Field of the Invention

This invention relates to compositions useful in making medical devices and useful in providing antimi- . crobial coatings on medical devices. The invention particularly relates to antimicrobial compositions use¬ ful as coatings for medical connection devices and for making medical connection devices which are susceptible to touch contamination. These compositions are also useful as antimicrobial coatings for access systems and lead devices (for example, shunts, cannulae, catheters, wires, enteral feeding tubes, endotracheal tubes, per¬ cutaneous devices and other solid or hollow tubular devices) used for a variety of medical purposes. In addition, the compositions may be used as antimicrobial coatings for wound coverings or in the manufacture of thin, flexible, skin-like wound coverings.

Background of the Invention

Indwelling urethral catheterization is performed in approximately 10 to 15 percent of hospitalized patients. About 25 percent of these patients contract bacterial infections of the urinary tract. Two studies of note are. Garibaldi, R. A.; Burke, J. P.; Diσkman, M. L. ; and Smith, C. B., "Factors Predisposing to Bacteriuria During Indwelling Urethral Cathiterization". New Engl. J. Med., 291:215, 1974 and Kunin, C. M. and McCormack, R. C. , "Prevention of Catheter-Induced Urinary-Tract Infections by Sterile Closed Drainage". New Engl. J. Med., 274:1155, 1966. T e incidence of catheter-induced urinary tract infection still remains a problem despite various pro¬ phylactic measures that have been tried. Attempts to

reduce the incidence of urinary tract infections have included the application of antibiotic ointments or other bactericidal agents to the surface of the cathe¬ ter, frequent bladder irrigation with concommittant prophylactic administration of antibiotics, or inhibi¬ tion of the growth of bacteria in urine drainage con¬ tainers. See, Akiyama, H. and Okamoto, S., "Prophylaxis of Indwelling Urethral Catheter Infection: Clinical Experience with a Modified Foley Catheter and Drainage System". The Journal of Urology, 121:40, 1979. United States Patent No. 4,054,139, Oligodynamic Catheter, to Crossley, teaches a catheter, or the like, which com¬ prises an oligodynamic agent such as metallic silver or its compounds, alone or in association with other heavy metals such as gold, for the purpose of reducing infection associated with these devices.

It would be desirable to provide compositions use¬ ful as coatings for urinary catheters, lead devices, medical connections susceptible to touch contamination and the like, and compositions useful as a material for making these various devices, whereby the proli¬ feration of bacteria thereon or in relatively close proximity thereto is inhibited. Inhibiting the proli¬ feration of bacteria on urinary catheters and catheter adapter connections would reduce the risk of urinary tract infections caused by bacteria accessing the urinary tract at these sites. It also would be de¬ sirable for the compositions to be easily applied as coatings on presently existing medical connections and devices. A desirable characteristic of such a composition would be an antimicrobial effect which is long lasting without being physiologically incompatible with nearby tissue.

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Description of the Invention

In accordance with this invention, antimicrobial compositions are provided which find particular utility as coatings which inhibit the proliferation of bacteria near the surface of urinary catheters and the connec¬ tion between the catheter and the drainage tube, namely, the catheter/catheter adapter --unction site. The anti¬ microbial coating on the catheter inhibits the prolifera¬ tion of bacteria in the area between the catheter and the walls of the urethra, and the antibacterial coating on the catheter adapter inhibits the proliferation of bacteria in the closed area connecting the catheter and the catheter adapter.

Catheters implanted in patients undergoing con- tinuous ambulatory peritoneal dialysis also can be coated with an antimicrobial composition of this in¬ vention. An antimicrobial composition of this inven¬ tion can be applied as a coating to medical shunts, cannulae, catheters, wires and other solid or hollow tubular devices used for medical purposes.

Preferably, the coating using an antimicrobial composition is prepared by mixing a suitable resin and a compound of a physiological , antimicrobial metal in an appropriate solvent for the resin. The solvent should not adversely effect the activity of the metal compound as an antimicrobial agent. The coating can be applied to a medical device by dipping in the mix¬ ture of resin, solvent, and physiological, antimicro¬ bial metal compound and thereafter allowing the solvent to evaporate. Both inside and outside surfaces may be coated. Alternatively, the medical articles may be sprayed with the mixture and the solvent allowed to evaporate. Where appropriate, particularly with a latex rubber resin, a volatile liquid carrier may be

used with the resin dispersed in the volatile liquid. An article may be dipped or sprayed with this prepara¬ tion. Upon evaporation of the volatile liquid and curing of the resin a coating for the article is pro- vided.

Indeed, articles can be made from a composition of a suitable resin and a compound of physiological, antimicrobial metal by molding the composition to form the article. The resins used in formulating the mixture include, for example, acrylonitrile-butadiene-styrene copolymer, rigid polyvinyl chloride, curable silicones, alkoxy cured RTV silicone rubber, polyesters, rubber latexes (e.g., natural or synthetic polyisoprene), polyurethanes, styreήe-block copolymers (e.g., Kraton-D and Kraton-G, manufactured by Shell), ethylene copolymers (e.g., vinyl acetate, ethyl acrylate, or mixtures thereof), ethylene copolymers of maleic anhydride, acrylic acid or both, polycarbonates, nylons, and polymethyl methacrylate. Into a mixture of resin and solvent is added a quantity of physiological, antimicrobial metal compound. Alternatively, a quantity of physiological, antimicro¬ bial metal compound may be mixed with a resin for direct molding of an article. Physiological, antimicrobial metals are meant to include the precious metals, such as silver, gold and platinum, and copper and zinc. Physiological, antimicrobial metal compounds used herein include oxides and salts of preferably silver and also gold, for example: silver acetate, silver benzoate, silver carbonate, silver citrate, silver chloride, sil¬ ver iodide, silver oxide, silver sulfate, gold chloride and gold oxide. Platinum compounds such as chloropla- tinic acid or its salts (e.g., sodium and calcium chlo- roplatinate) may also be used. Also, compounds of

copper and zinc may be used, for example: oxides and salts of copper and zinc such as those indicated above for silver. Single physiological, antimicrobial metal compounds or combinations of physiological, antimicrobial metal compounds may be used.

Preferred physiological, antimicrobial metal compounds used in this invention are silver acetate, silver oxide, silver sulfate, gold chloride and a combination of silver oxide and gold chloride. Pre- ferred quantities of physiological, antimicrobial metal compound are those sufficient to produce, within a 24 hour period, a solution of at least 10~ molar concentration of metal ion concentration in a stagnant film of liquid in contact with a surface of an article made from a composition of this invention or an article coated with a composition of this invention.

Brief Description of the Drawings

For a more complete understanding of this inven¬ tion, reference should now be had to the embodiments illustrated in greater detail in the accompanying drawings.

In the drawings:

Figure 1 is an elevational view of a catheter adapter showing one end coated with an antimicrobial composition of this invention. Figure 2 is an elevational view of a Foley catheter showing the portion of the catheter typically inserted into the urethra, coated with an antimicrobial compo¬ sition of this invention.

Figure 3 is a perspective view of the catheter adapter of this invention shown connecting a urinary drainage tube and a catheter.

Detailed Description of the Drawings

Turning now to the drawings. Figure 1 shows a conventional catheter adapter 10 after it has been coated with an antimicrobial composition of this in¬ vention. Catheter adapter 10 has drainage tube end 12, catheter end 14, and injection site 16.

Catheter end 14 is spray coated or dip coated with an antimicrobial composition of this invention. The shaded portion of catheter end 14 is illustrative of the coating.

Figure 2 shows urinary catheter 18. Catheter 18 has drainage connection 20 and inflation connection 22 for inflating the catheter balloon.

The shaded portion of catheter 18 illustrates the area coated by an antimicrobial composition of this invention. Typically, this coating will be applied to that portion of catheter 18 which resides in the urethra of a patient.

A typical connection of catheter adapter 10 is illustrated in Figure 3. Catheter adapter 10 has the coated catheter end 14 connected to drainage connec¬ tion 20 of the catheter. Drainage tube end 12 is connected to drainage tube 24 to complete the connec¬ tion. Drainage tube 24 drains into a urinary drainage bag (not shown).

The risk of touch contamination of catheter end 14 is reduced by coating catheter end 14 of catheter adapter 10 with an antimicrobial composition of the present invention. Reducing the risk of touch contami¬ nation of catheter end 14 reduces the risk of subsequent urinary tract infection caused by a contaminated catheter adapter.

The antimicrobial composition coating catheter 18 inhibits the proliferation and migration of bacteria

in a stagnant film between the coated catheter walls and the walls of the urethra. By inhibiting the pro¬ liferation and migration of bacteria through this route, subsequent urinary tract infection caused by such proliferation and migration of bacteria is re¬ duced.

The examples below are offered for illustrative purposes only and are not intended to limit the scope of the invention of this application, which is as de- fined in the claims below.

EXAMPLE 1 A mixture was made of 50 milliliters of methylene chloride, 5 grams of acrylonitrile-butadiene-styrene copolymer (LUSTRAN 240-29, a trademark of the Monsanto Company), and 1.2 grams of silver oxide powder. The mixture was stirred for approximately one hour. A polyvinyl chloride catheter adapter, used to connect a urinary catheter and drainage tubing for a urinary drainage connector, was coated on the exterior and the interior by dipping the connector into the mixture. Upon evaporation of the solvent, an antimicrobial coat¬ ing remained bonded to the catheter adapter. Catheter adapters can also be sprayed with the mixture.

EXAMPLE 2 A mixture was made by combining 50 milliliters of tetrahydrofuran, 5 grams of polyvinyl chloride (Alpha Plastics and Chemicals, clear rigid vinyl 2212/7-118), and 1.2 grams of silver oxide powder. The mixture was stirred for about one hour. Vinyl compatible catheter adapters may be either dip coated or spray coated with this mixture. By dip coating the catheter adapter, the exterior and interior

surfaces may be conveniently coated. Upon evaporation of the solvent, tetrahydrofuran, an antimicrobial coat¬ ing will remain bonded to the device.

EXAMPLE 3 Equivalent results may be obtained when a mixture is made by combining 25 milliliters of tetrahydrofuran, 25 milliliters of methylene chloride, 2.5 grams of acrylonitrile-butadiene-styrene copolymer (LUSTRAN 240-29), 2.5 grams of polyvinyl chloride (Alpha Plastics and Chemicals, clear rigid vinyl 2212/7-118), and 1.2 grams of silver oxide powder. The mixture may be stirred for about one hour.

A catheter adapter may be either dip coated or spray coated with this mixture. Upon evaporation of the solvents, an antimicrobial coating will remain bonded to the device.

EXAMPLE 4 A mixture was made by combining 10 milliliters of alkoxy curing RTV rubber, 65 milliliters of FREON TF solvent (FREON is a trademark of E. I. du pont de Nemours & Co.), and 5 grams of silver oxide powder. The mixture was stirred for about one hour.

A silicone rubber Foley catheter was dipped into this mixture and upon evaporation of the solvent and curing of the RTV, a flexible, antimicrobial coating on the interior and exterior surfaces of the silicone rubber catheter was provided. The coating adhered well to the catheter. Spray coating of the catheter is a viable alternative.

EXAMPLE 5

A mixture was made by combining 100 milliliters

of tetrahydrofuran, 5 grams of acrylonitrile-butadiene- styrene copolymer (LUSTRAN 240-29) , and 1 gram of silver acetate. The mixture was stirred for about one hour. Acrylonitrile-butadiene-styrene compatible devices may be spray or dip coated with the mixture. Upon evapora¬ tion of the solvent, an antimicrobial coating will remain on the device.

EXAMPLE 6 Equivalent results may be obtained when a mixture is made by combining 100 milliliters of methylene chlo¬ ride, 5 grams of acrylonitrile-butadiene-styrene copoly¬ mer (LUSTRAN 240-29), and 1 gram of silver sulfate. The mixture may be stirred for about one hour. Acrylonitrile¬ butadiene-styrene compatible devices may be spray or dip coated with the mixture. Upon evaporation of the solvent, an antimicrobial coating will remain on the device.

EXAMPLE 7 Equivalent results may be obtained when a mixture is made by combining 50 milliliters of tetrahydrofuran, 5 grams of polyvinyl chloride (Alpha Plastics and

Chemicals, clear rigid vinyl 2212/7-118), and 1.2 grams of gold chloride powder. The mixture may be stirred for about one hour. Polyvinyl chloride compatible de¬ vices may be spray or dip coated with the mixture. Upon evaporation of the solvent, an antimicrobial coating will remain on the device.

EXAMPLE 8 Equivalent results may be obtained when a mixture is made by combining 25 milliliters of tetrahydrofuran, 25 milliliters of methylene chloride, 2.5 grams of acrylonitrile-butadiene-styrene copolymer (LUSTRAN

240-29), 2.5 grams of polyvinyl chloride (Alpha Plastics and Chemicals, clear rigid vinyl 2212/7-118), and 1.2 grams of gold chloride powder. The mixture may be stirred for about one hour. Devices may be either dip coated or spray coated with this mixture. Upon evaporation of • the solvents, an antimicrobial coating remains bonded to the device.

EXAMPLE 9 Equivalent results may be obtained when a mixture is made by combining 10 milliliters of alkoxy curing RTV, 65 milliliters of FREON TF solvent and 5 grams of gold chloride powder. The mixture may be stirred for about one hour.

A silicone rubber Foley catheter or other silicone rubber medical device may be dipped into this mixture and upon evaporation of the solvent and curing of the RTV, a flexible, antimicrobial coating for the silicone rubber catheter will be provided. Spray coating of the catheter is also a viable alternative.

EXAMPLE 10

Equivalent results may be obtained when a mixture is made by combining 50 milliliters of tetrahydrofuran, 5 grams of polyvinyl chloride (Alpha Plastics and Chemicals, clear rigid vinyl 2212/7-118), 1.2 grams of silver oxide powder, and 0.1 gram of gold chloride powder. The mixture may be stirred for about one hour.

Vinyl compatible catheter adapters or other medi¬ cal devices may be either dip coated or spray coated with this mixture. Upon evaporation of the solvent, tetrahydrofuran, an antimicrobial coating will remain on the device.

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EXAMPLE 11 Equivalent results may be obtained when a mixture is made by combining 25 milliliters of tetrahydrofuran, 25 milliliters of methylene chloride, 2.5 grams of acrylonitrile-butadiene-stryrene copolymer (LUSTRAN

240-29), 2.5 grams of polyvinyl chloride (Alpha Plastics and Chemicals, clear rigid vinyl 2212/7-118), 1.2 grams of silver oxide powder, and 0.1 gram of gold chloride powder. The mixture may be stirred for about one hour. Devices may be either dip coated or spray coated with this mixture. Upon evaporation of the solvents, an antimicrobial coating will remain on the device.

EXAMPLE 12 Equivalent results may be obtained when a mixture is made by combining 10 milliliters of alkoxy curing RTV, 65 milliliters of FREON TF solvent, 5 grams of silver oxide powder, and 0.5 gram of gold chloride powder. The mixture may be stirred for about one hour. A silicone rubber Foley catheter or other silicone rubber medical device may be dipped into this mixture and upon evaporation of the solvent and curing of the RTV, a flexible, antimicrobial coating for the silicone rubber catheter is provided. Spray coating of the catheter is also an alternative application means.

EXAMPLE 13

Equivalent results may be obtained when a mixture is made by combining 100 milliliters of natural rubber latex with 10 grams of silver oxide powder. The mixture may be stirred until the silver oxide is dispersed.

Cured latex rubber devices may be dip coated with this

mixture. Upon evaporation of the volatile liquid car¬ rier and curing of the coating mixture, an antimicrobial coating having high elastomeric characteristics will remain adhered to the device.

EXAMPLE 14

Equivalent results may be obtained when a mixture is made by combining 50 milliliters of methylene chlo¬ ride, 5 grams of acrylonitrile-butadiene-styrene copoly¬ mer (LUSTRAN 240-29), and 1.2 grams of copper oxide powder. The mixture may be stirred for about one hour. A catheter adapter may be either dip coated or spray coated with this mixture. Upon evaporation of the solvent, an antimicrobial coating will remain bonded to the device.

EXAMPLE 15

Equivalent results may be obtained when a mixture is made by combining 50 milliliters of methylene chlo¬ ride, 5 grams of acrylonitrile-butadiene-styrene copoly¬ mer (LUSTRAN 240-29), and 1.2 grams of zinc oxide powder. The mixture may be stirred for about one hour. A cathe¬ ter adapter may be either dip coated or spray coated with this mixture. Upon evaporation of the solvent, an antimicrobial coating will remain bonded to the de¬ vice.

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