Antimicrobial medical devices containing chlorhexidine free base and salt

• US 7,329,412 B2
• Filed: 12/22/2000
• Issued: 02/12/2008
• Est. Priority Date: 12/22/2000
• Status: Expired due to Fees

• Current Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Original Assignee: Trustees Of Columbia University In The City Of New York (Columbia University)
• Inventors: Modak, Shanta M., Sampath, Lester A.
• Primary Examiner(s): Azpuru; Carlos A.
• Application Number:
  US09/746,670
• Publication Number:
  US 20020122876A1
• Time in Patent Office: 2,608 Days
• Field of Search: 424/423, 424/486, 424/422, 424/424, 424/428, 424/484, 424/485
• US Class Current: 424/423
• CPC Class Codes: A61K 31/155 Amidines (), e.g. guanidine (H2N—C(=NH)—NH2), isourea (N=C(OH)—NH2), isothiourea (—N=C(SH)—NH2)
• CPC Class Codes: A61K 47/32 Macromolecular compounds obtained by reactions only involving carbon-to-carbon unsaturated bonds, e.g. carbomers , poly(meth)acrylates, or polyvinyl pyrrolidone
• CPC Class Codes: A61K 9/7023 Transdermal patches and similar drug-containing composite devices, e.g. cataplasms galenical aspects of iontophoretic devices A61K9/0009; microneedle arrays A61K9/0021; buccal patches A61K9/006
• CPC Class Codes: A61L 15/44 Medicaments
• 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 27/54 Biologically active materials, e.g. therapeutic substances A61L27/227 takes precedence
• CPC Class Codes: A61L 29/16 Biologically active materials, e.g. therapeutic substances A61L29/048 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 takes precedence
• CPC Class Codes: C09D 175/04 Polyurethanes

Abstract

The present disclosure invention relates to medical devices treated with a solution comprising one or more solvents and a combination of chlorhexidine free base and a water-soluble chlorhexidine salt in a weight/weight ratio of between about 1:1 to about 1:5, preferably about 1:1.

Claims

1. An antimicrobial catheter prepared by treating a polymeric catheter, for an effective period of time, with a solution comprising a solvent and an antimicrobial mixture consisting essentially of chlorhexidine free base and a water-soluble chlorhexidine salt, wherein the weight/weight ratio of chlorhexidine free base and the water-soluble chlorhexidine salt in the solution is between 1:

1 to 1;

5.

2. The antimicrobial catheter of claim 1, wherein the ratio is 1:

1.

3. The antimicrobial catheter of claim 1, wherein the solvent is selected from the group consisting of water, alcohol, tetrahydrofuran, dimethylsulfoxide, dimethylformamide, N-methyl-2-pyrrolidone, and mixtures thereof.

4. The antimicrobial catheter of claim 3, wherein the solvent is a mixture of between 10 and 30 percent (volume/volume) tetrahydrofuran and 70 and 90 percent (volume/volume) ethanol.

5. The antimicrobial catheter of claim 3, wherein the solvent is a mixture of 20 percent (volume/volume) tefrahydrofuran and 80 percent (volume/volume) ethanol.

6. The antimicrobial catheter of claim 3, wherein the solvent is a mixture of between 75 and 95 percent (volume/volume) tetrahydrofuran and 5 and 25 percent (volume/volume) methanol.

7. The antimicrobial catheter of claim 3, wherein the solvent is a mixture of about 85 percent (volume/volume) tetrahydrofuran and 15 percent (volume/volume) methanol.

8. The antimicrobial catheter of claim 1, wherein the catheter is hydrophilic polymeric catheter.

9. The catheter of claim 1, wherein the catheter has a lumen that is treated for an effective period of time with a solution comprising a solvent and an antimicrobial mixture consisting essentially of chlorhexidine free base and a water-soluble chlorhexidine salt, wherein the weight/weight ratio if chlorhexidine free base and the water-soluble chlorhexidine salt in the solution is between 1:

1 to 1;

5.

10. The catheter of claim 1, wherein the water-soluble chlorhexidine salt is chlorhexidine diacetate.

11. The catheter of claim 9, wherein the water-soluble chlorhexidine salt is chlorhexidine diacetate.

12. An antimicrobial catheter prepared by treating a polymeric catheter, for an effective period of time, with a solution comprising (1) a solvent;

(2) an antimicrobial mixture consisting essentially of chlorhexidine free base and a water-soluble chlorhexidine salt; and

(3) a substance selected from the group consisting of (i) an organic acid, at a concentration of between 0.1 and 5 percent;

(ii) an anti-inflammatory agent, at a concentration of between 0.1 and 5 percent; and

(iii) a hydrogel at a concentration of between 0.5 to 10 percent, wherein the ratio of chlorhexidine free base and the water-soluble chlorhexidine salt in the solution is between 1;

1 to 1;

5.

13. The antimicrobial catheter of claim 12, wherein the concentration of organic acid in the solution is between 0.1 and 2 percent.

14. The antimicrobial catheter of claim 12, wherein the concentration of anti-inflammatory agent is between 0.1 and 1 percent.

15. The antimicrobial catheter of claim 12, wherein the concentration of hydrogel in the solution is between 1 and 5 percent.

16. A method of preparing a catheter comprising

(i) contacting the catheter with a solution comprising (a) a solvent selected from the group consisting of water, reagent alcohol, tetrahydrofuran, dimethylsulfoxide, dimethylformamide, N-methyl-2-pyrrolidone, and a mixture thereof;

and (b) an antimicrobial mixture consisting essentially of chlorhexidine free base and a water-soluble chlorhexidine salt, wherein the weight/weight ratio of chlorhexidine, free base and water soluble chlorhexidine salt in the solution is between 1;

1 and 1;

5;

(ii) allowing the catheter to stay in contact with the solution for an effective period of time to allow the medical article to swell;

(iii) removing the medical article from the solution; and

(iv) drying the medical article.

17. A method of preparing a catheter having a lumen comprising

(i) contacting the lumen with a solution comprising (a) a solvent selected from the group consisting of water, reagent alcohol, tetrahydrofuran, dimethylsulfoxide, dimethylformamide, N-methyl-2-pyrrolidone, and mixtures thereof;

and (b) a mixture consisting essentially of chlorhexidine free base and a water-soluble chlorhexidine salt, wherein the weight/weight ratio of chlorhexidine free base and water soluble chlorhexidine salt in the solution is between 1;

1 and 1;

5;

(ii) contacting the lumen with a solution for an effective period of time to allow the lumen to swell;

(iii) removing the solution from the lumen; and

(iv) drying the catheter.

18. A catheter prepared by treating a polymeric catheter for about thirty minutes to about one hour with a solution comprising a solvent and an antimicrobial mixture consisting essentially of chlorhexidine free base and a water soluble chlorhexidine salt, wherein the weight/weight ratio of the chlorhexidine free base and the water soluble chlorhexidine salt in the solution is between 1:

1 and 1;

5 and wherein the treated catheter exhibits sustained antimicrobial activity for at least about six days.

19. The catheter of claim 18, wherein the solvent comprises between 75 and 95 percent (volume/volume) tetrahydrofuran and 5 and 25 percent (volume/volume) methanol.