CN118695882A - A biocompatible absorbable composite material and preparation method thereof - Google Patents

Abstract

The present invention relates to a composite material comprising a plurality of compatible glass fibers in a thermoplastic polymer matrix, wherein the glass fibers and the polymer matrix are biocompatible and resorbable. The present invention also relates to a method for preparing a solid polymer composite material comprising a plurality of biocompatible resorbable glass fibers embedded in a biocompatible resorbable matrix polymer, wherein the matrix polymer is applied in the form of a solution from which the solvent is at least partially removed using an anti-solvent.

Description

A biocompatible absorbable composite material and preparation method thereof

Technical Field

The present invention relates to a method for preparing a solid polymer composite material, the solid polymer composite material comprising a plurality of biocompatible absorbable glass fibers embedded in a biocompatible absorbable matrix polymer, a glass fiber reinforced polymer composite material prepared by the method and a medical device comprising the composite material.

Background Art

The field of medical devices, such as implants, is a very active and rapidly growing field. As the average age of the human population continues to increase, this field is expected to continue to grow in the coming years. Therefore, there is a pressing need to improve the performance of medical implants and to improve the methods of manufacturing medical implants.

It is well known that many types of materials can be used to produce medical implants, such as metal alloys, ceramics, and polymers. Metal alloys are the traditional choice for manufacturing orthopedic implants (such as pins, screws, and plates) because they have strength and are well suited to withstand external loads. However, metal alloys are generally harder than the bone they are connected to (i.e., have a higher elastic modulus). Therefore, due to stress shielding, the bone density of the repair site will be reduced. In addition, metal alloys generally do not degrade in the body. Therefore, in order to avoid bone resorption, and because metal alloys are non-resorbable, they usually need to be removed after the bone heals, which requires a second operation.

New materials have been developed that better match the mechanical properties of bone and are resorbable by the body over time. These materials can minimize stress shielding issues and eliminate the need for secondary surgery.

EP2243500 describes how to make an implantable composite material consisting of a polymer matrix and glass fibers. The glass fibers are produced separately, cut into 10 mm lengths, and then mixed with a matrix polymer in an extruder. Alternatively, the fibers are produced separately and mixed with a molten polymer in a right-angle die. In either case, the matrix polymer must be in a molten state to be processed in an extruder, which means that the matrix material must be a thermoplastic resin and a higher processing temperature must be used to obtain a lower viscosity. Because the matrix polymer must be a thermoplastic polymer, the process of EP2243500 is limited. In addition, the heat required to achieve the low viscosity required by the thermoplastic polymer may cause thermal oxidative damage. The matrix polymer will thus undergo polymer degradation and a reduction in the associated molecular weight, resulting in a decrease in mechanical properties and a shortened in vivo absorption time.

There is therefore a need for a better method of producing polymer-based composites that allows for better control over the composition and properties of the final composite product.

Summary of the invention

The above problems can be solved by using the method of the present invention. The method is used to prepare a solid polymer composite material, which includes a plurality of biocompatible absorbable glass fibers embedded in a biocompatible absorbable matrix polymer, and the method comprises:

a) providing a plurality of glass fibers compatible with the matrix polymer,

b) providing a mixture comprising the matrix polymer and a solvent,

c) coating the mixture onto a plurality of glass fibers, and

d) removing the solvent from the mixture using an anti-solvent to obtain the solid composite material.

It is understood that the above method does not require heat-driven melt processing, and does not require the use of an extruder to provide a polymer melt for the melt pultrusion die. Therefore, it is not necessary to heat the matrix polymer to a high temperature, thereby greatly reducing the risk of polymer degradation. On the contrary, the matrix polymer solution can be applied at a relatively low and easy-to-handle temperature, such as room temperature or ambient temperature, without inducing polymer degradation. In addition, the glass fiber can be oriented and spread as required, and an easy-to-handle mixture consisting of a matrix polymer and a solvent can be applied. If necessary, a variety of mixtures can be applied to form a thicker matrix polymer layer.

The method of the present invention can be used for discontinuous (e.g., chopped) fibers. In addition and/or alternatively, the above method can also be used for longer (e.g., continuous or woven or knitted) fibers, thereby facilitating better tailoring of the properties of the glass reinforced polymer composite (GRP), thereby eliminating the need to break the glass fiber into relatively shorter fibers.

The present invention also relates to a polymer composite material, which comprises a plurality of biocompatible absorbable glass fibers present in a biocompatible absorbable polymer matrix, wherein the matrix polymer monomer content of the composite material is less than 2% by weight, more preferably 1% by weight, and even more preferably 0.5% by weight, calculated as the matrix polymer. Composite materials with low monomer content are beneficial because high monomer content indicates that the matrix polymer undergoes undesirable degradation, which can lead to mechanical strength loss of products (e.g. medical implants) made of the polymer composite material and this loss is uncontrollable. The composite material can be obtained by the method of the present invention or can be obtained by the method of the present invention.

The composite materials of the present invention are particularly suitable for use in medical devices such as medical implants, for example orthopedic implants and stents.

DETAILED DESCRIPTION

The present invention relates to a method for preparing a solid polymer composite material, the solid polymer composite material comprising a plurality of biocompatible absorbable glass fibers embedded in a biocompatible absorbable polymer matrix, the method comprising the following steps:

a) providing a plurality of glass fibers compatible with the matrix polymer,

b) providing a mixture comprising a matrix polymer and a solvent,

c) applying the mixture to a plurality of glass fibers, and

d) removing the solvent from the mixture coated on the plurality of glass fibers using an anti-solvent to obtain a solid composite material.

It has been found that the process of the present invention has a number of advantages over conventional processes using molten polymers. The first advantage is that the matrix polymer does not need to be processed at molten temperatures. This is attractive because it reduces the likelihood of thermal degradation of the polymer. Another advantage is that dissolving the matrix polymer in a solvent can form a low viscosity solution, thereby improving fiber spreadability and fiber wettability. Another advantage of using a solvent-antisolvent combination is that the matrix polymer present in the final product may have a lower content of monomers and low molecular weight oligomers than the starting matrix polymer. Since the high molecular weight polymer determines the properties of the composite material, it is considered advantageous to reduce the content of low molecular weight components.

Biocompatible resorbable glass fibers are known in the art. As used herein, the term "resorbable" refers to a material that disappears from the body by mineralization (ie, breakdown and ion release) and dissolution of ion products, while not significantly stimulating an inflammatory response during its breakdown.

In the context of the present specification, the term "composite material", sometimes also referred to as "polymer composite material", refers to a composite material comprising glass fibers embedded in a polymer matrix.

Unless otherwise defined, the terms used in this application are those agreed upon at the 1987 and 1992 consensus conferences on biomaterials, see Williams, DF (ed.): Definitions in biomaterials Proceedings of a consensus conference of the European Society for Biomaterials, Chester, England. March 3-5, 1986. Elsevier, Amsterdam 1987, and Williams DF, Black J, Doherty PJ. Second consensus conference on definitions in biomaterials. In: Doherty PJ, Williams RL, Williams DF, Lee AJ (eds). Biomaterial-Tissue Interfaces. Amsterdam: Elsevier, 1992.

In the context of the present invention, the compatibility of glass fiber and matrix polymer relates to the interface between glass fiber and surrounding matrix polymer. Therefore, it is understood that glass fiber is preferably compatible with matrix polymer. Therefore, preferably, the surface of glass fiber (which is substantially hydrophilic) is made compatible with the substantially hydrophobic matrix polymer in contact with the surface of glass. Usually, glass fiber is coated with a coating or glue layer to reduce surface energy. With regard to the concept of compatibility, the coating or glue layer is considered to be a component of glass fiber. Therefore, the coated or sizing glass fiber compatible with the matrix polymer layer means that the coating or glue layer is compatible with the matrix polymer, thereby providing good interfacial adhesion for load transfer. Therefore, in a preferred embodiment, the absorbable glass fiber compatible with the matrix polymer is an absorbable glass fiber with a coating or glue layer compatible with the matrix polymer on the surface.

In the method of the present invention, a mixture is provided, and this mixture comprises a matrix polymer and a solvent. In the present invention, a solution is usually used, i.e., the polymer is completely dissolved in the solvent. The solvent is a fluid, and the matrix polymer is dissolved therein with a certain concentration, thereby forming a pourable solution with dynamic viscosity, thereby being easy to process. Using the solution, a processable liquid can be obtained, thereby without the need to melt the polymer by a higher temperature. Any known method and equipment can be used to prepare the solution, for example, a container equipped with a matrix polymer and a solvent is provided, and a suitable polymer mixer is used to mix the matrix polymer and the solvent. It should be noted that the mixture can include solid components, such as hydroxyapatite or calcium phosphate.

Preferably, when the mixture is applied to a plurality of glass fibers, the dynamic viscosity of the mixture measured at 18° C. is preferably at most 10,000 Pa.s, more preferably at most 5,000 Pa.s, and most preferably at most 500 Pa.s, wherein 1 Pa.s is equal to 1,000 centipoise (cP). The dynamic viscosity of the solution measured at 18° C. is preferably 1-1,000 Pa.s, preferably 5-500 Pa.s, and more preferably 20-200 Pa.s. It is understood that the viscosity is measured, for example, using an Anton-Paar ViscoQC rotational viscometer according to ASTM D2196-20.

By controlling various parameters, including the nature of the solvent, the concentration of the polymer, and the degree of aging of the solution, it is possible to ensure that the mixture has the desired viscosity when in contact with the plurality of glass fibers. It is well known that polymer solutions, especially those of higher concentrations, may age over time, causing the polymers to align and thus increase in viscosity. If this occurs, the polymer aggregation can be reduced by agitating the mixture (e.g., by stirring, shaking, or vibrating), and optionally by slightly increasing the temperature, thereby reducing viscosity.

The concentration of the matrix polymer in the mixture is generally at least 1 wt %, preferably at least 5 wt %, more preferably at least 10 wt %, even more preferably at least 20 wt %. The concentration of the matrix polymer in the mixture is generally at most 70 wt %, preferably at most 50 wt %, more preferably at most 35 wt %, even more preferably at most 25 wt %.

In the context of the present invention, the term "anti-solvent" is used to refer to a fluid or liquid that is miscible with a solvent but in which the matrix polymer is insoluble in the presence of the anti-solvent. In other words, the anti-solvent used to solidify the matrix polymer is miscible with the solvent, but the matrix polymer is insoluble in the anti-solvent. Since the solvent and the anti-solvent are miscible, the addition of the anti-solvent can be used to reduce the solubility of the matrix polymer in the liquid.

In the method of the present invention, the addition of an anti-solvent can ensure that the matrix polymer solidifies. The solidification process of the present invention can also be described from the perspective of solvent quality, wherein the term solvent quality is used in its conventional sense to indicate the degree of solubility of a certain compound in a solvent. The solvent quality of the solvent of the matrix polymer is good, meaning that a large amount of the matrix polymer can be dissolved in the solvent. On the other hand, the solvent quality of the anti-solvent of the matrix polymer is poor, meaning that the amount of the polymer that can be dissolved in the anti-solvent is low. When the anti-solvent is added to the mixture of the matrix polymer and the solvent on multiple glass fibers, the solvent quality of the solvent on the glass fibers will decrease. Therefore, by adding an anti-solvent, the solvent quality of the solvent mixture of the matrix polymer will deteriorate, causing polymer gelation and solidification by phase separation with the solvent mixture. Therefore, the matrix polymer will be precipitated on the glass fibers, thereby forming a solid polymer composite.

It is understood that the preferred choice of solvent depends on the matrix polymer used, and the preferred choice of anti-solvent (mixture) depends on the selected solvent and matrix polymer. Matrix polymers are known in the art, and any known matrix polymer can be used in the method of the present invention as long as it is suitable for the present invention, that is, it is at least biocompatible and absorbable and compatible with glass fibers.

Preferably, the matrix polymer is a polyester, more preferably, the matrix polymer is a thermoplastic polyester. Most preferably, the matrix polymer is a polyester based on lactide. Additionally or alternatively, the matrix polymer is selected from the following group: polylactide (PLA), poly-L-lactide (PLLA), poly-DL-lactide (PDLLA), polyglycolide (PGA), poly(ε-caprolactone) (PCL), glycolide copolymer, glycolide/trimethylene carbonate copolymer (PGA/TMC), lactide/tetramethyl glycolide copolymer, lactide/trimethylene carbonate copolymer, lactide/d-valerolactone copolymer, lactide/ε-caprolactone copolymer, L-lactide/DL-lactide copolymer (PLDLA), glycolide/L-lactide copolymer (PLGA), polylactide-co-glycolide, lactide/glycolide/trimethylene carbonate terpolymer, lactide/glycolide/ε-caprolactone terpolymer Poly(ethylene oxide), PLA/polyethylene oxide copolymer, asymmetric 3,6-substituted poly-1,4-dioxane-2,5-dione, polyhydroxybutyrate (PHB), PHB/β-hydroxyvalerate copolymer (PHB/PHV), poly-β-hydroxypropionate (PHPA), poly(p-dioxanone) (PDO), poly-d-valerolactone-poly-ε-caprolactone, poly(ε-caprolactone-DL-lactide) copolymer, methyl methacrylate-N-vinyl pyrrolidone copolymer, polyester amide, oxalic acid polyester, polydihydropyran, polyalkyl-2-cyanoacrylate, polyurethane (PU), polyvinyl alcohol (PVA), polypeptide, poly-β-malic acid (PMLA), poly-β-alkanoic acid, polycarbonate, polyorthoester, polyphosphate, poly(ester anhydride) and mixtures thereof.

A matrix polymer selected from the following group can be preferably used: polylactide (PLA), poly-L-lactide (PLLA), poly-DL-lactide (PDLLA), polyglycolide (PGA), poly(ε-caprolactone) (PCL), glycolide copolymer, glycolide/trimethylene carbonate copolymer (PGA/TMC), lactide/tetramethyl glycolide copolymer, lactide/trimethylene carbonate copolymer, lactide/d-valerolactone copolymer, lactide/ε-caprolactone copolymer, L-lactide/DL-lactide copolymer (PLDLA), glycolide/L-lactide copolymer (PLGA), polylactide-co-glycolide, lactide/glycolide/trimethylene carbonate terpolymer, lactide/glycolide/ε-caprolactone terpolymer, PLA/polyethylene oxide copolymer, poly(ε-caprolactone-DL-lactide) copolymer and combinations thereof. It is particularly preferred to use a matrix polymer selected from the group consisting of polylactide, poly(lactide-co-glycolide), poly(lactide-co-ε-caprolactone), polyglycolide (PGA) and poly(ε-caprolactone) (PCL), and combinations thereof.

In a preferred embodiment of the method, the ratio of the intrinsic viscosity of the matrix polymer in the solid polymer composite to the intrinsic viscosity of the (original) matrix polymer provided in b) is between 0.5 and 1.5, preferably between 0.8 and 1.2, most preferably between 0.9 and 1.1. The property of intrinsic viscosity (IV) is known in the art and can be determined, for example, by dilute solution viscosity measurement using a glass capillary viscometer according to method ASTM 2857.

Generally speaking, the intrinsic viscosity of the matrix polymer in the solid polymer composite does not deviate much from the viscosity of the matrix polymer before it is combined with the solvent.

Preferably, the solvent comprises or consists of acetone, chloroform, dichloromethane, tetrahydrofuran and/or ethyl acetate. In all cases, relatively pure solvents are preferably used. Therefore, preferably the solvent comprises at least 80% by weight, particularly at least 90% by weight, more particularly at least 95% by weight, more particularly at least 98% by weight, or even at least 99% by weight of acetone, chloroform, dichloromethane, tetrahydrofuran or ethyl acetate. If the solvent comprises or consists of acetone, the anti-solvent is preferably selected from water, C ₁ -C ₆ alcohol, water-acetone mixture, water-C ₁ -C ₆ alcohol mixture and water-acetone- _{C 1} -C ₆ alcohol mixture. If the solvent comprises or consists of chloroform or dichloromethane, the anti-solvent is preferably selected from C ₁ -C ₆ alcohol-chloroform mixture, C ₁ -C ₆ alcohol-dichloromethane mixture, C ₁ -C ₆ alcohol or a mixture thereof. If the solvent comprises or consists of ethyl acetate, the antisolvent is preferably selected from water, C ₁ -C ₆ alcohols, water-acetone mixtures, water-C ₁ -C ₆ alcohol mixtures, water-acetone-C ₁ -C ₆ alcohol mixtures and acetone.

Of course, there are many (further) useful combinations of polymers, solvents and anti-solvents. Table 1 lists a list of preferred matrix polymers for the process of the present invention, as well as preferred choices of solvents and anti-solvents corresponding to the preferred matrix polymers. Although all combinations mentioned in Table 1 are considered as working examples of the present invention, it is emphasized that Table 1 is not exhaustive, as further combinations can also be made and the process of the present invention can use other polymers, solvents and/or anti-solvents.

Table 1: Examples of preferred matrix polymer, solvent and antisolvent combinations.

After the solid polymer composite is prepared in step d), the method of the present invention can be extended to include one or more additional steps. A preferred example of such a step (which can be marked as e) includes shaping the solid polymer composite obtained in step d), for example, into a medical device, such as an implantable device. Examples of suitable shapes are bands, strands, (hollow) rods, tubes, pellets, particles or monofilaments. Other examples of implantable devices (such as orthopedic implants) are screws, nails, wires, pin wires, anchors, cables, cable ties or wire ties, plates and screw systems, and external fixators or monofilaments. These are just a few examples of orthopedic implants based on polymer composites. The choice of material will depend on the specific requirements of each device, such as biocompatibility, mechanical strength and durability.

It should be understood that forming means treating the polymer composite material in a certain way so that the composite material final product has a certain desired shape. It can be achieved by any known means, including pressing, such as pressing into a certain shape, thermoforming, cutting, slitting, calendering and/or rolling. It should be understood that multiple operations can be combined, such as multiple rolling steps, which can further thin the rolled strip and optionally cut the rolled strip into strips. Other forming methods include, for example, injection molding, compression molding, stereolithography, extrusion or thermoforming. In injection molding, the polymer composite material is melted and injected into a mold, and then cooled and solidified to form a device. In compression molding, the polymer composite material is placed in a mold and high pressure and heat are applied to fuse the material into the desired shape. Stereolithography is a process that uses lasers to selectively solidify polymer composites layer by layer to create 3D shapes. Extrusion is a process in which a polymer composite material is melted and molded into a long, continuous shape, which can then be cut to the appropriate size. Thermoforming is a process in which a polymer composite material is heated and shaped in a mold using vacuum or pressure. The choice of molding method will depend on factors such as the desired shape, production volume, and the material properties of the polymer composite used.

In the method of the present invention, it is preferred to partially evaporate the solvent before adding the anti-solvent. This has the advantage that the amount of anti-solvent required to remove the solvent from the composite material can be reduced. Therefore, the method of the present invention preferably comprises a step c2) of evaporating at least part of the solvent from the mixture applied to the plurality of glass fibers.

In step d), the solvent is removed from the mixture using an anti-solvent to obtain the solid composite material, which can be carried out by contacting a glass fiber with the mixture with an anti-solvent, for example, by passing the glass fiber through an anti-solvent bath. Other methods will be apparent to those skilled in the art. The solid composite material is recovered from the anti-solvent bath, and the remaining anti-solvent can be removed by evaporation or the like.

The glass fiber may suitably have a diameter of 5-30 μm, preferably 6-20 μm, measured according to ASTM D1577-01 Option C. In one embodiment, the glass fiber used in the present invention preferably has a diameter of less than 30 μm, particularly less than 25 μm, more particularly less than 20 μm, and in some embodiments less than 15 μm.

In one embodiment, the glass fiber is applied in the form of a glass fiber bundle. In one embodiment, the linear density of the glass fiber bundle as a whole is between 5 and 5000 tex, preferably between 20 and 1300 tex, more preferably between 25 and 750 tex, more preferably between 50 and 500 tex, and even more preferably between 70 and 300 tex, measured according to ASTM D1577-01 Option A, i.e., according to ASTM D1577-01 A. The term linear density corresponds to the weight of a certain length of glass fiber bundle, and the unit tex corresponds to the weight (in grams) per 1000 meters of fiber.

The glass fiber bundles that can be used in the present invention preferably have at least 50 fibers, preferably at least 100 fibers, more preferably at least 150 fibers, and even more preferably at least 200 fibers. The maximum value can be 5000 fibers, more particularly 3000 fibers.

In one embodiment, the present invention uses a glass fiber bundle, wherein the coefficient of variation of the diameter of the glass fibers in the glass fiber bundle is at most 15%, in particular at most 10%. The coefficient of variation can be at most 8%, or at most 6%. It has been found that in some embodiments, the coefficient of variation can be at most 3%, which actually indicates that the diameter is very uniform. The method for determining the coefficient of variation is as follows: 30 glass fibers in the glass fiber bundle are measured. The average diameter and the standard deviation are calculated. The coefficient of variation is obtained by dividing the standard deviation by the average diameter, expressed in %.

In a preferred embodiment, the glass fiber is a bioactive glass fiber. Bioactive glass fibers are known in the art and have been designed to induce or modulate biological activity. Bioactive materials are typically surface-active materials that can interact with mammalian tissue. Bioactive glass can also be designed to leach ions or other chemicals, thereby having the beneficial effects of producing osteoconduction, osteoinduction, anti-infection and/or angiogenesis.

The glass fiber can be silicon-based, boron-based or phosphorus-based glass fiber, preferably silicon-based glass fiber.

The glass fibers used in the present invention preferably have a composition comprising a network former and a network modifier, wherein the molar ratio between the network former and the network modifier is between 1 and 4, preferably between 1.5 and 3.5, and more preferably between 2 and 3. It has been observed that a good glass quality particularly suitable for fiber formation can be obtained according to such a ratio, especially one of the preferred ranges.

The glass fiber preferably includes a network former selected from silicon oxides such as silicon dioxide (SiO ₂ ), boron oxides such as boron trioxide (B ₂ O ₃ ) and boron suboxide (B ₆ O), and phosphorus oxides such as phosphorus trioxide (P ₂ O ₃ ) and phosphorus pentoxide (P ₂ O ₅ or P ₄ O ₁₀ ). The glass fiber preferably includes a network modifier selected from sodium oxides such as Na ₂ O or Na ₂ O ₂ , magnesium oxides such as MgO, and calcium oxides such as CaO. More preferably, the glass fiber includes several network formers and several network modifiers.

The glass fiber preferably has a composition comprising the following components:

SiO ₂ , 50-75 wt %, in particular 55-75 wt %, more in particular 60-75 wt %,

B ₂ O ₃ , 0-15 wt %,

P ₂ O ₅ , 0.5-5 wt %, in particular 0.5-4 wt %, more in particular 0.5-3 wt %,

_Na2O , 5-20% by weight

CaO, 0-25 wt.%, in particular 2-25 wt.%, more in particular 5-25 wt.%,

MgO, 0-10% by weight

_Li2O , 0-1 wt%,

K ₂ O, 0-15 wt %, in particular 0-10 wt %, more in particular 0-4 wt %,

SrO, 0-4 wt%,

Al ₂ O ₃ , 0-5 wt %, and

Fe ₂ O ₃ , 0-5 wt % (excluding size, if present).

In one embodiment, the glass fibers (excluding size, if present) have a composition comprising the following components: 60-75 wt% _SiO2 , 0-15 wt% _B2O3 , 0.5-3 wt% _{P2O5 ,} 5-20 wt% _Na2O , 5-25 wt% CaO, 0-10 wt _% MgO, 0-1 wt% _Li2O , 0-4 wt% _K2O , 0-4 wt% SrO _, 0-5 wt% _Al2O3 , and 0-5 wt% _{Fe2O3 .}

In one embodiment, the glass composition comprises less than 10 wt %, in particular less than 5 wt % B ₂ O ₃ . In one embodiment, the glass composition comprises 7-20 wt % Na ₂ O. In one embodiment, the glass composition comprises 2-8 wt % MgO. In one embodiment, the glass composition comprises 5-15 wt % CaO.

The tensile strength of the glass fiber, measured by a tensile test according to DIN EN ISO 5079, is preferably in the range of 1000-3000 MPa, preferably 1200-2500 MPa, more preferably 1400-2200 MPa.

The elastic modulus of the glass fiber is preferably in the range of 20-100 GPa, preferably 35-85 GPa, and more preferably 50-70 GPa, measured by a tensile test according to DIN EN ISO 5079 "Determination of breaking force and elongation at break of individual fibers" (ISO 5079:2020).

An ideal glass fiber and glass fiber bundle that can be used in the present invention is described in a patent application having the same applicant, inventor and filing date as the present application, entitled "An absorbable and biocompatible glass fiber bundle having a defined diameter and a method for making the same", the entire text of which is incorporated herein by reference.

In a preferred method, multiple mixtures including a matrix polymer and a solvent are applied to the glass fiber. It is understood that this includes the case where the same mixture is applied multiple times, the case where multiple mixtures having the same matrix polymer but different concentrations are applied continuously, and/or the case where different mixtures having different matrix polymers and/or different solvents are applied continuously. Ideally, multiple mixtures are applied by performing b) and c) multiple times (e.g., 2, 5, 10 times) in a continuous manner.

It will therefore be appreciated that the present invention may relate to a method of preparing a solid composite material comprising a plurality of biocompatible absorbable glass fibers embedded in a biocompatible absorbable matrix polymer, the method comprising the steps of:

a) providing a plurality of biocompatible absorbable glass fibers,

b) providing a first mixture comprising a first biocompatible absorbable matrix polymer compatible with the glass fibers and a first solvent,

c) applying the first mixture to the plurality of glass fibers,

d) optionally removing the first solvent from the first mixture using a first anti-solvent,

e) optionally at least partially drying the glass fibers coated with the first matrix polymer,

f) providing a second mixture comprising a second biocompatible absorbable matrix polymer compatible with the glass fibers and/or the first biocompatible absorbable matrix polymer and a second solvent,

g) applying the second mixture to the plurality of glass fibers, and

h) removing the solvent from the mixture using an anti-solvent to obtain the solid composite material.

It should be understood that the anti-solvent in step h) needs to be at least the anti-solvent of the second mixture, and preferably the anti-solvent of the first and second mixtures. If step d) is omitted, the anti-solvent in step h) is preferably the anti-solvent of the first and second mixtures. It should be further understood that the first and second matrix polymers can be the same polymer or different polymers. In addition, the first and second solvents can be the same solvent or different solvents.

It is worth noting that, if necessary, the solvent may be partially removed from the system by evaporation before using the anti-solvent, between steps c) and d) and/or between steps g) and h).

In a preferred embodiment, the polymer concentration in the second mixture is higher than the polymer concentration in the first mixture. The polymer concentration in the second mixture is preferably at least 1.5 times that of the first mixture, preferably at least 2 times that of the first mixture, and more preferably at least 2.5 times that of the first mixture.

A particular advantage of the process of the present invention is that a composite material with a lower yellowness index (YI) can be produced compared to the processes of the prior art. Therefore, a preferred process is one in which the difference in yellowness index between the matrix polymer provided in step b) and the composite material produced is less than 20, preferably less than 10, more preferably less than 5, even more preferably less than 2. The term YI is known in the art and is preferably determined according to ASTM E313. Yellowness is usually caused by the use of heat treatment, which is not required by the process according to the present invention.

Preferably, the composite material has a yellowness index (YI) of less than 30, preferably less than 20, more preferably less than 15, and even more preferably less than 10, measured according to ASTM E313.

Another advantage of the present invention is that composite materials with very high glass fiber content can be produced. Therefore, the method of the present invention is preferably used to prepare a solid composite material comprising at least 60% by weight of a plurality of biocompatible absorbable glass fibers, preferably at least 70% by weight of a plurality of biocompatible absorbable glass fibers, more preferably at least 80% by weight of a plurality of biocompatible absorbable glass fibers, and even more preferably at least 90% by weight of a plurality of biocompatible absorbable glass fibers.

Another advantage of the method of the present invention is that there are fewer voids and/or bubbles at the glass/matrix interface compared to conventional melt techniques. These voids and/or bubbles scatter light and may give the composite an off-white appearance and/or appear white. Since voids or bubbles are usually formed along the glass fibers, white streaks appear. It is speculated that the molten matrix polymer in conventional melt techniques does not fully wet the glass fiber surface, resulting in the formation of voids and bubbles. The solvent method of the present invention does not have this disadvantage and can produce a composite material with no or at least few voids or bubbles, resulting in a more uniform appearance of the composite material.

The method of the present invention can add additives (such as bioactive additives) to the composite material. Therefore, in a preferred embodiment, the method according to the present invention also includes embedding additives (such as active pharmaceutical ingredients (API) or mineral components) in the composite material.

The present invention also relates to a composite material obtainable by the method according to the present invention. In addition, the present invention relates to a composite material obtainable by the method according to the present invention.

The present invention also relates to a composite material, comprising a plurality of glass fibers embedded in a polymer matrix, the polymer matrix being compatible with the plurality of glass fibers, wherein the glass fibers and the polymer matrix are biocompatible, absorbable and preferably bioactive, wherein the monomer content of the composite material is less than 1 wt %. Preferably, the monomer content is less than 0.5 wt %, more preferably less than 0.2 wt %, even more preferably less than 0.1 wt %. The monomer content is calculated based on the amount of the polymer matrix. These monomers can come from different sources, but an important source is the degradation caused by the high temperature required for preparing the composite material (i.e., the high temperature required for obtaining the polymer melt suitable for extrusion). It is beneficial to have a low monomer content because high monomer levels indicate a loss of strength and other mechanical properties. This is particularly important for the case of implants, wherein the composite material is placed in a mammal (preferably a human) for a long time. An attractive feature of the method of the present invention is that a composite material with a low monomer content can be manufactured. On the one hand, this is because the polymer does not need to reach a melting temperature, thereby avoiding thermal degradation. On the other hand, the use of a solvent-antisolvent combination inherently reduces the amount of monomer present in the polymer matrix, since extraction of residual monomer from the composite into the solvent and/or antisolvent would be an additional purification step for the matrix polymer.

Preferably, the plurality of glass fibers in the composite material are at least partially coated with a glue layer, in particular coated with a glue material comprising a compatibilizer compatible with the matrix polymer. Therefore, in a preferred embodiment, the absorbable glass fiber compatible with the matrix polymer is an absorbable glass fiber having a glue layer compatible with the matrix polymer on its surface. An ideal glue material and its application method are described in a patent application having the same applicant, inventor, filing date and priority date as the present application, and the name of the patent application is "An absorbable glass fiber coated with glue material and a method for preparing the same", which is incorporated herein by reference in its entirety. Further, the components of the glue material are known in the art and will not be described in detail herein.

In one embodiment, at least 10% of the structural units of the compatibilizer are identical to the structural units of the matrix polymer. This is a method to ensure that the glass fiber has good compatibility with the matrix material. In one embodiment, at least 20%, or at least 40%, or at least 60% of the structural units of the compatibilizer are identical to the structural units of the matrix polymer. In one embodiment, the compatibilizer and the matrix polymer both include at least 20% by weight, in particular at least 30% by weight of lactide units. In one embodiment, the compatibilizer and the matrix polymer both include at least 20% by weight, in particular at least 30% by weight of caprolactone units. In another embodiment, the compatibilizer and the matrix polymer both include at least 20% by weight, in particular at least 30% by weight of glycolide units.

Preferably, the composite material comprises an additive, such as an active pharmaceutical ingredient (API) or a mineral component, embedded within the composite material.

Preferably, the composite material has a small amount of bubbles and/or voids. It is understood that the bubbles and voids inside the composite material give the composite material a milky and white appearance. Therefore, preferably, the composite material according to the present invention is translucent, more preferably transparent. Therefore, it is understood that translucency and transparency are optical properties related to the transmittance of visible light, wherein visible light is light with a wavelength in the range of about 380 to about 750 nanometers in the visible spectrum. In one embodiment, the transmittance of the composite material to visible light is at least 50%, particularly at least 70%, and more particularly at least 80%. Preferably, the composition is radiopaque, which means that it blocks X-rays. It is understood that X-rays refer to high-energy radiation with a wavelength in the range of about 10 pm to 10 nm. Composite materials are radiopaque, which can be achieved by appropriately selecting glass fibers. Radiopaque composite materials are a good choice for implantable medical devices because the degradation of the composite material in the body can be monitored by X-rays.

In the composite material, the glass fibers or glass fiber bundles can be present in the form of continuous fibers and/or chopped fibers. If chopped fibers are used, their length range is generally 1-50 mm, particularly 1-25 mm, more particularly 1-20 mm, even more particularly 2-10 mm, most particularly 4 mm or less and 1 mm or more.

In one embodiment, the medical device comprises a unidirectional composite tape. The glass fiber base tape is known in the art. It comprises a biodegradable polymer and a plurality of unidirectionally arranged continuous glass fibers, wherein the fibers are arranged along the length direction of the tape. The width of the tape is generally at least 2 times, particularly at least 5 times, and more particularly at least 10 times, of its thickness. The length of the tape is generally at least 10 times, particularly at least 100 times, of its width. The thickness of the tape is preferably less than 0.3 mm, more preferably less than 0.2 mm, and even more preferably less than 0.15 mm. The length of the tape is preferably at least 1 m, more preferably at least 5 m, and even more preferably at least 10 m. The third dimension (i.e., width) is preferably between 0.5 cm and 10 cm, more preferably between 0.8 cm and 5 cm, and even more preferably between 1 cm and 2.5 cm. The composite tape can be prepared by, for example, spreading the fibers of the glass fiber bundle, contacting the glass fibers with the polymer matrix in the liquid phase, and solidifying the matrix. Preferably, the matrix content of the unidirectional composite tape is 2-40 wt %, in particular 5-30 wt %, more particularly 5-25 wt %, in a specific embodiment 10-20 wt %. The preferred properties given elsewhere regarding the matrix and glass fibers also apply here.

In one embodiment, the medical device comprises a plurality of layers, wherein one or more layers comprises one or more composite material strips.

Thus, in one embodiment, the composite material is formed into the form of a unidirectional composite tape as described above. In an alternative embodiment, the composite material is formed into strands, rods, pellets or granules. The strands/rods are round fiber reinforced polymers, preferably 5-50 mm in diameter. Pellets are small longitudinal sections of rods, about 5-50 mm in diameter, while granules are small granules, about 1-10 mm in diameter. The size of the pellets or granules can be adjusted to match the size of the feed screw used in polymer processing techniques (e.g., injection molding).

Preferably, the intrinsic viscosity of the matrix polymer in the composite material is between 1.5 and 4.0 dL/g, preferably between 1.8 and 3.0 dL/g, more preferably between 2.0 and 3.0 dL/g.

Generally, the polymer composite has a Young's modulus higher than that of the matrix polymer, preferably 110% to 1000%, more preferably 200% to 600%, most preferably 300% to 500% of that of the matrix polymer, as measured according to ASTM D7264/D7264M.

Preferably, the glass-reinforced polymer composite has a mechanical strength higher than the matrix polymer strength, preferably at least 110% of the matrix polymer, preferably at least 200% of the matrix polymer, and most preferably at least 400% of the matrix polymer, as measured by a three-point bending test (tested in accordance with ASTM D7264/D7264M) when the applied force is perpendicular to the reinforcing fibers.

Preferably, the glass fiber content of the polymer composite is 5-95 wt %, preferably 10-90 wt %, more preferably 15-80 wt %, even more preferably 20-70 wt %, most preferably 30-60 wt %, based on the total amount of glass and polymer. Alternatively, preferably, the glass fiber content of the polymer composite is at least 60 wt %, more preferably at least 70 wt %, even more preferably at least 80 wt %, even more preferably at least 90 wt %.

In addition to glass and polymer, the composite material of the present invention may also include, for example, up to 30 wt %, up to 20 wt %, or up to 10 wt % of other components. Examples of other components may be hydroxyapatite and calcium phosphate, such as tricalcium phosphate (TCP), such as β-TCP.

The glass-reinforced polymer composite material of the present invention is particularly suitable for medical devices, such as medical implants. Therefore, the present invention also relates to a medical device comprising the composite material of the present invention. Preferably, the medical device is an implant or a stent comprising the composite material of the present invention.

It is obvious to those skilled in the art that different embodiments of the present invention can be combined unless they contradict each other.

Unless otherwise indicated, all percentages used herein are by weight.

When amounts, concentrations, sizes and other parameters are expressed in the form of ranges, preferred ranges, upper limits, lower limits or preferred upper limits and limits, it should be understood that any range obtained by combining any upper limit or preferred value with any lower limit or preferred value is also specifically disclosed, regardless of whether the resulting range is explicitly mentioned in the context.

The present invention will be described below with reference to the following examples, but the present invention is not limited thereto or thereby.

Example

Measurement technology

Intrinsic viscosity

The intrinsic viscosity (IV) is based on the viscosity of a dilute solution of a polymer and is a measure of the average molecular weight of the polymer. It is based on the flow time of a sample solution through a narrow tube (i.e., an Ubbelohde viscometer) compared to the flow time of a known pure solvent through a tube of the same size. It is measured according to ASTM 2857.

To determine IV, three solutions of the matrix polymer were prepared with the composite sample at concentrations of 2, 1, and 0.5 g/dL. These solutions were prepared by dissolving the composite sample in chloroform and filtering the solution through a 0.2 μm filter to remove the glass fibers. The polymer concentration was corrected for the glass content determined using TGA. A blank solution containing only the solvent was also prepared. The measuring tube was rinsed with the sample solution filtered through a 0.2 μm filter. Subsequently, the filtered sample solution was added to the measuring tube until between the two lines and placed in a water bath set to 25°C. The flow time of the sample, t _o, was then measured and corrected with the Hagenbach correction factor, th _, to obtain t _g . The relative viscosity was calculated from the t _g of the sample and the t _g of the blank using η _rel = t _{g, sample} /t _{g, blank} . The intrinsic viscosity η _inh was calculated using η _inh = ln(η _rel )/C, where C is the concentration of the sample in g/dl. Therefore, the IV is in dL/g.

Record the resulting intrinsic viscosity and sample weight in the appropriate table in the batch record. Repeat the same procedure for the other solutions.

Yellowness Index

The yellowness index (YI) was measured using a Chromometer CR-410 from Konica Minolta in accordance with ASTM D1925. The measurement was repeated three times. The instrument was calibrated using a standard calibration plate (No. 12133209), where Y=85.6, X=0.3150, and y=0.3212.

Band size

The width of the tape was measured using a digital microscope. An image of the composite tape was taken and the width was measured using Zen core version 2.5 software or Keyence microscope software. The thickness was measured using a wide face thread micrometer (or caliper).

Three-point bending test

The test specimens were made by stacking thin layers of prefabricated composite tape in the same direction. The number of composite tape layers depends on the required composite thickness. In a rectangular (100mm x 100mm) compression mold, these composite layers were heated to above the polymer melting point (190-200°C), pressed under a load of 12kN for 5 minutes, and then quenched to obtain composite plates.

The composite panels were then cut into rectangular specimens and tested according to ASTM D7264/D7264M-15. The span to thickness ratio was 16:1. Standard width: 13 mm, specimen length was approximately 20% longer than the support span (10% on each side).

Determination of loss on ignition by thermogravimetric analysis (TGA)

The Loss on Ignition (LOI) technique is a suitable technique for determining the matrix content in glass fiber samples. The matrix content of a 1 ± 0.2 g sample was determined in a LECO 701 macro thermogravimetric analyzer (TGA). For the test, the sample is entered into the software and the initial (empty) crucible weight (with lid) is determined. After the initial weight is obtained, the sample is placed in the crucible at the appropriate position and the instrument measures the weight of the sample. The instrument is then heated to 110°C and held for 30 minutes. After 30 minutes, the instrument is heated to 565°C at a rate of 25°C/min and held at this temperature for 2 hours. While the instrument is running, weights are measured at fixed time intervals and the percent mass loss is calculated and reported for each step. The first step (the step at 110°C) obtains the moisture content of the sample without burning the sizing on the fiber. At a higher temperature (565°C), the matrix content is obtained by burning off the matrix polymer in the glass fiber.

Gas chromatography (GC)

The polymer in the composite sample (equivalent to 300 mg of polymer according to TGA data) was dissolved in 25 ml of chloroform and then filtered with a 0.2 μm filter. An Agilent 7820A GC system equipped with an FID detector, an autosampler (7650A) and an Agilent DB-225 capillary column was used. The temperature of the injector, detector and column oven was set to 200°C. High-purity nitrogen (purity of 99.999%) was used as the carrier gas. The injection volume of the autosampler was 1.0 μL. The injected sample solution was separated using a capillary column and detected using a flame ionization detector (FID). The concentration was measured by peak area.

Relative Gel Permeation Chromatography (GPC):

The relative number average molecular weight and weight average molecular weight ( _Mn and _Mw , respectively) of the compatibilizers relative to polystyrene standards were measured using a gel permeation chromatograph (Agilent 1200 series). The GPC consisted of a guard column and 2 PL gel mixed D columns and an evaporative light scattering detector (ELSD). HPLC grade chloroform stabilized with ethanol (Biosolve) was used as the mobile phase at a flow rate of 1 mL/min and the measurements were performed at 35°C. 15 mg of the compatibilizer sample was dissolved in 15 mL of chloroform and filtered with a 0.45 μm filter before GPC analysis. The GPC system was calibrated using narrow polystyrene standards.

Comparative Example A - Preparation of Composite Tapes Using a Polymer Melt

A multifilament glass fiber bundle (model NX-8) comprising 67.8 wt% SiO ₂ , 1.5 wt% P ₂ O ₅ , 2.3 wt% B ₂ O ₃ , 9 wt% CaO, 5.4 wt% MgO and 14 wt% Na ₂ O. The multifilament glass fiber bundle is prepared by melt spinning using a 204-pointed platinum sleeve apparatus, followed by in-line dip coating of a dispersion consisting of epoxy silane and a degradable acid-functionalized thermoplastic sizing agent, which is dried and cured onto the glass fibers at 35-140° C. Each fiber bundle has 204 fibers (also referred to as monofilaments), and the average diameter of the fibers is about 11 μm as confirmed by SEM.

The polymer melt was prepared using Purasorb PLDL 7028 polylactic acid (from Purac America Inc., Lenexa, KS) and dried under vacuum at room temperature before use. The intrinsic viscosity of the polylactic acid copolymer chips was measured to be 2.8 dL/g.

Multiple spools of these multifilament bioabsorbable NX-8 glass fiber were aligned and wound individually at 1-3 m/min through a pultrusion process from a horizontal axis of a creel toward a double-belt puller (equipped with PUR belts), providing the necessary force to pull the fiber through the polymer melt and unwind the spools in the creel.

The polymer melt was supplied by a twin-screw extruder at a feed rate of 500-2000 g/h, and the PLDL 7028 melt was fed into an electrically heated right-angle die at a maximum temperature of 235°C.

After the creel and before the right-angle die, the glass fiber bundles pass through horizontal pins (set temperature 275°C) under gentle tension to equalize the tension and spread the warp yarns, and then enter the feed side of the right-angle die.

In the right-angle die head, the hot polymer melt contacts the glass fiber warp while it passes above and below the fixed horizontal pins for further diffusion and wetting. The prepreg is then passed through a seam die with a desired shape (circular when preparing bundle/particle products and rectangular when preparing tape products) and geometry. When the final product is tape-shaped, the impregnated tape from the forming die is calendered under gentle pressure. The composite tape or strand is then cooled in air and then picked up by a tractor. After the tractor, the compacted composite tape or strand is collected on a bobbin. The round strand is formed into particles using a strand granulator after passing through the forming die and the tractor. Various experiments have been carried out using this method to study its possibility. The results thus obtained are listed in Table 2.

Example 1: Preparation of composite tape with poly(L-lactide) matrix

Purasorb PLDL 7020 (polylactic acid copolymer including 70 mol% L-lactide and 30 mol% D-lactide, intrinsic viscosity 2.0 dL/g, from Purac America Inc., Lenexa, KS) was dissolved in three mixing vessels at concentrations of 7, 12, and 20% w/w. Resorbable glass fibers were pulled from a creel. The resorbable glass fibers were coated with a covalently bonded sizing agent obtained by reacting an epoxy silane with an acid functionalized lactide-ε-caprolactone copolymer (Mn 5.6 kg/mol, Mw 8 kg/mol as measured by relative GPC). The target composition of the resorbable glass fibers was 67.8 wt% _SiO2 , 1.5 wt% _P2O5 , _2.3 wt% _{B2O3 ,} 9 wt% CaO, 5.4 wt% MgO, and 14 wt% _Na2O . According to ASTM D1577-01 A, the total target linear density of the combined fiber bundle is 2500 tex and the average fiber diameter is 14.7 μm.

From the creel, the glass fibers are guided by a horizontal reed through various parts of a composite production line with a row of alignment modules. The line consists of several baths filled with acetone or acetone solutions of polymers. In the first bath, the excess unreacted size is washed off and the glass fibers coated with size are spread with the help of concave and convex needles. A well-spread wide fiber warp is achieved. This fiber warp is then introduced into a bath of low-concentration (7% by weight) polymer solution so that all fibers are coated with a thin layer of polymer solution. This coated warp is air-dried and then introduced into a second medium-concentration (12%) polymer solution. The warp absorbs more polymer from the second bath and is then air-dried. At this point, the so-called prepreg is collected on bobbins and vacuum-dried overnight. The next day, the prepreg is loaded onto a creel and pulled through a bath of high-concentration (20%) polymer solution. The outlet of this bath is equipped with a rectangular die, which helps to shape the prepreg into the required flat shape. Subsequently, the desired shaped product having the desired polymer/glass fiber ratio is then passed through a finishing section consisting of three solvent exchange baths. The first anti-solvent bath contains a mixture of 70% acetone and 30% water at a temperature of -10°C, the second anti-solvent bath contains 50% acetone/50% water at a temperature of -10°C, and the third anti-solvent bath contains 100% water at a temperature of 50°C. The product stays in each bath for at least 90 seconds. After the third bath, the wet product is collected on a bobbin lined with a polypropylene mesh. The bobbin is then vacuum dried for 3 days to remove residual acetone and water. After drying for 3 days, the product is hot calendered and cut to obtain a tape product of the desired specifications (width and thickness). A radiopaque and transparent composite material is prepared. Various experiments were carried out using this method to study its feasibility. The results obtained are listed in Table 2.

As can be seen from Table 2, the method of the present invention can achieve a higher fiber content compared to the prior art method. In addition, the results show that the IV drop of the composite material of Example 1 during the production process is much lower than that of the comparative example. In addition, the monomer generation of the composite material of Example 1 is lower. It can therefore be seen that when the method of the present invention is used, the degradation of the matrix polymer during the composite material manufacturing process is less than that of the known method. In addition, it has been found that the diffusion of the matrix polymer around the glass fiber is improved, which means that the contact area between the glass fiber and the matrix is larger, and there are fewer voids, bubbles and white streaks. A larger contact area means that the load transfer in the composite material is improved, which is very useful for making a stronger composite material. The reduction of bubbles, voids and white streaks increases the transparency of the composite material because bubbles scatter light and cause a milky appearance.

Example 2: Preparation of composite tape with poly(L-lactide) matrix

Purasorb PL 24 (poly(L-lactide) homopolymer, intrinsic viscosity 2.4 dL/g) was dissolved in chloroform at a concentration of 10% (W/W) in a mixing vessel until completely dissolved. A bundle of glass fibers that absorb the coating size was pulled from a feed creel, the target composition of the glass fibers being 67.8 wt% SiO ₂ , 1.5 wt% P ₂ O ₅ , 2.3 wt% B ₂ O ₃ , 9 wt% CaO, 5.4 wt% MgO and 14 wt% Na ₂ O. The fibers were coated with a size made of epoxysilane and an acid functionalized lactide-ε-caprolactone copolymer (Mn 5.6 kg/mol, Mw 8 kg/mol as measured by relative GPC), which was covalently bonded to the glass fiber surface. The linear density of the fiber bundle is 140 tex (or g/km), corresponding to an average fiber diameter of 11 μm. The fibers are passed through a custom-made reel to various parts of a reel coater, which consists of various modules such as polymer and anti-solvent (ethanol) baths. The polymer bath is filled with a chloroform solution of the polymer (10 wt%). In the polymer bath, the glass fiber is spread with the help of an electrostatic needle and the matrix polymer is impregnated with the help of an immersion roller. Then, the narrow and flat prepreg strands are transferred to the anti-solvent bath by a guide roller, which is also immersed in the anti-solvent (ethanol). During the entire experiment, the line speed is kept constant at 1 m/min. After passing through the anti-solvent (ethanol) bath, the prepreg is non-sticky and almost dry before reaching the winder. The prepreg is then collected on a bobbin. The collected bobbin is loaded onto a pay-off frame and the prepreg is passed through the second production line. The prepreg is rolled with more polymer and then transferred to the anti-solvent (ethanol) bath like the first one. The flattened strands were then collected onto spools. The spools were finally dried in a vacuum oven to remove any residual solvent (CHCl ₃ ) and ethanol.

The resulting composite tape was subsequently analyzed and its properties are listed in Table 3. Comparison of the monomer content and the Mn of the composite tape before and after production shows that the degradation of the matrix polymer during the production process is very low. In addition, the resulting composite tape is very white, indicating a low YI.

Example 3: Preparation of composite tape with poly (L-D) lactide) matrix

Purasorb PLDL 7020 (polylactide copolymer, including 70 mol% L-lactide and 30 mol% D-lactide, intrinsic viscosity 2.0 dL/g) was dissolved in acetone at a concentration of 10 wt% in a mixing vessel. Powdered tricalcium phosphate (ground a-TCP from Cam Bioceramics (lot #13CAM02.97)) was gradually added to the polymer solution at a concentration of 10 wt%. A bundle of size-coated absorbent glass fibers was pulled from a creel, with a target composition of 67.8 wt% _SiO2 , 1.5 wt% _{P2O5 ,} 2.3 wt% _B2O3 , 9 wt% CaO, 5.4 wt% MgO, and 14 wt% _{Na2O .} The fibers were coated with a size made from epoxysilane and an acid-functionalized lactide-ε-caprolactone copolymer (Mn 5.6 kg/mol, Mw 8 kg/mol as measured by relative GPC) covalently bonded to the glass fiber surface. The average linear density of the fiber bundle was 140 tex (or g/km), corresponding to an average fiber diameter of 11 μm. The fibers were passed through a custom-made reel to various sections of a reel-to-reel coater, which consisted of various modules such as polymer and anti-solvent baths. The polymer bath contained a polymer/TCP mixed solution dissolved in acetone. In the polymer bath, individual glass fibers were spread with the help of electrostatic needles and impregnated with the matrix polymer/TCP with the help of an immersed roller. The narrow and flat prepreg strands were then transferred to the anti-solvent bath via a guide roller, which was also immersed in ethanol. For proof of concept, the anti-solvent bath contained 100% ethanol at room temperature. After passing through the anti-solvent bath, the prepreg is non-sticky and almost dry before reaching the winder. The prepreg is then collected onto spools. The collected spools are loaded onto a pay-off stand and the prepreg is passed through the second line. The prepreg rolls are coated with more polymer/TCP and transferred to the anti-solvent (alcohol) bath like the first line. The flat strands are again collected onto spools. The spools are finally dried in a vacuum oven to remove any residual dichloromethane and ethanol. The line speed was kept constant at 1m/min throughout the experiment.

The resulting composite tape was subsequently analyzed and its properties are listed in Table 3. Comparison of the monomer content and the Mn of the composite tape before and after production shows that the degradation of the matrix polymer during the production process is very low. In addition, the resulting composite tape is very white, indicating a low YI.

Table 2: Properties of the composite materials obtained in Comparative Example A and Example 1.

Table 3: Properties of the composite materials prepared in Examples 2 and 3

Embodiment 4: Provide a glass fiber coated with a sizing agent including polycaprolactone as a compatibilizer, and The fibers are incorporated into a polycaprolactone matrix to form a polycaprolactone glass fiber reinforced composite material, which is further processed to Forming composite panels

1. Preparation of Silane-treated Glass Fiber

The preparation method of the hydrolyzed silane solution is to dissolve 117g of 3-glycidyloxypropyltriethoxysilane in 10kg of ASTM II type pure water at a temperature of 50°C for 90 minutes. The hydrolyzed silane solution is then applied to the newly drawn glass fiber formed in the melt spinning process online by a contact roller. The composition of the glass corresponds to the composition applied in Example 5. The resulting fiber bundle is wound on a core for further processing. The wet glass fiber is air-dried and then vacuum-dried at room temperature to a humidity level of less than 1000ppm. The dried glass fiber is heat-treated at 90°C for 4 hours to covalently bond the silane to the hydroxyl groups on the surface of the glass fiber.

2. Preparation of water-based PC (IV 0.15) nanodispersion

40g of acid functionalized polycaprolactone (IV of 0.15dL/g (measured according to ASTM 2857), acid value of 39.4mgKOH/g) was dissolved in 1600g of acetone for 1 hour. After complete dissolution, triethylamine (TEA, from Sigma Aldrich) (molar ratio with acid is 1:1) was added to neutralize the acid end groups. After stirring for 15 minutes, the polymer solution was gradually added to ASTMII type purified water. After evaporation for 24 hours to remove acetone, an aqueous nano dispersion with a solid content of about 3% by weight was obtained. The average particle size (z-average) was measured by DLS (MalvernZetaSizer-nano) to be 37 nanometers and D90 to be 39 nanometers.

3. Preparation of PC (IV 0.15) coated glass fiber

The silane treated glass fibers (average diameter of 16 μm) prepared in step 1 above were further treated with the compatibilizer polymer (PC, IV 0.15 dL/g) prepared in step 2 above by continuously passing the fiber bundle through a polymer nanodispersion bath in an offline reel-to-reel sizing system at a line speed of 5 m/min. The sizing coated fibers were collected on a separate porous stainless steel (SS) core. The fibers were then vacuum dried at room temperature and cured at 90°C for 16 hours to promote the reaction between the acid end groups of the compatibilizer and the epoxy groups of the silane that had been covalently bonded to the glass surface. The TEA at the reaction site acted as a catalyst and was eventually removed by applying a vacuum.

After curing, the PC coated glass fiber samples were tested for the presence of a PC (IV 0.15) compatibilizer layer by TGA burn-off method. The results confirmed the presence of 1±0.5 wt% of the sizing agent on the glass fiber.

4. Preparation of composite materials composed of polycaprolactone polymer and fibers coated with polycaprolactone extender

At 50°C, a 10 wt% high molecular weight polycaprolactone (Purasorb PC17, IV 1.7 dL/g, commercially available from Corbion Purac) acetone solution was prepared. A bundle (576 filaments) of PC coated fibers prepared in step 3 was passed through a polymer solution bath in a continuous reel to reel sizing system to coat the polymer. The polymer solution bath was equipped with rollers and pins to spread the fibers so as to better wet the fibers. At room temperature, the fibers coated with the sizing were passed through an anti-solvent (ethanol) bath at a line speed of 2 m/min, and then air dried for 24 hours to remove the solvent. After drying, the fibers coated with the polymer were in the form of thin, narrow ribbons. The fiber/polymer content in the fibers coated with the sizing and dried was analyzed by LECO, TGA701 burn-out method. The polymer content was 14.2 wt%.

5. Preparation of composite panels by compression molding of a composite material consisting of polycaprolactone and glass fibers coated with a rubber compound

The composite tape obtained in step 4 is cut into strips of 100 mm in length, which are stacked in a predetermined amount in a uniform direction and evenly spread in the cavity of a preheated mold to prepare the samples required for mechanical testing. An additional polymer (Purasorb PC17, Tm 60°C) film is set as the top layer on the fiber stack coated with rubber so that the final molded part has 50% by weight of fibers. The cavity of the mold is 100mm x 100mm x 1mm. The fiber bundles coated with rubber and the polymer film layer are then heated to above the softening temperature of the polymer, pressed, then cooled, and demolded. A composite plate for analysis is obtained.

6. Mechanical testing of composite materials

The composite plate in step 5 above was cut into rectangular specimens (50x13x1mm; length x width x thickness), and its bending properties were tested according to ASTMD7264/D7264M-15 using a Lloyd general mechanical testing machine equipped with a 3-point bending fixture and a 2.5kN load cell (3-point bending test). The span-to-thickness ratio is 16:1. Standard product width: 13mm, the sample length is about 20% longer than the support span (10% on each side). Six test samples were measured, and the average strength was 147±7.6MPa (600% higher than the base polymer strength of 23MPa), and the modulus was 6.46±0.68GPa (58 times higher than the base polymer's 110MPa). The fiber content of the test samples was analyzed by the TGA burn-out method, and the results showed that the average fiber content was 50.4% by weight of the composite material.

Example 5: Providing glass fibers coated with a compatibilizer poly(DL-lactide) (PDL), and incorporating the coated fibers into a poly(DL-lactide) matrix to form a poly(DL-lactide) glass fiber reinforced composite material. Further processing the composite material to form a composite board

Epoxy-functionalized, silane-treated glass fibers were prepared as described in Example 4 above.

30 g of acid functionalized poly(DL-lactide) (50/50) polymer (IV of 0.4 dL/g, acid number of 4.1 mg KOH/g) was dissolved in 1500 g of acetone for 1 hour. After complete dissolution, TEA (molar ratio to acid of 1:1.3) was added to neutralize the acid end groups. After stirring the solution for 15 minutes, the polymer solution was gradually added to purified ASTM II type purified water. After evaporation for 24 hours to remove the acetone, an aqueous dispersion of about 3 wt% was obtained. The average particle size (z-average) was measured by DLS (Malvern ZetaSizer-nano) to be 30 nanometers and D90 was 24 nanometers.

The silane treated glass fibers were further treated with a compatibilizer polymer by continuously passing the fiber bundle through a bath of the above polymer nanodispersion in an offline reel-to-reel sizing system. The line speed was 5 m/min. The fibers after sizing were collected on a separate porous SS core. The fibers were dried under vacuum at room temperature and cured at 90°C for 16 hours to promote the reaction between the -COOH end groups of the compatibilizer polymer and the silane epoxy ends that had been covalently bonded to the glass surface. The TEA at the reaction site acted as a catalyst and was eventually removed by applying a vacuum.

After curing, the glass samples were tested for the presence of a glue layer by TGA burn-out method. The results confirmed the presence of 1±0.5 wt% of glue on the glass fibers.

A 10 wt% high molecular weight poly (DL-lactide) (IV 2.0 dL/g) acetone solution was prepared. A bundle (576 monofilaments) of the above-mentioned coated fibers (average diameter of 16 μm) was passed through a polymer solution bath in a continuous reel to reel sizing system to coat the high molecular weight poly (DL-lactide). The polymer solution bath was equipped with rollers and pins to spread the fibers so as to better wet the fibers. At room temperature, the coated fibers were passed through an anti-solvent (ethanol) bath at a line speed of 1 m/min to remove the solvent. The coated fibers were air-dried for 24 hours. After drying, the coated fibers appeared as thin and narrow ribbons. The fiber/polymer content in the coated and dried fibers was analyzed by the LECO TGA701 burn-out method. The polymer content was 15.4 wt%.

The obtained composite tape is cut into strips of 100 mm in length, which are stacked in a uniform direction according to a predetermined amount and evenly spread in the cavity of the preheated mold to make the samples required for mechanical testing. An additional polymer (Purasorb PLDL7020) film is added as a top layer to the fiber stack coated with the sizing material so that the final molded part has 50% by weight of fiber. The cavity of the mold is 100 mm x 100 mm x 1 mm. The fiber bundles and polymer film layers coated with the sizing material are then heated to above the softening temperature of the polymer, pressed, then cooled, and demoulded. A composite board for analysis is obtained.

The composite panels were then cut into rectangular specimens (50x13x1mm; length x width x thickness) and tested for bending properties (3-point bending test) using a Lloyd general mechanical testing machine equipped with a 3-point bending fixture and a 2.5kN load cell according to ASTM D7264/D7264M-15. The span-to-thickness ratio was 16:1. Standard width: 13mm, the sample length is about 20% longer than the support span (10% on each side). Six test samples were measured, and the average strength was 491.3±38.6MPa (446% higher than the base polymer strength of 110MPa) and the modulus was 12.72±1.5GPa (374% higher than the base polymer's 3.4GPa). The fiber content of the test samples was analyzed by TGA burn-out method, and the results showed that the average fiber content was 52% by weight of the composite material.

Example 6: Providing glass coated with a compound including poly(DL-lactide/glycolide) (PDLG) as a compatibilizer The fiber coated with the size is incorporated into a poly(DL-lactide/glycolide) matrix to form a poly(DL-lactide/glycolide) matrix. ester)

Glass fiber reinforced composite materials, which are further processed to form composite panels

Epoxy-functionalized, silane-treated glass fibers were prepared as described in Example 4 above.

30 g of acid functionalized poly(DL-lactide/glycolide) (50/50) (from Corbion, IV 0.4, acid number 4.1 mgKOH/g) was dissolved in 1500 g of acetone for 1 hour. After complete dissolution, triethylamine (molar ratio with acid 1:1.3) was added to neutralize the acid end groups. After stirring the solution for 15 minutes, the polymer solution was gradually added to purified ASTM II type purified water. After evaporation for 24 hours to remove the acetone, an aqueous dispersion of about 3 wt % was obtained. The average particle size (z-average) was 46 nm and the D90 was 46 nm as measured by DLS (Malvern ZetaSizer-nano).

The silane treated glass fibers were further treated with the above dispersion by passing the fiber bundle continuously through the above polymer nanodispersion bath in an offline reel-to-reel sizing system at a line speed of 5 m/min. The fibers after coating with size were collected on independent porous SS cores. The fibers were dried under vacuum at room temperature and then cured at 90°C for 16 hours to promote the reaction between the -COOH end groups of the compatibilizer polymer and the silane epoxy end groups that have been covalently bonded to the glass surface. The TEA at the reaction site acts as a catalyst and is eventually removed by applying vacuum.

After curing, the glass samples were tested for the presence of a glue layer by TGA burn-out method. The results confirmed the presence of 1±0.5 wt% of glue on the glass fibers.

A 10 wt% high molecular weight poly(DL-lactide/glycolide) (85/15) (IV of 2.3 dL/g) acetone solution was prepared at 50°C. A bundle (576 monofilaments) of the above-mentioned PDLG-coated fibers (average diameter of 16 μm) was passed through a polymer solution bath in a continuous reel-to-reel coater system to coat PDLG85/15. The polymer solution bath was equipped with rollers and pins to spread the fibers so as to better wet the fibers. At room temperature, the coated fibers were passed through an anti-solvent (alcohol) bath at a line speed of 2 m/min to remove the solvent. The coated fibers were air-dried for 24 hours. After drying, the coated fibers were in the form of thin, narrow ribbons. The fiber/polymer content in the coated and dried fibers was analyzed by the LECO TGA701 burn-out method. The polymer content was 32.6 wt%.

The obtained composite tape was cut into strips of 100 mm in length, which were uniformly stacked in a predetermined amount in a uniform direction and spread in the cavity of a preheated mold to prepare the samples required for mechanical testing. An additional polymer (Purasorb PLDG85/15) film was set as the top layer on the fiber stack coated with rubber, so that the final molded part had 50% by weight of fibers. The cavity of the mold was 100mm x 100mm x 1mm. These fiber bundles coated with rubber and the polymer film layer were then heated to above the softening temperature of the polymer, pressed, then cooled and demolded. The composite board for analysis was obtained.

The composite panels were cut into rectangular specimens (target dimensions 50 x 13 x 1 mm; length x width x thickness) and tested for flexural properties (3-point bend test) using a Lloyd general mechanical testing machine equipped with a 3-point bend fixture and a 2.5 kN load cell according to ASTM D7264/D7264M-15. The span to thickness ratio was 16:1. Standard width: 13 mm, the sample length was about 20% longer than the support span (10% on each side). Six test samples were measured and the average strength was 770.7 ± 131 MPa (an increase of 770% over the base polymer strength of 100 MPa) and the modulus was 23.9 ± 5.4 GPa (an increase of 570% over the base polymer's 4.2 GPa). The fiber content of the test samples was analyzed by TGA burn-out method, and the results showed that the average fiber content was 55.7% by weight of the composite material.

Claims (15)

1. A composite material comprising a plurality of glass fibers in a polymer matrix, the polymer matrix being compatible with the plurality of glass fibers, wherein the glass fibers and the polymer matrix are biocompatible, absorbable and preferably bioactive, wherein the monomer content of the composite material is less than 1 wt. %, preferably less than 0.5 wt. %, more preferably less than 0.2 wt. %, even more preferably less than 0.1 wt. %, based on the polymer matrix. 2. The composite material according to claim 1, wherein the composite material has a yellowness index (YI) of less than 30, preferably less than 20, more preferably less than 15, most preferably less than 10, measured according to ASTM E313, and/or wherein the composite material is translucent, preferably transparent, preferably radiopaque. 3. A composite material according to any one of the preceding claims, in the form of a unidirectional composite tape, or in the form of strands, rods, pellets or granules, in particular in the form of a unidirectional tape. 4. The composite material according to any one of the preceding claims, wherein the intrinsic viscosity of the matrix polymer in the composite material is between 1.5 and 4.0 dL/g, preferably between 1.8 and 3.0 dL/g, more preferably between 2.0 and 3.0 dL/g. 5. A medical device, such as an implant or a stent, comprising a composite material according to any one of the preceding claims. 6. A method for producing a solid polymer composite material comprising a plurality of biocompatible absorbable glass fibers embedded in a biocompatible absorbable matrix polymer, in particular a composite material according to any one of claims 1 to 5, the method comprising the following steps: a) providing the plurality of biocompatible absorbable glass fibers that are compatible with the matrix polymer, b) providing a mixture comprising the matrix polymer and a solvent, c) applying the mixture onto the plurality of glass fibers, and d) removing the solvent from the mixture coated on the plurality of glass fibers using an anti-solvent to obtain the solid polymer composite. 7. The method according to claim 6, wherein the solid polymer composite is shaped, preferably into a tape, a strand, a (hollow) rod, a tube, a pellet, a granule or a monofilament. 8. The method according to any one of claims 6 or 7, wherein the solvent is partially evaporated after applying the solvent to the glass fiber. 9. The method according to any one of claims 6 to 8, wherein the matrix polymer is a thermoplastic polyester, and in particular, preferably a polymer selected from the following group: polylactide (PLA), poly-L-lactide (PLLA), poly-DL-lactide (PDLLA), polyglycolide (PGA), poly(ε-caprolactone) (PCL), glycolide copolymer, glycolide/trimethylene carbonate copolymer (PGA/TMC), lactide/tetramethyl glycolide copolymer, lactide/trimethylene carbonate copolymer, lactide/d-valerolactone copolymer, lactide/ε-caprolactone copolymer The invention relates to a polymer comprising: a polylactide, a poly(lactide-co-glycolide), a poly(lactide-co-ε-caprolactone), a poly(glycolide-co-ε-caprolactone), a poly(lactide-co-glycolide), a poly(lactide-co-ε-caprolactone), a poly(glycolide-co-ε-caprolactone), a poly(lactide-co-glycolide), a poly(lactide-co-ε-caprolactone), a poly(glycolide-co-ε-caprolactone), a poly(PGA), and a poly(ε-caprolactone) (PCL), and a combination thereof. 10. The method according to any one of claims 6 to 9, wherein the method comprises: - providing a second mixture comprising a second matrix polymer and a second solvent, - applying the second mixture to the plurality of glass fibers coated with the matrix polymer, and - Optionally, partially removing the second solvent from the second mixture coated on the plurality of glass fibers coated with the matrix polymer using a second anti-solvent to obtain the solid polymer composite. 11. A method according to any one of claims 6 to 10, wherein the polymer concentration in the second mixture is higher than the polymer concentration in the previously applied mixture. 12. A process according to any one of claims 6 to 11, wherein the process comprises removing residual solvent and/or anti-solvent by evaporation. 13. The method according to any one of claims 6 to 12, wherein the ratio of the intrinsic viscosity of the matrix polymer in the solid composite material to the intrinsic viscosity of the original matrix polymer is between 0.70 and 1.30, preferably between 0.90 and 1.10, more preferably between 0.95 and 1.05. 14. A method according to any one of claims 6 to 13, wherein the difference in yellowness index between the original matrix polymer and the resulting composite material is less than 20, more preferably less than 10, measured according to ASTM E313. 15. The method according to any one of claims 6 to 14, further comprising the step of embedding additives, preferably active pharmaceutical ingredients (API) or mineral phases, into the composite material.