WO2025170968A1

WO2025170968A1 - Medical device with antibiotic and anti-adherence properties

Info

Publication number: WO2025170968A1
Application number: PCT/US2025/014543
Authority: WO
Inventors: Jeannette Ho; Alexandra Piotrowicz; Jiaqing ZUO; Antonio CILLERO RODRIGO; Quentin ATEN; Thomas B. BODEN; Richard Gould; Tanzil ISLAM
Original assignee: Evonik Canada Inc; Integra Lifesciences Corp
Current assignee: Evonik Canada Inc; Integra Lifesciences Corp
Priority date: 2024-02-05
Filing date: 2025-02-05
Publication date: 2025-08-14
Anticipated expiration: 2026-08-05

Abstract

Described herein are compositions, use and methods for manufacturing medical devices containing bioactive agents such as antimicrobials and surface modifying molecules, such that surfaces can reduce biological adhesion, the process prevents loss throughout the process, permits uniform distribution of the additives in the material, provides uniform elution rates of the antimicrobials, and permits surface modification. The compositions can be used as medical devices such as catheters, shunts, or as coatings for medical devices.

Description

MEDICAL DEVICE WITH ANTIBIOTIC AND ANTI-ADHERENCE PROPERTIES

BACKGROUND

Infection and occlusion due to biological adhesion are encountered for catheters, shunts, and other medical devices, it is desirable to develop improved implants that can reduce infection while also reducing the adhesion of blood products, proteins, immune response, reactive neurological cells, and other cells to extend operational lifespan by minimizing adhesion and obstruction once implanted in the body.

In order to develop such improved implants, it is desired to combine a surface modifying molecule (SMM) that is bioinert — such as a molecule with fluorinated end-groups — with the antimicrobials to achieve the combined benefit of the bioinert properties of the SMMs and the efficacy of the antimicrobials. Currently, the state-of-the-art does not provide for medical devices with the combined benefit of bioinert SMMs and effective antimicrobials. The state-of-the-art also does not incorporate SMMs and antimicrobials having similar solubility characteristics into a base silicone.

The higher molecular weight of the SMMs prevents imbibing via solvent swelling and incorporation into the bulk of the material. At the same time, the SMMs nearest to the surface of the polymer can be depleted and/or extracted through a solvent swelling process, effectively eliminating their bioinert surface modification.

When co-imbibing the material with both SMMs and antimicrobials via the solvent swelling method, both SMMs and antimicrobials may dissolve, but due to dissimilar diffusion rates of the SMMs and antimicrobials there is non-uniform distribution of the SMMs. This leads to a lack of surface functionalization by the SMMs.

For the application of antimicrobial coatings, the SMM must be compounded into the polymeric material prior to coating with antimicrobials. The coating is applied to post-forming of the base polymer material, resulting in the antimicrobials covering the SMMs and thus resulting in loss of effectiveness of the additives.

In antimicrobial particle compounding, the standard processes of particle compounding with silicone results in non-uniform distribution of the antimicrobials, and therefore causes non- uniform elution rates of the antimicrobials.

Pre-extrusion compounding of both the SMMs and antimicrobials may enable the incorporation of both additive types into the base polymer. A challenge remains to provide a uniform (non-crystalline, non-particulate) distribution of the antimicrobials within the polymer. Additionally, the compounded antimicrobials remain vulnerable to thermal degradation in traditional heat forming or heat curing processes and further degradation in sterilization.

US 2023338621 A1 discloses an admixture comprising oligofluorinated additive and base polymer. This document further discloses that the base polymer may contain suitable additives known to those of ordinary skill in the art, such as antimicrobials, antiseptics, antibiotics or other functional additives. Example antimicrobial, antiseptic or antibiotic agents include triclosan, silver sulfadiazine, chlorohexidine, rifampin or clindamycin. However, in antimicrobial particle compounding, the standard processes of particle compounding with silicone results in non- uniform distribution of the antimicrobials, and therefore causes nonuniform elution rates of the antimicrobials. Thus, devices formed using such processes would not reduce the infection while also reducing the adhesion of blood products, proteins, immune response, reactive neurological cells, and other cells to extend operational lifespan by minimizing adhesion and obstruction once implanted in the body.

US 2021268543 A1 discloses an admixture comprising oligofluorinated additive and base polymer wherein the surface of the admixture comprising oligofluorinated additive and base polymer is contacted with an antimicrobial, antiseptic, or disinfectant. This document discloses that the admixture comprising oligofluorinated additive and base polymer is externally exposed to antibiotic solution and therefore the antibiotics having an external effect.

What is needed are compositions and methods for manufacturing implants or coatings impregnated with antimicrobials and SMMs that prevents loss throughout the process, permits uniform distribution of the additives in the material, provides uniform elution rates of the antimicrobials, and permits surface functionalization of the SMMs after compounding. Yet, another object of the present invention is to provide an improved composition for manufacturing of implants/medical device that can reduce infection while also reducing the adhesion of blood products, proteins, immune response, reactive neurological cells, and other cells to extend operational lifespan by minimizing adhesion and obstruction once implanted in the body.

SUMMARY

One embodiment described herein is a composition comprising: a base polymer selected from one or more of thermosets, thermoplastics, or combinations thereof; an oligofluorinated additive; and one or more bioactive agents compatible with the oligofluorinated additive and the base polymer, wherein the base polymer, the oligofluorinated additive and the bioactive agent form a bioactive agent- oligofluorinated additive-base polymer solid dispersion, solid solution, or combination thereof. In one aspect, the base polymer is selected from one or more of polyurethane, silicone, polyamide, polyester, co-polyester, polyether, polyether-block-amide copolymer, polypropylene, polyethylene, polyvinylchloride, polysulfone, polyethersulfone, styrenic block copolymer, vulcanized rubber, polyetherimide, polycarbonate, polyetheretherketones, ethyl vinyl acetates, polyethylene terephthalate, polybutylene terephthalate, polymethylmethacrylate, parylene, or polyolefins. In another aspect, the base polymer is silicone or polyurethane. In another aspect, the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): wherein: A comprises a soft segment comprising a polyalkylene oxide, a polycarbonate, a polysulfone, a polydimethylsiloxane, a polyamide, a polyester, or a lactone; B comprises a hard segment comprising a urethane; B' comprises a hard segment comprising a urethane trimer, or a biuret trimer; B" comprises a polyalkylene oxide or a moiety of formula: surface-active group; and n is an integer from 0-10. In another aspect, G is a perfluoroalkyl group. In another aspect, G is: CH_mF(3-m)(CF2)_rCH2CH2- or CH_mF(3- m)(CF2)_s(CH₂CH2O)x-, wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10. In another aspect, the soft segment comprises one or more of hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co-butylene), (diethylene glycol ortho phthalic anhydride) polyester, (1 ,6-hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, polydimethylsiloxane, polysiloxane-polyethylene glycol block copolymer, polysiloxanepolypropylene glycol block copolymer, bisphenol A ethoxylate, polyethylene oxide)-b- poly(propylene oxide)-b-poly(ethylene oxide) (PLN), polyethylene oxide (PEO), polypropylene oxide (PPO), polytetramethylene oxide (PTMO), or a combination thereof. In another aspect, the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons. In another aspect, the oligofluorinated additive is present in an amount of 0.05-15 wt%, relative to the base polymer. In another aspect, use of the composition comprising: a base polymer selected from one or more of thermosets, thermoplastics, or combinations thereof; an oligofluorinated additive; and one or more bioactive agents compatible with the oligofluorinated additive and the base polymer, wherein the base polymer, the oligofluorinated additive and the bioactive agent form a bioactive agent- oligofluorinated additive-base polymer solid dispersion, solid solution, or combination thereof for manufacturing of a medical device. In another aspect, the medical device is selected from a hydrocephalus valve, a catheter, a ventricular catheter, a distal catheter, a vascular catheter, a drainage catheter, a subdural drain having a catheter, a neurological catheter, an infusion catheter, a parenteral feeding catheter, a stroke therapy catheter, a urological catheter, a shunt, a cannula, a stent, a graft, a stent-graft, an endoprosthesis angioplasty balloon, a biosensor, a birth control device, a reconstructive mesh, a tympanostomy tube, an ophthalmic device, an endotracheal tube, or a cerebral spinal fluid diversion conduit. In another aspect, the medical device comprises a subdural drain having a catheter. In another aspect, the medical device comprises an implantable sensor for measuring intracranial pressure, brain oxygen level, brain temperature, or one or more other patient parameters; wherein the medical device material forms a flexible membrane in the implantable sensor or a portion thereof. In another aspect, the one or more bioactive agents include one or more selected from antimicrobials, antiseptics, antibiotics, antifungals, antivirals, anti-inflammatory drugs, anti-proliferative drugs, anti-oxidants, proteins, peptides, carbohydrates, anti-coagulants, analgesics, or anesthetics. In another aspect, the one or more bioactive agents are present in an amount of 0.01-50 wt%. In another aspect, the one or more bioactive agents are antimicrobial. In another aspect, the antimicrobial bioactive agent comprises one or more of rifampin, clindamycin, minocycline, vancomycin, gentamycin, penicillin, miconazole, lincomycins, tetracyclines, cephalosporins, fluoroquinolones, or a combination thereof.

Another embodiment described herein is a method of making a medical device comprising the steps of: admixing an oligofluorinated additive with one or more bioactive agents to form a primary admixture, wherein the oligofluorinated additive and the bioactive agent form a bioactive agent- oligofluorinated additive dispersion, solution, or combination thereof, or a solid dispersion, solid solution, or combination thereof or a composition; compounding the primary admixture with a base polymer to form a secondary admixture, wherein the base polymer, the oligofluorinated additive and the bioactive agent form a bioactive agent- oligofluorinated additive-base polymer solid dispersion, solid solution, or combination thereof; and processing the secondary admixture to form the medical device. In one aspect, the oligofluorinated additive and the one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, the one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a homogenous bioactive agent- oligofluorinated additive homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solid solution, or combination thereof. In one aspect, the oligofluorinated additive and the one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, the one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a bioactive agent- oligofluorinated additive homogenous composition. In another aspect, the oligofluorinated additive is admixed with the one or more bioactive agents using one or more of mechanical stirring, homogenizing, vortexing, dual axis centrifugal mixing, or sonicating. In another aspect, the secondary admixture is formed into a shaped component. In another aspect, the base polymer is silicone, and the secondary admixture is extruded to form a flexible tube. In another aspect, the base polymer is selected from one or more of polyurethane, silicone, polyamide, polyester, co-polyester, polyether, polyether-block-amide co-polymer, polypropylene, polyethylene, polyvinylchloride, polysulfone, polyethersulfone, styrenic block copolymer, vulcanized rubber, polyetherimide, polycarbonate, polyetheretherketones, ethyl vinyl acetates, parylene, or polyolefins. In another aspect, the medical device is substantially or fully cured while under reduced pressure or inert atmosphere. In another aspect, the medical device is substantially or fully cured under reduced pressure at a temperature of 105-145 °C for 5-90 minutes. In another aspect, the primary admixture is admixed with the base polymer to form a bioactive agent- oligofluorinated additive-base polymer solid dispersion, solid solution, or combination thereof, using one or more of blending, compounding, or milling. In another aspect, the medical device has a surface, and wherein the oligofluorinated additive and the one or more bioactive agents are evenly distributed across the surface of the medical device. In another aspect, the one or more bioactive agents include one or more selected from antimicrobials, antiseptics, antibiotics, antifungals, antivirals, anti-inflammatory drugs, anti-proliferative drugs, anti-oxidants, proteins, peptides, carbohydrates, anti-coagulants, analgesics, or anesthetics. In another aspect, the medical device comprises of 0.05-15 wt% of the oligofluorinated additive relative to the base polymer. In another aspect, the base polymer is silicone. In another aspect, the polymer is platinum cured silicone. In another aspect, the polymer is cured using ultraviolet light in a wavelength range of 100-400 nm. In another aspect, the polymer is cured using heat. In another aspect, the polymer is cured using high-energy electrons or photons. In another aspect, the secondary admixture is formed into a medical device using one or more of extrusion, molding, or coating. In another aspect, the medical device is sterilized using an oxidizing gas selected from ethylene oxide and ozone. In another aspect, the medical device is sterilized using ionizing radiation at doses between 15-80 kGy selected from electron beam, gamma ray, and x- ray. In another aspect, the medical device is sterilized using one or more of most heat or dry heat. In another aspect, sterilization promotes functionalization based on providing energy through heat, high-energy electrons, or photons. In another aspect, the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): wherein: A comprises a soft segment comprising a polyalkylene oxide, a polycarbonate, a polysulfone, a polydimethylsiloxane, a polyamide, a polyester, or a lactone; B comprises a hard segment comprising a urethane; B' comprises a hard segment comprising a urethane trimer, or a biuret trimer; B" comprises a polyalkylene oxide or a moiety of formula: surface-active group; and n is an integer from 0-10. In another aspect, G is a perfluoroalkyl group. In another aspect, G is: CH_mF₍3-m)(CF2)_rCH2CH2- or CH_mF(₃. m)(CF2)s(CH2CH2O)_x- , wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10. In another aspect, the soft segment comprises one or more of hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co-butylene), (diethylene glycolortho phthalic anhydride) polyester, (1 ,6-hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, bisphenol A ethoxylate, polyethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PLN), polyethylene oxide (PEG), polypropylene oxide (PPO), polytetramethylene oxide (PTMO), or a combination thereof. In another aspect, the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons.

Another embodiment described herein is a medical device comprising a base polymer selected from one or more of thermosets, thermoplastics, or combinations thereof; an oligofluorinated additive; and one or more bioactive agents soluble or compatible with the oligofluorinated additive, comprising: admixing an oligofluorinated additive with the one or more bioactive agents to form a primary admixture; admixing the primary admixture is compounded with a base polymer into a secondary admixture; and processing the secondary admixture to form the medical device. In one aspect, the oligofluorinated additive and the one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, the one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solid solution, or combination thereof. In one aspect, the oligofluorinated additive and the one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, the one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a bioactive agent- oligofluorinated additive homogenous composition. In another aspect, the oligofluorinated additive is admixed with one or more bioactive agents using one or more of mechanical stirring, homogenizing, vortexing, dual axis centrifugal mixing, or sonicating. In another aspect, the primary admixture is admixed with the base polymer using one or more of blending, compounding, or milling. In another aspect, the secondary admixture is formed into a medical device using one or more of extrusion, molding, or coating. In another aspect, the secondary admixture is extruded to form a flexible tube. In another aspect, the medical device is substantially or fully cured while under reduced pressure or inert atmosphere. In another aspect, the medical device is substantially or fully cured under reduced pressure at a temperature of 105-145 °C for 5-90 minutes. In another aspect, medical device is sterilized using one or more of moist heat or dry heat. In another aspect, sterilization promotes functionalization based on providing energy through heat, high-energy electrons, or photons. In another aspect, the medical device is sterilized using an oxidizing gas selected from ethylene oxide and ozone. In another aspect, the medical device is sterilized using ionizing radiation at doses between 15-80 kGy selected from electron beam, gamma ray, and x-ray. In another aspect, the medical device has a surface, and wherein the oligofluorinated additive and the one or more bioactive agents are evenly distributed across the surface of the medical device. In another aspect, the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): wherein: A comprises a soft segment comprising a polyalkylene oxide, a polycarbonate, a polysulfone, a polydimethylsiloxane, a polyamide, a polyester, or a lactone; B comprises a hard segment comprising a urethane; B' comprises a hard segment comprising a urethane trimer, or a biuret trimer; B" comprises a polyalkylene oxide or a moiety of formula: surface-active group; and n is an integer from 0-10. In another aspect, G is a perfluoroalkyl group. In another aspect, G is: CH_mF(3-m)(CF2)_rCH2CH2- or CH_mF(3- m)(CF2)s(CH2CH2O)_x- , wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10. In another aspect, the soft segment comprises hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)- 1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co-butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6-hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, bisphenol A ethoxylate, polyethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PLN), polyethylene oxide (PEO), polypropylene oxide (PPO), polytetramethylene oxide (PTMO), or a combination thereof. In another aspect, the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons.

Another embodiment described herein is a method for draining fluid to reduce infection or bioaccumulation from using a medical device comprising a bioactive agent- oligofluorinated additive-base polymer solid dispersion, solid solution, or a combination thereof, wherein the method comprises: inserting the medical device that comprises a base polymer, an oligofluorinated additive and a bioactive agent into a burr hole of a patient; draining the fluid from the patient through a proximal end of the medical device; and controlling flow rate of the fluid through the medical device using a control mechanism. In one aspect, the medical device is selected from a hydrocephalus valve, a catheter, a ventricular catheter, a distal catheter, a vascular catheter, a drainage catheter, a subdural drain having a catheter, a neurological catheter, an infusion catheter, a parenteral feeding catheter, a stroke therapy catheter, a urological catheter, a shunt, a cannula, a stent, a graft, a stent-graft, an endoprosthesis angioplasty balloon, a biosensor, a birth control device, a reconstructive mesh, a tympanostomy tube, an ophthalmic device, an endotracheal tube, or a cerebral spinal fluid diversion conduit. In another aspect, the bioactive agent includes one or more selected from antimicrobials, antiseptics, antibiotics, antifungals, antivirals, anti-inflammatory drugs, anti-proliferative drugs, anti-oxidants, proteins, peptides, carbohydrates, anti-coagulants, analgesics, or anesthetics. In another aspect, the bioactive agent is present in an amount of 0.01-50 wt%. In another aspect, the bioactive agent is an antimicrobial. In another aspect, the antimicrobial bioactive agent comprises one or more of rifampin, clindamycin, minocycline, vancomycin, gentamycin, penicillin, miconazole, lincomycins, tetracyclines, cephalosporins, fluoroquinolones, or a combination thereof. In another aspect, the oligofluorinated additive is present in an amount of 0.05-0.15 wt%, relative to the polymer. In another aspect, the medical device further comprises a base polymer selected from one or more of polyurethane, silicone, polyamide, polyester, co-polyester, polyether, polyether- block-amide co-polymer, polypropylene, polyethylene, polyvinylchloride, polysulfone, polyethersulfone, styrenic block copolymer, vulcanized rubber, polyetherimide, polycarbonate, polyetheretherketones, ethyl vinyl acetates, parylene, or polyolefins. In another aspect, the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): G — PB — A1 — B — G

wherein: A comprises a soft segment comprising a polyalkylene oxide, a polycarbonate, a polysulfone, a polydimethylsiloxane, a polyamide, a polyester, or a lactone; B comprises a hard segment comprising a urethane; B' comprises a hard segment comprising a urethane trimer, or a biuret trimer; B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 1-10. In another aspect, G is a perfluoroalkyl group. In another aspect, G is: CH_mF(₃-m)(CF2)_rCH2CH2- or CH_mF(3-m)(CF2)s(CH2CH2O)_x-, wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10. In another aspect, B" is -(CH2CH2O)2-4- In another aspect, the oligofluorinated additive has a thermal degradation temperature of between about 200-450 °C. In another aspect, n is 1. In another aspect, the soft segment comprises one or more of hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)- 1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co-butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6-hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, bisphenol A ethoxylate, polyethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PLN), polyethylene oxide (PEG), polypropylene oxide (PPG), or polytetramethylene oxide (PTMO), or a combination thereof. In another aspect, the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons. In another aspect, the oligofluorinated additive comprises, by percent mass (wt%): 5-30% of the hard segment; 40-90% of the soft segment; and 25-55% of the surface active group. Another embodiment described herein is a medical device comprising a base polymer selected from one or more of thermosets, thermoplastics, or combinations thereof; an oligofluorinated additive; and a bioactive agent compatible with the oligofluorinated additive, comprising: admixing an oligofluorinated additive with a bioactive agent to form a primary admixture, wherein the oligofluorinated additive and the bioactive agent form a bioactive agent- oligofluorinated additive dispersion, solution, or combination thereof, or solid dispersion, solid solution, or combination thereof, or a composition; admixing the primary admixture is compounded with a base polymer into a secondary admixture, wherein the base polymer, the oligofluorinated additive and the bioactive agent form a bioactive agent- oligofluorinated additivebase polymer solid dispersion, solid solution, or combination thereof; and processing the secondary admixture to form the medical device. In one aspect, the oligofluorinated additive and the bioactive agent are admixed in one or more solvents, and the admixture of oligofluorinated additive, bioactive agent, and one or more solvents are dried to remove the one or more solvents to form a homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solid solution, or combination thereof. In one aspect, the oligofluorinated additive and the one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, the one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a bioactive agent- oligofluorinated additive homogenous composition. In another aspect, the oligofluorinated additive is admixed with the bioactive agent using one or more of mechanical stirring, homogenizing, vortexing, dual axis centrifugal mixing, or sonicating. In another aspect, the primary admixture is admixed with the base polymer using one or more of blending, compounding, or milling. In another aspect, the secondary admixture is formed into a medical device using one or more of extrusion, molding, or coating. In another aspect, the secondary admixture is extruded to form a flexible silicon tube. In another aspect, the medical device is substantially or fully cured while under reduced pressure or inert atmosphere. In another aspect, the medical device is substantially or fully cured under an inert atmosphere at a temperature of 105-145 °C for 5-90 minutes. In another aspect, medical device is autoclaved with an inert gas at a temperature greater than 121 °C between 15-90 minutes. In another aspect, autoclaving promotes functionalization. In another aspect, the medical device has a surface, and wherein the oligofluorinated additive and bioactive agent are evenly distributed across the surface of the medical device. In another aspect, the oligofluorinated additive is any one of Formula (I), G — PB — AI — B — G

(II), (III), or (IV): ¹ n

G is a surface-active group; and n is an integer from 1-10. In another aspect, G is a perfluoroalkyl group. In another aspect, G is: CH_mF(₃-m)(CF2)_rCH2CH2- or CH_mF(3-m)(CF2)s(CH2CH2O)_x-, wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10. In another aspect, B" is -(CH2CH2O)2-4- In another aspect, the oligofluorinated additive has a thermal degradation temperature of between about 200 °C and about 450 °C. In another aspect, wherein n is 1. In another aspect, the soft segment comprises hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)- 1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co-butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6-hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, bisphenol A ethoxylate, polyethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PLN), polyethylene oxide (PEG), polypropylene oxide (PPG), polytetramethylene oxide (PTMO), or a combination thereof. In another aspect, the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons. In another aspect, the oligofluorinated additive comprises, by percent mass (wt%): 5- 30% of the hard segment; 40-90% of the soft segment; and 25-55% of the surface active group. DESCRIPTION OF THE DRAWINGS

The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.

FIG. 1A-B show flowcharts of the manufacturing process.

FIG. 2A-C show a formulation of SMM (IBI-1006), and two antimicrobials (rifampicin and clindamycin) were successfully incorporated into the silicone material. FIG. 2A shows a hand-cut cured silicone + SMM (IBI-1006) + rifampicin + clindamycin. The uniform color indicated even distribution of antibiotics. FIG. 2B shows SEM image of silicone + antibiotics + SMM (IBI-1006) indicating uniform distribution of one SMM formulation. FIG. 2C shows EDS fluorine map showing 1.75% fluorine, indicating distribution of one SMM formulation (IBI-1006) at expected concentration.

FIG. 3 shows four formulations of SMM compared to a control silicone catheter without SMM for neurological tissue adhesion after 1 week. Bright blue spots indicate adhered cells on the catheter surface.

FIG. 4 shows 3 formulations of SMM compared to a control, non-antimicrobial catheter and Bactiseal for testing against gram negative bacteria. The yellow-colored surface of petri dish is cultured gram-negative bacteria. Circles around catheters showing the bottom surface of the petri dish indicate elimination of the gram-negative bacteria in that area. All catheters except the non-antimicrobial catheter demonstrate elimination of the gram-negative bacteria.

FIG. 5 shows two control catheters (Bactiseal and TraumaCath), one non-antimicrobial silicone-SMM catheter (IBI-1013) and three silicone-antimicrobial loaded catheters each with a different formulation of SMM for blood loop testing. The control catheters were covered in thrombus, while the catheter with SMM formulation I BI-1013 and the antimicrobial-loaded IBI- 1006, IBI-1012 and IBI-1013 had some significant benefit.

FIG. 6 shows three formulations of SMM compared to a control silicone catheter without SMM and Bactiseal for neurological tissue adhesion after 1 week and 2 weeks. Bright white spots indicate adhered cells on the catheter surface.

DETAILED DESCRIPTION

Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. For example, any nomenclatures used in connection with, and techniques of medical technology, polymer science, chemistry, and biochemistry described herein are well known and commonly used in the art. In case of conflict, the present disclosure, including definitions, will control. Exemplary methods and materials are described below, although methods and materials similar or equivalent to those described herein can be used in practice or testing of the embodiments and aspects described herein.

As used herein, the terms such as “include,” “including,” “contain,” “containing,” “having,” and the like mean “comprising.” The present disclosure also contemplates other embodiments “comprising,” “consisting of,” and “consisting essentially of,” the embodiments or elements presented herein, whether explicitly set forth or not.

As used herein, the term “a,” “an,” “the” and similar terms used in the context of the disclosure (especially in the context of the claims) are to be construed to cover both the singular and plural unless otherwise indicated herein or clearly contradicted by the context. In addition, “a,” “an,” or “the” means “one or more” unless otherwise specified.

As used herein, the term “or” can be conjunctive or disjunctive.

As used herein, the term “substantially” means to a great or significant extent, but not completely.

As used herein, the term “about” or “approximately” as applied to one or more values of interest, refers to a value that is similar to a stated reference value, or within an acceptable error range for the particular value as determined by one of ordinary skill in the art, which will depend in part on how the value is measured or determined, such as the limitations of the measurement system. In one aspect, the term “about’ refers to any values, including both integers and fractional components that are within a variation of up to ± 10% of the value modified by the term “about.” Alternatively, “about” can mean within 3 or more standard deviations, per the practice in the art. Alternatively, such as with respect to biological systems or processes, the term “about” can mean within an order of magnitude, in some embodiments within 5-fold, and in some embodiments within 2-fold, of a value. As used herein, the symbol means “about” or “approximately.”

All ranges disclosed herein include both end points as discrete values as well as all integers and fractions specified within the range. For example, a range of 0.1-2.0 includes 0.1 , 0.2, 0.3, 0.4 . . . 2.0. If the end points are modified by the term “about,” the range specified is expanded by a variation of up to ±10% of any value within the range or within 3 or more standard deviations, including the end points.

As used herein, the terms “control,” or “reference” are used herein interchangeably. A “reference” or “control” level may be a predetermined value, range, method, or composition, which is employed as a baseline or benchmark against which to assess a measured result. “Control” also refers to control experiments. As used herein, the terms “formulation” and “composition” are used interchangeably herein.

As used herein, “bioactive agent” refers to antibiotics, antifungals, antivirals, antimicrobial agents, antiseptics, anti-inflammatory drugs, anti-proliferative drugs, anti-oxidants, proteins, peptides, carbohydrates, anti-coagulants, analgesics, or anesthetics.

As used herein, “anti-adherence” or “anti-bioaccumulation” refer to agents that prevent or diminish the adherence or bioaccumulation of cells, bacteria, or biofilm to a medical device.

As used herein, “medical device’ includes catheters, implants, coatings for apparatus, and the like. Exemplary medical devices comprise catheters, vascular catheters, drainage catheters, neurological catheters, infusion catheter, parenteral feeding catheters, stroke therapy catheters, hydrocephalus valves, ventricular catheters, distal catheters, urological catheters, subdural drain having one or more catheters, shunts, stents, grafts, stent-grafts, devices for endoprosthesis, angioplasty balloons, biosensors, birth control devices, scaffolds, reconstructive meshes, wound dressings, tympanostomy tubes, ophthalmic devices, endotracheal tubes, cerebral spinal fluid diversion conduits, implantable sensors for measuring intracranial pressure, brain oxygen level sensors, brain temperature sensors or devices for measuring one or more medical parameters.

As used herein, “surface modifying molecule” or “SMM” refer to oligofluorinated additives.

As used herein, “soluble” or “solubility” refers to the ability of at least one first substance to form a solution with at least one second substance. Typically, solubility does not involve permanent modification of the first or second substance. Solubility includes, but is not limited to, the separation of ions or transient interactions between the at least first substance and the at least second substance. As used here, “transient interactions” are interactions that are not permanent. Non-limiting exemplary transient interactions include hydrogen bonding, van der Waals, and electrostatic.

As used herein, “compatible” or “compatibility” refers to the ability of at least two substances to stably exist or occur together without reacting or adversely affecting each other or additional components in a composition.

The term “molecular weight,” as used herein, refers to a theoretical weight of an Avogadro number of molecules of identical composition. As preparation of a surface modifying macromolecule can involve generation of a distribution of compounds, the term “molecular weight” refers to an idealized structure determined by the stoichiometry of the reactive ingredients. Thus, the term “molecular weight,” as used herein, refers to a theoretical molecular weight Compositions

I. Exemplary Base Polymers

In one aspect, the exemplary base polymers may be selected from a group of thermosets, thermoplastics, and combinations thereof.

In another aspect, the exemplary base polymers may be selected from one or more of polyurethane, silicone, polyamide, polyester, co-polyester, polyether, polyether-block-amide copolymer, polypropylene, polyethylene, polyvinylchloride, polysulfone, polyethersulfone, styrenic block copolymer, vulcanized rubber, polyetherimide, polycarbonate, polyetheretherketones, ethyl vinyl acetates, polyethylene terephthalate, polybutylene terephthalate, polymethylmethacrylate, parylene, or polyolefins.

In another aspect, the exemplary base polymers may be silicone or polyurethane.

In another aspect, the base polymer may contain other non-bioactive agents such as fillers, colorants, radiopacifiers, pigments, stabilizers, antioxidants, plasticizers, reinforcing agents, conductive agents, processing aids.

II. Exemplary Oligofluorinated Additives

In one aspect, the exemplary oligofluorinated additives may be any one of Formula (I), (II), wherein:

A comprises a soft segment comprising a polyalkylene oxide, a polycarbonate, a polysulfone, a polydimethylsiloxane, a polyamide, a polyester, or a lactone;

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer; B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 0-10.

In one aspect, the exemplary oligofluorinated additives may be one of any formula (I), (II), (III), or (IV), as described above, where G may be a perfluoroalkyl group.

In one aspect, the exemplary oligofluorinated additive may be one of any formula (I), (II), (III), or (IV), as described above, where G may be CH_mF(3-_m)(CF2)rCH2CH2- or CH_mF(3- m)(CF2)_s(CH2CH2O)x- , where m may be 0, 1 , 2, or 3; where r may be an integer between 2-20; where s may be an integer between 1-20; and x may be an integer between 1-10.

In one aspect, the exemplary oligofluorinated additives may be one of any formula (I), (II), (III), or (IV), as described above, where B" may be -(CH2CH2O)2-4-

In one aspect, the exemplary oligofluorinated additives may be one of any formula (I), (II), (III), or (IV), where the soft segment may be one or more of hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co-butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6- hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, polydimethylsiloxane, polysiloxane-polyethylene glycol block copolymer, polysiloxane-polypropylene glycol block copolymer, bisphenol A ethoxylate, polyethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PLN), polyethylene oxide (PEG), polypropylene oxide (PPG), polytetramethylene oxide (PTMO), or a combination thereof.

In one aspect, the exemplary oligofluorinated additives may be one of any formula (I), (II), (III), (IV), where the soft segment may have a number average molecular weight (M_n) of 500- 3500 Daltons.

In one aspect, the exemplary oligofluorinated additives may have a mass percent (wt%) relative to the base polymer between 0.05-15 wt%; 0.06-15 wt%; 0.07-15 wt%; 0.08-15 wt%; 0.09-15 wt%; 0.1-15 wt%; 0.11-15 wt%; 0.12-15 wt%; 0.13-15 wt%; 0.14-15 wt%; 0.2-15 wt%; 0.5-15 wt%; 1-15 wt%; 2-15 wt%; 3-15 wt%; 4-15 wt%; 5-15 wt%; 6-15 wt%; 7-15 wt%; 8-15 wt%; 9-15 wt%; 10-15 wt%; 11-15 wt%; 12-15 wt%; 13-15 wt%; 14-15 wt%. In another aspect, the oligofluorinated additives may have a mass percent (wt%) relative to the base polymer of no less than 0.05 wt%; no less than 0.07 wt%; no less than 0.09 wt%; no less than 0.11 wt%; no less than 0.13 wt%; no less than 0.5 wt%; no less than 1 wt%; no less than 3 wt%; no less than 5 wt%; no less than 7 wt%; no less than 9 wt%; no less than 11 wt%; no less than 13 wt%. In another aspect, the oligofluorinated additives may have a mass percent (wt%) relative to the base polymer of no greater than 15 wt%; no greater than 14 wt%; no greater than 12 wt%; no greater than 10 wt%; no greater than 8 wt%; no greater than 6 wt%; no greater than 4 wt%; no greater than 2 wt%; no greater than 0.8 wt%; no greater than 0.14 wt%; no greater than 0.12 wt%; no greater than 0.10 wt%; no greater than 0.08 wt%; or no greater than 0.06 wt%.

III. Exemplary Bioactive Agents

In one aspect, the exemplary bioactive agents may be selected from one or more of antimicrobials, antiseptics, antibiotics, antifungals, antivirals, anti-inflammatory drugs, antiproliferative drugs, anti-oxidants, proteins, peptides, carbohydrates, anti-coagulants, analgesics, or anesthetics.

In one aspect, the exemplary bioactive agent may be an antimicrobial. In another aspect, the antimicrobial may be one or more of rifampin, clindamycin, minocycline, vancomycin, gentamycin, penicillin, miconazole, lincomycins, tetracyclines, cephalosporins, fluoroquinolones, or a combination thereof.

In one aspect, the exemplary bioactive agents may be present in an amount between 0.01-50 wt%; 0.02-50 wt%; 0.03-50 wt%; 0.04-50 wt%; 0.05-50 wt%; 0.06-50 wt%; 0.07-50 wt%; 0.08-50 wt%; 0.09-50 wt%; 0.1-50 wt%; 0.15-50 wt%; 0.2-50 wt%; 0.3-50 wt%; 0.4-50 wt%; 0.5-50 wt%; 0.6-50 wt%; 0.7-50 wt%; 0.8-50 wt%; 0.9-50 wt%; 1-50 wt%; 2-50 wt%; 3- 50 wt%; 4-50 wt%; 5-50 wt%; 6-50 wt%; 7-50 wt%; 8-50 wt%; 9-50 wt%; 10-50 wt%; 15-50 wt%: 20-50 wt%; 25-50 wt%; 30-50 wt%; 35-50 wt%; 40-50 wt%; or 45-50 wt%, wherein 100 wt% is defined as total wt% of base polymer, oligofluorinated additive, and bioactive agent. In another aspect, the exemplary bioactive agents may be present in an amount of no less than 0.01 wt%; no less than 0.02 wt%; no less than 0.03 wt%; no less than 0.04 wt%; no less than 0.05 wt%; no less than 0.06 wt%; no less than 0.07 wt%; no less than 0.08 wt%; no less than 0.09 wt%; no less than 0.1 wt%; no less than 0.15 wt%; no less than 0.2 wt%; no less than 0.5 wt%; no less than 1 wt%; no less than 3 wt%; no less than 5 wt%; no less than 7 wt%; no less than 9 wt%; no less than 11 wt%; no less than 13 wt%; no less than 15 wt%; no less than 17 wt%; no less than 19 wt%; no less than 21 wt%; no less than 23 wt%; no less than 25 wt%; no less than

27 wt%; no less than 29 wt%; no less than 31 wt%; no less than 33 wt%; no less than 35 wt%; no less than 37 wt%; no less than 39 wt%; no less than 41 wt%; no less than 43 wt%; no less than 45 wt%; no less than 47 wt%; or no less than 49 wt%, wherein 100 wt% is defined as total wt% of base polymer, oligofluorinated additive, and bioactive agent. In another aspect, the exemplary bioactive agents may be present in an amount no greater than 50 wt%; no greater than 48 wt%; no greater than 46 wt%; no greater than 44 wt%; no greater than 42 wt%; no greater than 40 w%; no greater than 38 wt%; no greater than 36 wt%; no greater than 34 wt%; no greater than 32 wt%; no greater than 30 wt%; no greater than 28 wt%; no greater than 26 wt%; no greater than 24 wt%; no greater than 22 wt%; no greater than 20 wt%; no greater than 18 wt%; no greater than 16 wt%; no greater than 14 wt%; no greater than 12 wt%; no greater than 10 wt%; no greater than 8 wt%; no greater than 6 wt%; no greater than 4 wt%; no greater than 2 wt%; no greater than 1 wt%; no greater than 0.8 wt%; no greater than 0.4 wt%; no greater than 0.1 wt%; no greater than 0.05 wt%; or no greater than 0.02 wt%, wherein 100 wt% is defined as total wt% of base polymer, oligofluorinated additive, and bioactive agent.

Process for the preparation of the composition

Methods for imbibing SMMs along with antimicrobial agents (e.g., antibiotics, antifungals, or antivirals) may include solvent impregnation of antibiotics followed by separate physical compounding of the SMM into an uncured portion of the cross-linked base polymer; solvent impregnation of both the SMM and antimicrobials into an uncured portion of the cross-linked based polymer; and solvent impregnation of the antimicrobials into the surface modifying molecules followed by physical compounding of the resultant mixture into one or both parts of the cross-linked based polymer.

The process comprises:

1. admixing an oligofluorinated additive with one or more bioactive agents to form a primary admixture, wherein the oligofluorinated additive and the bioactive agent form a bioactive agent-oligofluorinated additive dispersion, solution, or combination thereof, or solid dispersion, solid solution, or combination thereof, or a composition;

2. compounding the primary admixture of step 1. with a base polymer to form a secondary admixture, wherein the base polymer, the oligofluorinated additive and the bioactive agent form a bioactive agent- oligofluorinated additive-base polymer solid dispersion, solid solution, or combination thereof.

In one aspect in step 1. the primary admixture obtained is in the form of bioactive agent- oligofluorinated additive homogenous dispersion, solution, or combination thereof, or homogenous solid dispersion, solid solution, or combination thereof, or a homogenous composition. In one aspect in step 1. the oligofluorinated additive and one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solid solution, or combination thereof. In one aspect, the oligofluorinated additive and the one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, the one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a bioactive agent- oligofluorinated additive homogenous composition. In another aspect, the oligofluorinated additive is admixed with the one or more bioactive agents using one or more of mechanical stirring, homogenizing, vortexing, dual axis centrifugal mixing, or sonicating. In another aspect, the primary admixture is admixed with the base polymer using one or more of blending, compounding, or milling. In another aspect, the oligofluorinated additive and the one or more bioactive agents are evenly distributed across the whole surface of the base polymer.

Manufacturing Methods

The medical device described herein overcomes the prevailing problem of implementing a process for concurrent surface functionalization with SMMs and release of one or more bioactive agents without compromising or eliminating the efficacy of either the SMM or bioactive agent.

One embodiment described herein is a method of making a medical device comprising a bioactive agent- oligofluorinated additive-base polymer solid dispersion, solid solution, or a combination thereof; wherein the method comprises: admixing an oligofluorinated additive with one or more bioactive agents to form a primary admixture, wherein the oligofluorinated additive and the bioactive agent form a bioactive agent-oligofluorinated additive dispersion, solution, or combination thereof, or a solid dispersion, solid solution, or combination thereof, or a composition thereof; compounding the primary admixture with a base polymer to form a secondary admixture, wherein the base polymer, the oligofluorinated additive and the bioactive agent form a bioactive agent- oligofluorinated additive-base polymer solid dispersion, solid solution, or combination thereof; and processing the secondary admixture to form the component of the medical device. In one aspect the oligofluorinated additive and one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solution, or combination thereof. In another aspect, the oligofluorinated additive is admixed with the one or more bioactive agents using one or more of mechanical stirring, homogenizing, vortexing, dual axis centrifugal mixing, or sonicating. In another aspect, the secondary admixture is formed into a shaped component. In another aspect, the base polymer is silicone, and the secondary admixture is extruded to form a flexible silicon tube. In another aspect, the medical device is substantially or fully cured while under reduced pressure or inert atmosphere. In another aspect, the medical device is substantially or fully cured under an inert atmosphere at a temperature of 105-145 °C for 5-90 minutes. In another aspect, the primary admixture is admixed with the base polymer using one or more of blending, compounding, or milling. In another aspect, the medical device has a surface, and wherein the oligofluorinated additive and the one or more bioactive agents are evenly distributed across the whole surface of the medical device. In another aspect, the one or more bioactive agents include one or more selected from antimicrobials, antiseptics, antibiotics, antifungals, antivirals, anti-inflammatory drugs, anti-proliferative drugs, anti-oxidants, proteins, peptides, carbohydrates, anti-coagulants, analgesics, or anesthetics. In another aspect, the base polymer is selected from one or more of polyurethane, silicone, polyamide, polyester, co-polyester, polyether, polyether-block-amide co-polymer, polypropylene, polyethylene, polyvinylchloride, polysulfone, polyethersulfone, styrenic block copolymer, vulcanized rubber, polyetherimide, polycarbonate, polyetheretherketones, ethyl vinyl acetates, parylene, or polyolefins. In another aspect, the medical device comprises of 0.05-15 wt% of the oligofluorinated additive relative to the base polymer. In another aspect, the base polymer is silicone. In another aspect, the polymer is platinum cured silicone. In another aspect, the energy for curing is ultraviolet light in the wavelength range of 100-400 nm. In another aspect, the energy for curing is heat. In another aspect, the energy for curing is provided by high-energy electrons or photons. In another aspect, the secondary admixture is formed into a medical device using one or more of extrusion, molding, or coating. In another aspect, the medical device is sterilized using one or more of moist heat or dry heat. In another aspect, the medical device is sterilized using an oxidizing gas selected from ethylene oxide and ozone. In another aspect the medical device is sterilized using ionizing radiation at doses between 15-80 kGy selected from electron beam, gamma ray, and x-ray. In another aspect, the sterilization process promotes functionalization based on providing energy through heat, high-energy electrons, or photons. In another aspect, the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): wherein:

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer;

B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 0-10.

In another aspect, G is a perfluoroalkyl group.

In another aspect, G is:

CH_mF(3-m)(CF2)_rCH2CH2- or CHmF(3-_m)(CF2)_s(CH2CH₂O)x-, wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10. In another aspect, B" is -(CH2CH2O)2-4-.

In another aspect, the soft segment comprises one or more of hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co-butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6- hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, bisphenol A ethoxylate, polyethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PLN), polyethylene oxide (PEG), polypropylene oxide (PPG), polytetramethylene oxide (PTMO), or a combination thereof. In another aspect, the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons.

Exemplary methods of manufacturing a medical device may comprise various operations. FIG. 1 shows example method 100 for manufacturing a medical device. As shown, method 100 includes admixing one or more bioactive agents and an oligofluorinated additive in one or more solvents to form a primary admixture (operation 102), determine whether the primary admixture includes one or more solvents (decision 104), drying the primary admixture (operation 106), imbibing a first portion of the primary admixture with a first portion of a base polymer that does not contain a catalyst to form a first polymeric material (operation 108), imbibing a second portion of the primary admixture with a second portion of a base polymer to form a second polymeric material that contains a catalyst to form a second polymeric material (operation 110), admixing the first polymeric material with the second polymeric material to form a secondary admixture (operation 112), and processing the secondary admixture to form a medical device (operation 114). Exemplary medical devices described and contemplated herein may be manufactured based on the operations of method 100.

Various embodiments are described below for the impregnation of the antimicrobials and a gel, liquid, or high consistency SMM into a two-part cross-linking elastomer, such as silicone rubber.

One embodiment of the manufacturing process which meets the above requirements includes the incorporation of both the SMM and the one or more bioactive agents into the first portion of the cross-linked based polymer containing the catalyst (Part A) and into the second portion of the based polymer without a catalyst (Part B) as described below.

In one aspect, a solution is prepared by admixing one or more bioactive agents and an oligofluorinated additive in one or more solvents to form a primary admixture (operation 102). In one aspect, the one or more solvents may include chloroform, methanol, tetrahydrofuran, dimethyl sulfoxide, dimethylformamide, ethanol, ethyl acetate, or methyl tertbutyl ether.

In one aspect, the one or more solvents may be combined in an appropriate ratio between 50/50 to 95/5; 50/50 to 90/10’ 50/50 to 85/15; 50/50 to 80/20; 50/50 to 75/25; 50/50 to 70/30; 50/50 to 65/35; 50/50 to 60/40; 50/50 to 55/45; or about 50/50. In another aspect, the one or more solvents may be combined in an appropriate ratio of no greater than 95/5; no greater than 90/10; no greater than 85/15; no greater than 80/20; no greater than 75/25; no greater than 70/30; no greater than 65/35; no greater than 60/40; or no greater than 55/45. In another aspect, the one or more solvents may be combined in an appropriate ratio of no less than 50/50; no less than 55/45; no less than 60/40; no less than 65/35; no less than 70/30; no less than 75/25; no less than 80/20; no less than 85/15; or no less than 90/10.

In one aspect, the one or more bioactive agents and oligofluorinated additive are dissolved into the one or more solvents using a method selected from a group of agitation, fluidic sheer induced mixing, and mechanical sheer mixing. In another aspect, the one or more bioactive agents and oligofluorinated additive are mixed into the one or more solvents until a homogeneous solution is provided, thereby forming a primary admixture.

In one aspect, determine whether the primary admixture includes one or more solvents (decision 104, YES branch). In another aspect, the primary admixture is dried (operation 106).

In one aspect, the primary admixture is dried under reduced pressure to remove the one or more solvents to form a bioactive agent- oligofluorinated additive homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solid solution, or combination thereof, or a homogenous composition.

In one aspect, the primary admixture is formed under agitation and, subsequently, drying under reduced pressure is applied to the primary admixture to remove the one or more solvents.

In one aspect, the primary admixture is dried at ambient temperatures

In one aspect, the primary admixture may undergo additional drying at atmospheric conditions. In another aspect, the primary admixture may undergo additional drying at moderate temperature under reduced pressure. In another aspect, the primary admixture may undergo additional drying under inert atmosphere at a temperature between 20 °C and 50 °C.

In one aspect, a first portion of the dried primary admixture is compounded with a first portion of a base polymer that does not contain a catalyst to form a first polymeric material (operation 108). In one aspect, a base polymer includes a polymer that may be processed by manual means, such as milling. In another aspect, the mass of the base polymer is divided into two (2) portions (i.e., Part A and Part B). In another aspect, Part A includes the first portion of the base polymer. In another aspect, Part B includes the second portion of the base polymer with a catalyst.

In one aspect, Part A and the first portion of the primary admixture undergo one or more milling passes until the first portion of the admixture is fully blended into Part A to form the first polymeric material. Qualitative testing known in the art may be used to determine whether the first portion of the primary admixture is fully blended into Part A.

In one aspect, a radiopaque material selected from a group of barium sulfate, or a colorant may be imbibed with Part A.

In one aspect, a second portion of the dried primary admixture may be imbibed into a second portion of the base polymer to form a second polymeric material (operation 110). In another aspect, the second portion of the base polymer is Part B.

In one aspect, Part B and a second portion of the primary admixture undergo one or more milling passes until the second portion of primary admixture is fully blended into Part B to form the second polymeric material. As discussed above, qualitative testing known in the art may be used to determine whether the second portion of the primary admixture is fully blended into Part B.

In one aspect, the first polymeric material and the second polymeric material are admixed together to form a secondary mixture (operation 112). Qualitative testing known in the art may be used to determine if the first polymeric material and the second polymeric material are fully blended.

In one aspect, the secondary admixture is processed to form a medical device (operation 114).

FIG. 2 shows example method 200 for manufacturing a medical device. In one aspect, method 200 may include the operations of method 100. As shown, method 200 includes extruding a secondary admixture to form a medical device (operation 202), curing the medical device (operation 204), and autoclaving the medical device to sterilize the medical device (operation 206). Exemplary medical devices described and contemplated herein may be manufactured based on the operations of method 200.

In one aspect, a secondary admixture (e.g., as described above in operation 112) is extruded (operation 204). In another aspect, the secondary admixture may be extruded through a vertical or horizontal extruder to form a medical device. In one aspect, the medical device is cured under reduced pressure condition between 5 minutes and 90 minutes. In another aspect, the medical device is cured under inert atmospheric conditions at a temperature between 105 °C and 145 °C, including all integers, endpoints, and subranges within the specified range.

In one aspect, the medical device is cured under reduced pressure at a chamber pressure less than 50 mbar. In another aspect, the medical device is cured under reduced pressure between 30 minutes and 240 minutes.

In one aspect, the medical device is autoclaved to sterilize the medical device (operation 206). In another aspect, the autoclave is a steam autoclave and may be performed with or without an inert atmosphere. In another aspect, the water source to produce the steam may be selected from a group of normal deionized, or degassed water.

Medical Devices

As described herein, the compositions and the methods of manufacture described above can be used to produce any one of the following medical devices including, but not limited to, a catheter, vascular catheter, drainage catheter, neurological catheter, infusion catheter, parenteral feeding catheter, stroke therapy catheter, hydrocephalus valve, ventricular catheter, distal catheter, urological catheter, subdural drain having a catheter, shunt, stent, graft, stent-graft, endoprosthesis, angioplasty balloon, biosensor, birth control device, scaffold, reconstructive mesh, wound dressing, tympanostomy tube, ophthalmic device, endotracheal tube, cerebral spinal fluid diversion conduit, implantable sensor for measuring intracranial pressure, brain oxygen level, brain temperature, or one or more other patient parameters; where the device material forms a flexible membrane in the implantable sensor or a portion thereof.

I. Exemplary Medical Devices

A. Catheter

One example embodiment of a medical device made of a polymeric material impregnated with bioactive (e.g., antimicrobial) agents capable of reducing device-related bacterial infection and SMMs which reduce occlusion and/or biological material adhesion to the device within the central nervous system (CNS) is a ventricular catheter consisting of a single lumen, optionally incorporating a closed bullet shaped tip for traumatically penetrating brain tissue. The catheter may further employ a radial pattern of flow holes or slits near the distal tip through which cerebral spinal fluid (CSF) enters the catheter lumen. The catheter may also have markings along its length to indicate the distance from its distal tip. The catheter may have the following exemplary dimensions:

Outer diameter 2.4-4.0 mm

Inner diameter 1.2-2.0 mm

Overall length 60-350 mm

Distal Perforations

Perforations may be holes, slots, slits 0.5-1.8 mm in diameter or width. Perforations may be arranged in a variety of patterns such as rows along the length of the catheter.

The dimensions of the catheter will be selected depending on if the ventricular catheter is used in a shunt system (typically smaller diameter, shorter) or as an EVD catheter (typically larger diameter, longer).

B. Distal Shunt

A distal shunt catheter is another embodiment of an implantable neurosurgical silicone medical device containing bioactive agents (e.g. antimicrobial) and SMMs which would benefit from reduced occlusion and/or biological material adhesion to the device. The distal shunt catheter consists of one or more lumens and may have perforations or slits near the distal most end of the catheter. The distal shunt catheter may have the following dimensions:

Outer diameter 2.0-3.0 mm

Inner diameter 0.7-1 .5 mm

Overall length 60-120 cm

Distal Perforations

Perforations may be holes, slots, slits 0.5 - 1 .8 mm in diameter or width. Perforations may be arranged in a variety of patterns such as rows along the length of the catheter.

The composition of the catheter described above is (all % are wt/wt): High consistency silicone elastomer with a durometer of 35-75 shore A. Optionally, the catheter may also contain a radiopaque marker such as barium sulphate or tantalum oxide. The radiopaque marker may be uniformly distributed throughout the catheter. For example, the catheter may contain a uniform distribution of 10-20% barium sulfate or concentrated in portions of the catheter. For example, the catheter may have a co-extruded stripe and a tip containing 10-30% barium sulfate, or the catheter may have tantalum oxide impregnated markings, or a tantalum oxide impregnated tip. Exemplary constituents may include: 0.5-10% SMM; 0.002-1.0% Rifampin; 0.002-1.0% Clindamycin; 0.1-5.0% biocompatible colorant.

The antimicrobial (AM) agents impregnated into the catheter may be either broad spectrum, gram negative specific, or gram positive specific antibiotics. The antimicrobial agents may also include antifungal or antiviral agents. Antimicrobial agents may be used singularly or in combination.

The SMM migrates to the catheter surfaces, resulting in a surface that exemplifies the chemistry of the SMM and renders the catheter surfaces more resistant to biological adhesion.

The SMM additive can comprise of two domains: fluorocarbon groups connected by a polymer chain. The fluorocarbon groups are immiscible with the base polymeric material and, as such, they migrate to the material’s surface during milling. However, the SMM backbone is sufficiently compatible to the base polymeric material such that the SMM additive becomes incorporated into the base polymeric material.

While not all molecules migrate to the surface, the compounding and extrusion, curing and sterilization process parameters can be controlled to ensure that a consistent portion of the catheter surface contains SMM.

The modified CNS catheter’s adhesion and antimicrobial properties address the issues of biological-based occlusions and infection simultaneously. The non-eluting, surface modifying molecules at the catheter surface render it less adhesive. Consequently, key biological cell types, such as platelets in the case of thrombus formation and astrocytes in the case of neurological tissue adhesion/occlusion, are less likely to adhere to the biologically inert catheter surface, thereby reducing thrombus adhesion/formation and neurological tissue adhesion. Thus, the device is less susceptible to biological-induced occlusion or obstruction. In combination with the slow-eluting antimicrobials, the modified CNS catheter may also reduce surface colonization of microorganisms such as gram negative bacteria and thereby reducing infection.

Shunt System Components

Shunt system components (valves, reservoirs, fluid connectors) are another embodiment of an implantable neurosurgical silicone medical device containing SMMs which would benefit from reduced occlusion and/or biological material adhesion to the device as well as reduce device-related infection. The flexible portions of the components (the dome on a reservoir), and the sleeves or casings around the components are often made of silicone. In this invention, the silicone components contain a fluorinated surface modifying macromolecule (SMM), which renders at least a portion of the device bioinert, while also containing the antimicrobials to reduce surface colonization of microorganisms such as gram negative bacteria and thereby reducing infection.

One such conventional adjustable or programmable implantable valve is the CODMAN ® HAKIM® Programmable Valve (CHPV), as disclosed in US Patent No. 4,595,390. Another programmable implantable drainage valve is the CODMAN ® CERTAS® or CERTAS-Plus® Programmable Valve. The pressure setting in these aforementioned conventional programmable implantable valves may be non-invasively adjusted post implantation in the body using a rotating construct or rotor with a pair of magnets. The proposed designs would include at least one thermoset cross-linked material like silicone wherein the material(s) include fluorinated macromolecular additive(s) (SMM) that fluorinates the valve surfaces, resulting in a surface that is bioinert, as well as antimicrobials that reduce surface colonization of microorganisms. This renders the catheter valve biologically inert and non-bioreactive (NB) while maintaining antimicrobial (AM) properties. The valve may also include additional components composed of other materials such as gemstone (ruby, sapphire, etc) and various metals (stainless steel, titanium, etc.) that do not include a SMM. In some embodiments, the materials without SMMs and antimicrobials are coated with a coating consisting of polymers containing SMMs and active antimicrobials.

C. Implantable Sensors

Other products, such as implantable sensors for measuring intercranial pressure or brain oxygen content are also at risk of biological adhesion and potential infection due to surgical insertion. Many implantable sensors incorporate a flexible polymer membrane which encapsulates the face of the sensor transducer. In this invention, a silicone polymer sensor membrane contains a SMMs which render the silicone polymer sensor membrane bioinert while also containing the antimicrobials to reduce surface colonization of microorganisms such as gramnegative bacteria and thereby reducing infection.

In another example, one or more implantable pressure and/or flow sensors are integrated into a central nervous system catheter. These sensors are an integral element of some CSF drainage catheters, providing feedback on the physiological effects of fluid drainage, enabling a practitioner and/or a fluid management system to provide the appropriate amount of drainage. The sensor(s) may be located in the primary lumen of the catheter, to sense the pressure and/or flow within the catheter lumen. The sensor(s) may also be incorporated into a separate lumen or within the wall of the catheter such that the sensor membrane is exposed on the exterior surface of the catheter to sense the pressure surrounding the catheter. The catheter and the sensor membrane both contain SMMs to render all exposed surfaces of the sensor membrane and the catheter body bio-inert. The SMMs in the catheter and the sensor membrane may have identical, or different formulations depending on the base material composition of the catheter and sensor membrane. The catheter and sensor membrane contain the active antimicrobials to reduce the surface colonization of micro-organisms.

In yet another example, implantable pressure and/or flow sensors are integrated into fluid shunting reservoirs and/or valves. These sensors are an integral element of some CSF shunting systems, providing feedback on the physiological effects of fluid drainage, enabling a practitioner and/or a fluid management system to provide the appropriate amount of drainage. The sensor(s) may be located in the reservoir/valve’s fluid path, embedded in the reservoir/valve’s housing walls, or in a dedicated compartment or chamber of the reservoir/valve. The sensor(s) may also be incorporated into the external wall or silicone casing of the reservoir/valve such that the sensor membrane is exposed on the exterior surface of the reservoir/valves to sense the surrounding pressure. The reservoir/valve and the sensor membrane both contain SMMs to render all exposed surfaces of the sensor membrane and the catheter body bio-inert. The SMMs in the reservoir/valve and the sensor membrane may have identical, or different formulations depending on the base material composition of the reservoir/valve and sensor membrane. The catheter and sensor membrane contain the active antimicrobials to reduce the surface colonization of microorganisms.

It both the case of sensors integrated with catheters, and sensors integrated with reservoirs/valves, it is advantageous to include the SMMs in the sensor membrane so that the sensor does not become a seeding location for biological material adhesion in an otherwise bioinert device or a microbial reservoir in another wise antimicrobial surface.

It will be apparent to one of ordinary skill in the relevant art that suitable modifications and adaptations to the compositions, formulations, methods, processes, and applications described herein can be made without departing from the scope of any embodiments or aspects thereof. The compositions and methods provided are exemplary and are not intended to limit the scope of any of the specified embodiments. All of the various embodiments, aspects, and options disclosed herein can be combined in any variations or iterations. The scope of the compositions, formulations, methods, and processes described herein include all actual or potential combinations of embodiments, aspects, options, examples, and preferences herein described. The exemplary compositions and formulations described herein may omit any component, substitute any component disclosed herein, or include any component disclosed elsewhere herein. The ratios of the mass of any component of any of the compositions or formulations disclosed herein to the mass of any other component in the formulation or to the total mass of the other components in the formulation are hereby disclosed as if they were expressly disclosed. Should the meaning of any terms in any of the patents or publications incorporated by reference conflict with the meaning of the terms used in this disclosure, the meanings of the terms or phrases in this disclosure are controlling. Furthermore, the foregoing discussion discloses and describes merely exemplary embodiments. All patents and publications cited herein are incorporated by reference herein for the specific teachings thereof.

Various embodiments and aspects of the inventions described herein are summarized by the following clauses:

Clause 1 . A composition comprising: a. a base polymer; b. an oligofluorinated additive; and c. one or more bioactive agents compatible with the oligofluorinated additive and the base polymer, wherein the base polymer, the oligofluorinated additive and the bioactive agent form a bioactive agent-oligofluorinated additive-base polymer solid dispersion, solid solution, or a combination thereof.

Clause 2. The composition of clause 1 , wherein the base polymer is selected from one or more of thermosets, thermoplastics, or combinations thereof.

Clause 3. The composition according to any one of the preceding clauses, wherein the base polymer is selected from one or more of polyurethane, silicone, polyamide, polyester, copolyester, polyether, polyether-block-amide co-polymer, polypropylene, polyethylene, polyvinylchloride, polysulfone, polyethersulfone, styrenic block copolymer, vulcanized rubber, polyetherimide, polycarbonate, polyetheretherketones, ethyl vinyl acetates, polyethylene terephthalate, polybutylene terephthalate, polymethylmethacrylate, parylene, or polyolefins.

Clause 4. The composition according to any one of the preceding clauses, wherein the base polymer is silicone or polyurethane.

Clause 5. The composition according to any one of the preceding clauses, wherein the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): G — PB — AI — B — G

(I) wherein:

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer;

B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 0-10.

Clause 6. The medical device according to any one of the preceding clauses, wherein G is a perfluoroalkyl group.

Clause 7. The medical device according to any one of the preceding clauses, wherein G is: CH_mF(3-m)(CF2)rCH2CH2- or CHmF(₃.m)(CF2)s(CH₂CH2O)x-, wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10.

Clause 8. The composition according to any one of the preceding clauses, wherein the soft segment comprises one or more of hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1,3-propylene carbonate), polybutadiene, poly(diethylene glycol) adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co-butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6- hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, polydimethylsiloxane, polysiloxanepolyethylene glycol block copolymer, polysiloxane-polypropylene glycol block copolymer, bisphenol A ethoxylate, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PLN), polyethylene oxide (PEO), polypropylene oxide (PPO), polytetramethylene oxide (PTMO), or a combination thereof.

Clause 9. The composition according to any one of the preceding clauses, wherein the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons.

Clause 10. The composition according to any one of the preceding clauses, wherein the oligofluorinated additive is present in an amount of 0.05-15 wt%, relative to the base polymer.

Clause H . The composition according to any one of the preceding clauses, wherein the medical device is selected from a hydrocephalus valve, a catheter, a ventricular catheter, a distal catheter, a vascular catheter, a drainage catheter, a subdural drain having a catheter, a neurological catheter, an infusion catheter, a parenteral feeding catheter, a stroke therapy catheter, a urological catheter, a shunt, a cannula, a stent, a graft, a stentgraft, an endoprosthesis angioplasty balloon, a biosensor, a birth control device, a reconstructive mesh, a tympanostomy tube, an ophthalmic device, an endotracheal tube, or a cerebral spinal fluid diversion conduit.

Clause 12. The composition according to any one of the preceding clauses, comprising a subdural drain having a catheter.

Clause 13. The composition according to any one of the preceding clauses, comprising an implantable sensor for measuring intracranial pressure, brain oxygen level, brain temperature, or one or more other patient parameters; wherein the medical device material forms a flexible membrane in the implantable sensor or a portion thereof.

Clause 14. The composition according to any one of the preceding clauses, wherein the one or more bioactive agents include one or more selected from antimicrobials, antiseptics, antibiotics, antifungals, antivirals, anti-inflammatory drugs, anti-proliferative drugs, antioxidants, proteins, peptides, carbohydrates, anti-coagulants, analgesics, or anesthetics.

Clause 15. The composition according to any one of the preceding clauses, wherein the one or more bioactive agents are present in an amount of 0.01-50 wt%, wherein 100 wt% is defined as total wt% of base polymer, oligofluorinated additive, and bioactive agent.

Clause 16. The composition according to any one of the preceding clauses, wherein the one or more bioactive agents are antimicrobial. Clause 17. The composition of clause 16, wherein the antimicrobial bioactive agent comprises one or more of rifampin, clindamycin, minocycline, vancomycin, gentamycin, penicillin, miconazole, lincomycins, tetracyclines, cephalosporins, fluoroquinolones, or a combination thereof.

Clause 18. A method of making a medical device comprising the steps of: admixing an oligofluorinated additive with one or more bioactive agents to form a primary admixture, wherein the oligofluorinated additive and the bioactive agent form a bioactive agent-oligofluorinated additive dispersion, solution, or combination thereof, or a solid dispersion, solid solution, or a combination thereof, or a composition; compounding the primary admixture with a base polymer to form a secondary admixture of a bioactive agent-oligofluorinated additive-base polymer as solid dispersion, solid solution, or a combination thereof; and processing the secondary admixture to form the medical device.

Clause 19. The method of clause 18, wherein the oligofluorinated additive and the one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, the one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solid solution, or combination thereof, or homogenous composition.

Clause 20. The method of clause 18 or 19, wherein the oligofluorinated additive is admixed with the one or more bioactive agents using one or more of mechanical stirring, homogenizing, vortexing, dual axis centrifugal mixing, or sonicating.

Clause 21. The method of any one of clauses 18-20, wherein the secondary admixture is formed into a shaped component.

Clause 22. The method of any one of clauses 18-21 , wherein the base polymer is silicone, and the secondary admixture is extruded to form a flexible tube.

Clause 23. The method of any one of clauses 18-22, wherein the base polymer is selected from one or more of polyurethane, silicone, polyamide, polyester, co-polyester, polyether, polyether-block-amide co-polymer, polypropylene, polyethylene, polyvinylchloride, polysulfone, polyethersulfone, styrenic block copolymer, vulcanized rubber, polyetherimide, polycarbonate, polyetheretherketones, ethyl vinyl acetates, parylene, or polyolefins. Clause 24. The method of any one of clauses 18-23, wherein the medical device is substantially or fully cured while under reduced pressure or inert atmosphere.

Clause 25. The method of any one of clauses 18-24, wherein the medical device is substantially or fully cured under an inert atmosphere at a temperature of 105-145 °C for 5-90 minutes.

Clause 26. The method of any one of clauses 18-25, wherein the primary admixture is admixed with the base polymer using one or more of blending, compounding, or milling.

Clause 27. The method of any one of clauses 18-26, wherein the medical device has a surface, and wherein the oligofluorinated additive and the one or more bioactive agents are evenly distributed across the surface of the medical device.

Clause 28. The method of any one of clauses 18-27, wherein the one or more bioactive agents include one or more selected from antimicrobials, antiseptics, antibiotics, antifungals, antivirals, anti-inflammatory drugs, anti-proliferative drugs, anti-oxidants, proteins, peptides, carbohydrates, anti-coagulants, analgesics, or anesthetics.

Clause 29. The method of any one of clauses 18-28, wherein the medical device comprises of 0.05-15 wt% of the oligofluorinated additive relative to the base polymer.

Clause 30. The method of any one of clauses 18-29, wherein the base polymer is silicone.

Clause 31. The method of any one of clauses 18-30, wherein the polymer is platinum cured silicone.

Clause 32. The method of any one of clauses 18-31, wherein the polymer is cured using ultraviolet light in a wavelength range of 100-400 nm.

Clause 33. The method of any one of clauses 18-32, wherein the polymer is cured using heat.

Clause 34. The method of any one of clauses 18-33, wherein the polymer is cured using high- energy electrons or photons.

Clause 35. The method of any one of clauses 18-34, wherein the secondary admixture is formed into a medical device using one or more of extrusion, molding, or coating.

Clause 36. The method of any one of clauses 18-35, wherein the medical device is sterilized using an oxidizing gas selected from ethylene oxide and ozone.

Clause 37. The method of any one of clauses 18-36, wherein the medical device is sterilized using ionizing radiation at doses between 15-80 kGy selected from electron beam, gamma ray, and x-ray.

Clause 38. The method of any one of clauses 18-37, wherein the medical device is sterilized using one or more of moist heat or dry heat. Clause 39. The method of any one of clauses 18-38, wherein sterilization promotes functionalization based on providing energy through heat, high-energy electrons, or photons.

Clause 40. The method of any one of clauses 18-39, wherein the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): wherein:

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer;

B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 0-10.

Clause 41. The method of any one of clauses 18-40, wherein G is a perfluoroalkyl group.

Clause 42. The method of any one of clauses 18-41 , wherein G is:

CH_mF(3-m)(CF2)_rCH2CH2- or CHmF(3-m)(CF2)s(CH₂CH2O)x-, wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10.

Clause 43. The method of any one of clauses40-42, wherein the soft segment comprises one or more of hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co- butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6-hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, bisphenol A ethoxylate, poly(ethylene oxide)-b-poly(propylene oxide)-b- poly(ethylene oxide) (PLN), polyethylene oxide (PEG), polypropylene oxide (PPO), polytetramethylene oxide (PTMO), or a combination thereof.

Clause 44. The method of any one of clauses40-43, wherein the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons.

Clause 45. A medical device comprising a base polymer selected from one or more of thermosets, thermoplastics, or combinations thereof; an oligofluorinated additive; and one or more bioactive agents soluble or compatible with the oligofluorinated additive, comprising: admixing an oligofluorinated additive with the one or more bioactive agents to form a primary admixture, wherein the oligofluorinated additive and the bioactive agent form a bioactive agent-oligofluorinated additive dispersion, solution, or combination thereof, or a solid dispersion, solid solution, or a combination thereof; admixing the primary admixture is compounded with a base polymer into a secondary admixture to form a base polymer-bioactive agent-oligofluorinated additive solid dispersion, solid solution, or a combination thereof; and processing the secondary admixture to form the medical device.

Clause 46. The medical device of clause 45, wherein the oligofluorinated additive and the one or more bioactive agents are admixed in one or more solvents, and the admixture of oligofluorinated additive, the one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solid solution, or combination thereof, or a homogenous composition.

Clause 47. The medical device of clause 45 or 46, wherein the oligofluorinated additive is admixed with one or more bioactive agents using one or more of mechanical stirring, homogenizing, vortexing, dual axis centrifugal mixing, or sonicating. Clause 48. The medical device of any one of clauses 45-47, wherein the primary admixture is admixed with the base polymer using one or more of blending, compounding, or milling. Clause 49. The medical device of any one of clauses 45-48, wherein the secondary admixture is formed into a medical device using one or more of extrusion, molding, or coating.

Clause 50. The medical device of any one of clauses 45-49, wherein the secondary admixture is extruded to form a flexible tube.

Clause 51. The medical device of any one of clauses 45-50, wherein the medical device is substantially or fully cured while under reduced pressure or inert atmosphere.

Clause 52. The medical device of any one of clauses 45-51 , wherein the medical device is substantially or fully cured under reduced pressure at a temperature of 105-145 °C for 5- 90 minutes.

Clause 53. The medical device of any one of clauses 45-52, wherein medical device is sterilized using one or more of moist heat or dry heat.

Clause 54. The medical device of any one of clauses 45-53, wherein sterilization promotes functionalization based on providing energy through heat, high-energy electrons, or photons.

Clause 55. The medical device of any one of clauses 45-54, wherein the medical device is sterilized using an oxidizing gas selected from ethylene oxide and ozone.

Clause 56. The medical device of any one of clauses 45-55, wherein the medical device is sterilized using ionizing radiation at doses between 15-80 kGy selected from electron beam, gamma ray, and x-ray.

Clause 57. The medical device of any one of clauses 45-56, wherein the medical device has a surface, and wherein the oligofluorinated additive and the one or more bioactive agents are evenly distributed across the surface of the medical device.

Clause 58. The medical device of any one of clauses 45-57, wherein the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): (IV) wherein:

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer;

B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 0-10.

Clause 59. The medical device of any one of clauses 45-58, wherein G is a perfluoroalkyl group.

Clause 60. The medical device of any one of clauses 45-59, wherein G is: CH_mF(3-m)(CF2)_rCH2CH2- or CHmF(3-m)(CF2)s(CH₂CH2O)x-, wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10.

Clause 61. The medical device of any one of clauses 58-60, wherein the soft segment comprises hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co- butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6-hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, bisphenol A ethoxylate, poly(ethylene oxide)-b-poly(propylene oxide)-b- poly(ethylene oxide) (PLN), polyethylene oxide (PEG), polypropylene oxide (PPG), polytetramethylene oxide (PTMO), or a combination thereof. Clause 62. The medical device of any one of clauses 58-61, wherein the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons.

Clause 63. A method for draining fluid to reduce infection or bioaccumulation from using a medical device comprising a bioactive agent-oligofluorinated additive-base polymer solid dispersion, solid solution, or a combination thereof, wherein the method comprises: inserting the medical device that comprises an oligofluorinated additive and a bioactive agent into a burr hole of a patient; draining the fluid from the patient through a proximal end of the medical device; and controlling flow rate of the fluid through the medical device using a control mechanism.

Clause 64. The method of clause 63, wherein the medical device is selected from a hydrocephalus valve, a catheter, a ventricular catheter, a distal catheter, a vascular catheter, a drainage catheter, a subdural drain having a catheter, a neurological catheter, an infusion catheter, a parenteral feeding catheter, a stroke therapy catheter, a urological catheter, a shunt, a cannula, a stent, a graft, a stent-graft, an endoprosthesis angioplasty balloon, a biosensor, a birth control device, a reconstructive mesh, a tympanostomy tube, an ophthalmic device, an endotracheal tube, or a cerebral spinal fluid diversion conduit.

Clause 65. The method of clause 63 or 64, wherein the bioactive agent includes one or more selected from antimicrobials, antiseptics, antibiotics, antifungals, antivirals, antiinflammatory drugs, anti-proliferative drugs, anti-oxidants, proteins, peptides, carbohydrates, anti-coagulants, analgesics, or anesthetics.

Clause 66. The method of any one of clauses 63-65, wherein the bioactive agent is present in an amount of 0.01-50 wt%, wherein 100 wt% is defined as total wt% of base polymer, oligofluorinated additive, and bioactive agent.

Clause 67. The method of any one of clauses 63-66, wherein the bioactive agent is an antimicrobial.

Clause 68. The method of clause 67, wherein the antimicrobial bioactive agent comprises one or more of rifampin, clindamycin, minocycline, vancomycin, gentamycin, penicillin, miconazole, lincomycins, tetracyclines, cephalosporins, fluoroquinolones, or a combination thereof.

Clause 69. The method of any one of clauses 63-68, wherein the oligofluorinated additive is present in an amount of 0.05-0.15 wt%, relative to the polymer.

Clause 70. The method of any one of clauses 63-69, wherein the medical device further comprises a base polymer selected from one or more of polyurethane, silicone, polyamide, polyester, co-polyester, polyether, polyether-block-amide co-polymer, polypropylene, polyethylene, polyvinylchloride, polysulfone, polyethersulfone, styrenic block copolymer, vulcanized rubber, polyetherimide, polycarbonate, polyetheretherketones, ethyl vinyl acetates, parylene, or polyolefins.

Clause 71. The method of any one of clauses 63-70, wherein the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): wherein:

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer;

B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 1-10.

Clause 72. The method of any one of clauses 63-71 , wherein G is a perfluoroalkyl group.

Clause 73. The method of any one of clauses 63-72, wherein G is:

Clause 74. The method of any one of clauses 62-72, wherein B" is -(CH₂CH₂O)₂_4-

Clause 75. The method of any one of clauses 63-74, wherein the oligofluorinated additive has a thermal degradation temperature of between about 200-450 °C.

Clause 76. The method of any one of clauses 63-75, wherein n is i .

Clause 77. The method of any one of clauses 71-76, wherein the soft segment comprises one or more of hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co- butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6-hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, bisphenol A ethoxylate, polyethylene oxide)-b-poly(propylene oxide)-b- poly(ethylene oxide) (PLN), polyethylene oxide (PEO), polypropylene oxide (PPO), or polytetramethylene oxide (PTMO), or a combination thereof.

Clause 78. The method of any one of clauses 71-77, wherein the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons.

Clause 79. The method of any one of clauses 71-78, wherein the oligofluorinated additive comprises, by percent mass (wt%): 5-30% of the hard segment;

40-90% of the soft segment; and

25-55% of the surface active group.

Clause 80. A medical device comprising a base polymer selected from one or more of thermosets, thermoplastics, or combinations thereof; an oligofluorinated additive; and a bioactive agent compatible with the oligofluorinated additive, comprising: admixing an oligofluorinated additive with a bioactive agent to form a primary admixture; admixing the primary admixture with a base polymer into a secondary admixture; and processing the secondary admixture to form the medical device.

Clause 81. The medical device of clause 80, wherein the oligofluorinated additive and the bioactive agent are admixed in one or more solvents, and the admixture of oligofluorinated additive, bioactive agent, and one or more solvents are dried to remove the one or more solvents to form a homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solid solution, or combination thereof, or a homogenous composition. Clause 82. The medical device of clause 80 or 81 , wherein the oligofluorinated additive is admixed with the bioactive agent using one or more of mechanical stirring, homogenizing, vortexing, dual axis centrifugal mixing, or sonicating.

Clause 83. The medical device of any one of clauses 80-82, wherein the primary admixture is admixed with the base polymer using one or more of blending, compounding, or milling.

Clause 84. The medical device of any one of clauses 80-83, wherein the secondary admixture is formed into a medical device using one or more of extrusion, molding, or coating.

Clause 85. The medical device of any one of clauses 80-84, wherein the secondary admixture is extruded to form a flexible silicon tube.

Clause 86. The medical device of any one of clauses 80-85, wherein the medical device is substantially or fully cured while under reduced pressure or inert atmosphere.

Clause 87. The medical device of any one of clauses 80-86, wherein the medical device is substantially or fully cured under an inert atmosphere at a temperature of 105-145 °C for 5-90 minutes.

Clause 88. The medical device of any one of clauses 80-87, wherein medical device is autoclaved with an inert gas at a temperature greater than 121 °C between 15-90 minutes.

Clause 89. The medical device of any one of clauses 80-88, wherein autoclaving promotes functionalization.

Clause 90. The medical device of any one of clauses 80-89, wherein the medical device has a surface, and wherein the oligofluorinated additive and bioactive agent are evenly distributed across the surface of the medical device.

Clause 91. The medical device of any one of clauses 80-90, wherein the oligofluorinated additive is any one of Formula (I), (II), (III), or (IV): wherein:

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer;

B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 1-10.

Clause 92. The medical device of any one of clauses 80-91 , wherein G is a perfluoroalkyl group.

Clause 93. The medical device of any one of clauses 80-92, wherein G is: CH_mF(3-m)(CF2)_rCH2CH2- or CHmF(3-m)(CF2)s(CH2CH₂O)x-, wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10.

Clause 94. The medical device of any one of clauses 80-93, wherein B" is -(CH2CH2O)2-4-

Clause 95. The medical device of any one of clauses 80-94, wherein the oligofluorinated additive has a thermal degradation temperature of between about 200 °C and about 450 °C.

Clause 96. The medical device of any one of clauses 80-95, wherein n is 1 .

Clause 97. The medical device of any one of clauses 91-96, wherein the soft segment comprises hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1 ,3-propylene carbonate), polybutadiene, poly(diethylene glycol)adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co- butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6-hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, bisphenol A ethoxylate, poly(ethylene oxide)-b-poly(propylene oxide)-b- poly(ethylene oxide) (PLN), polyethylene oxide (PEG), polypropylene oxide (PPG), polytetramethylene oxide (PTMO), or a combination thereof. Clause 98. The medical device of any one of clauses 91-97, wherein the soft segment has a number average molecular weight (M_n) of 500-3500 Daltons.

Clause 99. The medical device of any one of clauses 91-98, wherein the oligofluorinated additive comprises, by percent mass (wt%): 5-30% of the hard segment;

40-90% of the soft segment; and

25-55% of the surface active group.

Clause 101. Use of a composition according to any one of the clauses 1 to 17 for manufacture of a medical device.

Clause 102. The use according to clause101 , wherein the medical device is selected from a hydrocephalus valve, a catheter, a ventricular catheter, a distal catheter, a vascular catheter, a drainage catheter, a subdural drain having a catheter, a neurological catheter, an infusion catheter, a parenteral feeding catheter, a stroke therapy catheter, a urological catheter, a shunt, a cannula, a stent, a graft, a stent-graft, an endoprosthesis angioplasty balloon, a biosensor, a birth control device, a reconstructive mesh, a tympanostomy tube, an ophthalmic device, an endotracheal tube, or a cerebral spinal fluid diversion conduit.

Clause 103. The use according to any one of the clauses 101-102, wherein the medical device comprising a subdural drain having a catheter.

Clause 104. The use according to any one of the clauses101-103, wherein the medical device comprising an implantable sensor for measuring intracranial pressure, brain oxygen level, brain temperature, or one or more other patient parameters; wherein the medical device material forms a flexible membrane in the implantable sensor or a portion thereof.

Clause 105. The method of clause 18, or the medical device of clause 45, or the medical device of clause 80, wherein the primary admixture obtained is in the form of bioactive agent- oligofluorinated additive homogenous dispersion, solution, or combination thereof, or homogenous solid dispersion, solid solution, or combination thereof, or a homogenous composition.

EXAMPLES

Preparation of the Solution Containing Antimicrobials and the Surface-Modifying Molecule

The antimicrobials and the surface-modifying molecule, as described above, was dissolved in a single solvent or combination of solvents. The additives and the implant material of interest are soluble in the solvent(s). It was observed that the total amount of solvent(s) will depend on the desired amount of solution required for the amount of the material. It was also observed that when a combination of solvents was used, the solvents had to be combined in an appropriate ratio. For example, chloroform and methanol were combined in a ratio between 50/50 to 95/5.

After the solvent or combination of solvents was prepared, then a concentration of the antimicrobials and a weight percent of the surface-modifying molecules was prepared. A concentration of antimicrobials may range from 0.1-1000 mg/mL and the surface-modifying molecule may range from 0.5-10% by weight to final implant material mass.

The antimicrobials and the surface-modifying molecule were dissolved in an appropriate amount of solvent or combination of solvents. The antimicrobials and the surface-modifying molecules were mixed into the solvent or combination of solvents and a homogeneous solution was formed. Methods of mixing included, but were not limited to, agitation, fluidic sheer induced mixing, and mechanical sheer mixing.

To illustrate the process described above, non-limiting examples of the solution preparation are described below for two different concentrations of surface-modifying molecules for a total of 12 g of silicone:

1. 45 mg of clindamycin, 15 mg of rifampicin and 360 mg of SMM IBI-1006 were dissolved in 5 mL 95% CHCI3+ 5% MeOH solution, which resulted in a 2% concentration of IBI-1006. The solution of clindamycin, rifampicin, SMM IBI-1006 and 95% CHCl3⁺ 5% MeOH were mixed until a homogenous solution was formed.

2. 45 mg of clindamycin, 15 mg of rifampicin and 720 mg of SMM I Bl- 1012 or SMM I Bl- 1013 were dissolved in 5 mL 95% CHCI3 + 5% MeOH solution, which resulted in a 6% concentration of IBI-1012 or IBI-1013, respectively. The solution of clindamycin, rifampicin, SMM IBI-1006 and 95% CHCI3 + 5% MeOH were mixed until a homogenous solution was formed.

Drying the Solution Containing Antimicrobials and the Non-Bioreactive Surface- odifying Molecule

The resultant homogenous solution containing the solvent or combination of solvents with the antimicrobials and the surface-modifying molecule were dried, optionally with the assistance of reduced pressure, to remove the solvent or combination of solvents. The drying time was between 12-72 hours dependent on the total volume of solution and the vacuum pressure. It was observed that mixing under reduced pressure to dry the homogenous solution to remove the solvent or combination of solvents dramatically reduced the drying time. Based on, at least, the solvent or combination of solvents used, the resultant homogenous solution was also dried under moderate temperature under reduced pressure or inert atmosphere. For example, the resultant homogenous solution was dried for an additional 5-60 minutes at a temperature between 20-50 °C.

Antimicrobial Loading Procedure

The polymeric material for compounding of the dried, homogenous solution containing the antimicrobials and surface-modifying molecule was prepared. A polymer that can be processed by manual means such as milling was used. For example, a medical-grade silicone elastomer was used. 12 g of the polymer were weighed out, where 6 g of the polymer contained a crosslinking catalyst and 6 g of the polymer did not contain the catalyst. For this example, the portion of the polymer containing the catalyst is referred to as Part A and the portion of the polymer not containing the catalyst is referred to as Part B.

After the initial milling passes for Part A were complete, the dried homogenous solution or dispersion containing antimicrobials and the surface-modifying molecule was slowly incorporated into Part A. Small portions of the dried solution were added to the Part A of the polymer. The Part A of the polymer then underwent additional milling passes until the dried solution was fully blended into the Part A polymer. Homogeneous blending of the antimicrobials and the surfacemodifying molecule into the Part A of the polymer was observed, qualitatively, by color (e.g., antimicrobials with strong color such as Rifampicin) and whether the surface of the material felt less adhesive.

The loading procedure was used in silicone that had been previously compounded with a radiopaque material such as barium sulfate, or a colorant.

Milling Part A + Antimicrobials + SMMS with Part B Elastomer

Continuing from the example described above, Part B of the polymer which did not contain the catalyst was milled similarly to Part A, as described above.

After the initial milling passes were complete, the Part B was milled together with the previously processed Part A. The two portions were overlayed with one another and treated as one elastomer. The overlayed Part A and Part B were milled until the material exhibited full blending. Homogeneous distribution of the elastomer was assessed, qualitatively, by inspecting the color of the homogenous distribution and whether the surface of the material felt less adhesive. Extrusion

The fully blended silicone elastomer was transferred to an extrusion machine. Extrusion machines may include vertical or horizontal extrusion with appropriately dimensioned extrusion heads to achieve the desired dimensions of the tube. For example, a catheter was extruded with appropriate inner and outer diameters.

Curing

The resultant catheter, compounded with antimicrobial and surface-modifying molecules, was cured in appropriate atmospheric conditions to prevent degradation of the antimicrobials. For example, atmospheric conditions included reduced pressure or inert atmosphere such as carbon dioxide, nitrogen, or argon.

When the resultant catheter was cured under inert atmosphere: The curing process was performed under inert atmosphere for 5-90 minutes at a temperature between 105-145 °C.

When the resultant catheter was cured under reduced pressure: The curing process was performed under reduced pressure for 30-240 minutes at a temperature between 150-190 °C and at a pressure of less than 50 mbar.

Autoclave

Steam sterilization was performed with or without inert atmosphere to preserve the imbibed antimicrobials for 15-90 minutes at a temperature of greater than 121 °C. Additionally, the water source included normal, deionized, or degassed water.

In some aspects, the medical device is sterilized with one or more of moist heat or dry heat.

While the embodiment previously described above is attributed to thermoset cross-linked polymer tubing for CNS catheters, a similar process may also be utilized for other geometric implementations of such polymers, as described herein. Thus, the above process may be utilized to produce thermoset cross-linked polymers such as silicone for medical devices, as described above, to provide the devices with reduced biofouling and with antimicrobial properties.

Claims

What is claimed:

1. A composition comprising : a. a base polymer ; b. an oligofluorinated additive; and c. one or more bioactive agents compatible with the oligofluorinated additive and the base polymer; wherein the base polymer, the oligofluorinated additive and the bioactive agent form a bioactive agent-oligofluorinated additive-base polymer solid dispersion, solid solution, or a combination thereof.

2. The composition of claim 1 , wherein the base polymer is selected from one or more of thermosets, thermoplastics, or combinations thereof.

3. The composition of claim 2, wherein the thermosets, or thermoplastics polymer is selected from one or more of polyurethane, silicone, polyamide, polyester, co-polyester, polyether, polyether-block-amide co-polymer, polypropylene, polyethylene, polyvinylchloride, polysulfone, polyethersulfone, styrenic block copolymer, vulcanized rubber, polyetherimide, polycarbonate, polyetheretherketone, ethyl vinyl acetate, polyethylene terephthalate, polybutylene terephthalate, polymethylmethacrylate, parylene, or polyolefins.

4. The composition according to any one of the preceding claims, wherein the base polymer is silicone or polyurethane.

5. The composition according to any one of the preceding claims, wherein the oligofluorinated additive is selected any one of Formula (I), (II), (III), or (IV):

G— pB— A-] — B — G

(I) ^{1 J n} wherein:

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer;

B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 0-10.

6. The medical device according to any one of the preceding claims, wherein G is: CH_mF(3-m)(CF2)rCH2CH2- or CHmF(3-m)(CF2)s(CH2CH₂O)x-, wherein: m is 0, 1 , 2, or 3; r is an integer between 2-20; s is an integer between 1-20; and x is an integer between 1-10.

7. The composition according to any one of the preceding claims, wherein the soft segment comprises one or more of hydrogenated polybutadiene (HLBH), hydrogenated polyisoprene (HHTPI), poly((2, 2-dimethyl)-1,3-propylene carbonate), polybutadiene, poly(diethylene glycol) adipate (PEGA), poly(hexamethylene carbonate) (PHCN), poly(ethylene-co-butylene), (diethylene glycol-ortho phthalic anhydride) polyester, (1 ,6- hexanediol-ortho phthalic anhydride) polyester, (neopentyl glycol-ortho phthalic anhydride) polyester (PDP), a polysiloxane, polydimethylsiloxane, polysiloxane- polyethylene glycol block copolymer, polysiloxane-polypropylene glycol block copolymer, bisphenol A ethoxylate, poly(ethylene oxide)-b-poly(propylene oxide)-b-poly(ethylene oxide) (PLN), polyethylene oxide (PEO), polypropylene oxide (PPO), polytetramethylene oxide (PTMO), or a combination thereof.

8. The composition according to any one of the preceding claims, wherein the oligofluorinated additive is present in an amount of 0.05-15 wt%, relative to the base polymer.

9. The composition according to any one of the preceding claims, wherein the one or more bioactive agents are present in an amount of 0.01-50 wt%, wherein 100 wt% is defined as total wt% of base polymer, oligofluorinated additive, and bioactive agent.

10. A method of making a medical device comprising a bioactive agent-oligofluorinated additive-base polymer solid dispersion, solid solution, or a combination thereof, wherein the method comprises: i. admixing an oligofluorinated additive with one or more bioactive agents to form a primary admixture in the form of a bioactive agent-oligofluorinated additive dispersion, solution, or a combination thereof, or solid dispersion, solid solution, or combination thereof, or a composition; ii. compounding the primary admixture obtained in step i. with a base polymer to form a secondary admixture in the form of a bioactive agent-oligofluorinated additive-base polymer solid dispersion, solid solution, or a combination thereof; and iii. processing the secondary admixture obtained in step ii. to form the medical device.

11. The method of claim 10, wherein the oligofluorinated additive and the one or more bioactive agents are admixed in one or more solvents, and a resulting admixture of oligofluorinated additive, the one or more bioactive agents, and one or more solvents are dried to remove the one or more solvents to form a homogenous dispersion, solution, or combination thereof, or a homogenous solid dispersion, solid solution, or combination thereof, or a homogenous composition. The method of any one of claims 10-11, wherein the oligofluorinated additive is selected from any one of Formula (I), (II), (III), or (IV): wherein:

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer;

B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 0-10.

13. Use of a composition according to any one of the claims 1 to 9 for the manufacturing of a medical device.

14. The use according to claim 13, wherein the oligofluorinated additive is selected from any one of Formula (

G— |-B—

(I) ¹

wherein:

B comprises a hard segment comprising a urethane;

B' comprises a hard segment comprising a urethane trimer, or a biuret trimer;

B" comprises a polyalkylene oxide or a moiety of formula:

G is a surface-active group; and n is an integer from 0-10.

15. The use according to any one of the claims 13-14, wherein the medical device is selected from a hydrocephalus valve, a catheter, a ventricular catheter, a distal catheter, a vascular catheter, a drainage catheter, a subdural drain having a catheter, a neurological catheter, an infusion catheter, a parenteral feeding catheter, a stroke therapy catheter, a urological catheter, a shunt, a cannula, a stent, a graft, a stent-graft, an endoprosthesis angioplasty balloon, a biosensor, a birth control device, a reconstructive mesh, a tympanostomy tube, an ophthalmic device, an endotracheal tube, or a cerebral spinal fluid diversion conduit.