Method and composition for producing catheters with antibacterial property

• US 20040106912A1
• Filed: 12/02/2002
• Published: 06/03/2004
• Est. Priority Date: 12/02/2002
• Status: Active Grant

• Current Assignee: Shenkar College Of Engineering And Design
• Original Assignee: Shenkar College Of Engineering And Design
• Inventors: Rosinskaya, Cecilia, Weinberg, Amotz
• Granted Patent: US 7,597,903 B2
• Time in Patent Office: Days
• US Class Current: 604/500
• CPC Class Codes: A61L 2300/206 Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/208 Quaternary ammonium compounds
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 29/085 Macromolecular materials
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: C08L 5/08 Chitin; Chondroitin sulfate; Hyaluronic acid; Derivatives thereof

Abstract

A medical device and a method for imparting antibacterial properties to the device, made from hydrophobic polymer, particularly to urinary latex catheters comprises treatment of the device by spreading, dipping or spraying and consequent drying with natural biodegradable polymers (A), composition including a cross-linking agent (B) for partial cross-linking the mentioned polymer and an anti-microbial agent compatible with A and B.

The polymer may be from a group of polysachharides, for example polyglucosamine-chitosan. For partial cross-linking of the polymer substances having aldehyde groups such as glucose or evolving aldehydes such as hexamethylenetetramine or their mixtures are used.

The polymer is able to form on the surface of the medical device a thin film that swells in wet or moisturized state once inserted into the body. In the swollen state it will gradually release an anti-microbial agent.

Anti-microbial agent substances with anti-infective properties having cationic nature such as chorhexidine may be used.

Claims

1. A medical device coated at least on its outer surface with a slow-release antibacterial composition, comprising a mixture of:

a biodegradable polymer swelling when in contact with body fluids;

a cross-linking agent causing partial cross-linking of said polymer; and

an anti-microbial agent compatible with said polymer and said cross-linking agent and slowly releasable therefrom on swelling of said polymer and method of its production.

2. The medical device as claimed in claim 1, wherein said medical device is a urinary Foley latex catheter.

3. The medical device as claimed in claim 2, wherein said medical device is silicone treated.

4. The medical device as claimed in claim 1, wherein said polymer is a polysaccharide.

5. The medical device as claimed in claim 4, wherein said polysaccharide is polyglucosamine-chitosan.

6. The medical device as claimed in claim 5, wherein said polymer-chitosan has a molecular weight at range:

10⁴-10⁶ and degree of deacetylation at range;

75% and 87%.

7. The method of claim 5 wherein the said natural biodegradable polymer chitosan (polyglucosamine) is used at concentration in the solution at range 1.5-4.5 (w/w) %.

8. The medical device as claimed in claim 1, wherein said cross-linking agent is a monosaccharide.

9. The medical device as claimed in claim 8, wherein said cross-linking agent is dextrose.

10. The medical device as claimed in claim 9 wherein said cross-linking agent-dextrose is used at range of concentrations 0.5-5.0% of own weight of dry chitosan, preferably 0.5-2.0%.

11. The medical device as claimed in claim 1, wherein said cross-linking agent evolves a substance containing aldehyde groups.

12. The medical device as claimed in claim 11, wherein said cross-linking agent is hexamethylentetramine (urotropin).

13. The medical device as claimed in claim 12 wherein said cross-linking agent hexamethylentetramine (urotropin) is used at range of concentrations 0.5-3.0% of own weight of dry chitosan, preferably 1.0-1.5%.

14. The medical device as claimed in claim 1, wherein said cross-linking agent is a mixture of hexamethylentetramine and monosaccharide-dextrose.

15. The medical device as claimed in claim 14 wherein said cross-linking agent is a mixture of monosaccharide (dextrose) and hexamethylenetetramine (urotropin) by ratio of weights hexamethylenetetramine to dextrose, varying from 5:

1 to 1;

5, besides the concentration of dextrose is in limits 0.5-5.0% of own weight of dry chitosan and concentration of hexamethylentetramine is in limits 0.5-3.0% of own weight of dry chitosan.

16. The medical device as claimed in claim 1, wherein said anti-microbial agent is a biguanide.

17. The medical device as claimed in claim 16, wherein said anti-microbial agent is chlorhexidine diacetate and/or chorhexidine digluconate.

18. The method of claim 17 wherein the said anti-bacterial agent chlorhexidine digluconate or diacetate is used at range of concentrations 2.0-10.0 g/kg of composition, preferably 3.0-6.0 g/kg.

19. The medical device as claimed in claim 1, wherein hexamethylentetramine (urotropin) is used at a concentration allowing said substance to act both as a cross-linking agent and as an anti-microbial agent. It is used at a range of concentrations 1.0-10.0% of own weight of dry chitosan, preferably 2.0-4.0%.

20. The medical device as claimed in claim 1, wherein said anti-microbial agent is a quaternary ammonium compound.

21. The medical device as claimed in claim 20 wherein antibacterial agents are quaternary ammonium compounds such as benzalkonium choride, N-cetyl-N,N,N-trimethylammonium bromide, 1,10 bis (dimethylcarbomethoxymethylammonium) dichloride at a range of concentrations of 5.0-20.0 g/kg, preferably 10-15 g/kg of the composition.

24. A method for coating a tubular medical article as claimed in claim 18, wherein said polymer is dissolved in a 1.0-1.5% water solution of CH3COOH and stirred to produce a homogenized'"'"' translucent viscous solution.

22. A medical device coated at least on its outer surface with a slow-release antibacterial composition, substantially as described hereinbefore.

23. A method for coating a medical device, comprising the steps:

a) preparing an aqueous solution of a biodegradable polymer, a cross-linking agent causing partial cross-linking of said polymer and an anti-microbial agent compatible with said polymer and said cross-linking agent;

b) applying said solution to said device

c) drying the medical device