WO2024015022A1

WO2024015022A1 - A composition and an article

Info

Publication number: WO2024015022A1
Application number: PCT/SG2023/050495
Authority: WO
Inventors: Yin Chiang Boey; Yingying HUANG; Foo Cheong NG
Original assignee: National University Of Singapore; Singapore Health Services Pte Ltd
Priority date: 2022-07-15
Filing date: 2023-07-14
Publication date: 2024-01-18

Abstract

There are provided a composition and a method of preparing the composition. The composition comprises a composite powder material and an elastomer, wherein the composite powder material comprises a) tourmaline particles, b) rare-earth mineral particles, c) silicate mineral particles, d) metal oxide particles, and e) a binder, and wherein the sizes of the a), b), c) and d) are 5 pm or less. There are also provided an article and a method of preparing an article. There are further provided methods of using and uses of the article in the form of catheters, particularly urinary catheters.

Description

A Composition And An Article

References to Related Application

This application claims priority to Singapore application number 10202250483R filed with the Intellectual Property Office of Singapore on 15 July 2022, the contents of which are hereby incorporated by reference.

Technical Field

The present invention generally relates to a composition and a method of preparing a composition. The present invention further relates to an article and a method of preparing an article. The present invention further relates to methods of using and uses of the article in the form of catheters, particularly urinary catheters.

Background Art

A urinary tract infection (UTI) is an infection in any part of the urinary system, including kidneys, ureters, bladder, and urethra. Most infections involve the lower urinary tract (bladder and urethra). Among UTIs acquired in the hospital, approximately 75% are associated with a urinary catheter. Catheter associated urinary tract infections (CAUTI) account for over 1 million cases in the US alone and almost 80% of the nosocomial infection worldwide. Annual treatment costs exceed $350 million every year, which illustrate the urgency of the situation.

Encrustation and biofilm formation are two main issues that afflict conventional urinary catheters and make CAUTIs harder to treat, they can overlap and make condition worse in an infection. While encrustation and biofilm formation are caused by different factors, encrustation begins with the colonization of urease-positive pathogens. Urease is an enzyme that catalyzes the hydrolysis of urea into ammonia and carbamate. The presence of urine in conventional urinary catheters creates a suitable environment for urease-positive pathogens. Ammonia is alkaline, and increases the pH of urine, leading to deposition of calcium and magnesium phosphate crystals on the catheter, which eventually leads to complete occlusion of the catheter through encrustation. Free-floating or planktonic bacteria may come across a surface submerged in the fluid and become attached to the surface within a few minutes. The attached bacteria produce slimy, extracellular polymeric substances (EPS) that colonize the surface and form the conditioning biofilm. Extracellular polymeric substance production allows the emerging biofilm community to develop a complex, three-dimensional structure that is influenced by a variety of environmental factors. Biofilms have been reported to be approximately 200 pm in thickness, which occasionally reach a thickness of 500 pm.

Various conventional approaches have been evaluated to prevent CAUTI, including improving catheter design, fabricating urinary catheter coating, and emphasizing short-term use. Despite many efforts to solve CAUTIs, most conventional approaches have failed due to microbial resistance. According to the WHO, microbes develop resistance upon exposure to antimicrobial drugs. Antibiotic resistance has led to the development of “superbugs” that are resistant to many antimicrobial therapies for treatment of nosocomial infection.

Accordingly, there is a need to provide a urinary catheter that ameliorates or addresses the problems as described above.

Summary

In one aspect, there is provided a composition comprising a composite powder material and an elastomer, wherein the composite powder material comprises a) tourmaline particles; b) rare-earth mineral particles; c) silicate mineral particles; d) metal oxide particles; and e) a binder, and wherein the sizes of the a) tourmalines particles, the b) rare earth mineral particles, the c) silicate mineral particles and the d) metal oxide particles are 5 pm or less.

In another aspect, there is provided a preparing a composition, comprising the step of mixing a composite powder material and an elastomer, wherein the composite powder material comprises a) tourmaline particles; b) rare-earth mineral particles; c) silicate mineral particles; d) metal oxide particles; and e) a binder, and wherein the sizes of the a) tourmalines particles, the b) rare earth mineral particles, the c) silicate mineral particles and the d) metal oxide particles are 5 pm or less.

In another aspect, there is provided an article comprising the composition as described herein.

In another aspect, there is provided a method of preparing an article, comprising the steps of: a) heating the composition as described herein to form a blend; b) extruding the blend of step (a) in an extruder to form composite fibres; and c) forming the article from the composite fibres of step (b).

In another aspect, there is provided a method of preventing or treating an infection in a urinary tract, a blood system, implanted devices, intracorporeal or intracavitary drainage systems in a subject, comprising the step of applying the catheter as described herein in the subject.

In another aspect, there is provided a method of releasing urine from a subject, comprising the step of applying the urinary catheter as described herein in a urinary tract of the subject.

In another aspect, there is provided a method of preventing or treating a urinary tract infection in a subject, comprising the step of applying the urinary catheter as described herein in a urinary tract of the subject.

In another aspect, there is provided the urinary catheter as described herein for use in preventing or treating a urinary tract infection.

In another aspect, there is provided the urinary catheter as described herein when used in preventing or treating a urinary tract infection.

Definitions

The following words and terms used herein shall have the meaning indicated:

The term “elastomer” as used herein when referring to a substance describes that the substance is capable of recovering its original shape after being stretched to great extents.

The term “biodegradable” as used herein when referring to a substance describes that the substance’s chemical and physical characteristics undergo deterioration and that the substance completely degrades when exposed to microorganisms, aerobic, and anaerobic processes.

The term “antifouling” as used herein when referring to a substance describes that the substance repel or prevent the attachment of protein or microorganisms that attach to the substance.

The word “substantially” does not exclude “completely” e.g. a composition which is “substantially free” from Y may be completely free from Y. Where necessary, the word “substantially” may be omitted from the definition of the invention.

Unless specified otherwise, the terms "comprising" and "comprise", and grammatical variants thereof, are intended to represent "open" or "inclusive" language such that they include recited elements but also permit inclusion of additional, unrecited elements.

The term "about" as used herein typically means +/- 5 % of the stated value, more typically +/- 4 % of the stated value, more typically +/- 3 % of the stated value, more typically, +/- 2 % of the stated value, even more typically +/- 1 % of the stated value, and even more typically +/- 0.5 % of the stated value.

Throughout this disclosure, certain embodiments may be disclosed in a range format. It should be understood that the description in range format is merely for convenience and brevity and should not be construed as an inflexible limitation on the scope of the disclosed ranges. Accordingly, the description of a range should be considered to have specifically disclosed all the possible sub-ranges as well as individual numerical values within that range. For example, description of a range such as from 1 to 6 should be considered to have specifically disclosed sub-ranges such as from 1 to 3, from 1 to 4, from 1 to 5, from 2 to 4, from 2 to 6, from 3 to 6 etc., as well as individual numbers within that range, for example, 1, 2, 3, 4, 5, and 6. This applies regardless of the breadth of the range.

Certain embodiments may also be described broadly and generically herein. Each of the narrower species and subgeneric groupings falling within the generic disclosure also form part of the disclosure. This includes the generic description of the embodiments with a proviso or negative limitation removing any subject matter from the genus, regardless of whether or not the excised material is specifically recited herein.

Detailed Disclosure of Embodiments

Exemplary, non-limiting embodiments of a composition will now be disclosed. The composition comprises a composite powder material and an elastomer, wherein the composite powder material comprises a) tourmaline particles; b) rare-earth mineral particles; c) silicate mineral particles; d) metal oxide particles; and e) a binder, and wherein the sizes of the a) tourmalines particles, the b) rare earth mineral particles, the c) silicate mineral particles and the d) metal oxide particles are 5 pm or less.

The composition may consist of the composite powder material and the elastomer. The composition may consist essentially of the composite powder material and the elastomer. The composite powder material may produce negative ions by Jules-Renard effect, utilizing tourmaline or natural energy of other negative ion mineral materials to excite air ionization to produce the negative ions. Utilizing natural negative ion generating material to obtain negative ions has the advantage of low cost as an economical production method.

The composite powder material may be uniformly distributed within the composition.

Advantageously, the composition may be made into an article with a uniform distribution of the composite powder material within the article. This may prevent the composite powder material from leaking out of the article. As the composite powder material has antibacterial properties, the article made from the composition may retain a desirable antibacterial performance through a prolonged exposure to bacteria.

The article may kill bacteria without substantially developing resistance in the bacteria. As another example, the article may kill bacteria without developing resistance in the bacteria. As another example, the article may not be substantially carcinogenic or mutagenic. As another example, the article may not be carcinogenic or mutagenic. Therefore, the article may be considered to be safe to mammals (including human).

The a) tourmalines particles, the b) rare earth mineral particles, the c) silicate mineral particles and the d) metal oxide particles may have a size in the range of about 0.01 pm to about 5 pm, about 0.05 pm to about 5 pm, about 0.1 pm to about 5 pm, about 0.5 pm to about 5 pm, about 1 pm to about 5 pm, about 3 pm to about 5 pm, about 0.01 pm to about 3 pm, about 0.01 pm to about 1 pm, about 0.01 pm to about 0.5 pm, about 0.01 pm to about 0.1 pm, or about 0.01 pm to about 0.05 pm. The size may refer to the average size of the a) tourmalines particles, the b) rare earth mineral particles, the c) silicate mineral particles and the d) metal oxide particles. The size may be regarded as the diameter or equivalent diameter (such as equivalent spherical diameter) of the a) tourmalines particles, the b) rare earth mineral particles, the c) silicate mineral particles and the d) metal oxide particles.

The tourmaline particles may have a weight percentage in the range of about 20 weight% to about 60 weight%, about 25 weight% to about 60 weight%, about 30 weight% to about 60 weight%, about 35 weight% to about 60 weight%, about 40 weight% to about 60 weight%, about 45 weight% to about 60 weight%, about 50 weight% to about 60 weight%, about 55 weight% to about 60 weight%, about 20 weight% to about 55 weight%, about 20 weight% to about 50 weight%, about 20 weight% to about 45 weight%, about 20 weight% to about 40 weight%, about 20 weight% to about 35 weight%, about 20 weight% to about 30 weight%, about 20 weight% to about 25 weight% based on the total weight of the composite powder material. The rare earth mineral particles may have a weight percentage in the range of about 20 weight% to about 40 weight%, about 25 weight% to about 40 weight%, about 30 weight% to about 40 weight%, about 35 weight% to about 40 weight%, about 20 weight% to about 35 weight%, about 20 weight% to about 30 weight%, about 20 weight% to about 25 weight% based on the total weight of the composite powder material.

The rare-earth mineral particles may be selected from the group consisting of monazite, bastnaesite, xenotime and mixtures thereof.

The silicate particles may have a weight percentage in the range of about 20 weight% to about 50 weight%, about 25 weight% to about 50 weight%, about 30 weight% to about 50 weight%, about 35 weight% to about 50 weight%, about 40 weight% to about 50 weight%, about 45 weight% to about 50 weight%, about 20 weight% to about 45 weight%, about 20 weight% to about 40 weight%, about 20 weight% to about 35 weight%, about 20 weight% to about 30 weight%, about 20 weight% to about 25 weight% based on the total weight of the composite powder material.

The silicate particles may be muscovite. The silicate particles may further comprise zeolite, diatomite, bentonite or other silicate particles to make up the required quantity for the composite materials. The silicate particles may further comprise zeolite.

The metal oxide particles may have a weight percentage in the range of about 1 weight% to about 30 weight%, about 1 weight% to about 30 weight%, about 3 weight% to about 30 weight%, about 5 weight% to about 30 weight%, about 7 weight% to about 30 weight%, about 10 weight% to about 30 weight%, about 15 weight% to about 30 weight%, about 20 weight% to about 30 weight%, about 25 weight% to about 30 weight%, about 1 weight% to about 25 weight%, about 1 weight% to about 20 weight%, about 1 weight% to about 15 weight%, about 1 weight% to about 10 weight%, about 1 weight% to about 7 weight%, about 1 weight% to about 5 weight%, or about 1 weight% to about 3 weight% based on the total weight of the composite powder material.

The metal oxide may be zinc oxide, copper oxide, titanium oxide or zinc peroxide. The metal oxide may be an enhancer of the antibacterial property of the composite powder material. The tourmaline particles and the rare-earth mineral particles may kill bacteria without physical contact. The metal oxide can kill bacteria upon physical contact. These types of antibacterial effect are complementary to each other. The metal oxide may also be a binding agent and photocatalyst for air purification. The metal oxide may further comprise a rare-earth oxide selected from the group consisting of cerium oxide, ytterbium oxide, lanthanum oxide, neodymium oxide, holmium oxide, thulium oxide, lutetium oxide and mixtures thereof. The rare-earth oxide may also be an enhancer of an antibacterial property of the composite powder material. The binder may have a weight percentage in the range of about 1 weight% to about 20 weight%, about 1 weight% to about 20 weight%, about 3 weight% to about 20 weight%, about 5 weight% to about 20 weight%, about 10 weight% to about 20 weight%, about 15 weight% to about 20 weight%, about 1 weight% to about 15 weight%, about 1 weight% to about 10 weight%, about 1 weight% to about 5 weight%, about 1 weight% to about 3 weight% based on the total weight of the composite powder material.

The binder may be selected from the group consisting of acrylic acid, polyvinylpyrrolidone (PVP), acrylates, acrylamides, and their copolymers/mixtures thereof. Any other polymer that may be used as a binder may also be applicable. The binder may be a film forming agent.

The composite powder material may further comprise other mineral particles, such as silicon dioxide, germanium oxide, arsenic oxide, boron oxide. The other mineral particles may act as a support for making up the component of the composite powder material. The composite powder material may further comprise silicon dioxide.

The composite powder material may further comprise silver particles or other antibacterial particles known in the art.

The composite powder material may comprise:

20 to 60 weight% of tourmaline particles;

20 to 40 weight% of monazite;

20 to 40 weight% of muscovite;

1 to 10 weight% of zeolite;

1 to 10 weight% of silicon dioxide

1 to 10 weight% of zinc oxide; and

1 to 20 weight% of acrylic acid.

In the composition, the composite powder material may have a weight percentage in the range of about 0.01 weight% to about 50 weight%, about 1 weight% to about 50 weight%, about 10 weight% to about 50 weight%, about 0.01 weight% to about 10 weight% or about 0.01 weight% to about 1 weight%, based on the total weight of the composition. Advantageously, keeping the weight percentage of the composite powder material at less than or equal to about 50 weight% based on the total weight of the composition may prevent phase separation in the composition, thus improving properties of the article formed from the composition. Non-limiting examples of the elastomer include thermoplastic polyurethane (TPU), polyurethane (PU), silicone, latex and a combination thereof. The elastomer may be thermoplastic polyurethane (TPU).

The composition may be in the form of pellets.

Exemplary, non-limiting embodiments of a method of preparing a composition will now be disclosed. The method comprises the step of mixing a composite powder material and an elastomer, wherein the composite powder material comprises a) tourmaline particles; b) rare-earth mineral particles; c) silicate mineral particles; d) metal oxide particles; and e) a binder, and wherein the sizes of the a) tourmalines particles, the b) rare earth mineral particles, the c) silicate mineral particles and the d) metal oxide particles are 5 pm or less.

The method may further comprise the following steps before the mixing step to prepare the composite powder material: a) grinding a mixture of tourmaline, rare-earth mineral, silicate mineral, and metal oxide particles having particle sizes of 5 pm or less to form a ground mixture; b) adding a binder to the ground mixture of step a); and c) drying the ground mixture of step b) to obtain the composite powder material.

The mixing step may be undertaken by mechanical stirring of the composite powder material and the elastomer. The mixing step may alternatively or additionally be undertaken using two roll rubber mixing mills.

Exemplary, non-limiting embodiments of an article will now be disclosed. The article comprises the composition as described herein.

The article may be in the form of a film, a tubing, a catheter, a stent, an implanted device and the like. The article may be a urinary catheter, a bladder drainage catheter, a urinary system stent, a kidney drainage catheter, an intravenous access plug, an intravascular catheter, an intravascular stent, an implanted device (e,g, a cardiac device such as a cardiac pacemaker, an implantable cardiac defibrillator or a coronary stent; a reconstructive joint replacement such as a hip or a knee; a functional implant such as an artificial urinary sphincter, a penile prosthesis, a cochlear implant or a spinal nerve modulator; a device for access such as an intraocular lens, a portacath, a central venous catheter or a peripheral inserted central cather; an electrical lead; an electrical battery; a neuromodulator; a tissue engineered construct; a drug delivery system; a device for drainage such as an abdominal drain, a chest tube, a nephrostomy tube, a suprapubic catheter or a peritoneal venous shunt or a cosmetic implant such as a breast implant or a testicular implant) or an intracorporeal or intracavitary drainage system (such as a postoperative surgical drain or a percutaneous drainage catheter).

Advantageously, the article may have a uniform distribution of the composite powder material. This may prevent the composite powder material from leaking out of the article. As the composite powder material has antibacterial properties, the article may retain a desirable antibacterial performance through a prolonged exposure to bacteria.

The article may further comprise a coating on a surface.

The coating may be single-layered or multi-layered.

The coating may comprise a biodegradable polymer, an antifouling polymer or combinations thereof.

The biodegradable polymer may degrade and slough away when a biofilm forms on the surface of the article that is coated. This may prevent or reduce a formation of the biofilm.

The antifouling polymer may not kill microorganisms directly. The antifouling polymer may prevent an attachment of microorganisms on the surface of the article that is coated. This may prevent formation of biofilm by mechanisms such as steric repulsion, electrostatic repulsion, and low surface energy.

Non-limiting examples of the biodegradable polymer include poly(lactic-co-glycolic acid) (PLGA), polycaprolactone (PCL), poly(L-lactide-co-s-caprolactone) (PLC) and combinations thereof.

Non-limiting examples of the antifouling polymer include poly(ethylene glycol) (PEG), poly (acrylamide), poly(acrylates), betaine -based zwitterionic polymers, amphiphilic polymers and combinations thereof.

The coating may further comprise an additive. The additive may be a urological beneficial agent. The additive may be nitric oxide (NO), nitric oxide releasing materials, nitric oxide donor or combinations thereof. The additive may be NO-donor sodium nitroprusside (SNP).

The urological beneficial agent may be released from the coating at a controllable release rate. The release rate may be controlled via diffusion and degradation control. About 80% of the urological beneficial agent may be released in about 4 weeks to about 12 weeks.

Exemplary, non-limiting embodiments of a method of preparing an article will now be disclosed. The method comprises the steps of: a) heating the composition as described herein to form a blend; b) extruding the blend of step a) in an extruder to form composite fibres; and c) forming the article from the composite fibres of step b).

The heating step a) may be undertaken at a temperature in the range of about 180 °C to about 210 °C, about 190 °C to about 210 °C, about 200 °C to about 210 °C, about 180 °C to about 200 °C or about 180 °C to about 190 °C.

The extruder in extruding step b) may be a twin screw extruder. The extruding step b) may be undertaken by feeding the twin screw extruder with the blend of step a). The twin screw extruder may be rotating at a rotation speed of about 10 rounds per minute to about 15 rounds per minute, about 12 rounds per minute to about 15 rounds per minute or about 10 rounds per minute to about 12 rounds per minute.

The extruding step b) and the forming step c) may be undertaken for a total duration in the range of about 10 minutes to about 20 minutes, about 15 minutes to about 20 minutes or about 10 minutes to about 15 minutes.

Exemplary, non-limiting embodiments of a method of preventing or treating an infection in a urinary tract, a blood system, implanted devices, intracorporeal or intracavitary drainage systems in a subject will now be disclosed. The method comprises the step of applying the catheter as described herein in the subject.

Exemplary, non-limiting embodiments of a method of releasing urine from a subject will now be disclosed. The method comprises the step of applying the urinary catheter as described herein in a urinary tract of the subject.

Exemplary, non-limiting embodiments of a method of preventing or treating a urinary tract infection in a subject will now be disclosed. The method comprises the step of applying the urinary catheter as described herein in a urinary tract of the subject.

Exemplary, non-limiting embodiments of the urinary catheter as described herein for use in preventing or treating a urinary tract infection will now be disclosed.

Exemplary, non-limiting embodiments of the urinary catheter as described herein when used in preventing or treating a urinary tract infection will now be disclosed.

Brief Description of Drawings

The accompanying drawings illustrate a disclosed embodiment and serve to explain the principles of the disclosed embodiment. It is to be understood, however, that the drawings are designed for purposes of illustration only, and not as a definition of the limits of the invention. FIG. 1

[FIG. 1] shows a schematic diagram of a bladder (11) and a urethra (12) with the deployment of a urinary catheter (21) according to one embodiment of the present disclosure with inflated balloon (22).

FIG. 2

[FIG. 2] shows a schematic diagram of a urinary catheter (21) according to one embodiment of the present disclosure with balloon (22), balloon port (23), bladder opening (24) and urine drainage port (25).

FIG. 3

[FIG. 3] shows a cross-sectional view of a urinary catheter (21) with a multilayer coating according to one embodiment of the present disclosure.

FIG. 4

[FIG. 4] shows a cross-sectional view of a urinary catheter (21) according to one embodiment of the present disclosure comprising a biostable catheter tubing (31) loaded with the composite powder material of the present disclosure (34) only.

FIG. 5

[FIG. 5] shows a cross-sectional view of a urinary catheter (21) according to one embodiment of the present disclosure comprising a biostable catheter tubing (31) and a biodegradable layer (32).

FIG. 6

[FIG. 6] shows a cross-sectional view of a urinary catheter (21) according to one embodiment of the present disclosure comprising a biostable catheter tubing (31) and a zwitterionic layer (33).

FIG. 7

[FIG. 7] shows a cross-sectional view of a urinary catheter (21) with a multilayer coating according to one embodiment of the present disclosure.

Detailed Description of Drawings

FIG. 3

[FIG. 3] shows a cross-sectional view of a urinary catheter (21) with a multilayer coating according to one embodiment of the present disclosure. The multilayer coating comprises a biostable catheter tubing (31), a biodegradable layer (32), a zwitterionic layer (33) as topcoat. The biostable catheter tubing (31) is loaded with the composite powder material of the present disclosure (34). FIG. 7

[FIG. 7] shows a cross-sectional view of a urinary catheter (21) with a multilayer coating according to one embodiment of the present disclosure. The multilayer coating comprises a biostable catheter tubing (31), a biodegradable layer (32), a zwitterionic layer (33) as topcoat; and a hydration layer (35) formed when the urinary catheter is in contact with liquid. The biostable catheter tubing (31) is loaded with the composite powder material of the present disclosure (34).

Examples

Non- limiting examples of the invention will be further described in greater detail by reference to specific Examples, which should not be construed as in any way limiting the scope of the invention.

Example 1 - Preparation of Composite Powder Material

40 grams of tourmaline (purchased from Hebei Longcai Mineral Co., Ltd, Hebei, China), 30 grams of monazite (purchased from Hebei Longcai Mineral Co., Ltd, Hebei, China), 30 grams of muscovite (purchased from Hebei Longcai Mineral Co., Ltd, Hebei, China), 5.5 grams of zeolite (purchased from Jiangxi Xintao Tech Pte Ltd, Hebei, China), 5.5 grams of zinc oxide (purchased from Chong Qing Yumeco Import & Export Co. ltd, Chong Qing, China) and 5.5 grams of silicon dioxide (purchased from Taiwan Haiweisheng Biotechnology Pte Ltd, Taiwan) were mixed and grinded in a ball mill machine (Simoloyer CM08) until the particle sizes were less than 5 pm. Zirconia (purchased from Chong Qing Yumeco Import & Export Co. ltd, Chong Qing, China) was used as grinding media. The mixture was grinded for 8 to 12 hours and powders were removed off from bottle wall every 2 hours as the powders would stick to bottle wall. Total usage amount of zirconia beads was 28 to 35% of volume ratio of tank. The proportion of 80 mm beads was 80 to 100% and the proportion of 20 mm beads was 20 to 0%.

26.25 mL of 40 weight% acrylic acid in water (purchased from Ningbo Meichengjiahe Pharmaceutical Technology Co., LTD, Zhejiang, China) was subsequently added. The mixture was dried at 80 °C for 120 minutes to obtain the composite powder material.

Example 2 - Preparation of Urinary Catheter

Eirstly, polyurethane (PU, purchased from Lubrizol Corporation, Ohio, USA) was mixed with the composite powder material as described in Example 1 at a ratio of 10:1 mechanically to form a blend.

Secondly, the blend was heated, and further blended in its molten state, using shear forces in twin-screw extruders. In details, less than 1 weight% of the composite powder material (based on the total weight of the urinary catheter to be formed) was weighed and incorporated with 10 weight% polyurethane (based on the total weight of the urinary catheter to be formed) throughout the compounding process. The core of the compounders was a vertically positioned, liquid-tight barrel with two easily detachable, conical mixing screws. Both screws and housing were specially engineered to minimize wear and to resist chemicals in a wide temperature range. The robust design ensured the generation of reproducible and stable data for years. The vertical position of the liquid-tight barrel allowed the processing of low viscous fluids down to ca. 10 Pa.s. The liquid-tight barrel containing two easily detachable, conical mixing screws was then heated to 180 to 210 °C to improve the mixing and extrusion of the composite material. The polyurethane and the composite power material were fed manually with a rotation speed of 12 rounds per minute (RPM) by the twin screws. Continuous composite fibres were drawn out using a Cast Film Device (35mm) and the total duration of compounding and extruding was set to be within 15 minutes. The duration of compounding was critical to improve mixing of the polyurethane and the composite powder material, which required at least 5 minutes. The fibres were cut into small pieces for a second extrusion.

Thirdly, the extruded fibres were blended with the remaining more than 89 weight% polyurethane (based on the total weight of the urinary catheter to be formed) at ratios predetermined according to the previous steps and the second step was repeated.

Eventually, a long, thin tube was made by pouring the blending material into a room temperature vulcanization (RTV) mold, which was in the desired shape and diameter of the catheter.

The material was then cured with heat for a duration of 0.5 to 40 hours and subsequently cooled down. Once it was cool, the tube was pulled out from the mold.

The tube had one opening formed by the mold and another small opening was punched at the distal end of the tube. A thin band of cured latex was covered by hand over the tube so that it formed a sheath over where the opening was made.

To keep the catheter in place inside the body, a balloon was created along one opening of the tube. This balloon was formed by dipping the entire tube length in latex, thus creating an overcoat layer and bonding to the distal and proximal ends of the cured latex band.

At the proximal end of the cured latex band, the tube forked into two shorter tubes - one for the attachment of the urine bag and the other for injection of sterile water via a needleless syringe in order to fill the balloon.

Example 3 - Antibacterial Test Results

Method and materials: Sample: PU loaded with composite powder material (< 1%)

Sample size: LxWxT=5x5xl cm (n=3)

Method: ISO 22196:2011

Results: The antibacterial activity value of test samples after an 18-hour treatment of Escherichia coli 8099 was greater than 6.6, and the antibacterial activity value of test samples after an 18-hour treatment of Staphylococcus aureus ATCC 6538 was greater than 5.9. This showed that the antibacterial rate was greater than 99 % (An antibacterial value of >2.0 (>99% killing ratio) of a treated article with antimicrobial agent might be considered as “Antibacterial Article”). Table 1. Antibacterial Test I

Method and materials:

Sample: PU loaded with composite powder material (< 1%)

Sample size: LxWxT=5x5xl cm (n=3)

Method: ISO 22196:2011 Results: The antibacterial rate of test sample was greater than 99.9% after a 24-hour treatment of Klebsiella pneumoniae ATCC 4352, the antibacterial rate of test sample was 99.9 after a 24-hour treatment of Pseudomonas aeruginosa ATCC 9027, and the antibacterial rate of test sample was 99.5 after a 24-hour treatment of Enterococcus faecalis ATCC 29212. Table 2. Antibacterial Test II

The positive outcome of the antibacterial tests indicated that the present composition and article would be able to kill bacteria, reduce bacteria attached and eventually reduce biofilm formation (as shown in in vitro anti-biofilm formation tests described below) when used, e.g., as a catheter.

In vitro anti-biofilm formation tests

The anti-biofilm capacity of the present composition and article was evaluated using an immersion suspension method for 24 or 48 hours. As a urinary tract infection (UTI) associated strain, Klebsiella pneumoniae (ATCC® 700603™) was used in the evaluation. At both 24-hour and 48-hour marks, a significant reduction of biofilm formation (at least 1-log or 10-fold) was observed in an article as described herein, in comparison with control materials (which did not show significant reduction of biofilm formation). This result demonstrates that the present composition and article can effectively reduce biofilm formation.

Industrial Applicability

The composition and the article of the disclosure may be used in a variety of applications such as urinary catheters for the prevention or treatment of an infection in a urinary tract, a blood system, implanted devices, intracorporeal or intracavitary drainage systems in a subject, such as a urinary tract infection.

It will be apparent that various other modifications and adaptations of the invention will be apparent to the person skilled in the art after reading the foregoing disclosure without departing from the spirit and scope of the invention and it is intended that all such modifications and adaptations come within the scope of the appended claims.

Claims

1. A composition comprising a composite powder material and an elastomer, wherein the composite powder material comprises a) tourmaline particles; b) rare-earth mineral particles; c) silicate mineral particles; d) metal oxide particles; and e) a binder, and wherein the sizes of the a) tourmalines particles, the b) rare earth mineral particles, the c) silicate mineral particles and the d) metal oxide particles are 5 pm or less.

2. The composition of claim 1, wherein the composition consists of the composite powder material and the elastomer.

3. The composition of claim 1 or 2, wherein the composite powder material has a weight percentage in the range of 0.01 weight% to 50 weight% based on the total weight of the composition.

4. The composition of any one of claims 1 to 3, wherein the elastomer is selected from the group consisting of thermoplastic polyurethane (TPU), polyurethane (PU), silicone and combinations thereof.

5. The composition of any one of claims 1 to 4, wherein the composition is in the form of pellets.

6. A method of preparing a composition, comprising the step of mixing a composite powder material and an elastomer, wherein the composite powder material comprises a) tourmaline particles; b) rare-earth mineral particles; c) silicate mineral particles; d) metal oxide particles; and e) a binder, and wherein the sizes of the a) tourmalines particles, the b) rare earth mineral particles, the c) silicate mineral particles and the d) metal oxide particles are 5 pm or less.

7. The method of claim 6, wherein the method further comprises, before the mixing step, the steps of: a) grinding a mixture of tourmaline, rare-earth mineral, silicate mineral, and metal oxide particles having particle sizes of 5 pm or less to form a ground mixture; b) adding a binder to the ground mixture of step a); and c) drying the ground mixture of step b) to obtain the composite powder material.

8. An article comprising the composition of any one of claims 1 to 5.

9. The article of claim 8, wherein the article is in the form of a catheter.

10. The article of claim 9, wherein the catheter is a urinary catheter.

11. The article of any one of claims 8 to 10, wherein the article further comprises a coating on a surface.

12. The article of claim 11, wherein the coating comprises a biodegradable polymer, an antifouling polymer or a combination thereof.

13. The article of claim 12, wherein the coating further comprises a urological beneficial agent.

14. A method of preparing an article, comprising the steps of: a) heating the composition of any one of claims 1 to 5 to form a blend; b) extruding the blend of step a) in an extruder to form composite fibres; and c) forming the article from the composite fibres of step b).

15. The method of claim 14, wherein the extruding step b) and the forming step c) are undertaken for a total duration in the range of 10 minutes to 20 minutes.

16. A method of preventing or treating an infection in a urinary tract, a blood system, implanted devices, intracorporeal or intracavitary drainage systems in a subject, comprising the step of applying the catheter as defined in claim 9 in the subject.

17. A method of releasing urine from a subject, comprising the step of applying the urinary catheter as defined in claim 10 in a urinary tract of the subject.

18. A method of preventing or treating a urinary tract infection in a subject, comprising the step of applying the urinary catheter as defined in claim 10 in a urinary tract of the subject.

19. The urinary catheter as defined in claim 10 for use in preventing or treating a urinary tract infection.

20. The urinary catheter as defined in claim 10 when used in preventing or treating a urinary tract infection.