Methods of forming lubricious coated medical devices

Abstract

In one aspect, the present disclosure pertains to a method of forming a lubricious coated medical device, the method comprising forming a lubricious coating suspension, wherein the lubricious coating suspension comprises a lubricious polyethylene polymer and a polar solvent, wherein the lubricious coating suspension is per- and polyfluoroalkyl substance (PFAS)-free, and applying the lubricious coating suspension to a substrate to form a lubricious coated medical device.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS

[0001] This application claims the benefit of priority under 35 U.S.C. § 119 of U.S. Provisional Application No. 63 / 736,929, filed Dec. 20, 2024, the entire disclosure of which is hereby incorporated by reference.TECHNICAL FIELD

[0002] The disclosure relates to lubricious coatings on medical devices. More particularly, the disclosure is directed to methods of forming lubricious coated medical devices and the resultant lubricious coated medical devices.BACKGROUND

[0003] A wide variety of intracorporeal medical devices have been developed for medical use, for example, surgical and / or intravascular use. Some of these devices include guidewires, catheters, medical device delivery systems (e.g., for stents, grafts, replacement valves, etc.), and the like. These devices are manufactured by any one of a variety of different manufacturing methods and may be used according to any one of a variety of methods. There is an ongoing need to provide alternative medical devices as well as alternative methods for manufacturing and / or using medical devices. For example, as minimally invasive surgical techniques have improved, it has become increasingly common to insert and retrieve medical devices through catheters and the like having considerable length. Accordingly, it is desirable to minimize friction between the catheters that carry such devices and the devices themselves as well as with tissue with which they may come in contact. In the past, the industry has employed various hydrophobic oils and coatings such as olive oil, silicone, and the like as lubricants. One traditional material that has been commonly used to provide a low friction surface is polytetrafluoroethylene (PTFE). Hydrophilic coatings, particularly hydrogels, also have been employed to impart lubricity to a variety of medical devices.SUMMARY

[0004] In an aspect, a method of forming a lubricious coated medical device is provided. The method comprising: forming a lubricious coating suspension, wherein the lubricious coating suspension comprises a lubricious polyethylene polymer and a polar solvent, wherein the lubricious coating suspension is per- and polyfluoroalkyl substance (PFAS)-free; and applying the lubricious coating suspension to a substrate to form a lubricious coated medical device.

[0005] In some aspects, which may be used in combination with one or more aspects herein, the lubricious polyethylene polymer has a molecular weight in a range from about 500,000 Daltons to about 11,000,000 Daltons.

[0006] In some aspects, which may be used in combination with one or more aspects herein, the lubricious polyethylene polymer is an ultra-high molecular weight polyethylene (UHMWPE) having a weight average molecular weight of greater than about 4,000,000 Daltons.

[0007] In some aspects, which may be used in combination with one or more aspects herein, the UHMWPE is present in a range from about 5 weight percent to about 50 weight percent based on a total weight of the lubricious coating suspension.

[0008] In some aspects, which may be used in combination with one or more aspects herein, the polar solvent is present in a range from about 50 weight percent to about 95 weight percent based on a total weight of the lubricious coating suspension.

[0009] In some aspects, which may be used in combination with one or more aspects herein, the polar solvent is water, ethanol, methanol, isopropyl alcohol, acetone, dimethyl sulfoxide, glycerol, propylene glycol, or any combination thereof.

[0010] In some aspects, which may be used in combination with one or more aspects herein, wherein the lubricious coating suspension further comprises a surfactant.

[0011] In some aspects, which may be used in combination with one or more aspects herein, the surfactant is a non-ionic surfactant.

[0012] In some aspects, which may be used in combination with one or more aspects herein, the surfactant is a bifunctional non-ionic surfactant.

[0013] In some aspects, which may be used in combination with one or more aspects herein, the surfactant is a polysorbate based non-ionic surfactant or an ethoxylated octylphenol based non-ionic surfactant.

[0014] In some aspects, which may be used in combination with one or more aspects herein, the surfactant is present in a range from about 0.1 weight percent to about 5.0 weight percent based on a total weight of the lubricious coating suspension.

[0015] In some aspects, which may be used in combination with one or more aspects herein, forming the lubricious coating suspension at ambient temperature; and applying the lubricious coating suspension to the substrate to form a coated medical device at the ambient temperature.

[0016] In some aspects, which may be used in combination with one or more aspects herein, the forming is carried out by agitating a pre-suspension mixture of the polar solvent and the lubricious polyethylene polymer to form the lubricious coating suspension.

[0017] In some aspects, which may be used in combination with one or more aspects herein, the forming is carried out by agitating a pre-suspension mixture of the polar solvent, the lubricious polyethylene polymer, and the surfactant to form the lubricious coating suspension.

[0018] In some aspects, which may be used in combination with one or more aspects herein, a ratio of the UHMWPE to the polar solvent is about 1:1.

[0019] In some aspects, which may be used in combination with one or more aspects herein, further comprising post processing the coated medical device by heating the coated medical device in an environment at a temperature in a range of about 135 degrees Celsius and 500 degrees Celsius.

[0020] In some aspects, which may be used in combination with one or more aspects herein, the applying is carried out by a coating method selected from a group including spraying, dipping, brushing, or extruding.

[0021] In another aspect, a method of forming a lubricious coated medical device is provided. The method comprising forming a lubricious coating suspension, wherein the lubricious coating suspension comprises an ultra-high molecular weight polyethylene (UHMWPE) and a polar solvent, and a surfactant, wherein the lubricious coating suspension is per- and polyfluoroalkyl substance (PFAS)-free; and applying the lubricious coating suspension to a substrate to form a lubricious coated medical device.

[0022] In some aspects, which may be used in combination with one or more aspects herein, the UHMWPE is present in a range from about 5 weight percent to about 50 weight percent based on a total weight of the lubricious coating suspension; the polar solvent is present in a range from about 50 weight percent to about 95 weight percent based on the total weight of the lubricious coating suspension; and the surfactant is present in a range from about 0.1 weight percent to about 5.0 weight percent based on a total weight of the lubricious coating suspension.

[0023] In another aspect, a lubricious coated medical device is provided. The lubricious coated medical device comprising: a substrate and a lubricious coating disposed on the substrate, the lubricious coating comprising polyethylene polymer and a polar solvent.

[0024] In some aspects, which may be used in combination with one or more aspects herein, the lubricious coated medical device exhibits: an initial lubricity and durability performance that is substantially equal to or better than a durability of a comparative PFAS coating disposed on the substrate; and continued lubricity and durability performance that is substantially equal to or better than a comparative solution cast polyethylene polymer coating disposed on the substrate.

[0025] In some aspects, which may be used in combination with one or more aspects herein, the lubricious polyethylene polymer is present in a range from about 95 weight percent to about 100 weight percent based on a total weight of the lubricious coating.

[0026] The above summary of some example embodiments is not intended to describe each disclosed embodiment or every implementation of the invention.BRIEF DESCRIPTION OF THE DRAWINGS

[0027] The disclosure may be more completely understood in consideration of the following detailed description of various embodiments in conjunction with the accompanying drawings, in which:

[0028] FIG. 1 illustrates the lubricity and durability of various coating compositions.

[0029] While aspects of the disclosure are amenable to various modifications and alternative forms, specifics thereof have been shown by way of example in the drawings and will be described in detail. It should be understood, however, that the intention is not to limit aspects of the disclosure to the particular embodiments described. On the contrary, the intention is to cover all modifications, equivalents, and alternatives falling within the spirit and scope of the disclosure.DETAILED DESCRIPTION

[0030] For the following defined terms, these definitions shall be applied, unless a different definition is given in the claims or elsewhere in this specification.

[0031] All numeric values are herein assumed to be modified by the term “about”, whether or not explicitly indicated. The term “about” generally refers to a range of numbers that one of skill in the art would consider equivalent to the recited value (i.e., having the same function or result). In many instances, the term “about” may be indicative as including numbers that are rounded to the nearest significant figure.

[0032] The recitation of numerical ranges by endpoints includes all numbers within that range (e.g., 1 to 5 includes 1, 1.5, 2, 2.75, 3, 3.80, 4, and 5).

[0033] Although some suitable dimensions ranges and / or values pertaining to various components, features and / or specifications are disclosed, one of skill in the art, incited by the present disclosure, would understand desired dimensions, ranges and / or values may deviate from those expressly disclosed.

[0034] As used in this specification and the appended claims, the singular forms “a”, “an”, and “the” include plural referents unless the content clearly dictates otherwise. As used in this specification and the appended claims, the term “or” is generally employed in its sense including “and / or” unless the content clearly dictates otherwise.

[0035] The following detailed description should be read with reference to the drawings in which similar elements in different drawings are numbered the same. The detailed description and the drawings, which are not necessarily to scale, depict illustrative embodiments and are not intended to limit the scope of the invention. The illustrative embodiments depicted are intended only as exemplary. Selected features of any illustrative embodiment may be incorporated into an additional embodiment unless clearly stated to the contrary.

[0036] It is generally known to provide substrates, for instance medical devices or parts of such devices, with a coating for the purpose of reducing the friction between medical devices themselves or between a medical device and a tissue when the device is introduced in an aqueous environment, such as the human body, or within another medical device. Such coatings have also been referred to as lubricious or “slippery” coatings. Catheters and other medical devices used for introduction in blood vessels, urethra, body conduits and the like and guide wires used with such devices are examples of articles which may be provided with coatings. Catheters for balloon angioplasty and biopsy are specific examples of such catheters. Other illustrative medical devices may include, but are not limited to, stents, embolic filters, implantable devices, treatment devices, diagnostic devices, guide catheters, sheaths, etc.

[0037] One traditional material that has been commonly used to provide a low friction surface is polytetrafluoroethylene (PTFE). However, because of its very low coefficient of friction, it is difficult to wet out the surface of PTFE. Consequently, it can be difficult to adhere other polymers to PTFE, making it difficult to use as a low friction coating. Furthermore, PTFE is very difficult to process. Additionally, use of PTFE along with other per- and polyfluoroalkyl substances (PFAS) may increasingly be subject to various regulatory considerations, environmental concerns, and / or may otherwise be costly. As such, some other approaches seek a lubricious coating that provides similar or improved performance (e.g., lubricity and durability) to traditional coatings such as those that employ PTFE, but is PTFE-free (e.g., does not include any PTFE).

[0038] For instance, another material that may provide a low friction surface is ultra-high molecular weight polyethylene (UHMWPE). UHMWPE is a polymer of interest due to its properties including having similar lubricity as polytetrafluoroethylene (PTFE), while offering significantly better wear resistance. The low friction coefficient and high wear resistance of UHMWPE make it suitable for some medical applications such as those that utilize solid UHMWPE implants. Moreover, UHMWPE is not subject to the environmental and / or regulatory considerations associated with PTFE.

[0039] However, methods of applying UHMWPE coatings to medical devices have relied on solution casting techniques. For instance, solution casting methods may involve dissolving UHMWPE powder into solution using hazardous non-polar solvents at high temperatures, often around or above 130° C. Hence, the solution casting techniques are reliant on the use of hazardous solvents (e.g., hazardous non-polar solvents) to dissolve the UHMPWE to create a homogenous mixture where the UHMPWE is completely dissolved in the non-polar solvent. Examples of hazardous solvents employed in solution casting approaches include decalin, p-xylene, pentane, hexane, heptane, limonene, dibutyl ketone, isophorone, dodecane, benzene, toluene, acetic acid, chloroform, diethyl ether, ethyl acetate, methylene chloride, dodecane, hexadecane, and pyridine, among others. Moreover, the solution casting approaches require maintaining an elevated processing temperature during casting (e.g., the solution needs to be maintained at a high temperature to permit solution casting of the UHMWPE). As such, the solution casting techniques are hazardous, energy intensive, costly, and require additional equipment (e.g., heating elements). Hence, solution casting approaches for forming UHMWPE coatings present several drawbacks.

[0040] As such, the present disclosure avoids the drawbacks of solution casting UHMWPE coatings by providing methods of forming a lubricious coated medical device with a lubricious coating suspension. The lubricious coating suspension includes a lubricious polyethylene polymer (e.g., UHMWPE) and a polar solvent (e.g., water)) in a heterogenous mixture where the polyethylene polymer may be suspended in the polar solvent as large particles that can be visibly seen, appearing, e.g., as a cloudy mixture that can separate over time if left undisturbed. In some embodiments, the lubricious coating suspension includes a lubricious polyethylene polymer (e.g., UHMWPE), a polar solvent (e.g., water), and a surfactant (e.g., a non-ionic surfactant). Unlike solution casting techniques, the suspension casting methods herein can be employed at ambient conditions (e.g., ambient temperature) and can be employed in an absence of hazardous solvent (e.g., hazardous non-polar solvents such as those described above). Hence, the approaches herein can yield various advantages at least in terms of safety and processing as compared to other approaches such as those that utilize PTFE and / or solution casting approaches. Yet, the coated medical devices formed via the suspension casting approaches herein demonstrate similar lubricity to coated medical devices produced via solution casting approaches.

[0041] In one example, the present disclosure pertains to methods of forming lubricious coating compositions for various articles, namely lubricious coated medical devices. In some embodiments, the lubricious coating suspensions herein may comprise a lubricious polyethylene polymer (e.g., an ultra-high molecular weight polyethylene (UHMWPE)), a solvent such as a polar solvent, and a surfactant such as a non-ionic surfactant. Notably, the presence of the particular polar solvents, optionally the surfactants (e.g., non-ionic surfactants), and the UHMWPE in the relative amounts described herein appear to mitigate or eliminate processing issues that are typically associated with UHMWPE such as those associated with solution casting of UHMWPE coatings on medical devices.

[0042] The lubricious coating suspensions herein can be applied in a variety of manners (e.g., dip coating, spray coating, etc.) to form relatively thin lubricious coatings having desirable properties. The resultant lubricious coated medical devices can exhibit desirable durability and lubricity (e.g., similar or even improved durability and lubricity compared to a traditional PTFE coated medical devices), even with the absence of PTFE in the coated medical devices, as detailed herein. Moreover, unlike other coatings, the lubricious coated medical devices herein exhibit a surprising and unexpected increase in lubricity, as detailed herein. While various embodiments herein reference thin UHMWPE based coatings for forming coated medical devices, the approaches herein are also amenable to forming thin UHMWPE based liners suitable for forming lined medical devices, among other types of applications (e.g., heat shrink applications, etc.).

[0043] Examples of lubricious polyethylene materials useful in the present disclosure include high density polyethylene (HDPE) and ultra-high molecular weight polyethylene (UHMWPE). In some embodiments, the lubricious polyethylene polymer can have a weight average molecular weight from about 500,000 Daltons to about 11,000,000 Daltons. All individual values and sub-ranges from about 500,000 Daltons to about 11,000,000 Daltons are included. For instance, in some embodiments the lubricious polyethylene polymer can have a weight average molecular weight in a range having a lower value of about 500,000 Daltons, about 1,000,000 Daltons, about 2,000,000 Daltons, or about 3,000,000 Daltons and an upper value of about 11,000,000 Daltons, about 10,000,000 Daltons, about 9,000,000 Daltons, about 8,000,000 Daltons, about 7,000,000 Daltons, about 6,000,000 Daltons, about 5,000,000 Daltons, or about 4,000,000 Daltons, among other possibilities. Without wishing to be bound by theory, it is believed that employing a lubricious polyethylene polymer with a higher weight average molecular weight may promote aspects herein. For instance, in some embodiments the lubricious polyethylene polymer can have a weight average molecular weight that is greater than about 4,000,000 Daltons, greater than about 5,000,000 Daltons, greater than about 6,000,000 Daltons, greater than about 7,000,000 Daltons, greater than about 8,000,000 Daltons, greater than about 9,000,000 Daltons, or greater than about 10,000,000 Daltons.

[0044] In some embodiments, the lubricious polyethylene polymer can include a UHMWPE. In some embodiments, the lubricious polyethylene polymer can consist essentially of UHMWPE. In some embodiments, the lubricious polyethylene polymer can consist of UHMWPE. In some embodiments, the lubricious polyethylene polymer can consist essentially of UHMWPE and a solvent such as the solvents described herein. In some embodiments, the lubricious polyethylene polymer can consist of UHMWPE and a solvent such as the solvents described herein. In such embodiments, the lubricious polyethylene polymer and solvent may additionally include a relatively small portion of other components (e.g., less than about 5 weight percent of other components e.g., a surfactant such as a non-ionic surfactant based on a total weight of a composition that predominantly includes the UHMWPE and the solvent).

[0045] In some embodiments, the lubricious polyethylene polymer such as UHMWPE can be present in a range from about 5 weight percent to about 50 based on a total weight of the lubricious coating suspension. All individual values and sub-ranges from about 5 weight percent to about 50 weight percent are included. For example, the lubricious polyethylene polymer can be present in a range from about 5 weight percent to about 50 weight percent, from about 10 weight percent to about 50 weight percent, from about 15 weight percent to about 50 weight percent, from about 35 weight percent to about 50 weight percent, from about 40 weight percent to about 50 weight percent, from about 40 weight percent to about 50 weight percent, from about 45 weight percent to about 50 weight percent, from about 48 weight percent to about 50 weight percent, or from about 49 weight percent to about 50 weight percent based on a total weight of the lubricious coating suspension. For instance, the lubricious polyethylene polymer can comprise about 50 weight percent, or about 49 weight percent based on a total weight of the lubricious coating suspension.

[0046] As mentioned, the lubricious coating suspensions herein can include a polar solvent. Examples of suitable polar solvents include water, ethanol, methanol, isopropyl alcohol, acetone, dimethyl sulfoxide, glycerol, propylene glycol, or any combination thereof. Hence, in some embodiments the polar solvent is selected from a group water, ethanol, methanol, isopropyl alcohol, acetone, dimethyl sulfoxide, glycerol, propylene glycol, or any combination thereof. In some embodiments, the polar solvent can be selected from a group including water, ethanol, methanol, and isopropyl alcohol, along with any combination thereof. In some embodiments, the polar solvent can include water. In some embodiments, the polar solvent can consist essentially of water (e.g., may include trace amounts of other polar solvents but not any other component such as non-polar solvents). In some embodiments, the polar solvent can include only water (e.g., does not include any other solvent). Employing at least water as the polar solvent can promote aspects herein, e.g., as water is highly polar, biocompatible, and readily permits formation of a suspension with UHMWPE. However, in some embodiments the polar solvent can include ethanol. In some embodiments, the polar solvent can include methanol. In some embodiments, the polar solvent can include isopropyl alcohol. In some embodiments, the polar solvent can include acetone. In some embodiments, the polar solvent can include dimethyl sulfoxide. In some embodiments, the polar solvent can include glycerol. In some embodiments, the polar solvent can be a solution including water and one or more polar solvents that a miscible in water. For instance, such a solution can include water along with one or more of ethanol, methanol, isopropyl alcohol, acetone, dimethyl sulfoxide, glycerol, propylene glycol.

[0047] In some embodiments, the polar solvent is present in a range from about 50 weight percent to about 95 weight percent based on a total weight of the lubricious coating suspension. All individual values and subranges from about 50 weight percent to about 95 weight percent are included. For example, the polar solvent can be present in a range from about 50 to about 95 weight percent, from about 55 to about 95 weight percent, from about 60 weight percent to about 90 weight percent, or from about 70 weight percent to about 95 weight percent. For instance, the polar solvent can be about 95 weight percent, about 90 weight percent, about 80 weight percent, about 75 weight percent, about 65 weight percent, about 55 weight percent, or about 50 weight percent based on a total weight of the lubricious coating suspension.

[0048] As mentioned, the lubricious coating suspension can include a surfactant. In some embodiments, the surfactant can be an ionic surfactant or non-ionic surfactant. The surfactant such as an ionic surfactant or a non-ionic surfactant can be a liquid at ambient conditions (e.g., at approximately 25 degrees Celsius). In some embodiments, the non-ionic surfactant can be a polyfunctional non-ionic surfactant having both hydrophilic and hydrophobic ends. For instance, the non-ionic surfactant can be liquid at room temperature and can be a bifunctional e.g., having both hydrophilic and hydrophobic ends. In some embodiments, the non-ionic surfactant can be a polysorbate based non-ionic surfactant, an ethoxylated octylphenol based non-ionic surfactant, or a combination of polysorbate based non-ionic surfactant, an ethoxylated octylphenol based non-ionic surfactant. In some embodiments, the non-ionic surfactant can consist essentially of polysorbate based non-ionic surfactant (e.g., may include trace amounts of other non-ionic surfactants but does not include any other components). In some embodiments, the non-ionic surfactant can consist essentially of an ethoxylated octylphenol based non-ionic surfactant (e.g., may include trace amounts of other non-ionic surfactants but does not include any other components). In some embodiments, the non-ionic surfactant can consist of polysorbate based non-ionic surfactant. In some embodiments, the non-ionic surfactant can consist essentially of an ethoxylated octylphenol based non-ionic surfactant.

[0049] Examples of suitable polysorbate based non-ionic surfactants include TWEEN™ (polysorbate 20) which is derived from lauric acid, TWEEN™ 21 (polysorbate 21) which is derived from myristic acid, TWEEN™ 40 (polysorbate 40) which is derived from palmitic acid, TWEEN™ 60 (polysoate 60) which is derived from steric acid, TWEEN™ 61 (polysorbate 61) which is derived from steric acid, TWEEN™ 65 (polysorbate 65) which is derived from steric acid, TWEEN™ 80 (polysorbate 80) which is derived from oleic acid, TWEEN™ 81 (polysorbate 81) which is derived from oleic acid, and TWEEN™ 85 (polysorbate 85) which is derived from trioleate. For example, TWEEN™ 20 includes a hydrophilic group manifested as a polyethylene glycol (PEG) chain, which contains approximately 20 ethylene oxide (EO) units, that is polar and thus is capable of forming hydrogen bonds with polar solvents such as water. TWEEN™ 20 additionally includes a hydrophobic group manifested as a sorbitan structure (sorbitan monolaurate) that is nonpolar and hydrophobic and thus permits attachment to a lubricious polyethylene polymer UHMWPE.

[0050] Examples of suitable ethoxylated octylphenol based non-ionic surfactants include TRITON™ X-100 (available from The DOW Chemical Company) which includes octylphenol ethoxylate, TRITION™ X-100V which includes octylphenol ethoxylate, TRITION™ X-45 which includes octylphenol ethoxylate, and TRITION™ X-114 which includes octylphenol ethoxylate. For example, TRITON™ X-100 includes a hydrophilic group manifested as a polyethylene glycol (PEG) chain, which contains approximately 9-ethylene oxide (EO) units, that is polar and capable of forming hydrogen bonds with polar solvents such as water. TRITON™ X-100 additionally includes a hydrophobic group manifested as the octylphenol structure, e.g., that includes an octyl group (C8H17) that is nonpolar and hydrophobic and thus permits attachment to a lubricious polyethylene polymer UHMWPE. TRITON™ X-45 is based on octylphenol ethoxylate, with a hydrophilic (water-attracting) ethylene oxide chain where the “45” in the name indicates the average degree of ethoxylation.

[0051] In some embodiments, the surfactant such as a non-ionic surfactant is present in a range from about 0.1 weight percent to about 5.0 weight percent based on a total weight of the lubricious coating suspension. Any individual values and sub-ranges from about 0.1 weight percent to about 5.0 weight percent are included. For example, the surfactant is present in a range from about 0.1 weight percent to about 4.0 weight percent, 0.5 weight percent to about 4.0 weight percent, from about 0.5 weight percent to about 3.5 weight percent, from about 0.5 weight percent to about 3.0 weight percent, from about 0.5 weight percent to about 2.5 weight percent, from about 1.0 weight percent to about 2.5 weight percent, from about 1.0 weight percent to about 2.0 weight percent, or from about 0.5 weight percent to about 1.5 weight percent based on a total weight of the lubricious coating suspension. For instance, the non-ionic surfactant can be about 0.1 weight percent, about 0.5 weight percent, about 1.0 weight percent, from about 1.5 weight percent, or about 2.0 weight percent based on a total weight of the lubricious coating suspension.

[0052] In some embodiments, a ratio of the lubricious polyethylene polymer (e.g., UHMWPE) to the polar solvent can be about 1:1. In some embodiments, the lubricious polyethylene polymer and the polar solvent can together form at least 70 weight percent, at least 80 weight percent, at least 90 weight percent, at least 95 weight percent, at least 96 weight percent, at least 97 weight percent, at least 98 weight percent, at least 99 weight percent, or 100 weight percent of a total weight of the lubricious coating suspension. In such embodiments, a balance of the lubricious coating suspension can be manifested at least in part by the surfactant such as a non-ionic surfactant. Stated differently, in some embodiments the lubricious polyethylene polymer such as a UHMWPE, the solvent such as water, and a non-ionic surfactant can collectively form the entire weight of a lubricious coating suspension. For instance, in some embodiments, the lubricious polyethylene polymer can be present at about 50 weight percent, the polar solvent can be present at about 49 weight percent, and the surfactant can be present about 1 weight percent of a total weight of the lubricious coating suspension, among other possible values. However, in some embodiments, the lubricious coating suspensions herein can include additional components (e.g., additives), as described herein.

[0053] In some embodiments, the lubricious coating suspension and / or a pre-suspension mixture can be agitated. For instance, a magnetic stir-bar or other agitation mechanism can be employed to agitate a pre-suspension mixture including the lubricious polyethylene polymer, the solvent such as a polar solvent, and the surfactant such as a non-ionic surfactant thereby forming the lubricious coating suspension. In such embodiments, the resultant lubricious coating suspension can continue to be agitated e.g., to ensure that the lubricious polyethylene remains emulsified in the lubricious coating suspension.

[0054] In some embodiments, the lubricious coating suspension can be formed at ambient conditions such as ambient temperature. In some embodiments, applying the lubricious coating suspension to the substrate to form a coated medical device can occur at ambient conditions such as ambient temperature. For example, in some embodiments, the lubricious coating suspension can be formed at ambient conditions such as ambient temperature and the lubricious coating suspension can be applied to the substrate to form a coated medical device can occur at the ambient conditions. Hence, unlike other approaches such as solution casting approaches, the methods herein can readily form lubricious coated medical devices in an absence of heating to elevated temperatures (e.g., an elevated temperature in a range from about 120 degrees Celsius to about 200 degrees Celsius).

[0055] Without wishing to be bound by theory, the presence of the particular polar solvents in conjunction with the particular surfactants such as non-ionic surfactants in the amounts described herein improve processability (e.g., polymer rheology in terms of forming and / or maintaining a suspension) and / or deliverability of the lubricious polyethylene polymer (e.g., UHMWPE) to the substrate. For instance, the resultant lubricious coating suspension can be a relatively uniform suspension of the lubricious polyethylene polymer in the polar solvent, and thus can promote aspects herein such as formation of a relatively thin (e.g., about 1 micrometer to about 50 micrometers), yet durable and lubricious coating on a substrate of a medical device. For instance, the lubricious coating suspension may be employed to suspension cast or otherwise form a thin lubricious coating on the substrate of the substrate of a medical device.

[0056] The lubricious coating suspensions and the resultant lubricious coated medical devices, as detailed herein, are PFAS-free. For instance, unlike some previous approaches and resultant coated medical devices, the lubricious coating suspension and the resultant coated medical devices herein are fluorinated ethylene propylene (FEP)-free and PTFE-free. As used herein, being PFAS-free generally refers to including no appreciable or detectable amount of PFAS.

[0057] In some embodiments, a hydrophilic polymer may also be included in the lubricious coating suspensions (e.g., in the absence of a surfactant). Examples of such polymers include polyethylene glycol, polypropylene glycol, polyvinylpryrrolidone, and / or hydrophilic urethane polymers, including acrylated urethanes, for example. The polymer may comprise monomer units from one or more monomers having organic acid functional groups. Examples of such monomers include acrylic acid, methacrylic acid, and / or isocrotonic acid. However, in some embodiments, a hydrophobic polymer may be included in the lubricious coating suspension (e.g., in the presences of a surfactant). That is, the coating suspensions herein can include a hydrophilic polymer such as a hydrophilic UHMWPE or a hydrophobic polymer such as a hydrophobic UHMWPE.

[0058] In some embodiments, a free radical initiator may also be included in the lubricious coating suspensions. The free radical initiator may be, for example, a photoinitiator. Non-limiting examples of free radical photoinitiators that may be employed include benzophenones, ketones, acrylated amine synergists, alpha-amino ketones, acyl phosphine oxides including bis-acyl phosphine oxides, and benzil ketals. More specific examples of photoinitiators suitable for use herein include, but are not limited to, 2-phenyl-1-indanone; IRGACURE 184 from Ciba Specialty Chemicals, BENACURE 184 from Mayzo and SARCURE SR1122 from Sartomer, all of which are 1-hydroxylcyclohexylphenyl ketone (HCPK) initiators; BENACURE BP benzophenone; BENACURE 651 and IRGACURE 651, both of which are benzil dimethyl ketal or 2,2′dimethoxy-2-phenylacetophenone; BENACURE 1732 hydroxy-2-methyl-1-phenyl-1-propanone; IRGACURE 819 bis(2,4,6-trimethylbenzoyl)-phenylphosphineoxide, IRGACURE 907 2-Methyl-1-[4-(methylthio)phenyl]-2-(4-morpholinyl)-1-propanone; IRGACURE 369 morpholinoketone; and so forth and blends thereof. Photoinitiators are also available commercially in a variety of blends. Examples of commercially available blends include, but are not limited to, SARCURE SR1136 is a blend of 4-methylbenzophenone and benzophenone; SARCURE SR1137 is a blend of trimethylbenzophenone and methylbenzophenone; and BENACURE 500, a blend of 1-hydroxylcyclohexylphenyl ketone and benzophenone.

[0059] Other optional additives may be used in the lubricious coating suspensions of the present disclosure including flow or viscosity modifiers, antioxidants, coupling agents, surfactants, and / or therapeutic agents. Any such additives may be incorporated into the composition at levels of 10 percent or less (e.g., ranging from 10 percent to 5 percent to 2 percent to 1 percent to 0.5 percent or less), based on the dry weight (e.g., excluding solvent) of the composition.

[0060] Typically, the lubricious coating suspensions for use in forming the lubricious coated medical devices herein may contain from about 0.25 percent to about 10 percent solids, about 0.5 percent to about 10 percent solids, about 1 percent to about 10 percent solids, or about 2 percent to about 7 percent solids, or about 3 percent to about 6 percent solids. The solids of the lubricious coating suspensions may include or may be limited to the lubricious polyethylene polymer.

[0061] The lubricious coating suspension may be applied to the medical device by any method known in the art including, but not limited to, spraying, dipping, rolling, painting (e.g., brush painting, sponge painting, etc.), and so forth. In some embodiments, the lubricious coating compositions herein are applied to the surface of substrate of a medical article as a suspension. The coating may then be allowed to dry, by evaporation of the solvent. The solvent may be more readily evaporated at an elevated temperature, although room temperature drying is typically acceptable.

[0062] In some embodiments, the coated medical articles that have been coated with the lubricious coating suspension can undergo post processing. For instance, the coated medical device can be post processed by heating the coated medical device in an environment (e.g., an oven) at a temperature in a range from about 135 degrees Celsius and 500 degrees Celsius for a period of time (e.g., about 10 minutes, etc.). Such post processing can enhance a smoothness or lubricity of the coated medical article. For example, without wishing to be bound by theory, such post processing is believed to cause sintering, melting, and / or annealing of the lubricious polyethylene polymer and thereby impart increased uniformity in an exterior surface of the coated medical device.

[0063] A variety of substrate materials may be used in conjunction with the present disclosure including organic and inorganic substrates, typically polymer substrates, metal substrates and glass substrates, among others. Examples of metal substrates include pure metals such as platinum, gold, iridium and titanium, plated metals (e.g., silver plated copper), or metal alloys such as stainless-steel including platinum enriched stainless steel (PERSS), Nitinol alloys, and cobalt chromium alloys. An example of a suitable metal substrate is MP35N, a nickel cobalt alloy.

[0064] Examples of polymer substrates include the following: (a) olefin homopolymers and copolymers, including homopolymers and copolymers of C2-C8 alkenes, for example, polyethylene and polypropylene, ethylene-vinyl acetate copolymers (EVA), and isobutylene-styrene copolymers, including block copolymers comprising one or more polystyrene blocks and one or more polyisobutylene blocks, for instance, poly(styrene-b-isobutylene-b-styrene) (SIBS), among others, (b) polyamides such as nylons, polyether-polyamide block copolymers such as poly (tetramethylene oxide-b-polyamide-12) block copolymer, available from Elf Atochem as PEBAX, among others, (c) fluoropolymers, including homopolymers and copolymers of C2-C8 alkenes in which one or more hydrogen atoms are substituted with fluorine, for example, polytetrafluoroethylene (PTFE), polyhexafluoropropene (PVDF), polyvinylidene fluoride (PVDF), and poly(vinylidene fluoride-co-hexafluoropropene) (PVDF-HFP), among others, (d) polyurethane copolymers, including copolymers that are polyether based, polyester based, polycarbonate based, aromatic based and aliphatic based, including polyisobutylene based polyurethanes (PIB-PU), (e) silicone homopolymers and copolymers (also referred to as polysiloxanes) such as polydimethylsiloxane, and (f) various thermoplastics such as polyether ether ketone (PEEK).

[0065] Examples of substrates include medical article substrates, specific examples of which include medical device substrates, for instance, implantable or insertable medical device substrates. A variety of devices may thus be partially or completely coated with compositions in accordance with the present disclosure, including, for example, catheters (e.g., renal or vascular catheters), balloons, catheter shafts, guide wires, filters (e.g., vena cava filters), stents (including coronary vascular stents, cerebral stents, urethral stents, ureteral stents, biliary stents, tracheal stents, gastrointestinal stents and esophageal stents), stent grafts, cerebral aneurysm filler coils (including Guglilmi detachable coils and metal coils), vascular grafts, myocardial plugs, patches, pacemakers and pacemaker leads, heart valves, vascular valves, tissue engineering scaffolds for cartilage, bone, skin and other in vivo tissue regeneration.

[0066] Lubricious coating suspensions in accordance with the present disclosure may be cured, for example, by exposing the coating composition to heat or actinic radiation such as UV light for a short period of time and / or allowing drying (solvent evaporation). In some instances, drying can be performed at an elevated temperature. The amount of time needed to dry or cure the surface is dependent on the source of energy, the relative amounts of constituents in the composition, the thickness of the coating desired, and other factors. Generally, the amount of time required for drying or thermal cure can be less than one minute such as about 3 seconds or less at an elevated temperature. Curing around and along the substrate can be accomplished by incrementally or continuously using irradiation from multiple angles using spaced lamps and / or reflectors; rotation of the substrate, light source or light beam; longitudinal movement of the substrate, light source or light beam; or a combination of such techniques.

[0067] In some embodiments, a thickness of the lubricious coating on the substrate may be in a range from about 2 micrometers to about 300 micrometers or from about 1 micrometer to about 50 micrometers. In some embodiments, a thickness of the lubricious coating on the substrate may be in the range of from 0.1 micrometers or less to 20 micrometers or more (e.g., from 0.1 to 0.2 to 0.5 to 1 to 2 to 5 to 10 to 20 micrometers), or about 0.1 to about 5 micrometers. The lubricious coating thickness will be affected by the percent solids in the coating and the technique of application, among other factors. Multiple coatings may be applied to achieve a desired coating thickness. However, in some embodiments the lubricious coating can be formed from an individual coating (e.g., an individual application of the lubricious coating suspension to the substrate).

[0068] In some embodiments, the lubricious coatings herein can be sterilized. In some embodiments the lubricious coatings described herein may comprise a therapeutic agent, for example, selected from antimicrobial agents, antibiotic agents, anti-cancer agents, anti-oxidizing agents (e.g., Vitamin E), agents for treating calcifications, antirestenotic agents and antithrombotic agents, and combinations thereof. The therapeutic agent(s) may be added to the lubricious coating prior to curing or drying or applied onto the coating after it has been dried, cured, and / or sterilized. In some embodiments, therapeutic agent(s) carried in the lubricious polyethylene polymer-based coating may remain in the coating or elute out of the coating when the coating is wet, thereby delivering the therapeutic agent(s) to immediately adjacent areas of the body.

[0069] The invention is illustrated by the following non-limiting examples.Examples 1-2 and Comparative Examples 1-3

[0070] The coating thickness for each of the examples was approximately 50.8 micrometers [0.002 inches] or less. Unless otherwise indicated, the materials herein were procured from SIGMA-ALDRICH.

[0071] Examples 1 and the comparative examples 1-2 were formed as follows.

[0072] Comparative Example 1 (CE 1-Bare Wire): A nitinol bare wire (0.023″) available from FORT WAYNE MATERIALS was provided as comparative example 1 (CE 1).

[0073] Comparative Example 2 (CE 2-PFAS Coating): A PTFE coated wire available from MERIT MEDICAL DURASKIN (PES / PTFE) was provided as comparative example 2 (CE 2).

[0074] Comparative Example 3 (CE 3-Solution Coating): A lubricious polyethylene powder (UHMWPE powder with average molecular weight of about 4,200,000 Daltons; tradename GUR2126; available from Celanese) was dissolved in about 1 weight percent decalin at about 130 degrees Celsius under agitation with a magnetic stir bar to form a lubricious coating solution. A nitinol catheter wire (available from FORT WAYNE MATERIALS) was dipped into the lubricious coating solution and allowed to dry at about 90 degrees Celsius for about 5 minutes to form a final coated medical article. This PFAS-free solution cast coated final medical article corresponds to comparative example 3 (CE 3).

[0075] Example 1 (EX 1-Suspension Casting: Surfactant-Free): A lubricious polyethylene polymer powder (2.43 grams of a hydrophilic UHMWPE powder with average molecular weight of about 4,200,000 Daltons; tradename GUR2126-2; available from Celanese) was dissolved in water (7.43 grams water) at ambient conditions under agitation with a magnetic stir bar to form a lubricious coating solution in an absence of a surfactant (with 0 weight percent surfactant based on a total weight of the lubricious coating solution). A nitinol catheter wire (available from FORT WAYNE MATERIALS) was dipped into the lubricious coating solution and allowed to dry to form a coated medical article. The coated medical article was sintered at about 170 degrees Celsius for about 20 minutes to yield the final coated medical article. This final PFAS-free solution cast coated medical article corresponds to example 1 (EX 1).

[0076] Example 2 (EX 2-Suspension casting: Non-ionic surfactant): A lubricious polyethylene polymer powder (4.5 grams of a hydrophobic UHMWPE powder with average molecular weight of about 4,200,000 Daltons; tradename GUR2126; available from Celanese) was dissolved in water (15.00 grams) and nonionic surfactant (0.044 grams of TRITON x45) at ambient conditions under agitation with a magnetic stir bar to form a lubricious coating solution. A nitinol catheter wire (available from FORT WAYNE MATERIALS) was dipped into the lubricious coating solution and allowed to dry to form a coated medical article. The coated medical article was sintered at about 170 degrees Celsius for about 40 minutes. The coated and sintered medical article was dipped into the lubricious coating solution again to yield a subsequent coated medical article. The subsequent coated medical article was sintered at about 170 degrees Celsius for about 40 minutes to yield the final coated medical article. This final PFAS-free solution cast coated medical article corresponds to example 2 (EX 2).

[0077] The lubricious coating on the coated medical article e.g., once dried and the polar solvent has substantially evaporated can predominantly include UHMWPE (e.g., including greater than or equal to 99 weight percent UHMWPE or 100 weight percent UHMWPE). In some embodiments, trace amounts of the residual polar solvent and / or trace amounts of residual non-ionic surfactant that may remain from the lubricious coating suspension.

[0078] CE1-3 and EX 1-2 were tested for lubricity and durability (L&D). To test for L&D, the bare wire of CE 1, the PTFE coated wire of CE 2 and the coated wires of CE 3 and EX 1-2 are secured by a clamping mechanism at a normal force of about 300 grams (g). The force required to pull the articles of CE 1-3 and EX 1-2 through the clamp is measured over a thirty-cycle test. Lower frictional force (grams) indicates improved lubricity.

[0079] The lubricity and durability testing was conducted under both dry and wet conditions. As used herein, dry conditions refer to contacting the materials under test with a dry silicone pad in the clamping mechanism. As used herein, wet conditions refer to contacting the materials under test with a silicone pad in the clamping mechanism that is immersed in water.

[0080] Lubricity and durability performance of the articles of CE 1-3 and EX 1-2 was determined based on observed frictional forces of the materials undertest after a given quantity of cycles (e.g., after each cycle from 1 to 30 cycles). FIG. 1 illustrates a graph 100 of the force required (in grams) to pull an example wire through the clamp for each of the coating compositions under dry conditions over a number of cycles (e.g., up to 30 cycles). Table 1 provides the lubricity and durability performance data that is the basis for FIG. 1.TABLE 1CE 1 -EX 1 -EX 2-CE 3 -BareCE 2 -SurfactantNonionicSolutionCyclesWirePTFEFreeSurfactantCast1432.262376.376370.888290.008293.4272477.737348.458352.02288.513244.4163525.038329.638338.453294.964233.5254559.009323.641337.803297.931230.295578.169331.853333.63299.301226.1196595.619343.142334.844298.377224.5847609.452354.189333.435301.759228.2718621.336359.888338.007301.36224.7479625.747362.08330.898301.407223.63410630.291367.451330.1299.074221.49411633.074370.442321.723302.871220.8612636.363375.014321.566303.599223.9613635.171N / A324.893306.12221.40314652.044374.693324.565306.644219.0515646.228377.01325.778306.879219.33616660.705379.742313.667N / A217.55317664.14382.514315.131307.271215.96318663.655382.678321.918305.83217.26919670.87385.403324.283307.2221.25620666.576384.33312.727304.374226.19821673.957381.222316.971303.795220.60822667.999386.436313.213N / A219.51723677.708389.035303.513297.406218.06924682.757386.131317.354277.826219.57325682.316385.082N / A289.593214.38226677.216387.806304.014292.263214.29727678.184387.61309.815299.497217.5628694.361389.99318.662299.536218.23729692.786387.931315.875301.61214.91830690.905390.374309.361306.637215.08“N / A”—denotes no data available

[0081] As can be seen in FIG. 1, the examples that utilized a lubricious coating formed at least of a lubricious polyethylene polymer (e.g., a hydrophilic UHMWPE or a hydrophobic UHMWPE) with a surfactant (e.g., in examples utilizing a hydrophobic UHMWPE) or without a surfactant (e.g., in examples utilizing a hydrophilic UHMWPE) realized comparable or improved lubricity and durability performance, illustrated as EX 1-2 in FIG. 1, to the comparative examples CE 1-3. Thus, EX 1-2 exhibited satisfactory lubricity and durability performance for the entire duration of the lubricity and durability testing (e.g., at each of 1 cycle, 10 cycles, and 30 cycles). Such lubricity and durability performance can be particularly advantageous for the implantable or insertable medical devices herein such as those may encounter fluids during implantation and / or insertion.

[0082] Although various embodiments are specifically illustrated and described herein, it will be appreciated that modifications and variations of the present disclosure are covered by the above teachings and are within the purview of the appended claims without departing from the spirit and intended scope of the invention.

Claims

1. A method of forming a lubricious coated medical device, the method comprising:forming a lubricious coating suspension, wherein the lubricious coating suspension comprises a lubricious polyethylene polymer and a polar solvent, wherein the lubricious coating suspension is per- and polyfluoroalkyl substance (PFAS)-free; andapplying the lubricious coating suspension to a substrate to form a lubricious coated medical device.

2. The method ofclaim 1, wherein the lubricious polyethylene polymer has a molecular weight in a range from about 500,000 Daltons to about 11,000,000 Daltons.

3. The method of claim 1, wherein the lubricious polyethylene polymer is an ultra-high molecular weight polyethylene (UHMWPE) having a weight average molecular weight of greater than about 4,000,000 Daltons.

4. The method of claim 3, wherein the UHMWPE is present in a range from about 5 weight percent to about 50 weight percent based on a total weight of the lubricious coating suspension.

5. The method of claim 1, wherein the polar solvent is present in a range from about 50 weight percent to about 95 weight percent based on a total weight of the lubricious coating suspension.

6. The method of claim 1, wherein the polar solvent is water, ethanol, methanol, isopropyl alcohol, acetone, dimethyl sulfoxide, glycerol, propylene glycol, or any combination thereof.

7. The method of claim 1, wherein the lubricious coating suspension further comprises a surfactant.

8. The method of claim 1, wherein the surfactant is a non-ionic surfactant.

9. The method of claim 7, wherein the non-ionic surfactant is a polysorbate based non-ionic surfactant or an ethoxylated octylphenol based non-ionic surfactant.

10. The method of claim 7, wherein the surfactant is present in a range from about 0.1 weight percent to about 5.0 weight percent based on a total weight of the lubricious coating suspension.

11. The method of claim 1, further comprising:forming the lubricious coating suspension at ambient temperature; andapplying the lubricious coating suspension to the substrate to form a coated medical device at the ambient temperature.

12. The method of claim 1, wherein the forming is carried out by agitating a pre-suspension mixture of the polar solvent and the lubricious polyethylene polymer to form the lubricious coating suspension.

13. The method of claim 1, wherein a ratio of the UHMWPE to the polar solvent is about 1:1.

14. The method of claim 1, further comprising post processing the coated medical device by heating the coated medical device in an environment at a temperature in a range of about 135 degrees Celsius and 500 degrees Celsius.

15. The method of claim 1, wherein the applying is carried out by a coating method selected from a group including spraying, dipping, brushing, or extruding.

16. A method of forming a lubricious coated medical device, the method comprising:forming a lubricious coating suspension, wherein the lubricious coating suspension comprises an ultra-high molecular weight polyethylene (UHMWPE), a polar solvent, and a surfactant, wherein the lubricious coating suspension is per- and polyfluoroalkyl substance (PFAS)-free; andapplying the lubricious coating suspension to a substrate to form a lubricious coated medical device.

17. The method of claim 16, wherein:the UHMWPE is present in a range from about 5 weight percent to about 95 weight percent based on a total weight of the lubricious coating suspension;the polar solvent is present in a range from about 50 weight percent to about 95 weight percent based on the total weight of the lubricious coating suspension; andthe surfactant is present in a range from about 0.1 weight percent to about 5.0 weight percent based on a total weight of the lubricious coating suspension.

18. A lubricious coated medical device comprising:a substrate; anda lubricious coating disposed on the substrate, the lubricious coating comprising a lubricious polyethylene polymer and a polar solvent.

19. The lubricious coated medical device of claim 18, wherein the lubricious coated medical device exhibits:an initial lubricity and durability performance that is substantially equal to or better than a durability of a comparative solution cast polyethylene polymer coating disposed on the substrate; andcontinued lubricity and durability performance that is substantially equal to or better than a comparative solution cast polyethylene polymer coating disposed on the substrate.

20. The lubricious coated medical device of claim 18, wherein the lubricious polyethylene polymer is present in a range from about 95 weight percent to about 100 weight percent based on a total weight of the lubricious coating.

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