Sustained release bactericidal cannula

• US 5,482,740 A
• Filed: 11/08/1993
• Issued: 01/09/1996
• Est. Priority Date: 01/10/1990
• Status: Expired due to Term

• Current Assignee: Rochester Medical Corporation (Becton, Dickinson & Co)
• Original Assignee: Rochester Medical Corporation (Becton, Dickinson & Co)
• Inventors: Conway, Anthony J., Fryar, Richard D. Jr., Conway, Philip J.
• Primary Examiner(s): DUDASH, DIANA L
• Application Number:
  US08/148,995
• Time in Patent Office: 792 Days
• Field of Search: 427/2, 427/2.28, 427/2.3, 427/387, 427/412.1, 427/414
• US Class Current: 427/2.28
• CPC Class Codes: A61L 2300/204 with nitrogen-containing functional groups, e.g. aminoxides, nitriles, guanidines
• CPC Class Codes: A61L 2300/222 Steroids, e.g. corticosteroids
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/41 Anti-inflammatory agents, e.g. NSAIDs
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/602 Type of release, e.g. controlled, sustained, slow
• CPC Class Codes: A61L 2300/606 Coatings
• CPC Class Codes: A61L 29/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
• 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: A61M 2025/0062 having features to improve the sliding of one part within another by using lubricants or surfaces with low friction
• CPC Class Codes: A61M 2025/1075 having a balloon composed of several layers, e.g. by coating or embedding
• CPC Class Codes: A61M 25/0009 Making of catheters or other medical or surgical tubes
• CPC Class Codes: A61M 25/0017 specially adapted for long-term hygiene care, e.g. urethral or indwelling catheters to prevent infections
• CPC Class Codes: A61M 25/0045 multi-layered, e.g. coated coating materials A61L29/08
• CPC Class Codes: A61M 25/10 Balloon catheters A61M25/0125 takes precedence; embolectomy A61B17/22032; retractors A61B17/02; inflatable balloons for placing stents or stent-grafts A61F2/958 ; stomach balloons for treatment of obesity A61F5/0003; oesophagal tubes A61J15/00
• CPC Class Codes: A61M 25/1011 Multiple balloon catheters
• CPC Class Codes: A61M 25/1029 Production methods of the balloon members, e.g. blow-moulding, extruding, deposition or by wrapping a plurality of layers of balloon material around a mandril
• CPC Class Codes: C08L 83/04 Polysiloxanes

Abstract

Methods of making sustained release bactericidal cannulas or catheters through which aqueous biological fluids can pass. The bactericidal cannula for catheter including a tube having an inner surface, defining and interior lumen, and an outer surface. The tube has a polymeric matrix and antibacterial agent residing within at least a portion of the polymeric matrix. The polymeric matrix includes cured silicon rubber and the antibacterial agent is a finely divided nitrofuran compound which is soluble in water and effective to prevent proliferation of certain bacteria in an otherwise growth supporting aqueous environment when dissolved in the aqueous environment to the limit of its solubility therein at 37° C. The solubility of the nitrofuran compound is about 0.2% by weight or less at a pH of about 6 and a temperature of about 25° C. A portion of the polymeric matrix proximate the outer surface includes an amount of from about 10 to about 60% by weight of the nitrofuran compound and the amount of the nitrofuran compound and the solubility thereof cooperate to provide a potential for a sustained release diffusion thereof for a period of not less than about three weeks during normal use of the cannula within the human body.

Claims

1. A method for making a sustained release bactericidal cannula, the cannula being made from a tube, the tube having an inner surface, defining an inner lumen passing through the tube, and an uncured silicone rubber outer surface, said method comprising the steps of:

(a) providing an antibacterial agent containing mixture including uncured silicone rubber and particles of a solid antibacterial agent, wherein the antibacterial agent is a nitrofuran compound having a solubility in water of 0.2% by weight or less and wherein the mixture has a different composition from that of the uncured silicone rubber outer surface;

(b) coating at least a portion of the outer surface of the tube with the antibacterial agent containing mixture to form an uncured nitrofuran containing silicone rubber outer layer; and

(c) curing the silicone rubber of both the uncured silicone rubber outer surface and the uncured nitrofuran containing silicone rubber outer layer to form a cured antibacterial agent containing silicone rubber outer layer bonded to the silicone rubber outer surface;

wherein the step of providing includes providing an antibacterial agent containing mixture containing a sufficient amount of the nitrofuran compound that the cured antibacterial agent containing silicone rubber outer layer contains about 10 to about 60 percent by weight of the nitrofuran compound.

2. The method of claim 1 wherein the step of coating includes dipping the tube in the antibacterial agent containing fluid mixture to form the uncured nitrofuran containing silicone rubber outer layer.

3. The method of claim 1 wherein the step of curing includes heating the tube to a temperature of at least about 140°

F. to cure silicone rubber of both the uncured silicone rubber outer surface and the uncured nitrofuran containing silicone rubber outer layer to form the controlled release bactericidal cannula.

4. The method of claim 1 wherein the tube includes a second lumen and a balloon cavity between the inner surface and the outer surface and encircling the inner lumen, wherein the outer surface proximate the balloon cavity defines a balloon portion and the step of coating includes coating at least a portion of the balloon portion with the antibacterial agent containing fluid mixture.

5. The method of claim 1 wherein the particles of the solid antibacterial agent have a mean particle diameter of not more than about 200 microns.

6. The method of claim 4 wherein the antibacterial agent is selected from the group consisting of nitrofurazone, nitrofurantoin, furaltadone, furazolidone, nifuradene, nidroxyzone, nifuroxime and nihydrazone.

7. The method of claim 6 wherein the antibacterial agent has a solubility in water, at a pH of about 6 and a temperature of about 25°

C., of about 0.001 to about 0.2% by weight.

8. The method of claim 4 wherein the antibacterial agent is selected from the group consisting of nitrofurazone, nitrofurantoin, furaltadone and furazolidone.

9. The method of claim 5 wherein the antibacterial agent is selected from the group consisting of nitrofurazone, nitrofurantoin, furaltadone and furazolidone.

10. The method of claim 1 wherein the cannula is a urinary catheter through which aqueous biological fluids can pass, said catheter within a urinary tract of a human body.

11. The method of claim 1 wherein the mixture in step (a) further includes an additional silicone fluid.

13. The method of claim 2 wherein the outer layer contains an amount of the anti-inflammatory compound in a range from about 10 to about 60% by weight thereof and the anti-inflammatory compound is hydrocortisone compound having a solubility of about 0.2% by weight or less in water at a pH of about 6 and a temperature of about 25°

C.

12. A method for making a sustained release bactericidal cannula, the cannula being made from a tube, the tube having an inner surface, defining an inner lumen passing through the tube, and an uncured silicone rubber outer surface, said method comprising the steps of:

(a) providing an antibacterial agent containing mixture including uncured silicone rubber, an additional silicone fluid, and particles of a solid antibacterial agent, wherein the antibacterial agent is a nitrofuran compound having a solubility in water of 0.2% by weight or less;

(b) coating at least a portion of the outer surface of the tube with the antibacterial agent containing mixture to form an uncured nitrofuran containing silicone rubber outer layer; and

(c) curing the silicone rubber of both the uncured silicone rubber outer surface and the uncured nitrofuran containing silicone rubber outer layer to form a cured antibacterial agent containing silicone rubber outer layer bonded to the silicone rubber outer surface wherein the step of providing includes providing an antibacterial agent containing mixture containing a sufficient amount of the nitrofuran compound that the cured antibacterial agent containing silicone rubber outer layer contains about 10 to about 60 percent by weight of the nitrofuran compound and wherein the outer layer contains about 2 to about 80 percent by weight of a water-soluble anti-inflammatory agent.

14. The method of claim 12 wherein the outer layer contains an amount of the anti-inflammatory compound is a hydrocortisone compound having a solubility of about 0.1% by weight.

15. A method for making a sustained release bactericidal cannula, the cannula being made from a tube, the tube having an inner surface, defining an inner lumen passing through the tube, and an uncured silicone rubber outer surface, said method comprising the steps of:

(a) providing an antibacterial agent containing mixture including uncured silicone rubber, an additional silicone fluid, and particles of a solid antibacterial agent, wherein the antibacterial agent is a nitrofuran compound having a solubility in water of 0.2% by weight or less;

(b) coating at least a portion of the outer surface of the tube with the antibacterial agent containing mixture to form an uncured nitrofuran containing silicone rubber outer layer; and

(c) curing the silicone rubber of both the uncured silicone rubber outer surface and the uncured nitrofuran containing silicone rubber outer layer to form a cured antibacterial agent containing silicone rubber outer layer bonded to the silicone rubber outer surface;

wherein the step of providing includes providing an antibacterial agent containing mixture containing a sufficient amount of the nitrofuran compound that the cured antibacterial agent containing silicone rubber outer layer contains about 10 to about 60 percent by weight of the nitrofuran compound;

wherein said cannula has an enclosed sleeve cavity located between the respective inner and outer surfaces and encircling the inner lumen, said cannula further comprising a resilient sleeve portion encircling the inner lumen and the sleeve cavity, the sleeve cavity containing a lubricating substance.

16. A method for making a sustained release bactericidal cannula, the cannula being made from a tube, the tube having an inner surface, defining an inner lumen passing through the tube, and an uncured silicone rubber outer surface, said method comprising the steps of:

(a) forming the tube with an uncured silicone rubber outer surface by coating a polymeric tube with a polymeric bonding composition containing an uncured silicone rubber, said polymeric tube having on a portion thereof a coating of bond preventing agent;

(b) coating at least a portion of the outer surface of the tube having an uncured silicone rubber outer surface with an antibacterial agent containing mixture to form an uncured nitrofuran containing silicone rubber outer layer, wherein the an antibacterial agent containing mixture includes uncured silicone rubber and particles of a solid antibacterial agent and wherein the antibacterial agent is a nitrofuran compound having a solubility in water of 0.2% by weight or less; and

(c) curing the silicone rubber of both the uncured silicone rubber outer surface and the uncured nitrofuran containing silicone rubber outer layer to form a cured antibacterial agent containing silicone rubber outer layer bonded to the silicone rubber outer surface, wherein the step of providing includes providing an antibacterial agent containing mixture containing a sufficient amount of the nitrofuran compound that the cured antibacterial agent containing silicone rubber outer layer contains about 10 to about 60 percent by weight of the nitrofuran compound.