WO1994022522A1

WO1994022522A1 - Medical devices having antimicrobial properties and methods of making and using

Info

Publication number: WO1994022522A1
Application number: PCT/US1994/002327
Authority: WO
Inventors: John C. Toomey
Original assignee: Medex, Inc.
Priority date: 1993-03-30
Filing date: 1994-03-03
Publication date: 1994-10-13
Also published as: AU6443394A; CA2158477A1; EP0691869A1; JPH08508421A

Abstract

Disposable medical devices having antimicrobial properties, systems incorporating such devices, and methods of making and using such devices are disclosed. Medical devices of the present invention, such as valves, injection sites, stopcocks, manifolds, dead-enders, movable and resilient plug bodies of the type used as the septums in sample site devices, etc., include a housing (12) having a fluid path (14) therein and at least one port (15) for coupling to a source of fluid. The device further includes an associated access control member (16) which communicates with the fluid path of the housing (12) to selectively control access thereto. The access control member may preferably comprise a synthetic resin material and an antimicrobial agent molded therein.

Description

MEDICAL DEVICES HAVING ANTIMICROBIAL PROPERTIES AND METHODS OF MAKING AND USING

FIELD OF THE INVENTION

This invention relates to disposable medical devices, and more particularly to medical devices having antimicrobial properties and methods of making and using such devices.

BACKGROUND OF THE INVENTION

There is increasingly heightened awareness in the medical community regarding contamination control and infection reduction, particularly in hospital environments. One of the primary sources of nosocomial (hospital related) infections stems from the use of medical devices and systems incorporating medical devices, such as fluid administration sets and blood pressure monitoring sets, for example, in which fluids received by a patient (i.e., blood, plasma, saline, etc.) contact the devices and pick up infection-causing bacteria.

Attempts have been made to address the problems of nosocomial infections by utilizing antimicrobial compositions in connection with various types of medical devices. In particular, certain medical articles are known to have coatings of an antimicrobial-containing material thereon. Examples include catheters, tubing, drainage bags, etc. The following U.S. patents generally relate to medical devices of various types which include some form of antimicrobial composition: see U.S. Patent Nos. 3,987,007, 4,563,485, 4,581,028, 4,605,654, 4,054,139 and 4,483,688. While it is known to utilize antimicrobial agents in connection with certain medical articles and devices, heretofore there has been no teaching or suggestion of medical devices having antimicrobial properties in accordance with the present invention and as described herein. SUMMARY OF THE INVENTION

The present invention encompasses medical devices having antimicrobial properties, systems incorporating such devices, and methods of making and using such devices. The invention has particular applicability to fluid administration sets and pressure monitoring sets, and the medical device components thereof which contact fluids that in turn contact patients. For example, the present invention contemplates a wide variety of medical devices, including valves, injection sites, stopcocks, manifolds, dead-enders, and both movable and resilient plug bodies, such as the septums in sample site devices.

In its broadest aspects, one embodiment of the invention is directed to medical devices which include a housing having a fluid path therein and at least one port for coupling to a source of fluid. The device further includes a member associated with the housing which is in communication with the fluid path to selectively control access to the fluid path. This member, referred to herein as an "access control member," has a composition comprising a synthetic resin material and an antimicrobial agent. Suitable synthetic resin materials include high density polyethylene (HDPE) , polyurethane, polycarbonate, etc. With respect to the antimicrobial agent, it is known that certain metal ions such as silver, copper, zinc, and derivatives thereof, are "oligodynamic"; in other words, they exhibit antimicrobial activity, and thus can be utilized as the active component in the antimicrobial agent in devices of the present invention.

In one embodiment, the housings of medical devices according to the present invention have substantially no antimicrobial agent molded therein. The access control member associated with the housing and which communicates with the fluid path does include an antimicrobial agent exposed on at least one surface which communicates with the fluid path in the housing. Examples of suitable antimicrobial materials are glass microspheres, platelets or fibers coated with elemental silver. It will be appreciated by persons skilled in the art, however, that various other known antimicrobial materials can be utilized in the devices of the present invention. In a preferred embodiment, the access control member is comprised of synthetic resin in the range of about 75% to 99% by weight, and antimicrobial agent in the range of about 1% to 25% by weight.

In an alternative embodiment, the access control member of the device has an antimicrobial agent surface layer adhesively secured to a surface thereof which is in communication with the fluid path in the housing. In yet another alternative embodiment, the access control member of the medical device has an antimicrobial agent at least partially exposed on at least one surface thereof and which is applied thereto by ion beam implantation. Another aspect of the present invention relates to methods of making medical device components which include a synthetic resin material and an antimicrobial agent. Methods according to this aspect of the invention preferably include the steps of (1) compounding a synthetic resin material and an antimicrobial agent to form a mixture; (2) molding the mixture to produce a medical device component (access control member) ; and (3) ablating at least one surface of the component to at least partially expose the antimicrobial agent. The ablating step may comprise exposing the component or a specific desired surface thereof to an oxygen- containing plasma. This step is believed to remove small amounts of the resin material at the surface layer to expose the antimicrobial agent to a greater extent than may otherwise occur during the molding step. Yet another aspect of the present invention is directed to methods of reducing the incidence of nosocomial infections in patients who are exposed to fluids susceptible of containing infection-causing bacteria. Methods according to this aspect of the invention comprise coupling the fluid into a housing having a fluid path therein and at least one port for coupling to a source of the fluid. Provided in association with the housing and in communication with the fluid path is an access control member for selectively controlling access to the fluid path. The access control member is of the type described hereinabove and has a composition which includes a synthetic resin material and an effective amount of an antimicrobial agent to kill infection-causing bacteria in the fluid.

In a further aspect of the present invention, systems for adminstering fluid to patients are contemplated. Such systems include a fluid source; a fluid conduit connected to the fluid source and adapted to be placed in fluidic communication with a patient; a housing having a fluid path and at least two ports for coupling the fluid path in series with the fluid conduit; and an access control member associated with the housing and in communication with the fluid path for selectively controlling access to the fluid path. The access control member has a composition comprising a synthetic resin material and an antimicrobial agent. The antimicrobial agent may be of any suitable type, particularly any of those described herein, and the access control member may be a valve, a dead end plug, a movable plug body, a resilient plug body, a syringe plunger, etc. These and other features and advantages of the present invention will become apparent to persons skilled in the art upon review of the drawings taken in conjunction with the detailed description of the invention. BRIEF DESCRIPTION OF THE DRAWINGS

Fig. 1 is a perspective view, partially broken away, of a medical device (stopcock) according to one embodiment of the present invention;

Fig. 2A is a perspective view of two medical devices (stopcock and dead-ender) of the present invention coupled together; Fig. 2B is a cross-sectional view of the dead-ender shown in Fig. 2A with a portion of the stopcock shown in phantom;

Fig. 3 is a cross-sectional view, partially broken away, of an alternative embodiment of a medical device (sample site) of the present invention;

Fig. 4 is a plan view, partially broken away and in partial cross-section, of another alternative embodiment (syringe with plunger) of the present invention;

Fig. 5 is a schematic representation of a fluid administration system according to the present invention; Fig. 6A is a schematic representation, in cross-section, of an access control member of the present invention;

Fig. 6B shows the access control member of Fig. 6A subsequent to a surface treatment in accordance with the principles of the present invention;

Fig. 7 is a schematic representation, in cross-section, of an alternative embodiment of an access control member of the present invention; and Fig. 8 is a schematic representation, in cross-section, of another alternative embodiment of an access control member of the present invention. DETAILED DESCRIPTION OF THE DRAWINGS

In accordance with general principles of the present invention, medical devices are contemplated which include a housing having a fluid path therein, at least one port for coupling to a source of fluid, and an access control member associated with the housing which is in communication with the fluid path for selectively controlling access to the fluid path. Figs. 1-4 show specific examples of medical device embodiments of the present invention. Fig. 5 is a schematic representation of a fluid administration system in accordance with the present invention and which incorporates medical devices of the present invention. Figs. 6A-8 are schematic representations of alternative embodiments of access control members.

With reference to Fig. 1, a stopcock 10 is shown which includes a housing 12 having a fluid path 14 therein and a plurality of ports 15 adapted to be coupled to a fluid source. Fluids which may contain infection-causing bacteria and which contact a patient will flow through fluid path 14 during use of device 10. Stopcock 10 further includes an access control member such as valve 16 which is in communication with fluid path 14 and selectively controls access to the fluid path. Valve 16 is comprised of a synthetic resin material and an antimicrobial agent. With reference to Figs. 6A and B, there is shown alternative embodiments, in schematic form and in cross-section, of a portion designated generally as 20, of an access control member, which comprises a synthetic resin material designated generally as 22 and an antimicrobial agent molded therein designated generally as 24. A suitable antimicrobial agent, which will be described hereinbelow, is compounded with a synthetic resin material and molded to form the medical device component, such as the access control member (valve) 16 of Fig. 1. As shown in Fig. 6A, portion 20 has the antimicrobial agent 24 at least partially exposed at a surface 26 thereof. In accordance with further principles of the present invention, surface 26 may be subjected to a treatment, such as plasma etching, to remove resin 22 from the surface layer to thereby expose additional antimicrobial, as represented in schematic form in Fig. 6B. The new surface is designated 26'. Suitable surface treatments for exposing additional antimicrobial agent will be described hereinafter.

Fig. 2A shows an alternative embodiment of a medical device of the present invention. More particularly, the device shown is a dead-ender 28 received in a port 30 of a stopcock 10. Fig. 2B shows dead-ender 28 in cross-section, with port 30 of stopcock 10 shown in phantom. Dead-ender 28 comprises a synthetic resin material 22 having an antimicrobial agent 24 dispersed therein. When dead- ender 28 is inserted into port 30 of stopcock 10, stem portion 32 engages port 30 in a friction fit and thus communicates with fluid path 14 to selectively control access to that fluid path.

Fig. 3 shows another alternative medical device in accordance with the principles of the present invention. Shown is a sample site or injection site device 34 which comprises a housing 36 having a fluid path 38 therein, and an access control member 40 which communicates with fluid path 38 to selectively control access to the fluid path. In this embodiment, access control member 40 may take the form of a resilient plug such as a rubber septum 42 having an antimicrobial agent 44 molded therein. Alternatively, access control member 40 could be a valve such as seal member 38 shown and described in U.S. patent application Serial No. 07/855,147, filed March 20, 1992, the disclosure of which is fully incorporated herein by reference.

Yet another alternative medical device of the present invention is shown in Fig. 4. Syringe 46 has a housing 48 with a fluid path 50 therein. Syringe 46 further includes a plunger 52 which is in communication with and selectively controls access to fluid path 50. Plunger 52 is preferably comprised of a synthetic resin material, such as rubber, having an antimicrobial agent molded therein, as shown. Fig. 7 shows, in sc ^matic form, an alternative embodiment of a portion of an access control member for use in medical devices of the present invention. In this embodiment, access control member portion 60 has a layer 62 containing an antimicrobial agent 63 adhesively secured thereto along a surface 64. Antimicrobial-containing layer 62 is preferably secured to a surface 64 which is in communication with a fluid path in the medical device.

Fig. 8 is a schematic representation of an alternative access control member portion 66 in which a surface 68 thereof, which is to be in communication with a fluid path in a medical device, has an antimicrobial agent 70 implanted therein by ion beam implantation, as described in greater detail below. Fig. 5 is a schematic representation of a blood pressure monitoring/blood sampling system 100. The present invention is also intended to encompass although not specifically shown, systems such as fluid administration sets. System 100 shows a catheter 102 inserted into a patient 103 and connected by tubing 104 to a sample site device 34, which may be of the type shown in Fig. 3. Tubing 104 also connects sample site 34 to stopcock 10, which may be of the type shown herein in Fig. 1, and which may have a dead-ender 28, of the type shown in Figs. 2A and 2B, coupled thereto to close one of its outlet ports. Tubing 104 is further connected to a source of saline 110. As is well known, saline source 110 may be pressurized by pressure infuser 112 and its associated squeeze bulb 114. Another stopcock 10 is included in the tubing line between squeeze bulb 114 and pressure infuser 112. During use, fluid samples may be withdrawn from system 100 via sample site 34 by means of a syringe 46, which may be of the type shown in Fig. 4. There are a variety of suitable materials useful in the fabrication of devices and systems of the present invention. For example, in medical devices such as stopcocks, syringes, valves, manifolds, etc., the housing portion is typically molded polycarbonate, which possesses desirable strength qualities while being transparent. Access control members utilized in stopcocks and dead- enders, as described herein, are preferably molded of high density polyethylene (HDPE) . Other access control members, such as the resilient plugs in injection and sample site devices, are typically molded of elastomeric materials, such as latex. It will be appreciated by persons skilled in the art, however, that various other synthetic resin materials, or natural materials may be utilized in the practice of the present invention without departing from the scope thereof. Various antimicrobial agents have been identified which may be used in the devices of the present invention. One such material is synthetic hydroxyapatite (HAP) in which some of the calcium atoms within the crystal structure are replaced with silver ions. One source of a suitable HAP is Sangi Group America (SGA) , Los Angeles, CA, available under the trade name APACIDER-AW. Alternatively, silver- coated solid glass spheres may also be utilized as the antimicrobial agent. CONDUCT-O-FIL silver-coated glass microspheres, which have been found to be particularly useful in the practice of the present invention, are available from Potters Industries, Inc. of Parsippany, NJ, under the trade designations S-2429-S and S-5000-S2. It is believed that silver- coated glass platelets and fibers may also be successfully utilized; such materials are available from the PQ Corporation of Chattanooga, TN, under the trade names "AgClad Platelets" and "AgClad Filaments." While the specific materials identified above incorporate silver as the metal ion having antimicrobial properties, it will be appreciated that other metal ions such as copper and zinc, and derivatives thereof, may also possess suitable antimicrobial properties for use in medical devices according to the present invention.

The present invention further encompasses methods of making medical devices, and particularly the component parts thereof containing the antimicrobial material. In one embodiment, a synthetic resin such as high density polyethylene, in the range of about 75% to 99% by weight, is compounded with an antimicrobial agent in the range of about 1% to 25% by weight, and which may be any one of the above described materials, or any other suitable antimicrobial material, to form a mixture thereof. This mixture is subsequently molded, e.g., by injection molding, to form the desired medical device component. The components molded in this manner are typically the access control members used in the medical devices as described herein, since those members will contact the fluids containing infection-causing bacteria. The invention also contemplates, in an alternative embodiment, molding the housing portion of such medical devices with an antimicrobial additive, although under some circumstances doing so may deleteriously effect the physical properties of the housing. To be effective in killing infection-causing bacteria, it is necessary that the antimicrobial material be at least partially exposed on at least one surface of the medical device component which communicates with a fluid path in the device. It may be possible to promote migration of the antimicrobial additive to the surface of molded resin parts by utilizing lower injection pressures, lower injection speed and colder mold temperatures during the injection molding process.

It has been advantageously determined that increasing the exposure of antimicrobial agent in components of the present invention can be accomplished by ablating at least one surface of the component. One surface treatment which is particularly useful, and which itself is well known in the art, is a plasma ablation treatment in which the medical device component is exposed to an oxygen- containing plasma, and preferably an oxygen/carbon tetrafluoride (0₂/CF₄) plasma for approximately five minutes. The effect of such a plasma ablation treatment is represented in Figs. 6A and 6B, which show, respectively, an antimicrobial-containing resin component before and after the surface treatment. As shown in Fig. 6B, some of the resin material has been removed from surface 26 and thus a greater amount of the antimicrobial agent 24 is exposed at the new surface 26'.

In another alternative embodiment, shown in Fig. 7, the fluid-contacting surface or surfaces of an access control member used in a medical device of the present invention may have a coating of elemental silver adhesively secured thereto by means of a standard, hot stamp transfer procedure. In such procedures, a silver-containing coating or film 62 is created by standard techniques, i.e., laying down a thin film of elemental silver on a polyester film, followed by an adhesive, and this film 62 is subsequently transferred to the surface 64 of the access control member to which it is adhesively secured.

Alternatively, and as represented in Fig. 8, the surface 68 of a medical device component 66 which is to be in communication with a fluid path has a thin film 70 of an antimicrobial (e.g., elemental silver) deposited thereon by electron beam, DC or RF sputtering. Furthermore, to improve the adhesion of the silver to the surface of elements made of low surface energy resins (i.e., polyolefins) ion beam implantation can be used following the thin film deposition to mix the deposited silver atoms into the surface. Ion beam enhanced deposition contemplates depositing the thin film of silver concurrent with ion beam bombardment. This approach optimizes adhesion of the silver to the surface. Thin film deposition, ion beam implantation, and ion beam enhanced deposition are all well known techniques for depositing and implanting thin metal films and ions onto exposed surfaces.

While the present invention has been illustrated by the description of embodiments thereof, and while the embodiments have been described in detail, it is not the intention of the inventors to restrict or in any way limit the scope of the appended claims to such detail. Additional advantages and modifications will readily appear to those skilled in the art. It will be understood that the specific medical device examples described herein are exemplary only, and additional medical devices not specifically described can be produced in accordance with the principles of the present invention to incorporate antimicrobial properties therein. The invention in its broader aspects is therefore not limited to the specific details, representative apparatus and methods, and illustrative examples shown and described. Accordingly, departures may be made from such details without departing from the spirit or scope of the inventors' general inventive concept.

What is claimed is:

Claims

1. A medical device comprising: a housing having a fluid path therein and at least one port for coupling to a source of fluid; and a member associated with said housing and in communication with said fluid path to selectively control access to said fluid path, characterized in that said access control member having a composition comprising a synthetic resin material and an antimicrobial agent.

2. The device of claim 1, said synthetic resin material including polyethylene.

3. The device of claim 1, said antimicrobial agent having as an active ingredient silver or a derivative thereof.

4. The device of claim 3, said antimicrobial agent comprising glass microspheres coated with elemental silver.

5. The device of claim 3, said antimicrobial agent comprising glass platelets coated with silver.

6. The device of claim 3, said antimicrobial agent comprising glass fibers coated with silver.

7. The device of claim 1, said antimicrobial agent having as an active ingredient a metal selected from the group consisting of silver, copper, zinc, and derivatives thereof.

8. The device of claim 1, said antimicrobial agent compounded with said synthetic resin material and molded to form said access control member.

9. The device of claim 8, said antimicrobial agent at least partially exposed on at least one surface of said access control member.

10. The device of claim 8, said access control member having at least one ablated surface to at least partially expose said antimicrobial agent.

11. The device of claim 1 , said antimicrobial agent in the form of a surface layer adhesively secured to at least one surface of said access control member.

12. The device of claim 1, said antimicrobial agent at least partially exposed on at least one surface of said access control member and applied thereto by ion beam implantation.

13. The device of claim 1, said access control member comprising in the range of about 75% to 99% by weight synthetic resin material and about 1% to 25% by weight antimicrobial agent.

14. The device of claim 13, said access control member comprising about 75% by weight synthetic resin material and about 25% by weight antimicrobial agent.

15. The device of claim 1, said housing comprised substantially of a synthetic resin material.

16. The device of claim 15, said synthetic resin material including polycarbonate.

17. The device of claim 1, said housing being substantially devoid of an antimicrobial agent.

18. The device of claim 1 further comprising a second port; said access control member being a valve situated between said first and second ports and operable to selectively control fluid communication between said second port and said fluid path.

19. The device of claim 1 further comprising a second port; said access control member being a dead-end plug receivable in the second port to seal same.

20. The device of claim l further comprising a second port communicating with said fluid path; said access control member being a moveable plug body in said second port.

21. The device of claim 1 further comprising a second port communicating with said fluid path; said access control member being a resilient plug body in the second port.

22. The device of claim 1, said housing including a syringe body; said access control member being a syringe plunger movable within said syringe body.

23. A medical device comprising: a housing having a fluid path therein and at least one port for coupling to a source of fluid; and a member associated with said housing and in communication with sai fluid path to selectively control access to said fluid path, characterized in that said access control member comprising a synthetic resin material and having a layer of an antimicrobial agent adhesively secured to at least one surface thereof which is in communication with said fluid path.

24. A method of making a medical device component including a synthetic resin material and an antimicrobial agent, said method comprising the steps of: compounding a synthetic resin material and an antimicrobial agent to form a mixture thereof; molding said mixture to produce a medical device component; and ablating at least one surface of said component to at least partially expose said antimicrobial agent.

25. The method of claim 24, said ablating step comprising exposing said at least one surface to an oxygen-containing plasma.

26. The method of claim 25, said plasma ablating step having a duration of about 5 minutes.

27. The method of claim 24, said antimicrobial agent having as an active ingredient silver-coated glass beads.

28. The method of claim 24, said antimicrobial agent having as an active ingredient silver coated glass platelets.

29. The method of claim 24, said antimicrobial agent having as an active ingredient silver coated glass fibers.

30. The method of claim 24, said antimicrobial agent having as an active ingredient a metal selected from the group consisting of silver, copper, zinc, and derivatives thereof.

31. A method of reducing the incidence of nosocomial infections in patients who are exposed to fluid susceptible of containing infection-causing bacteria, said method comprising: coupling said fluid into a housing having a fluid path therein and at least one port for coupling to a source of the fluid, providing in association with said housing and in communication with said fluid path, an access control member by which to selectively control access to said fluid path, characterized in that said access control member having a composition comprising a synthetic resin material and an effective amount of an antimicrobial agent to kill infection-causing bacteria in said fluid.

32. A system for the administration of fluid to a patient, said system comprising: a fluid source; a fluid conduit connected to said fluid source and adapted to be placed in fluidic communication with a patient; a housing having a fluid path therein and at least two ports for coupling said fluid path in series with said fluid conduit; and a member associated with said housing and in communication with said fluid path to selectively control access to said fluid path, characterized in that said access control member having a composition comprising a synthetic resin material and an antimicrobial agent.

33. The device of claim 32, said synthetic resin material including polyethylene.

34. The device of claim 32, said antimicrobial agent having as an active ingredient silver or a derivative thereof.

35. The device of claim 34, said antimicrobial agent comprising glass microspheres coated with elemental silver.

36. The device of claim 34, said antimicrobial agent comprising glass platelets coated with silver.

37. The device of claim 34, said antimicrobial agent comprising glass fibers coated with silver.

38. The device of claim 32, said antimicrobial agent having as an active ingredient a metal selected from the group consisting of silver, copper, zinc, and derivatives thereof.

39. The device of claim 32, said antimicrobial agent compounded with said synthetic resin material and molded to form said access control member.

40. The device of claim 39, said antimicrobial agent at least partially exposed on at least one surface of said access control member.

41. The device of claim 39, said access control member having at least one ablated surface to at least partially expose said antimicrobial agent.

42. The device of claim 32, said access control member comprising in the range of about 75% to 99% by weight synthetic resin material and about 1% to 25% by weight antimicrobial agent.

43. The device of claim 42, said access control member comprising about 75% by weight synthetic resin material and about 25% by weight antimicrobial agent.

44. The device of claim 32, said housing comprised substantially of a synthetic resin material.

45. The device of claim 44, said synthetic resin material including polycarbonate.

46. The device of claim 32, said housing being substantially devoid of an antimicrobial agent.

47. The device of claim 32, said housing having first and second ports; said access control member being a valve situated between said first and second ports and operable to selectively control fluid communication between said second port and said fluid path.

48. The device of claim 32, said housing having first and second ports; said access control member being a dead-end plug receivable in the second port to seal same.

49. The device of claim 32, said housing having first and second ports communicating with said fluid path; said access control member being a moveable plug body in said second port.

50. The device of claim 32, said housing having first and second ports communicating with said fluid path; said access control member being a resilient plug body in the second port.

51. The device of claim 32, said access control member being a syringe plunger movable within said syringe body.