of the same compounded latex used in Example 1, 10 parts of acetate of 1,6-di-(4-chlorophenylbiguanide)hexane (solubility in water at 20°C is approximately 1.8 wt%) was added in advance. distilled water 12
When the latex was uniformly dispersed into a paste and added to the mixture while stirring, the latex was uniformly dispersed without agglomeration. When the obtained composition was subjected to the same test as in Example 1, the film showed antibacterial properties. Example 4 Anionic styrene with a solid content concentration of approximately 50 wt%
To 100 parts of butadiene copolymer latex (PH=9.5), 10 parts of 1,6-di-(4-chlorophenylbiguanide)hexane sulfate (solubility in water at 20°C is approximately 0.01 wt%) was added in advance to distilled water. 12
When the latex was added while stirring, the latex was uniformly dispersed without agglomeration. When the obtained composition was subjected to the same test as in Example 1, the film showed antibacterial properties. Example 5 Anionic vinyl chloride-vinylidene chloride copolymer latex with a solid content concentration of approximately 45 wt% (PH = 9.0)
100 parts of 1,6-di(aminohexyl biguanide)hexane phosphate (solubility in water is approx.
When 10 parts of 0.05wt%) were uniformly dispersed in 12 parts of distilled water in advance, the latex bath liquid was uniformly dispersed without agglomeration. When the obtained composition was subjected to the same test as in Example 1, the film showed antibacterial properties.

Claims (1)

[Scope of Claims] 1. An antibacterial latex composition comprising natural rubber latex or synthetic polymer latex and a poorly water-soluble biguanide compound or its salt. 2 The poorly water-soluble biguanide compound is 1,6-di-
The antibacterial latex composition according to claim 1, which is (4-chlorophenylbiguanide)hexane.