Absorbable segmented copolymer and preparation method therefor and use thereof, and absorbable binding strap

Abstract

The present invention relates to the technical field of medical instruments. Particularly disclosed are an absorbable segmented copolymer and a preparation method therefor and the use thereof, and an absorbable binding strap. The absorbable segmented copolymer comprises a chain segment A, which is a first segment and is a crystalline prepolymer formed by the polymerization of L-lactide, the weight percentage content thereof in the segmented copolymer being 50-75%; and a chain segment B, which is a second segment, the weight percentage content thereof in the segmented copolymer being 25-50%, wherein the monomer of the chain segment B comprises ε-caprolactone or a mixture of ε-caprolactone and other monomers, the other monomers comprising glycolide, trimethylene carbonate, p-dioxanone, DL lactide or L-lactide. In the present invention, the absorbable segmented copolymer is obtained by first polymerizing L-lactide that serves as a hard segment and then polymerizing a soft segment (containing ε-caprolactone); and the absorbable segmented copolymer can provide high strength, high toughness and appropriate degradation time which are required by an absorbable binding strap, and is more suitable for use in the preparation of an absorbable binding strap for orthopedic internal fixation.

Description

Absorbable segmented copolymer, preparation method, application and absorbable binding band Technical Field

[0001] The present invention relates to the technical field of medical instruments, and in particular to an absorbable segmented copolymer, a preparation method, an application and an absorbable binding belt. Background Art

[0002] Currently, most fractures are fixed with metal nail plates and metal intramedullary fixation systems. However, for general long oblique fractures, split fractures, avulsion fractures, comminuted fracture fragments, and smaller fracture fragments, simpler binding fixation is often used. Binding materials commonly used are steel wire and silk thread. However, due to the high rigidity and high elastic modulus of steel wire, the contact area with the bone during fixation is small, which can easily cut the fixed bone fragment, thereby disrupting the blood supply to the bone cortex. The steel wire can also easily slip into the fracture gap, causing nonunion, which can ultimately lead to nonunion or delayed healing. In addition, the steel wire requires a second surgical procedure to remove, and removal is difficult due to the indentation.

[0003] Non-absorbable suture materials, such as silk, possess a certain tensile strength and good plasticity. For comminuted fractures, they can effectively connect the bones together, forming a single unit. Flexible fixation with silk allows for adjustments to the steps that rigid fixation tends to create, allowing the binding to better fit the bone fragment, ensuring optimal fracture surface alignment without cutting the bone fragment. The disadvantages of silk are that it is not sufficiently strong, has a narrow fixation area per thread, and is not absorbed by the body.

[0004] Chinese patent CN201101572Y discloses an absorbable binding tape. It consists of a head, body, and tail made of a material that can be absorbed by the human body. Both the body and head have different tooth structures, and the binding is achieved by the locking force generated when the body passes through the hollow head. The absorbable materials used are poly-DL-lactic acid, poly-L-lactic acid, polyglycolic acid, polyoxydicyclohexanone, and poly-ε-caprolactone. However, none of these polymers, when used alone, meet the performance requirements.

[0005] Although poly-DL-lactic acid (PDLLA), poly-L-lactic acid (PLLA), and polyglycolic acid (PGA) materials have high mechanical strength, usually with a tensile strength of more than 50 MPa, their elastic modulus is also high, usually 2.5-4.5 GPa. Therefore, the material is too hard and lacks flexibility, resulting in poor adhesion between the belt body and the bone block, easy brittle fracture, and difficulty in inserting the belt head to achieve tooth engagement. Forced insertion will damage the tooth shape of the belt head.

[0006] The elastic modulus of polycyclohexanone (PPDO) is about 1.0 GPa, which makes it flexible and has good tensile strength (about 30 MPa). It has good fit with the bone and good fixation strength, but it degrades too quickly and its strength can only be maintained for about 4 weeks. Poly-ε-caprolactone (PCL) has good flexibility, but its elastic modulus is too low (about 0.3 GPa). The binding belt of the present invention made of PCL has a soft belt body and insufficient locking force. In addition, the degradation and absorption of this material is too slow, usually taking 3-4 years.

[0007] Among the copolymers of absorbable materials, these materials, used as commercial surgical sutures, all have good strength and flexibility, similar to PPDO. For example, glycolide-trimethylene carbonate block copolymer, the material used in MAXON single-strand absorbable sutures, degrades too quickly in the body, and its strength can only be maintained for about 4 weeks; glycolide-ε-caprolactone block copolymer, the material used in MONOCRYL single-strand absorbable sutures, maintains its strength for only about 2 weeks and cannot be used as an orthopedic internal fixation material.

[0008] Chinese patent CN 108997564 A discloses a semicrystalline, bioabsorbable, segmented PLC copolymer intended for use as an absorbable suture. The copolymer is obtained via a two-step polymerization process, comprising the following reactive segments: (a) an amorphous prepolymer formed by random copolymerization of ε-caprolactone and lactide, and (b) a lactide monomer. Because segment (a) is an amorphous prepolymer, the two-stage copolymer exhibits relatively low mechanical properties and rapid degradation, making it suitable for use as an absorbable suture but unsuitable for use as an absorbable binding tape.

[0009] Summary of the Invention

[0010] The object of the present invention is to provide an absorbable segmented copolymer having high strength, high toughness and suitable degradation time, which can meet the requirements of absorbable binding bands.

[0011] In addition, the present invention also provides the absorbable segmented copolymer and its preparation method and application.

[0012] In addition, the present invention also provides an absorbable binding band prepared from the absorbable segmented copolymer.

[0013] The present invention is achieved through the following technical solutions:

[0014] An absorbable segmented copolymer comprising:

[0015] Segment A is the first segment and is a hard segment. It is a crystalline prepolymer (PLLA) formed by polymerization of L-lactide. Its weight percentage in the segmented copolymer is 50% to 75%;

[0016] The B segment is the second segment and is a soft segment, and its weight percentage in the segmented copolymer is 25% to 50%; the monomer of the B segment includes ε-caprolactone or a mixture of ε-caprolactone and other monomers, and the other monomers include glycolide, trimethylene carbonate, p-dioxanone, DL-lactide or L-lactide.

[0017] The segmented copolymer of the present invention refers to a copolymer in which monomers are added in stages, wherein the polymer formed by copolymerization of the first added monomers is the first segment, and the polymer formed by polymerization of the later added monomers is the second segment.

[0018] That is, in the present invention, the A segment is first polymerized to form the A segment, and then the monomer of the B segment is added to the A segment to polymerize to form the B segment.

[0019] The applicant has found that the performance of the segmented copolymer is related to the ratio of segment A to segment B, and also to the composition of the two segments A and B.

[0020] The A segment of the present invention is a hard segment, the first polymer segment, which plays a role in improving the mechanical strength of the segmented copolymer. If its content is less than 50%, the mechanical strength will be low, and if its content is higher than 75%, it is difficult to obtain a uniform segmented copolymer.

[0021] The B segment is the soft segment, the second polymer segment, and a polymer segment formed with ε-caprolactone (CL) as a monomer. This segment is also crystalline. If its content is less than 25%, it is not easy to penetrate into the PLLA matrix to form a uniform segmented copolymer. If its content is higher than 50%, the mechanical strength will be low.

[0022] In the prior art, block copolymers or segmented copolymers with soft and hard segment structures typically polymerize the soft segments first (e.g., CL or CL-based segments) and the hard segments (LA segments) later. This is because the relatively high content of the hard segments better dissolves the relatively small soft segments. Examples include the glycolide and trimethylene carbonate copolymers reported by Elena Díaz-Celorio et al.; the glycolide and CL copolymers reported by Rao S. Bezwada et al.; and the LA and CL copolymers reported by Jin Kon Kim et al. and disclosed in Chinese Patent CN 108997564 A.

[0023] However, the applicant of this application found that when the A segment is a LA polymerization unit, that is, LA is first polymerized into the A segment (PLLA), and the B segment of ε-caprolactone is polymerized later, the segmented copolymer formed at this time has a higher degree of crystallinity and a higher mechanical strength. This is because in the segmented copolymer, the contribution to strength is mainly from the A segment (PLLA), even if ε-caprolactone is the B segment formed by mixing it with other monomers. High crystallinity is beneficial to the mechanical properties of the material, and the prepared segmented copolymer can achieve high strength, high toughness and suitable degradation time, which can meet the needs of absorbent binding bands.

[0024] After testing, the tensile strength of the absorbable segmented copolymer is not less than 30MPa, and the Young's modulus is not greater than 2GPa; its mechanical properties are maintained for not less than 12 weeks in a phosphate buffer solution at 37°C, which can meet the needs of absorbable binding bands.

[0025] Furthermore, the intrinsic viscosity of segment A in chloroform at a concentration of 0.1 g / dl at 25°C is 1.3 to 3.0 dl / g. If the intrinsic viscosity of segment A is lower than 1.3 dl / g, it is difficult to obtain a segmented copolymer with a higher molecular weight. If the intrinsic viscosity of segment A is higher than 3.0 dl / g, the melt is too viscous, making it difficult to mix evenly with the monomer of segment B.

[0026] Furthermore, the absorbable segmented copolymer has an intrinsic viscosity of 1.0-3.0 dl / g at 25°C in chloroform at a concentration of 0.1 g / dl. Material characterization shows that this intrinsic viscosity range provides good processing, mechanical, and degradation properties. The intrinsic viscosity of the segmented copolymer is controlled by the intrinsic viscosity of the A segment and the polymerization process.

[0027] Preferably, the absorbable segmented copolymer has an intrinsic viscosity of 1.3 to 2.3 dl / g in chloroform at a concentration of 0.1 g / dl at 25° C. This range is more conducive to processing and molding without affecting the performance of the binding belt.

[0028] A method for preparing an absorbable segmented copolymer comprises the following steps:

[0029] S1. Using a hydroxyl-containing compound as an initiator and in the presence of a catalyst, L-lactide is added to an air-tight reactor, and ring-opening polymerization is carried out above the melting temperature of L-lactide to obtain segment A;

[0030] S2. Melt-blending the monomer of segment B with the segment A prepared in step S1, and polymerizing them in an air-isolated reactor at 130° C. to 190° C. to form an absorbable segmented copolymer containing segment A and segment B.

[0031] Furthermore, in step S1, the preparation of segment A includes the following components in weight percentage:

[0032] The initiator is 0.02% to 0.2%, the catalyst is 0.01% to 0.1%, and the balance is L-lactide.

[0033] Furthermore, in step S1, the melting temperature is 150° C. to 180° C., and the reaction temperature is maintained for 8 to 24 hours to obtain the A segment by ring-opening polymerization.

[0034] Furthermore, in step S1, the initiator includes a monohydric alcohol, a dihydric alcohol or a polyhydric alcohol; the catalyst includes a tin salt, and the tin salt may be stannous octoate.

[0035] That is, the synthesis method of step S1 is:

[0036] With 0.02% to 0.2% by weight of diethylene glycol as an initiator and 0.01% to 0.1% by weight of stannous octoate as a catalyst, L-lactide is added into a reactor under nitrogen protection or vacuum, the temperature is raised to 150° C. to 180° C., the reaction temperature is maintained for 8 to 24 hours, and the A segment is obtained by ring-opening polymerization.

[0037] Furthermore, in step S2, the melt blending process is:

[0038] Raise the temperature to 170-180°C, maintain for at least half an hour, then lower the temperature to 150-170°C and carry out polymerization for 10-25 hours.

[0039] Application of absorbable segmented copolymers in the preparation of medical absorbable devices.

[0040] An absorbable binding belt is made of the absorbable segmented copolymer.

[0041] The absorbable binding band can be injection molded. During injection molding, according to the general consensus in this field, various additives can be conventionally added to achieve different purposes, including but not limited to plasticizers, lubricants, dyes, antioxidants, anti-hydrolysis agents, melt thickeners, chain extenders, reinforcing agents, and polymer modifiers. These additives help to improve the processing performance of the absorbable binding band.

[0042] After the absorbable binding band is injection molded, its intrinsic viscosity at 25° C. in chloroform at a concentration of 0.1 g / dl is not less than 1.0 dl / g.

[0043] Preferably, the absorbable binding band of the present invention has an intrinsic viscosity of 1.2 to 2.0 dl / g at 25° C. in chloroform at a concentration of 0.1 g / dl after injection molding.

[0044] Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0045] The present invention obtains an absorbable segmented copolymer by first polymerizing the L-lactide of the hard segment and then polymerizing the soft segment containing ε-caprolactone. The copolymer can simultaneously provide the high strength, high toughness and suitable degradation time that an absorbable binding band should have, and is more suitable for preparing an absorbable binding band for orthopedic internal fixation. BRIEF DESCRIPTION OF THE DRAWINGS

[0046] The drawings described herein are used to provide a further understanding of the embodiments of the present invention, constitute a part of this application, and do not constitute a limitation of the embodiments of the present invention. In the drawings:

[0047] FIG1 is a structural schematic diagram of an absorbable binding belt according to the present invention;

[0048] FIG2 is a second structural diagram of the absorbable binding belt of the present invention;

[0049] FIG3 is a schematic diagram of the binding of the absorbable binding band of the present invention;

[0050] FIG4 is a diagram showing the tensile strength test of the absorbable binding belt of the present invention;

[0051] FIG5 is a diagram showing the buckle force test of the absorbable binding belt of the present invention;

[0052] FIG6 is a DSC diagram of a PLC segmented copolymer and a PLCW random copolymer;

[0053] FIG7 is an H-NMR spectrum of the PLC segmented copolymer.

[0054] The marks and corresponding parts names in the accompanying drawings are: 1-belt head; 2-belt body; 3-belt tail; 4-hollow lock structure; 5-transverse teeth; 6-pressing head. DETAILED DESCRIPTION

[0055] In order to make the objectives, technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with examples and drawings. The exemplary embodiments of the present invention and their descriptions are only used to explain the present invention and are not intended to limit the present invention.

[0056] In the following description, numerous specific details are set forth to provide a thorough understanding of the present invention. However, it will be apparent to one of ordinary skill in the art that these specific details are not necessarily employed to practice the present invention. In other embodiments, well-known structures, materials, or methods are not specifically described to avoid obscuring the present invention.

[0057] Existing materials cannot meet the demand for absorbable binding bands for orthopedic internal fixation. Therefore, the present invention provides an absorbable segmented copolymer, comprising:

[0058] Segment A is the first segment and is a hard segment. It is a crystalline prepolymer formed by polymerization of L-lactide and its weight percentage in the segmented copolymer is 50%-75%;

[0059] The B segment, which is the second segment, is a soft segment and has a weight percentage of 25%-50% in the segmented copolymer; the B segment contains ε-caprolactone, that is, the monomer of ε-caprolactone is ε-caprolactone or a mixture of ε-caprolactone and other monomers, and the other monomers include glycolide, trimethylene carbonate, p-dioxanone, DL-lactide or L-lactide.

[0060] Preferably, the intrinsic viscosity of the A segment in chloroform at a concentration of 0.1 g / dl at 25°C is 1.3 to 3.0 dl / g; the intrinsic viscosity of the absorbable segmented copolymer in chloroform at a concentration of 0.1 g / dl at 25°C is 1.0-3.0 dl / g. Material characterization shows that this intrinsic viscosity range provides good processing, mechanical, and degradation properties. The intrinsic viscosity range of the segmented copolymer is controlled by the intrinsic viscosity of the A segment and the polymerization process. Preferably, the intrinsic viscosity of the absorbable segmented copolymer in chloroform at a concentration of 0.1 g / dl at 25°C is 1.3-2.3 dl / g.

[0061] The preparation method of the absorbable segmented copolymer comprises the following steps:

[0062] S1. Using a hydroxyl-containing compound as an initiator and in the presence of a catalyst, L-lactide is added to an air-tight reactor, and ring-opening polymerization is carried out above the melting temperature of L-lactide to obtain segment A;

[0063] S2. Melt-blending the monomer of segment B with the segment A prepared in step S1, and polymerizing them in an air-isolated reactor at 130° C.-190° C. to form an absorbable segmented copolymer containing segment A and segment B.

[0064] The compound containing hydroxyl group can be aliphatic monohydric alcohol, dihydric alcohol or polyhydric alcohol. The catalyst includes stannous octoate

[0065] Preferably, the synthesis method comprises the following steps: using 0.02% to 0.2% by weight of diethylene glycol as an initiator and 0.01% to 0.1% by weight of stannous octoate as a catalyst, adding L-lactide to a reactor under nitrogen protection or vacuum, heating the reactor to 150° C. to 180° C., maintaining the reaction temperature for 8 to 24 hours, and performing ring-opening polymerization to obtain the A segment; then, melt-blending the monomer of the B segment containing ε-caprolactone with the A segment, and carrying out polymerization reaction at 150° C. to 180° C. for 10 to 25 hours under nitrogen protection or vacuum to obtain the L-lactide / ε-caprolactone segmented copolymer.

[0066] Preferably, in step S2, the process of melt blending is:

[0067] Raise the temperature to 170-180°C, maintain for at least half an hour, then lower the temperature to 150-170°C and carry out polymerization for 10-25 hours.

[0068] The structure of the absorbable binding band prepared from the above absorbable segmented copolymer is shown in Figures 1 and 2:

[0069] The above-mentioned absorbent segmented copolymer is injection molded into a flat belt structure at a molding temperature of 180°C-220°C. The absorbent binding belt comprises a belt head 1, a belt body 2 and a belt tail 3. The belt head 1 is a hollow locking structure 4. One side of the belt body 2 contains a plurality of transverse teeth 5. The hollow locking structure 4 contains a pressure head 6. The belt tail 3 is a flat surface. As shown in FIG3 , the belt tail 3 of the above-mentioned absorbent binding belt can pass through the hollow belt head 1. The transverse teeth 5 on the belt body are tightly engaged with the pressure head 6 in the belt head 1 to achieve binding.

[0070] In order to better illustrate the technology of the present invention, the following specific examples are used for illustration. For the convenience of explanation, the B segments in the following examples are all illustrated with ε-caprolactone. ε-caprolactone can be replaced by a mixture of ε-caprolactone and other monomers, such as glycolide, trimethylene carbonate, p-dioxanone, DL-lactide or L-lactide.

[0071] Example 1:

[0072] Preparation of segmented copolymer 1 of L-lactide / ε-caprolactone (PLC1):

[0073] Preparation of segment A: 500 g of recrystallized and purified L-lactide monomer (LA) was placed in a 3 L stainless steel reactor, followed by the addition of 0.06 wt % stannous octoate catalyst and 0.06 wt % diethylene glycol. Under nitrogen, the system temperature was raised to 170° C., and polymerization was carried out for 10 hours at a stirring speed of 5-20 rpm to obtain segment A (PLLA). The intrinsic viscosity of the PLLA was 1.89 dl / g at 25° C. in 0.1 g / dl chloroform, the melting peak temperature was 174.5° C., and the tensile strength of the segment A, as determined by mechanical testing, was 65.5 MPa.

[0074] Preparation of an L-lactide / ε-caprolactone segmented copolymer (PLC): 500 g of ε-caprolactone (CL) as a monomer for segment B was added to the aforementioned segment A, with the weight ratio of segment A to segment B being 50:50. Under nitrogen protection, the temperature was raised to 180°C and maintained for 1 hour, then lowered to 165°C and reacted for 16 hours. During this reaction, at the higher temperature, CL permeated into the PLLA and further dissolved the PLLA, and then CL polymerized to form segment B, resulting in an L-lactide / ε-caprolactone segmented copolymer containing segment A (PLLA) and segment B (PCL). The copolymer had an intrinsic viscosity of 1.67 dl / g, measured at 25°C in chloroform at a concentration of 0.1 g / dl.

[0075] pass 1 The molar percentages of L-lactide and ε-caprolactone in the segmented copolymers were determined by H NMR spectroscopy. Deuterated chloroform was used as solvent. 1 The characteristic peak a of the lactide methine group in the H NMR spectrum is between 5.0 and 5.3 ppm, and the characteristic peak b of the caprolactone methylene group is between 4.0 and 4.3 ppm, as shown in Figure 7. The molar percentage of L-lactide (Lm) is calculated by the following formula:

[0076] The weight percentage of L-lactide (Lw) is calculated by the following formula:

[0077] The data of the embodiments and comparative examples are shown in Table 1.

[0078] The above segmented copolymer was injection molded at 180-210° C. to produce a dumbbell plate with a thickness of 2 mm. The material was stretched at a speed of 10 mm / min on a universal mechanical testing machine to test the tensile strength at break and the elongation at break. The material was stretched at a speed of 1 mm / min to test the Young's modulus, as shown in Table 1.

[0079] The crystallinity of the segmented copolymer synthesized above was tested by differential scanning calorimetry (DSC) at a heating rate of 10°C / min. The crystallinity refers to the crystallinity C of the LA segment (PLLA) in the segmented copolymer, and is calculated as follows:

[0080] Where a is the difference (J / g) between the melting heat of the LA segment (PLLA) and its crystallization heat (if any) in the DSC spectrum, 93 is the melting heat of fully crystallized PLLA (J / g, Sarasua, JR, Prud'homme, R.E., Wisniewski, M., Le Borgne, A., Spassky, N., 1998. Macromolecules 31, 3895–3905), and A is the percentage of LA segments.

[0081] Example 2:

[0082] Preparation of segmented copolymer 2 (PLC2) of L-lactide / ε-caprolactone:

[0083] Preparation of Segment A: 550 g of recrystallized and purified L-lactide monomer (LA) was placed in a 3 L stainless steel reactor, followed by the addition of 0.04 wt % stannous octoate catalyst and 0.20 wt % octadecyl alcohol. Under nitrogen, the system temperature was raised to 165° C., and polymerization was carried out for 12 hours at a stirring speed of 5-20 rpm to obtain Segment A. Segment A had an intrinsic viscosity of 2.05 dl / g at 25° C. in 0.1 g / dl chloroform, and a melting peak temperature of 176.5° C. as measured by DSC.

[0084] Preparation of an L-lactide / ε-caprolactone segmented copolymer (PLC): 450 g of ε-caprolactone as a monomer for segment B was added to the above-mentioned segment A, with the weight ratio of segment A to segment B being 55:45. Under nitrogen protection, the temperature was raised to 175°C and maintained for 1 hour. The temperature was then lowered to 165°C and reacted for 18 hours to obtain an L-lactide / ε-caprolactone segmented copolymer containing segments A and B. The intrinsic viscosity of the copolymer, measured at 25°C in 0.1 g / dl chloroform, was 1.81 dl / g.

[0085] Segmented copolymer 1 The H NMR component determination, mechanical property and crystallinity testing methods were the same as in Example 1, and the results are shown in Table 1. The product prepared in this example had the same peak positions of the lactide methine and caprolactone methylene in the structure as in Example 1.

[0086] Example 3:

[0087] Preparation of segmented copolymer 3 of L-lactide / ε-caprolactone (PLC3):

[0088] Preparation of Segment A: 600 g of recrystallized and purified L-lactide monomer (LA) was placed in a 3 L stainless steel reactor, followed by the addition of 0.03 wt % stannous octoate catalyst and 0.08 wt % diethylene glycol. Under nitrogen, the system temperature was raised to 175° C., and polymerization was carried out for 12 hours at a stirring speed of 5-20 rpm to obtain Segment A, which had an intrinsic viscosity of 1.65 dl / g at 25° C. in 0.1 g / dl chloroform and a melting peak temperature of 174.0° C. as measured by DSC.

[0089] Preparation of a segmented L-lactide / ε-caprolactone copolymer: 400 g of ε-caprolactone was added as a segment B unit to the above-mentioned segment A, with a weight ratio of segment A to segment B of 60:40. Under nitrogen protection, the temperature was raised to 180°C and maintained for 0.5 hour. The temperature was then lowered to 168°C and reacted for 16 hours to obtain an L-lactide / ε-caprolactone segmented copolymer having an intrinsic viscosity of 1.66 dl / g, measured in 0.1 g / dl chloroform at 25°C.

[0090] Segmented copolymer 1 The H NMR component determination, mechanical properties, and crystallinity testing methods were the same as in Example 1, and the results are shown in Table 1. The product prepared in this example had the same peak locations for the lactide methine and caprolactone methylene groups as in Example 1.

[0091] Example 4:

[0092] Preparation of segmented copolymer 4 of L-lactide / ε-caprolactone (PLC4):

[0093] Preparation of segment A: 650 g of recrystallized and purified L-lactide monomer (LA) was placed in a 3 L stainless steel reactor, followed by the addition of 0.04 wt % stannous octoate catalyst and 0.03 wt % diethylene glycol. Under nitrogen, the system temperature was raised to 160° C., and polymerization was carried out for 12 hours at a stirring speed of 5-20 rpm to obtain segment A. The intrinsic viscosity of the segment A, measured in 0.1 g / dl chloroform at 25° C., was 2.65 dl / g. The melting peak temperature, as measured by DSC, was 177.5° C. The tensile strength of the segment A, as determined by mechanical testing, was 69.3 MPa.

[0094] Preparation of a segmented L-lactide / ε-caprolactone copolymer: 350 g of ε-caprolactone was added as a segment B unit to the above-mentioned segment A, with a weight ratio of segment A to segment B of 65:35. Under nitrogen protection, the temperature was raised to 170°C and maintained for 1.5 hours. The temperature was then lowered to 155°C and reacted for 20 hours to obtain an L-lactide / ε-caprolactone segmented copolymer having an intrinsic viscosity of 2.56 dl / g measured in 0.1 g / dl chloroform at 25°C.

[0095] Segmented copolymer 1 The H NMR component determination, mechanical property and crystallinity testing methods were the same as in Example 1, and the results are shown in Table 1. The product prepared in this example had the same peak positions of the lactide methine and caprolactone methylene in the structure as in Example 1.

[0096] Example 5:

[0097] Preparation of segmented copolymer 5 of L-lactide / ε-caprolactone (PLC5):

[0098] Preparation of Segment A: 700 g of recrystallized and purified L-lactide monomer (LA) was placed in a 3 L stainless steel reactor, followed by the addition of 0.03 wt % stannous octoate catalyst and 0.05 wt % diethylene glycol. Under nitrogen, the system temperature was raised to 160°C, and polymerization was carried out for 12 hours at a stirring speed of 5-20 rpm to obtain Segment A. Segment A had an intrinsic viscosity of 2.23 dl / g (measured in 0.1 g / dl chloroform at 25°C) and a melting peak temperature of 178.0°C (measured by DSC).

[0099] Preparation of a segmented L-lactide / ε-caprolactone copolymer: 300 g of ε-caprolactone was added as a segment B unit to the above-mentioned segment A, with a weight ratio of segment A to segment B of 70:30. Under vacuum, the temperature was raised to 172°C and maintained for 1.5 hours. The temperature was then lowered to 158°C and reacted for 20 hours to obtain an L-lactide / ε-caprolactone segmented copolymer having an intrinsic viscosity of 2.06 dl / g measured in 0.1 g / dl chloroform at 25°C.

[0100] Segmented copolymer 1 The H NMR component determination, mechanical property and crystallinity testing methods were the same as in Example 1, and the results are shown in Table 1. The product prepared in this example had the same peak positions of the lactide methine and caprolactone methylene in the structure as in Example 1.

[0101] Example 6:

[0102] Preparation of segmented copolymer 6 of L-lactide / ε-caprolactone (PLC6):

[0103] Preparation of Segment A: 750 g of recrystallized and purified L-lactide monomer (LA) was placed in a 3 L stainless steel reactor, followed by the addition of 0.02 wt % stannous octoate catalyst and 0.10 wt % diethylene glycol. Under nitrogen, the system temperature was raised to 160° C., and polymerization was carried out for 15 hours at a stirring speed of 5-20 rpm to obtain Segment A, which had an intrinsic viscosity of 1.65 dl / g at 25° C. in 0.1 g / dl chloroform and a melting peak temperature of 178.1° C. as measured by DSC.

[0104] Preparation of a segmented L-lactide / ε-caprolactone copolymer: 250 g of ε-caprolactone was added as a segment B unit to the above-mentioned segment A, with a weight ratio of segment A to segment B of 75:25. Under nitrogen protection, the temperature was raised to 175°C and maintained for 1 hour. The temperature was then lowered to 160°C and reacted for 20 hours to obtain an L-lactide / ε-caprolactone segmented copolymer having an intrinsic viscosity of 1.56 dl / g, measured in 0.1 g / dl chloroform at 25°C.

[0105] Segmented copolymer 1 The H NMR component determination, mechanical property and crystallinity testing methods were the same as in Example 1, and the results are shown in Table 1. The product prepared in this example had the same peak positions of the lactide methine and caprolactone methylene in the structure as in Example 1.

[0106] Comparative Example 1:

[0107] Preparation of the A segment: 300 g of ε-caprolactone monomer (CL) purified by vacuum distillation and 300 g of L-lactide monomer (LA) purified by recrystallization were placed in a 3 L stainless steel reactor in a weight ratio of CL to LA of 50:50. 0.03% by weight of stannous octoate catalyst and 0.05% by weight of diethylene glycol were then added. Under nitrogen protection, the system temperature was raised to 170° C. and polymerization was carried out for 18 hours at a stirring speed of 5-20 rpm to obtain an A segment mainly composed of ε-caprolactone. The A segment had an intrinsic viscosity of 2.29 dl / g measured in 0.1 g / dl chloroform at 25° C., and no melting peak was observed on the DSC curve, indicating that the prepolymer was amorphous. The tensile strength of the A segment, as determined by mechanical testing, was 9.8 MPa.

[0108] Preparation of a segmented L-lactide / ε-caprolactone copolymer: 600 g of L-lactide was added as a segment B unit to the aforementioned segment A, with a weight ratio of segment A to segment B of 50:50. The mixture was stirred at 175°C for 1 hour, followed by a reaction at 160°C for 18 hours to obtain an L-lactide / ε-caprolactone segmented copolymer containing segments A and B. The copolymer had an intrinsic viscosity of 2.20 dl / g, measured at 25°C in 0.1 g / dl chloroform.

[0109] Segmented copolymer 1 The methods for determining the components by H NMR spectroscopy, and testing the mechanical properties and crystallinity were the same as those in Example 1. The results are shown in Table 1.

[0110] Comparative Example 2:

[0111] Preparation of the A segment: 288 g of ε-caprolactone monomer (CL) purified by vacuum distillation and 72 g of L-lactide monomer (LA) purified by recrystallization were placed in a 3 L stainless steel reactor in a weight ratio of CL to LA of 80:20. 0.04 wt % stannous octoate catalyst and 0.05 wt % diethylene glycol were then added. Under nitrogen, the system temperature was raised to 170° C. and polymerization was carried out for 18 hours at a stirring speed of 5-20 rpm to obtain the A segment mainly composed of ε-caprolactone. The A segment had an intrinsic viscosity of 2.35 dl / g, measured in 0.1 g / dl chloroform at 25° C.

[0112] Preparation of a segmented L-lactide / ε-caprolactone copolymer: 840 g of L-lactide was added as a segment B unit to the above-mentioned segment A, with a weight ratio of segment A to segment B of 30:70. The mixture was reacted at 165°C for 18 hours to obtain an L-lactide / ε-caprolactone segmented copolymer containing segments A and B. The copolymer had an intrinsic viscosity of 2.19 dl / g, measured in 0.1 g / dl chloroform at 25°C.

[0113] Segmented copolymer 1 The methods for determining the components by H NMR spectroscopy, and testing the mechanical properties and crystallinity were the same as those in Example 1. The results are shown in Table 1.

[0114] Comparative Example 3:

[0115] Preparation of segment A: 300 g of ε-caprolactone monomer (CL) purified by vacuum distillation was placed in a 3 L stainless steel reactor, and then 0.04% by weight of stannous octoate catalyst and 0.05% by weight of diethylene glycol were added. Under nitrogen protection, the temperature was raised to 170°C and maintained for 1.5 hours. The temperature was then lowered to 155°C and reacted for 20 hours to obtain segment A containing ε-caprolactone homopolymer (PCL). The intrinsic viscosity of the segment A measured at 25°C in 0.1 g / dl chloroform was 2.24 dl / g, and the melting peak temperature measured by DSC was 60.1°C, which was the melting peak of PCL. The tensile strength of the segment A obtained by mechanical experiments was 29.8 MPa.

[0116] Preparation of a segmented L-lactide / ε-caprolactone copolymer: 700 g of L-lactide was added as a segment B unit to the above-mentioned segment A, with a weight ratio of segment A to segment B of 30:70. The mixture was reacted at 165°C for 19 hours to obtain an L-lactide / ε-caprolactone segmented copolymer containing segments A and B. The copolymer had an intrinsic viscosity of 1.92 dl / g, measured at 25°C in 0.1 g / dl chloroform.

[0117] Segmented copolymer 1 The methods for determining the components by H NMR spectroscopy, and testing the mechanical properties and crystallinity were the same as those in Example 1. The results are shown in Table 1.

[0118] Comparative Example 4:

[0119] Preparation of the A segment: 240 g of ε-caprolactone monomer (CL) purified by vacuum distillation was placed in a 3 L stainless steel reactor, and then 0.05 wt % stannous octoate catalyst and 0.05 wt % diethylene glycol were added. The system temperature was raised to 150° C. under nitrogen protection, and the polymerization reaction was carried out at a stirring speed of 5-20 rpm for 20 hours to obtain an A segment containing an ε-caprolactone homopolymer (PCL). The intrinsic viscosity of the PCL segment was 2.33 dl / g at 25° C. in 0.1 g / dl chloroform. The melting peak temperature measured by DSC was 60.6° C., which was the melting peak of PCL.

[0120] Preparation of a segmented L-lactide / ε-caprolactone copolymer: 760 g of L-lactide was added as a segment B unit to the above-mentioned segment A, with a weight ratio of segment A to segment B of 24:76. Under nitrogen protection, the temperature was raised to 175°C and maintained for 1.5 hours. The temperature was then lowered to 160°C and reacted for 20 hours to obtain an L-lactide / ε-caprolactone segmented copolymer containing segments A and B. The intrinsic viscosity of the copolymer, measured in 0.1 g / dl chloroform at 25°C, was 1.92 dl / g.

[0121] Segmented copolymer 1 The methods for determining the components by H NMR spectroscopy, and testing the mechanical properties and crystallinity were the same as those in Example 1. The results are shown in Table 1.

[0122] Comparative Example 5:

[0123] Preparation of the A segment: 240 g of ε-caprolactone monomer (CL) purified by vacuum distillation was placed in a 3 L stainless steel reactor, and then 0.05 wt% stannous octoate catalyst and 0.05 wt% diethylene glycol were added. The system temperature was raised to 160°C under nitrogen protection, and the polymerization reaction was carried out at a stirring speed of 5-20 rpm for 20 hours to obtain an A segment containing ε-caprolactone homopolymer (PCL). The intrinsic viscosity of the PCL segment was 1.96 dl / g at 25°C in 0.1 g / dl chloroform, and the melting peak temperature measured by DSC was 60.3°C, which was the melting peak of PCL.

[0124] Preparation of a segmented L-lactide / ε-caprolactone copolymer: 760 g of L-lactide was added as a segment B unit to the above-mentioned segment A, with a weight ratio of segment A to segment B of 24:76. Under nitrogen protection, the temperature was raised to 175°C and maintained for 1.5 hours. The temperature was then lowered to 160°C and reacted for 20 hours to obtain an L-lactide / ε-caprolactone segmented copolymer containing segments A and B. The copolymer had an intrinsic viscosity of 1.98 dl / g, measured in 0.1 g / dl chloroform at 25°C.

[0125] Segmented copolymer 1 The methods for determining the components by H NMR spectroscopy, and testing the mechanical properties and crystallinity were the same as those in Example 1. The results are shown in Table 1.

[0126] Comparative Example 6:

[0127] Preparation of L-lactide / ε-caprolactone random copolymer (PLCW):

[0128] 710 g of L-lactide monomer (LA) purified by recrystallization and 290 g of ε-caprolactone monomer (CL) purified by reduced pressure were placed in a 3 L stainless steel reactor with an LA / CL feed ratio of 71 / 29. 0.03% stannous octoate catalyst and 0.02% by weight of lauryl alcohol were then added. Under nitrogen protection, the system temperature was raised to 160° C. and the reaction was carried out for 25 hours. The copolymer in the reactor was transferred, further crushed, and vacuum-dried in a 90° C. vacuum oven for 24 hours to obtain an L-lactide / ε-caprolactone random copolymer (PLCW) having an intrinsic viscosity of 2.5 dl / g measured in 0.1 g / dl chloroform at 25° C.

[0129] The DSC graphs of the random copolymer (PLCW) prepared in Comparative Example 6, the segmented copolymer prepared in Comparative Example 4, and the PLC segmented copolymer prepared in Example 6 are shown in Figure 6: the upper curve is Comparative Example 6, which is a random copolymer having no melting point and a crystallinity of 0; the middle curve is Comparative Example 4, which is a segmented polymer obtained by first polymerizing ε-caprolactone and then polymerizing L-lactide, with a melting point of 172°C and a relative crystallinity of 28.9%; the lower curve is Example 6, which is a segmented polymer obtained by first polymerizing L-lactide and then polymerizing ε-caprolactone, with a melting point of 190°C and a relative crystallinity of 42.3%.

[0130] Random copolymer 1 The methods for determining the components by H NMR spectroscopy, and testing the mechanical properties and crystallinity were the same as those in Example 1. The results are shown in Table 1.

[0131] Table 1

[0132] The above embodiments and comparative examples can further illustrate the characteristics and principles of the present invention.

[0133] Table 1 shows that the segmented copolymers in which LA is polymerized first as the A segment, such as PLC5 and PLC6, have significantly higher tensile strength than the segmented copolymers in which CL is polymerized first as the A segment (Comparative Examples 3 and 4), when the total ratio of CL to LA is similar. They also have lower modulus and higher elongation at break.

[0134] In commonly reported prior art, block copolymers or segmented copolymers with soft and hard segment structures typically polymerize the soft segments first (e.g., CL or CL-based segments) and the hard segments (LA segments) later. This is because the relatively high content of the hard segments better dissolves the relatively small soft segments. Examples include the glycolide and trimethylene carbonate copolymers reported by Elena Díaz-Celorio et al.; the glycolide and CL copolymers reported by Rao S. Bezwada et al.; and the LA and CL copolymers reported by Jin Kon Kim et al. and disclosed in Chinese Patent CN 108997564 A.

[0135] In the segmented copolymers of the present invention, CL is a soft segment with flexibility, while LA is a hard segment. The present inventors discovered that prioritizing the CL soft segment can compromise the integrity of the subsequent hard segment LA, resulting in reduced crystallinity in the LA segment. Consequently, the crystallinity of the LA segment in the segmented copolymers of the present invention is significantly higher than that of the comparative examples.

[0136] The present invention discovered that after LA is polymerized first, even if the content of the subsequently added monomer CL is relatively low, CL is a good solvent for PLLA at high temperatures. It can well penetrate into the A-segment polymer PLLA and achieve polymerization. This is a phenomenon observed by the present invention. The advantage of this is that the subsequently added CL monomer is less likely to affect the integrity of the already polymerized LA segment during the polymerization process, which is reflected in the higher crystallinity of the LA segment of the segmented copolymer formed in this way, and therefore better mechanical properties.

[0137] In Comparative Examples 1 and 2, the A segment mainly composed of CL is polymerized first, and a small amount of LA is added to the A segment, which reduces the crystallization performance of the A segment. The LA segment is polymerized later, and its mechanical properties are also worse than those of the embodiments of the present invention, and the crystallinity is also lower.

[0138] Table 1 also shows that in PLC1-PLC6, as the content of A segment (LA hard segment) increases, its tensile strength and modulus increase, while its elongation at break decreases. Generally speaking, it has good mechanical strength and good flexibility. However, when the A segment content exceeds 75% by weight, the segmented copolymerization becomes too hard and its toughness decreases. Compared with PLLA homopolymer materials, although PLLA has a higher tensile strength, up to 70MPa, its elongation at break is very low, less than 10%, and its elastic modulus is greater than 2GPa. It is a strong but brittle material (POLY (LACTIC ACID), Synthesis, Structures, Properties, Processing, and Applications, p141, 2010), which is not suitable for use in the binding tape of the present invention.

[0139] Example 7:

[0140] Preparation of absorbable bandage:

[0141] The PLC segmented copolymer of the present invention, the comparative copolymer, PPDO (polydioxanone), and PLLA (poly-L-lactic acid) were injection molded into a flat ribbon-shaped binding tape. The temperature of the injection molding machine head and nozzle was 190°C-200°C, the injection pressure was 100 MPa, the injection speed was greater than 100 mm / second, and the cooling temperature was from room temperature to 60°C. The absorbable binding tape after injection molding had a certain degree of reduction in intrinsic viscosity based on the raw materials. This is due to natural thermal degradation during processing. The product formed by this process has an intrinsic viscosity reduction rate of no more than 30%, and the lower the molecular weight of the material, the smaller the intrinsic viscosity reduction rate.

[0142] The formed absorbable binding belt is 220mm in length, 5mm in width, and 0.8-1.1mm in thickness, including the head, body, and tail.

[0143] The belt head has a hollow locking structure with a one-way pressure head (tongue) structure installed inside the head. When the belt body passes through the hollow belt head, the pressure head, relying on the elasticity of the absorbent material, makes room for the belt body to pass forward. The pressure head immediately snaps into the horizontal teeth on the belt body due to its resilience, hindering reverse pull and achieving a locking effect. Therefore, the toughness and resilience of the material are crucial to the locking and fixing. If the material is too hard and lacks elasticity, such as polylactic acid homopolymer, the belt body will be damaged when forced through the pressure head, and the locking effect will not be achieved. If the material is too tough and too soft, the locking is not secure and it is easy to slip under stress. The better the material strength and elasticity, the greater the locking force.

[0144] One side of the belt body contains multiple transverse teeth, which are used to engage with the pressure head to complete the locking action.

[0145] The belt tail is a flat surface, and its main function is to guide the belt body to pass through the belt head more easily.

[0146] The mechanical properties of absorbable binding bands made of different materials were tested. On a universal mechanical testing machine, as shown in Figure 4, the bands were stretched at a rate of 10 mm / min to measure the tensile force (unit: Newton) at break. The results are shown in Table 2. For binding bands, the greater the breaking force, the better the binding.

[0147] This embodiment also tested another important mechanical property, the locking force, of absorbable binding tapes made of different materials. As shown in Figure 5, the tape body was cut from the middle section, and the tail of the tape was passed through the hollow structure of the head. The head was equipped with a one-way pressure head structure. The tail of the tape was pulled until the tape body and the head were firmly engaged. On a universal mechanical testing machine, the tape was stretched at a speed of 10 mm / min, and the tail and the head of the tape were pulled in opposite directions to test the locking force (unit: Newton N) of the binding tape. The results are shown in Table 2. For binding tapes, the greater the locking force, the less likely the binding will loosen.

[0148] Table 2

[0149] The results in Table 2 further illustrate the particularity of the binding band of the present invention, especially the locking force performance after buckling. A significant difference can only be seen after the material is made into an absorbable binding band.

[0150] Comparing the segmented copolymer PLC of the present invention with the materials of Comparative Examples 1-6, the present invention exhibits significant advantages in breaking strength and locking force, despite having similar flexibility. This is primarily due to the higher crystallinity of the A segments in the PLC, resulting in better tensile strength. Furthermore, the unidirectional pressure head within the strap head also exhibits good resilience, resulting in a more secure locking mechanism.

[0151] In the embodiments of the present invention, when the LA content is equal to or lower than 50% by weight, such as the PLC of Example 1, the breaking force and locking force of the strapping are relatively weak; when it is higher than or equal to 75% by weight, such as the PLC6 of Example 1, although the breaking force is large, the locking force begins to decrease.

[0152] The PPDO binding tape used as a control example in Table 2 has good tensile properties and locking force. However, the in vitro degradation performance evaluation in the present invention shows that its degradation rate is too fast and is not suitable for use in fracture internal fixation.

[0153] As the control example in Table 2, the binding strap made of PLLA (poly-L-lactic acid) is difficult to pass through the strap head (large resistance), which will damage the pressure head or make it unable to rebound and reset, resulting in loss of locking force. Although the breaking force is the largest, its locking force is the smallest.

[0154] The above results indicate that the absorbable binding belt of the present invention has good mechanical strength without sacrificing toughness, thereby ensuring sufficient breaking force and locking force during use.

[0155] Example 8:

[0156] Evaluation of in vitro degradation mechanical properties of absorbable binding tape:

[0157] This example evaluated two important mechanical properties of absorbable binding bands: breaking force and locking force. The in vitro degradation of the absorbable binding bands of the present invention and the comparative binding bands was conducted in a phosphate buffer solution at 37°C. The binding bands were tied to a plastic round rod with a diameter of 40 mm, and the binding bands were allowed to degrade under stress, which is closer to the actual situation. The entire band was then placed in a phosphate buffer solution at 37°C. The binding bands were periodically removed and clamped on a universal mechanical testing machine to test the breaking force and locking force. The results are shown in Table 3:

[0158] Table 3

[0159] Note: “0” means the mechanical testing machine cannot hold the sample, or the sample breaks as soon as it is clamped.

[0160] A comparison of the properties of absorbable bandages made from the above-mentioned different materials is shown in Table 3. The results show that the bandage made from the L-lactide / ε-caprolactone random copolymer (Comparative Example 6) maintains its mechanical properties for a shorter period of time during degradation than the bandage of the present invention, at approximately two months, because it is an amorphous polymer with no crystallinity.

[0161] Comparative Examples 1-6 are also binding bands made of segmented copolymers. The maintenance time of their mechanical properties during the degradation process is shorter than that of the absorbable binding band of the present invention, especially the locking force, which is difficult to maintain for 3 months. Under stress in the body, the degradation time will be even shorter. Therefore, there is a greater risk in using them in the field of orthopedics.

[0162] PPDO (polydioxanone) strapping has very good mechanical properties, but the mechanical properties of the strapping are maintained for too short a time during the degradation process, and the strapping loses its strength within two months.

[0163] The specific implementation methods described above further illustrate the objectives, technical solutions and beneficial effects of the present invention in detail. It should be understood that the above description is only a specific implementation method of the present invention and is not intended to limit the scope of protection of the present invention. Any modifications, equivalent substitutions, improvements, etc. made within the spirit and principles of the present invention should be included in the scope of protection of the present invention.

Claims

1. An absorbable segmented copolymer, characterized in that: include: Segment A, the first segment, is a crystalline prepolymer formed by polymerization of L-lactide, and its weight percentage in the segmented copolymer is 50% to 75%; The B segment is the second segment, and its weight percentage in the segmented copolymer is 25% to 50%; the monomer of the B segment includes ε-caprolactone or a mixture of ε-caprolactone and other monomers, and the other monomers include glycolide, trimethylene carbonate, p-dioxanone, DL-lactide or L-lactide.

2. The absorbable segmented copolymer according to claim 1, characterized in that: The intrinsic viscosity of the A segment in chloroform at a concentration of 0.1 g / dl at 25° C. is 1.3 to 3.0 dl / g; the intrinsic viscosity of the absorbable segmented copolymer in chloroform at a concentration of 0.1 g / dl at 25° C. is 1.0 to 3.0 dl / g.

3. The absorbable segmented copolymer according to claim 2, characterized in that: The absorbable segmented copolymer has an intrinsic viscosity of 1.3 to 2.3 dl / g at 25° C. in chloroform at a concentration of 0.1 g / dl.

4. The method for preparing the absorbable segmented copolymer according to any one of claims 1 to 3, characterized in that: The following steps are involved: S1. Using a hydroxyl-containing compound as an initiator, in the presence of a catalyst, L-lactide is added to an air-isolated reactor, and ring-opening polymerization is performed above the melting temperature of L-lactide to obtain segment A; S2. Melt and blend the monomer of the B segment and the A segment prepared in step S1 uniformly, and polymerize them in an air-isolated reactor to form an absorbable segmented copolymer containing the A segment and the B segment.

5. The preparation method according to claim 4, characterized in that: In step S1, the preparation of segment A includes the following components in weight percentage: The initiator is 0.02% to 0.2%, the catalyst is 0.01% to 0.1%, and the balance is L-lactide.

6. The preparation method according to claim 4, characterized in that: In step S1, the melting temperature is 150°C to 180°C, and the reaction temperature is maintained for 8 to 24 hours to obtain the A segment by ring-opening polymerization.

7. The preparation method according to claim 4, characterized in that: In step S1, the initiator includes a monohydric alcohol, a dihydric alcohol or a polyhydric alcohol; and the catalyst includes a tin salt.

8. The preparation method according to claim 4, characterized in that: In step S2, the process of melt blending is: Raise the temperature to 170°C to 180°C, maintain for at least half an hour, then lower the temperature to 150°C to 170°C, and allow the polymerization to proceed for 10 to 25 hours.

9. Use of the absorbable segmented copolymer according to any one of claims 1 to 3 in the preparation of medical absorbable devices.

10. An absorbable binding belt, characterized in that: It is made of the absorbable segmented copolymer described in any one of claims 1 to 3.

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