Radiopaque polymer formulation comprising thermoplastic polymer, tungsten and barium sulfate

Abstract

Embodiments of the present disclosure relate to radiopaque polymeric formulations comprising a thermoplastic polymer and a filler. The filler includes 25% to 45% by weight of tungsten and 35% to 55% by weight of barium sulfate.

Description

[0001] Claiming priority

[0002] This application claims the benefit of priority to U.S. Provisional Patent Application Serial No. 63 / 328,489, filed on April 7, 2022, with Attorney Docket No. 1202205, which is incorporated herein by reference in its entirety. Technical Field

[0003] Embodiments of the present disclosure are generally directed to radiopaque polymer formulations comprising a thermoplastic polymer and a filler comprising tungsten and barium sulfate. Background Art

[0004] Polymers used to produce catheters and other medical devices inserted into the body for diagnostic or interventional procedures are often filled with substances that are opaque to x-rays, making the devices visible under fluoroscopy or x-ray imaging. Tungsten and barium sulfate are widely used as fillers in medical devices. However, these fillers may not provide the dielectric strength, absorptivity, and relatively low reflectivity required for medical applications.

[0005] Thus, there is a continuing need for fillers for radiopaque polymer formulations that provide the desired dielectric strength, absorptivity, and reflectivity without degrading the mechanical properties of the base polymer, such as tensile strength, tensile elongation, flexural modulus, Charpy impact strength, Izod impact strength, melt flow rate, or combinations thereof. Summary of the invention

[0006] Embodiments of the present disclosure relate to radiopaque polymer formulations that alleviate the above-mentioned problems. Specifically, the radiopaque polymer formulations disclosed herein comprise a thermoplastic polymer and a filler comprising tungsten and barium sulfate, which produces the desired dielectric strength and the desired absorption and reflectivity of the radiopaque polymer formulation before and / or after x-ray exposure, while maintaining the mechanical properties of the thermoplastic polymer.

[0007] According to one embodiment, a radiopaque polymer formulation is provided. The radiopaque polymer formulation comprises a thermoplastic polymer and a filler. Based on the total amount of the radiopaque polymer formulation, the filler comprises 25 weight percent (wt%) to 45 weight percent tungsten and 35 weight percent to 55 weight percent barium sulfate.

[0008] According to one embodiment, a medical device comprising a radioactive polymer is provided, the polymer comprising a thermoplastic polymer and a filler. The filler comprises 25 weight percent (wt%) to 45 weight percent tungsten and 35 weight percent to 55 weight percent barium sulfate based on the total amount of the radiopaque polymer formulation. In some embodiments, the medical device can be an X-ray shielding component.

[0009] Other features and advantages of the embodiments described herein will be given in the detailed description below. For those skilled in the art, they can be easily understood from these descriptions, or some of the features and advantages thereof can be recognized by practicing the embodiments described herein, including the following specific embodiments and claims. DETAILED DESCRIPTION

[0010] Reference will now be made in detail to various embodiments of the formulation, particularly a radiopaque polymer formulation comprising a thermoplastic polymer and a filler. The filler comprises 25 to 45 wt% tungsten and 35 to 55 wt% barium sulfate based on the total amount of the radiopaque polymer formulation.

[0011] The present disclosure should not be understood to be limited to the embodiments described herein. Rather, these embodiments are provided to make the present disclosure thorough and complete and to fully convey the subject matter to those skilled in the art.

[0012] definition

[0013] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art.The terminology used in the present disclosure is for describing particular embodiments only and is not intended to be limiting.

[0014] Herein, ranges may be expressed as from "about" one particular value and / or to "about" another particular value. When such a range is expressed, another embodiment includes from the one particular value and / or to the other particular value. Similarly, when a value is expressed as an approximation by using the preposition "about," it is understood that the particular value constitutes another embodiment. It will also be understood that the endpoints of each range are meaningful both in relation to the other endpoint and independently of the other endpoint.

[0015] Unless otherwise expressly stated, any method described herein should not be construed as requiring that its steps be performed in a particular order, nor should any device have a particular orientation. Therefore, in the absence of an actual description of the order in which its steps are to be followed in a method claim, or an actual description of the order or orientation of the components in any device claim, or an explicit description in other ways in the claims or specification that the steps should be limited to a particular order, or a description of a particular order or orientation of the device components, no order or orientation should be inferred in any respect. This applies to any possible non-explicit basis for expression, including: logical issues involving step settings, operational flows, component order or component orientation; concise meaning derived from grammatical organization or punctuation, and the number or type of embodiments described in the specification.

[0016] Throughout this specification and the appended claims, the singular forms "a," "an," and "the" include the plural forms as well, unless the context clearly dictates otherwise. Thus, for example, reference to "a" component includes aspects having two or more such components, unless the context dictates otherwise.

[0017] As used herein, the term "consisting essentially of" or "consisting substantially of" limits the scope of a material to the specified material components and components that do not materially affect the basic properties of the material.

[0018] Unless otherwise indicated, the term "weight percent" or "weight % / wt %" as used herein refers to the weight fraction of a component of a radiopaque polymer formulation based on the total amount (ie, weight) of the radiopaque polymer formulation.

[0019] As used herein, the term "Charpy impact strength" refers to the toughness of a material as measured by the Charpy impact test according to ISO 179-1:2010.

[0020] As used herein, the term "Izod impact strength" refers to the strength of a material measured by an Izod impact test according to ISO 180:2019.

[0021] As used herein, the term "tensile strength at break" refers to the maximum stress that a material can withstand before tensile breakage, measured at 23°C and a strain rate of 5 mm / min according to ISO 527-2:2012.

[0022] The term "tensile elongation at break" described herein refers to the ratio between the increased length after break and the initial length measured at 23° C. and a strain rate of 5 mm / min according to ISO 527-2:2012.

[0023] The term "flexural modulus" as described herein refers to the ratio of stress to strain upon bending deformation measured at 23°C and a strain rate of 2 mm / min according to ISO 178:2019.

[0024] As used herein, the term "melt flow rate" refers to the ability of a material melt to flow under pressure as measured at 230°C and 5 kg according to ASTM D1238 or ISO 1133-2:2011.

[0025] As used herein, the term "dielectric strength" or "breakdown strength" refers to the minimum voltage at which spark breakdown occurs across a material in a uniform electric field generated between electrodes, measured in accordance with VDE 0370 / Teil 5 / 96.

[0026] As used herein, the term "breakdown strength after X-ray exposure" refers to the minimum voltage at which spark breakdown occurs on a material when a uniform electric field is generated between electrodes after the material is exposed to 900 kGy (kilogray) X-rays, measured according to VDE 0370 / Teil5 / 96.

[0027] As used herein, the term "absorbance at 1 mm Pb" refers to a measurement of the amount of 1 mm Pb light absorbed by a material as measured using a Smiths Heimann Detection Hi-Ray 10X.

[0028] The term "density" as described herein refers to the mass per unit volume of a substance measured at 23°C according to ISO 1183-1:2019.

[0029] As used herein, the term "copolymer" refers to a polymer formed when two or more types or species of monomers are linked in the same chain.

[0030] As used herein, the term "radio-opaque" refers to a substance that blocks radiation in the wavelength range of about 10 -8 Up to 10 -12 The ability of a substance to block x-rays (e.g., by absorption) makes it visible under fluoroscopy or x-ray imaging. In contrast, a non-radiopaque substance allows x-rays to pass through the substance or, to a lesser extent, only partially obscures the substance.

[0031] As used herein, the term "thermoplastic polymer" refers to a polymer material that is capable of becoming soft or moldable when the temperature is raised above a certain temperature and solidifying when cooled below a certain temperature.

[0032] As used herein, the term "thermoplastic polyolefin" refers to a polyolefin material that is capable of becoming soft or moldable when the temperature is raised above a certain temperature and solidifying when cooled below a certain temperature.

[0033] As used herein, the term "thermoplastic elastomer" refers to an elastomeric material that is capable of becoming soft or moldable when the temperature is raised above a certain temperature and solidifying when cooled below a certain temperature.

[0034] As used herein, the terms "reflectivity" or "reflectivity" refer to the ability of a material to reflect energy incident on its surface.

[0035] As used herein, the term "low reflectivity" refers to a reflectivity that is lower than the reflectivity of tungsten.

[0036] As used herein, the term "high reflectivity" refers to the reflectivity of tungsten.

[0037] As used herein, the term "high dielectric strength" refers to a dielectric strength greater than or equal to 3 kV / mm under DC load.

[0038] As used herein, the term "high absorptivity" refers to an absorptivity of 1 mm lead (Pb) greater than or equal to 5 mm.

[0039] Polymers used to produce catheters and other medical devices inserted into the body for diagnostic or interventional procedures are often filled with substances that are opaque to x-rays, making the devices visible under fluoroscopy or x-ray imaging. These fillers affect the energy attenuation of photons as the x-ray beam passes through the substance, reducing the intensity of the photons by absorbing or deflecting them. Image contrast and sharpness can vary depending on the type and amount of filler used, and can be tailored to the specific application of the medical device.

[0040] Since newer X-ray machines operate at higher energy levels than older X-ray machines, higher dielectric strength is required to provide adequate stability after X-ray exposure while maintaining high absorptivity. Tungsten and barium sulfate are widely used as fillers in medical devices, but these fillers may not provide the dielectric strength, absorptivity, and relatively low reflectivity required for medical applications. For example, tungsten has high dielectric strength but has relatively high reflectivity. Barium sulfate has high dielectric strength and high absorptivity but may not have the reflectivity level required for X-ray applications. In addition, increasing the amount of filler may reduce the mechanical properties of the base polymer.

[0041] Disclosed herein is a radiopaque polymer formulation that can alleviate the above-mentioned problems. Specifically, the radiopaque polymer formulation disclosed herein comprises a thermoplastic polymer and a filler including tungsten and barium sulfate, which results in the radiopaque polymer formulation having the required dielectric strength and high absorptivity and low reflectivity that may be required in medical applications before and / or after x-ray exposure, while maintaining the mechanical properties of the thermoplastic polymer, such as tensile strength, tensile elongation, flexural modulus, Charpy impact strength, Izod impact strength, melt flow rate or a combination thereof. Thermoplastic polymers affect the required mechanical properties (e.g., tensile strength, tensile elongation, flexural modulus, Charpy impact strength, Izod impact strength, melt flow rate or a combination thereof). Tungsten provides a relatively high dielectric strength and reflectivity required for x-ray applications. Barium sulfate provides a relatively high dielectric strength and high absorptivity that may be required in medical applications (e.g., x-ray equipment).

[0042] The radiopaque polymer formulations disclosed herein can generally be described as comprising a thermoplastic polymer and a filler.

[0043] Thermoplastic polymers

[0044] As described above, the presence and specific amounts of fillers and thermoplastic polymers produce a radiopaque polymer formulation that has the desired dielectric strength and high absorption and low reflectivity before and / or after x-ray exposure, but does not degrade the mechanical properties of the base polymer, i.e., tensile strength, tensile elongation, flexural modulus, Charpy impact strength, Izod impact strength, melt flow rate, or a combination thereof. Specifically, the thermoplastic polymer imparts the desired mechanical properties to the radiopaque polymer formulation. The thermoplastic polymer can be the base polymer of the radiopaque polymer formulation.

[0045] A variety of thermoplastic polymers are considered suitable for use in the radiopaque polymer formulations of the present invention. In some embodiments, the thermoplastic polymer may include a thermoplastic polyolefin and / or a thermoplastic elastomer.

[0046] In some embodiments, the thermoplastic polymer may include polyethylene, polypropylene (PP), polyphenylene sulfide (PPS), polybutylene terephthalate (PBT), thermoplastic polyester elastomer (TPC), polycarbonate, acrylonitrile butadiene styrene (ABS), or combinations thereof.

[0047] In some embodiments, the polypropylene may include a polypropylene homopolymer (i.e., composed of propylene monomers) or a polypropylene homopolymer having greater than 50 wt.% propylene monomers and other comonomers (e.g., C3-C 12 Polypropylene copolymers with α-olefins.

[0048] In some embodiments, the polypropylene may include maleic anhydride modified homopolypropylene.

[0049] In some embodiments, the polyethylene may include a polyethylene homopolymer (i.e., composed of ethylene monomers) or a polyethylene homopolymer having greater than 50% by weight of ethylene monomers and other comonomers (e.g., C3-C 12 Polyethylene copolymers of α-olefins.

[0050] In some embodiments, the amount of thermoplastic polymer in the radiopaque polymer formulation can be greater than 7 wt%, greater than or equal to 8 wt%, greater than or equal to 9 wt%, greater than or equal to 10 wt%, or even greater than or equal to 11 wt%. In some embodiments, the amount of thermoplastic polymer in the radiopaque polymer formulation can be less than or equal to 35 wt%, less than or equal to 34 wt%, less than or equal to 33 wt%, less than or equal to 32 wt%, less than or equal to 31 wt%, or even less than or equal to 30 wt%. In some embodiments, the amount of thermoplastic polymer in the radiopaque polymer formulation can be 7 wt % to 35 wt %, 7 wt % to 34 wt %, 7 wt % to 33 wt %, 7 wt % to 32 wt %, 7 wt % to 31 wt %, 7 wt % to 30 wt %, 8 wt % to 35 wt %, 8 wt % to 34 wt %, 8 wt % to 33 wt %, 8 wt % to 32 wt %, 8 wt % to 31 wt %, 8 wt % to 30 wt %, 9 wt % to 35 wt %, 9 wt % to 34 wt %, 9 wt % to 33 wt %, 9 wt % to 34 wt %, 9 wt % to 35 wt %, 9 wt % to 36 wt %, 9 wt % to 37 wt %, 9 wt % to 38 wt %. %, 11 wt % to 35 wt %, 11 wt % to 34 wt %, 11 wt % to 33 wt %, 11 wt % to 32 wt %, 11 wt % to 33 wt %, 11 wt % to 32 wt %, 11 wt % to 31 wt %, or even 11 wt % to 30 wt %, or any and all subranges formed by any of these endpoints.

[0051] In some embodiments, the density of the thermoplastic polymer may be greater than or equal to 0.7 g / cm 3 , or even greater than or equal to 0.8 g / cm 3 In some embodiments, the density of the thermoplastic polymer may be less than or equal to 1.3 g / cm 3 , or even less than or equal to 1.2 g / cm 3 In some embodiments, the density of the thermoplastic polymer may be 0.7 g / cm 3 Up to 1.3g / cm 3 , 0.7g / cm 3 Up to 1.2g / cm 3 , 0.8g / cm 3 Up to 1.3g / cm 3 , or even 0.8 g / cm 3 Up to 1.2g / cm 3 , or any and all sub-ranges formed by any of these endpoints.

[0052] In some embodiments, the melting point of the thermoplastic polymer may be greater than or equal to 110° C. or even greater than or equal to 120° C. In some embodiments, the melting point of the thermoplastic polymer may be less than or equal to 190° C. or even less than or equal to 180° C. In some embodiments, the melting point of the thermoplastic polymer may be from 110° C. to 190° C., from 110° C. to 180° C., from 120° C. to 190° C., or even from 120° C. to 180° C., or any and all subranges formed by any of these endpoints.

[0053] In some embodiments, the thermoplastic polymer may have a tensile elongation at break of 600% (percent), 650% or more, or even 700% or more. In some embodiments, the thermoplastic polymer may have a tensile elongation at break of 1000% or less, 950% or less, or even 900% or less. In some embodiments, the thermoplastic polymer may have a tensile elongation at break of 600% to 1000%, 600% to 950%, 600% to 900%, 650% to 1000%, 650% to 950%, 650% to 900%, 700% to 1000%, 700% to 950%, or even 700% to 900%, or any and all subranges formed by any of these endpoints.

[0054] In some embodiments, the tensile strength at break of the thermoplastic polymer may be greater than or equal to 10 megapascals (mPa), greater than or equal to 15 mPa, or even greater than or equal to 20 mPa. In some embodiments, the tensile strength at break of the thermoplastic polymer may be less than or equal to 80 mPa, less than or equal to 70 mPa, or even less than or equal to 60 mPa. In some embodiments, the tensile strength at break of the thermoplastic polymer may be from 10 mPa to 80 mPa, from 10 mPa to 70 mPa, from 10 mPa to 60 mPa, from 15 mPa to 80 mPa, from 15 mPa to 70 mPa, from 15 mPa to 60 mPa, from 20 mPa to 80 mPa, from 20 mPa to 70 mPa, or even from 20 mPa to 60 mPa, or any and all subranges formed by any of these endpoints.

[0055] In some embodiments, the flexural modulus of the thermoplastic polymer may be greater than or equal to 1000 mPa, greater than or equal to 1100 mPa, or even greater than or equal to 1200 mPa. In some embodiments, the flexural modulus of the thermoplastic polymer may be less than or equal to 1700 mPa, less than or equal to 1600 mPa, or even less than or equal to 1500 mPa. In some embodiments, the flexural modulus of the thermoplastic polymer may be from 1000 mPa to 1700 mPa, from 1000 mPa to 1600 mPa, from 1000 mPa to 1500 mPa, from 1100 mPa to 1700 mPa, from 1100 mPa to 1600 mPa, from 1100 mPa to 1500 mPa, from 1200 mPa to 1700 mPa, from 1200 mPa to 1600 mPa, or even from 1200 mPa to 1500 mPa, or any and all subranges formed by any of these endpoints.

[0056] In some embodiments, the melt flow rate of the thermoplastic polymer can be greater than or equal to 30 g / 10 min, greater than or equal to 35 g / 10 min, or even greater than or equal to 40 g / 10 min. In some embodiments, the melt flow rate of the thermoplastic polymer can be less than or equal to 90 g / 10 min, less than or equal to 85 g / 10 min, or even less than or equal to 80 g / 10 min. In some embodiments, the thermoplastic polymer can have a melt flow rate of 30 g / 10 min to 90 g / 10 min, 30 g / 10 min to 85 g / 10 min, 30 g / 10 min to 80 g / 10 min, 35 g / 10 min to 90 g / 10 min, 35 g / 10 min to 85 g / 10 min, 35 g / 10 min to 80 g / 10 min, 40 g / 10 min to 90 g / 10 min, 40 g / 10 min to 85 g / 10 min, or even 40 g / 10 min to 80 g / 10 min, or any and all subranges formed by any of these endpoints.

[0057] In some embodiments, the thermoplastic polymer may have an Izod impact strength (notched) of greater than or equal to 4.5 g / m2 measured at 23°C. 2 , greater than or equal to 5.0g / m 2 Or even greater than or equal to 5.5g / m 2 In some embodiments, the thermoplastic polymer may have an Izod impact strength (notched) of less than or equal to 8.0 g / m measured at 23°C. 2 , less than or equal to 7.5g / m 2 Or even less than or equal to 7.0 g / m 2In some embodiments, the thermoplastic polymer may have an Izod impact strength (notched) of 4.5 g / m2 measured at 23°C. 2 Up to 7.0g / m 2 4.5g / m 2 Up to 7.5g / m 2 4.5g / m 2 Up to 8.0g / m 2 5.0g / m 2 Up to 7.0g / m 2 5.0g / m 2 Up to 7.5g / m 2 5.0g / m 2 Up to 8.0g / m 2 5.5g / m 2 Up to 7.0g / m 2 5.5g / m 2 Up to 7.5g / m 2 Or even 5.5g / m 2 Up to 8.0g / m 2 , or any and all subranges formed by any of these endpoints.

[0058] In some embodiments, the Izod impact strength (notched) of the thermoplastic polymer measured at -20°C may be greater than or equal to 2.5 g / m 2 , greater than or equal to 3.0g / m 2 Or even greater than or equal to 3.5g / m 2 In some embodiments, the Izod impact strength (notched) of the thermoplastic polymer measured at -20°C may be less than or equal to 6.0 g / m 2 , less than or equal to 5.5g / m 2 Or even less than or equal to 5.0g / m 2 In some embodiments, the Izod impact strength (notched) of the thermoplastic polymer measured at -20°C may be 2.5 g / m 2 Up to 5.0g / m 2 , 2.5g / m 2 Up to 5.5g / m 2 , 2.5g / m 2 Up to 6.0g / m 2 3.0g / m 2 Up to 5.0g / m 2 3.0g / m 2 Up to 5.5g / m 2 3.0g / m 2 Up to 6.0g / m 2 3.5g / m 2 Up to 5.0g / m2 3.5g / m 2 Up to 5.5g / m 2 Or even 3.5g / m 2 Up to 6.0g / m 2 , or any and all subranges formed by any of these endpoints.

[0059] Suitable commercial embodiments of thermoplastic polymers are available from Formosa Plastics under the FORMOLENE brand, such as polypropylene homopolymer grade 1102KR; Sipolprene brand from SPA, such as 25170; Rigidex brand from INEOS GROUP, such as 450-HP60; NHU brand from Zhejiang NHU Special Materials Co., Ltd., such as 1150C; or Bondyram brand from Polyram, such as 1001.

[0060] filler

[0061] As described herein, the use of fillers including tungsten and barium sulfate can produce radiopaque polymer formulations that have desirable dielectric strength and desirable high absorptivity and low reflectivity both before and / or after x-ray exposure while maintaining the mechanical properties of thermoplastic polymers.

[0062] Fillers composed of tungsten have high dielectric properties and also have high reflective properties. Fillers composed of barium sulfate have high dielectric stability and absorptivity, but do not have the reflectivity required for x-ray applications. The presence and specific amounts of tungsten and barium sulfate provide the dielectric strength required before and / or after x-ray exposure, as well as the high absorptivity and low reflectivity required for radiopaque polymer formulations. Tungsten provides the dielectric strength and reflectivity required for x-ray applications. Barium sulfate provides relatively high dielectric strength and absorptivity that may be required in medical applications. Radiopaque polymer formulations containing fillers containing tungsten and barium sulfate remain stable after high intensity x-ray exposure (e.g., greater than or equal to 900 kGy (kilograys)) while having the required absorptivity.

[0063] In some embodiments, the filler may consist essentially of tungsten and barium sulfate. In some embodiments, the filler may not include bismuth subcarbonate, bismuth trioxide, bismuth oxychloride, or a combination thereof. In some embodiments, the filler may also include a non-radiopaque filler.

[0064] The filler may include tungsten. Tungsten has reflective properties because, at high loads, its electrical shielding properties dominate.

[0065] A variety of tungsten are considered suitable for use as fillers in the radiopaque polymer formulations of the present invention. In some embodiments, the tungsten may be in the form of an oxide. In some embodiments, the tungsten may be in the form of a powder.

[0066] In some embodiments, the average particle size of tungsten can be greater than or equal to 4 micrometers (μm), greater than or equal to 4.5 μm, or even greater than or equal to 5 μm. In some embodiments, the average particle size of tungsten can be less than or equal to 16 μm, less than or equal to 15.5 μm, or even less than or equal to 15 μm. In some embodiments, the average particle size of tungsten can be 4 μm to 16 μm, 4 μm to 15.5 μm, 4 μm to 15 μm, 4.5 μm to 16 μm, 4.5 μm to 15.5 μm, 4.5 μm to 15 μm, 5 μm to 16 μm, 5 μm to 15.5 μm, or even 5 μm to 15 μm, or any and all sub-ranges formed by any of these endpoints.

[0067] In some embodiments, tungsten is included in an amount greater than or equal to 25 wt%, greater than or equal to 28 wt%, or even greater than or equal to 30 wt%. In some embodiments, the amount of tungsten in the radiopaque polymer formulation can be less than or equal to 45 wt%, less than or equal to 43 wt%, or even less than or equal to 42 wt%. In some embodiments, the amount of thermoplastic polymer in the radiopaque polymer formulation can be 25 wt% to 45 wt%, 25 wt% to 43 wt%, 25 wt% to 42 wt%, 28 wt% to 45 wt%, 28 wt% to 43 wt%, 28 wt% to 42 wt%, 30 wt% to 45 wt%, 30 wt% to 43 wt%, or even 30 wt% to 42 wt%, or any and all subranges formed by any of these endpoints. When the amount of tungsten in the radiopaque polymer formulation is less than 25 wt%, the radiopaque polymer formulation may not have the reflectivity required for medical applications such as X-ray applications. When the amount of tungsten in the radiopaque polymer formulation is greater than 45 wt %, the radiopaque polymer formulation may not have desired dielectric strength and absorptivity.

[0068] Suitable commercial embodiments of tungsten are available from HC Starck GmbH under the HC Starck brand, for example HC grade tungsten metal powder.

[0069] The filler may include barium sulfate. Barium sulfate has attenuation properties due to its insulating and moderate thermal properties.

[0070] A variety of barium sulfates are considered suitable for use as fillers in the radiopaque polymer formulations of the present invention. In some embodiments, the barium sulfate may be in powder form.

[0071] In some embodiments, the median size D50 of barium sulfate can be greater than or equal to 0.01 μm, greater than or equal to 0.05 μm, or even greater than or equal to 0.1 μm. In some embodiments, the median size D50 of barium sulfate can be less than or equal to 0.5 μm, less than or equal to 0.4 μm, or even less than or equal to 0.3 μm. In some embodiments, the median size D50 of barium sulfate can be 0.01 μm to 0.5 μm, 0.01 μm to 0.4 μm, 0.01 μm to 0.3 μm, 0.05 μm to 0.5 μm, 0.05 μm to 0.4 μm, 0.05 μm to 0.3 μm, 0.1 μm to 0.5 μm, 0.1 μm to 0.4 μm, or even 0.1 μm to 0.3 μm, or any and all subranges formed by any of these endpoints.

[0072] In some embodiments, barium sulfate is included in an amount greater than or equal to 35 wt%, greater than or equal to 38 wt%, or even greater than or equal to 40 wt%. In some embodiments, the amount of barium sulfate in the radiopaque polymer formulation can be less than or equal to 55 wt%, less than or equal to 53 wt%, or even less than or equal to 51 wt%. In some embodiments, the amount of thermoplastic polymer in the radiopaque polymer formulation can be 35 wt% to 55 wt%, 35 wt% to 53 wt%, 35 wt% to 51 wt%, 38 wt% to 55 wt%, 38 wt% to 53 wt%, 38 wt% to 51 wt%, 40 wt% to 55 wt%, 40 wt% to 53 wt%, or even 40 wt% to 51 wt%, or any and all subranges formed by any of these endpoints. When the amount of barium sulfate in the radiopaque polymer formulation is less than 35 wt%, the radiopaque polymer formulation may not have the desired absorption rate. When the amount of barium sulfate in the radiopaque polymer formulation is greater than 55 weight percent, the radiopaque polymer formulation may have too high a dielectric strength both before and / or after x-ray exposure.

[0073] Suitable commercial embodiments of barium sulfate are available under the BLANC FIX brand from BLANC FIXE Micro or the BARIFLOR brand, for example BARIFLOR 8410, from Minerals Girona SA.

[0074] In some embodiments, the amount of filler in the radiopaque polymer formulation can be greater than 55 wt%, greater than or equal to 57 wt%, greater than or equal to 60 wt%, greater than or equal to 62 wt%, or even greater than or equal to 65 wt%. In some embodiments, the amount of filler in the radiopaque polymer formulation can be less than or equal to 95 wt%, less than or equal to 94 wt%, less than or equal to 93 wt%, less than or equal to 92 wt%, less than or equal to 91 wt%, or even less than or equal to 90 wt%. In some embodiments, the amount of filler in the radiopaque polymer formulation can be 55 wt % to 95 wt %, 55 wt % to 94 wt %, 55 wt % to 93 wt %, 55 wt % to 92 wt %, 55 wt % to 91 wt %, 55 wt % to 90 wt %, 57 wt % to 95 wt %, 57 wt % to 94 wt %, 57 wt % to 93 wt %, 57 wt % to 92 wt %, 57 wt % to 91 wt %, 57 wt % to 90 wt %, 60 wt % to 95 wt %, 60 wt % to 94 wt %, 60 wt % to 93 wt % %, 60 wt % to 92 wt %, 60 wt % to 91 wt %, 60 wt % to 90 wt %, 62 wt % to 95 wt %, 62 wt % to 94 wt %, 62 wt % to 93 wt %, 62 wt % to 92 wt %, 62 wt % to 91 wt %, 62 wt % to 90 wt %, 65 wt % to 95 wt %, 65 wt % to 94 wt %, 65 wt % to 93 wt %, 65 wt % to 92 wt %, 65 wt % to 91 wt %, or even 65 wt % to 90 wt %, or any and all subranges formed by any of these endpoints.

[0075] Radiopaque polymer preparations

[0076] As described herein, the use of fillers including tungsten and barium sulfate can produce radiopaque polymer formulations that have desirable dielectric strength and desirable high absorptivity and low reflectivity both before and / or after x-ray exposure while maintaining the mechanical properties of thermoplastic polymers.

[0077] In some embodiments, the radiopaque polymer formulation may not include manganese-zinc (Mn-Zn) ferrite.

[0078] In some embodiments, the dielectric strength of the radiopaque polymer formulation under DC load may be greater than or equal to 3 kV / mm, greater than or equal to 3.5 kV / mm, or even greater than or equal to 4 kV / mm. In some embodiments, the dielectric strength of the radiopaque polymer formulation under DC load may be less than or equal to 6 kV / mm, less than or equal to 5.5 kV / mm, or even less than or equal to 5 kV / mm. In some embodiments, the dielectric strength of the radiopaque polymer formulation under DC load can be 3 kV / mm to 6 kV / mm, 3 kV / mm to 5.5 kV / mm, 3 kV / mm to 5 kV / mm, 3.5 kV / mm to 6 kV / mm, 3.5 kV / mm to 5.5 kV / mm, 3.5 kV / mm to 5 kV / mm, 4 kV / mm to 6 kV / mm, 4 kV / mm to 5.5 kV / mm, or even 4 kV / mm to 5 kV / mm, or any and all sub-ranges formed by any of these endpoints.

[0079] In some embodiments, the breakdown strength of the radiopaque polymer formulation under DC load may be greater than or equal to 10 kV / mm, greater than or equal to 12 kV / mm, or even greater than or equal to 15 kV / mm. In some embodiments, the breakdown strength of the radiopaque polymer formulation under DC load may be less than or equal to 65 kV / mm, less than or equal to 60 kV / mm, or even less than or equal to 55 kV / mm. In some embodiments, the breakdown strength of the radiopaque polymer formulation under DC load can be 10 kV / mm to 65 kV / mm, 10 kV / mm to 60 kV / mm, 10 kV / mm to 55 kV / mm, 12 kV / mm to 65 kV / mm, 12 kV / mm to 60 kV / mm, 12 kV / mm to 55 kV / mm, 15 kV / mm to 65 kV / mm, 15 kV / mm to 60 kV / mm, or even 15 kV / mm to 55 kV / mm, or any and all sub-ranges formed by any of these endpoints.

[0080] In some embodiments, after exposure to X-rays of greater than or equal to 900 kGy, the breakdown strength of the radiopaque polymer formulation under DC load may be greater than or equal to 5 kV / mm, greater than or equal to 6 kV / mm, or even greater than or equal to 8 kV / mm. In some embodiments, after exposure to X-rays of greater than or equal to 900 kGy, the breakdown strength of the radiopaque polymer formulation under DC load may be less than or equal to 35 kV / mm, less than or equal to 32 kV / mm, or even less than or equal to 30 kV / mm. In some embodiments, the breakdown strength of the radiopaque polymer formulation under DC load after exposure to greater than or equal to 900 kGy of X-rays may be 5 kV / mm to 35 kV / mm, 5 kV / mm to 32 kV / mm, 5 kV / mm to 30 kV / mm, 6 kV / mm to 35 kV / mm, 6 kV / mm to 32 kV / mm, 6 kV / mm to 30 kV / mm, 8 kV / mm to 35 kV / mm, 8 kV / mm to 32 kV / mm, or even 8 kV / mm to 30 kV / mm, or any and all subranges formed by any of these endpoints.

[0081] In some embodiments, the radiopaque polymer formulation may have an absorptivity of 1 mm lead (Pb) of 5 mm or more, 5.5 mm or more, or even 6 mm or more. In some embodiments, the radiopaque polymer formulation may have an absorptivity of 1 mm Pb of 10 mm or less, 8.5 mm or less, or even 7 mm or less. In some embodiments, the radiopaque polymer formulation may have an absorptivity of 1 mm Pb of 5 mm to 10 mm, 5 mm to 8.5 mm, 5 mm to 7 mm, 5.5 mm to 10 mm, 5.5 mm to 8.5 mm, 5.5 mm to 7 mm, 6 mm to 10 mm, 6 mm to 8.5 mm, or even 6 mm to 7 mm, or any and all subranges formed by any of these endpoints.

[0082] In some embodiments, the radiopaque polymer formulation may have a Charpy impact strength (notched) of greater than or equal to 1.3 kJ / m 2 , greater than or equal to 1.4 kJ / m 2 Or even greater than or equal to 1.5 kJ / m 2 In some embodiments, the radiopaque polymer formulation may have a Charpy impact strength (notched) of less than or equal to 6.5 kJ / m 2 , less than or equal to 6.2kJ / m 2 Or even less than or equal to 6.0 kJ / m 2 In some embodiments, the Charpy impact strength (notched) of the radiopaque polymer formulation may be 1.3 kJ / m2 Up to 6.5 kJ / m 2 , 1.3kJ / m 2 Up to 6.2 kJ / m 2 , 1.3kJ / m 2 Up to 6.0 kJ / m 2 , 1.4kJ / m 2 Up to 6.5 kJ / m 2 , 1.4kJ / m 2 Up to 6.2 kJ / m 2 , 1.4kJ / m 2 Up to 6.0 kJ / m 2 , 1.5kJ / m 2 Up to 6.5 kJ / m 2 , 1.5kJ / m 2 Up to 6.2 kJ / m 2 Or even 1.5 kJ / m 2 Up to 6.0 kJ / m 2 , or any and all subranges formed by any of these endpoints.

[0083] In some embodiments, the radiopaque polymer formulation may have a Charpy impact strength (unnotched) of greater than or equal to 1.0 kJ / m 2 , greater than or equal to 1.5 kJ / m 2 Or even greater than or equal to 2.0 kJ / m 2 In some embodiments, the radiopaque polymer formulation may have a Charpy impact strength (unnotched) of less than or equal to 30.0 kJ / m 2 , less than or equal to 28.0kJ / m 2 Or even less than or equal to 26.0 kJ / m 2 In some embodiments, the Charpy impact strength (unnotched) of the radiopaque polymer formulation may be 1.0 kJ / m 2 Up to 30.0kJ / m 2 , 1.0kJ / m 2 Up to 28.0kJ / m 2 , 1.0kJ / m 2 Up to 26.0kJ / m 2 , 1.5kJ / m 2 Up to 30.0kJ / m 2 , 1.5kJ / m 2 Up to 28.0kJ / m 2 , 1.5kJ / m 2 Up to 26.0 kJ / m 2 , 2.0kJ / m 2 Up to 30.0kJ / m 2 , 2.0kJ / m2 Up to 28.0kJ / m 2 Or even 2.0 kJ / m 2 Up to 26.0 kJ / m 2 , or any and all subranges formed by any of these endpoints.

[0084] In some embodiments, the tensile strength at break of the radiopaque polymer formulation may be greater than or equal to 5 MPa, greater than or equal to 6 MPa, or even greater than or equal to 7 MPa. In some embodiments, the tensile strength at break of the radiopaque polymer formulation may be less than or equal to 45 MPa, less than or equal to 42 MPa, or even less than or equal to 40 MPa. In some embodiments, the tensile strength at break of the radiopaque polymer formulation may be 5 MPa to 45 MPa, 5 MPa to 42 MPa, 5 MPa to 40 MPa, 6 MPa to 45 MPa, 6 MPa to 42 MPa, 6 MPa to 40 MPa, 7 MPa to 45 MPa, 7 MPa to 42 MPa, or even 7 MPa to 40 MPa, or any and all subranges formed by any of these endpoints.

[0085] In some embodiments, the radiopaque polymer formulation may have a tensile elongation at break of greater than or equal to 0.15%, greater than or equal to 0.2%, or even greater than or equal to 0.25%. In some embodiments, the radiopaque polymer formulation may have a tensile elongation at break of less than or equal to 5.5%, less than or equal to 5.0%, or even less than or equal to 4.5%. In some embodiments, the radiopaque polymer formulation may have a tensile elongation at break of 0.15% to 5.5%, 0.15% to 5.0%, 0.15% to 4.5%, 0.2% to 5.5%, 0.2% to 5.0%, 0.2% to 4.5%, 0.25% to 5.5%, 0.25% to 5.0%, or even 0.25% to 4.5%, or any and all subranges formed by any of these endpoints.

[0086] The radiopaque polymer formulations described herein comprising a thermoplastic polymer and a filler including tungsten and barium sulfate exhibit desired dielectric strength and desired absorptivity before and / or after x-ray exposure while maintaining the mechanical properties of the thermoplastic polymer.

[0087] Antioxidants

[0088] In some embodiments, the radiopaque polymer formulations described herein may further comprise an antioxidant. In some embodiments, the antioxidant may be a primary phenolic light stabilizer, a hindered amine light stabilizer, or a combination thereof.

[0089] In some embodiments, the antioxidant may include tetrakis[methylene-3-(3,5-di-tert-butyl-4-hydroxyphenylpropionate)]methane. In some embodiments, the antioxidant may include a phenolic antioxidant.

[0090] In some embodiments, the amount of antioxidant in the radiopaque polymer formulation can be greater than or equal to 0.001 wt%, greater than or equal to 0.005 wt%, or even greater than or equal to 0.01 wt%. In some embodiments, the amount of antioxidant in the radiopaque polymer formulation can be less than or equal to 2 wt%, less than or equal to 1.5 wt%, or even less than or equal to 1 wt%. In some embodiments, the amount of antioxidant in the radiopaque polymer formulation can be 0.001 wt% to 2 wt%, 0.001 wt% to 1.5 wt%, 0.001 wt% to 1 wt%, 0.005 wt% to 2 wt%, 0.005 wt% to 1.5 wt%, 0.005 wt% to 1 wt%, 0.01 wt% to 2 wt%, 0.01 wt% to 1.5 wt%, or even 0.01 wt% to 1 wt%, or any and all subranges formed by any of these endpoints.

[0091] A suitable commercial embodiment of an antioxidant is available under the IRGANOX brand of BASF, for example grade 1010.

[0092] Fatty acid amide

[0093] In some embodiments, the radiopaque polymer formulations described herein may further comprise fatty acid amides to improve processing of the radiopaque polymer during extrusion and injection molding.

[0094] In some embodiments, the fatty acid amide may include ethylene bisstearamide (EBS).

[0095] In some embodiments, the amount of fatty acid amide in the radiopaque polymer formulation can be greater than or equal to 0.001 wt%, greater than or equal to 0.005 wt%, or even greater than or equal to 0.01 wt%. In some embodiments, the amount of fatty acid amide in the radiopaque polymer formulation can be less than or equal to 2 wt%, less than or equal to 1.5 wt%, or even less than or equal to 1 wt%. In some embodiments, the amount of fatty acid amide in the radiopaque polymer formulation can be 0.001 wt% to 2 wt%, 0.001 wt% to 1.5 wt%, 0.001 wt% to 1 wt%, 0.005 wt% to 2 wt%, 0.005 wt% to 1.5 wt%, 0.005 wt% to 1 wt%, 0.01 wt% to 2 wt%, 0.01 wt% to 1.5 wt%, or even 0.01 wt% to 1 wt%, or any and all subranges formed by any of these endpoints.

[0096] Suitable commercial embodiments of fatty acid amides are available from Croda Industrial Chemicals under the Crodamide brand, such as EBS.

[0097] Thioesters

[0098] In some embodiments, the radiopaque polymer formulations described herein may also include thioesters to improve processing and stability of the radiopaque polymer molding during extrusion and injection molding.

[0099] In some embodiments, the thioester may include a dialkyl ester of thiodipropionic acid.

[0100] In some embodiments, the amount of thioester in the radiopaque polymer formulation can be greater than or equal to 0.001 wt%, greater than or equal to 0.005 wt%, or even greater than or equal to 0.01 wt%. In some embodiments, the amount of thioester in the radiopaque polymer formulation can be less than or equal to 2 wt%, less than or equal to 1.5 wt%, or even less than or equal to 1 wt%. In some embodiments, the amount of thioester in the radiopaque polymer formulation can be 0.001 wt% to 2 wt%, 0.001 wt% to 1.5 wt%, 0.001 wt% to 1 wt%, 0.005 wt% to 2 wt%, 0.005 wt% to 1.5 wt%, 0.005 wt% to 1 wt%, 0.01 wt% to 2 wt%, 0.01 wt% to 1.5 wt%, or even 0.01 wt% to 1 wt%, or any and all subranges formed by any of these endpoints.

[0101] Suitable commercial embodiments of thioesters are available from BASF under the IRGANOX brand, for example PS 880FL.

[0102] additive

[0103] In some embodiments, the radiopaque polymer formulation may further include additives. In some embodiments, the additives may include: adhesion promoters; biocides; antifogging agents; antistatic agents; foaming and blowing agents; binders and binding polymers; polar copolymers (e.g., ethylene vinyl acetate (EVA), ethylene butyl acrylate (EBA), or ethyl methacrylate (EMA)); dispersants; flame retardants and smoke suppressants; mineral fillers; initiators; lubricants; mica; pigments, colorants and dyes; processing aids; mold release agents; silanes, titanates / esters and zirconates / esters; slip agents and anti-caking agents; ultraviolet light stabilizers; viscosity modifiers; waxes; or combinations thereof. In some embodiments, the additives may include calcium stearate and / or didodecyl-3,3'-thiodipropionate.

[0104] In some embodiments, the amount of additive in the radiopaque polymer formulation can be greater than or equal to 0.001 wt%, greater than or equal to 0.005 wt%, or even greater than or equal to 0.01 wt%. In some embodiments, the amount of additive in the radiopaque polymer formulation can be less than or equal to 2 wt%, less than or equal to 1.5 wt%, or even less than or equal to 1 wt%. In some embodiments, the amount of additive in the radiopaque polymer formulation can be 0.001 wt% to 2 wt%, 0.001 wt% to 1.5 wt%, 0.001 wt% to 1 wt%, 0.005 wt% to 2 wt%, 0.005 wt% to 1.5 wt%, 0.005 wt% to 1 wt%, 0.01 wt% to 2 wt%, 0.01 wt% to 1.5 wt%, or even 0.01 wt% to 1 wt%, or any and all subranges formed by any of these endpoints.

[0105] Technology

[0106] In some embodiments, the radiopaque polymer formulations described herein can be prepared by a batch process or a continuous process.

[0107] In some embodiments, the components of the radiopaque polymer formulation include a thermoplastic polymer and a filler (which includes tungsten and barium sulfate), which can be added to an extruder (e.g., a ZSK 26MC Coperion extruder) and blended. In some embodiments, blending (e.g., in the barrel of an extruder) can be performed at a temperature of 80° C. to 350° C.

[0108] Blending (also known as admixing) devices are well known to those skilled in the art and generally include feeding means, in particular at least one hopper for powdered materials and / or at least one injection pump for liquid materials; high shear mixing means, such as a co-rotating or counter-rotating twin-screw extruder, typically comprising a feed screw placed in a heating barrel (or tube); an output head that gives the extrudate shape; and means for cooling the extrudate by air cooling or by water circulation. The extrudate is generally in the form of a rod that continuously leaves the device, and it can be cut or formed into pellets. However, other forms can be obtained by assembling a die of the desired shape on the output die. For example, in some embodiments, the process may include profile extrusion, including forcing the extrudate to be cut into the desired linear shape (e.g., channel or tube) of the final radiopaque polymer formulation through a die.

[0109] Obviously, modifications and variations are possible without departing from the scope of the disclosure as defined in the appended claims.More specifically, although some aspects of the present disclosure are identified herein as preferred or particularly advantageous, it is contemplated that the present disclosure is not necessarily limited to these aspects.

Claims

1. A radiopaque polymer formulation comprising: Thermoplastic polymers; as well as A filler comprising: 25 weight percent (wt %) to 45 weight percent tungsten based on the total amount of the radiopaque polymer formulation; and 35 weight percent (wt %) to 55 wt % of barium sulfate based on the total amount of the radiopaque polymer formulation.

2. The radiopaque polymer formulation of claim 1, wherein: The radiopaque polymer formulation has a dielectric strength under DC load of 3 kV / mm to 6 kV / mm or 4 kV / mm to 5 kV / mm.

3. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein The radiopaque polymer formulation has a 1 millimeter (mm) lead (Pb) absorption rate of 5 to 10 mm or 6 to 7 mm.

4. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein The radiopaque polymer formulation includes 7 wt % to 35 wt %, 9 wt % to 32 wt %, or 11 wt % to 30 wt % of the thermoplastic polymer, based on the total amount of the radiopaque polymer formulation.

5. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein Thermoplastic polymers include thermoplastic polyolefins, thermoplastic elastomers, or thermoplastic polyolefins and thermoplastic elastomers.

6. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein The thermoplastic polymer includes polypropylene (PP), polyphenylene sulfide (PPS), polybutylene terephthalate (PBT), thermoplastic polyester elastomer (TPC), or a combination thereof.

7. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein The radiopaque polymer formulation includes 28 wt % to 43 wt % tungsten or 30 wt % to 42 wt % tungsten based on the total amount of the radiopaque polymer formulation.

8. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein The radiopaque polymer formulation includes 38 wt % to 53 wt % of barium sulfate or 40 wt % to 51 wt % of barium sulfate, based on the total amount of the radiopaque polymer formulation.

9. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein The radiopaque polymer formulation further comprises 0.01 wt % to 1 wt % of an antioxidant based on the total amount of the radiopaque polymer formulation.

10. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein The radiopaque polymer formulation further comprises 0.01 wt % to 1 wt % of a fatty acid amide, based on the total amount of the radiopaque polymer formulation.

11. The radiopaque polymer formulation of claim 10, wherein: Fatty acid amides include ethylene bisstearamide (EBS).

12. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein The radiopaque polymer formulation further comprises 0.01 wt % to 1 wt % of a thioester based on the total amount of the radiopaque polymer formulation.

13. The radiopaque polymer formulation of claim 12, wherein: Thioesters include dialkyl esters of thiodipropionic acid.

14. A radiopaque polymer formulation as claimed in any one of the preceding claims, wherein The formulation further comprises 0.01 wt % to 1 wt % of additives based on the total amount of the radiopaque polymer formulation.

15. A medical device comprising a radiopaque polymer formulation as claimed in any one of the preceding claims.

16. The medical device of claim 15, wherein: The medical device is an X-ray shielding component.