complex

Abstract

The present invention relates to a method of making a composite, a composite, and a polymeric valve for a heart. The composite comprises: (a) pyrolized lignocellulosic biomass particles having an average particle size of at most about 10 µm; and (b) a polycarbonate polyurethane polymer. The amount of pyrolized lignocellulosic biomass particles is from about 1 wt.% to about 75 wt.% relative to the weight of the polyurethane polymer. The method comprises: (i) pyrolizing lignocellulosic biomass particles by heating to a temperature of from about 250°C to about 1000°C for a time of from about 30 minutes to about 3 hours in an inert or mildly oxidative atmosphere to provide (a) pyrolized lignocellulosic biomass particles; and (ii) mixing together (a) pyrolized lignocellulosic biomass particles and (b) a polycarbonate polyurethane polymer to provide the composite.

Description

Technical Field

[0001] This invention relates to a composite, a polymeric valve for the heart comprising the composite, and methods for preparing the same. Background Technology

[0002] Heart valves (HVs) are unique components of the cardiovascular system, functioning to provide a smooth, unidirectional flow of blood through the heart chambers and vascular system by regularly opening and closing during each cardiac cycle. Depending on their anatomical location and structural configuration, HVs are subjected to varying dynamic workloads and mechanical conditions.

[0003] When a heart valve (HV) is severely damaged and unable to maintain its normal physiological function, heart valve replacement (HVR) is usually required. As an HVR, polymeric heart valves (PHVs) offer significant potential advantages over currently available bioprosthetic (pig / bovine) heart valves (which exhibit limited durability and risk of rejection) and mechanical heart valves (which require lifelong anticoagulation therapy and often necessitate reoperation).

[0004] While replacement of other HVs (tricuspid, pulmonary, and mitral valves) is also feasible, we initially focused on aortic valve replacement (AVR). The UK AVR market has grown steadily by approximately 30% over the past few years, with about 60% of implantations performed via conventional surgery and about 40% via transcatheter implantation.

[0005] Based on data from 2016 to 2019, approximately 82.5% of aortic valve (AV) implants were bioprosthetics, while 17.3% were mechanical valves, and the remaining 0.2% used tissue extracted from the same patient for replacement (allogeneic / autologous graft implantation). Polymerized HV is not yet widely used due to its susceptibility to thrombosis and material degradation, which can lead to leaflet stiffening and tearing under fatigue loads.

[0006] Furthermore, it is known that biological tissues in human AV are highly anisotropic, exhibiting very different mechanical properties in the circumferential (rigid) and radial (flexible) directions. Such mechanical properties are difficult to achieve using homogeneous polymers, as polymers are naturally isotropic.

[0007] Therefore, there is a need in the art to provide the synthesis of suitable synthetic tissues to replace current biological prostheses and mechanical implants.

[0008] Conventional heart valve replacements typically have a lifespan of up to 10 years before needing replacement. This is not ideal for younger patients, who may require multiple replacements throughout their lives. Furthermore, the increasing global population aging trend underscores the growing importance of heart valve replacement. As lifespans increase, the need for durable heart valves that can withstand the test of time becomes even more critical. Therefore, heart valve replacements with longer durability and lifespans are also required. Summary of the Invention

[0009] In a first aspect, a method for preparing a composite is provided, wherein the composite comprises: (a) pyrolytic lignocellulosic biomass (LCB) particles with an average particle size of up to about 10 µm; and (b) a polycarbonate polyurethane polymer; wherein the amount of the pyrolytic lignocellulosic biomass particles is about 1 wt.% to about 75 wt.% relative to the weight of the polyurethane polymer; wherein the method includes:

[0010] (i) Pyrolyzing lignocellulose biomass pellets by heating them in an inert or mildly oxidizing atmosphere at a temperature of about 250°C to about 1000°C for about 30 minutes to about 1 hour to provide (a) pyrolyzed lignocellulose biomass pellets; and

[0011] (ii) Combining (a) pyrolytic lignocellulose biomass pellets and (b) polycarbonate polyurethane polymer together to provide the composite.

[0012] In a second aspect, a method for preparing a polymer valve is provided, comprising preparing a composite according to the first aspect and molding the composite into the form of a polymer valve.

[0013] In a third aspect, a composite that can be obtained by the method of the first aspect or a polymer valve that can be obtained by the method of the second aspect is provided.

[0014] In a fourth aspect, a complex is provided comprising:

[0015] (a) Polycarbonate polyurethane polymer, and

[0016] (b) Pyrolytic lignocellulose biomass pellets with an average particle size of about 1 µm to about 10 µm.

[0017] The pyrolytic lignocellulose biomass pellets are present in an amount of about 1 wt.% to about 75 wt.% based on the weight of the polycarbonate polyurethane polymer, and

[0018] The pyrolytic lignocellulose biomass particles are dispersed and mixed throughout the (b) polycarbonate polyurethane polymer. Attached Figure Description

[0019] Figure 1 SEM images showing the morphology of SpEC capsules (approximately 25 × 25 μm in size) before pyrolysis.

[0020] Figure 2 The images show composites prepared according to the present invention with different proportions of LCB biochar, wherein the LCB biochar is uniformly dispersed in a polymer membrane.

[0021] Figure 3a shows the tensile stress and strain properties of the composite prepared according to the present invention compared with the pure polymer at different thicknesses and strains from 0 to 50%.

[0022] Figure 3b shows the tensile stress and strain properties of the composite prepared according to the present invention compared with the pure polymer at different thicknesses and strains from 0 to 900%.

[0023] Figures 4(A) and (B) show uniaxial cyclic tensile tests performed on the composite leaflet, where (A) shows a decrease in tensile strain during the last cycle, while (B) shows an increase in Young's modulus with a decrease in hysteresis-related energy loss, which is calculated as the work dissipated through hysteresis (W). dis ) and the total work stored in the sample during the loading phase (W) i The ratio of ). Detailed Implementation

[0024] Methods for preparing complexes

[0025] In a first aspect, a method for preparing a composite is provided, wherein the composite comprises (a) pyrolytic lignocellulose biomass particles with an average particle size of up to about 10 µm; and (b) a polycarbonate polyurethane polymer; wherein the amount of the pyrolytic lignocellulose biomass particles is about 1 wt.% to about 75 wt.% relative to the weight of the polyurethane polymer.

[0026] This method includes:

[0027] (i) Pyrolyzing lignocellulose biomass pellets by heating them in an inert or mildly oxidizing atmosphere at a temperature of about 250°C to about 1000°C for about 30 minutes to about 1 hour to provide (a) pyrolyzed lignocellulose biomass pellets; and

[0028] (ii) Combining (a) pyrolytic lignocellulose biomass pellets and (b) polycarbonate polyurethane polymer together to provide the composite.

[0029] Lignocellulose biomass pellets

[0030] LCB refers to plant dry matter. LCB contains carbohydrate polymers, including cellulose and hemicellulose, as well as the aromatic polymer lignin, which together form the plant cell wall.

[0031] The LCB particles useful in this invention are preferably sporopollenin exinecapsule (SpEC), which are derived from the original sporopollenin of Lycopodium clavatum. Figure 1 An example of the microstructure of a sporophytin exocapsule (SpEC) obtained from the original Northeast lycophyte sporophytin is shown. SpECs can be obtained using methods known in the art.

[0032] One method for obtaining sporopollenin SpEC is extraction from L. clavatum spores. Such extractions are known in the art and are carried out using, for example, acids, bases, or organic solvents. The exopodium of the sporopollenin is separated from the remaining components of the spore, such as the cytoplasm and inner wall, to provide only the SpEC material. Preferably, the extraction method uses 6% NaOH at 80°C for 24 hours to extract SpEC from L. clavatum spores, followed by washing and drying steps to obtain a finally purified SpEC powder. Suitable extraction methods are described in Industrial Crops & Products 154 (2020) 112714, which is incorporated herein by reference in its entirety, with particular attention to section 2.1.2.2 on page 3, which is also incorporated herein by reference. Other suitable extraction methods are found in RSC Adv., 2016, 6, 16533, which is also incorporated herein by reference.

[0033] Step (i): Pyrolysis and optional physical activation

[0034] The method involves pyrolyzing lignocellulosic biomass pellets by heating them in an inert or mildly oxidizing atmosphere at a temperature of about 250°C to about 1000°C for about 30 minutes to about 3 hours to provide (a) pyrolyzed lignocellulosic biomass pellets (hereinafter sometimes simply referred to as "biochar pellets").

[0035] Heating can be carried out in a ventilated preheated oven, optionally accompanied by periodic mixing of the particles.

[0036] Preferably, the method may include a pyrolysis step of heating in an inert atmosphere (e.g., N2 or Ar) to about 250 to about 600°C, more preferably about 250 to about 350°C, for about 30 minutes to about 1.5 hours, and most preferably about 45 minutes to 1 hour. For example, the method may include a step of heating in an inert atmosphere to about 300°C for about 1 hour. For example, the heating step may be carried out in a temperature ramp manner under a constant inert gas (e.g., N2) flow, for example, starting from 250°C and increasing by 10°C per minute. -1 The rate of temperature increase is maintained for a set time period.

[0037] Without being bound by theory, it is believed that this pyrolysis step provides lignocellulose biomass pellets with increased surface area and pore volume (see Table 1).

[0038] The pyrolysis step may also include a second step of heating in a mildly oxidizing atmosphere to a temperature of about 700 to about 1000°C, preferably about 900°C, for about 30 minutes to about 4 hours.

[0039] Not wanting to be bound by theory, it is believed that this second heating step physically activates the particles and provides a further increase in surface area and porosity (see, for example, Table 1). This step can be carried out in a temperature ramp manner under a constant CO2 and inert gas flow, for example, starting from 700°C and increasing by 10°C min. -1 The gas is heated to 1000°C at a rate that is maintained for a set time period. Once the second heating step is complete, the gas flow is preferably switched back to an inert gas (e.g., N2) before cooling.

[0040] Particularly preferred is that the first and second steps can be performed sequentially as part of a continuous temperature ramp, during which the gas flow switches from inert to mildly oxidizing. For example, biomass can be fed at a constant N2 flow at a temperature ramp of 300 to 900 °C for 10 °C min. -1 Carbonization is carried out at a heating rate. Once the temperature reaches 900°C, the gas stream can be switched from N2 to CO2 to physically activate the particles, lasting for about 3 hours.

[0041] It should be understood that the temperature and heating time can be adjusted individually within the above range to adjust the surface area and porosity of the biomass particles, which in turn affects the mechanical properties of the resulting composite.

[0042] The pyrolytic lignocellulose biomass pellets of the present invention have an average particle size of up to about 10 µm. This can be achieved, for example, by tip sonication in a deionized aqueous solution. The tip-sonicated solid can then be dried, for example, in a dryer.

[0043] Therefore, the method may include a step of reducing particle size by tip sonication following pyrolysis (and optional physical activation), preferably performed in a deionized water (0°C) bath for about 2 hours. Tip sonication may be performed at a frequency of about 10-20 kHz and a power of about 500 W.

[0044] The pyrolytic lignocellulose biomass pellets may have an average particle size of about 0.1 µm to about 10 µm, preferably about 1 µm to about 10 µm, and more preferably about 3 µm to about 5 µm.

[0045] The average particle size can be measured using laser diffraction spectroscopy, for example using a laser diffraction spectrometer such as the Mastersizer 2000 from Malvern Instruments.

[0046] Pyrolytic lignocellulose biomass pellets, as a result of the pyrolysis process, can have a particle size of approximately 800 to 1200 m³. 2 g -1 The surface area, and / or about 0.2 to about 0.4 cm². 3 g -1 Porosity.

[0047] The pyrolysis step provides lignocellulose biomass pellets with increased surface area and pore volume (see Example 1 and Table 1).

[0048] Without being bound by theory, it is believed that the pyrolysis steps according to the invention provide biochar particles with a desired combination of porosity, morphology and surface chemistry, thereby allowing them to bond properly with polymers.

[0049] Polycarbonate polyurethane polymer

[0050] The composite of the present invention comprises a polycarbonate polyurethane polymer.

[0051] "Polycarbonate polyurethane polymer" is the reaction product of a polycarbonate diol having at least terminal hydroxyl groups and a diisocyanate having terminal isocyanate groups. The polymer backbone has repeating urethane and / or urea groups.

[0052] The polycarbonate polyurethane polymer can be a silicone polycarbonate polyurethane polymer, preferably a thermoplastic silicone polycarbonate polyurethane polymer.

[0053] Polycarbonate polyurethane polymers are appropriately biocompatible. "Biocompatibility" refers to the ability of a material to behave in accordance with the appropriate host response in a given application. In the context of composite materials used in implants, biocompatibility refers to the ability of a material to be accepted by the body without causing adverse reactions such as inflammation or rejection.

[0054] Polycarbonate polyurethane polymers may contain terminal silicone groups.

[0055] The silicone content of the polycarbonate polyurethane polymer can be from about 5% to about 25%, preferably about 20%.

[0056] The polycarbonate polyurethane polymer is preferably a segmented block copolymer, comprising:

[0057] a) Polycarbonate or polytetramethylene carbonate hard segment blocks, made of aromatic diisocyanates such as 4,4'-methylenebis(phenylisocyanate) and polycarbonate or polytetramethylene carbonate diol;

[0058] b) Polysiloxane soft segment blocks containing polydimethylsiloxane;

[0059] c) A polymer having surface-modified end groups selected from hydroxyl-terminated polydimethylsiloxane, amine-terminated polydimethylsiloxane, or methoxy-terminated polyethylene oxide.

[0060] The polycarbonate-polyurethane segmented block copolymer may preferably also contain:

[0061] d) The weight ratio of hard chain segments to soft chain segments ranging from 95:5 to 50:50;

[0062] e) Number-average molecular weight of soft segments ranging from approximately 1,000 to approximately 20,000 g / mol; and

[0063] f) Number-average molecular weight of hard segments from approximately 300 to approximately 6000 g / mol.

[0064] Unless otherwise explicitly stated, the average molecular weight of the polymers used in this article was measured by gel permeation chromatography (GPC).

[0065] Polycarbonate polyurethane polymers can be appropriately processed by extrusion, injection molding or solution casting.

[0066] Polycarbonate polyurethane polymers suitably possess one or more of the following properties:

[0067] (a) Density is from about 1.00 to about 1.25 g.cm³ 3 ;

[0068] (b) Tensile strength is about 30 to about 50 MPa;

[0069] (c) Elongation of about 300% to about 500%; and

[0070] (d) The melt flow rate is approximately 10 to approximately 60 g / 10 min at 224 °C; and

[0071] (e) The glass transition temperature (Tg) is about -20 to about 20°C.

[0072] One example of a preferred polycarbonate-polyurethane polymer is CarboSil® thermoplastic silicone-polycarbonate-polyurethane, which is commercially available from DSM.

[0073] Polycarbonate polyurethane polymers can be block polymers combining siloxane and carbonate segments. Such block polymers may comprise:

[0074] a) Polycarbonate hard-chain segments made from aromatic diisocyanates (such as 4,4-methylene diphenyl diisocyanate (4,4-MDI)) and polycarbonate diols; and

[0075] b) Polysiloxane soft segment blocks containing polydimethylsiloxane.

[0076] The most preferred is a triblock polyurethane polymer comprising the following structure:

[0077]

[0078] Where n, x, y, and z are positive integers. For example, n, x, y, and z can each be independently from 1 to 100, preferably independently from 1 to 50.

[0079] Without being bound by theory, the polycarbonate polyurethane polymers according to the present invention are believed to be suitable for cardiovascular applications because of their biological stability, resistance to calcification, and the favorable mechanical and viscoelastic properties they exhibit.

[0080] Step (ii): Mixing

[0081] The method includes (ii) mixing (a) pyrolytic lignocellulose biomass pellets and (b) polycarbonate polyurethane polymer together to provide the composite.

[0082] (a) Pyrolytic lignocellulose biomass (biochar) pellets and (b) polycarbonate polyurethane polymer can be mixed in any suitable manner, preferably as long as the pyrolytic lignocellulose biomass pellets are dispersed and mixed throughout the (b) polycarbonate polyurethane polymer. For example, the biochar pellets and polyurethane polymer can be mixed using a standard magnetic stirrer.

[0083] Preferably, the polymer is first dissolved in a solvent such as dimethylacetamide (DMAc) before being mixed with biochar particles, and then the solvent is removed, for example, by drying.

[0084] If a polymeric valve is formed from this composite, the composite can be placed in a mold before the solvent is removed by drying, thereby providing the composite in the form of a polymeric valve.

[0085] In this composite, the amount of pyrolyzed lignocellulose biomass pellets is about 1 wt.% to about 75 wt.% relative to the weight of the polycarbonate polyurethane polymer, preferably about 1 wt.% to about 50 wt.%, about 1 wt.% to about 25 wt.%, or about 2 to about 10 wt.%, most preferably about 3 to about 6 wt.%.

[0086] The amount of pyrolyzed lignocellulosic biomass pellets may be from about 10 wt.% to about 75 wt.%, from about 10 wt.% to about 60 wt.%, or from about 10 wt.% to about 30 wt.% relative to the weight of the polycarbonate polyurethane polymer.

[0087] Not wanting to be bound by theory, it is believed that the biocompatibility of the complex is guaranteed by the polymer that completely encapsulates the pyrolytic particles.

[0088] The ability to change the amount of pyrolyzed biomass in the final composite advantageously allows for the adjustment of the properties of the resulting composite (e.g., strain, tensile strength, etc.) according to the needs of a specific application.

[0089] complex

[0090] On the other hand, a complex is provided that can be obtained by the method of the first aspect.

[0091] The term "composite" in this article is a noun referring to a composite material made by combining two or more materials with different properties to produce a final material with enhanced overall performance and properties.

[0092] On the other hand, a complex is provided comprising:

[0093] (a) Polycarbonate polyurethane polymer, and

[0094] (b) Pyrolytic lignocellulose biomass pellets with an average particle size of about 1 µm to about 10 µm.

[0095] The pyrolytic lignocellulose biomass pellets are present in an amount of about 1 wt.% to about 75 wt.% based on the weight of the polycarbonate polyurethane polymer, and

[0096] The pyrolytic lignocellulose biomass particles are dispersed and mixed throughout the (b) polycarbonate polyurethane polymer.

[0097] Pyrolytic lignocellulose biomass pellets can have a diameter of approximately 800 to approximately 1200 m³. 2 g -1 The surface area and / or approximately 0.2 to approximately 0.4 cm² 3 g -1The porosity. These were measured using the standard Brunauer-Emmett-Teller (BET) method, which is widely used to measure both surface area and porosity.

[0098] (b) The pyrolyzed LCB particles have preferably been pyrolyzed according to the pyrolysis method defined herein in relation to the first aspect, thereby increasing the surface area and pore volume of the particles. It is not desired to be bound by theory, but it is believed that the ability to adjust the surface area and / or porosity of the biochar particles as defined herein allows for better bonding with polyurethane polymers.

[0099] Lignocellulose biomass pellets can be pyrolyzed by heating at a temperature of about 250°C to about 1000°C for about 30 minutes to about 3 hours in an inert or slightly oxidizing atmosphere, preferably by heating at a temperature of about 250°C to about 600°C for about 30 minutes to about 1.5 hours in an inert atmosphere.

[0100] It should be understood that the features related to the first aspect, particularly those concerning the pyrolytic lignocellulose biomass pellets and the polycarbonate polyurethane polymer, also apply to this composite.

[0101] Polymer valves for the heart

[0102] In a second aspect, a method for preparing a polymeric valve is provided, comprising preparing a composite according to the first aspect and molding the composite into the form of a polymeric valve. Preferably, the composite may be molded into the form of a leaflet for use in a polymeric valve.

[0103] Preferably, the valve can be a heart valve.

[0104] The valve may comprise a stent and multiple leaflets (e.g., three). The stent may be made of the composite material of the invention described herein, or of metal or plastic mesh, and it provides a basic framework for the attachment of the polymer valve leaflets. The stent may also have an embedded metal reinforcing frame to provide additional structural support and stiffness when needed.

[0105] The leaflets can be movable blades or pointed valves, which open and close to regulate blood flow through the valve. The leaflets can rhythmically open and close their operating ends relative to each other in response to changes in blood flow and pressure. The valve may contain two, three, or four leaflets, preferably three.

[0106] In another aspect, a method for preparing a polymeric valve comprising a composite is provided, wherein the method includes preparing the composite according to a first aspect and molding the composite into the form of at least a portion of a polymeric valve. Preferably, the composite is molded into the form of a leaflet for a polymeric valve.

[0107] The composite can be molded into the form of a polymer valve according to any suitable method known in the art. The composite provided by this method can be deformable, for example, due to the addition of a solvent.

[0108] Molding the composite into the form of a polymer valve may include the following steps:

[0109] a) Place the composite into a mold, wherein the mold is shaped like a polymer valve;

[0110] b) The composite is cured in the mold to provide the composite in the form of a polymer flap, wherein the composite is preferably cured by removing the solvent (e.g., by drying).

[0111] Alternatively, polymer valves can be formed by dip coating.

[0112] Advantageously, the preparation of polymer valves by using the composite according to the invention provides polymer valves that can be thinner while still achieving the desired mechanical properties.

[0113] Preferably, the thickness of the polymer valve in this document is from about 0.12 mm to about 0.25 mm, more preferably 0.17 mm. Preferably, the thickness of the leaflets of the polymer valve in this document is from about 0.12 mm to about 0.25 mm.

[0114] Figure 3A and 3B The results show that even at these low thicknesses, the composites according to the invention exhibit improved mechanical properties, with favorable tensile and tensile stress properties, while allowing for very thin heart valve leaflets.

[0115] It should be understood that the characteristics associated with the method and complex of the first aspect, particularly those relating to the pyrolytic lignocellulose biomass pellets and the polycarbonate polyurethane polymer, also apply to this polymer valve.

[0116] Polymer heart valves, as described herein, are also provided in methods for treating patients with valvular heart disease.

[0117] A method for treating valvular heart disease in patients is also provided, including:

[0118] a. Removing a patient's defective or diseased heart valve; and

[0119] b. Implantation of a polymer valve as described herein.

[0120] The heart valve disease can be aortic stenosis, aortic regurgitation, mitral stenosis, tricuspid stenosis, pulmonary stenosis, pulmonary regurgitation, or rheumatic heart disease, with aortic regurgitation, mitral stenosis, or mitral regurgitation being the preferred conditions.

[0121] The aspects provided in this document are also described in the following clauses:

[0122] 1. A method for preparing a composite, wherein the composite comprises (a) pyrolytic lignocellulose biomass particles with an average particle size of up to about 10 µm; and (b) a polycarbonate polyurethane polymer; wherein the amount of the pyrolytic lignocellulose biomass particles is about 1 wt.% to about 75 wt.% relative to the weight of the polyurethane polymer; wherein the method comprises:

[0123] (i) Pyrolyzing lignocellulose biomass pellets by heating them in an inert or mildly oxidizing atmosphere at a temperature of about 250°C to about 1000°C for about 30 minutes to about 3 hours to provide (a) pyrolyzed lignocellulose biomass pellets; and

[0124] (ii) Combining (a) pyrolytic lignocellulose biomass pellets and (b) polycarbonate polyurethane polymer together to provide the composite.

[0125] 1a. The method according to Clause 1, wherein the amount of pyrolyzed lignocellulosic biomass pellets is from about 1 wt.% to about 50 wt.% relative to the weight of the polyurethane polymer.

[0126] 1b. The method according to Clause 1, wherein the amount of pyrolyzed lignocellulosic biomass pellets is from about 1 wt.% to about 25 wt.% or from about 1 wt.% to about 15 wt.% relative to the weight of the polyurethane polymer.

[0127] 1c. The method according to Clause 1, wherein the amount of pyrolyzed lignocellulosic biomass pellets is about 10 wt.% to about 75 wt.%, about 10 wt.% to about 60 wt.%, or about 10 wt.% to about 30 wt.% relative to the weight of the polycarbonate polyurethane polymer.

[0128] 2. The method according to clause 1 or 1a or 1b or 1c, wherein the step of pyrolyzing lignocellulosic biomass pellets includes heating in an inert atmosphere at a temperature of about 250 to about 600°C for about 30 minutes to about 3 hours, preferably 45 minutes to about 1.5 hours.

[0129] 3. The method according to Clause 2, wherein the step of pyrolyzing lignocellulosic biomass pellets includes heating in an inert atmosphere at a temperature of about 250 to about 350°C for about 45 minutes to about 1.2 hours.

[0130] 4. The method according to Clause 3, wherein the step of pyrolyzing lignocellulosic biomass pellets includes heating in an inert atmosphere to a temperature of about 300°C for about 1 hour.

[0131] 5. The method according to any one of clauses 1 to 4, wherein the inert atmosphere is N2 or Ar gas.

[0132] 6. The method according to Clauses 2 to 5, wherein the step of pyrolyzing lignocellulosic biomass pellets includes the further step of heating in an inert atmosphere followed by heating in a mildly oxidizing atmosphere at a temperature of about 700 to about 1000°C for about 30 minutes to about 4 hours.

[0133] 6a. The method according to Clause 6, wherein after heating in an inert atmosphere, the further heating step includes heating to a temperature of about 800 to about 950°C for a duration of about 2 hours to about 4 hours.

[0134] 7. The method according to Clause 6 or 6a, wherein the mildly oxidizing atmosphere consists of 10% to 100% v / v CO2, with the remainder being inert gases.

[0135] 8. The method according to any one of clauses 1 to 7, wherein the lignocellulose biomass pellets are sporophytin exosphere pellets.

[0136] 9. The method according to Clause 8, wherein the sporophytin exowall particles (SpEC) are obtained from the original Northeast lycophyte sporophytin.

[0137] 10. The method according to Clause 9, wherein the sporophyll exocell particles (SpEC) are obtained from the original Northeast lycophyll sporophyll by extraction with sodium hydroxide solution.

[0138] 11. The method according to any one of the preceding clauses, wherein the average particle size of the lignocellulose biomass pellets is about 0.5 µm to about 10 µm.

[0139] 12. The method according to Clause 11, wherein the average particle size of the lignocellulose biomass pellets is about 3 µm to about 5 µm.

[0140] 13. The method according to any one of the preceding clauses, wherein the average particle size is measured by laser diffraction spectroscopy.

[0141] 14. The method according to any one of the preceding clauses, wherein the method includes the step of subjecting pyrolytic lignocellulose biomass pellets to advanced ultrasonic treatment to provide a desired average particle size.

[0142] 15. The method according to any one of the preceding clauses, wherein the polycarbonate polyurethane polymer is a silicone polycarbonate polyurethane polymer.

[0143] 16. The method according to Clause 15, wherein the silicone polycarbonate polyurethane polymer is a thermoplastic silicone polycarbonate polyurethane polymer.

[0144] 17. The method according to any one of the preceding clauses, wherein the polycarbonate polyurethane polymer comprises terminal silicone groups.

[0145] 18. The method according to any one of the preceding clauses, wherein the silicone content of the polycarbonate polyurethane polymer is from about 5 to about 25% w / w.

[0146] 19. The method according to any one of the preceding clauses, wherein the polycarbonate polyurethane polymer comprises polycarbonate polyurethane hard segments and polydimethylsiloxane (PDMS) soft segments.

[0147] 20. The method according to any one of the preceding clauses, wherein the polycarbonate polyurethane polymer is a segmented block copolymer comprising:

[0148] a) Polycarbonate or polytetramethylene carbonate hard segment blocks, made of aromatic diisocyanate and polycarbonate or polytetramethylene carbonate diol;

[0149] b) Polysiloxane soft segment blocks containing polydimethylsiloxane;

[0150] c) A polymer having surface-modified end groups selected from hydroxyl-terminated polydimethylsiloxane, amine-terminated polydimethylsiloxane, or methoxy-terminated polyethylene oxide.

[0151] 21. The method according to any one of the preceding clauses, wherein the segmented block copolymer comprises:

[0152] d) The weight ratio of hard chain segments to soft chain segments ranging from 95:5 to 50:50;

[0153] e) Number-average molecular weight of soft segments ranging from approximately 1,000 to approximately 20,000 g / mol; and

[0154] f) Number-average molecular weight of hard segments from about 300 to about 6000 g / mol, wherein the number-average molecular weight is measured by gel permeation chromatography (GPC).

[0155] 22. The method according to any one of the preceding clauses, wherein the polycarbonate polyurethane polymer has one or more of the following properties:

[0156] (a) Density is from about 1.00 to about 1.25 g / cm³ 3 ;

[0157] (b) Tensile strength is about 30 to about 50 MPa;

[0158] (c) Elongation of about 300% to about 500%; and

[0159] (d) The melt flow rate is approximately 10 to approximately 60 g / 10 min at 224 °C; and

[0160] (e) The glass transition temperature (Tg) is about -20 to about 20°C.

[0161] 23. The method according to any one of the preceding clauses, wherein the polycarbonate polyurethane polymer is biocompatible.

[0162] 23a. The method according to any one of the preceding clauses, wherein the polycarbonate polyurethane polymer is a block polyurethane incorporating siloxane and carbonate segments.

[0163] 23b. The method according to any one of the preceding clauses, wherein the polycarbonate polyurethane polymer comprises the following structure:

[0164]

[0165] Where n, x, y, and z are positive integers, and can each be independently between 1 and 100.

[0166] 24. The method according to any one of the preceding clauses, wherein the method includes step (ia) of dissolving the polycarbonate polyurethane polymer in a solvent prior to mixing step (ii).

[0167] 25. The method according to any one of the preceding clauses, wherein the amount of pyrolyzed lignocellulosic biomass pellets is about 1 wt.% to about 15 wt.% relative to the weight of the polycarbonate polyurethane polymer.

[0168] 26. The method according to any one of the preceding clauses, wherein the amount of pyrolyzed lignocellulosic biomass pellets is about 2 wt.% to about 10 wt.% relative to the weight of the polycarbonate polyurethane polymer.

[0169] 27. The method according to any one of the preceding clauses, wherein the amount of pyrolyzed lignocellulosic biomass pellets is about 3 wt.% to about 6 wt.% relative to the weight of the polycarbonate polyurethane polymer.

[0170] 28. A method for preparing a polymer valve comprising a complex, the method comprising:

[0171] (i) The complex is prepared according to the method described in any one of the preceding clauses, and

[0172] (ii) The composite is shaped into a polymer valve.

[0173] 29. The method for preparing a polymer valve according to Clause 28, wherein molding the composite comprises:

[0174] (iia) The composite is placed in a mold, wherein the mold is in the shape of a polymer valve;

[0175] The composite is cured in the mold (iib) to provide the composite in the form of a polymer valve.

[0176] 29a. The method for preparing a polymer valve according to Clause 28, wherein molding the composite comprises:

[0177] iia) provides the complex as a solution,

[0178] iib) Dip the mold into the composite solution, wherein the mold is in the shape of a polymer valve;

[0179] (iic) solidifies the composite, thereby providing the composite in the form of a polymer valve.

[0180] 30. The method of preparing a polymer valve according to clause 29 or 29a, wherein the composite is cured by removing the solvent.

[0181] 31. A method for preparing a polymer valve according to any one of clauses 28 to 30, wherein the thickness of the plurality of leaflets of the polymer valve is from about 0.12 mm to about 0.25 mm.

[0182] 31a. A method of preparing a polymeric valve according to any one of clauses 28 to 31, wherein the polymeric valve comprises a scaffold attached to a plurality of leaflets.

[0183] 31b. The method of preparing a polymer valve according to clause 31a, wherein the polymer valve comprises three leaflets.

[0184] 31c. A method for preparing a polymeric valve according to clause 31a or 31b, wherein the stent is made of metal or plastic.

[0185] 31d. A method for preparing a polymeric valve according to any one of clauses 31a to 31c, wherein the valve is a heart valve.

[0186] 32. A composite that can be obtained by any one of the methods in Clauses 1 to 27 or a polymeric valve that can be obtained by any one of the methods in Clauses 28 to 31d.

[0187] 33. A complex comprising:

[0188] (a) Polycarbonate polyurethane polymer, and

[0189] (b) Pyrolytic lignocellulose biomass pellets with an average particle size of about 1 µm to about 10 µm, wherein the pyrolytic lignocellulose biomass pellets are present in an amount of about 1 wt.% to about 75 wt.% based on the weight of the polycarbonate polyurethane polymer, and

[0190] The pyrolytic lignocellulose biomass particles are dispersed and mixed throughout the (b) polycarbonate polyurethane polymer.

[0191] 33a. The complex according to Clause 33, wherein the pyrolytic lignocellulosic biomass particles are present in an amount of about 1 wt.% to about 50 wt.% based on the weight of the polycarbonate polyurethane polymer.

[0192] 33b. The complex according to Clause 33, wherein the pyrolytic lignocellulosic biomass particles are present in an amount of about 1 wt.% to about 25 wt.% or about 1 wt.% to about 15 wt.% based on the weight of the polycarbonate polyurethane polymer.

[0193] 33c. The complex according to Clause 33, wherein the pyrolytic lignocellulosic biomass particles are present in an amount of about 10 wt.% to about 75 wt.%, about 10 wt.% to about 60 wt.%, or about 10 wt.% to about 30 wt.% based on the weight of the polycarbonate polyurethane polymer.

[0194] 34. The complex according to any one of clauses 33 or 33a to 33c, wherein the surface area of ​​the pyrolyzed lignocellulose biomass pellets is about 800 to about 1200 m². 2 / g.

[0195] 35. The complex according to any one of clauses 33 or 33a to 33c or clause 34, wherein the porosity of the pyrolytic lignocellulose biomass particles is from about 0.2 to about 0.4 cm. 3 / g.

[0196] 36. The complex according to any one of clauses 33 to 35, wherein the lignocellulose biomass particles are sporophytin exosphere particles.

[0197] 37. The composite according to any one of clauses 33 to 36, wherein the polycarbonate polyurethane polymer is a silicone polycarbonate polyurethane polymer.

[0198] 38. The composite according to any one of clauses 33 to 37, wherein the polycarbonate polyurethane polymer comprises terminal silicone groups.

[0199] 39. The composite according to any one of clauses 33 to 38, wherein the polycarbonate polyurethane polymer has a silicone content of 5 to 25%.

[0200] 40. The composite according to any one of clauses 33 to 39, wherein the polycarbonate polyurethane polymer comprises polycarbonate polyurethane hard segments and polydimethylsiloxane (PDMS) soft segments.

[0201] 41. The composite according to any one of clauses 33 to 40, wherein the polycarbonate polyurethane polymer comprises the following structure:

[0202]

[0203] Where n, x, y, and z are positive integers, and can each be independently between 1 and 100.

[0204] 42. The composite according to any one of clauses 33 to 41, wherein the polycarbonate polyurethane polymer has one or more of the following properties:

[0205] (a) Density is from about 1.00 to about 1.25 g.cm³ 3 ;

[0206] (b) Tensile strength is about 30 to about 50 MPa;

[0207] (c) Elongation of about 300% to about 500%; and

[0208] (d) The melt flow rate is approximately 10 to approximately 60 g / 10 min at 224 °C; and

[0209] (e) Glass transition temperature (T) g The temperature ranges from approximately -20°C to approximately 20°C.

[0210] 43. A polymeric valve comprising a complex according to any one of clauses 32 to 42.

[0211] 44. The polymer valve as described in Clause 44, wherein the polymer valve includes a stent attached to a plurality of leaflets.

[0212] 45. The polymer valve according to any one of clauses 43 to 44, wherein the polymer valve comprises three leaflets.

[0213] 46. ​​The polymer valve according to any one of clauses 43 to 45, wherein the stent is made of metal or plastic.

[0214] 47. The polymer valve according to any one of clauses 44 to 46, wherein the thickness of the plurality of leaflets of the polymer valve is from about 0.12 mm to about 0.25 mm.

[0215] 48. The polymer valve according to any one of clauses 43 to 47, wherein the valve is a heart valve.

[0216] 49. A method for treating a patient's valvular heart disease, comprising:

[0217] a. Remove the patient's defective or diseased heart valve; and

[0218] b. Implantation of a polymer valve as described in clauses 31d or 48.

[0219] 50. A polymer valve as described in any one of Clauses 28 to 31d or Clause 48, used in a method of treating a patient with valvular heart disease.

[0220] Example

[0221] The present invention will now be described with reference to the following embodiments. These embodiments should not be construed as limiting the invention.

[0222] Example 1a - Pyrolysis of Biomass

[0223] The pyrolysis granules (biochar) are prepared as follows:

[0224] 1. Sporopyrrolidone exocapsule (SpEC) is derived from native Northeast lycophyte sporopyrrolidone, which is commercially available from various sources and extracted with 6% sodium hydroxide for 24 hours. The complete and detailed method for capsule extraction can be found in Industrial Crops & Products 154(2020) 112714 (see section 2.1.2.2 on page 3).

[0225] 2. Place the extracted capsules in a preheated ventilated oven at 300°C and maintain the temperature at 300°C for 1 hour, then allow them to cool naturally to room temperature.

[0226] 3. The carbonized SpEC was then collected and subjected to high-precision sonication in a deionized aqueous solution at a ratio of 0.1 g SpEC per 25 ml of deionized water, and cooled in an ice bath (0°C) for 4 hours. The effective sonication time was 2 hours, with a total pause interval of 2 hours. The pulse interval consisted of 1 second of effective sonication followed by 1 second of pause, at a frequency of 15 kHz.

[0227] 4. Then, store the prepared solid in a desiccator and mix it with the polymer.

[0228] Surface area and pore volume were measured before and after pyrolysis. The results are shown in Table 1 below, which shows that the pyrolysis step provides particles with a significantly increased surface area and pore volume compared to untreated capsules.

[0229] Example 1b - Physical activation of biomass

[0230] Example 1a was repeated, except that after the heating step in an inert atmosphere, the particles were further heated to a higher temperature (about 900°C) in a mildly oxidizing atmosphere including CO2 and an inert gas to physically activate SpEC.

[0231] This leads to a further significant increase in surface area and porosity, as clearly seen in the results shown in Table 1.

[0232] Table 1: Surface area and pore volume of SpEC before and after pyrolysis step

[0233]

[0234] Not wanting to be bound by theory, it is believed that increased surface area and pore volume contribute to improved mechanical properties of the final composite.

[0235] Example 2 - Preparation of the complex

[0236] The complex was prepared as follows:

[0237] 1. Mix 4.25g of dimethylacetamide (DMAc) with 0.75g of TSPCU (CarboSil). TM 80A, obtained from DSM Medical, product name: FP70060 Carbosil 20 80A UR TSPCU) is mixed to provide a mixture.

[0238] 2. Then, pyrolyzed biomass from Example 1 is added in amounts ranging from 0.015 g to 0.075 g (corresponding to 2 wt% to 10 wt% of TSPCU polymer) and mixed to provide a homogeneous mixture.

[0239] 3. The mixture is then placed in a flat glass dish and cured for 24 hours at room temperature in a sealed container using forced air drying technology at 2 liters per minute (LPM) to provide a cured composite.

[0240] It should be understood that in Example 2, the compound was cured on a petri dish, thus obtaining a flat shape (see [link]). Figure 2However, various shapes, especially the shapes of valve leaflets used to form polymer heart valves, can be obtained in the same way, for example, by curing the composite on a molding die.

[0241] Example 3 - Testing the properties of the prepared complex

[0242] Composites containing 3 wt.% and 6 wt.% pyrolyzed biomass (SpEC) with thicknesses of 0.12 mm, 0.16 mm, 0.20 mm, and 0.23 mm were prepared according to the method of Example 2, and their tensile stress (MPa) and strain % properties were tested. The results were compared with control samples (“polymer”) containing only the polymer (i.e., without any biochar filler), with thicknesses of 0.06 mm and 0.08 mm. The results are shown in… Figure 3A and 3B middle.

[0243] from Figure 3A and 3B It can be seen that there is a clear correlation between the increase in biochar (pyrolytic lignocellulose biomass pellets) content and the decrease in maximum stress and the increase in maximum strain. The increase in maximum strain is advantageous because higher strain is associated with higher durability, and the stress of 25 MPa to 30 MPa is an order of magnitude higher than the expected stress during polymeric heart valve operation.

[0244] Figure 3A and 3B The stress-strain curves of the samples containing pyrolytic biomass exhibit viscoelasticity suitable for heart valves. In particular, the Young's modulus (curve slope) for strains between 0 and 30% remains within the expected range for heart valve operation (results comparable to those of polymer-only samples). Furthermore, these results have been demonstrated to be obtained using samples with low thickness. The reduction in thickness significantly decreases tissue bending stiffness (which is proportional to the cube of the thickness), and is therefore desirable.

[0245] Advantageously, from Figure 3B As can be seen, the sample containing pyrolytic biomass exhibits a significantly increased strain percentage. A clear correlation exists between the amount of pyrolytic biomass contained in the sample and the strain percentage. That is, the composite containing pyrolytic biomass demonstrates increased durability, which in turn allows for a longer lifespan of the polymeric heart valve. As mentioned above, this could potentially lead to a reduction in the number of heart valve replacements required by a patient throughout their lifetime.

[0246] Example 4 - Uniaxial cyclic tensile test (50 cycles) on composite leaflet

[0247] In this embodiment, the composite prepared according to Example 2 was subjected to uniaxial cyclic tensile tests. These tests involved subjecting the composite to test conditions that more closely resembled physiological loads.

[0248] The composite leaflets were subjected to uniaxial cyclic tensile tests for 50 cycles, with a maximum stress of 5 MPa. The sample thickness was 110–120 µm, containing 0–25% w / w pyrolytic biomass filler (relative to the weight of the polyurethane polymer). Figure 4(A) shows the final cycle, demonstrating a decrease in tensile strain. Figure 4(B) shows an increase in Young's modulus along with a decrease in hysteresis-related energy loss, calculated as work dissipated through hysteresis (W). dis ) and the total work stored in the sample during the loading phase (W) i The ratio of ).

[0249] As can be seen from Figures 4 (A and B), the experiment shows that:

[0250] 1) For higher concentrations of filler, Young's modulus increases and maximum strain decreases (Figure 4(A)); and

[0251] 2) When the filler content is higher than 10% w / w, the hysteresis decreases with the increase of Young's modulus (Figure 4(B)).

[0252] These results indicate that the filler improves the mechanical response of the leaflets under physiological load.

Claims

1. A method for preparing a composite, wherein the composite comprises: (a) pyrolytic lignocellulose biomass particles with an average particle size of up to about 10 µm; and (b) a polycarbonate polyurethane polymer; wherein the amount of the pyrolytic lignocellulose biomass particles is from about 1 wt.% to about 75 wt.% relative to the weight of the polyurethane polymer. The method includes: (i) Pyrolysis of lignocellulose biomass pellets by heating in an inert or mildly oxidizing atmosphere at a temperature of about 250°C to about 1000°C for about 30 minutes to about 3 hours to provide the (a) pyrolyzed lignocellulose biomass pellets. and (ii) The (a) pyrolytic lignocellulose biomass pellets and (b) polycarbonate polyurethane polymer are mixed together to provide the composite.

2. The method according to claim 1, wherein step (i) of pyrolyzing lignocellulosic biomass pellets comprises heating in an inert atmosphere at a temperature of about 250°C to about 600°C for about 30 minutes to about 3 hours.

3. The method according to claim 2, wherein step (i) of pyrolyzing lignocellulose biomass pellets comprises: The step involves heating in an inert atmosphere followed by heating in a slightly oxidizing atmosphere at a temperature of about 700°C to about 1000°C for about 30 minutes to about 4 hours.

4. The method according to any one of the preceding claims, wherein the lignocellulose biomass particles are sporophytin exosphere particles.

5. The method according to any one of the preceding claims, wherein the polycarbonate polyurethane polymer is a silicone polycarbonate polyurethane polymer.

6. The method according to any one of the preceding claims, wherein the polycarbonate polyurethane polymer comprises terminal silicone groups.

7. The method according to any one of the preceding claims, wherein the silicone content of the polycarbonate polyurethane polymer is from about 5% to about 25%.

8. The method according to any one of the preceding claims, wherein the polycarbonate polyurethane polymer comprises polycarbonate polyurethane hard segments and polydimethylsiloxane (PDMS) soft segments.

9. The method according to any one of the preceding claims, wherein the polycarbonate polyurethane polymer comprises the following structure: Where n, x, y, and z are positive integers, and can each be independently between 1 and 100.

10. A method for preparing a polymer valve comprising a composite, the method comprising: (i) The composite is prepared according to the method of any one of the preceding claims, and (ii) The composite is shaped into a polymer valve.

11. A composite that can be obtained by the method of any one of claims 1 to 9 or a polymeric valve that can be obtained by the method of claim 10.

12. A complex comprising: (a) Polycarbonate polyurethane polymer, and (b) Pyrolytic lignocellulose biomass pellets with an average particle size of up to about 10 µm. The pyrolytic lignocellulose biomass pellets are present in an amount of about 1 wt.% to about 75 wt.% based on the weight of the polycarbonate polyurethane polymer, and The pyrolytic lignocellulose biomass particles are dispersed and mixed throughout (b) the polycarbonate polyurethane polymer.

13. The complex according to claim 12, wherein the lignocellulose biomass particles are sporophytin exosphere particles.

14. The composite according to any one of claims 12 to 13, wherein the polycarbonate polyurethane polymer is a silicone polycarbonate polyurethane polymer.

15. The composite according to any one of claims 12 to 14, wherein the polycarbonate polyurethane polymer comprises terminal silicone groups.

16. The composite according to any one of claims 12 to 15, wherein the polycarbonate polyurethane polymer has a silicone content of 5% to 25%.

17. The composite according to any one of claims 12 to 16, wherein the polycarbonate polyurethane polymer comprises polycarbonate polyurethane hard segments and polydimethylsiloxane (PDMS) soft segments.

18. The composite according to any one of claims 12 to 17, wherein the polycarbonate polyurethane polymer has the following structure: Where n, x, y, and z are positive integers, and can each be independently between 1 and 100.

19. The composite according to any one of claims 12 to 18, wherein the polycarbonate polyurethane polymer has one or more of the following properties: (a) Density is approximately 1.00 g / cm³ 3 Approximately 1.25 g / cm³ 3 ; (b) Tensile strength is from about 30 MPa to about 50 MPa; (c) Elongation of about 300% to about 500%; and (d) The melt flow rate is from about 10 g / 10 min to about 60 g / 10 min at 224 °C; and (e) Glass transition temperature (T) g The temperature ranges from approximately -20°C to approximately 20°C.

20. A polymeric valve comprising the composite according to any one of claims 12 to 19.

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