JPH119681A - Antimicrobial urethral catheterization catheter - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an antimicrobial urethral catheterization catheter with which the excellent antimicrobial property is maintained for a long period. SOLUTION: This antimicrobial urethral catheterization catheter consists of natural rubber latex introduced with a silver compd. or quaternary ammonium or quaternary phosphonium on its surface. The natural rubber latex is molded of natural rubber latex dispersed together with the silver compd. or the compd. connectable with quaternary ammonium or quaternary phosphonium.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to an antibacterial urinary catheter. More specifically, a urinary catheter molded from a natural rubber latex in which a compound capable of binding to an antibacterial substance is dispersed in a natural rubber latex as a base material is provided with silver ions or quaternary ammonium or quaternary ammonium as an antibacterial substance. The present invention relates to an antimicrobial urinary catheter in which quaternary phosphonium is mainly introduced into the surface by ionic bonding.

[0002]

2. Description of the Related Art Urinary catheters, which are one type of medical device to be placed in a living body, have been disinfected, sterilized, and used in some way prior to their use, but most of them are used for a long period of time. Often, the sterility of the urine catheter itself is not maintained, and improvements are desired.
The reason that the sterility cannot be maintained is that bacteria enter from outside through the inside and outside of the lumen of the catheter. Some invading bacteria can ascend against the flow of urine, causing infections such as urethritis, cystitis, and pyelonephritis.

As a countermeasure to date, there has been chemotherapy in which antibiotics and the like are administered prophylactically. However, in this method, since a large amount of antibiotics is administered, the problem of side effects cannot be avoided depending on the type of antibiotics. Once infected, chemotherapy temporarily eliminates bacteria, but re-infection is likely to occur due to the emergence of resistant bacteria, so there is a problem with easy chemotherapy.

[0004] As the most effective measure, there is a method of imparting antibacterial properties to the entire urinary catheter or the surface thereof.

[0005] Typical antibacterial substances include gold, silver, copper,
There are heavy metals such as zinc and their metal compounds. These have a broad antibacterial spectrum against bacteria and fungi in extremely small amounts in the form of metal ions. Up to now, attempts have been made to manufacture urinary catheters containing these metal compounds in a matrix to impart antibacterial properties.

[0006] In addition to the above-mentioned metal compounds, quaternary ammonium salts as cationic antibacterial substances are compounds having antibacterial properties. Since these compounds also show strong antibacterial activity against bacteria, attempts have been made to use them in urinary catheters which are contained in a matrix as in metal compounds to impart antibacterial properties.

A method disclosed in Japanese Patent Publication No. 6-34817 is one in which a silver-based antibacterial substance is applied to a urinary catheter. Here, a method of forming a urinary catheter coated with a latex containing silver protein is described.

[0008] Japanese Patent Publication No. 3-64143 discloses a urinary catheter containing a cationic antibacterial substance. In this method, a poorly water-soluble quaternary ammonium salt is contained on the surface of a urinary catheter.

As a method for introducing antibacterial properties, besides a method of processing by dispersing an antibacterial substance in a base material, Japanese Patent Publication No.
341 discloses a method of absorbing a solution of a water-soluble antibacterial substance into a urinary catheter, and then converting the antibacterial substance into a poorly water-soluble compound.

As disclosed in Japanese Patent Application Laid-Open No. 4-502111, there is a method of introducing an antibacterial substance between the leaching step and the curing step in producing a natural rubber product. Further, as disclosed in Japanese Patent Publication No. 24544/1990, there is a production method in which a coating having a maleic anhydride group is formed on the surface of a urinary catheter, the maleic acid group is hydrolyzed, and then an antibacterial substance is bound thereto.

When a compound having a strong antibacterial property against bacteria, such as protein silver or a quaternary ammonium salt, is dispersed in natural rubber latex and processed, a stable dispersion state is maintained in the latex for a long time. It is difficult to carry out, and aggregation of latex particles and sedimentation of antibacterial substances (particularly metal compounds) are apt to occur, so that the coating layer becomes uneven and it is difficult to obtain stable antibacterial properties. In addition, the antibacterial substance is dispersed in latex and exposed to a high temperature in a post-treatment process such as vulcanization after coating, and the antibacterial substance is oxidized or thermally decomposed, resulting in darkening and decomposition due to silver precipitation. There is a fear that the stability may decrease due to the material.

Regarding the method of applying the antibacterial substance other than mixing the antibacterial substance into the base material, the method of absorbing the antibacterial substance solution into the urinary catheter has a disadvantage in that the rate of penetration of the antibacterial substance into the base material is slow. It takes many days to complete the process, which is not an economical manufacturing method. Also, in the method of forming a maleic anhydride coating on the catheter surface and binding it with an antibacterial substance,
Processing steps such as forming a maleic acid film and hydrolyzing are increased.

[0013]

DISCLOSURE OF THE INVENTION The present invention solves the above-mentioned problems when an antibacterial substance is added to latex, shows excellent antibacterial properties, and shows the antibacterial properties over a long period of time. It is to provide an antimicrobial urinary catheter that is maintained.

[0014]

Means for Solving the Problems As a result of intensive studies to solve the above problems, the present inventors have found that a silver compound or quaternary ammonium or quaternary phosphonium is used as a substance having antibacterial properties, and urinary urea is introduced. The antibacterial property is imparted by being introduced either before or after the heat treatment after the catheter is molded, that is, the substance having the antibacterial property is not directly mixed into the base material prior to the processing. The present invention was found to be useful, and reached the present invention.

That is, the present invention has the following configuration. (1) An antimicrobial urinary catheter made of a natural rubber latex having a silver compound introduced on its surface, wherein the natural rubber latex is made of a natural rubber latex dispersed together with a compound having an amino acid residue capable of binding to silver ions. (2) An antimicrobial urinary catheter made of natural rubber latex having quaternary ammonium or quaternary phosphonium introduced on its surface, wherein the natural rubber latex is 4th
Antibacterial urinary catheter molded from natural rubber latex dispersed together with a compound capable of binding to quaternary ammonium or quaternary phosphonium (3) Antibacterial urinary catheter wherein silver compound is silver nitrate or silver acetate (4) An antimicrobial urinary catheter having a compound capable of binding to a quaternary ammonium or a quaternary phosphonium having the structure of the following formula [1] (5) A compound having an amino acid capable of binding to silver ions or a quaternary An antimicrobial urinary catheter in which the natural rubber latex dispersed together with a compound capable of binding to ammonium or a quaternary phosphonium has a pH of 5 or more. In either case, silver compound or quaternary ammonium or quaternary phosphonium Antimicrobial urinary catheter inserted

[0016]

Embedded image

In the formula [1], R ¹ and R ^{2 each} have 1 carbon atom.
_{N represents} an alkyl group of ₁ to 12, or a compound of 1 to 12 represented by CnH2n ₊ 1OH. Note that R ¹ and R ² may be the same or different.

[0018]

BEST MODE FOR CARRYING OUT THE INVENTION The antibacterial substance used in the antibacterial urinary catheter of the present invention is a silver compound or a quaternary ammonium salt or a quaternary phosphonium salt (hereinafter referred to as silver compound or quaternary phosphonium salt). A quaternary ammonium salt or a quaternary phosphonium salt is called an antibacterial substance).

In the present invention, the silver compound is preferably either silver nitrate or silver acetate from the viewpoint of good solubility in a solvent and high reactivity because of its low molecular weight.

Examples of the compound having an amino acid residue capable of binding to silver ions dispersed in natural rubber latex, which is a base material of the antimicrobial urinary catheter of the present invention, include, for example, amino acid monomers, amino acid oligomers, amino acid polymers, and the like.
Amino acid derivatives and the like. Only one of these may be used, or several may be used simultaneously.

Here, the amino acid oligomer means one having 2 to 10 amino acid residues. Further, the amino acid polymer refers to those having 11 or more amino acid residues, preferably those having 11 to 500 amino acid residues,
Those having 11 to 200 are more preferable. Specific examples include sodium poly-L-glutamate. Further, an amino acid derivative is a compound in which a part of an amino acid is bonded to another compound, and examples thereof include sodium stearoyl-L-glutamate.

In the present invention, the quaternary ammonium and the quaternary phosphonium are preferably those represented by the following formula [2].

[0023]

Embedded image

In the formula [2], R ¹ , R ² and R ^{3 each} represent an alkyl group having 1 to 12 carbon atoms, preferably 1 to 8 carbon atoms, an aryl group having 6 to 12 carbon atoms, preferably 6 to 10 carbon atoms, or And represents 7 to 20 aralkyl groups. R ⁴ has 1 carbon atom
２５25 or 3-20, more preferably 6-20
Represents an alkyl group. R ¹ , R ² , R ³ , and R ⁴ may be the same or different. A is a nitrogen atom or a phosphorus atom, and X is a chlorine atom or a bromine atom.

Specific examples of the quaternary ammonium and the quaternary phosphonium include, for example, tributyl lauryl ammonium, tributyl myristyl ammonium, tributyl cetyl ammonium, tributyl stearyl ammonium, triphenyl lauryl ammonium, triphenyl myristyl ammonium and triphenyl Cetyl ammonium, triphenyl stearyl ammonium, benzyl dimethyl lauryl ammonium, benzyl dimethyl myristyl ammonium, benzyl dimethyl cetyl ammonium, benzyl dimethyl stearyl ammonium, tributyl lauryl phosphonium, tributyl myristyl phosphonium, tributyl cetyl phosphonium, tributyl stearyl phosphonium, triphenyl lauryl phosphonium , Triphenylmyristylphosphonium, triphenylcetylphosphonium, triphenylstearylphosphonium, benzyldimethyllaurylphosphonium, benzyldimethylmyristylphosphonium, benzyldimethylcetylphosphonium, benzyldimethylstearylphosphonium, etc., which are represented by the formula [2]. If the compound has the structure
It is not particularly limited to these. In addition, these compounds are
A single type may be used, or a plurality of types may be used simultaneously.

The compound represented by the formula [1], which is a compound capable of binding to quaternary ammonium or quaternary phosphonium dispersed in the substrate of the antimicrobial urinary catheter of the present invention, is, for example, dimethyl-5-sulfo. Isophthalate sodium salt, diethyl-5-sulfoisophthalate sodium salt, dibutyl-5-sulfoisophthalate sodium salt, dihexyl-5-sulfoisophthalate sodium salt, dioctyl-5-sulfoisophthalate sodium salt, di (6-hydroxy Hexamethylene) -5-sulfoisophthalate sodium salt, di (6-hydroxyoctamethylene) -5-sulfoisophthalate sodium salt and the like have been confirmed to be safe for living organisms. Of these, only one type may be used, or two or more types may be used simultaneously.

The compound having an amino acid capable of binding to silver ions or the compound capable of binding to quaternary ammonium or quaternary phosphonium may be directly incorporated into the substrate, or a compound such as a dispersant may be added. The mixture may be mixed in a state of being well dispersed by a ball mill.

The amount of the compound having an amino acid capable of binding to silver ions or the compound capable of binding to quaternary ammonium or quaternary phosphonium in the substrate varies depending on the type and combination of the compounds. Is 0.001 to 50% by weight, more preferably 0.01 to 25% by weight, based on the substrate. In this case, 0.00
If the amount is less than 1% by weight, the amount of the antibacterial substance that can be bound is too small, so that the antibacterial property cannot be sufficiently exhibited. On the other hand, if it is 50% by weight or more, the physical properties of the base material may be impaired.

The natural rubber latex dispersed together with a compound capable of binding to an antibacterial substance serving as a base material of the antibacterial urinary catheter according to the present invention has a pH of from the viewpoint of dispersibility of components.
Is preferably 5 or more. More preferably pH 7
The pH is more preferably pH 7-12.

The method of introducing an antimicrobial substance into an antimicrobial urinary catheter according to the present invention is such that a heat treatment is performed after the urinary catheter is molded, and immersion in a solution of the antimicrobial substance before or after the heat treatment step. Features. Preferred conditions for the heat treatment performed after molding the urinary catheter in the present invention are 50 to 150 ° C. for 30 minutes to 24 hours.

The antimicrobial urinary catheter obtained by the above steps does not need to consider the dispersibility of the substrate and the antimicrobial substance, and the step of imparting antimicrobial properties can be performed under mild processing conditions. Application of antibacterial substances is possible. In addition, since the antimicrobial substance is efficiently chemically bonded only to the surface of the urinary catheter that requires antimicrobial performance,
It is economical because no extra antibacterial substance is required, and the antibacterial property can be maintained for a long time because the antibacterial substance is bonded by a chemical bond.

The treatment conditions of the antibacterial substance to be processed into the antibacterial urinary catheter of the present invention vary depending on the kind and combination, but generally, an aqueous solution of 0.01 to 50% by weight or an aqueous solution of 10 to 20% methanol is used. Appropriate. More preferably, 0.1 to 20% by weight is appropriate.
In this case, when the amount is 0.1% by weight or less, a sufficient amount of the antibacterial substance does not bind to the catheter, and when the amount is 50% by weight or more, the compound does not sufficiently dissolve or the viscosity of the solution itself increases,
Not suitable because it becomes difficult to handle.

The catheter is immersed in the antibacterial substance solution satisfying the above conditions. The conditions are not limited as long as they do not adversely affect the catheter base material and the antibacterial substance. Usually, the temperature is 20 to 100C, particularly preferably 30 to 80C, and in this case, it is preferable to shake.
The preferred immersion time depends on the immersion temperature.
At a temperature of 5 ° C., 5 minutes to 1 week, preferably 1 minute
0 minutes to 3 days.

The antimicrobial substance bound to the antimicrobial urinary catheter of the present invention is water-soluble before binding to the compound dispersed in the urinary catheter base, but is contained in the urinary catheter base. By exhibiting the property of lowering the water solubility when bound to a bondable compound than before binding, the antibacterial component is less likely to be washed away by urine or the like during use, and long-term antibacterial properties are obtained.

As described above, the antimicrobial urinary catheter of the present invention can bind an antimicrobial substance to the inner and outer surfaces of the catheter lumen under mild conditions as compared with the conventional antimicrobial urinary catheter. Also, unlike the coating method, it is easy to finish the inner and outer diameters of about 8 to 30 Fr, which are the sizes generally used in the case of urinary catheters.

[0036]

The present invention will be described below with reference to examples. The present invention is not particularly limited by the examples.

Example 1 0.3 part of zinc dimethyldithiocarbamate, 1.5 parts of colloidal sulfur, 3.0 parts of active zinc were added to 100 parts of natural rubber latex having a solid content of 60%.
1.2 parts of stearic acid and 10 parts of dimethyl-5-sulfoisophthalate sodium were added to prepare a natural rubber latex solution. The pH of the natural rubber latex solution was 10.

Next, the immersion type for urinary catheter was immersed in the above natural rubber latex solution and dried (80 ° C., 10 minutes) repeatedly to a thickness of 1.6 mm. The last is 70 ° C, 12
After drying for 1 hour, then washing in running water for 1 week and drying, a urinary catheter was prepared. The urinary catheter was immersed in a 10% aqueous solution of tributyldodecylphosphonium chloride and shaken at 40 ° C. for 6 hours. Thereafter, the urinary catheter was washed with water and dried at 70 ° C. to obtain an antibacterial urinary catheter.

The above antibacterial urinary catheter is 5 cm long.
And sterilized with ethylene oxide gas. A Pseudomonas aeruginosa suspension having a bacterial count of about 1 × 10 ⁵ cells / ml was prepared with a broth solution (diluted 50-fold with physiological saline), and the antibacterial urinary catheter was immersed in the suspension. Shaking culture was performed at 37 ° C. for 24 hours. The number of bacteria in the liquid after the culture was measured by a smear method to evaluate antibacterial properties. The same evaluation was performed for Escherichia coli and Staphylococcus aureus. The results are shown in Table 1.

Example 2 0.5 parts of 2-mercaptobenzothiazole zinc salt, 1.5 parts of colloidal sulfur, and 1 part of active zinc were added to 100 parts of natural rubber latex having a solid content of 60%.
0 parts, 1.0 part of stearic acid and 10 parts of taurine were added to prepare a natural rubber latex solution. The pH of the natural rubber latex solution was 10. Next, the immersion mold for urinary catheter is immersed in the above-mentioned natural rubber latex solution, and dried (80 ° C, 1 ° C).
0 min) was repeated to a thickness of 1.6 mm. The last is 70
C., dried for 12 hours, washed in running water for one week, and dried to prepare a urinary catheter.

The urinary catheter was immersed in a 10% aqueous solution of tributyltetradecylphosphonium chloride and shaken at 40 ° C. for 6 hours. Thereafter, the urinary catheter was washed with water and dried at 70 ° C. to obtain an antibacterial urinary catheter. Antibacterial evaluation was performed in the same manner as in Example 1. The results are shown in Table 1.

Example 3 0.5 parts of 2-mercaptobenzothiazole sodium salt, 1.5 parts of colloidal sulfur, 1.0 part of active zinc, and 1.0 part of stearic acid were added to 100 parts of natural rubber latex having a solid content of 60%. 0 parts, stearoyl-L
-5 parts of disodium glutamate was added to prepare a natural rubber latex solution. PH of natural rubber latex liquid is 10
Met. Next, the immersion type for urinary catheter was immersed in the above-mentioned natural rubber latex solution and dried (80 ° C., 10 minutes).
Repeated to a thickness of 6 mm. Finally, it was dried at 70 ° C. for 12 hours, then washed in running water for one week and dried to prepare a urinary catheter.

The above catheter was immersed in a 5% aqueous solution of silver nitrate and shaken at 37 ° C. for 3 hours. Thereafter, the urinary catheter was washed with water and dried at 70 ° C. to obtain an antibacterial urinary catheter. Antibacterial evaluation was performed in the same manner as in Example 1. The results are shown in Table 1.

Example 4 0.5 parts of 2-mercaptobenzothiazole sodium salt, 1.5 parts of colloidal sulfur, 1.0 part of active zinc, and 1.0 part of stearic acid were added to 100 parts of natural rubber latex having a solid content of 60%. 0 parts, stearoyl-L
After adding 5 parts of disodium glutamate, the natural rubber latex solution was adjusted to pH 6.0 with hydrochloric acid. Next, the immersion mold for urinary catheter was immersed in the above-mentioned natural rubber latex liquid and dried (80 ° C., 10 minutes) to a thickness of 1.6 mm. Finally, it was dried at 70 ° C. for 12 hours, then washed in running water for one week and dried to prepare a urinary catheter.

Comparative Example 1 0.3 part of zinc dimethyldithiocarbamate, 1.5 parts of colloidal sulfur, 3.0 parts of active zinc were added to 100 parts of natural rubber latex having a solid content of 60%.
1.2 parts of stearic acid was added to prepare a natural rubber latex solution. The pH of the natural rubber latex solution was 10.

Next, the immersion type for urinary catheter was immersed in the above-mentioned natural rubber latex solution and dried (80 ° C., 10 minutes) to a thickness of 1.6 mm. The last is 70 ° C, 12
After drying for 1 hour, then washing in running water for 1 week and drying, a urinary catheter was prepared. Antibacterial evaluation was performed in the same manner as in Example 1. The results are shown in Table 1.

Comparative Example 2 0.3 part of zinc dimethyldithiocarbamate, 1.5 parts of colloidal sulfur, 3.0 parts of active zinc were added to 100 parts of natural rubber latex having a solid content of 60%.
1.2 parts of stearic acid and 10 parts of dimethyl-5-sulfoisophthalate sodium were added to prepare a natural rubber latex solution. The pH of the natural rubber latex solution was 10. Next, the immersion type for urinary catheter was immersed in the above-mentioned natural rubber latex solution and dried (80 ° C., 10 minutes) at 1.6 mm.
To the thickness of Finally, dry at 70 ° C for 12 hours,
Thereafter, it was washed and dried in running water for one week to prepare a urinary catheter. The antibacterial property was evaluated in the same manner as in Example 1. The results are shown in Table 1.

Comparative Example 3 0.3 part of zinc dimethyldithiocarbamate, 1.5 parts of colloidal sulfur, 3.0 parts of active zinc were added to 100 parts of natural rubber latex having a solid content of 60%.
1.2 parts of stearic acid was added to prepare a natural rubber latex solution. The pH of the natural rubber latex solution was 10.
Next, the immersion mold for urinary catheter was immersed in the above-mentioned natural rubber latex liquid and dried (80 ° C., 10 minutes) to a thickness of 1.6 mm. Finally, it was dried at 70 ° C. for 12 hours, then washed in running water for one week and dried to prepare a urinary catheter.

The urinary catheter was immersed in a 10% aqueous solution of tributyldodecylphosphonium chloride and shaken at 40 ° C. for 6 hours. Thereafter, the urinary catheter was washed with water and dried at 70 ° C. to obtain an antibacterial urinary catheter.
Antibacterial properties were evaluated in the same manner as in Example 1. Table 1 shows the results
It was shown to.

Comparative Example 4 0.3 part of zinc dimethyldithiocarbamate, 1.5 parts of colloidal sulfur, 3.0 parts of active zinc were added to 100 parts of natural rubber latex having a solid content of 60%.
After adding 1.2 parts of stearic acid and 10 parts of dimethyl-5-sulfoisophthalate sodium, the mixture is adjusted to pH 4.0 with hydrochloric acid.
As a result, the latex liquid aggregated, and it was not possible to prepare a catheter having a uniform surface.

[0051]

[Table 1]

[0052]

The antibacterial urinary catheter according to the present invention has excellent antibacterial performance immediately after use since a silver compound or an antibacterial substance such as quaternary ammonium or quaternary phosphonium is present on the catheter surface. In addition, since the antibacterial substance binds to the compound in the base material and is hardly soluble in water, the antibacterial property is maintained for a long time. Furthermore, since the inner diameter and the outer diameter of the urinary catheter are not changed by ion-bonding the above antibacterial substance, the antibacterial urinary catheter according to the standard can be manufactured.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Masakazu Tanaka, Inventor 2-1-1 Katata, Otsu-shi, Shiga Inside Toyobo Co., Ltd. (72) Inventor Sou Arimori 2-1-1 Katata, Otsu-shi, Shiga No. Toyobo Co., Ltd.

Claims (6)

[Claims] 1. An antimicrobial urinary catheter made of natural rubber latex having a silver compound introduced on its surface, wherein the natural rubber latex is dispersed together with a compound having an amino acid residue capable of binding to silver ions. An antibacterial urinary catheter molded from latex. 2. An antimicrobial urinary catheter comprising a natural rubber latex having quaternary ammonium or quaternary phosphonium introduced on its surface, wherein the natural rubber latex binds to quaternary ammonium or quaternary phosphonium. An antibacterial urinary catheter characterized by being molded from natural rubber latex dispersed with possible compounds. 3. The antimicrobial urinary catheter according to claim 1, wherein the silver compound is silver nitrate or silver acetate. 4. The antimicrobial urinary catheter according to claim 2, wherein the compound capable of binding to quaternary ammonium or quaternary phosphonium has a structure represented by the following formula [1]. Embedded image (In the formula [1], R ¹ and R ^{2 each} represent an alkyl group having 1 to 12 carbon atoms or _{n represented by} C _n H _{2n + 1} OH is 1 to
12 compounds, wherein R ¹ and R ² may be the same or different.) 5. The natural rubber latex dispersed together with the compound having an amino acid capable of binding to silver ions according to claim 1 or the compound capable of binding to quaternary ammonium or quaternary phosphonium according to claim 2 has a pH of 5. The antimicrobial urinary catheter according to any one of claims 1 to 4, wherein the number is 5 or more. 6. The method according to claim 1, wherein a heat treatment is performed after the urinary catheter is formed, and a silver compound or a quaternary ammonium or a quaternary phosphonium is introduced before or after the heat treatment. The antimicrobial urinary catheter according to item 1.