Alcohol-resistant silicated polycarbonate polyurethane and medical devices incorporating the alcohol-resistant silicated polycarbonate polyurethane

Abstract

The alcohol-resistant silicated polycarbonate polyurethane may comprise soft segments and hard segments. The soft segments may comprise a polycarbonate polyol and a polysiloxane, and the polysiloxane may be present in an amount less than that of the polycarbonate polyol. The hard segments may comprise an isocyanate and a chain extender. A peripherally inserted central catheter (PICC) device may comprise one or more components formed at least in part from one or more formulations of the silicated polycarbonate polyurethane catheter. The PICC device may be resistant to alcohol locking and may be power injectable both before and after an alcohol locking event.

Description

[0001] Cross - Reference to Related Applications

[0002] This application claims priority to U.S. Provisional Patent Application 62 / 587,761, filed on November 17, 2017, entitled "ALCOHOL - RESISTANT SILICONIZED POLYCARBONATE POLYURETHANES AND MEDICAL DEVICES INCORPORATING THE SAME", and U.S. Provisional Patent Application 62 / 617,051, filed on January 12, 2018, entitled "ALCOHOL - RESISTANT SILICONIZED POLYCARBONATE POLYURETHANES AND MEDICAL DEVICES INCORPORATING THE SAME", the entire content of each of these patent applications is hereby incorporated by reference herein. Technical Field

[0003] Certain embodiments described herein relate generally to polyurethanes and, more particularly, to polycarbonate polyurethanes. Another embodiment relates generally to medical devices incorporating such polycarbonate polyurethanes, such as catheters. Background Art

[0004] Polyurethanes are versatile plastic materials applicable to a variety of applications. For example, polyurethanes have been used in insulation panels, gaskets, hoses, tires, wheels, synthetic fibers, surface coatings, furniture, footwear, adhesives, medical devices, and a variety of other materials and devices. Generally, polyurethanes are formed by reacting a polyol with a diisocyanate or other polyisocyanate in the presence of suitable catalysts, additives, etc. Since a variety of raw materials can be used, a broad spectrum of polyurethane materials can be prepared to meet the needs of a variety of specific applications.

[0005] Polycarbonate polyurethanes, or polyurethanes formed from polycarbonate polyols, can be used in a variety of applications. However, known polycarbonate polyurethanes suffer from various disadvantages or limitations when used in certain medical devices such as certain catheters. The embodiments disclosed herein overcome the disadvantages of existing polycarbonate polyurethanes in at least this regard, as will be apparent from the following discussion. Brief Description of the Drawings

[0006] The written disclosure herein describes non - limiting and non - exhaustive illustrative embodiments. Reference is made to certain of such illustrative embodiments depicted or otherwise described in the accompanying drawings, wherein:

[0007] Figure 1An exemplary embodiment of a catheter shaft, which can suitably be formed at least in part of any of the various embodiments of the silicated polycarbonate polyurethane disclosed herein;

[0008] Figure 2A is a cross-sectional view of the catheter shaft taken along Figure 1 the viewing line 2A-2A in Figure 1 ;

[0009] Figure 2B is a cross-sectional view of the catheter shaft taken along Figure 1 the viewing line 2B-2B in Figure 1 ;

[0010] Figure 3 is a graph of the burst pressure exhibited by various catheters, the catheters including Figure 1 , 2A and catheter shafts in the form shown in 2B, the catheter shafts being extruded from different embodiments of the silicated polycarbonate polyurethane according to the present disclosure;

[0011] Figures 4A - 4C is a graph of the tensile strength exhibited by individual portions cut from Figure 1 , 2A and catheter shafts in the form shown in 2B, the catheter shafts being extruded from different embodiments of the silicated polycarbonate polyurethane according to the present disclosure;

[0012] Figures 5A - 5C is a graph of the fracture strain or ultimate elongation exhibited by individual portions cut from Figure 1 , 2A and catheter shafts in the form shown in 2B, the catheter shafts being extruded from different embodiments of the silicated polycarbonate polyurethane according to the present disclosure;

[0013] Figure 6 is a graph of the burst pressure exhibited by various catheters, the catheters including Figure 1 , 2A and catheter shafts in the form shown in 2B, the catheter shafts being extruded from aliphatic polyether polyurethane, aromatic polycarbonate polyurethane, and embodiments of the silicated polycarbonate polyurethane according to the present disclosure;

[0014] Figure 7 is a perspective view of an embodiment of a peripherally inserted central catheter (PICC) device or assembly, which includes Figure 1 , Figure 2A and 2B catheter shafts in the form shown, the catheter shafts being connected to the extension leg via a two-part or two-layer overmolded fitting hub, wherein each of the two layers of the catheter shaft, the extension leg, and the fitting hub includes one or more embodiments of the silicated polycarbonate polyurethane according to the present disclosure;

[0015] Figures 8A - 8C is a schematic plan view showing successive stages in an exemplary method for connecting a catheter shaft and an extension leg via a two-piece engagement hub Figure 1 ;

[0016] Figure 9 is a graph of the average operating pressure experienced by a group of 40 PICC catheters (such as the catheter shown) Figure 7 during power injection events over a 10-day period, where each catheter was alcohol locked and allowed a one-hour recovery period before each power injection;

[0017] Figure 10 is a graph of the average operating pressure experienced by a group of 40 PICC catheters (such as the catheter shown and that has been subjected to a 6-month accelerated aging conditioning) Figure 7 during power injection events over a 10-day period, where each catheter was alcohol locked and allowed a one-hour recovery period before each power injection; and

[0018] Figure 11 is a graph comparing thrombus formation on the outer surfaces of three different types of catheter shafts for fifteen separate experimental runs. DETAILED DESCRIPTION

[0019] The present disclosure generally relates to alcohol-resistant polymers, which can be particularly useful in medical applications. More specifically, the present disclosure relates to alcohol-resistant silicated polycarbonate polyurethanes or polycarbonate polyurethanes containing a polysiloxane component, which can be formulated to facilitate use in medical devices (such as catheters). Silicated polycarbonate polyurethanes can be referred to as silicated polycarbonate polyurethanes; polycarbonate polyurethanes containing siloxane or containing siloxane; polysiloxane, polycarbonate polyurethanes; or polyurethane-siloxane copolymers, where each such term is intended to identify a polycarbonate polyurethane containing a polysiloxane component. Specifically, these terms name polyurethanes containing soft segments, and each of the polycarbonate and polysiloxane components is chemically bonded to the soft segments.

[0020] In some embodiments, a catheter (such as a central venous catheter (CVC), or more specifically, a peripherally inserted central catheter (PICC)) includes one or more components each at least partially formed of one or more formulations of alcohol-resistant silicated polycarbonate polyurethane. For example, in some embodiments, a PICC shaft defining at least one lumen comprises a formulation of silicated polycarbonate polyurethane that enables the lumen of the shaft to be disinfected or sterilized, cleared, or otherwise treated by alcohol lock (also referred to as ethanol lock), wherein alcohol (typically ethanol) is retained within the lumen and for a treatment period or exposure period (e.g., at least one hour) to achieve a particular treatment or goal (e.g., disinfection and / or occlusion removal). In various embodiments, the silicated polycarbonate polyurethane can recover substantially completely from alcohol lock within a recovery period (e.g., not less than one hour), which can be short enough to allow alcohol lock and subsequent power injection of the catheter to occur, for example, in an outpatient clinical setting. In various embodiments, the PICC device can be power injectable both before and after alcohol lock (e.g., after a particular recovery period). In another embodiment, the PICC device can be adapted to be used as a pediatric PICC or other catheter, including for very small patients (e.g., in neonates as low as 2.3 kg in weight).

[0021] In some embodiments, a PICC device includes a shaft comprising a first formulation of silicated polycarbonate polyurethane according to the present disclosure, one or more extension tubes comprising a second formulation of silicated polycarbonate polyurethane according to the present disclosure, and a connection hub comprising a third formulation of silicated polycarbonate polyurethane according to the present disclosure. One or more of the first, second, and third formulations can be the same as or different from one or more of the remaining formulations of the first, second, and third formulations. Before and after an alcohol lock event, during normal use (e.g., at relatively low injection or aspiration pressures, after repeatedly opening and closing the extension tube via a clamp, etc.) and / or during power injection, the PICC can exhibit substantially no leakage or rupture. The present invention also discloses many other or additional embodiments and advantages.

[0022] I. Definitions and Disclosure Provisions

[0023] As used herein, "medical catheter" or "catheter" each refers to a medical device including a flexible shaft that contains one or more lumens that can be inserted into a subject and / or into any suitable part of its anatomy or system in any suitable manner for introducing materials such as fluids, nutrients, drugs, blood products; monitoring the subject, such as with respect to pressure, temperature, fluids, analytes, etc.; removing substances such as one or more body fluids; deploying balloons, stents, grafts, or other devices; or any combination thereof. The catheter may also include various accessory components such as extension tubes, fitting hubs (e.g., hubs overmolded to the shaft and / or extension tube), fittings, connectors, etc. The catheter may also have various tip and shaft features including holes, slits, tapers, overmolded tips, or lugs, etc.

[0024] As used herein, "vascular access device" refers to a device that provides access to a patient's vascular system, such as the venous system, or in some specific cases, the central venous circulation system. This includes but is not limited to central venous catheters; peripherally inserted central catheters such as peripheral intravenous (PIV) lines; midlines; ports (e.g., implantable devices); dialysis catheters; and blood separation catheters. The vascular access device can remain in place from several days to several years. A typical configuration of a vascular access catheter includes a flexible shaft having one or more lumens, the flexible shaft having various tips, slits, tapers, etc., and the flexible shaft is connected to an extension tube with a luer fitting for attachment to other devices.

[0025] As used herein, "central access device" refers to a device that provides direct access to the central venous circulation system. As used herein, "central venous catheter" or "CVC" refers to a catheter that is configured such that its tip is placed directly in the central venous circulation system. The term includes any such device that delivers drugs to the central part of the heart, such as the vena cava, whether fully implanted or partially implanted (e.g., via percutaneous insertion). A central venous catheter is an example of a central access device.

[0026] As used herein, "peripherally inserted central catheter" or "PICC" refers to a central venous catheter that is configured to enter the patient's body through the skin (i.e., percutaneously) at a peripheral site and extend through the patient's vasculature such that its distal end is positioned directly in the central venous circulation system, such as in the superior vena cava. A PICC may also be referred to as a peripherally inserted central line. A PICC can remain in place or stay within the vasculature for an extended period of time (e.g., several days, weeks, months, or years).

[0027] As used herein, a "pediatric catheter" refers to a catheter that is configured for use in the vasculature of a patient 18 years of age or younger. Some pediatric catheters may be suitable for children, such as children 5 years old, 3 years old, or 1 year old or younger. Some pediatric catheters may be suitable for infants or neonates, such as infants weighing not less than, for example, 2.3 kg in some cases, and in other cases, infants weighing even less than 2.3 kg.

[0028] As used herein, "power injection" is consistent with the generally accepted definition of the term and refers to a pressurized infusion that occurs at a high flow rate (such as up to 4.0 mL / s or up to 5.0 mL / s); this typically involves injecting a viscous material, such as a material having a viscosity of 11.8 cP + / - 0.3 cP (e.g., a contrast medium); and it occurs at a high pressure. In a similar manner, a "power injectable" catheter is a catheter that is capable of sustaining power injection without leaking, rupturing, or swelling to a size that is not usable within the vasculature. For example, a power injectable catheter may be a catheter that meets the power injection specifications of International Organization for Standardization (ISO) standard ISO 10555-1. Thus, for example, a power injectable PICC is a PICC that is configured to sustain power injection. A PICC may also be used for other functions, such as intravenous injection therapy at lower pressures or standard infusion and aspiration or blood sampling.

[0029] As used herein, "biocompatible" means compatible with a patient or suitable for use within a patient, such as over an extended period of time (e.g., weeks or months). This term may be used to indicate compliance with generally accepted standards or regulations governing a particular device, such as a catheter. For example, biocompatibility may mean compliance with one or more of ISO standards ISO 10993-1, 4, 5, 6, 10, or 11, and / or compliance with the regulations of a particular jurisdiction, such as those set forth by the Food and Drug Administration of the Unites States of America. A biocompatible catheter may be a non-cytotoxic, non-sensitizing, non-irritating, non-toxic, non-pyrogenic, non-hemolytic catheter that does not activate the complement system, has a minimal effect on partial thromboplastin time, has an acceptable interaction with blood (e.g., acceptable clotting activity), and / or can be implanted and remain for a desired period of time without significant adverse effects.

[0030] The term "patient" is used herein in a broad sense and is not intended to be limiting. A patient can be, for example, any individual into whom a catheter or other medical device discussed herein can be placed, whether in a hospital, clinic, or other setting. The term "patient" includes humans, mammals, or any other animal having an anatomical structure compatible with the embodiments described herein.

[0031] As used in this specification and the appended claims, the singular forms "a", "an", and "the" include plural referents unless the context clearly dictates otherwise. Thus, for example, reference to "a device" can include one or more such devices, reference to "an isocyanate" can include reference to one or more isocyanates, and reference to "a silicated polycarbonate polyurethane" can include reference to one or more such compounds.

[0032] The terms "comprising", "including", "containing", "having", etc. can have the meanings given to them under United States patent law and can mean "including", "containing", etc., and are generally interpreted as open-ended terms. If an item is said to comprise, include (etc.) a list of one or more components, structures, steps, or other items, the list can be non-exclusive or non-exhaustive, or alternatively it can be exclusive or exhaustive. The term "consisting of" is a closed-ended term and includes only the components, structures, steps, etc. specifically listed in conjunction with such term, and in accordance with the terms of United States patent law. "Consisting essentially of" has the meaning generally given to it under United States patent law. Specifically, such terms are generally closed-ended terms, with the difference that additional items, materials, components, steps, or elements are permitted that do not materially affect the basic and novel characteristics or functions of one or more of the items used in conjunction with them. For example, if present in language of "consisting essentially of", trace elements present in a composition but not affecting the properties or characteristics of the composition can be permitted, even if not expressly shown in the list of items following such term. In this written specification, when open-ended terms such as "comprising" or "including" are used, it should be understood that direct support should also be provided to language of "consisting essentially of" as well as "consisting of", as if expressly stated, and vice versa.

[0033] The terms "first", "second", "third", "fourth", etc. (if any) in the specification and claims are used to distinguish similar elements and are not necessarily used to describe a particular order, chronological order, preferred order, or other order. It should be understood that any such terms are interchangeable under appropriate circumstances such that the embodiments described herein, for example, can be operated in an order other than those shown or otherwise described herein. Similarly, if a method is described herein as including a series of steps, the order of such steps as shown herein is not necessarily the only order in which such steps can be performed, and some of the steps may be omitted and / or some other steps not described herein may be added to the method.

[0034] The terms "left", "right", "front", "back", "top", "bottom", "above", "below", etc. (if any) in the specification and claims are used for descriptive purposes and are not necessarily used to describe a permanent relative position. It should be understood that the terms so used are interchangeable under appropriate circumstances, such that the embodiments described herein can, for example, be operated in orientations other than those shown or otherwise described herein. As used herein, the term "coupled" is defined as connected directly or indirectly in any suitable manner. Objects described herein as being "adjacent" to each other may be in physical contact with each other, in dose proximity to each other, or in the same general area or zone as each other, as applicable to the context in which the phrase is used.

[0035] As used herein, and unless otherwise expressly defined, the term "substantially" means the full or nearly full extent or degree of an action, characteristic, property, state, structure, item, or result. For example, a "substantially" enclosed object may mean that the object is fully enclosed or nearly fully enclosed. In some cases, the exact allowable degree of deviation from absolute completeness may depend on the particular context. However, generally speaking, approaching fullness will have the same overall result as when achieving absolute and total fullness. When used in a negative sense, the use of "substantially" also applies to mean completely or nearly completely without an action, characteristic, property, state, structure, item, or result. For example, a composition that is "substantially free of particles" will be completely free of particles, or thus nearly completely free of particles, such that the effect can be the same as when completely free of particles. In other words, a composition that is "substantially free of" a component or element may still actually contain such items, as long as there is no measurable effect thereof.

[0036] As used herein, the term "about" is used to provide flexibility to numerical range endpoints by assuming that a given value can be "slightly higher" or "slightly lower" than the endpoint. Unless otherwise stated, the use of the term "about" with respect to a particular number or numerical range should also be understood to provide support for such numerical terms or ranges without the term "about". For example, for convenience and brevity, the numerical range of "about 50 angstroms to about 80 angstroms" should also be understood to provide support for the range of "50 angstroms to 80 angstroms". In addition, it should be understood that in this specification, even when the term "about" is used with an actual numerical value, support for that actual numerical value is provided. For example, the expression "about" 30 should be understood to provide support not only for values slightly higher and slightly lower than 30, but also for the actual numerical value of 30.

[0037] As used herein, for convenience, a number of items, structural elements, components, and / or materials may be presented in a common list. However, these lists should be understood as if each member of the list was individually identified as a separate and unique member. Thus, any single member of such a list should not be construed as actually equivalent to any other member of the same list solely based on their appearance in a common group without an indication to the contrary.

[0038] Concentrations, amounts, and other numerical data may be expressed or presented herein in a range format. It should be understood that such range formats are used merely for convenience and brevity and should therefore be interpreted flexibly to include not only the explicitly recited values as the limits of the range, but also all individual values or sub-ranges subsumed within that range as if each individual value and sub-range was explicitly recited. By way of example, a numerical range of "about 1 to about 5" should be understood to include not only the explicitly recited values of about 1 to about 5, but also individual values and sub-ranges within the indicated range. Thus, included within this numerical range are the individual values (e.g., 2, 3, and 4) and sub-ranges (such as 1 - 3, 2 - 4, and 3 - 5, etc.) as well as the individual 1, 2, 3, 4, and 5.

[0039] The same principle applies to ranges that recite only one numerical value as a minimum or maximum. In addition, such interpretation shall apply regardless of the width of the range or the nature of the property being described.

[0040] Compositions, systems, or methods that provide "improved" or "enhanced" performance may be referred to in this patent application. It should be understood that unless otherwise specified, such "improvement" or "enhancement" is a measure of the beneficial effect obtained based on a comparison with prior art compositions, systems, or methods. In addition, it should be understood that the degree of improved or enhanced performance may vary between the disclosed embodiments, and no assumption is made as to the universality of the amount, degree, or attainment of equivalence or consistency of the improvement or enhancement.

[0041] As used throughout this specification, the terms "example" or "embodiment" mean that the particular features, structures, or characteristics described in connection with the example or embodiment are included in at least one embodiment. Thus, the phrases "in an example" or "in an embodiment" that appear throughout this specification are not necessarily all referring to the same embodiment.

[0042] It should also be noted that, for the sake of brevity, various features are sometimes combined together in a single embodiment, drawing, or its description. However, this method of description is not intended to require any given claim to include more features than those explicitly recited in that claim. Instead, as reflected in the claims that follow this disclosure, inventive aspects may be presented in a form that is less than the combination of all features presented in any single example disclosed herein.

[0043] II. Exemplary Unmet Needs Addressed by Various Embodiments

[0044] As described above, polyurethanes are typically formed by reacting a polyol (meaning a compound containing multiple hydroxyl functional groups that can be used in organic reactions) with a diisocyanate or other polyisocyanate. Additionally, polyurethanes can include both hard and soft segments. The hard segments typically can include a combination of the isocyanate component of the polyurethane and a chain extender. The soft segments typically can include the polyol component of the polyurethane. In some examples, the type of polyol employed can depend on the environment in which the polyurethane will be used. For example, in cases where the polyurethane is intended for use in an aqueous environment, it may be advantageous to use a polyether-based polyol. In other examples, in cases where the polyurethane is intended for use in a hydrocarbon environment, it may be desirable to use a polyester-based polyol. Additionally, the molecular weight, composition ratio, chemical type, and other properties of the hard and soft segments can be varied to achieve the desired properties of the polyurethane.

[0045] However, many polyurethane materials constructed for use in aqueous environments do not have suitable resilience or organic solvent resistance to organic solvents. For example, some polyurethane materials constructed for use in aqueous environments (such as biological environments) can experience swelling, rupture, reduced hardness, reduced mechanical strength, etc. when exposed to organic solvents. Thus, it can be challenging to prepare polyurethane materials that have resilience in both aqueous and organic environments. In some cases, polyurethanes improved in this way or designed to be generally usable in aqueous environments and resistant to occasional exposure to organic solvents can have specific uses in certain medical devices, such as catheters.

[0046] For example, certain catheters can be introduced into a patient's vascular system (e.g., the venous system) for various purposes. For example, a catheter can be introduced into the vascular system for the purpose of delivering fluids, nutrients, blood, glucose solutions, drugs, diagnostic agents, etc. A catheter can also be introduced for the purpose of, for example, withdrawing blood from the vascular system in order to process the blood, diagnose the blood, etc.

[0047] Catheter shafts (including those for central venous catheters) are typically made of polymers. Suitable polymers are generally biocompatible, can be formed into tubing of various diameters, including some diameters small enough to reside within the vasculature, and can be flexible enough to be guided through the vasculature without harming the patient. When formed into tubing, the selected polymer can also advantageously provide sufficient strength to ensure that the lumen does not collapse within the vasculature and resists repeated bending. The shaft material can advantageously provide chemical resistance, burst resistance, radiopacity, durability, and / or additional properties. Polymers based on siloxane or polyurethane are typically employed to meet these criteria, however polyurethane catheters may be preferred because they generally have greater mechanical strength. In some cases, thermoplastic polyurethane can be advantageously used for catheters. Thermoplastic polyurethane can be melt-processable and can be extruded and / or molded using thermal processing, whereas thermoset polyurethane can be cast molded.

[0048] During the performance of a medically necessary or desired task, or during an indwelling period between such tasks, a catheter can become colonized by microorganisms (such as bacteria or fungi) that can harm the patient. Additionally, in cases such as the delivery of nutrients, the catheter can become completely or partially occluded by lipids. The presence of microbial and / or lipid occlusion can be particularly problematic for central venous catheters that can reside within a patient for extended periods of time.

[0049] Certain methods for reducing or eliminating microbial or lipid occlusion can involve directly and prolonged exposure of the catheter to an alcohol, such as isopropyl alcohol or ethanol. One such method of exposing the catheter to an alcohol is referred to by clinicians as alcohol lock. Alcohol lock of a catheter generally refers to the technique or procedure in which an alcohol is introduced into the catheter lumen and maintained within the lumen for a therapeutic period (e.g., greater than about 10 minutes, greater than about 30 minutes, greater than about one hour, or about one hour or longer), where the alcohol (e.g., ethanol) concentration is between 25% and 100% (e.g., 70%) for the purpose of disinfection or sterilization and / or elimination of lipid occlusion. The practice of alcohol lock or other internal or external applications of liquid alcohol are each referred to herein as direct and prolonged alcohol exposure.

[0050] When directly and prolonged exposed to an alcohol, siloxane catheters are generally used as central venous catheters. However, compared to polyurethane catheters, siloxane catheters can suffer from certain disadvantages, such as poor mechanical strength and durability. However, clinicians and manufacturers are also well aware that when polyurethane catheters are subjected to direct and prolonged exposure to an alcohol, the mechanical properties of the polyurethane catheters can be adversely affected. Thus, when direct and prolonged exposure to an alcohol is not used or not anticipated, clinicians generally prefer to use polyurethane catheters over their siloxane counterparts due to the increased durability achievable with polyurethane, specifically in high-flow and associated high-pressure power injection applications.

[0051] In the presence of alcohols, water, and other polar solvents, certain thermoplastic polyurethanes can undergo swelling. For example, when a central venous catheter formed from such a thermoplastic polyurethane is exposed to these agents, the catheter can soften, swell, and lose its mechanical properties, such as modulus of elasticity and tensile strength. This effect can also be accelerated at body temperature (e.g., 37 °C). The resulting loss of these mechanical properties can lead to central venous catheter failure, which includes but is not limited to tip instability, tip misalignment, excessive swelling and / or bursting during power injection, lumen collapse during fluid aspiration, cyclic fatigue failure due to repeated bending or clamping, and leakage from the extension leg or catheter shaft at the junction hub. Thus, in many applications, medical device manufacturers are required to design or specify the conditions under which polyurethane central venous catheters can be used in terms of safety factors. In many cases, manufacturers explicitly warn against or prohibit (e.g., provide a warning in the instructions for use) the use of alcohols and other materials in conjunction with the catheter to prevent these failures. In other words, polyurethane central venous catheters are generally incompatible with alcohol lock because the catheters can degrade rapidly to the point where they can no longer be used as intended, specifically in cases where the catheter can be power injected.

[0052] For another example, certain catheters made of polyurethane (e.g., or each purchased from Lubrizol Advanced Materials, Cleveland, Ohio; or each purchased from Biomerics, LLC, Salt Lake City, Utah; purchased from AdvanSource Biomaterials Corp., Wilmington, Massachusetts; etc.) can degrade during or after prolonged exposure to alcohol or otherwise suffer a reduction in performance. For example, such catheters can rupture during power injection or leak due to cyclic kinking. This loss of performance is directly related to a decline in alcohol-related mechanical properties, such as increased swelling, reduced stress crack resistance, and loss of certain mechanical properties (such as hardness, modulus, and strength). Thus, in many cases, manufacturers of central venous catheters explicitly prohibit the direct and prolonged exposure of their catheters to alcohol.

[0053] Regarding alcohol lockup, polycarbonate polyurethanes can be superior to polyether polyurethanes because polycarbonate polyurethanes generally degrade less. Additionally, the aromatic type of any polyurethane is generally superior to the aliphatic type. Thus, alcohol lockup can result in different amounts of degradation to the following materials, which are generally listed in order from greatest degradation to least degradation: aliphatic polyether polyurethane, aromatic polyether polyurethane, aliphatic polycarbonate polyurethane, aromatic polycarbonate polyurethane. However, even aromatic polycarbonate polyurethanes, when formed into catheter shafts, typically cannot withstand the stringent requirements of power injection after an alcohol lockup event or after many such alcohol lockup events.

[0054] This disclosure relates to alcohol-resistant aromatic polycarbonate polyurethanes that include polysiloxane in their soft segments. Embodiments of silicated polycarbonate polyurethanes can exhibit improved alcohol resistance compared to, for example, polycarbonate polyurethanes. Alcohol-resistant catheters that include the alcohol-resistant silicated polycarbonate polyurethanes disclosed herein are also disclosed. In some embodiments, compared to other polyurethanes, the catheters exhibit reduced swelling upon exposure to alcohol, improved stress crack resistance, and / or greater retention of certain mechanical properties (such as hardness, modulus, and strength). Embodiments of the catheters are power injectable. Additionally, the catheters can recover well after alcohol lockup and are suitable for long-term use in patients. For example, some embodiments include PICC devices suitable for long-term use in patients (including pediatric patients).

[0055] Certain embodiments of catheters that include silicated polycarbonate polyurethanes can also perform well when retaining compounded additives therein. For example, the catheters can retain radiopaque agents, such as barium sulfate, well enough to allow the catheters to be used with children and even neonates. In other words, when the material is extruded into a catheter shaft, relatively little leachate can be produced when the shaft is positioned within a patient. The foregoing advantages and / or other advantages of silicated polycarbonate polyurethanes and / or embodiments of devices into which these materials can be incorporated are further discussed below and / or will be apparent from this disclosure.

[0056] III. Silicated Polycarbonate Polyurethane

[0057] This disclosure particularly describes embodiments of silicated polycarbonate polyurethanes that are suitable for aqueous environments and have good tolerance or resiliency to a variety of organic solvents, such as alcohols (e.g., ethanol). The silicated polycarbonate polyurethanes can include soft segments and hard segments. The soft segments can include polycarbonate polyols and polysiloxane. In some cases, the polycarbonate polyols can be present in an amount greater than or equal to the amount of polysiloxane. In some embodiments, formulations in which the polysiloxane forms a particular percentage of the soft segment are particularly well-suited for catheters, such as power injectable PICC catheters. The hard segments can include isocyanates and chain extenders.

[0058] More specifically, a variety of polycarbonate polyols or combinations of polycarbonate polyols can be used to prepare the soft segments of polyurethanes. In some examples, the polycarbonate polyol can be or include a polycarbonate diol. In some examples, the polycarbonate polyol can have a structure according to formula (I):

[0059]

[0060] wherein R is selected from linear or branched, substituted or unsubstituted C1-C 24 alkyl or alkylene groups, A is selected from hydrogen (H) or R’OH, and n is an integer from 2 to 30. In some specific examples, A can be H. In other examples, A can be R’OH. In some such cases, R and R’ can be the same. In other cases, R and R’ can be different. In either case, R’ can be selected from linear or branched, substituted or unsubstituted C1-C 24 alkyl or alkylene groups. In some examples, R and R’ can independently be selected from C4-C 12 linear or branched, substituted or unsubstituted alkyl or alkylene groups. In some examples, R, R’, or both can be linear alkyl or alkylene groups. Thus, in some examples, the polycarbonate polyol can have a structure similar to formula (II) or have a structure according to formula (II):

[0061]

[0062] In other examples, R, R’, or both can be branched alkyl or alkylene groups. When R, R’, or both include a branch, any suitable number of branches can be present. In some specific examples, one or two branches can be present for each R group, R’ group, or both. In some examples, the branch can include a substituted or unsubstituted C1-C6 alkyl or alkylene group. In some specific examples, the branch can include a methyl, ethyl, propyl, or butyl group, or a combination thereof. Thus, for example, in some cases, the polycarbonate polyol can have a structure similar to formula (III) or have a structure according to formula (III):

[0063]

[0064] In some specific examples, one or more carbon groups in R, R’, or both can be substituted. When R, R’, or both are substituted, the substitution can include oxygen, nitrogen, sulfur, hydroxyl, amino, nitro, mercapto, carboxyl, another suitable substituent, or a combination thereof. In some specific examples, R and R’ are independently selected from linear unsubstituted C4-C 10Alkyl groups. In some examples, R and R’ can be independently selected from pentyl, hexyl, or heptyl groups. In some examples, n can be an integer from 5 to 25, or from 10 to 15.

[0065] The polycarbonate polyol can have a variety of molecular weights, depending on the desired material properties of the silicated polycarbonate polyurethane. For example, in some cases, increasing the molecular weight of the polycarbonate polyol can reduce the mechanical strength of the silicated polycarbonate polyurethane and decrease the stiffness of the material. Conversely, in some cases, decreasing the molecular weight of the polycarbonate polyol can increase the mechanical strength and stiffness of the silicated polycarbonate polyurethane. In some examples, the polycarbonate polyol can have a number average molecular weight (M n ) of from about 500 g / mol to about 5000 g / mol. In other examples, the polycarbonate polyol can have an M n of from about 500 g / mol to about 2500 g / mol, from about 1000 g / mol to about 4000 g / mol, from about 1500 g / mol to about 2500 g / mol, from about 1800 g / mol to about 2200 g / mol, or from about 1840 g / mol to about 2200 g / mol.

[0066] Generally speaking, the polycarbonate polyol can constitute more than 50 wt% of the soft segment. In some examples, the polycarbonate polyol can constitute greater than or equal to 80 wt%, 85 wt%, 88 wt%, 89 wt%, or 90 wt% of the soft segment. In some specific examples, the soft segment can contain from about 50 wt% to about 98 wt% of the polycarbonate polyol, but other amounts can also be used as needed. In some examples, the soft segment can contain from about 70 wt% to about 96 wt%, from about 75 wt% to about 85 wt%, from about 85 wt% to about 95 wt%, from about 88 wt% to about 94 wt%, from about 88 wt% to about 92 wt%, from about 89 wt% to about 91 wt% of the polycarbonate polyol.

[0067] Conversely, the polysiloxane generally can constitute less than 50 wt% of the soft segment. In some examples, the polysiloxane can constitute less than or equal to 20 wt%, 15 wt%, 12 wt%, 11 wt%, or 10 wt% of the soft segment. In some specific examples, the soft segment can contain from about 2 wt% to about 50 wt% of the polysiloxane, but other amounts can be used as needed. In some examples, the soft segment can contain from about 4 wt% to about 30 wt%, from about 15 wt% to about 25 wt%, from about 5 wt% to about 15 wt%, from about 6 wt% to about 12 wt%, from about 8 wt% to about 12 wt%, from about 9 wt% to about 11 wt%, or from about 9.5% to about 10.5% of the polysiloxane.

[0068] A variety of polysiloxanes or combinations of polysiloxanes can be used to prepare the soft segments of silicated polycarbonate polyurethanes. In some examples, the polysiloxane can have a structure according to formula (IV):

[0069]

[0070] wherein R1 and R2 are independently selected from straight-chain C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C 12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30. In some examples, one or more of R1 and R2 can be different. In other examples, each of R1 and R2 can be the same. In some examples, one or more of R1 and R2 can be hydrogen. In some examples, one or more of R1 and R2 can be a methyl group. In some specific examples, each of R1 and R2 can be a methyl group. In some examples, R3 and R5 can be independently selected from C1-C8 alkyl or alkylene groups. In some examples, R3 and R5 can be independently selected from C2-C8 alkyl groups. In some specific examples, both R3 and R5 can be ethyl, propyl or butyl groups. In some examples, R4 and R6 can be independently selected from C1-C4 alkyl or alkylene groups. In some examples, R4 and R6 can be independently selected from C1-C4 alkyl groups. In some specific examples, both R4 and R6 can be methyl, ethyl or propyl groups. In some examples, m can be an integer from 2 to 20, or from 6 to 14.

[0071] The polysiloxane can have a variety of molecular weights, depending on the specific material properties desired for the silicated polycarbonate polyurethane. In some examples, the polysiloxane can have an M n of about 300 g / mol to about 3000 g / mol. In some examples, the polysiloxane can have an M n of about 500 g / mol to about 1500 g / mol, about 800 g / mol to about 1200 g / mol, about 1500 g / mol to about 2500 g / mol, or about 700 g / mol to about 2300 g / mol.

[0072] The polycarbonate polyol and the polysiloxane can be present in the soft segment in a variety of weight ratios. In some examples, the polycarbonate polyol and the polysiloxane can be present in a weight ratio of polycarbonate polyol to polysiloxane of about 20:1 to about 1:1. In other examples, the polycarbonate polyol and the polysiloxane can be present in a weight ratio of polycarbonate polyol to polysiloxane of about 20:1 to about 4:1, about 20:1 to about 8:1, about 19:1 to about 9:1, about 11:1 to about 8:1, about 11:1 to about 9:1, about 10:1 to about 9:1, or about 10:1 to about 8:1.

[0073] The amounts of the soft segments and the hard segments in the adjustable silicated polycarbonate polyurethane can be adjusted to achieve desired material properties. For example, while relatively larger amounts of hard segments generally increase the hardness of the material and vice versa, other material properties can also be affected by changing the relative percentages of the hard segments and the soft segments. In some examples, the silicated polycarbonate polyurethane can include from about 30 wt% to about 80 wt% of soft segments. In other examples, the silicated polycarbonate polyurethane can include from about 30 wt% to about 60 wt% of soft segments. In other examples, the silicated polycarbonate polyurethane can include from about 40 wt% to about 70 wt% of soft segments. In other examples, the silicated polycarbonate polyurethane can include from about 30 wt% to about 40 wt%, from about 35 wt% to about 45 wt%, from about 40 wt% to about 50 wt%, from about 45 wt% to about 55 wt%, from about 50 wt% to about 60 wt%, from about 55 wt% to about 65 wt%, from about 54 wt% to about 58 wt%, from about 60 wt% to about 70 wt%, or from about 65 wt% to about 75 wt% of soft segments. In various embodiments, the silicated polycarbonate polyurethane can include about 69 wt%, about 56 wt% or about 50 wt% of soft segments.

[0074] Conversely, the silicated polycarbonate polyurethane can include from about 10 wt% to about 60 wt% of hard segments. In other examples, the silicated polycarbonate polyurethane can include from about 10 wt% to about 30 wt%, or from about 20 wt% to about 40 wt% of hard segments. In other examples, the silicated polycarbonate polyurethane can include from about 30 wt% to about 50 wt% of hard segments. In other examples, the silicated polycarbonate polyurethane can include from about 20 wt% to about 30 wt%, from about 25 wt% to about 35 wt%, from about 30 wt% to about 40 wt%, from about 35 wt% to about 45 wt%, from about 42 wt% to about 46 wt%, from about 40 wt% to about 50 wt%, from about 45 wt% to about 55 wt%, or from about 50 wt% to about 60 wt% of hard segments. In various embodiments, the silicated polycarbonate polyurethane can include about 31 wt%, about 44 wt% or about 50 wt% of hard segments.

[0075] The silicated polycarbonate polyurethane can include the soft segments and the hard segments in various weight ratios. In some examples, the soft segments and the hard segments can be present in a weight ratio of the soft segments to the hard segments of from about 5:1 to about 1:3. In other examples, the soft segments and the hard segments can be present in a weight ratio of the soft segments to the hard segments of from about 3:1 to about 1:2. In other examples, the soft segments can be present in a weight ratio of the soft segments to the hard segments of from about 3:1 to about 1:1, from about 3:1 to about 3:2, from about 2:1 to about 1:2, or from about 2:1 to about 1:1.

[0076] As described above, the hard segment may include an isocyanate and a chain extender. It should be noted that as used herein, "isocyanate" or "isocyanate compound" refers to a compound having multiple isocyanate groups. Thus, "isocyanate" or "isocyanate compound" may refer to a diisocyanate or other polyisocyanate. Accordingly, the isocyanate may include a diisocyanate, other polyisocyanates, or a combination thereof. A variety of isocyanates may be used in the silicated polycarbonate polyurethane. Non-limiting examples may include 4,4'-methylenediphenyl diisocyanate, dibenzylidene diisocyanate, methylenebis(cyclohexyl isocyanate), p-phenylene diisocyanate, trans-cyclohexane-1,4-diisocyanate, 1,6-diisocyanatohexane, 1,5-naphthalene diisocyanate, p-tetramethylxylene diisocyanate, m-tetramethylxylene diisocyanate, 2,4-toluene diisocyanate, isophorone diisocyanate, other diisocyanates or polyisocyanates, or combinations thereof. In some specific examples, the isocyanate may be or may include 4,4'-methylenediphenyl diisocyanate. In some cases, the isocyanate may be an aromatic isocyanate.

[0077] The hard segment may include different amounts of isocyanate, depending on the desired material properties of the silicated polycarbonate polyurethane. In some examples, the hard segment may contain from about 50 wt% to about 90 wt% isocyanate. In some additional examples, the hard segment may contain from about 60 wt% to about 90 wt% isocyanate. In some specific examples, the hard segment may contain from about 70 wt% to about 80 wt%, from about 75 wt% to about 85 wt%, or from about 80 wt% to about 90 wt% isocyanate.

[0078] A variety of chain extenders may be included in the hard segment of the silicated polycarbonate polyurethane. Non-limiting examples may include 1,2-propanediol, 1,3-propanediol, 2,2-dimethylpropane-1,3-diol, 2-ethyl-2-(hydroxymethyl)propane-1,3-diol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, 1,11-undecanediol, 1,12-dodecanediol, 1,4-cyclohexanediol, 1,4-cyclohexanedimethanol, 1,4-bis(2-hydroxyethoxy)benzene, p-xylene glycol, 1,3-bis(4-hydroxybutyl)tetramethyldisiloxane, 1,3-bis(6-hydroxyethoxypropyl)tetramethyldisiloxane, trimethylolpropane, and combinations thereof. In some specific examples, the chain extender may be or may include 1,4-butanediol.

[0079] The chain extender can be included in the hard segment in various amounts, depending on the desired material properties of the silicated polycarbonate polyurethane. In some examples, the hard segment can include from about 10 wt% to about 50 wt% of the chain extender. In some additional examples, the hard segment can include from about 10 wt% to about 40 wt% of the chain extender. In some specific examples, the hard segment can include from about 20 wt% to about 30 wt%, from about 15 wt% to about 25 wt%, from about 10 wt% to about 20 wt%, or from about 20 wt% to about 22 wt% of the chain extender.

[0080] The isocyanate and the chain extender can be present in the hard segment in a variety of weight ratios. In some examples, the isocyanate and the chain extender can be present in the hard segment in a weight ratio of isocyanate to chain extender of from about 10:1 to about 1:1. In other examples, the isocyanate and the chain extender can be present in the hard segment in a weight ratio of isocyanate to chain extender of from about 5:1 to about 1:1. In additional examples, the isocyanate and the chain extender can be present in a weight ratio of isocyanate to chain extender of from about 10:1 to about 5:1, from about 7:1 to about 3:1, or from about 4:1 to about 2:1.

[0081] In some embodiments, one or more crosslinking agents can be used such that the silicated polycarbonate polyurethane includes crosslinked chains, thereby resulting in, for example, greater mechanical and / or thermal stability compared to other identical silicated polycarbonate polyurethanes in which no crosslinking agent is employed. Non-limiting examples of crosslinking agents can include trimethylolpropane, castor oil, poly(vinyl alcohol), glycerol, one or more of the above polyisocyanates, or combinations thereof.

[0082] Unless otherwise specified, the silicated polycarbonate polyurethane can also include a variety of other additives that are not typically considered to be part of the hard segment or the soft segment. For example, in some cases, the silicated polycarbonate polyurethane can include radiopaque agents, lubricants, catalysts, antioxidants, free radical inhibitors, colorants, fillers, nucleating agents (e.g., pyrogenic silica), etc., or combinations thereof.

[0083] In some specific examples, siliconized polycarbonate polyurethane can include radiopaque agent.Generally speaking, radiopaque agent is dense filler, and it is added in polymer so that the medical device (comprising catheter shaft) of gained is for example able to observe under radiography when in vivo.The non-limiting example of radiopaque agent can include barium sulfate, tungsten metal, tungsten carbide, bismuth metal, bismuth oxide, bismuth oxychloride, bismuth subcarbonate, platinum, palladium, gold, zirconium oxide etc. or their combination.When using radiopaque agent, it can be included in the siliconized polycarbonate polyurethane with the amount of about 5 weight % to about 45 weight %, about 10 weight % to about 30 weight %, about 15 weight % to about 40 weight % or about 25 weight % to about 35 weight % usually.In various embodiments, radiopaque agent can exist in the amount of not less than 20%, 25% or 30%.

[0084] In some cases, adding higher amounts of fillers and / or denser fillers can increase the radiopacity of the resulting medical catheter shaft, but can also degrade the mechanical properties of the material (e.g., elongation, tensile strength, burst strength, biocompatibility, modulus, and chemical resistance). Therefore, the amount of filler added to the catheter material can depend on the specific application requirements of the material. For example, in small diameter, thin-walled catheters (which may become difficult to see under radiography), the appropriate amount of filler can be highly dependent on the parameters of the device and the intended use of the device. In addition, for catheters that can remain in the patient's body for a long time, such as PICC devices, it is desirable to reduce the amount of radiopaque agent that seeps into the blood. Reduction in leachables can be achieved by reducing the amount of radiopaque agent compounded into the polymer material, but this can make the catheter darker or otherwise less visible under radiography. However, the embodiments disclosed herein can advantageously retain the radiopaque agent (e.g., barium sulfate) within the polymer, thereby reducing the amount of radiopaque agent leachables, but without sacrificing a high radiopaque agent content with good imaging visibility.

[0085] In some additional specific examples, the siliconized polycarbonate polyurethane may include a lubricant, such as a lubricant or release agent that can be used for extrusion. Non-limiting examples of suitable lubricants may include polyethylene, fluorocarbon polymers (e.g., polytetrafluoroethylene), silicone resins, organic waxes (e.g., stearate waxes, bisamide waxes, including ethylene bis stearamide (EBS), etc.), etc., or combinations thereof. An exemplary example of a suitable lubricant is GLYCOLUBE®. TM VL, which is available from Lonza, Switzerland. Where a lubricant is used, the lubricant may be present in the siliconized polycarbonate polyurethane in an amount from about 0.05 wt % to about 5 wt %, or from about 0.1 wt % to about 0.5 wt %.

[0086] In other specific examples, the polyurethane polycarbonate may include a colorant. The colorant may include any suitable dye or pigment or a combination thereof, and may impart any suitable color to the silicated polycarbonate polyurethane. When a colorant is used, it may be present in the silicated polycarbonate polyurethane in an amount of about 0.1 wt% to about 10 wt%, or about 0.3 wt% to about 3 wt%.

[0087] The silicated polycarbonate polyurethane may have a variety of molecular weights. Generally, the silicated polycarbonate polyurethane may have a weight average molecular weight (Mw) of about 50,000 g / mol to about 300,000 g / mol. In some examples, the silicated polycarbonate polyurethane may have an Mw of about 70,000 g / mol to about 300,000 g / mol. In other examples, the silicated polycarbonate polyurethane may have an Mw of about 120,000 g / mol to about 250,000 g / mol. In other examples, the silicated polycarbonate polyurethane may have an Mw of about 50,000 g / mol to about 150,000 g / mol, about 150,000 g / mol to about 220,000 g / mol, about 160,000 g / mol to about 200,000 g / mol, about 150,000 g / mol to about 190,000 g / mol, or about 170,000 g / mol to about 210,000 g / mol.

[0088] The silicated polycarbonate polyurethane may also have any one of a variety of isocyanate indices. In some examples, the silicated polycarbonate polyurethane may have an isocyanate index (i.e., the number of moles of isocyanate groups / the number of moles of hydroxyl groups) of about 0.98 to about 1.10, such as about 1.00 to about 1.10. In other examples, the silicated polycarbonate polyurethane may have an isocyanate index of about 1.00 to about 1.08, about 0.98 to about 1.00, about 1.00 to 1.02, about 1.02 to about 1.05, about 1.03 to about 1.08, about 1.03 to about 1.08, about 1.04 to about 1.10, about 1.01 to about 1.06, about 1.02 to about 1.04, about 1.03 to about 1.04, about 1.04 to about 1.08, or about 1.045 to about 1.055.

[0089] The silicated polycarbonate polyurethane can also have a range of durometer values. In some examples, the silicated polycarbonate polyurethane can have a Shore A durometer value of from about 65 to about 100. In other examples, the silicated polycarbonate polyurethane can have a Shore A durometer value of from about 70 to about 90, from about 75 to about 85, from about 91 to about 100, from about 94 to about 98, from about 96 to about 100, from about 95 to about 99, from about 96 to about 98, or from about 97 to about 100 (including values slightly beyond the upper limit of the Shore A scale or harder than 100). In other examples, the silicated polycarbonate polyurethane can have a Shore D durometer value of from about 15 to about 85, from about 60 to about 80, or from about 65 to about 75.

[0090] The present invention also discloses a method for preparing a silicated polycarbonate polyurethane. In some examples, the method can include mixing or combining a polycarbonate polyol, a polysiloxane, an isocyanate, and a chain extender to prepare the silicated polycarbonate polyurethane. The polycarbonate polyol can be present in an amount greater than or equal to the amount of the polysiloxane.

[0091] In some examples, one or more of the raw materials can be melted or otherwise pretreated before being combined with the other components of the silicated polycarbonate polyurethane. For example, in some cases, the polycarbonate polyol can be melted before being combined with the other components of the silicated polycarbonate polyurethane. For example, certain polycarbonate polyols can be pre-melted at a temperature of from about 160°F to about 200°F. In other cases, such as in the case of certain polycarbonate diols, the pre-melting temperature can be lower, such as from about 90°F to about 150°F. In some examples, the polycarbonate polyol can be stored at a temperature of from about 160°F to about 175°F, melted or not melted as described above, before being combined with one or more other components. In some additional examples, the polycarbonate polyol can be stored in a nitrogen atmosphere, an argon atmosphere, or other suitable atmosphere to prevent moisture before being combined with one or more other components.

[0092] In some examples, the polysiloxane can also be stored at an elevated temperature, such as from about 140°F to about 160°F, before being combined with one or more other components. In some additional examples, the polysiloxane can be stored in a nitrogen atmosphere, an argon atmosphere, or other suitable atmosphere to prevent moisture before being combined with one or more other components.

[0093] In some examples, the isocyanate may be melted at a temperature of about 125°F to about 160°F. In some additional examples, the isocyanate may be decanted from insoluble dimers that precipitate out of the liquid phase. In certain such cases, the decanted isocyanate may be stored at about 125°F to about 140°F for subsequent use. In some additional examples, the isocyanate may be titrated to determine the percentage of isocyanate content. This may allow formulation adjustment as needed to maintain an appropriate or desired isocyanate index. In some examples, the chain extender may also be melted prior to mixing as needed.

[0094] The polycarbonate polyol, polysiloxane, isocyanate, and chain extender can be combined or mixed in a variety of ways and / or in one or more steps. For example, in some cases, the polycarbonate polyol, polysiloxane, isocyanate, and chain extender can all be added together into a common container and mixed simultaneously, or in other words, combined in a single mixing process. In some cases, the components are mixed for a set period of time, such as in the range of about 30 seconds to about 20 minutes. In other or additional cases, the components are mixed until a threshold, target, or predetermined temperature is reached. For example, the reaction can be exothermic, and the temperature of the mixture can increase from about 120°F to about 230°F or higher as mixing continues. In some cases, when the threshold temperature is reached, it may be desirable to stop mixing and pour out the mixture from the container. In various cases, the threshold temperature can be in the range of about 200°F to about 230°F.

[0095] In some cases, the temperature of the mixture can be controlled during mixing, such as by introducing heat to the mixture from an external source or by removing heat from the mixture in a controlled manner. In other cases such as those just described, the temperature of the mixture is not controlled as the reaction proceeds. For example, although the starting temperature of the various reactants can be maintained at a desired starting point, once the reactants are added to the mixture, no further control of its temperature can be externally imposed. Instead, although the temperature of the mixture may then change, this change occurs naturally (e.g., increases) due to the exothermic nature of the reaction and heat dissipation to the surrounding environment. The temperature can be monitored via any suitable temperature monitoring device, for example. The method of temperature monitoring and the use of such temperature monitoring devices are equally applicable to other parts of the present disclosure involving the determination of the temperature of various mixtures. In multiple embodiments, regardless of whether the temperature is controlled during the reaction, it can be said that the mixing of the mixture occurs at a temperature (e.g.) of about 120°F to about 230°F. This convention of indicating that mixing "occurs at" a certain temperature or temperature range is used throughout the present disclosure and the claims, regardless of whether the temperature is actively controlled to remain within the specified temperature or temperature range.

[0096] In some examples, the mixing of the components can be carried out in a multi-step process. For example, in some cases, the polysiloxane and the polycarbonate polyol can be mixed before adding the isocyanate and the chain extender. In some such cases, the polysiloxane and the polycarbonate polyol can typically be added together to a first mixture and mixed at a temperature of from about 120°F to about 200°F for a suitable mixing period, such as from about 30 seconds to about 15 minutes. In other words, the temperature of the mixture can naturally increase within the range of about 120°F to about 200°F as the mixing proceeds, rather than controlling or maintaining the temperature of the mixture during mixing. In some examples, the polysiloxane and the polycarbonate polyol can be mixed under vacuum for 12 hours to 48 hours to remove moisture and dissolved gases. In some examples, the isocyanate can then be added to the mixture of the polycarbonate polyol and the polysiloxane before adding the chain extender. In other words, after completing the mixing of the first mixture, a second mixture can be formed by adding the isocyanate to the first mixture, and subsequently, a third mixture can be formed by adding the chain extender to the second mixture. The mixture of the polycarbonate polyol, the polysiloxane, and the isocyanate (i.e., the second mixture) can be mixed for a suitable mixing period, such as from about 2 minutes to about 30 minutes. In some cases, the temperature at which the mixing occurs is not specifically or actively controlled, or in other words, not maintained within a specific or predetermined range. For example, in some cases, the isocyanate (in a preheated state, as described above) is added to the mixture of the polycarbonate polyol and the polysiloxane and mixed therewith, but no further heat is applied to the mixture. Any temperature change that may occur during mixing at this stage may be due to heating caused by the exothermic nature of the reaction and cooling caused by heat transfer from the reaction vessel. After mixing the polycarbonate polyol, the polysiloxane, and the isocyanate (i.e., after mixing the second mixture), the chain extender can be added to the mixture (i.e., a third mixture can be formed) and mixed. As the mixing continues, the temperature of the third mixture can be within the range of about 160°F to about 230°F. In some cases, the mixing is carried out for a suitable or predetermined mixing period, such as from about 30 seconds to about 15 minutes. In other or additional cases, the mixing is carried out until a target temperature is reached. In various cases, the target temperature can be within the range of about 200°F to about 230°F.

[0097] It can be said that the first mixture is mixed and continued for the first time period. After completion of the first time period, a second mixture is formed and mixed and continued for the second time period. After completion of the second time period, a third mixture is formed and mixed and continued for the third time period. The term "after completion" means at the termination point or at any point thereafter. For example, the first time period may terminate while the second mixture is being formed, such as by introducing an isocyanate into the polycarbonate / polysiloxane mixture. In other cases, a certain amount of time may elapse between completion of the first mixing time period and formation of the second mixture. This convention of indicating that some events occur "after completion" of the mixing time period is used throughout the present disclosure and the claims, regardless of whether the event occurs immediately at the termination of the mixing time period or at some point in time thereafter.

[0098] In other examples, the diisocyanate and the chain extender may be added simultaneously to a mixture of a polycarbonate polyol and a polysiloxane. In other words, the first mixture may comprise the polycarbonate polyol and the polysiloxane, and the second mixture may be formed by adding both the isocyanate and the chain extender to the first mixture. In some cases, the components (i.e., the components of the second mixture) are then mixed, and as the mixing continues, the temperature of the mixture may be in the range of about 120°F to about 230°F. In some cases, the mixing is carried out for a suitable or predetermined mixing time period, such as about 30 seconds to about 15 minutes. In other or additional cases, the mixing is carried out until a target temperature is reached. In various cases, the target temperature may be in the range of about 200°F to about 230°F.

[0099] In other examples, the polysiloxane and the isocyanate may be mixed before adding the polycarbonate polyol and the chain extender. In other words, the first mixture may comprise the polysiloxane and the isocyanate. In certain such cases, the polysiloxane and the isocyanate may be mixed, for example, at a temperature of about 120°F to about 180°F and continued for a suitable mixing time period, such as about 2 minutes to about 30 minutes.

[0100] In some examples, the polycarbonate polyol can then be added to the mixture of polyorganosiloxane and isocyanate before adding the chain extender. In other words, a second mixture can be formed by adding the polycarbonate polyol to the first mixture, and subsequently, a third mixture can be formed by adding the chain extender to the second mixture. The mixture of polyorganosiloxane, isocyanate, and polycarbonate polyol (i.e., the second mixture) can be mixed at a temperature of 130°F to 190°F for a suitable mixing period, such as about 2 minutes to about 30 minutes. Then the chain extender can be added to the mixture of polyorganosiloxane, isocyanate, and polycarbonate polyol (i.e., the third mixture can be formed) and mixed at a temperature of 160°F to 230°F for a suitable mixing period, such as about 30 seconds to about 15 minutes. In other or additional cases, mixing is carried out until a target temperature is reached. In various cases, the target temperature can be in the range of about 200°F to about 230°F.

[0101] In other examples, the polycarbonate polyol and the chain extender can be added to the mixture of polyorganosiloxane and isocyanate simultaneously. In other words, a second mixture can be formed by adding both the polycarbonate polyol and the chain extender to the first mixture comprising polyorganosiloxane and isocyanate. The second mixture can be mixed at a temperature of 130°F to 230°F for a suitable mixing period, such as about 2 minutes to about 15 minutes. In other or additional cases, mixing is carried out until a target temperature is reached. In various cases, the target temperature can be in the range of about 200°F to about 230°F.

[0102] Mixing such as that described in the foregoing paragraphs can be achieved via any suitable mixing equipment. For example, in some cases, an overhead stirrer can be used. In some such cases, the overhead stirrer can be used with a gate paddle or other suitable attachments and can be operated at a medium speed.

[0103] In some examples, a lubricant, an antioxidant, a catalyst, or other suitable additives or combinations thereof can be added to a suitable mixture of polycarbonate polyol, polyorganosiloxane, isocyanate, and chain extender to provide a silicated polycarbonate polyurethane having desired properties. In some examples, the additives can be added in an amount of about 0.05 wt% to about 5 wt%, or about 0.1 wt% to about 0.5 wt% of the silicated polycarbonate polyurethane.

[0104] In some examples, the mixture of polycarbonate polyol, polyorganosiloxane, isocyanate, chain extender, and optional additives can be cured. Curing can generally be carried out at a temperature of about 210°F to about 250°F, but other curing temperatures can also be used with some formulations or as desired. Additionally, curing can generally be carried out for a curing period of about 12 hours to about 36 hours, but other curing periods can also be used as desired.

[0105] If desired, it can be cured to prepare a cured silicated polycarbonate polyurethane, and the cured silicated polycarbonate polyurethane can optionally be further compounded or otherwise processed to prepare a silicated polycarbonate polyurethane. For example, in some cases, the cured silicated polycarbonate polyurethane can be granulated. In certain such cases, the silicated polycarbonate polyurethane can be granulated to have an average particle size of, for example, about 1 mm to about 10 mm, or about 2 mm to about 8 mm.

[0106] In some examples, the granular silicated polycarbonate polyurethane can be further compounded with a radiopaque agent, a colorant, a wax and / or a lubricant, a nucleating agent or other suitable compounding agents or combinations thereof to prepare a silicated polycarbonate polyurethane. In some examples, the compounding agent, the granular silicated polycarbonate polyurethane or both can be dried before compounding. The compounding agent can be added in various amounts, depending on the type of compounding agent and the desired properties of the silicated polycarbonate polyurethane. In some examples, the compounding agent can be added in an amount of about 5 wt% to about 45 wt%, about 10 wt% to about 30 wt%, about 15 wt% to about 40 wt%, or about 25 wt% to about 35 wt%. In other examples, the compounding agent can be added in an amount of about 0.1 wt% to about 10 wt%, or about 0.3 wt% to about 3 wt%.

[0107] In some additional examples, the granular silicated polycarbonate polyurethane, optionally mixed with a compounding agent, can be further extruded and granulated for subsequent use. Any suitable extrusion device can be contemplated. Two exemplary examples are model LSM30.34 and ZSE 27, which are purchased from Leistritz, Germany. In some cases, the extrusion is achieved via a twin-screw or single-screw extrusion. In certain such embodiments, the temperature of various extruder zones can be set, for example, between about 300°F and about 600°F. In some cases, the extruder zone temperature can be in the range of about 340°F to about 520°F. In additional cases, for any suitable length / diameter (L / D) ratio of one or more screw conveyors, a screw speed of about 50 RPM to about 500 rpm can be employed. For example, in various embodiments, the screw conveyor diameter can be in the range of about 25 mm to about 35 mm, and the L / D ratio can be in the range of about 25 to about 55. In certain cases, the screw speed can be about 100 RPM, where one or more screw conveyors each have, for example, a diameter of 34 mm and an L / D ratio of 30, or each have a diameter of 27 mm and an L / D ratio of 50. In various cases, the extrudate can be strand granulated or underwater granulated to obtain pellets for subsequent use.

[0108] Another embodiment of the silicated polycarbonate polyurethane and an exemplary method of forming the same will now be described, followed by more specific examples.

[0109] Any of the above polycarbonate polyols is provided in liquid form or melted prior to use. In some cases, the polycarbonate polyol is melted at a temperature of about 160°F to about 200°F. The polycarbonate polyol may optionally be stored prior to use. In some cases, the polycarbonate polyol is stored at a temperature in the range of about 160°F to about 175°F until use. In some cases, during storage prior to use, the polycarbonate polyol is protected from moisture (e.g., under nitrogen or other gases). Exemplary examples of the polycarbonate polyol include poly(hexamethylene carbonate) diol according to the above formula (II), including but not limited to those having a number average molecular weight (M n ) in the range of about 1840 g / mol to about 2200 g / mol.

[0110] Any of the above polysiloxane polyols is used at room temperature or stored at a temperature in the range of about 140°F to about 160°F until use. In some cases, during storage prior to use, the polysiloxane polyol is protected from moisture (e.g., under nitrogen or other gases). An exemplary example of the polysiloxane polyol is methanol-modified polydimethylsiloxane according to the following formula (V), including but not limited to those having a number average molecular weight (M n ) in the range of about 925 g / mol to about 1025 g / mol, which exhibits reactivity at both ends.

[0111]

[0112] As previously described above with respect to formula (IV), m is an integer from 2 to 30. The polysiloxane polyol exhibits relatively high reactivity, which in some cases may advantageously allow it to be easily incorporated into the polyurethane chain. The polysiloxane polyol may also exhibit good miscibility with other polyols, which may be advantageous in some cases. For example, such increased miscibility may improve the absorption of the polysiloxane into the resulting polycarbonate polyurethane. In other examples, the polysiloxane polyol may have a structure similar to the above formula (V), but with a different linking group between the polydimethylsiloxane center and the terminal hydroxyl functional groups of the chain.

[0113] Any of the above isocyanates is provided in liquid form or melted prior to use. In some cases, the isocyanate is melted at about 140°F. In other cases, the melted isocyanate is decanted to remove insoluble dimers that precipitate out of the liquid phase. The decanted (e.g., clarified) portion can be stored at an elevated temperature until use, such as in the range of about 125°F to about 140°F. In some cases, the isocyanate is protected from moisture during storage prior to use (e.g., under nitrogen or other gas). Samples of the decanted liquid can be taken for titration to adjust the overall formulation. Specifically, the percentage of NCO can be determined by titration. Exemplary examples of isocyanates are methylene diphenyl diisocyanate (MDI).

[0114] Any of the above chain extenders is provided in liquid form or melted prior to use. The chain extender can be stored at an elevated temperature prior to use, such as at about 80°F. In some cases, the chain extender is protected from moisture during storage prior to use (e.g., under nitrogen or other gas). Exemplary examples of chain extenders are 1,4 - butanediol (BDO).

[0115] The amount of each of the above components (polycarbonate polyol, polysiloxane polyol, isocyanate, chain extender) can be selected to achieve a desired isocyanate index that can fall within any of the ranges described above. For example, the isocyanate index can be in the range of about 1.00 to about 1.10. In other words, the formulation of the silicated polycarbonate polyurethane can be adjusted or fine - tuned prior to combining any of the components. In formulating the adjustment, the hydroxyl number and H2O percentage of each polyol, the NCO percentage of the isocyanate, and the H2O percentage of the chain extender can be used. In some cases, adjusting the isocyanate index can represent a very small change in the mass ratio of the various components but can have a significant impact on the properties of the final silicated polycarbonate polyurethane.

[0116] In some cases, the isocyanate and the polysiloxane polyol are poured into a common container and mixed for a suitable period of time, such as described above. For example, the mixing can be carried out for a period of time in the range of about 2 minutes to about 30 minutes. In some cases, the mixing can be carried out for about 5 minutes. In some cases, combining the isocyanate and the polysiloxane first can result in a more thorough and / or more uniform distribution of the polysiloxane in the final silicated polycarbonate polyurethane material.

[0117] In some cases, the polycarbonate polyol is then added to the mixture. The mixture can be remixed for an additional period of time, such as about two minutes to about fifteen minutes. In other cases, the mixing period is about 5 minutes.

[0118] Then a chain extender can be added to the mixture of polysiloxane, isocyanate, and polycarbonate polyol and mixed at a temperature of 160°F to 230°F for a suitable mixing period, such as about 30 seconds to about 15 minutes. Alternatively, the temperature of the mixture can be monitored, and mixing can be terminated when the temperature reaches a threshold, which can correspond to the point at which the mixture begins to thicken. In various embodiments, the threshold can be in the range of about 200°F to about 230°F. In some specific cases, the mixing time is in the range of about 1 minute to about 2 minutes and / or the temperature threshold is in the range of about 200°F to about 210°F.

[0119] Upon completion of mixing, the mixture can be poured into a pan or sheet of any suitable size and configuration (e.g., coated with Teflon). The mixture can then be cured in an oven at, for example, about 230°F for about 16 hours to about 24 hours.

[0120] In some cases, the cured cake is removed from the pan and cut into smaller bricks. The bricks are then ground or pelletized to a size small enough to feed into a compounding machine. Any of the above pellet sizes are contemplated.

[0121] In some cases, the granular silicated polycarbonate polyurethane is dried, for example, in a temperature range of about 140°F to about 180°F. In additional cases, it may be desirable to compound a radiopaque agent with the silicated polycarbonate polyurethane. In some such cases, the radiopaque agent may also be dried. For example, in some embodiments, barium sulfate is dried before compounding.

[0122] In some cases, the granular and dried silicated polycarbonate polyurethane is compounded with any of the above additives, such as one or more radiopaque agents and / or colorants. In some embodiments, the silicated polycarbonate polyurethane, the radiopaque agent (e.g., barium sulfate), and the colorant are weighed and then introduced into a bag, such as a large polymer bag. The bag can be closed and tumbled (e.g., in a cement mixer) for blending.

[0123] After blending, the mixed materials are fed into a preheated extruder, such as a twin-screw extruder. The extrudate can be pelletized into any of the pellet sizes such as those described above. In additional cases, the pellets can then be introduced into a separate extruder to form medical components, such as catheter shafts.

[0124] Example 1

[0125] Five test samples (Samples 1 - 5) of the silicated polycarbonate polyurethane material were formulated according to a fractional factorial design of experiments (DoE) to test the effect of varying each of three parameters at low, medium, and high target values. The first parameter was the mass percentage of the hard segment relative to the total weight of the formulation, where the low target value was approximately 37%, the medium target value was approximately 41%, and the high target value was approximately 44%. The second parameter was the mass percentage of the polysiloxane polyol relative to the total weight of the polyol content, where the low target value was approximately 10%, the medium target value was approximately 20%, and the high target value was approximately 30%. The third parameter was the isocyanate index of the formulation, where the low target value was approximately 1.02, the medium target value was approximately 1.035, and the high target value was approximately 1.05. The actual formulations for each of Samples 1 - 5 are provided in Table 1 below.

[0126] Table 1

[0127]

[0128]

[0129] For each of Samples 1 - 5, the polycarbonate polyol was poly(hexamethylene carbonate) diol (PHMCD) with a molecular weight of 2020 g / mol ± 180 g / mol. The polycarbonate polyol was melted at a temperature of 160°F to 200°F and then stored at a temperature of 160°F to 175°F until use. During storage, the polycarbonate polyol was protected from moisture under nitrogen.

[0130] For each of Samples 1 - 5, the polysiloxane polyol was methanol - modified polydimethylsiloxane (PDMS) according to the above formula (V), where the molecular weight was 975 g / mol ± 50 g / mol. The polysiloxane polyol was stored at room temperature and protected from moisture under nitrogen until use.

[0131] For each of Samples 1 - 5, the isocyanate was monomeric diphenylmethane 4,4'-diisocyanate. The isocyanate was melted at 140°F and decanted to remove insoluble dimers that precipitated from the liquid phase. The decanted portion was stored at a temperature of 125°F to 140°F and protected from moisture under nitrogen until use. Samples of the decanted liquid were taken for titration to determine the NCO concentration, and the overall formulation was adjusted based on the NCO concentration according to the DoE isocyanate index target.

[0132] For each of Samples 1 - 5, the chain extender was 1,4 - butanediol. The chain extender was stored at 80°F and protected from moisture under nitrogen until use.

[0133] For each of Samples 1 - 5, polysiloxane polyol and molten MDI were added to a bucket and mixed for 5 minutes at medium speed via an overhead stirrer. Then, polycarbonate diol was added to the bucket and the mixture was mixed for an additional 5 minutes at medium speed via the overhead stirrer. Then, BDO was added to the bucket and the mixture was mixed for an additional 1 to 2 minutes at medium speed via the overhead stirrer. Then, the overhead stirrer was stopped and the mixture was poured onto a baking sheet and cured overnight in an oven at 230°F.

[0134] After curing, the material was removed from the baking sheet and mechanically ground into particles with an average particle size of less than about 10 mm. The particles were then dried in a desiccant dryer and subsequently stored for later use.

[0135] For each of Samples 1 - 5, a small amount of dry silicated polycarbonate polyurethane particles were injection molded to form test plates, which were then tested using a Check - Line HPSA manual hardness tester according to ASTM D2240 standard. The measured hardness was recorded in the last column of Table 1.

[0136] Example 2

[0137] Five batches of material (Batches 1 - 5) were prepared separately using portions of each of Samples 1 - 5 of Example 1 above. To prepare each of Batches 1 - 5, an amount of one of the silicated polycarbonate polyurethanes of Samples 1 - 5, along with an amount of barium sulfate suitable to achieve radiopacity of the material (e.g., when extruded into a catheter shaft), and an amount of powdered colorant suitable to achieve the desired and consistent coloring of the material were introduced into a polymer bag. Specifically, the relative amounts of the components were 69.1% silicated polycarbonate polyurethane, 29.6% barium sulfate, and 1.3% colorant. This is summarized in Table 2 below. The bag was sealed and tumbled in a cement mixer to thoroughly blend the components. Then each mixture was fed into a twin - screw extruder for compounding, pelletizing, and then drying. Batches 1 - 5 were stored for later use.

[0138] Table 2

[0139]

[0140] An amount of each of Batches 1 - 5 was extruded into multiple Figure 1 、 2A and double - lumen, tapered catheter shafts in the form shown in 2B. Then, the effect of alcohol locking on the burst pressure of the catheter shaft was tested.

[0141] Specifically, as Figure 1As shown, a catheter 100 of a particular form extends from a proximal end 102 to a distal end 104. The proximal end 102 of the catheter 100 terminates at a proximal terminus 106, and the distal end 104 terminates at a distal terminus 108.

[0142] The proximal end 102 includes a connection region 110 at which any suitable connection means can be coupled to the catheter shaft 100. For example, in some cases, a connection hub can be overmolded onto the connection region 110, and the connection hub can also be connected to one or more extension legs, each of which can be coupled to a connector (e.g., a Luer connector). For each of the catheter shafts of the present Example 2, a female Luer connector (not shown) is directly adhered to the connection region 110.

[0143] The catheter shaft 100 also includes a tapered region 112 (which can alternatively be referred to as a lug) and a reduced-diameter region 114 (which extends from the distal end of the tapered region 112 to the distal terminus 108 of the catheter shaft 100). For the catheter shafts of the present Example 2, the length L of the connection region 110 C is in the range of 0.35 inches to 0.51 inches, the length L of the tapered region 112 T is not greater than 2 inches, and the effective length L of the catheter shaft 100 (which includes the tapered region 112 and the reduced-diameter region 114) E is not less than 26 inches. Thus, the length of the reduced-diameter region 114 is at least about 23.5 inches. The reduced-diameter region 114 can also be referred to as the insertion region.

[0144] As Figure 2A and 2B shown, the catheter shaft 100 defines two lumens 122, 124 that are separated from each other along the entire length of the catheter shaft 100 by an inner wall 126, which can also be referred to as a septum or a central barrier and which defines the inner surface of each lumen. In typical use, each lumen 122, 124 can be separately accessed, such as via a separate extension tube that is in fluid communication with only one of the lumens 122, 124. However, for each of the catheter shafts of the present Example 2, a female Luer connector (not shown) that accesses both lumens 122, 124 simultaneously is adhered to the connection region 110 via Loctite 4011 adhesive.

[0145] Figure 2A A cross-section through the enlarged connection region 110 is shown, and Figure 2B a cross-section through the reduced-diameter region 114 is shown. The inner wall 126 defines a first width W in the connection region 110 IW1 and a second width W in the reduced-diameter region 114 IW2The width of the inner wall 126 may taper along the length L of the tapered region 112 T from a first width W IW1 to a second width W IW2 For the catheter shaft of this Example 2, the first width W IW1 is not less than 0.007 inches, and the second width W IW2 is not less than 0.005 inches.

[0146] Continuing to refer to Figure 2A and 2B , the outer surface of each lumen 122, 124 extending from one end of the inner surface to its opposite end is defined by a sidewall 128. The sidewall 128 extends around the entire circumference of the catheter shaft 100. The sidewall 128 defines a first width W in the connection region 110 SW1 and a second width W in the reduced diameter region 114 SW2 . The width of the sidewall 128 may taper along the length L of the tapered region 112 T from a first width W SW1 to a second width W SW2 For the catheter shaft of this Example 2, the first width W SW1 is not less than 0.007 inches, and the second width W SW2 is not less than 0.004 inches.

[0147] The outer surface of the sidewall 128 defines the outer diameter of the catheter shaft at each position along its entire length. The sidewall 128 defines a first outer diameter OD1 in the connection region 110 and a second outer diameter OD2 in the reduced diameter region 114. The outer diameter of the sidewall 128 may taper along the length L of the tapered region 112 T from a first outer diameter OD1 to a second outer diameter OD2. For the catheter shaft of Example 2 of the present invention, the first outer diameter OD1 is not greater than about 6 French, and the second outer diameter OD2 is 5 French. The catheter shaft 100 may define the second outer diameter OD2 along not less than 75%, 80%, 90% or 95% of the insertable portion of the effective length L E . The catheter shaft 100 may be referred to as a 5 French, double lumen, tapered (or lugged) catheter shaft. A shaft of such a configuration may be particularly suitable for, for example, a power injectable PICC device.

[0148] Initial burst pressure tests were performed on samples of multiple catheter shafts extruded from batches 1 - 5 to determine the feasibility for further testing. The catheter shafts formed from batch 2 did not meet the minimum performance benchmark, so further testing was performed only on the catheter shafts formed from batches 1, 3, 4, and 5.

[0149] The test catheters, including the catheter shafts formed from lots 1, 3, 4, and 5 and the concave luer connectors adhered thereto, were conditioned in a variety of ways and then tested to determine the pressure at which rupture occurred under each condition. Unless otherwise specified, at least five (5) catheters from each of lots 1, 3, 4, and 5 were tested for each condition.

[0150] The first group of test catheters was subjected to a "no flush" condition, in which each catheter was immersed in a 0.9% saline bath at 37 °C for a period of at least two hours. This condition is referred to as "no flush" because it does not involve perfusing the catheter with ethanol and then flushing the perfused catheter with saline, as in other conditions. The catheter was then removed from the saline bath and tested.

[0151] The second group of test catheters was subjected to a "flush" condition, in which each catheter was first subjected to the no flush condition described above and then removed from the saline solution bath. The concave luer fitting of the catheter was then coupled to a 10 mL syringe filled with 70% ethanol. The syringe was used to flush and perfuse the catheter shaft with 70% ethanol. With the syringe not removed from the concave luer connector, the distal end of the catheter was folded and clamped with a long tail clip to clamp the shaft closed. The syringe was then removed and immediately replaced with a male luer lock cap. The catheter was then immersed again in a 0.9% saline bath at 37 °C for a period between 60 and 70 minutes. The catheter was then removed again from the 0.9% saline bath. The male luer lock cap was removed and immediately replaced with a 10 mL syringe filled with 0.9% saline at 37 °C. The long tail clip was removed and the syringe was used to flush the catheter shaft. After having been subjected to this flush conditioning, the catheter was then tested.

[0152] Rinsing modulation during a period of perfusion of the catheter with 70% ethanol and immersion in a 0.9% saline bath for a period of 60 to 70 minutes may also be referred to as alcohol lock or ethanol lock and is similar to alcohol lock in a clinical setting. For example, when in a patient, a PICC catheter may be infected with bacteria or other microorganisms and / or may be at least partially occluded with lipids and / or other materials. In such an environment, ethanol or isopropanol may be introduced into the catheter such that the catheter (specifically, the inner surface of the catheter defining one or more lumens into which the alcohol has been introduced) remains in direct and prolonged exposure to the alcohol. Such exposure may disinfect one or more lumens and / or may clear occluding lipids or other substances. In a clinical setting, an alcohol lock event may advantageously occur and persist for a period of at least one hour. In some cases, the alcohol lock period may be longer or shorter. However, an alcohol lock of at least one hour generally achieves clinical goals and may thus be referred to herein as a clinically acceptable, clinically relevant, or clinically effective lock period. Depending on the goals to be achieved by the alcohol lock event, in various cases, a clinically effective lock period may be no less than about 10 minutes, 20 minutes, 30 minutes, 45 minutes, or 60 minutes.

[0153] Subject additional groups of test catheters to a "rinse ## minutes" condition, where each catheter is first subjected to the above-described no-rinse and rinse conditions and then immersed in a 0.9% saline bath at 37 °C for a recovery period specified by the "## minutes" term. Test recovery periods of 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 105 minutes. Thus, for example, a catheter subjected to the rinse and 15-minute condition is first subjected to the no-rinse condition, then the rinse condition, and then immersed in a 0.9% saline bath for a 15-minute recovery period. At the completion of the immersion during the recovery period, the catheter is removed from the saline bath and tested.

[0154] Upon completion of preconditioning, the catheter is clamped at the distal end by folding approximately 1 inch of the distal end of the tube and securing the folded end with a long-tail clip. The catheter is then coupled to the test device via a female Luer connector. The test device fills the catheter with nitrogen and increases the pressure of the gas until the catheter shaft bursts, and the pressure at which bursting occurs is recorded. As previously described, the catheter is configured to have a female Luer connector that establishes simultaneous fluid communication with two lumens of the catheter shaft. Thus, during pressurization of the catheter shaft, both lumens are simultaneously exposed to the same pressure conditions. When either of the lumens is damaged (i.e., when the sidewall 128 ruptures), the bursting pressure of the shaft is reached.

[0155] The test results are provided in Table 3 below and Figure 3 in Figure 3Depicts graph 200 with separate curves 211, 213, 214, 215 that connect data points of conduits associated with each of batches 1, 3, 4, and 5 respectively. In graph 200, in each case, the uniform horizontal spacing between adjacent test conditions does not accurately depict the amount of time associated with those conditions. In other words, in all cases, the horizontal axis is not scaled precisely with respect to time.

[0156] Table 3

[0157]

[0158] Conduits having a conduit shaft formed from the material of batch 3 exhibit the highest burst pressures under various preconditionings. Additionally, these conduits are more resistant to alcohol lockup (i.e., flushing conditions) than conduits from the remaining batches. Specifically, a comparison of burst pressures for no flush and flush conditions shows that conduits of batch 1 suffered a 45% decrease, conduits of batch 4 suffered a 49% decrease, and conduits of batch 5 suffered a 46% decrease, whereas conduits of batch 3 suffered only a 40% decrease. Additionally, conduits of batch 3 recover from alcohol lockup at approximately the same rate as those of the remaining batches.

[0159] These are surprising, unexpected, and unpredictable results, specifically when comparing the material properties of batch 3 with those of batch 4. Referring again to Table 1, samples 3 and 4 of silicated polycarbonate polyurethanes for batch 3 and batch 4 respectively are very similar. These materials have nearly the same ratio of soft segments to hard segments and exhibit very similar hardnesses. However, these polyurethanes differ in the percentage of soft segments composed of polysiloxane polyol: 10.2% for batch 3 compared to 29.4% for batch 4.

[0160] For conduits from these batches that were subjected to non-flush conditions, the average burst pressure of batch 3 conduits exceeded that of batch 4 conduits by less than 2%. Given the similarity between the substances just discussed, this is not surprising. However, for conduits that were subjected to flush conditions (i.e., alcohol lockup), the average burst pressure of batch 3 conduits exceeded that of batch 4 conduits by 17%. Thus, batch 3 conduits are significantly more resistant to alcohol lockup than batch 4 conduits, which is very surprising. As previously discussed, it is known that siloxanes resist polar organic solvents such as alcohols and can therefore be used in conduits that are able to withstand alcohol lockup. Thus, it was expected that a greater siloxane content in the soft segments would result in improved alcohol resistance, but the opposite was observed in this series of tests.

[0161] The Lot 3 catheter is able to withstand high pressure even after an alcohol lock event. Specifically, the Lot 3 catheter is subjected to an alcohol lock for a lock period of not less than one hour and then directly subjected to a burst test or a burst test after multiple recovery periods. Even without any recovery period, the Lot 3 catheter will be suitable for use at power injection pressure. Specifically, immediately following flushing conditioning (i.e., a lock period of at least one hour), the Lot 3 catheter has a burst pressure of 247 ± 5 psi. Thus, these catheters will be able to operate at pressures up to approximately 180 psi, 190 psi, 200 psi, 210 psi, 220 psi, 230 psi, or even 240 psi. The performance of the catheter improves steadily after recovery periods of 15 minutes, 30 minutes, 45 minutes, 60 minutes, and 105 minutes. For example, after a 15-minute recovery period, the catheter will be able to operate at pressures up to approximately 180 psi, 190 psi, 200 psi, 210 psi, 220 psi, 230 psi, 240 psi, or even 250 psi. After a 45-minute recovery period, the catheter will be able to operate at pressures up to approximately 180 psi, 190 psi, 200 psi, 210 psi, 220 psi, 230 psi, 240 psi, 250 psi, or even 260 psi. After a 60-minute recovery period, the catheter will be able to operate at pressures up to approximately 180 psi, 190 psi, 200 psi, 210 psi, 220 psi, 230 psi, 240 psi, 250 psi, 260 psi, or even 270 psi. And after a 105-minute recovery period, the catheter will be able to operate at pressures up to approximately 180 psi, 190 psi, 200 psi, 210 psi, 220 psi, 230 psi, 240 psi, 250 psi, 260 psi, 270 psi, or even 280 psi.

[0162] Example 3

[0163] An amount of each of Lot 1, 3, 4, and 5 as described above with respect to Example 2 is extruded into a plurality of double lumen tapered catheter shafts having the forms described with respect to Example 2 and Figure 1 、 2A and as shown in 2B. Then the effect of alcohol lock on the tensile strength and strain of the catheter shaft is tested at three separate regions of the shaft. Specifically, the tension required to break three different portions of the extruded tubing is measured for a variety of conditions. For each condition, five to ten catheters of each of Lot 1, 3, and 5 are tested. The average results of the tensile strength tests are shown in Graphs 301, 302, and 303 of Figure 4A 、 4B and 4C, respectively, and the average results of the stress tests are shown inFigure 5A , 5B and shown in the graphs 401, 402, and 403 of 5C. In these graphs, the curves 311, 313, 315; 321, 323, 325; 331, 333, 335; 411, 413, 415; 421, 423, 425; and 431, 433, 435 connect the data points of the conduits associated with each of batches 1, 3, and 5, respectively. Additionally, in these graphs, in each case, the uniform horizontal spacing between adjacent test conditions does not accurately depict the amount of time associated with those conditions. In other words, in all cases, the horizontal axis is not scaled precisely relative to time.

[0164] For the first set of test conduit shafts, each shaft was cut into three separate three-inch long segments from three specific portions of the shaft, which are identified herein as portions 1, 2, and 3. Referring again to Figure 1 , portion 1 represents a three-inch region of the proximal end of the conduit shaft that includes the entire tapered region 112 and, at each of its ends, includes a small portion of each of the connection region 110 and the reduced diameter region 114. Portion 2 represents a three-inch region that is generally positioned at the center of the reduced diameter region 114. Portion 3 represents a three-inch region that is positioned slightly proximal to the distal end 108. After cutting, each segment was then clamped in a testing device and tested for ultimate tensile strength and strain.

[0165] This first set of test conduit shafts did not undergo any preconditioning involving exposure to saline or other solutions. Thus, this condition is referred to herein as "dry". The dry tensile strength and strain of the conduit shafts formed from batch 4 were also tested, but the dry tensile strength and strain were sufficiently lower than those of batches 1, 3, and 5 to determine that no further testing would be performed on these conduit shafts. Thus, Figure 4A , 4B and the graphs 301, 302, and 303 in 4C relate only to the test results of batches 1, 3, and 5, respectively.

[0166] Additional groups of test conduits were subjected to the no-rinse, rinse, and rinse ## minute conditions described above with respect to Example 2. Recovery times of 15 minutes, 30 minutes, 45 minutes, and 60 minutes were tested. For each group, each conduit shaft was then cut into portions 1, 2, and 3, and then each portion was tested.

[0167] These tests revealed additional surprising, unexpected, and unpredictable results. Regarding ultimate tensile strength, as Figures 4A - 4CAs shown, the catheter shafts formed from the materials of batches 1, 3, and 5 behave very similarly to each other, but the batch 1 group generally exhibits the highest ultimate tensile strength, while the batch 3 group generally exhibits the lowest ultimate tensile strength. It was expected that those materials showing the highest ultimate tensile strength would also show the highest burst resistance. This was not observed. Although under all test conditions, with respect to ultimate tensile strength, batch 1 generally performed better than the remaining batches, and batch 3 generally performed the worst, the opposite was true for the burst pressure test (see Figure 3 ). In some cases, due to the high pressure associated with power injection and the accompanying importance of burst resistance, the materials of batch 3 may be superior to those of batch 1 for forming power-injectable catheters. In other words, in such cases, batch 3 may be superior to batch 1 because excellent burst resistance performance may be more relevant to meeting the stringent requirements of power injection compared to excellent ultimate tensile strength performance.

[0168] Figures 5A - 5C Surprising results were also shown for the materials of batch 3. When subjected to an aqueous environment at elevated temperatures, polyurethane properties generally deteriorate. However, the materials of batch 3 showed consistent and significant improvement in strain after being subjected to non-flush conditions (i.e., after being soaked in a saline solution at 37 °C). In the case of catheter shafts formed from the materials of batches 1 and 5, this result was less obvious or non-existent. In addition, the materials of batch 3 recovered quickly from the flush condition (i.e., recovered quickly from alcohol lock).

[0169] Example 4

[0170] For comparison purposes, test catheters were formed from three different materials of similar hardness. The first material was formed from approximately 69 wt% of a catheter-grade aliphatic polyether polyurethane sold under the trademark , which was purchased from Biomerics, and this catheter-grade aliphatic polyether polyurethane was compounded with 30 wt% barium sulfate and approximately 1 wt% colorant. The second material was formed from 69 wt% of a catheter-grade aromatic polycarbonate polyurethane formed from poly(hexamethylene carbonate) diol, methylene diphenyl diisocyanate, and 1,4-butanediol, which was compounded with 30 wt% barium sulfate and 1 wt% colorant. The third material was a quantity of batch 3, as described above with respect to Example 2, and thus contained 69.1 wt% of the sample 3 silicated aromatic polycarbonate polyurethane described in Example 1, 29.6 wt% barium sulfate, and 1.3 wt% colorant. Each test catheter included a catheter shaft and a luer connector, which had the same construction as described above with respect to Example 2. The catheters were subjected to preconditioning such as described above with respect to Example 2, and then the burst pressure was tested.

[0171] Figure 6 A graph 500 of test results is provided. For each data point, three to six catheters were tested and their average values are shown, except for the data points identified with an asterisk (for which a single catheter was tested). Separate curves 511, 512, 513 connect the data points for the catheters associated with aromatic polycarbonate polyurethane and the Batch 3 material. In some cases, an additional "lower specification limit" (LSL) at 236 psi is also shown, which represents the pressure at which, in some cases, certain catheters can be expected or required to operate without bursting in order to be considered power injectable. The conditions labeled no flush, flush, and flush ## minutes on the horizontal axis of graph 500 are the same as the similarly named conditions described above with respect to Example 2. Similar to Figures 3 - 5C the curves in Figure 1 the sample, in all cases, the horizontal axis is not precisely scaled with respect to time.

[0172] It is evident that the silicated aromatic polycarbonate polyurethane is significantly superior to the aromatic polycarbonate polyurethane and aliphatic polyether polyurethane. These results also indicate that even after an alcohol lock event, the catheters formed from the silicated aromatic polycarbonate can withstand the stringent requirements of power injection.

[0173] Example 5

[0174] A series of analytical tests were performed on the materials using various amounts of Batch 3 as described in Example 2 above, and the results are provided in Table 4 below. The tests were conducted according to the ASTM standards determined in Table 4. Although the measured values are not expressed with a specific level of uncertainty, it should be understood that there is at least some uncertainty in these values. Thus, each value can be encompassed by a small range of values. Additionally, as previously discussed, a range of acceptable values for the raw materials is also possible, such that the accompanying ranges of the values measured in Table 4 are also contemplated.

[0175] Table 4

[0176]

[0177] IV. PICC Device

[0178] Figure 7 is a perspective view of an exemplary embodiment depicting a catheter device 600 that can be constructed using the embodiments of the present disclosure. The PICC device 600 shown is specifically a power injectable double-lumen PICC and can thus also be referred to herein as a PICC device or a PICC assembly. The catheter device 600 is only exemplary of the various forms of catheter devices that can be constructed at least in part from the embodiments of the materials disclosed herein. For example, in other cases, similar to Figure 7The catheter device shown may include different numbers of extension legs and lumens and may have a catheter shaft with different dimensions (e.g., larger or smaller outer diameter, wall thickness, septum thickness, length), etc. More generally, the PICC device 600 exemplarily shows various forms of medical devices that may be constructed at least in part from embodiments of the materials disclosed herein. Other suitable medical devices may include, for example, any of a variety of implantable devices, such as an implantable vascular access port.

[0179] In the illustrated embodiment, the PICC device 600 includes a dual-lumen catheter shaft 602, extension legs 611, 612, and a connection hub 640. The long, insertable distal portion of the catheter shaft 602 (also referred to herein as the reduced-diameter portion 114 (see Figure 1 )) is substantially uniform along its entire length and may be trimmed to a desired length for accurate placement at a target region with the patient's anatomy. This region may include markings to assist in the accuracy of such trimming.

[0180] The extension legs 611, 612 each include extension tubes 613, 614, each of which is in fluid communication with a separate catheter shaft lumen. The extension legs 611, 612 also each include a female Luer connector 621, 622 at the proximal end of each extension tube 613, 614 and clamps 631, 632 disposed on each extension tube 613, 614. The connection hub 640 connects the extension legs 611, 612 to the catheter shaft 602. The engagement hub 640 is formed of two parts. Specifically, the engagement hub 640 includes an engagement core 642 (see Figure 8B ) and an engagement cover 644. In various embodiments, at least the catheter shaft 602, the extension legs 611, 612, the engagement core 642, and the engagement cover 644 are formed from embodiments of the silicified polycarbonate polyurethane disclosed herein. Any combination of the formulations of the silicified polycarbonate polyurethane disclosed herein is contemplated.

[0181] Figures 8A - 8C Stages of an exemplary method for assembling or manufacturing the PICC device 600 are shown. Prior to the Figure 8A stage shown, the Luer connectors 621, 622 are overmolded onto the proximal ends of the extension tubes 613, 614 using techniques and equipment commonly known in the art (e.g.), and the clamps 631, 632 may be advanced over the distal ends of the extension tubes 613, 614. As Figure 8A shown, core pins 651, 652 may be inserted through the extension tubes 613, 614 and into the corresponding lumens of the catheter shaft 602. The lumens are similar to the lumens 122, 124 of the catheter shaft 100, as Figure 2A and Figure 2B shown.

[0182] SeeFigure 8B The bonding core 642 can be overmolded onto the proximal end of the catheter shaft 602 and the distal ends of the extension tubes 613, 614. See Figure 8C Then, the connection cover 644 can be overmolded onto the bonding core 642, the proximal end of the catheter shaft 602, and the distal ends of the extension tubes 613, 614. Then, the core pins 651, 652 can be removed proximally through the extension tubes 613, 614, leaving fluid channels or passages 661, 662 through the bonding core 642, each of which fluidly connects one of the extension tubes 613, 614 to a corresponding one of the lumens in the catheter shaft 602.

[0183] Once the PICC device 600 has been formed, it includes two fluid paths 663, 664 along which fluid can be introduced into and / or removed from the patient. Fluid path 663 passes through the extension leg 611, the connection hub 640, and the catheter shaft 602. In other words, fluid path 663 includes the fluid channel through the connector 621, the lumen of the extension tube 613, the passage 661 through the connection hub 640, and one of the two lumens in the catheter shaft 602. Similarly, fluid path 664 passes through the extension leg 612, the connection hub 640, and the catheter shaft 602. In other words, fluid path 664 includes the fluid channel through the connector 622, the lumen of the extension tube 614, the passage 662 through the connection hub 640, and the other of the two lumens in the catheter shaft 602.

[0184] In some embodiments, a single-layer or single-trigger bonding hub 640 can alternatively be used. However, the double-layer or double-trigger bonding hub 640 of the present example may be advantageous for certain applications. For example, in some cases, such as in power injection applications, it may be desirable for the bonding core 642 to be significantly harder than the materials of the extension tubes 613, 614 and / or the catheter shaft 602. During power injection, the pressure can be elevated more towards the proximal region of the PICC device 600 and can decrease in the distal direction from a minimum at the distal end of the catheter shaft 602. The harder bonding core 642 can more easily withstand these elevated pressures in the proximal region and can be more resistant to swelling. Additionally, the harder bonding core 642 can be more resistant to alcohol exposure during an alcohol lock event.

[0185] In other cases, it may be desirable to include a softer engagement cover 644, particularly in cases where a hard engagement core 642 is used. The joint cover can make the joint 640 more comfortable for the patient. In some cases, this can have particular utility relative to a PICC catheter, where the patient can typically come into contact with the exposed joint 640 during an extended period of time during which a PICC is typically used. In some cases, the engagement cover 644 can be not only softer than the engagement core 642, but can also be softer than the extension tubes 613, 614 and / or the catheter shaft 602.

[0186] In some cases, the catheter shaft 602 and the extension tubes 613, 614 can be formed of the same material and / or can have the same hardness. For example, in some cases, the catheter shaft 602 and the extension tubes 613, 614 can be formed of a material having the same chemical formulation. In other cases, the material can be uncompounded with any additives or can be physically compounded with the same additives.

[0187] In other cases, the catheter shaft 602 and the extension tubes 613, 614 can be formed of different materials and / or can have different hardness values. For example, in some embodiments, the extension tubes 613, 614 can be formed of a silicated polycarbonate polyurethane that has a relatively greater proportion of hard segments compared to the silicated polycarbonate polyurethane forming the catheter shaft 602. Alternatively stated, the extension tubes 613, 614 can be formed of a silicated polycarbonate polyurethane that has a different chemical formulation compared to the silicated polycarbonate polyurethane forming the catheter shaft 602. In some cases, when a harder material is used for the extension tubes 613, 614, then, in some cases, the extension tubes can better withstand deformation from repeated and / or prolonged closure by the clamps 631, 632. In other or alternative embodiments, depending on the overall configuration of the PICC device 600 and / or the catheter shaft 602, the harder extension tubes 613, 614 can better tolerate elevated pressures compared to what the at least proximal end of the catheter shaft 602 may experience.

[0188] In some cases, the material of the catheter shaft 602 and the material of the extension tubes 613, 614 can vary with respect to the additives contained therein. For example, in some embodiments, the catheter shaft 602 can be compounded with one or more radiopaque agents, whereas the material of the extension tubes 613, 614 may not be compounded therewith. Additionally, one or more of the catheter shaft 602 and the extension tubes 613, 614 can be compounded with different types and / or amounts of colorants. For example, in some embodiments, the extension tubes 613, 614 and the catheter shaft 602 can be formed of a silicified polycarbonate polyurethane having the same chemical formulation but differing in the presence or absence of additives physically compounded therewith. In other cases, the chemical formulations of the silicified polycarbonate polyurethanes can be different, and in additional cases, these polyurethanes are physically compounded with different types and / or amounts of colorants and / or other additives.

[0189] In some cases, the extension tubes 613, 614 are formed of the same material, which may or may not be the same material as that used for the catheter shaft 602. In other embodiments, each extension tube 613, 614 is formed of a different material. For example, in some embodiments, one extension tube 613 is formed of a silicified polycarbonate polyurethane having a first chemical formulation, and the other extension tube 614 is formed of a silicified polycarbonate polyurethane having a second chemical formulation. In some cases, the first chemical formulation and the second chemical formulation are the same as each other, but the polyurethanes are physically compounded with different types and / or amounts of colorants and / or other additives. For example, the extension tubes 613, 614 can be differently colored to denote different functions or names of each extension tube 613, 614 (e.g., one extension tube 613, 614 can be designated for power injection, whereas the other may not be designated for power injection). In other cases, the first chemical formulation and the second chemical formulation can be different, and in additional cases, the polyurethanes are physically compounded with different types and / or amounts of colorants and / or other additives.

[0190] In the case where the bonding core 642 is joined to the catheter shaft 602 and the extension tubes 613, 614 by overmolding, as in the illustrated embodiment, it may be advantageous to ensure overmolding compatibility of the materials forming these components. Specifically, these materials should be able to bond firmly to each other during overmolding. In other words, when the molten bonding core 642 material is introduced around the ends of the catheter 602 and the extension tubes 613, 614 at an elevated temperature, the various materials in contact with each other should be able to flow together easily and harden into a strong bond upon cooling. For a catheter that can be power-injected, these bonds should be able to withstand high pressure, or in other words, the bonds should be leak-proof at the elevated pressures associated with power injection.

[0191] In some embodiments, the catheter shaft 602, extension tubes 613, 614, and engagement core 642 are formed of the same or different embodiments of the silicified polycarbonate polyurethane according to the present disclosure. For example, in some embodiments, the catheter shaft 602 and extension tubes 613, 614 may each comprise the same silicified polycarbonate polyurethane material, or in other words, the polyurethane component of each material may have the same chemical formulation. In additional embodiments, the silicified polycarbonate polyurethane of the catheter shaft 602 may be compounded with a radiopaque agent and a first amount of a colorant and optional other additives, whereas the same silicified polycarbonate polyurethane of the extension tubes 613, 614 may not be compounded with any radiopaque agent, but may be compounded with a second amount of a colorant and optional other additives. In various embodiments, the first and second amounts of the colorant may be different. For example, in some cases, the first amount of the colorant is greater than the second amount of the colorant, such that the catheter shaft 602 may be opaque, whereas the extension tubes 613, 614 may be transparent or translucent. In additional embodiments, different types of colorants may be used to achieve different hues.

[0192] In additional embodiments, the engagement core 642 is formed of a different embodiment of the silicified polycarbonate polyurethane according to the present disclosure. In other words, the silicified polycarbonate polyurethane of the engagement core 642 may have a chemical formulation different from that of one or more of the extension tubes 613, 614 and / or the catheter shaft 602. For example, the silicified polycarbonate polyurethane may have a higher hard segment content, or in other words, the isocyanate and chain extender may be present in a greater relative amount for the engagement core 642. In some embodiments, although the soft segments are thus present in a smaller amount for the engagement core 642, the relative content of the soft segments may be substantially the same as the relative content of the soft segments of the materials used for the catheter shaft 602 and extension tubes 613, 614. In other words, in the chemical formulations of different silicified polycarbonate polyurethanes, the weight percentage of the polysiloxane relative to the total weight of the polysiloxane and polycarbonate may be substantially the same. In various embodiments, the weight percentage of the polysiloxane relative to the soft component may vary between different materials by no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 1.5%, 2%, 3%, or 5%. In certain embodiments, a similar polysiloxane content relative to the soft segments may result in a strong and reliable bond between different silicified polycarbonate polyurethanes, such as may be particularly suitable for withstanding elevated pressures during power injection.

[0193] In additional embodiments, compared to embodiments that bond the core 642 and / or the catheter shaft 602 and one or more of the extension tubes 613, 614, the bonding cover 644 is formed from different embodiments of the silicopolycarbonate polyurethane according to the present disclosure. For example, the silicopolycarbonate polyurethane of the bonding cover 644 may have a lower hard segment content than each of the other silicopolycarbonate polyurethanes, or in other words, the isocyanate and chain extender may be present in relatively smaller amounts for the bonding cover 644. In some embodiments, although the soft segments are thus present in greater amounts, the relative content of the soft segments may be substantially the same as the relative content of the soft segments of the materials used for the bonding core 642, the catheter shaft 602, and / or the extension tubes 613, 614. In other words, in the formulations of the various silicopolycarbonate polyurethanes, the weight percentage of the polysiloxane relative to the total weight of the polysiloxane and polycarbonate may be substantially the same in the various materials. In various embodiments of the PICC device 600, the weight percentage of the polysiloxane relative to the soft components may differ by no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 1.5%, 2%, 3%, or 5% between any two different materials, and may differ by no more than about 0.1%, 0.2%, 0.3%, 0.4%, 0.5%, 0.75%, 1%, 1.5%, 2%, 3%, 5%, 7.5%, or 10% in all different materials. In certain embodiments, a similar polysiloxane content relative to the soft segments may result in a strong and reliable bond between different silicopolycarbonate polyurethanes, such as may be particularly suitable for withstanding elevated pressures during power injection. The bond may also ensure a reliable soft contact cover for the bonding core 642, which will remain reliably attached thereto.

[0194] In other or additional embodiments, the silicopolycarbonate polyurethanes of the various components (extension tubes, catheter shafts, bonding cores, and / or bonding covers) may also have a range of durometer values. In various examples, the silicopolycarbonate polyurethane of the catheter shaft may have a Shore A durometer value of about 65 to about 100, about 70 to about 90, about 75 to about <85>, about 91 to about 100, about 94 to about 98, about 96 to about 100, about 95 to about 99, about 96 to about 98, or about 97 to about 100 (including slightly deviating from the upper limit of the Shore A scale, or a hardness harder than 100). In other or additional examples, the silicopolycarbonate polyurethane of the bonding core may have a Shore D durometer value of about 15 to about 85, about 60 to about 80, or about 65 to about 75. In other or additional embodiments, the silicopolycarbonate polyurethane of the bonding cover may have a Shore A durometer value of about 65 to about 100, about 70 to about 90, about 75 to about 85, or about 90 to about 100.

[0195] In other or alternative embodiments, only a portion of one or more of the components comprises a silicated polycarbonate polyurethane. For example, in some embodiments, the catheter shaft 602 may generally be formed of a different material (e.g., a different type of polyurethane), and the inner surface of the lumen may be coated with a silicated polycarbonate polyurethane. In other or alternative embodiments, the catheter shaft 602 may be formed as a co-extrusion of a silicated polycarbonate polyurethane and a different type of polyurethane.

[0196] The Luer connectors 621, 622 may be formed of any suitable material and in some cases may be overmolded onto the proximal ends of the extension tubes 613, 614. In some embodiments, the connectors 621, 622 may be formed of a rigid thermoplastic polyurethane, such as those available from Biomerics The thermoformed bond between the connectors 621, 622 and the extension tubes 613, 614 may advantageously be strong enough to withstand the high pressures associated with power injection.

[0197] Example 6

[0198] In one example, the PICC device 600 includes a catheter shaft 602 in the same form as described above with respect to Example 2 Figure 1 and 2A as shown in FIGS. 2B. Specifically, referring to Figure 1 , the various dimensions of the catheter shaft 602 are as follows: L C is between 0.35 inches and 0.51 inches, L T is not greater than 2.0 inches (generally between 1.3 inches and 1.6 inches), and L E is approximately 22.4 inches (generally between 22.3 inches and 22.5 inches; i.e., approximately 57.0 cm, and generally between 56.8 cm and 57.2 cm). Referring to Figure 2A , the various dimensions of the connection region 110 are as follows: W SW1 is not less than 0.007 inches, W IW1 is not less than 0.007 inches, and OD1 is 0.092 inches (+0.002 / -0.003 inches). Referring to Figure 2B ， The various dimensions of the reduced diameter region 114 are as follows: W SW2 is not less than 0.004 inches (generally about 0.007 inches), W IW2 is not less than 0.005 inches, and OD2 is 0.069 inches (+0.002 / -0.003 inches).

[0199] The PICC device 600 also includes substantially identical extension tubes 613, 614, each of which defines a substantially cylindrical hollow tube having an inner diameter of 0.066 ± 0.002 inches and an outer diameter of 0.106 ± 0.003 inches. The extension tubes 613, 614 are initially extruded into long tubes, the long tubes are cut into lengths of 3.75 inches, and then overmolded at their proximal ends with Luer connectors 621, 622 and at their distal ends with mating cores 642. After overmolding, the exposed length ranges from 2.75 inches to 3.25 inches (typically 2.9 ± 0.03 inches).

[0200] The clamps 631, 632 are formed of rigid plastic. Each of the clamps 631, 632 includes a flexible latch arm through which selective opening and closing of the extension tubes 613, 614 is achieved. The clamps 631, 632 close the extension tubes 613, 614 by compressing and deforming the tubes to clamp them, and lock the clamps (in a selectively releasable manner) to hold the tubes in the deformed closed state.

[0201] The catheter shaft 602, the extension tubes 613, 614, the mating core 642, and the mating cover 644 are each formed of a material including an embodiment of a silicated polycarbonate polyurethane according to the present disclosure. The materials are prepared using the starting materials and methods described in Example 1 and, where applicable, the additional methods described in Example 2 above. However, GLYCOLUBE TM VL additive is added during polymerization but does not participate in the reaction. Instead, the additive is dispersed throughout the mixture during polymerization and is ultimately physically blended into the cured polymer. The materials used for the catheter shaft 602 and the extension tubes 613, 614 each include the silicated polycarbonate polyurethane identified as Sample 3 in Example 1 above. In addition, the material designated as Batch 3 in Example 2 above is used for the catheter shaft 602. The formulations of the materials are provided in Table 5 below.

[0202] Table 5

[0203]

[0204]

[0205] The following table 6 lists the various properties of the compounding materials determined in table 5. These properties are measured for a large number of materials that have not been extruded into a tube or shaft and have not been overmolded, or in other words, have not been formed into any of the PICC device components. For each property, testing is performed according to the ASTM standards determined in table 6. Although the measured values are not expressed with a specific level of uncertainty, it should be understood that there is at least some uncertainty in these values. Therefore, each value can be encompassed by a small range of values. In addition, a range of acceptable values for the raw materials is also possible, such that the accompanying ranges of the values measured in table 6 are also contemplated. For example, the concentration of barium sulfate can be present in an amount of 29.6 ± 2 wt%, and the amounts of the remaining components can be adjusted accordingly. In other words, in some cases, the target amount of barium sulfate (e.g., the amount shown for formulating the specifications of the final product) is 29.6 wt%, with a tolerance of ±2 wt%.

[0206] Table 6

[0207]

[0208]

[0209] Example 7

[0210] Assemble a first test group (group 1) of 40 PICC devices according to the specifications of Example 6 and then sterilize them via standard ethylene oxide sterilization techniques (referred to herein as sterilization conditioning). Then thermally condition the PICC devices according to standard ASTM D4332-14 at the following parameters: -18 ± 2 °C, at uncontrolled relative humidity, for a minimum of 72 hours; 23 °C ± 5 °C, at 50% relative humidity (RH) ± 10% RH, for a minimum of 12 hours; and 40 °C ± 2 °C, at 90% RH ± 5% RH, for a minimum of 72 hours. Subject the PICC devices to additional immersion conditioning, where they are immersed in a 0.9% saline solution maintained at a temperature of 37 ± 2 °C for a minimum of 2 hours. Test the catheter shafts of each such pre-conditioned device to determine the tensile strength, modulus, secant modulus, and elongation (peak force strain) of the device.

[0211] A second test group (Group 2) of 40 PICC devices was manufactured in the same manner as Group 1 and subjected to sterilization and heat conditioning, and then subjected to accelerated aging to achieve an equivalent of 6 months of natural aging (referred to herein as accelerated aging conditioning). The accelerated aging process consists of storing the PICC devices at 50 °C and ambient relative humidity for at least 28 days. As previously described, the aged devices were subjected to immersion conditioning. The catheter shafts of each device were tested to determine the tensile strength, modulus, secant modulus, and elongation (peak force strain) of the device. The results for Group 1 (identified as T = 0 to indicate lack of accelerated aging) and Group 2 (identified as T = 6Mo.AA to represent 6 months of accelerated aging) are provided in Table 7.

[0212] Table 7

[0213] Test Group Tensile Strength (lbf) Elastic Modulus (psi) Secant Modulus (psi) Elongation (%) 1:T＝0 8.5±0.4 1174±55 1268±59 267±15 2: T = 6Mo.AA 9.5±0.6 1311±67 1450±90 267±15

[0214] Example 8

[0215] A test group (Group 3) of 40 PICC devices according to the specifications of Example 6 was assembled, sterilized, and heat conditioned. Another test group (Group 4) was subjected to the same conditioning as Group 3 and additionally subjected to six months of accelerated aging conditioning.

[0216] Both Group 3 and Group 4 were subjected to immersion conditions and then locked with 70% ethanol for 60 minutes, with a tolerance of +15 / -0 minutes. Specifically, one of the female Luer connectors was coupled to a 10-mL syringe filled with 70% ethanol. The syringe was used to flush and perfuse one lumen of the catheter shaft with 70% ethanol. Without removing the syringe from the female Luer connector, the distal end of the catheter was folded and clamped with a long-tail clip to clamp the shaft closed. The syringe was then removed and immediately replaced with a male Luer lock cap. The long-tail clip was then removed from the distal end of the catheter shaft. The catheter was then immersed again in a 0.9% saline bath at 37 ± 2 °C for a period of 60 minutes (+15 / -0 minutes). The catheter was then removed again from the 0.9% saline bath. The male Luer lock cap was removed and immediately replaced with a 10 mL syringe filled with 0.9% saline at 37 ± 2 °C. The syringe was then used to flush the catheter shaft and subsequently removed. At the end of the ethanol lock and flush, each sample was placed back in the saline at 37 ± 2 °C for a 60-minute (+15 / -0 minutes) recovery period. Then, power injection of the test PICC devices was performed at the end of the recovery period, as described below.

[0217] One test procedure verified that the PICC devices met the power injection specifications in accordance with ISO 10555-1. These tests subjected the catheters to pressures equal to or higher than those they would observe under normal use conditions and confirmed their leak resistance or burst resistance after multiple rounds of power injection.

[0218] For the T = 0 samples (Group 3), power injection was performed using Visipaque heated to approximately 37°C and having a viscosity of 11.8 cP + / - 0.3 cP. If not within the range, deionized water or additional contrast agent (Visipaque) was added to adjust the viscosity range of the power injection fluid. For the 6-month AA samples (Group 4), power injection was performed using a glycerol solution heated to 37 ± 2°C and having a viscosity of 11.8 cP + / - 0.3 cP. Similarly, if the viscosity was not within the range, additional glycerol or deionized water was added to adjust the range.

[0219] Groups 3 and 4 were subjected to pre-conditioning as described above, including ethanol lock, followed by a recovery period of 60 minutes +15 / -0 minutes in a saline bath. At the end of the recovery period for each catheter, the catheter was removed from the saline bath and one of the Luer connectors was coupled to the power injection test device. The device then delivered 120 mL of a large dose of viscous fluid (11.8 cP + / - 0.3 cP solution, Visipaque for Group 3 or glycerol for Group 4) through a single lumen of the catheter at a rate of 5 mL / sec. The catheter was then separated from the device and returned to the 0.9% saline bath at 37°C and soaked overnight. At the end of each overnight soak period, each catheter was subjected to another ethanol lock, rinsing, a 60-minute +15 / -0 minute recovery period in the saline bath, followed immediately by a single power injection of 120 mL of the large dose of viscous fluid, and then returned to the bath for another overnight soak. This process was repeated for a total of ten days, resulting in a total of 800 power injections: 400 power injections for Group 3 (40 catheters for 10 days), and 400 power injections for Group 4 (40 catheters for 10 days). For each of the 800 power injections, no leakage or rupture events were observed (also discussed below with respect to Example 11).

[0220] Example 9

[0221] During power injection, no part of the implanted length of the catheter should swell by more than twice the catheter marked size (e.g., 5 French in this example). The degree of swelling exhibited by the catheter is directly related to pressure, wall thickness, and material modulus properties. Commercially available PICC devices that are power injectable, such as certain variants that have received FDA approval in the United States, have been determined to have acceptable OD swelling characteristics. For example, the 5 French Triple Lumen named by CR Bard The 5 French power injectable catheter sold by HF has been shown to have acceptable swelling characteristics under the pressure of power injection in clinical applications. The catheter is indicated for power injection up to 5 cc / sec (5 mL / sec). Therefore, regarding OD swelling, a comparison can be made between the test catheter of this embodiment and the 5FR PowerPICC HF.

[0222] When comparing the factors indicating OD swelling during injection, the following points can be noted: (1) The outer wall thickness of the test PICC device of the present invention is substantially the same as the power injectable outer wall of the 5FR TL PowerPICC HF, (2) Both catheters are of a trim-to-length design with an implanted length of 55 cm, (3) Both catheters are subjected to the operating pressure generated by the injection of up to 5 cc / sec of contrast agent, (4) Both catheters are made of compliant polyurethane material.

[0223] With similar design dimensions of lumen area, length, and wall thickness, and an injection pressure of up to 5 cc / sec for both, the factor that can cause different OD swelling properties between the 5FR TL PowerPICC HF and the sample of the present embodiment is the modulus. Therefore, a comparison of the modulus between the material of the 5FR TL PowerPICC HF and the material of the test PICC is sufficient to demonstrate the acceptable swelling performance of the test PICC. If the elastic modulus of the test catheter is greater than the elastic modulus of the Bard 5FR TL PowerPICC HF, the OD swelling of the test catheter will be acceptable for power injection.

[0224] Test the shafts of five test catheters and five 5FR TL PowerPICC HFs. The results are provided in Table 8 below.

[0225] Table 8

[0226] Catheter Shaft Elastic Modulus (psi) Secant Modulus (psi) Test PICC(5) 1219±37 1320±45 PowerPICC(5) 1007±51 1076±114

[0227] Based on the modulus results seen above, this test catheter should swell no more than the Bard 5FR TL PowerPICC HF and thus has an OD swelling suitable for power injection.

[0228] Example 10

[0229] Another test procedure evaluates the stability of the distal end of the catheter during power injection. A stable catheter tip during power injection is desirable because an oscillating tip can, for example, damage the vasculature. During power injection, a PICC line is vulnerable to unstable oscillations (also known as tip flutter), which can result in damage to the vasculature, tip displacement, and / or misalignment of the catheter. Tip flutter occurs when the thrust from the power injection exceeds the flexural stiffness within a section of tubing anchored at a single point.

[0230] Another test group (Group 5) of 40 PICC devices according to the specifications of Example 6 was assembled, sterilized, and subjected to heat and soak conditioning as described above. The stable length of the PICC device was then tested. The stable length is the length at which unstable oscillations of the cantilevered catheter will begin during power injection. Measuring the stable length of the catheter shaft or the length at which the unsupported cantilevered end of the shaft begins to flutter can provide important information about the likelihood of tip flutter and misalignment of the catheter tip when positioned within the patient's vasculature. Specifically, the greater the stable length, the less likely a particular catheter design will be to exhibit tip flutter.

[0231] The stable length test involves coupling one extension leg of the PICC device to a power injection device. The distal end of the catheter hub is then inserted through an elastomeric septum and advanced until the catheter shaft extends at least 15 centimeters in length from the septum. Thus, the distal length of the catheter hub is unsupported or is cantilevered from its contact with the septum. The distal end of the catheter hub and the septum are then immersed in a heating bath of deionized water maintained at a temperature of 37°C. Then, power injection of deionized water is delivered through the extension leg at a delivery rate of 5.8 mL / sec. The use of deionized water at a specific delivery rate achieves the same thrust at the distal end of the catheter as the contrast agent delivered at 5.0 mL / sec. As the power injection proceeds, the catheter shaft is slowly retracted through the septum to decrease the unsupported length of the catheter shaft until the catheter stops fluttering or oscillating. The unsupported length at which the oscillation stops is the stable length of the PICC device. Testing the Group 5 PICC devices in the manner described above showed an average stable length of the catheter shaft of 12.1 ± .4 centimeters.

[0232] The stable length is affected by the modulus, lumen area, and moment of inertia of the area, where larger values result in a greater stable length of the cantilevered tube (e.g., a cylindrical catheter shaft). Although there is no generally accepted minimum average stable length for a power-injectable catheter, as described above, the PICC device has a greater modulus when compared to the Bard 5FR TL PowerPICC HF catheter discussed in Example 9 above. Thus, the stable length of the Group 5 PICC devices is likely to exceed the stable length of the Bard 5FR TL PowerPICC HF catheter and further indicates the suitability of the PICC device for power injection.

[0233] Example 11

[0234] Multiple tests were conducted to confirm the strength and stability of the bonded portions of the components (which were previously described in detail). Some tests further confirmed the strength, alcohol resistance, and resilience of the silicified polycarbonate polyurethane components (specifically the catheter shaft and extension tube).

[0235] Some tests were performed on 40 PICC components in Test Group 1 and 40 PICC components in Test Group 2, as described in Example 7 above. As previously mentioned, the PICC components in Test Group 1 were subjected to sterilization and heat conditioning, and the PICC components in Test Group 2 were additionally subjected to six months of accelerated aging conditioning. Before testing, all PICC components were subjected to immersion conditioning.

[0236] For each PICC component in Groups 1 and 2, a portion of the catheter sleeve was cut and its tensile strength, modulus, and ultimate elongation were tested, as previously described in Example 7 and detailed in Table 7. Each PICC component was further cut into additional sheets for further tensile strength testing. Specifically, one of the extension legs was cut from each PICC component, leaving a partial component including the remaining extension leg, the connecting hub, and the proximal portion of the catheter shaft. Then, a female Luer connector was cut from each of the remaining extension legs such that the partial component included a portion of the extension tube at its proximal end and a portion of the catheter shaft at its distal end, where each of the extension tube and catheter shaft portions remained connected to the connecting hub.

[0237] Then the tensile strength of each partial component was tested. The extension tube portion was clamped in a first set of clamps, the catheter sleeve portion was clamped in a second set of clamps, and then one of the first set of clamps and the second set of clamps was pulled away from the other (e.g., in opposite directions) until failure occurred to determine the ultimate tensile strength of the component. This particularly tested the bond strength between the extension tube and the engagement hub and between the engagement hub and the catheter shaft. The results of this test were as follows:

[0238] Table 9

[0239]

[0240] For each extension leg cut from the PICC components in Groups 1 and 2, the Luer connector was fixed in a fixture held by a first set of clamps, and the extension tube was clamped in a second set of clamps. Then the Luer connector and the extension tube were pulled in opposite directions. This particularly tested the bond strength between the Luer fitting and the extension tube. The results were as follows:

[0241] Table 10

[0242]

[0243] In addition, leak tests were also performed, which demonstrated the strength of the overmolded bond. The tests confirmed that no water leaked from any of the bonds for a positive pressure of not less than 43.5 psi. Positive pressure tests using air at elevated pressures also confirmed the leak resistance and also implied that at lower levels of negative pressure (such as the negative pressure that would exist during aspiration), the bond prevents external air from being entrained into the PICC.

[0244] All samples passed the leak test in the dry state after sterilization (EO) and heat conditioning (TC). A total of 298 samples were leak tested under immersion conditions, of which 118 of the 298 samples were subjected to cyclic kink conditioning (described further below with respect to Example 12) before the leak test, and 40 of the 298 samples were subjected to 10 days of power injection and 10 days of EtOH lockup, as described above with respect to Example 8. All samples passed the ISO 10555-1 hydraulic leak test.

[0245] For PICC devices that underwent 6 months of accelerated aging conditioning, a total of 58 samples were tested under immersion conditions before the leak test, of which 40 of the 58 samples were subjected to 10 days of power injection and 10 days of EtOH lockup, as described above with respect to Example 8. All samples passed the ISO 10555-1 hydraulic leak test.

[0246] The hydraulic burst pressure of the components was also tested. The burst pressure was compared with the use pressure (i.e., the pressure encountered during power injection) to confirm that the highest use pressure during power injection encountered during the test was far below the burst pressure. In other words, the burst pressure exceeded the peak pressure (use pressure) present in the catheter under maximum flow conditions during power injection. That is, burst tests were performed to ensure that the PICC device could withstand extreme use and injection pressures at maximum flow rates. Table 11 summarizes the test data for the component burst pressures. The table identifies the various conditioning that the PICC devices in each test group underwent prior to testing. Specifically, in Table 11, "EO" indicates ethylene oxide sterilization, "TC" indicates temperature conditioning, and "immersion" indicates immersion conditioning, as previously described with respect to Example 7. In addition, the "10-day power injection" and "EtOH (ethanol) lockup" conditioning are as previously described with respect to Example 8. "Cyclic kink" is discussed below with respect to Example 12, and "lipid lock" is discussed below with respect to Example 13. Groups 3 and 4 in the last two columns of Table 11 are as previously described with respect to Example 8.

[0247] Table 11

[0248]

[0249]

[0250] For each set of conditioning, the PICC device (or more specifically, its fluid path) exhibits a high burst pressure, thus indicating their suitability for power injection even after an alcohol lock event. In fact, regardless of what pre-conditioning the fluid path of the PICC device undergoes (even including multiple ethanol lock events followed by a recovery period as described above), the PICC device can operate at pressures up to 180 psi, 190 psi, 200 psi, 210 psi, 220 psi, 230 psi, 240 psi, 250 psi, 260 psi, 270 psi, 280 psi or even 285 psi.

[0251] The use pressures during power injection are shown in Table 12 below. The use pressures (as measured daily) are plotted in Figure 9 and 10 In Figure 9 the graph 700 is a box plot of the data collected from 40 PICC devices in Group 3 of Example 8. In Figure 10 the graph 800 is a box plot of the data collected from 40 PICC devices in Group 4 of Example 8.

[0252] Table 12

[0253]

[0254] The use pressure is defined as the peak pressure encountered during power injection. As can be seen in each of Figure 9 and 10 the use pressure does not vary greatly from day to day. In fact, for test group 3 ( Figure 9 ), the difference between the maximum and minimum average use pressures is no more than 5%. For test group 4 ( Figure 10 ), the difference between the maximum and minimum average use pressures is no more than 1.5%. In various embodiments, the use pressure of the catheter from day to day (or in other words, after at least one overnight period including at least one alcohol lock and recovery period sequence) is no greater than for example 1%, 2%, 3%, 4%, 5% or 10%. Additionally, the use pressure does not show any appreciable degradation of the PICC device over time or due to repeated alcohol lock events and repeated power injections.

[0255] Table 13 below compares the burst pressures and use pressures (i.e., burst pressure - maximum use pressure) for two groups (Group 3 and Group 4).

[0256] Table 13

[0257]

[0258] Therefore, the burst pressure far exceeds the maximum service pressure encountered during testing. In most cases, the service pressure appears to be consistent and shows slightly higher pressure on the first day. Regardless of conditioning, the burst pressure remains consistent across all groups. When compared to the baseline burst of sterilization conditioning, heat conditioning, and soak conditioning, the mean and median burst values do not appear to be affected by power injection, ethanol lock, cyclic kinking conditioning (explained below), or 6-month accelerated aging. The PICC device is not adversely affected by the worst-case simulated service conditioning protocol.

[0259] Burst performance and acceptability were determined by subtracting the maximum service pressure observed in the catheter during 10 power injections from the burst values measured in the same catheter samples. A total of 40 data points were collected for distribution analysis and showed a normal distribution far above the acceptance criteria, with a mean difference of 86 psi for the T = 0 samples and a mean difference of 93 psi for the T = 6-month accelerated aging samples.

[0260] These test results demonstrate the ability of the PICC device to withstand extreme use, including 10 power injections at a maximum flow rate of 5 cc / sec, and prior to each such injection, performing an intraluminal ethanol lock for 1 hour (with a 1-hour recovery period). The PICC device is able to sustain use at the high pressures associated with power injection. For example, even after repeated ethanol lock events, the PICC device is able to maintain injection pressures up to 180 psi, 190 psi, 200 psi, 210 psi, 220 psi, 230 psi, 240 psi, 250 psi, 260 psi, or 270 psi without leakage or bursting.

[0261] In addition, it is well known that increasing catheter length increases operating pressure. Since the burst pressure of these 57.0-cm PICC devices is much higher than their service pressure, it should be possible to increase the length significantly beyond 57.0 cm, which may be beneficial for, e.g., larger patients (such as obese patients). In other words, this test demonstrates that in additional embodiments, PICC devices that can perform power injections before and after ethanol lock can have an effective length greater than 57 cm.

[0262] Example 12

[0263] The kink diameters of 40 PICC devices constructed according to Example 6 were measured and subjected to sterilization conditioning, heat conditioning, and soak conditioning as described in Example 7. The kink diameter is the diameter at which the catheter shaft will kink. That is, at the kink diameter and at diameters less than the kink diameter, the catheter shaft will kink, whereas the catheter shaft will not kink at diameters greater than the kink diameter. The results are provided in Table 14.

[0264] Table 14

[0265]

[0266] Testing of cyclic kinking was also performed. The purpose of this procedure was to simulate the stresses from extreme use in the clinic and to verify whether the catheter shaft could withstand the kinking that can occur during dressing changes. This test also demonstrated the flex fatigue tolerance since cyclic kinking conditioning applied both tensile and compressive stresses on the samples and simulated the device manipulation for an expected one-year use. At the catheter connection (i.e., at the location adjacent to the connection hub) near the zero mark, each of a set of 118 samples was kinked 365 times. After cyclic kinking, the samples were burst tested to evaluate any material damage.

[0267] Cyclic kinking was designed to simulate dressing changes during which the catheter can be manipulated and folded to clean the skin near the insertion site. This typically occurs near the zero mark toward the proximal end of the shaft tubing. Relative to PICC line maintenance, typical dressing changes occur every 7 days. This results in approximately 26 dressing changes over a six-month period and approximately 52 dressing changes over the course of a year. However, a “worst-case” assessment for a one-year period can be made by assuming daily line manipulation. Thus, cyclic kinking was performed for 365 cycles prior to evaluating the PICC line for leaks and ruptures.

[0268] In this procedure, the catheter shaft was folded at the location near the connection hub until kinking was observed. The catheter shaft was then unfolded back to the straight position. This process was repeated 365 times for each sample. Thereafter, the PICC assembly was tested for air leaks or hydraulic leaks at a minimum of 43.5 psi in the manner described previously. A sample size of 118 PICC devices was evaluated. All 118 samples passed the cyclic kinking test without any leaks.

[0269] The durability of the extension leg tubing was similarly evaluated. Prior to burst testing, each of a set of 40 samples of the extension leg was subjected to 1095 clamping cycles using a device thumb clamp.

[0270] The catheter durability test conditioned the extension leg with 1095 clamping cycles via the device thumb clamp. This conditioning exposed the test sample to typical handling for one year of use. Problematic leakage from the clamp conditioning was only possible when the clamp weakened the material to the point where the burst pressure dropped below the pressure used for power injection (5 cc / sec). The results of the extension leg burst test are provided in Table 15. The results clearly show that after clamp conditioning, the extension leg tubing was not damaged to below acceptable performance.

[0271] Table 15

[0272]

[0273] Example 13

[0274] PICC devices can be used to accommodate total parenteral nutrition (TPN) therapy and are thus exposed to a variety of chemical agents, including amino acids, sugars, lipids, and electrolytes. For example, PICC is often used with pediatric patients to whom TPN is administered via the PICC. This is the case for many conditions, including, for example, short bowel syndrome.

[0275] The most common parenteral nutrition fat source for lipid emulsions used in the United States is soybean oil. G.L. Fell et al., “Intravenous Lipid Emulsions in Parenteral Nutrition,” Adv Nutr, 2015. Additionally, commonly used fat emulsions (such as Intralipid, Omegaven, SMOFlipid, and Clinolipid) are supplied at lipid concentrations of 10% or 20% in the emulsion. Fell et al.

[0276] The adult patient dose of triglycerides consists of up to 3 g of triglycerides per kilogram of body weight per day. Baxter Healthcare CORP specifies that up to 70% of the maximum adult dose allowing supplementation of triglycerides with Intralipid 20% (20% soybean oil lipid emulsion). Assuming an average adult patient weight of 70 kg, the maximum daily dose of Intralipid 20% based on soybean oil would be 735 mL / day.

[0277] On average, acute care parenteral nutrition has a duration of 10 - 14 days. J. Mirtallo et al., “Safe Practices for Parenteral Nutrition,” Journal of Parenteral and Enteral Nutrition, Vol. 28, No. 6, 2004. The upper limit of the infusion rate of lipid emulsion is determined based on patient fat clearance and is set at a maximum of 500 mL every 5 hours in adult patients using Intralipid. Considering the maximum daily dose and maximum infusion rate, the PICC line will be exposed to 20% lipid emulsion (most likely soybean oil) for 7.35 hours per day and for a total of 102.9 hours over 14 days of parenteral nutrition.

[0278] A soybean oil concentration five times that of Intralipid 20% was used to establish the compatibility of the PICC device with the lipid. Thus, the exposure time was reduced by less than five times. Therefore, the intraluminal exposure of the PICC device to 100% soybean oil lasts at least 20 hours and 35 minutes.

[0279] To evaluate the effect of lipids on the properties of silicated polycarbonate polyurethane, a single lipid conditioning step was performed on the power injection samples prior to the first alcohol lock and power injection. Lipid conditioning consisted of locking the PICC samples with 100% soybean oil and soaking them in 0.9% saline for at least 20.58 hours. Burst testing was used to characterize any detrimental effects from lipid, ethanol, and power injection conditioning and to verify the functional ability after lipid conditioning.

[0280] The minimum duration of 20.58 hours of intraluminal exposure to 100% soybean oil provides clinically relevant conditions for evaluating the interaction of lipids with the silicated polycarbonate polyurethane material.

[0281] The conditioning was as follows. Using a 10 mL syringe, the lumen to be power injected was perfused with 100% soybean oil. Without removing the syringe from the Luer connector, the distal end of the catheter shaft was folded and clamped with a long - tail clip to clamp. The syringe was removed and immediately replaced with a male Luer lock cap. The sample was returned to a 0.9% saline immersion bath at 37°C. The sample was soaked while locked with soybean oil for at least 20 hours and 35 minutes. Prior to subsequent conditioning and testing, both lumens of each PICC device sample were rinsed with deionized water.

[0282] Regarding Tables 11, 12, and 13 and Figure 9The PICC devices of Group 3 in the graph 700, showing test results related to lipid pre-conditioning, as just described. For Group 3 that underwent lipid conditioning prior to all power injection tests, no leakage was observed during a total of 400 power injections. Additionally, all 40 test units passed the gas leakage test. Further, it should be noted that power injection was performed after lipid exposure, demonstrating that ethanol lock can be used to remove lipid occlusions in the PICC device.

[0283] Example 14

[0284] Multiple PICC devices according to Example 6 were manufactured and their biocompatibility was tested. The tests were conducted under the appropriate ISO 10993 standards (including ISO 10993-1:2009, -3:2014, -4:2009, -4:2017, -5, -6:2016, -10:2010, -11:2006, -12:2012, -17:2008, -17:2012, and -18:2013); ISO 14971:2007 / (R)2010; and the EU Medical Device Directive 93 / 42 / EEC. It was determined that the devices were non-cytotoxic, non-sensitizing, non-irritating, non-toxic, non-pyrogenic, and non-hemolytic; there was no statistical difference regarding the activation of the complement system compared to a reference commercially available PICC catheter (specifically, the above-mentioned 5 French, three-lumen PowerPICC HF), and it had a platelet aggregation time similar to that of the commercially available PICC catheter. The device was also determined to be non-thrombogenic via a dog thrombogenicity test. Overall, the PICC device was determined to be non-irritating and biocompatible.

[0285] Some of the sample PICC devices were subjected to extractable / leachable analysis according to ISO 10993-18:2013. The devices were extracted in triplicate by complete immersion in purified water and isopropyl alcohol (IPA) at 50 °C for 72 hours. The metals in the water extract were analyzed by inductively coupled plasma-mass spectrometry (ICP / MS) and cold vapor atomic absorption spectrometry (CVAAS), and the volatiles, semi-volatiles, and a limited group of non-volatile organic compounds in the water extract were analyzed by gas chromatography-mass spectrometry (GC / MS). The semi-volatile organic compounds in the IPA extract were analyzed by the GC / MS method. Using these analytical chemistry techniques, the extractable / leachable compounds were identified and quantified to determine the chemical dose to the user. The identified compounds were then evaluated in a toxicological risk assessment.

[0286] Specifically, a toxicological risk assessment was conducted on the following compounds identified in the chemical extractable / leachable tests: barium (CAS 7440-39-3) / barium sulfate (CAS 7727-43-7), boron, caprolactam (CAS 105-60-2), bis(2-ethylhexyl) phthalate (CAS 117-81-7), di-n-butyl phthalate (CAS 84-74-2), n-octadecane (CAS 593-45-3), silicon / silica, and strontium. The purpose of the risk assessment was to carefully examine the toxicological risks of the identified compounds and to evaluate and address any risks associated with the biological endpoints of subacute / subchronic and chronic toxicity, genotoxicity, and carcinogenicity in adult and pediatric populations. The tolerable intake (TI), tolerable exposure (TE), and margin of safety (MOS) were calculated in accordance with ISO 10993-17:2008: Biological evaluation of medical devices - Part 17: Establishment of allowable limits for leachable substances. A MOS greater than one indicates that the substance being evaluated has low toxicological risk. Based on the margin of safety calculated in the toxicological risk assessment, the likelihood of adverse effects from the device was considered low for all compounds. The assessment also indicated that subacute / subchronic and chronic toxicity, genotoxicity, and carcinogenicity due to the use of the device were not anticipated. Additionally, the results within the toxicological risk assessment demonstrated that the toxicological safety of the device was supported in neonates weighing as low as 2.3 kg (based on the lowest calculated MOS value for silicon / silica in neonates).

[0287] That is, the toxicological risk assessment tests demonstrated that the PICC device is safe in neonates weighing as low as 2.3 kg. Additionally, although the toxicological risk assessment tested for the presence of barium and barium sulfate (due to potential leaching of compounded barium sulfate from the catheter material), the safety limit was based on the lowest calculated MOS value for silicon / silica in neonates. This indicates that the catheter material performs well in retaining the compounded barium sulfate, or in other words, leaches this component (which constitutes 30% of the total weight of the material) in very small amounts.

[0288] These results are particularly impressive because the 5 French catheter was tested, for which there is significantly more material compared to smaller diameter (e.g., lower flow) catheters, and correspondingly, a larger surface area from which leaching can occur.

[0289] In addition, the silicon / silica leached from the test PICC device (which is the limiting leachate on which the 2.3 kg value is based) may be due to the presence of lubricants used during extrusion. As mentioned elsewhere herein, certain embodiments of silicated polycarbonate polyurethanes can be extruded in the absence of such lubricant additives. In other words, the silicated polycarbonate polyurethane forming one or more of the catheter shaft, the fitting hub, and / or the extension tube can be free of lubricant additives. In certain such embodiments, a 5 French PICC device containing, for example, up to 30 wt% barium sulfate can be safely used in neonates weighing less than 2.3 kg.

[0290] V. Additional Embodiments

[0291] Example 15

[0292] Three additional silicated polycarbonate polyurethanes were prepared, having different formulations and polymerization processes, and their hardnesses were evaluated. The test formulations and the hardness of each formulation are summarized in Table 16.

[0293] Table 16

[0294]

[0295]

[0296] For each of Test Formulations 1, 2, and 3, the polycarbonate polyol, the polysiloxane polyol, the isocyanate, and the chain extender were the same as those described above with respect to Example 1. In addition, as described with respect to Example 1, each reactant was preheated.

[0297] For Test Formulation 1, the preheated PHMCD, PDMS, and MDI were added to a common container and mixed for 5 minutes without separately controlling the heat. That is, the reaction was allowed to occur on its own, where the heat increased due to the exothermic nature of the reaction. Then the preheated BDO was added to the mixture, and the mixture was mixed for an additional approximately one minute.

[0298] Test Formulation 2 contains the same general composition as Test Formulation 1 but was prepared by a different method. Specifically, the preheated PDMS and MDI were added to a common container and mixed for 5 minutes. Then the preheated PHMCD was added to the mixture, and it was then mixed for an additional 5 minutes. Finally, the preheated BDO was added and the mixture was mixed for an additional approximately one minute.

[0299] Test formulation 3 contains a composition different from Test formulation 1 and is prepared via substantially the same method as that used for formulation 2. Specifically, preheated PDMS and MDI are added to a common container and mixed for 5 minutes. Then preheated PHMCD is added to the mixture, and it is then mixed for an additional 5 minutes. Finally, preheated BDO is added and the mixture is mixed for an additional approximately one minute.

[0300] For each of Test formulations 1, 2, and 3, at the completion of mixing, the mixture is poured onto a baking plate and cured overnight in an oven at 230°F. After curing, the material is removed from the baking plate and mechanically ground into particles with an average particle size of less than about 10 millimeters. The particles are then dried in a desiccant dryer and subsequently stored for later use. A quantity of the particles is then molded into test plates for hardness testing, and the test plates are evaluated using a Check-Line HPSA manual hardness tester in accordance with ASTM D2240.

[0301] Example 16

[0302] The test plates are molded from the silicated polycarbonate polyurethanes of each of Test formulations 1, 2, and 3 of Example 15 above. Smaller samples are cut from each of these test plates and soaked in 70% ethanol at 37°C for 46 hours. For each test formulation, the swelling (measured as % mass increase) of the silicated polycarbonate polyurethane samples is approximately 5 - 7%. This result is compared with the commercially available aromatic polyether polyurethane 2363 - 65D (which shows 16% swelling) and the commercially available aliphatic polyether polyurethane ALE (GFLEX - ALE - 91A - B30 - 003 - 002, which shows 41% swelling), as summarized in Table 17 below. Although Test formulations 1, 2, and 3 and PELLETHANE are formed directly into test plates without physical blending with other additives, the QUADRAFLEX material is blended with 30 wt% barium sulfate and a colorant.

[0303] Table 17

[0304] Materials % Swelling in 70% Ethanol Test Preparation 1 5.5 Test Preparation 2 5.5 Test Preparation 3 6.3 PELLETHANE 16.2 QUADRAFLEX 40.5

[0305] Although the swelling difference between Test Formulations 1 and 2 is small, other factors indicate that the "three-shot" method of Test Formulation 2 may be preferred for materials intended for use in PICC devices. For example, the moduli of Test Formulation 1 and 2 materials were each tested before and after ethanol exposure (70% EtOH), and although the moduli were very similar before exposure, the Formulation 2 material was slightly higher after exposure. In addition, molded test plates of both materials showed some delamination and debonding, which was slightly less apparent for the three-shot Test Formulation 2 material. Without being bound by theory, this would seem to indicate a better distribution of the PDMS material of Test Formulation 2.

[0306] Example 17

[0307] A PICC device having the components and physical dimensions shown in Example 6 above can be assembled from the formulation materials shown in Table 18 below. The method of forming such materials can be carried out, for example, in any of the ways disclosed herein. Some variability from the target values listed in Table 18 can be envisioned. For example, barium sulfate can be present in an amount of 30 ± 2 wt%, and the amounts of the remaining components can be adjusted accordingly. In other words, in some cases, the target amount of barium sulfate is 30 wt% with a tolerance of ±2 wt%.

[0308] Table 18

[0309]

[0310] Example 18

[0311] A PICC device having the components and physical dimensions shown in Example 6 above can be assembled from the formulation materials shown in Table 19 below. The method of forming such materials can be carried out, for example, in any of the ways disclosed herein. Some variability from the target values listed in Table 19 can be envisioned. For example, barium sulfate can be present in an amount of 30 ± 2 wt%, and the amounts of the remaining components can be adjusted accordingly. In other words, in some cases, the target amount of barium sulfate is 30 wt% with a tolerance of ±2 wt%.

[0312] Table 19

[0313]

[0314]

[0315] For the extrusion assemblies of this example and other extrusion assemblies disclosed herein, lubricants and / or mold release agents were omitted from the overall formulation of the material, such as Fumed silica and the like. Such omissions are also possible for molded parts. In other words, in some embodiments, no lubricant or mold release agent is added to the material during the polymerization stage, during compounding, and / or during extrusion or molding. Instead, the silicated polycarbonate polyurethane itself can be sufficiently lubricated or can achieve extrusion (e.g., pellets do not stick together and clog the hopper) or molding without the assistance of other materials.

[0316] This property of the material can be a significant advantage. Lubricants (including mold release agents) and / or other additives (such as nucleating agents) typically contribute to the toxicity and / or thrombogenicity of the extrudate or molded part. Therefore, eliminating such materials from, for example, a catheter shaft and / or from an extension tube can enhance the performance of the device (PICC, midline, PIV, etc.) formed therefrom in a patient's body.

[0317] By way of illustration, in Example 12 above, the PICC device for which a toxicological risk assessment was performed included in the extension tube and fumed silica in the extension tube and catheter shaft. Even with the use of these additives, the amount of leachate was very small, thus demonstrating that the material is advantageously resistant to leaching. In fact, the finding that a 5 French PICC device is suitable for use with neonates as small as 2.3 kg in body weight is very good. However, a limiting factor in the determination was the presence of silicon / silica. Omitting and fumed silica from the extruded material should make PICC devices of a similar configuration suitable for use with even smaller patients, or in other words, suitable for patients weighing less than 2.3 kg.

[0318] Example 19

[0319] To evaluate relative thrombus accumulation, fifteen (15) 5 French double-lumen catheter shafts having the dimensions and configuration described in Example 2 were extruded from the silicated polycarbonate polyurethane of the formulation shown in Table 20 below. The polycarbonate polyol, polysiloxane polyol, isocyanate, and chain extender, as well as the method of preparing the material, were the same as those described above with respect to Example 1. These are identified herein as Group I catheter shafts. For comparison, fifteen (15) 5 French double-lumen catheter shafts having the dimensions and configuration described in Example 2 were extruded from a material having approximately 69 wt% catheter-grade aliphatic polyether polyurethane, sold under the trade name Fifteen (15) commercially available 5 French double lumen power injectable PICC catheter assemblies (purchased from Teleflex, Wayne, Pennsylvania) were sold and fifteen (15) catheter shafts were cut, which are identified herein as Group III catheter shafts.

[0320] Table 20

[0321]

[0322] Notably, pyrogenic silica is not used in the formulation, or any other lubricant and / or demolding agent. As previously mentioned, such materials can increase the thrombogenicity of the extrudate or molded component. Therefore, omitting such materials from the formulation can enhance the antithrombotic properties (e.g., reduce thrombogenicity) of the medical devices (PICC, midline, PIV, any suitable type of implant, etc.) formed therefrom in a patient's body.

[0323] A total of 15 blood circulation experiments were conducted. In each experiment, three blood circulation test circuits were used, each of which included a water bath at 37°C, a container positioned in the water bath containing fresh heparinized bovine blood and autologous radiolabeled platelets, and a portion of tubing having opposite ends inserted into the bovine blood and passing through a roller pump to continuously pass the blood through the middle portion of the tubing. In each test circuit, the end of the catheter shaft was inserted to allow blood to flow around the outer surface of the shaft, thus simulating the insertion of the catheter within the patient's vasculature. The insertion tip of the catheter shaft sample was sealed with epoxy resin to eliminate lumen blood entry and focus the study on the outer surface of the catheter. Each test circuit accommodated a sample from Group I, Group II, or Group III. At the end of each experiment, the catheter shaft was removed from the tubing, rinsed with saline, and placed in a gamma counter for thrombus quantification.

[0324] Each experiment consisted of three independent blood circulation test circuits (each corresponding to one of Group I, Group II, or Group III), with each circulating blood from the same animal. This enabled simultaneous comparison without cross-effects. Blood from fifteen (15) different animals was tested.

[0325] The experimental parameters are shown in Table 21.

[0326] Table 21

[0327]

[0328] *Blood from different animals was used in each repeat (i.e., a unique blood batch was used in each repeat).

[0329] The raw data from 15 experiments are provided in Table 22.

[0330] Table 22

[0331]

[0332]

[0333] The distributions of all groups were non - normal. Due to the inherent blood differences between experiments, the variability of the study was high. However, this variability was determined to be appropriate as it would also be expected in the case between human patients. In Figure 11 Figure 900 compares the results of Group II and Group III within each experiment with the results of Group I.

[0334] The percentage increase evaluated relative to Group I at the experiment level showed that Group II had on average 300% more thrombus accumulation and Group III had on average 227% more thrombus accumulation. Additionally, when comparing the means and medians of Group I and Group II, statistical significance was found. Due to the distribution deviation and outliers, it may be advantageous to use non - parametric tests. Since the data were paired, the two - sample two - tailed Wilcoxon signed - rank test could be used to confirm that the distribution of Group I was significantly lower than that of Group II (p - value = 0.015), where Group II reported a median 88% larger than the median of Group I. Group III reported a 17% median increase when compared to the median of Group I; however, the distribution of Group I was not significantly lower than that of Group III (p - value = 0.71).

[0335] Therefore, in the foregoing in vitro blood circuit study evaluating thrombus accumulation, the catheter shaft of Group I formed from silicated polycarbonate polyurethane according to one embodiment of the present disclosure is superior to the catheter shafts of Group II (which are widely used in known commercially available power - injectable PICCs) and the catheter shafts of Group III. Statistical significance was shown in the median comparison between Group I and Group II, where the Group I shaft recorded a lower median of thrombus accumulation. Based on these results, it is expected that the catheter (Group I) formed from silicated polycarbonate polyurethane of the formulation shown in Table 20 will have less thrombus accumulation in clinical use compared to competing PICC products (Group II) that employ at least shafts (such as those formed). Additionally, the thrombus accumulation performance of Group I is at least as good as that of the commercially available power - injectable PICC products associated with Group III.

[0336] Example 20

[0337] To evaluate surface energy, four (4) 5 French double lumen catheter shafts having the dimensions and construction described in Example 2 were extruded from the silicated polycarbonate polyurethane (SPCPU) of the formulation shown in Table 20 above. Thus, the SPCPU catheter shafts were substantially the same as those of Group I in Example 19. Additionally, a commercially available 5 French catheter was obtained.

[0338] Testing of the catheter shafts was performed as follows. A catheter body sample was fixed to a horizontal stage located within the field of view of a microscope camera. A drop of water was deposited onto the surface of the catheter body sample in a sessile drop arrangement. An enlarged image of the sessile drop was captured for measurement analysis. The drops were deposited and measured at three or four different locations along each catheter body. The contact angle was determined by measuring the angle formed between the liquid-solid interface and the liquid-vapor interface. The test results are provided in Table 23.

[0339] Table 23

[0340]

[0341] The average contact angle of the SPCPU catheter body was 74.6 degrees with a standard deviation of 11.3, and the average contact angle of the catheter body was 99 degrees with a standard deviation of 4.9. Based on the above results, the SPCPU surface appears to be less hydrophobic, which is believed to indicate a greater surface free energy. In fact, it is said that it is much more difficult to keep a drop of water on the small tube surface of the device than on the SPCPU tube. Many water drops drip from the surface, such that the values shown in Table 23 may be at the lower end of the actual population distribution. In contrast, it is relatively easy to place a drop of water on the SPCPU tube, which appears to correspond well to the smaller contact angle data shown in Table 23.

[0342] According to Xu et al., Proteins, Platelets, and Blood Coagulation at Biomaterial Interfaces, Colloids Suf B Biointerfaces, December 1, 2014, 124:49-68, the surface energy of a biomaterial can play an important role in the extent to which the biomaterial activates thrombosis. The process of thrombosis associated with a biomaterial consists of both platelet-mediated reactions (platelet adhesion, activation, and aggregation) and plasma coagulation. The interaction of plasma proteins with the surface triggers the blood coagulation cascade, leading to the production of thrombi and the formation of fibrin clots. Coagulation involves a series of self-amplifying zymogen-enzyme conversions, which are traditionally grouped into the intrinsic pathway and the extrinsic pathway.

[0343] Xu et al. noted that the initiation of the intrinsic pathway, often referred to as contact activation, mainly involves coagulation factor XII (FXII, Hageman factor) and three other proteins. Traditional biochemistry of contact activation shows that FXII is converted into the active enzyme form FXIIa, which can be generated through at least three different biochemical reactions. One of these reactions is called contact autoactivation, in which FXII interacts with a procoagulant surface and, due to conformational structural changes after FXII binds to the surface, is converted into the active enzyme form FXIIa through autoactivation. Then, this conversion leads to subsequent coagulation cascades.

[0344] Xu et al. claimed that FXII contact activation is surface-dependent. Without being bound by theory, it is believed that the surface energy or wettability of a biomaterial can have a significant impact on the degree to which the biomaterial causes contact activation of FXII. Since common observations clearly show that plasma clotting is more effectively activated by contact with anionic or hydrophilic surfaces, based on traditional biochemical theory, it was once concluded that the contact autoactivation of FXII is more specific for hydrophilic surfaces than for hydrophobic surfaces. However, experimental evidence has shown that hydrophobic and hydrophilic surfaces have almost equal autoactivation properties in a pure buffer solution of FXII. That is, the contact activation of FXII is not specific for anionic hydrophilic surfaces in a pure buffer solution. In fact, when scaled according to surface energy, the contact activation of FXII in a pure buffer solution exhibits a roughly parabolic profile. Almost equal activation is observed at both extremes of factor water wettability (e.g., non-wetting and fully wetting), and the minimum range is found when the water contact angle θ is in the range of about 55 degrees to about 75 degrees. Relatively low activation also exists just outside either end of the aforementioned range. The contact angle range corresponds to a surface energy τ in the range of about 20 dyn / cm (at θ = about 75 degrees) to about 40 dyn / cm (at θ = about 55 degrees), and the energy just outside either end of this range also exhibits relatively low activation.

[0345] Thus, biomaterials exhibiting a water contact angle θ in the range of from about 55 degrees to about 75 degrees, or even from about 50 degrees to about 80 degrees, can exhibit excellent antithrombogenic properties because they are less prone to activate thrombosis. This corresponds to the observations of the catheter shafts in Examples 20 and 19 of the present invention (described above). Specifically, under the given experimental conditions, the average contact angle of the SPCPU catheter body of Example 20 of the present invention (which is formed identically to the catheter shaft of Example 19) was 74.6 degrees. This falls within the 55-degree to 75-degree water contact angle range for minimal FXII contact activation as confirmed by Xu et al. Without being bound by theory, the surface energy of the catheter shafts in Group I can at least partially explain the reduction in thrombus formation. In addition, it has been observed that hydrophilic surfaces lacking ionic charges and lacking strong hydrogen bonding groups can be desirable for minimizing platelet activation. See Griggs et al., Thrombosis and Thromboembolism Associated with Intravascular Catheter Biomaterials, Medical Device Evaluation Center, Salt Lake City, Utah, U.S.A., May 20, 2008; see also, Samuel Eric Wilson, Vascular Access: Principles and Practice, page 60.

[0346] In various embodiments, a catheter body formed of any of the various embodiments of the silicated polycarbonate polyurethanes disclosed herein may exhibit a water contact angle in the following ranges: from about 55 degrees to about 75 degrees, from about 55 degrees to about 70 degrees, from about 55 degrees to about 65 degrees, from about 55 degrees to about 60 degrees, from about 60 degrees to about 75 degrees, from about 60 degrees to about 70 degrees, from about 60 degrees to about 65 degrees, from about 65 degrees to about 75 degrees, from about 65 degrees to about 70 degrees, from about 70 degrees to about 75 degrees, from about 50 degrees to about 80 degrees, from about 50 degrees to about 65 degrees, from about 50 degrees to about 60 degrees, from about 50 degrees to about 55 degrees, from about 65 degrees to about 80 degrees, from about 70 degrees to about 80 degrees, or from about 75 degrees to about 80 degrees, or about 50 degrees, about 55 degrees, about 60 degrees, about 65 degrees, about 70 degrees, about 75 degrees, or about 80 degrees. In various embodiments, a catheter body formed of the various embodiments of the silicated polycarbonate polyurethanes disclosed herein may have a surface energy in the following ranges: from about 20 dyn / cm to about 40 dyn / cm, from about 20 dyn / cm to about 35 dyn / cm, from about 20 dyn / cm to about 30 dyn / cm, from about 20 dyn / cm to about 25 dyn / cm, from about 25 dyn / cm to about 40 dyn / cm, from about 25 dyn / cm to about 35 dyn / cm, from about 25 dyn / cm to about 30 dyn / cm, from about 30 dyn / cm to about 40 dyn / cm, from about 30 dyn / cm to about 35 dyn / cm, or from about 35 dyn / cm to about 40 dyn / cm, from about 15 dyn / cm to about 45 dyn / cm, from about 15 dyn / cm to about 30 dyn / cm, from about 15 dyn / cm to about 25 dyn / cm, from about 15 dyn / cm to about 20 dyn / cm, from about 30 dyn / cm to about 45 dyn / cm, from about 35 dyn / cm to about 45 dyn / cm, or from about 40 dyn / cm to about 45 dyn / cm, or about 15 dyn / cm, 20 dyn / cm, 25 dyn / cm, 30 dyn / cm, 35 dyn / cm, 40 dyn / cm, or 45 dyn / cm. In various embodiments of the foregoing embodiments, the catheter tubing may have an outer diameter of 4 French, 5 French or 6 French. Additionally, in various of the above embodiments, the silicated polycarbonate polyurethane material may be free of additive lubricants, release agents, nucleating agents, etc. (e.g., pyrogenic silica), which may otherwise result in greater thrombus formation. In various of the foregoing embodiments, the catheter shaft may be incorporated into a catheter assembly such as previously described, which catheter assembly may be used as a PICC catheter, or in other cases, may be used as a power injectable PICC catheter such as previously described. In other cases, the catheter (e.g., power injectable PICC) may be ethanol lock resistant or compatible, such as previously described.

[0347] As will be apparent from the foregoing disclosure, including various combinations or compilations of the foregoing embodiments, certain materials described herein are extremely well-suited for medical devices, and in particular, power injectable PICCs. Specifically, the inventors have found that certain types of polycarbonate polyols, polysiloxanes, and isocyanates can react in a specific manner, including in relative amounts that fall within very specific ranges, to achieve a silicated polycarbonate polyurethane that simultaneously meets many performance goals of a power injectable PICC. Certain properties exhibited by the resulting materials are even unexpected.

[0348] A PICC formed from such materials is advantageously capable of repeated operation at elevated power injection pressures without performance degradation. Thus, the material is robust and elastic. In addition, the PICC is capable of repeated ethanol or alcohol locking. The PICC also exhibits impressive antithrombogenicity, which may be caused at least in part by having a surface energy that appears to fall within the desired or expected range for the inactivation of factor XII. In addition, the extent to which the PICC prevents leaching is such that even relatively large diameter PICCs are suitable for very small pediatric patients, including neonates as low as 2.3 kg in some cases, and in other cases, even smaller or lighter patients.

[0349] In some embodiments, a PICC device, such as any of those described above, is included in a kit. In addition to the PICC device, the kit may also include a guidewire. The kit may include instructions for use, which may provide instructions on any of the methods disclosed herein. The instructions for use may specifically recommend or direct the user to employ alcohol locking, as described herein. For example, in the case of infection and / or lipid occlusion, the instructions may direct alcohol locking for a clinically effective period sufficient to resolve the problem, including any of those previously disclosed (e.g., one hour), and may also instruct the user to wait a recovery period, including any of those previously disclosed (e.g., one hour), prior to power injection via the catheter, for example. In various embodiments, the kit (and, specifically, its instructions for use) may be approved or authorized by a regulatory agency in a particular jurisdiction. For example, the kit and its instructions for use may be approved or authorized by the Food and Drug Administration in the United States and / or may comply with the regulations of other jurisdictions, such as obtaining CE marking certification in the European Union.

[0350] In certain embodiments discussed above, a clinically effective treatment period for alcohol lock was discussed as one hour (e.g., 60 minutes + 15 / -0 minutes) and a recovery period as one hour (e.g., 60 minutes + 15 / -0 minutes). Other suitable time periods are conceivable. For example, in various embodiments, the alcohol lock can be carried out for a clinically effective treatment period of at least about 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, or 60 minutes. In other or additional embodiments, the PICC device can be adapted for use after a recovery period of at least about 10 minutes, 15 minutes, 20 minutes, 25 minutes, 30 minutes, 35 minutes, 40 minutes, 45 minutes, 50 minutes, 55 minutes, or 60 minutes after such an alcohol lock event (e.g., after the alcohol has been flushed from the device).

[0351] Although much of the foregoing discussion has been dedicated to catheters and, specifically, PICC catheters, the materials and other teachings of the present disclosure are more generally applicable. For example, these can be adapted for or applied to a variety of other medical devices and catheters. The medical device or its components can be formed at least in part from one of a variety of materials. The medical device can include, for example, any suitable kind of medical catheter, vascular access device, central access device, midline catheter, IV catheter, implantable port, and the like. For example, any one of a variety of medical devices that are not catheters can be manufactured from any of the materials disclosed herein, including in any of the embodiments or in any other part of the present disclosure.

[0352] Any method disclosed herein includes one or more steps or actions for performing the method. Method steps and / or actions can be interchanged with one another. In other words, unless the correct operation of an embodiment requires a particular order of steps or actions, the order and / or use of particular steps and / or actions can be modified.

[0353] The claims that follow this written disclosure are hereby expressly incorporated into this written disclosure, with each claim standing alone as a separate embodiment. This disclosure includes all permutations and combinations of the independent claims and their dependent claims. In addition, additional embodiments that can be derived from the following independent and dependent claims are expressly incorporated into the written description of the invention. These additional embodiments are determined by replacing the dependency of a given dependent claim with the phrase "any of the preceding claims up to and including claim [x]", where the bracketed term "[x]" is replaced by the number of the most recently cited independent claim. For example, for the first set of claims starting with independent claim 1, claim 3 can depend on either of claims 1 and 2, where these individual dependencies result in two different embodiments; claim 4 can depend on any of claims 1, 2, or 3, where these individual dependencies result in three different embodiments; claim 5 can depend on any of claims 1, 2, 3, or 4, where these individual dependencies result in four different embodiments; and so on. The same holds for the following examples:

[0354] Examples 21 - 215

[0355] 21. An alcohol-resistant silylated polycarbonate polyurethane, comprising:

[0356] a soft segment comprising a polycarbonate polyol and a polysiloxane, wherein the polycarbonate polyol is present in an amount greater than or equal to the amount of the polysiloxane; and

[0357] a hard segment comprising an isocyanate and a chain extender.

[0358] 22. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 21, wherein the silylated polycarbonate polyurethane has a weight average molecular weight (Mw) of 50,000 g / mol to 300,000 g / mol.

[0359] 23. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 21, wherein the soft segment comprises 50 wt% to 98 wt% of the polycarbonate polyol.

[0360] 24. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 21, wherein the polycarbonate polyol has a structure according to formula (I):

[0361]

[0362] wherein R is selected from linear or branched, substituted or unsubstituted C1-C 24 alkyl or alkylene groups, A is selected from hydrogen and R'OH, and n is an integer from 2 to 30.

[0363] 25. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 24, wherein R and R' are independently selected from linear or branched C4-C 12 alkyl groups.

[0364] 26. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 21, wherein the polycarbonate polyol has a number average molecular weight (M n ) of 500 g / mol to 5000 g / mol.

[0365] 27. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 21, wherein the polysiloxane has a structure according to formula (IV):

[0366]

[0367] wherein R1 and R2 are independently selected from linear C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C 12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30.

[0368] 28. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 27, wherein R3 and R5 are independently selected from C1-C8 alkyl or alkylene groups.

[0369] 29. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 27, wherein R4 and R6 are independently selected from C1-C4 alkyl or alkylene groups.

[0370] 30. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 21, wherein the polysiloxane has a number average molecular weight (M n ) of 300 g / mol to 3000 g / mol.

[0371] 31. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 21, wherein the soft segment contains 2 wt% to 50 wt% of polysiloxane.

[0372] 32. The alcohol-resistant silylated polycarbonate polyurethane according to claim 21, wherein the polycarbonate polyol and the polysiloxane are present in a weight ratio of 20:1 to 1:1.

[0373] 33. The alcohol-resistant silylated polycarbonate polyurethane according to embodiment 21, wherein the silylated polycarbonate polyurethane contains 30 wt% to 80 wt% of soft segments.

[0374] 34. The alcohol-resistant silicated polycarbonate polyurethane according to Embodiment 21, wherein the silicated polycarbonate polyurethane contains 10% to 60% by weight of hard segments.

[0375] 35. The alcohol-resistant silicated polycarbonate polyurethane according to Embodiment 21, wherein the isocyanate is a member selected from the following: 4,4'-methylenediphenyl diisocyanate, dibenzylidene diisocyanate, methylenebis(cyclohexyl isocyanate), p-phenylene diisocyanate, trans-cyclohexane-1,4-diisocyanate, 1,6-diisocyanatohexane, 1,5-naphthalene diisocyanate, p-tetramethylxylene diisocyanate, m-tetramethylxylene diisocyanate, 2,4-toluene diisocyanate, isophorone diisocyanate, and combinations thereof.

[0376] 36. The alcohol-resistant silicated polycarbonate polyurethane according to Embodiment 21, wherein the hard segments contain 50% to 90% by weight of isocyanate.

[0377] 37. The alcohol-resistant silicated polycarbonate polyurethane according to Embodiment 21, wherein the chain extender is a member selected from the following: 1,2-propanediol, 1,3-propanediol, 2,2-dimethylpropane-1,3-diol, 2-ethyl-2-(hydroxymethyl)propane-1,3-diol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, 1,11-undecanediol, 1,12-dodecanediol, 1,4-cyclohexanediol, 1,4-cyclohexanedimethanol, 1,4-bis(2-hydroxyethoxy)benzene, p-xylene glycol, 1,3-bis(4-hydroxybutyl)tetramethyldisiloxane, 1,3-bis(6-hydroxyethoxypropyl)tetramethyldisiloxane, trimethylolpropane, and combinations thereof.

[0378] 38. The alcohol-resistant silicated polycarbonate polyurethane according to Embodiment 21, wherein the hard segments contain 10% to 50% by weight of the chain extender.

[0379] 39. The alcohol-resistant silicated polycarbonate polyurethane according to Embodiment 21, wherein the isocyanate and the chain extender are present in a weight ratio of 10:1 to 1:1.

[0380] 40. The alcohol-resistant silicated polycarbonate polyurethane according to Embodiment 21, which further comprises additives selected from: radiopaque agents, lubricants, catalysts, antioxidants, free radical inhibitors, colorants, fillers, and combinations thereof.

[0381] 41. The alcohol-resistant silicated polycarbonate polyurethane according to Embodiment 21, wherein the silicated polycarbonate polyurethane has an isocyanate index of 0.98 to 1.10.

[0382] 42. The alcohol-resistant silicated polycarbonate polyurethane according to Embodiment 21, wherein the silicated polycarbonate polyurethane has a Shore A durometer value of about 65 to about 100.

[0383] 43. A medical device, the medical device comprising one or more components, each of the one or more components being formed at least in part from the alcohol-resistant silicated polycarbonate polyurethane according to one or more of Embodiments 21 to 42.

[0384] 44. The medical device according to Embodiment 43, wherein the medical device comprises a catheter.

[0385] 45. The medical device according to Embodiment 43, wherein the medical device comprises a peripherally inserted central catheter (PICC) device.

[0386] 46. The medical device according to Embodiment 45, wherein the PICC device comprises at least one fluid path that can be power-injected.

[0387] 47. The medical device according to Embodiment 46, wherein after (1) having undergone an ethanol lock event and for a period sufficient to disinfect the at least one fluid path and (2) having been flushed and allowed to recover for a recovery period after the ethanol lock event, the at least one fluid path of the PICC device is power-injectable.

[0388] 48. The medical device according to Embodiment 47, wherein the recovery period is not less than one hour.

[0389] 49. The medical device according to Embodiment 45, wherein the PICC device comprises at least one fluid path that can maintain an injection pressure of up to 180 psi without bursting or leaking.

[0390] 50. The medical device according to Embodiment 49, wherein the at least one fluid path comprises the lumen of an extension tube, the passage through a connection hub, and the lumen of a catheter shaft, the connection hub being coupled to the distal end of the extension tube and to the proximal end of the catheter shaft.

[0391] 51. The medical device according to Embodiment 50, wherein the connection hub is overmolded onto the extension tube and the catheter shaft.

[0392] 52. The medical device according to embodiment 51, wherein the extension tube, the connection hub, and the catheter shaft each comprise alcohol-resistant silicated polycarbonate polyurethane, the alcohol-resistant silicated polycarbonate polyurethane comprising soft segments, the soft segments comprising polycarbonate polyol and polysiloxane, wherein each soft segment comprises from 5 wt% to 15 wt% of polysiloxane.

[0393] 53. The medical device according to embodiment 52, wherein the alcohol-resistant silicated polycarbonate polyurethane of the connection hub is harder than the alcohol-resistant silicated polycarbonate polyurethanes of the extension tube and the catheter shaft.

[0394] 54. The medical device according to embodiment 52, wherein the alcohol-resistant silicated polycarbonate polyurethane of the extension tube is different from the alcohol-resistant silicated polycarbonate polyurethane of the catheter shaft.

[0395] 55. The medical device according to embodiment 54, wherein the alcohol-resistant silicated polycarbonate polyurethane of the catheter shaft is compounded with a radiopaque agent, whereas the alcohol-resistant silicated polycarbonate polyurethane of the extension tube is not compounded with a radiopaque agent.

[0396] 56. The medical device according to embodiment 55, wherein the alcohol-resistant silicated polycarbonate polyurethanes of the catheter shaft and the extension tube have the same chemical formulation.

[0397] 57. The medical device according to embodiment 44, wherein the catheter comprises a surface energy in the range of from about 15 dyn / cm to about 45 dyn / cm.

[0398] 58. The medical device according to embodiment 57, wherein the surface energy is in the range of from about 15 dyn / cm to about 30 dyn / cm.

[0399] 59. The medical device according to embodiment 58, wherein the surface energy is in the range of from about 20 dyn / cm to about 30 dyn / cm.

[0400] 60. The medical device according to embodiment 44, wherein the catheter exhibits a water contact angle in the range of from about 50 degrees to about 80 degrees.

[0401] 61. The medical device according to embodiment 60, wherein the catheter exhibits a water contact angle in the range of from about 70 degrees to about 80 degrees.

[0402] 62. The medical device according to embodiment 44, wherein the catheter does not contain fumed silica.

[0403] 63. The medical device according to embodiment 44, wherein the catheter does not contain a lubricant additive.

[0404] 64. A method for preparing a silicated polycarbonate polyurethane, the method comprising:

[0405] Mixing a polycarbonate polyol, a polysiloxane, an isocyanate, and a chain extender to prepare a silicated polycarbonate polyurethane, wherein the polycarbonate polyol is present in an amount greater than or equal to the amount of the polysiloxane.

[0406] 65. The method according to embodiment 64, wherein the polycarbonate polyol, the polysiloxane, the isocyanate, and the chain extender are mixed at a temperature of 120°F to 230°F.

[0407] 66. The method according to embodiment 64, wherein the polysiloxane and the polycarbonate polyol are mixed before adding the isocyanate and the chain extender.

[0408] 67. The method according to embodiment 64, wherein the polysiloxane and the isocyanate are mixed before adding the polycarbonate polyol and the chain extender.

[0409] 68. The method according to embodiment 67, wherein the polysiloxane and the isocyanate are mixed and maintained for a period of 2 minutes to 30 minutes before adding the polycarbonate polyol, the chain extender, or both.

[0410] 69. The method according to embodiment 68, wherein the polycarbonate polyol is added to the mixture of the polysiloxane and the isocyanate before adding the chain extender.

[0411] 70. The method according to embodiment 69, wherein the combination of the polysiloxane, the isocyanate, and the polycarbonate polyol is mixed and maintained for a period of 2 minutes to 30 minutes before adding the chain extender.

[0412] 71. The method according to embodiment 70, wherein the combination of the polysiloxane, the isocyanate, the polycarbonate polyol, and the chain extender is further mixed and maintained for a period of about 30 seconds to 15 minutes.

[0413] 72. The method according to embodiment 64, further comprising mixing a lubricant with the polycarbonate polyol, the polysiloxane, the isocyanate, and the chain extender to prepare a silicated polycarbonate polyurethane.

[0414] 73. The method according to embodiment 64, further comprising curing the combination of the polysiloxane, the isocyanate, the polycarbonate polyol, and the chain extender at a temperature of 210°F to 250°F for a period of 12 hours to 36 hours to prepare a cured silicated polycarbonate polyurethane.

[0415] 74. The method according to embodiment 73, further comprising granulating the cured silicated polycarbonate polyurethane into a particle size of 1 mm to 10 mm to form a granular silicated polycarbonate polyurethane.

[0416] 75. The method according to embodiment 74, further comprising compounding the granular silicated polycarbonate polyurethane with a radiopaque agent, a colorant, or both to form a silicated polycarbonate polyurethane.

[0417] 76. A method of preparing an alcohol-resistant silicated polycarbonate polyurethane, the method comprising:

[0418] forming a first mixture comprising a polysiloxane and an isocyanate, the polysiloxane having a structure according to formula (IV):

[0419]

[0420] wherein R1 and R2 are independently selected from straight-chain C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30;

[0421] mixing the first mixture and continuing for a first period of time;

[0422] after completion of the first period of time, forming a second mixture comprising the first mixture and a polycarbonate polyol, the polycarbonate polyol having a structure according to formula (I):

[0423]

[0424] wherein R is selected from straight-chain or branched, substituted or unsubstituted C1-C 24 alkyl or alkylene groups, A is selected from hydrogen (H) or R'OH, and n is an integer from 2 to 30; and

[0425] mixing the second mixture and continuing for a second period of time.

[0426] 77. The method according to embodiment 76, further comprising:

[0427] after completion of the second period of time, forming a third mixture comprising the second mixture and a chain extender; and

[0428] mixing the third mixture and continuing for a third period of time.

[0429] 78. The method according to embodiment 77, further comprising monitoring the temperature of the third mixture, wherein the third period of time terminates when the temperature of the third mixture rises to a threshold.

[0430] 79. The method according to embodiment 78, wherein the threshold is in the range of about 200°F to about 230°F.

[0431] 80. The method according to embodiment 77, wherein the first time period is from about 2 minutes to about 30 minutes, the second time period is from about 2 minutes to about 30 minutes, and the third time period is from about 30 seconds to about 15 minutes.

[0432] 81. The method according to embodiment 76, wherein forming the second mixture comprises adding the polycarbonate polyol and the chain extender to the first mixture.

[0433] 82. The method according to embodiment 81, further comprising monitoring the temperature of the second mixture, wherein the second time period terminates when the temperature of the second mixture rises to a threshold.

[0434] 83. The method according to embodiment 81, wherein the first time period is from about 2 minutes to about 30 minutes, and the second time period is from about 2 minutes to about 15 minutes.

[0435] 84. The method according to embodiment 76, wherein the first mixture is mixed at a temperature of from about 120°F to about 180°F.

[0436] 85. The method according to embodiment 84, wherein the second mixture is mixed at a temperature of from about 130°F to 190°F.

[0437] 86. The method according to embodiment 84, wherein the second mixture is mixed at a temperature of from about 130°F to 230°F.

[0438] 87. The method according to embodiment 76, further comprising mixing a chain extender with an isocyanate, a polysiloxane, and a polycarbonate polyol.

[0439] 88. The method according to embodiment 87, further comprising mixing a lubricant with an isocyanate, a polysiloxane, and a polycarbonate polyol.

[0440] 89. The method according to embodiment 87, further comprising curing a combination of a polysiloxane, an isocyanate, a polycarbonate polyol, and a chain extender at a temperature of from 210°F to 250°F for a time period of from 12 hours to 36 hours to prepare a cured silicated polycarbonate polyurethane.

[0441] 90. The method according to embodiment 89, further comprising granulating the cured silicated polycarbonate polyurethane to a particle size of from 1 millimeter to 10 millimeters to form granular silicated polycarbonate polyurethane.

[0442] 91. The method according to embodiment 90, further comprising compounding the granular silicated polycarbonate polyurethane with a radiopaque agent, a colorant, or both.

[0443] 92. The method according to embodiment 76, wherein the weight ratio of the polycarbonate polyol to the polysiloxane is from about 11:1 to about 9:1.

[0444] 93. The method according to embodiment 76, wherein the combined weight of the polysiloxane and the polycarbonate polyol accounts for 50% to 60% of the total weight of all reactants used in the method.

[0445] 94. The method according to embodiment 93, wherein the weight of the polysiloxane accounts for 9% to 11% of the combined weight of the polysiloxane and the polycarbonate polyol.

[0446] 95. The method according to embodiment 76, wherein the polysiloxane is a carbonyl-modified polydimethylsiloxane having a structure according to formula (V):

[0447]

[0448] wherein m is an integer from 2 to 30.

[0449] 96. The method according to embodiment 95, wherein the polysiloxane has a number average molecular weight (M n ) of from about 925 g / mol to about 1025 g / mol.

[0450] 97. The method according to embodiment 96, wherein the polycarbonate polyol has a number average molecular weight (M n ) of from about 1840 g / mol to about 2200 g / mol.

[0451] 98. The method according to embodiment 97, wherein the weight ratio of the polycarbonate polyol to the polysiloxane is from about 11:1 to about 9:1.

[0452] 99. The method according to embodiment 97, wherein the weight of the polysiloxane accounts for 9% to 11% of the combined weight of the polysiloxane and the polycarbonate polyol.

[0453] 100. The method according to embodiment 97, wherein the combined weight of the polysiloxane and the polycarbonate polyol accounts for 50% to 60% of the total weight of all reactants used in the method.

[0454] 101. The method according to embodiment 100, wherein the weight of the polysiloxane accounts for 9% to 11% of the combined weight of the polysiloxane and the polycarbonate polyol.

[0455] 102. A medical device, the medical device comprising one or more components, each of the one or more components being at least partially formed of one or more alcohol-resistant silicated polycarbonate polyurethanes, the one or more alcohol-resistant silicated polycarbonate polyurethanes being prepared via the method according to one or more of Examples 76 to 101.

[0456] 103. The medical device according to Example 102, wherein the medical device comprises a catheter.

[0457] 104. The medical device according to Example 102, wherein the medical device comprises a peripherally inserted central catheter (PICC) device.

[0458] 105. The medical device according to Example 104, wherein the PICC device comprises at least one fluid path that is power injectable.

[0459] 106. The medical device according to Example 105, wherein the at least one fluid path of the PICC device is power injectable after (1) having undergone an ethanol lock event for a period sufficient to disinfect the at least one fluid path and (2) having been flushed and allowed to recover for a recovery period after the ethanol lock event.

[0460] 107. The medical device according to Example 106, wherein the recovery period is not less than one hour.

[0461] 108. The medical device according to Example 104, wherein the PICC device comprises at least one fluid path that is capable of maintaining an injection pressure of up to 180 psi without rupture and without leakage.

[0462] 109. The medical device according to Example 108, wherein the at least one fluid path comprises the lumen of an extension tube, a passage through a connection hub, and the lumen of a catheter shaft, the connection hub being coupled to the distal end of the extension tube and to the proximal end of the catheter shaft.

[0463] 110. The medical device according to Example 109, wherein the connection hub is overmolded onto the extension tube and the catheter shaft.

[0464] 111. The medical device according to Example 110, wherein the extension tube, the connection hub, and the catheter shaft each comprise an alcohol-resistant silicated polycarbonate polyurethane, the alcohol-resistant silicated polycarbonate polyurethane comprising a soft segment, the soft segment comprising a polycarbonate polyol and a polysiloxane, wherein each soft segment comprises from 5 wt% to 15 wt% of the polysiloxane.

[0465] 112. The medical device according to embodiment 112, wherein the alcohol-resistant silylated polycarbonate polyurethane of the connection hub is harder than the alcohol-resistant silylated polycarbonate polyurethanes of the extension tube and the catheter shaft.

[0466] 113. A catheter, the catheter comprising:

[0467] An extruded shaft, the extruded shaft comprising:

[0468] A lumen extending from a proximal end of the shaft to a distal end thereof; and

[0469] A sidewall defining at least a portion of the lumen, the sidewall comprising an alcohol-resistant silylated polycarbonate polyurethane, the alcohol-resistant silylated polycarbonate polyurethane comprising:

[0470] A polycarbonate polyol having a structure according to formula (I):

[0471]

[0472] wherein R is selected from straight-chain or branched, substituted or unsubstituted C1-C 24 alkyl or alkylene groups, A is selected from hydrogen (H) or R'OH, and n is an integer from 2 to 30;

[0473] A polysiloxane having a structure according to formula (IV):

[0474]

[0475] wherein R1 and R2 are independently selected from straight-chain C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30;

[0476] An isocyanate; and

[0477] A chain extender,

[0478] The alcohol-resistant silylated polycarbonate polyurethane comprises:

[0479] Hard segments;

[0480] Soft segments, the soft segments comprising from 5 wt% to 15 wt% of polysiloxane; and

[0481] An isocyanate index of 1.01 to 1.06.

[0482] 114. The catheter according to embodiment 113, further comprising a connector coupled to the shaft, the connector being in fluid communication with the lumen of the shaft.

[0483] 115. The catheter according to embodiment 113, further comprising:

[0484] An extension tube; and

[0485] A connection hub overmolded onto the shaft and the extension tube, the connection hub including a portion defining a passageway that provides fluid communication between the lumen of the extension tube and the shaft.

[0486] 116. The catheter according to embodiment 115, further comprising a connector attached to the proximal end of the extension tube.

[0487] 117. The catheter according to embodiment 115, wherein the extension tube comprises alcohol-resistant silicated polycarbonate polyurethane having the same chemical formulation as the alcohol-resistant silicated polycarbonate polyurethane of the shaft.

[0488] 118. The catheter according to embodiment 117, wherein the alcohol-resistant silicated polycarbonate polyurethane of the shaft comprises a radiopaque agent physically compounded therewith.

[0489] 119. The catheter according to embodiment 118, wherein the radiopaque agent comprises barium sulfate.

[0490] 120. The catheter according to embodiment 118, wherein the alcohol-resistant silicated polycarbonate polyurethane of the extension tube does not contain a radiopaque agent.

[0491] 121. The catheter according to embodiment 117, wherein the connection hub comprises alcohol-resistant silicated polycarbonate polyurethane having a chemical formulation different from the chemical formulations of the alcohol-resistant silicated polycarbonate polyurethanes of the shaft and the extension tube.

[0492] 122. The catheter according to embodiment 121, wherein the alcohol-resistant silicated polycarbonate polyurethane of the connection hub is harder than the alcohol-resistant silicated polycarbonate polyurethanes of the shaft and the extension tube.

[0493] 123. The catheter according to embodiment 115, wherein the portion of the connection hub defining the passageway comprises alcohol-resistant silicated polycarbonate polyurethane having a chemical formulation different from the chemical formulations of the alcohol-resistant silicated polycarbonate polyurethanes of the shaft and the extension tube.

[0494] 124. The catheter according to embodiment 123, wherein the alcohol-resistant silicated polycarbonate polyurethane of the portion of the connection hub defining the passageway is harder than the alcohol-resistant silicated polycarbonate polyurethanes of the shaft and the extension tube.

[0495] 125. The catheter according to embodiment 124, wherein the engagement hub includes a cover positioned over a portion of the engagement hub that defines the channel, wherein the cover includes additional alcohol-resistant silicated polycarbonate polyurethane that is softer than the alcohol-resistant silicated polycarbonate polyurethane of the portion of the engagement hub that defines the channel.

[0496] 126. The catheter according to embodiment 125, wherein the alcohol-resistant silicated polycarbonate polyurethane of the cover is softer than the alcohol-resistant silicated polycarbonate polyurethane of the shaft and the extension tube.

[0497] 127. The catheter according to embodiment 123, wherein each of the alcohol-resistant silicated polycarbonate polyurethanes of the extension tube and the connection hub includes hard segments and soft segments, and wherein the ratio of the hard segments to the soft segments of the alcohol-resistant silicated polycarbonate polyurethane of the connection hub is greater than the ratio of the hard segments to the soft segments of each of the alcohol-resistant silicated polycarbonate polyurethanes of the shaft and the extension tube.

[0498] 128. The catheter according to embodiment 127, wherein each of the alcohol-resistant silicated polycarbonate polyurethanes of the extension tube and the connection hub includes soft segments formed in part from polysiloxane, wherein the polysiloxane for each of the shaft, the extension tube, and the connection hub defines the weight percentage of the corresponding soft segments, and wherein the weight percentage of each of the shaft, the extension tube, and the connection hub differs from the weight percentage of each of the remaining two of the shaft, the extension tube, and the connection hub by no more than 5%.

[0499] 129. The catheter according to embodiment 128, wherein the polysiloxane of the alcohol-resistant silicated polycarbonate polyurethane used to form each of the extension tube and the connection hub has a structure according to formula (IV):

[0500]

[0501] wherein R1 and R2 are independently selected from straight-chain C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30.

[0502] 130. The catheter according to embodiment 129, wherein the polycarbonate polyol of the alcohol-resistant silicated polycarbonate polyurethane used to form each of the extension tube and the connection hub has a structure according to formula (I):

[0503]

[0504] wherein R is selected from linear or branched, substituted or unsubstituted C1-C24 alkyl or alkylene groups, A is selected from hydrogen (H) or R’OH, and n is an integer from 2 to 30.

[0505] 131. The catheter according to embodiment 115, wherein the extension tube comprises a silicated polycarbonate polyurethane, the silicated polycarbonate polyurethane comprising:

[0506] a polycarbonate polyol having a structure according to formula (I):

[0507]

[0508] wherein R is selected from linear or branched, substituted or unsubstituted C1-C 24 alkyl or alkylene groups, A is selected from hydrogen (H) or R’OH, and n is an integer from 2 to 30;

[0509] a polysiloxane having a structure according to formula (IV):

[0510]

[0511] wherein R1 and R2 are independently selected from linear C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30;

[0512] an isocyanate; and

[0513] a chain extender,

[0514] the alcohol-resistant silicated polycarbonate polyurethane comprising:

[0515] hard segments;

[0516] soft segments, the soft segments comprising from 5 wt% to 15 wt% of polysiloxane; and

[0517] an isocyanate index of 1.01 to 1.06.

[0518] 132. The catheter according to embodiment 131, wherein the fitting hub comprises a silicated polycarbonate polyurethane, the silicated polycarbonate polyurethane comprising:

[0519] a polycarbonate polyol having a structure according to formula (I):

[0520]

[0521] wherein R is selected from linear or branched, substituted or unsubstituted C1-C 24an alkyl or alkylene group, A is selected from hydrogen (H) or R’OH, and n is an integer from 2 to 30;

[0522] a polysiloxane having a structure according to formula (IV):

[0523]

[0524] wherein R1 and R2 are independently selected from straight-chain C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30;

[0525] an isocyanate; and

[0526] a chain extender,

[0527] The alcohol-resistant silylated polycarbonate polyurethane comprises:

[0528] hard segments;

[0529] soft segments, the soft segments comprising 5 wt% to 15 wt% of polysiloxane; and

[0530] an isocyanate index of 1.01 to 1.06.

[0531] 133. The catheter according to embodiment 132, wherein the ratio of the hard segments to the soft segments of the alcohol-resistant silylated polycarbonate polyurethane of the connection hub is greater than the ratio of the hard segments to the soft segments of each of the alcohol-resistant silylated polycarbonate polyurethanes of the shaft and the extension tube.

[0532] 134. The catheter according to embodiment 133, wherein the polysiloxane for each of the shaft, the extension tube, and the connection hub defines the weight percentage of the corresponding soft segment, and wherein the weight percentage of each of the shaft, the extension tube, and the connection hub differs from the weight percentage of each of the remaining two of the shaft, the extension tube, and the connection hub by no more than 5%.

[0533] 135. The catheter according to embodiment 113, wherein the catheter is power injectable.

[0534] 136. The catheter according to embodiment 135, wherein the catheter is power injectable after (1) subjecting the lumen to an ethanol lock event for a period sufficient to disinfect the lumen and (2) flushing after the ethanol lock event and then waiting for a recovery period.

[0535] 137. The catheter according to embodiment 136, wherein the recovery period is not less than 15 minutes.

[0536] 138. The catheter according to embodiment 137, wherein the recovery period is not less than one hour.

[0537] 139. The catheter according to embodiment 137, wherein the shaft is long enough to allow the catheter to be used as a peripherally inserted central catheter (PICC) device.

[0538] 140. The catheter according to embodiment 113, wherein after (1) subjecting the lumen to an ethanol lock event for a lock period sufficient to disinfect the lumen and (2) flushing after the ethanol lock event and then waiting for a recovery period, the burst pressure of the lumen of the shaft is not less than 180 psi.

[0539] 141. The catheter according to embodiment 140, wherein the lock period is at least one hour.

[0540] 142. The catheter according to embodiment 141, wherein the recovery period is at least 15 minutes.

[0541] 143. The catheter according to embodiment 141, wherein the recovery period is at least one hour.

[0542] 144. The catheter according to embodiment 140, wherein the recovery period is at least 15 minutes.

[0543] 145. The catheter according to embodiment 140, wherein the recovery period is at least one hour.

[0544] 146. The catheter according to embodiment 113, further comprising:

[0545] A connection hub attached to the shaft, the connection hub defining a channel in fluid communication with the lumen; and

[0546] An extension tube attached to the connection hub, the extension tube defining a lumen in fluid communication with the channel of the connection hub,

[0547] wherein the fluid path includes the lumen of the shaft, the channel, and the lumen of the extension tube.

[0548] 147. The catheter according to embodiment 146, wherein after (1) subjecting the fluid path to an ethanol lock event for a period sufficient to disinfect the fluid path and (2) flushing the fluid path after the ethanol lock event and then waiting for a recovery period, the fluid path of the catheter is power injectable.

[0549] 148. The catheter according to embodiment 146, wherein after (1) subjecting the fluid path to an ethanol lock event for a lock period sufficient to disinfect the fluid path, and (2) flushing the fluid path after the ethanol lock event and then waiting for a recovery period, the burst pressure of the fluid path is not less than 180 psi.

[0550] 149. The catheter according to embodiment 146, wherein after (1) subjecting the fluid path to an ethanol lock event for a lock period sufficient to disinfect the fluid path, and (2) flushing the fluid path after the ethanol lock event and then waiting for a recovery period, the burst pressure of the fluid path is not less than 200 psi.

[0551] 150. The catheter according to embodiment 146, wherein after (1) subjecting the fluid path to an ethanol lock event for a lock period sufficient to disinfect the fluid path, and (2) flushing the fluid path after the ethanol lock event and then waiting for a recovery period, the burst pressure of the fluid path is not less than 220 psi.

[0552] 151. The catheter according to any one of embodiments 147 to 150, wherein the lock period is at least one hour.

[0553] 152. The catheter according to embodiment 151, wherein the recovery period is at least 15 minutes.

[0554] 153. The catheter according to embodiment 151, wherein the recovery period is at least one hour.

[0555] 154. The catheter according to any one of embodiments 147 to 150, wherein the recovery period is at least 15 minutes.

[0556] 155. The catheter according to any one of embodiments 147 to 150, wherein the recovery period is at least one hour.

[0557] 156. The catheter according to any one of embodiments 147 to 150, wherein the difference between the first peak operating pressure of the fluid path during a first power injection and the second peak operating pressure of the fluid path during a second power injection does not exceed 10%, wherein the fluid path is subjected to the ethanol lock event, the flushing, and the recovery period between the first power injection and the second power injection.

[0558] 157. The catheter according to embodiment 156, wherein the difference between the first peak operating pressure and the second peak operating pressure is not greater than 5%.

[0559] 158. The catheter according to embodiment 156, wherein the difference between the first peak operating pressure and the second peak operating pressure is no greater than 2%.

[0560] 159. The catheter according to embodiment 113, wherein the alcohol-resistant silicated polycarbonate polyurethane does not contain a lubricant additive.

[0561] 160. The catheter according to embodiment 113, wherein along at least 75% of the length of the shaft configured to be inserted into a patient during use, the shaft defines an outer diameter of at least 5 French.

[0562] 161. The catheter according to embodiment 160, wherein when the shaft is in a patient, the silicated polycarbonate polyurethane is compounded with barium sulfate in an amount sufficient to permit radiographic visualization of the shaft.

[0563] 162. The catheter according to embodiment 161, wherein the barium sulfate is present in an amount of at least 20% of the total weight of the compounded silicated polycarbonate polyurethane.

[0564] 163. The catheter according to embodiment 161, wherein the shaft is sufficiently leach-resistant to permit its non-toxic use in a patient weighing at least 2.3 kilograms.

[0565] 164. The catheter according to embodiment 113, wherein the alcohol-resistant silicated polycarbonate polyurethane is formed by a method comprising the steps of:

[0566] Forming a first mixture comprising the polysiloxane and the isocyanate;

[0567] Mixing the first mixture for a first period of time;

[0568] After completion of the first period of time, forming a second mixture comprising the first mixture and the polycarbonate polyol; and

[0569] Mixing the second mixture for a second period of time.

[0570] 165. The catheter according to embodiment 164, wherein the method further comprises:

[0571] After completion of the second period of time, forming a third mixture comprising the second mixture and the chain extender; and

[0572] Mixing the third mixture for a third period of time.

[0573] 166. The catheter according to embodiment 165, wherein the third period of time terminates when the temperature of the third mixture rises to a threshold.

[0574] 167. The catheter according to embodiment 166, wherein the threshold is in the range of about 200°F to about 230°F.

[0575] 168. The catheter according to embodiment 164, wherein forming the second mixture comprises adding both a polycarbonate polyol and a chain extender to the first mixture.

[0576] 169. The catheter according to embodiment 168, wherein the second time period terminates when the temperature of the second mixture rises to a threshold.

[0577] 170. The catheter according to embodiment 169, wherein the threshold is in the range of about 200°F to about 230°F.

[0578] 171. The catheter according to embodiment 164, wherein the first time period is from about 2 minutes to about 30 minutes.

[0579] 172. The catheter according to embodiment 171, wherein the second time period is from about 2 minutes to about 30 minutes.

[0580] 173. The catheter according to embodiment 171, wherein the second time period is from about 2 minutes to about 15 minutes.

[0581] 174. The catheter according to embodiment 113, wherein the weight ratio of polycarbonate polyol to polysiloxane is from about 11:1 to about 9:1.

[0582] 175. The catheter according to embodiment 113, wherein the combined weight of the polysiloxane and the polycarbonate polyol accounts for 50% to 60% of the total weight of all reactants used in the method.

[0583] 176. The catheter according to embodiment 175, wherein the weight of the polysiloxane accounts for 9% to 11% of the combined weight of the polysiloxane and the polycarbonate polyol.

[0584] 177. The catheter according to embodiment 113, wherein the polysiloxane is a carbonyl-modified polydimethylsiloxane having a structure according to formula (V):

[0585]

[0586] wherein m is an integer from 2 to 30.

[0587] 178. The catheter according to embodiment 177, wherein the polysiloxane has a number average molecular weight (M n ) of about 925 g / mol to about 1025 g / mol.

[0588] 179. The catheter according to embodiment 178, wherein the polycarbonate polyol has a number average molecular weight (M n ) of from about 1840 g / mol to about 2200 g / mol.

[0589] 180. The catheter according to embodiment 179, wherein the weight ratio of the polycarbonate polyol to the polysiloxane is from about 11:1 to about 9:1.

[0590] 181. The catheter according to embodiment 179, wherein the weight of the polysiloxane accounts for 9% to 11% of the combined weight of the polysiloxane and the polycarbonate polyol.

[0591] 182. The catheter according to embodiment 179, wherein the combined weight of the polysiloxane and the polycarbonate polyol accounts for 50% to 60% of the total weight of all the reactants used in the method.

[0592] 183. The catheter according to embodiment 182, wherein the weight of the polysiloxane accounts for 9% to 11% of the combined weight of the polysiloxane and the polycarbonate polyol.

[0593] 184. A kit, the kit comprising:

[0594] a catheter according to any one of embodiments 113 to 183; and

[0595] instructions for using the catheter, the instructions providing guidance on:

[0596] introducing an alcohol into the lumen of the catheter and maintaining the alcohol therein for a clinically effective locking period;

[0597] flushing the alcohol from the lumen of the catheter; and

[0598] waiting for a recovery period after flushing the alcohol from the lumen and then using the lumen for injection.

[0599] 185. The kit according to embodiment 184, wherein the recovery period is one hour.

[0600] 186. The kit according to embodiment 184, wherein the recovery period is at least one hour.

[0601] 187. The kit according to embodiment 184, wherein the length of the shaft configured to be introduced into a patient's vasculature defines a 5 French outer diameter.

[0602] 188. The kit according to embodiment 187, wherein the instructions for use indicate that the catheter can be used for patients weighing at least 2.3 kg.

[0603] 189. The kit according to embodiment 188, wherein the alcohol-resistant silicated polycarbonate polyurethane of the shaft is compounded with a radiopaque agent in an amount sufficient to render the shaft visible under radiography when the shaft is in a patient's body.

[0604] 190. The kit according to embodiment 189, wherein the radiopaque agent comprises barium sulfate.

[0605] 191. The kit according to embodiment 184, wherein the injection is a power injection.

[0606] 192. A catheter comprising:

[0607] a shaft comprising a first alcohol-resistant silicated polycarbonate polyurethane

[0608] an extension tube comprising a second alcohol-resistant silicated polycarbonate polyurethane; and

[0609] a fitting hub overmolded onto a proximal end of the shaft and a distal end of the extension tube, the fitting hub comprising a third alcohol-resistant silicated polycarbonate polyurethane,

[0610] wherein each of the first alcohol-resistant silicated polycarbonate polyurethane, the second alcohol-resistant silicated polycarbonate polyurethane, and the third alcohol-resistant silicated polycarbonate polyurethane comprises:

[0611] a polycarbonate polyol; and

[0612] a polysiloxane having a structure according to formula (IV):

[0613]

[0614] wherein R1 and R2 are independently selected from straight-chain C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30, and

[0615] wherein the polysiloxane accounts for 5 wt% to 15 wt% of the combined weight of the polycarbonate polyol and the polysiloxane.

[0616] 193. The catheter according to embodiment 192, wherein each of the shaft and the extension tube is formed as an extrudate comprising the first alcohol-resistant silicated polycarbonate polyurethane and the second alcohol-resistant silicated polycarbonate polyurethane, respectively.

[0617] 194. The catheter according to embodiment 192, wherein the engagement hub includes a core and a cover, wherein the core comprises a third alcohol-resistant silicated polycarbonate polyurethane, and wherein the cover comprises a fourth alcohol-resistant silicated polyurethane, the fourth alcohol-resistant silicated polyurethane comprising:

[0618] a polycarbonate polyol; and

[0619] a polysiloxane having a structure according to formula (IV):

[0620]

[0621] wherein R1 and R2 are independently selected from straight-chain C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30, and

[0622] wherein the polysiloxane accounts for 5 wt% to 15 wt% of the combined weight of the polycarbonate polyol and the polysiloxane.

[0623] 195. The catheter according to embodiment 192, wherein the cover is softer than the core of the engagement hub.

[0624] 196. The catheter according to embodiment 195, wherein the cover is softer than each of the shaft and the extension tube, and wherein the core is harder than each of the shaft and the extension tube.

[0625] 197. The catheter according to embodiment 192, wherein the third alcohol-resistant polycarbonate polyurethane is harder than each of the first alcohol-resistant polycarbonate polyurethane and the second alcohol-resistant polycarbonate polyurethane.

[0626] 198. The catheter according to embodiment 197, wherein the third alcohol-resistant polycarbonate polyurethane has a Shore D durometer value of about 15 to about 85, and wherein each of the first alcohol-resistant polycarbonate polyurethane and the second alcohol-resistant polycarbonate polyurethane has a Shore A durometer value of about 95 to about 99.

[0627] 199. The catheter according to embodiment 192, wherein for each of the first alcohol-resistant silicated polycarbonate polyurethane, the second alcohol-resistant silicated polycarbonate polyurethane, and the third alcohol-resistant silicated polycarbonate polyurethane, the polysiloxane is a carbonyl-modified polydimethylsiloxane having a structure according to formula (V):

[0628]

[0629] wherein m is an integer from 2 to 30.

[0630] 200. The catheter according to embodiment 199, wherein for each of the first alcohol-resistant silylated polycarbonate polyurethane, the second alcohol-resistant silylated polycarbonate polyurethane, and the third alcohol-resistant silylated polycarbonate polyurethane, the polysiloxane has a number-average molecular weight (M n ) of from about 925 g / mol to about 1025 g / mol.

[0631] 201. The catheter according to embodiment 200, wherein for each of the first alcohol-resistant silylated polycarbonate polyurethane, the second alcohol-resistant silylated polycarbonate polyurethane, and the third alcohol-resistant silylated polycarbonate polyurethane, the polycarbonate polyol has a number-average molecular weight (M n ) of from about 1840 g / mol to about 2200 g / mol.

[0632] 202. The catheter according to embodiment 201, wherein for each of the first alcohol-resistant silylated polycarbonate polyurethane, the second alcohol-resistant silylated polycarbonate polyurethane, and the third alcohol-resistant silylated polycarbonate polyurethane, the weight ratio of the polycarbonate polyol to the polysiloxane is from about 11:1 to about 9:1.

[0633] 203. The catheter according to embodiment 192, wherein for each of the first alcohol-resistant silylated polycarbonate polyurethane, the second alcohol-resistant silylated polycarbonate polyurethane, and the third alcohol-resistant silylated polycarbonate polyurethane, the polysiloxane accounts for 9% to 11% of the combined weight of the polysiloxane and the polycarbonate polyol.

[0634] 204. The catheter according to embodiment 192, wherein for each of the first alcohol-resistant silylated polycarbonate polyurethane, the second alcohol-resistant silylated polycarbonate polyurethane, and the third alcohol-resistant silylated polycarbonate polyurethane, the weight percentage of the polysiloxane relative to the combined weight of the polysiloxane and the polycarbonate polyol differs by no more than 5% from the weight percentage of each of the remaining two of the first alcohol-resistant silylated polycarbonate polyurethane, the second alcohol-resistant silylated polycarbonate polyurethane, and the third alcohol-resistant silylated polycarbonate polyurethane.

[0635] 205. A catheter comprising:

[0636] An extrusion shaft comprising an alcohol-resistant silylated polycarbonate polyurethane formed from reactants comprising:

[0637] A polycarbonate polyol;

[0638] A polysiloxane;

[0639] An isocyanate; and

[0640] Chain extender,

[0641] wherein the extruded shaft and the alcohol-resistant silicated polycarbonate polyurethane thereof contain no lubricant additives.

[0642] 206. The catheter according to embodiment 205, wherein the polysiloxane accounts for 5 wt% to 15 wt% of the combined weight of the polycarbonate polyol and the polysiloxane,

[0643] 207. The catheter according to embodiment 206, wherein the polysiloxane has a structure according to formula (IV):

[0644]

[0645] wherein R1 and R2 are independently selected from straight-chain C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C12 alkyl or alkylene groups, R4 and R6 are independently selected from C1-C8 alkyl or alkylene groups, and m is an integer from 2 to 30.

[0646] 208. The catheter according to embodiment 205, further comprising an extension tube and a connection hub coupled to the distal end of the extension tube and the proximal end of the catheter shaft, wherein each of the extension tube and the connection hub comprises an alcohol-resistant silicated polycarbonate polyurethane that does not contain lubricant additives.

[0647] 209. A catheter, the catheter comprising:

[0648] An extension tube defining a lumen;

[0649] A connection hub attached to the extension tube, the connection hub defining a channel in fluid communication with the lumen of the extension tube; and

[0650] An extruded shaft attached to the connection hub, the shaft defining a lumen in fluid communication with the channel of the connection hub, the shaft comprising an alcohol-resistant silicated polycarbonate polyurethane formed from reactants comprising:

[0651] Polycarbonate polyol;

[0652] Polysiloxane;

[0653] Isocyanate; and

[0654] Chain extender,

[0655] wherein after the fluid path has been alcohol-locked for a clinically effective period and has been allowed to recover from the alcohol lock for a recovery period, the catheter can be power-injected along a fluid path including the lumen of the extension tube, the lumen of the connection hub, and the lumen of the shaft.

[0656] 210. The catheter according to embodiment 209, wherein the effective length of the shaft is not less than 57 cm.

[0657] 211. The catheter according to embodiment 209, wherein the extruded shaft and its alcohol-resistant silicated polycarbonate polyurethane do not contain any lubricant additives.

[0658] 212. The catheter according to embodiment 209, wherein the insertable portion of the shaft defines a 5 French outer diameter.

[0659] 213. The catheter according to embodiment 212, wherein the silicated polycarbonate polyurethane is compounded with at least 25 wt% barium sulfate.

[0660] 214. The catheter according to embodiment 213, wherein the amount of barium sulfate leachate from the catheter is small enough to allow the catheter to be safely used by a neonate weighing not less than 2.3 kg.

[0661] 215. The catheter according to embodiment 209, wherein each of the extension tube and the connection hub comprises silicated polycarbonate polyurethane.

[0662] The expression of the term "first" in the claims with respect to a characteristic structure or element does not necessarily imply the existence of a second or additional such characteristic structure or element. The embodiments of the present invention for which exclusive properties or privileges are claimed are defined as follows.

Claims

1. An alcohol-resistant silicated polycarbonate polyurethane formed from reactants comprising: A polycarbonate polyol having a structure according to formula (I): wherein R is selected from linear or branched, substituted or unsubstituted C1-C 24 alkylene groups, A is selected from hydrogen (H) or R’OH, and n is an integer from 2 to 30, and wherein R’ is selected from linear or branched, substituted or unsubstituted C1-C 24 alkylene groups, And is the same as or different from R; A polysiloxane having a structure according to formula (IV): wherein R1 and R2 are independently selected from straight-chain C1-C6 alkyl groups or hydrogen groups, R3 and R5 are independently selected from C1-C 12 alkylene groups, R4 and R6 are independently selected from C1-C8 alkylene groups, and m is an integer from 2 to 30; An isocyanate; and A chain extender, The silicated polycarbonate polyurethane comprises: Hard segments; Soft segments, the soft segments containing from 5% to 15% by weight of polysiloxane; and An isocyanate index of 1.01 to 1.06, Wherein the silicated polycarbonate polyurethane has a weight average molecular weight (Mw) of 50,000 to 300,000, and Wherein the soft segments are 30% to 80% by weight of the silicated polycarbonate polyurethane.

2. The polysiloxane of the polysiloxane-based polycarbonate polyurethane according to claim 1 has a number average molecular weight (M n ) of from 925 g / mol to 1025 g / mol.

3. The silicated polycarbonate polyurethane according to claim 2, wherein the soft segments contain from 9% to 11% by weight of the polysiloxane.

4. The silicated polycarbonate polyurethane according to claim 3, wherein the isocyanate index is 1.03 to 1.

06.

5. The silicated polycarbonate polyurethane according to claim 1, wherein the polysiloxane is a carbonyl-modified polydimethylsiloxane having a structure according to formula (V): Where m is an integer from 2 to 30.

6. The silicated polycarbonate polyurethane according to claim 5, wherein the polysiloxane has a number average molecular weight (M n ) of from 925 g / mol to 1025 g / mol.

7. The silicated polycarbonate polyurethane according to claim 6, wherein the polycarbonate polyol has a number average molecular weight (M n ) of from 1840 g / mol to 2200 g / mol.

8. The silicated polycarbonate polyurethane according to claim 7, wherein the isocyanate index is in the range of 1.03 to 1.

06.

9. The silicated polycarbonate polyurethane according to claim 8, wherein the polycarbonate polyol comprises poly(hexamethylene carbonate) diol.

10. The silicated polycarbonate polyurethane according to claim 8, wherein the isocyanate is aromatic.

11. The silicated polycarbonate polyurethane according to claim 10, wherein the isocyanate comprises methylene diphenyl diisocyanate.

12. The silicated polycarbonate polyurethane according to claim 10, wherein the chain extender comprises 1,4-butanediol.

13. The silicated polycarbonate polyurethane according to claim 1, wherein the hard segments are present in an amount between 40% and 50% by weight, and the soft segments are present in an amount between 50% and 60% by weight.

14. The silicated polycarbonate polyurethane according to claim 13, wherein the silicated polycarbonate polyurethane has a Shore A durometer value between 96 and 100.

15. The silicated polycarbonate polyurethane according to claim 1, wherein R3 and R5 are independently selected from C1-C8 alkylene groups.

16. The silicated polycarbonate polyurethane according to claim 15, wherein R4 and R6 are independently selected from C1-C4 alkylene groups.

17. The silicated polycarbonate polyurethane according to claim 1, wherein R4 and R6 are independently selected from C1-C4 alkylene groups.

18. The polycarbonate polyurethane silicate according to claim 1, wherein the polysiloxane has a number average molecular weight (M n ) of from 300 to 3000.

19. The silicated polycarbonate polyurethane according to claim 1, wherein the isocyanate is a member selected from the following: 4,4'-methylenediphenyl diisocyanate, dibenzylidene diisocyanate, methylenebis(cyclohexyl isocyanate), p-phenylene diisocyanate, trans-cyclohexane-1,4-diisocyanate, 1,6-diisocyanatohexane, 1,5-naphthalene diisocyanate, p-tetramethylxylene diisocyanate, m-tetramethylxylene diisocyanate, 2,4-toluene diisocyanate, isophorone diisocyanate, and combinations thereof.

20. The silicated polycarbonate polyurethane according to claim 1, wherein the chain extender is a member selected from the following: 1,2-propanediol, 1,3-propanediol, 2-ethyl-2-(hydroxymethyl)propane-1,3-diol, 1,4-butanediol, 1,5-pentanediol, 1,6-hexanediol, 1,7-heptanediol, 1,8-octanediol, 1,9-nonanediol, 1,10-decanediol, 1,11-undecanediol, 1,12-dodecanediol, 1,4-cyclohexanediol, 1,4-cyclohexanedimethanol, 1,4-bis(2-hydroxyethoxy)benzene, p-xylene glycol, 1,3-bis(4-hydroxybutyl)tetramethyldisiloxane, 1,3-bis(6-hydroxyethoxypropyl)tetramethyldisiloxane, and combinations thereof.

21. The silicated polycarbonate polyurethane according to claim 1, further comprising additives selected from: radiopaque agents, lubricants, catalysts, antioxidants, free radical inhibitors, colorants, fillers, and combinations thereof.

22. The silicated polycarbonate polyurethane according to claim 1, which is formed by a method comprising the following steps: Forming a first mixture comprising the polysiloxane and the isocyanate; Mixing the first mixture for a first period of time; After completion of the first period of time, forming a second mixture comprising the first mixture and the polycarbonate polyol; and Mixing the second mixture for a second period of time.

23. The silicated polycarbonate polyurethane according to claim 22, wherein the method further comprises: After completion of the second period of time, forming a third mixture comprising the second mixture and the chain extender; And Mixing the third mixture for a third period of time.

24. The silicated polycarbonate polyurethane according to claim 23, wherein the third period of time terminates when the temperature of the third mixture rises to a threshold.

25. The silicated polycarbonate polyurethane according to claim 24, wherein the threshold is in the range of 200°F to 230°F.

26. The silicated polycarbonate polyurethane according to claim 22, wherein forming the second mixture comprises adding both the polycarbonate polyol and the chain extender to the first mixture.

27. The silicated polycarbonate polyurethane according to claim 26, wherein the second period of time terminates when the temperature of the second mixture rises to a threshold.

28. The silicated polycarbonate polyurethane according to claim 27, wherein the threshold is in the range of 200°F to 230°F.

29. The silicated polycarbonate polyurethane according to claim 22, wherein the first time period is from 2 minutes to 30 minutes.

30. The silicated polycarbonate polyurethane according to claim 29, wherein the second time period is from 2 minutes to 30 minutes.

31. The silicated polycarbonate polyurethane according to claim 29, wherein the second time period is from 2 minutes to 15 minutes.

32. A medical device comprising at least one component containing the silicated polycarbonate polyurethane according to any one of claims 1 to 31.

33. The medical device according to claim 32, wherein the medical device comprises a catheter.

34. The medical device according to claim 32, wherein the medical device comprises a peripherally inserted central catheter device.

35. The medical device according to claim 34, wherein the peripherally inserted central catheter device comprises at least one fluid path that can be power injected.

36. The medical device according to claim 35, wherein the at least one fluid path of the peripherally inserted central catheter device is power injectable after (1) having undergone an ethanol lock event for a period sufficient to disinfect the at least one fluid path and (2) having been flushed and allowed to recover for a recovery period after the ethanol lock event.

37. The medical device according to claim 36, wherein the recovery period is not less than one hour.

38. The medical device according to claim 34, wherein the peripherally inserted central catheter device comprises at least one fluid path capable of maintaining an injection pressure of up to 180 psi without rupture or leakage.

39. The medical device according to claim 38, wherein the at least one fluid path comprises the lumen of an extension tube, a passage through a connection hub, and the lumen of a catheter shaft, the connection hub being coupled to the distal end of the extension tube and to the proximal end of the catheter shaft.

40. The medical device according to claim 39, wherein the connection hub is overmolded onto the extension tube and the catheter shaft.

41. The medical device according to claim 40, wherein the extension tube, the connection hub, and the catheter shaft each comprise a different alcohol-resistant silicated polycarbonate polyurethane.

42. The medical device according to claim 41, wherein the alcohol-resistant silicated polycarbonate polyurethane of the connection hub is harder than the alcohol-resistant silicated polycarbonate polyurethanes of the extension tube and the catheter shaft.

43. The medical device according to claim 42, wherein the alcohol-resistant silicated polycarbonate polyurethane of the catheter shaft is compounded with a radiopaque agent.

44. The medical device according to claim 43, wherein the alcohol-resistant silicated polycarbonate polyurethanes of the catheter shaft and the extension tube have the same chemical formulation.

45. A kit comprising: A catheter, said catheter comprising at least one component, said at least one component comprising a silicated polycarbonate polyurethane according to any one of claims 1 to 31; and Instructions for using said catheter, said instructions providing guidance on: introducing an alcohol into the lumen of said catheter and maintaining said alcohol therein for a clinically effective locking period; flushing said alcohol from the lumen of said catheter; and waiting for a recovery period after flushing said alcohol from said lumen and then using said lumen for injection.

46. The kit according to claim 45, wherein said recovery period is one hour.

47. The kit according to claim 45, wherein said recovery period is at least one hour.

48. The kit according to claim 45, wherein the length of the shaft of said catheter configured to be introduced into a patient's vasculature defines a 5 French outer diameter.

49. The kit according to claim 48, wherein said instructions for use indicate that said catheter can be used in patients weighing at least 2.3 kg.

50. The kit according to claim 49, wherein said alcohol-resistant silicated polycarbonate polyurethane of said shaft is compounded with a radiopaque agent in an amount sufficient to render said shaft visible under radiography when said shaft is in a patient's body.

51. The kit according to claim 50, wherein said radiopaque agent comprises barium sulfate.

52. The kit according to claim 45, wherein said injection is a power injection.

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