Antimicrobial barrier device

• US 9,950,106 B2
• Filed: 12/02/2013
• Issued: 04/24/2018
• Est. Priority Date: 12/05/2012
• Status: Active Grant

• Current Assignee: Cook Medical Technologies, LLC (Cook Group Incorporated)
• Original Assignee: Cook Medical Technologies, LLC (Cook Group Incorporated)
• Inventors: Isch, Andrew P., Charlebois, Steven J.
• Primary Examiner(s): PACKARD, BENJAMIN J
• Application Number:
  US14/094,182
• Publication Number:
  US 20140155844A1
• Time in Patent Office: 1,604 Days
• CPC Class Codes: A61L 2300/202 with halogen atoms, e.g. triclosan, povidone-iodine
• 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 31/06 obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds A61L31/041 takes precedence
• CPC Class Codes: A61L 31/16 Biologically active materials, e.g. therapeutic substances A61L31/047 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 2025/0273 having slits to place the pad around a catheter puncturing site
• CPC Class Codes: A61M 25/00 Catheters; Hollow probes dilators A61M29/00; peritoneal catheters A61M1/285; tracheal tubes A61M16/04; for drainage A61M27/00; for uterus, vagina or rectum A61M31/00 ; for measuring or testing A61B; materials for catheters A61L29/00
• CPC Class Codes: A61M 39/16 having provision for disinfection or sterilisation A61M39/143 takes precedence; methods or apparatus for disinfection or sterilisation A61L2/00
• CPC Class Codes: A61M 39/18 Methods or apparatus for making the connection under sterile conditions, i.e. sterile docking
• CPC Class Codes: A61M 5/001 Apparatus specially adapted for cleaning or sterilising syringes or needles
• CPC Class Codes: C08L 83/04 Polysiloxanes

Abstract

The invention relates to an antimicrobial barrier device and methods of manufacture. The antimicrobial barrier comprises one or more antimicrobial drugs that inhibit biofilm formation and bacterial and/or fungal growth. The antimicrobial barrier is suited for use with insertable devices (e.g., catheters) to reduce the incidence of infection at and around the insertion site.

Claims

1. An antimicrobial barrier device comprising:

a soft durometer cured silicone body having 10 A to about 80 A durometer, being greater in width (L1) than thickness (L2), and having an outer edge, the soft durometer cured silicone body comprising one or more directly incorporated antimicrobial drugs selected from the group consisting of an antifungal agent and an antibacterial agent, the soft durometer cured silicone body being substantially resistant to microbial colonization thereon, and having

a) a first surface adapted to conform to a treatment area;

b) a hole extending therethrough, the hole being adapted to receive and seal to an insertable medical device, the size of the hole being equal to or smaller than the circumference of the insertable medical device, the hole having a shape selected from the group consisting of substantially round or rounded, scalloped oval, and eclipse;

c) an outer edge; and

d) at least one of an adhesive, tape, bandages, ties, sutures, or straps for adhering the first surface to the treatment area;

wherein the antimicrobial barrier device inhibits bacterial growth in a zone of inhibition of about 10 mm to 30 mm from the outer edge.

2. The antimicrobial barrier device of claim 1 wherein the soft durometer cured silicone body is 10 A to about 50 A durometer silicone.

3. The antimicrobial barrier device of claim 1 wherein the soft durometer cured silicone body is about 50 A durometer silicone.

4. The antimicrobial barrier device of claim 1 wherein the one or more directly incorporated antimicrobial drugs is selected from the group consisting of a rifamycin, rifampicin, nitrofurantoin, triclosan, trimethoprim, nalidixic acid, vancomycin, a tetracycline, doxycycline, minocycline, tetracycline, an aminoglycoside, amikacin, gentamicin, neomycin, tobramycin, a fluoroquinolone, ciprofloxacin, levofloxacin, trovafloxacin, gemifloxacin, gentian violet, flucytosine, an azole drug, fluconazole, miconazole, itraconazole, ketoconazole, clotrimazole, and chlorhexidine.

5. The antimicrobial barrier device of claim 4 wherein the one or more directly incorporated antimicrobial drugs is directly incorporated in a concentration of about 1 mg to about 30 mg per gram of soft durometer cured silicone body.

6. The antimicrobial barrier device of claim 1 wherein the one or more directly incorporated antimicrobial drugs is directly incorporated in a concentration in mg per gram of soft durometer cured silicone body, wherein the directly incorporated antimicrobial drugs and concentrations are:

a) about 10 mg/g to about 20 mg/g ciprofloxacin;

b) about 4 mg/g to about 20 mg/g levofloxacin;

c) about 20 mg/g to about 30 mg/g minocycline;

d) about 10 mg/g to about 20 mg/g triclosan;

e) about 10 mg/g to about 20 mg/g trimethoprim;

f) about 1 mg/g to about 6 mg/g fluconazole;

g) about 1 mg/g to about 6 mg/g itraconazole;

or

h) about 1 mg/g to about 6 mg/g gentian violet.

7. The antimicrobial barrier device of claim 1 wherein the one or more directly incorporated antimicrobial drugs is one or more antibacterial drugs and one or more antifungal drugs, each directly incorporated in a concentration in mg per gram of soft durometer cured silicone body, wherein the antibacterial drugs and concentrations are:

a) about 10 mg/g to about 20 mg/g ciprofloxacin;

b) about 4 mg/g to about 20 mg/g levofloxacin;

c) about 20 mg/g to about 30 mg/g minocycline;

d) about 10 mg/g to about 20 mg/g triclosan;

or

e) about 10 mg/g to about 20 mg/g trimethoprim;

and wherein the antifungal drugs and concentrations are

f) about 1 mg/g to about 6 mg/g fluconazole;

g) about 1 mg/g to about 6 mg/g itraconazole;

or

h) about 1 mg/g to about 6 mg/g gentian violet.

8. The antimicrobial barrier device of claim 1, wherein an adhesive is coated onto the first surface.

9. The antimicrobial barrier device of claim 8 further comprising a cover, the cover being removably attached to the adhesive.

10. The antimicrobial barrier device of claim 6, wherein the cured silicone body elutes the one or more directly incorporated antimicrobial drugs when contacted with the treatment area.

11. The antimicrobial barrier device of claim 1, wherein the soft durometer cured silicone body comprises about 1 mg/g to about 30 mg/g of the one or more directly incorporated antimicrobial drugs, wherein the soft durometer cured silicone body:

a) is about 50 A durometer silicone;

b) elutes about 1% to about 15% of the one or more directly incorporated antimicrobial drugs after exposure to artificial urine for about 1-3 days, and

c) inhibits at least about 80% biofilm formation thereon.

12. The antimicrobial barrier device of claim 1, wherein the soft durometer cured silicone body comprises about 1 mg/g to about 30 mg/g of the one or more directly incorporated antimicrobial drugs, wherein the soft durometer cured silicone body:

a) is about 50 A durometer silicone;

b) elutes about 1% to about 15% of the one or more directly incorporated antimicrobial drugs after exposure to artificial urine for about 1-3 days, and

c) inhibits substantially all biofilm formation thereon.

13. The antimicrobial barrier device of claim 1 further comprising a slit.

14. A kit comprising:

an insertable medical device; and

the antimicrobial barrier device of claim 1.

15. The kit of claim 14 wherein the insertable medical device is a catheter, a needle, an infusion device, a peripheral venous catheter, a peripheral venous catheter needle, an indwelling infusion needle, a butterfly needle, a subcutaneous access device, an insulin pump needle, a patient controlled analgesia pump needle, an arterial catheter, a central venous catheter, a dialysis catheter, a peritoneal dialysis catheter, a nephrostomy catheter, a percutaneous cystostomy catheter, an indwelling paracentesis or pleurocentesis catheter or drain, a percutaneous nephrostomy, a cystostomy tube, a spinal or epidural catheter or a sensor.

16. A method of manufacturing the antimicrobial barrier device of claim 1 by directly incorporating an antimicrobial drug into a soft durometer cured silicone body comprising the steps of:

a) dissolving one or more antimicrobial drugs in one or more solvents to provide a dissolved one or more antimicrobial drugs;

b) mixing the dissolved one or more antimicrobial drugs with a first silicone elastomer to provide a first silicone elastomer mixture;

c) evaporation of the one or more solvents from the first silicone elastomer mixture to provide a second silicone elastomer mixture;

d) mixing the second silicone elastomer mixture with a second silicone elastomer to provide a third silicone elastomer mixture;

e) transferring the third silicone elastomer mixture to a mold; and

f) curing the third silicone elastomer mixture in the mold.

17. The method of claim 16, wherein the first, second, and third silicone elastomer mixtures are homogeneous mixtures.

18. The method of claim 17, wherein the antimicrobial drug is selected from the group consisting of a rifamycin, rifampicin, nitrofurantoin, triclosan, trimethoprim, nalidixic acid, vancomycin, a tetracycline, doxycycline, minocycline, tetracycline, an aminoglycoside, amikacin, gentamicin, neomycin, tobramycin, a fluoroquinolone, ciprofloxacin, levofloxacin, trovafloxacin, gemifloxacin, gentian violet, flucytosine, an azole drug, fluconazole, miconazole, itraconazole, ketoconazole, clotrimazole, and chlorhexidine.

20. The antimicrobial barrier device of claim 8, further comprising a peel-away layer applied over the adhesive.

19. An antimicrobial barrier device comprising:

a soft durometer cured silicone body being greater in width (L1) than thickness (L2), having an outer edge, and comprising one or more directly incorporated antimicrobial drugs selected from the group consisting of an antifungal agent and an antibacterial agent, the soft durometer cured silicone body being substantially resistant to microbial colonization thereon, and having

a) a first surface adapted to conform to a treatment area;

b) a hole extending therethrough, the hole being adapted to receive and seal to an insertable medical device, the size of the hole being equal to or smaller than the circumference of the insertable medical device, the hole having a shape selected from the group consisting of substantially round or rounded, scalloped oval, and eclipse;

c) an outer edge; and

d) at least one of an adhesive, tape, bandages, ties, sutures, or straps for adhering the first surface to the treatment area;

wherein the one or more directly incorporated antimicrobial drugs is selected from the group consisting of a rifamycin, rifampicin, nitrofurantoin, trimethoprim, nalidixic acid, vancomycin, a tetracycline, doxycycline, minocycline, tetracycline, an aminoglycoside, amikacin, gentamicin, neomycin, tobramycin, a fluoroquinolone, ciprofloxacin, levofloxacin, trovafloxacin, gemifloxacin, flucytosine, an azole drug, fluconazole, miconazole, itraconazole, ketoconazole, clotrimazole, and chlorhexidine, and

wherein the antimicrobial barrier device inhibits bacterial growth in a zone of inhibition of about 10 mm to 30 mm from the outer edge.