Polyethyleneimine copolymer compositions and methods for enhancing antiviral and antibacterial properties of medical devices and instruments

Abstract

The present invention provides compositions and methods for infusing antibacterial and antiviral polyethylenimine compounds into materials customarily used in medical devices and instruments, including materials such as vinyl, polyvinyl chloride, latex, rubber, silicone and plastic materials, to enhance the safety and antiviral properties of such medical equipment.

Description

[Technical Field]

[0001] CROSS-REFERENCE TO RELATED APPLICATIONS This application is related to U.S. Provisional Patent Application No. 63 / 438,386, filed January 11, 2023, the contents of which are incorporated herein in their entirety.

[0002] The present disclosure relates to the field of embedding antibacterial and antiviral polyethyleneimine compounds into conventional materials used in medical devices, including materials such as vinyl, polyvinyl chloride, latex, rubber, silicone, and plastic materials. [Background technology]

[0003] The current pandemic and the persistent problems of hospital-acquired infections and iatrogenic diseases have brought clear attention to and emphasized the need to add and enhance the antiviral and antibacterial properties of medical instruments and devices that are already supposed to be "sterile," including catheters, syringes, and similar common medical equipment. As recent studies have shown, a significant number of nosocomial, i.e., hospital-acquired, urinary tract infections are caused by urinary catheters commonly used in the general hospitalized patient population. Notably, the annual cost of treating urinary tract infections in the United States exceeds $451 million. The need to mitigate and alleviate these exorbitant and unnecessary medical costs offers great promise for medical innovations that can address this issue. Summary of the Invention

[0004] The present disclosure provides compositions and methods for adding and infusing polyethyleneimine solutions into base compositions of medical devices, including adding polyethyleneimine to vinyl and polyvinyl chloride catheters and medical tubing to add and enhance the safety and sterility of such medical devices and devices, reducing the incidence and severity of hospital-acquired infections, such as urinary tract infections, in the medical patient population.

[0005] The present invention provides a novel copolymer of polyethyleneimine and silicone. Rather than a polyethyleneimine surface coating on a silicone base, this copolymer material exhibits significantly greater durability and utility than a surface coating. In particular, the presence of the copolymer throughout the material means that the antiviral active properties do not fragment, peel, or "fall off," as occurs with antiviral agents applied strictly as a coating or surface coating to an underlying base material.

[0006] The present invention is equally useful and effective across a variety of common medical device materials, including latex, silicone, vinyl and polyvinyl chloride. [Brief explanation of the drawings]

[0007] [Figure 1] FIG. 1 shows the chemical structure of (linear) polyethyleneimine and an expanded representation of the structure of linear polyethyleneimine. [Figure 2] FIG. 2 shows a typical representation of a branched polyethyleneimine. DETAILED DESCRIPTION OF THE INVENTION

[0008] Detailed Description of the Invention To enable those skilled in the art to make and use various embodiments, the present application is described in detail below in conjunction with figures and specific embodiments. Descriptions of specific devices, techniques, and applications are provided as examples. Various modifications to the examples described herein will be readily apparent to those skilled in the art, and the general principles defined herein may be applied to other examples and applications without departing from the spirit and scope of the present invention. Therefore, the disclosed invention is not intended to be limited to the examples described herein, but is to be accorded the widest breadth and scope consistent with the appended claims.

[0009] In the present invention, polyethyleneimine, as shown in its linear form in Figure 1, and alternatively, polyethyleneimine, as shown in its branched form in Figure 2, are blended with silane and chitosan at effective concentrations to generate a surface charge that can be substantially three times stronger than existing formulations. The resulting material is readily adaptable for fabrication and use as tubes, plates, and gels. The materials of the present invention exhibit effective antiviral and antibacterial activity, thus offering great potential for anti-infective applications in medical devices and instruments, including catheters, implantable devices, and tubes.

[0010] In a preferred embodiment of the composition and method of the present invention, 14.72 g of E41 silicone is mixed with 1.28 g of polyethyleneimine (8% of the silicone mass) on a silicone gel plate. In another preferred embodiment, the amount of polyethyleneimine ranges from substantially about 2% to substantially about 10% of the silicone mass. The mixture is allowed to stand for 27 hours. The mixture (and silicone gel plate) is then conditioned in an oven at a temperature of 60°C or less for 12 hours to allow polymerization and crosslinking to occur.

[0011] Continuing with the method of the preferred embodiment of the present invention, the silicone gel plate is removed from the mixture and the mixture is then allowed to stand at room temperature for 7 days.

[0012] In a preferred method of the present invention, after 7 days of standing, the mixture is immersed in 400 ml of deionized water for 24 hours to allow dynamic equilibrium between the polyethyleneimine and silicone to be reached, and finally, the mixture is conditioned in an oven at a temperature of 60°C or less for 1 hour to extract the water from the silicone.

[0013] In a preferred embodiment of the present invention, rather than washing the silicone with ultrasonic methods, the novel polyethyleneimine-silicone copolymer is soaked overnight under stable and fixed conditions, allowing the polyethyleneimine to redistribute throughout the silicone material, achieving a dynamic equilibrium between the aqueous solution and the silicone material, which can then produce a non-cytotoxic material with potent antibacterial and antiviral properties.

[0014] In a preferred embodiment of the present invention, the positive polarity of the polyethyleneimine / silicone copolymer surface promotes effective reduction of blood clotting, since the positive polarity repels iron in the blood.

[0015] In the present invention, copolymerization of polyethyleneimine with silicone does not affect or diminish the physical functionality of the silicone material, as the concentration of polyethyleneimine is low enough to promote beneficial therapeutic functionality while also avoiding adverse effects on the physical and functional properties of the silicone material itself.

[0016] The effective concentration for obtaining good antimicrobial activity with the structures and methods of the present invention encompasses a narrow range that also encompasses other beneficial characteristics, including (low) cytotoxicity, effectiveness against blood clotting, and preservation of a range of expected and desirable physical characteristics of the medical device itself.

[0017] The copolymer compositions of the present invention may be used in a myriad of medical, dental, and other commercial applications, and preferred embodiments of the present invention include use in: Catheters, including but not limited to vascular catheters, cardiovascular catheters, pulmonary artery catheters, central venous catheters, intraventricular shunts, peripheral venous catheters, urinary catheters, peritoneal catheters, epidural catheters, and central nervous system catheters; Medical tubes, such as breathing tubes, tracheostomy tubes, endotracheal tubes, nasogastric tubes, endotracheal tubes, percutaneous gastric tubes, percutaneous jejunostomy tubes, nasojejunal tubes, nephrostomy tubes; Medical grade electrodes, clips, fasteners, containers, syringes, hoses, CPAP machine hoses, CPAP face masks, asthma hoses, ventilators, biofilms and biofilaments.

[0018] Additionally, as indicated, the methods and compositions of the present invention may be incorporated with equally beneficial results and functionality into the production, manufacture, and use of related medical instruments, tools, and devices, including but not limited to catheters, tubing, or syringes: Blood exchange devices, Implantable devices, such as stents, biliary stents, arterial lines, pacemakers, shunts, ports, vascular access ports, infusion and injection ports, wiring, extracorporeal circuits, implantable prosthetic limbs, dental implants, breast implants, penile implants, sexual aids, condoms, tendons, cranial / facial tendons, ligaments, menisci, intervertebral discs, rods, artificial vocal cords, artificial bones, artificial joints, artificial organs, pumps, heart valves, vascular grafts, etc. Scopes, such as those used in endoscopic or laparoscopic procedures; Bandages, adhesive plasters, and Sutures, such as cardiovascular sutures. The methods and compositions of the present invention may also be used in ancillary applications and products with similar beneficial properties, including antiviral efficacy and functionality, including, for example: Non-medical tubing, clips, fasteners, containers, food storage containers, cell phone cases, non-medical respirators, scuba or other diving or aviation breathing face masks, hoses and equipment, syringes, hoses, paints, drywall / sheetrock, false ceiling and other building materials, construction, and fabrics.

[0019] While various embodiments of the invention have been described, it will be apparent to those skilled in the art that many more embodiments and implementations are possible that are within the scope of the invention. In addition, the various features, elements, and embodiments described herein may be included in or combined with the claims in any combination or arrangement.

Claims

1. 1. An antiviral medical device material comprising a cationic polymeric space charge electret material having antiviral properties bonded to the medical device material, the cationic polymer is natural, semi-synthetic, or synthetic; Further, the cationic polymer has a linear, branched, hyperbranched, or dendrimer-like structure, and the cationic polymer includes at least a cationic carrying group located in the main chain or a side chain of the cationic polymer; and An antiviral medical device material, wherein the medical device material is vinyl, polyvinyl chloride, latex, rubber, silicone, or plastic.

2. 2. The antiviral medical device material of claim 1, wherein the cationic polymer is selected from the group consisting of PEI, linear polyethyleneimine, branched polyethyleneimine, gelatin, chitosan, cationic peptides, cationic cyclodextrin, cationic dextran, cationic cellulose, polylysine, polyamidonamine, poly(amino coester), or poly[2-(N,N-dimethylamino)ethyl methacrylate], polyethyleneimine.

3. 3. The antiviral medical material according to claim 2, wherein the cationic polymer is polyethyleneimine.

4. 4. The antiviral medical material according to claim 3, wherein the space charge electret material comprises 0.195% to 10% by weight of the polyethyleneimine cationic polymer.

5. 5. The antiviral medical device material of claim 4, wherein the space charge electret material comprises substantially 2% to 8% by weight of polyethyleneimine cationic polymer.

6. Substantially uniform surface charge with a minimum average positive surface charge of 2-35 nCcm -2 The antiviral device material according to claim 1,

7. 10. The antiviral medical device material of claim 1, which retains its antiviral efficacy when interwoven, bonded, blended, or mixed with other non-antiviral materials.

8. 10. The antiviral device material of claim 1 formed as a flexible hollow tubular structure.

9. 1. A method for manufacturing an antiviral medical device material, comprising the steps of: Dissolving a space charge electret material in a suitable solvent to form a space charge electret material / solvent mixture, wherein the concentration of the space charge electret material in the solvent is 0.195% to 10% by weight; mixing a space charge electret with a silicone material on a silicone gel plate; allowing the mixture to stand for 0 to 24 hours; conditioning the mixture at a temperature below 60°C for 0 to 24 hours; then removing and removing the silicone gel plate to provide the antiviral medical device material; A method comprising:

10. 10. The method of claim 9, wherein the space charge electret material is dissolved in a solvent that has no added salts.

11. The method of claim 10 wherein the solvent is water.

12. 11. The method of claim 10, wherein the solvent is methanol.

13. 10. The method of claim 9, wherein the space charge electret material is 0.195% to 10% by weight polyethyleneimine.

14. 14. The method of claim 13, wherein the space charge electret material is substantially 2% to 8% by weight polyethyleneimine.

15. The resulting antiviral medical material has a substantially uniform surface charge and a minimum average positive surface charge of 2 to 35 nCcm -2 The method of claim 9, wherein

16. 16. The method of claim 15, wherein the antiviral medical material is formed as a flexible hollow silicone tube.

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