Anti-infective and antithrombogenic medical articles and method for their preparation

• US 5,451,424 A
• Filed: 11/24/1992
• Issued: 09/19/1995
• Est. Priority Date: 01/18/1989
• Status: Expired due to Term

• Current Assignee: Becton, Dickinson & Co
• Original Assignee: Becton, Dickinson & Co
• Inventors: Solomon, Donald D., Byron, M. Parke
• Primary Examiner(s): Rosenbaum, C. Fred
• Assistant Examiner(s): Stright, Jr., Ronald K.
• Application Number:
  US07/980,984
• Time in Patent Office: 1,029 Days
• Field of Search: 424/78.08, 424/81, 424/83, 514/822, 604/264-266, 604/49, 604/53, 524/916, 524/195, 523/112, 523/122, 623/12, 427/2.1-2.3
• US Class Current: 427/2.1
• CPC Class Codes: A61L 2300/104 Silver, e.g. silver sulfadiazine
• CPC Class Codes: A61L 2300/206 Biguanides, e.g. chlorohexidine
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/406 Antibiotics
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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: A61M 2025/0056 provided with an antibacterial agent, e.g. by coating, residing in the polymer matrix or releasing an agent out of a reservoir
• CPC Class Codes: C08L 75/00 Compositions of polyureas or polyurethanes; Compositions of derivatives of such polymers
• CPC Class Codes: C08L 75/04 Polyurethanes

Abstract

An anti-infective medical article has chlorhexidine bulk distributed throughout a polyurethane base layer and may have a coating layer on the base layer. The coating layer may be chlorhexidine permeated into the surface or it may be an antibiotic, antithrombogenic agent or a polymeric surface layer laminated onto the base layer. The invention includes a method for preparing the article wherein a homogeneous melt of polymer and chlorhexidine is prepared by twin screw compounding and the melt is extruded to give a medical article having bulk distributed chlorhexidine.

Claims

1. A method for preparing a medical article comprising:

a) preparing a blend of an anti-infective agent comprising chlorhexide, with pellets of a base polymer having a water absorption of at least 0.6% by weight;

b) heating said blend to a temperature from about 160°

C. to about 250°

C. and for a sufficient time to form a homogenous melt of said polymer having said anti-infective agent uniformly distributed therein; and

c) extruding said melt through a die to form a medical article having said anti-infective agent bulk distributed throughout said polymer.

2. The method of claim 1 further comprising applying to a surface of said article a coating of an agent selected from the group consisting of anti-infective agent comprising chlorhexidine, a surface active agent and an antithrombogenic agent.

3. The method in accordance with claim 2 wherein said applying step is performed by steeping said article in a solution of said agent.

4. The method in accordance with claim 2 further comprising ionically bonding an agent selected from the group consisting of an antibiotic and an antithrombogenic agent to said surface active agent.

5. The method of claim 1 further comprising coating the article with a layer of laminating polymer having a water absorption of at least 0.6% by weight and anti-infective agent comprising chlorhexidine bulk distributed therein to give a coated article.

6. The method of claim 5 wherein said coating step is performed by steeping the article in a solution of said laminating polymer and chlorhexidine.

7. The method of claim 5 further comprising applying a surface active agent to the surface of said coated article and reacting the surface active agent with a reagent selected from the group consisting of an antibiotic and an antithrombogenic agent.

8. The method in accordance with claim 1 wherein said chlorhexidine is selected from the group consisting of chlorhexidine base and a salt thereof.

9. The method in accordance with claim 8 wherein said salt of chlorhexidine is selected from the group consisting of the hydrochloride, acetate and gluconate.

10. The method in accordance with claim 1 wherein said based polymer is selected from the group consisting of polyurethane, polyurethaneurea and siloxane-urethane block copolymer.

11. The method in accordance with claim 1 wherein said chlorhexidine is about 0.1 to 10% by weight of said polymer.

12. The method in accordance with claim 1 wherein said melt is formed by twin screw compounding.

13. The method in accordance with claim 1 further comprising wetting said pellets with a polyol prior to said preparing.

14. A method for preparing a medical article comprising preparing a homogeneous melt of a polymer having a water absorption of at least 0.6% by weight and an anti-infective agent at a temperature range from about 160°

C. to about 250°

C. and extruding said melt through a die to form a medical article having said agent bulk distributed throughout said polymer.