Medical polyhydroxyalkanoate monofilament as well as preparation method and application thereof

Abstract

The embodiment of the invention provides a medical polyhydroxyalkanoate monofilament as well as a preparation method and application thereof, and the preparation method comprises the following steps: preparing the monofilament by using medical polyhydroxyalkanoate as a raw material through a melt extrusion method; immersing the monofilaments in hot water at 40-60 DEG C to obtain pre-crystallized monofilaments; 5-20 times of drafting is carried out on the pre-crystallized monofilament, and the drafted monofilament is obtained; and winding the drafted monofilament to obtain a medical polyhydroxyalkanoate monofilament finished product. According to the invention, the problem that the strength and toughness of the obtained monofilament can meet the requirements only by mixing multi-component raw materials in the prior art is solved, the single medical PHA material is successfully drawn, the component of the obtained monofilament is only single PHA, and the corresponding strength and toughness can be maintained; and a solid foundation is laid for clinical conversion application of the monofilament.

Description

TECHNICAL FIELD

[0001] The present application relates to a medical polyhydroxyalkanoate monofilament and a preparation method and application thereof, and belongs to the technical field of medical devices used in biomedical tissue engineering repair. BACKGROUND

[0002] Medical monofilament is a basic wire material required for the preparation of many medical devices. For example, absorbable surgical sutures, hernia patches, artificial blood vessels, artificial esophagus, embolization springs and other medical devices are all based on monofilaments, which are processed into final products through braiding and other forms. Traditionally, polypropylene monofilament, nylon monofilament, polyglycolide (PGA) monofilament, p-dimethylhydroxyhexanone (PDO), lactic acid monofilament and the like are common medical monofilaments. Although these monofilaments have achieved some satisfactory clinical results, some materials cannot be degraded, leading to secondary surgical injury and accompanying some safety problems; some materials can be degraded, but the degradation mode is hydrolysis and the like, and the strength is lost in a short time (about 2 months), and the measurable strength of the medical monofilament is required to be maintained for 6 months or more in the clinic, so there is an urgent need for a new type of biocompatible material monofilament that can be absorbed and is beneficial to tissue repair.

[0003] For the common medical monofilaments currently used, from the perspective of preparation technology, they are generally prepared by melt extrusion, and in order to achieve the strength and toughness requirements of the monofilament, a mixture of multiple materials is often used for the preparation of the monofilament. These material combinations are, for example, PHBHHX+PLA, PHB+P34HB+adjuvant, etc. Although this preparation method can improve the performance of the obtained monofilament to some extent, the raw material components used are many, and many of the materials are not in compliance with the record of the drug regulatory department or some adjuvants are not allowed to be used in absorbable devices, leading to complex and long-term clinical research, which cannot be truly applied to the clinic. Moreover, most of the preparation technologies related to medical monofilaments are based on industrial-grade or scientific-grade materials, and the preparation of monofilaments using medical-grade materials is still blank. The difference in material grade leads to different processing technologies.

[0004] In summary, in the process of realizing the concept of the present application, the inventors have found that at least the following problems exist in the related art: 1) the monofilament is generally prepared by melt extrusion in the prior art, and the strength and toughness of the obtained monofilament cannot meet the requirements; and 2) the components of the monofilament raw material commonly used in the prior art are numerous, and many of the components are not in compliance with the record of the drug regulatory department or some adjuvants are not allowed to be used in absorbable devices, leading to complex and long-term clinical research, which cannot be truly applied to the clinic.

[0005] Therefore, it has become a technical problem urgently needed to be solved in the field to provide a new type of medical polyhydroxyalkanoate (PHA) monofilament and a preparation method and application thereof. Summary of the Invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide a medical polyhydroxyalkanoate monofilament and its preparation method and application, which solves the problem that the strength and toughness of the obtained monofilament can only be met by mixing multiple raw materials in the prior art.

[0007] To address the aforementioned technical problems, a specific embodiment of the present invention provides a method for preparing medical-grade polyhydroxyalkanoate monofilaments, wherein the preparation method includes:

[0008] Step (1): Monofilaments are obtained by melt extrusion using medical-grade polyhydroxyalkanoate as raw material;

[0009] Step (2): Immerse the monofilament in hot water at 40-60℃ to obtain pre-crystallized monofilament;

[0010] Step (3): The pre-crystallized monofilament is drawn 5-20 times to obtain the drawn monofilament;

[0011] Step (4): The stretched monofilament is wound up to obtain the finished medical polyhydroxyalkanoate monofilament.

[0012] In one embodiment of the present invention, the molecular weight of the medical polyhydroxyalkanoate is 50,000 to 1,000,000.

[0013] In one embodiment of the present invention, the medical polyhydroxy fatty acid ester includes PHB, P34HB or PHBHHX, etc., preferably P34HB.

[0014] In one embodiment of the present invention, the medical polyhydroxy fatty acid ester is in the form of granules.

[0015] In one embodiment of the present invention, step (1) includes melting and extruding medical polyhydroxy fatty acid ester raw material in the barrel area of ​​a single screw extruder to form monofilament; specifically, it includes: medical polyhydroxy fatty acid ester raw material is melt-extruded sequentially through barrel area 1, barrel area 2 and barrel area 3 of a single screw extruder to obtain monofilament;

[0016] The temperatures in zones 1, 2, and 3 of the material cylinder are different, and the temperature range for each zone is 145-200℃. For example, when the medical-grade polyhydroxyalkanoate is P34HB, the temperatures in zones 1, 2, and 3 are 150±3℃, 170±3℃, and 168±3℃, respectively.

[0017] In the single-screw extruder, barrel section 1 is close to the feed inlet, and barrel section 3 is close to the die opening.

[0018] In one embodiment of the present application, in step (2), the length of the monofilament immersed in water is 40-120 cm.

[0019] In one embodiment of the present application, in step (2), the depth of the monofilament immersed in water is 1-3 cm.

[0020] In step (2) of the above-mentioned preparation method of the present application, the monofilament is immersed in hot water at 40-60°C to complete the pre-crystallization process.

[0021] In some embodiments of the present application, in step (3), the draw ratio of the drawing is, for example, 5, 5.5, 6, 6.5, 7, 7.5, 8, 8.5, 9, 9.5, 10, 10.5, 11, 11.5, 12, 12.5, 13, 13.5, 14, 14.5, 15, 15.5, 16, 16.5, 17, 17.5, 18, 18.5, 19, 19.5, 20, etc.

[0022] In one embodiment of the present application, in step (3), the drawing is two-stage drawing, wherein the speed of the first drawing roller is 5-20 m / s, the speed of the second drawing roller is 5-20 m / s, and the speed of the third drawing roller is 5-20 m / s.

[0023] In one embodiment of the present application, in step (3), the draw ratio of the first-stage drawing is 1-4 times, and the draw ratio of the second-stage drawing is 2-5 times.

[0024] In step (3) of the above-mentioned preparation method of the present application, the pre-crystallized monofilament is drawn by 5-20 times to maintain and improve its toughness.

[0025] In one embodiment of the present application, in step (4), the linear speed of the winding is 2-20 m / min.

[0026] The specific embodiments of the present application also provide a medical polyhydroxyalkanoate monofilament prepared by the above-mentioned preparation method of the medical polyhydroxyalkanoate monofilament.

[0027] The specific embodiments of the present application also provide the use of the above-mentioned medical polyhydroxyalkanoate monofilament as a base wire in the preparation of medical devices.

[0028] In one embodiment of the present application, the medical device includes absorbable surgical sutures, hernia patches, artificial blood vessels, artificial esophagi, or embolism springs, etc.

[0029] Compared with the prior art, the technical scheme of the present application can achieve at least the following beneficial technical effects:

[0030] The medical polyhydroxyalkanoate monofilament is prepared only by using a single raw material of medical polyhydroxyalkanoate, the obtained monofilament only has a single PHA, without any auxiliary agent and additive, and the monofilament has high strength and high toughness. The medical polyhydroxyalkanoate monofilament provided by the application can maintain a certain strength for a long time during clinical use, which is beneficial to tissue repair. In addition, the degradation time of the medical polyhydroxyalkanoate monofilament provided by the application is consistent with the tissue repair time, so that it has a wide application prospect in the field of tissue repair.

[0031] In conclusion, the application overcomes the problem that the prior art can only meet the requirements of strength and toughness of the obtained monofilament by using a multi-component raw material mixture, successfully realizes drawing of a single medical PHA material, so that the obtained monofilament only has a single PHA and can maintain corresponding strength and toughness, thereby laying a solid foundation for clinical conversion and application of the monofilament.

[0032] It should be understood that the foregoing general description and the following detailed description are only exemplary and explanatory, and cannot limit the scope of the application claimed. BRIEF DESCRIPTION OF DRAWINGS

[0033] The following accompanying drawings are part of the specification of the application, which illustrate exemplary embodiments of the application, and together with the description of the specification, serve to explain the principles of the application.

[0034] Figure 1 is a process flow schematic diagram of preparing medical polyhydroxyalkanoate monofilament by two-stage drawing method in one embodiment of the application.

[0035] Figure 2a and Figure 2b are respectively effect pictures of 0818 batch of warp-knitted patch before and after heat pressing in test example 2.

[0036] Figure 2c and Figure 2d are respectively effect pictures of 0825 batch of warp-knitted patch before and after heat pressing in test example 2.

[0037] Explanation of reference signs:

[0038] 1 single screw extruder; 2 temperature-controlled water tank;

[0039] 3 drawing machine; 4 winding machine;

[0040] 31 first drawing roller; 32 second drawing roller;

[0041] 33 third drawing roller. DETAILED DESCRIPTION

[0042] To make the purposes, technical solutions and advantages of the embodiments of the present application clearer, the following will clearly explain the spirits of the present application with the attached drawings and detailed descriptions. Any person skilled in the art can make changes and modifications to the technology taught by the present application without departing from the spirits and scopes of the present application.

[0043] The illustrative embodiments of the present application and their description serve the purpose of explaining the present application. They are, however, not to be taken in their restrictive sense. Same or similar elements / components are denoted by the same or similar reference numerals throughout the drawings and the embodiments.

[0044] As to "first", "second", "third", etc. used in the present disclosure, these are not intended to refer to an ordinal number or a sequential number, but are used to distinguish elements or operations distinguished by the same technical terms.

[0045] As to the directional terms used in the present disclosure, such as "upper", "lower", "left", "right", "front" or "rear", etc., these are only referred to the directions in the drawings. Therefore, the directional terms used are used to explain, but not to limit the present application.

[0046] As to "comprise", "include", "have", "contain", etc. used in the present disclosure, these are open terms, i.e. meaning comprising but not limited to.

[0047] As to "and / or" used in the present disclosure, this includes any or all combinations of the things mentioned.

[0048] As to "plurality" in the present disclosure, this includes "two" and "more than two"; as to "plurality of groups" in the present disclosure, this includes "two groups" and "more than two groups".

[0049] As to the terms "approximately", "about", etc. used in the present disclosure, these are used to modify any quantity or error that can be slightly changed, but these slight changes or errors do not change the nature. Generally, the slight changes or errors modified by such terms can be 20% in some embodiments, 10% in some embodiments, 5% or other values in some embodiments. Those skilled in the art should understand that the aforementioned values can be adjusted according to actual needs, and are not limited thereto.

[0050] All terms used herein (including technical and scientific terms) have the meanings commonly understood by one of ordinary skill in the art, unless otherwise defined. It should be noted that the terms used herein should be interpreted as having meanings consistent with the context of the present specification, and should not be interpreted in an idealized or overly formal manner.

[0051] In the event that a phrase such as "at least one of A, B, and C, etc." is used wherein A, B, and C represent a list of items, examples of the phrase "at least one of A, B, and C" shall be construed to mean A alone, B alone, C alone, A and B in combination, A and C in combination, B and C in combination, or A, B, and C in combination. In the event that a phrase such as "at most one of A, B, and C, etc." is used wherein A, B, and C represent a list of items, examples of the phrase "at most one of A, B, and C" shall be construed to mean A alone, B alone, C alone, or A, B, and C in combination. In the event that a phrase such as "at least one of A or B" is used, examples of the phrase "at least one of A or B" shall be construed to mean A alone, B alone, or A and B in combination. In the event that a phrase such as "at most one of A or B" is used, examples of the phrase "at most one of A or B" shall be construed to mean A alone, B alone, or A and B in combination. It is further understood that any disjunctive word or phrase, such as "only one," "at least one," "one," "one," "one," "an," or "one of the other like phrases, in the examples herein are used to

[0052] "RANGES" disclosed herein are presented in the form of a lower limit and an upper limit. There can be one or more lower limits, and one or more upper limits. A given range is defined by selecting a lower limit and an upper limit. The selected lower limit and upper limit define the boundaries of a particular range. All ranges defined in this manner are combinable, i.e., any lower limit can be combined with any upper limit to form a range. For example, where ranges of 60-120 and 80-110 are listed for a particular parameter, it is understood that ranges of 60-110 and 80-120 are also contemplated. In addition, if a minimum range value of 1 and 2 is listed, and a maximum range value of 3, 4, and 5 is listed, then the following ranges are all contemplated: 1-3, 1-4, 1-5, 2-3, 2-4, and 2-5.

[0053] In the present application, a numerical range "a-b" represents a shorthand manner of describing all the real combinations between a and b, where a and b are real numbers, unless otherwise indicated. For example, the numerical range "0-5" means that all the real numbers between "0-5" have been listed in the present application, and "0-5" is just a shorthand manner of describing these numerical combinations.

[0054] In the present application, if not otherwise specified, all the steps mentioned herein can be performed in sequence or randomly, but preferably in sequence. For example, the method comprises steps (a) and (b), which means that the method can comprise steps (a) and (b) in sequence, or steps (b) and (a) in sequence. For example, the method mentioned herein can further comprise step (c), which means that step (c) can be added to the method in any sequence, for example, the method can comprise steps (a), (b) and (c), or steps (a), (c) and (b), or steps (c), (a) and (b), etc.

[0055] Unless otherwise specified, the examples were carried out under conventional conditions or under the conditions recommended by the manufacturer. Unless otherwise specified, the reagents or instruments used were conventional products that can be commercially purchased.

[0056] Figure 1 A process flow diagram for preparing medical polyhydroxyalkanoate monofilament by two-stage drawing method according to an embodiment of the present application is shown. The medical polyhydroxyalkanoate raw material is melt-extruded by a single-screw extruder 1 to obtain a monofilament, the monofilament extruded by the single-screw extruder 1 is drawn to a first drawing roller 31 (first pair of rollers) of a drawing machine 3, the monofilament is immersed in hot water contained in a temperature-controlled water tank 2 by adjusting the fixed roller of the temperature-controlled water tank 2, and a pre-crystallized monofilament is obtained; the drawing machine 3 is opened and the speed and drawing multiple of the first drawing roller 31, a second drawing roller 32 (second pair of rollers) and a third drawing roller (third pair of rollers) 33 are set, so that the pre-crystallized monofilament is drawn by the first drawing roller 31 and the second drawing roller 32, and then further drawn by the second drawing roller 32 and the third drawing roller 33, and after the target drawing multiple is completed, a drawn monofilament is obtained; finally, the drawn monofilament is wound in a winding machine 4, and a medical polyhydroxyalkanoate monofilament product is obtained.

[0057] The material information used in the embodiments of the present application is shown in Table 1 below.

[0058] Table 1

[0059] Material name Company Model / size P34HB granules ZhuHai Medipoly Biotech Co. Ltd Medical grade MDF2000

[0060] The equipment information used in the embodiments of the present application is shown in Table 2 below.

[0061] Table 2

[0062]

[0063] Embodiments 1-17

[0064] The series of embodiments provide a series of medical polyhydroxyalkanoate monofilaments, which are prepared by a preparation method comprising the following specific steps:

[0065] I. Preparation:

[0066] Extruder:

[0067] Connect the power supply and turn on the heating function of the extruder. Set all three temperature zones of Zone 1, Zone 2, and Zone 3 of the barrel to 180℃, and wait for the temperature to stabilize for 10 minutes.

[0068] Temperature-controlled water tank:

[0069] Fill the temperature-controlled water tank with purified water to a height of about 14 cm. Place the heating rod, connect the power supply, and set the temperature to 50℃. Wait for the water temperature to stabilize for 10 minutes.

[0070] Stretching machine:

[0071] Connect the power supply; connect the air pipe; turn on the power switch and start the machine.

[0072] Tension winding machine with laser diameter measurement:

[0073] Connect the power supply, turn on the power switch and start the machine; pass the wire reel through the winding screw, use a plastic nut to rotate the wire reel clockwise until it is fixed and does not loosen. Turn on the laser diameter measurement switch.

[0074] II. Operation steps:

[0075] Step (1): After the Zone 1, Zone 2, and Zone 3 of the extruder have been stabilized at 180℃ for 10 minutes, add about 300g of P34HB particles (molecular weight range: 300-800 thousand) to the hopper, and set the screw speed to 16rpm. This time, the material is used as a cleaning material to observe whether the extruded material has obvious impurities. If there are impurities, continue to add cleaning materials to clean the machine until the extruded material is free of impurities.

[0076] If the die is blocked by the last processed material and the cleaning material cannot be extruded, use the high temperature setting of the double-temperature hot air gun to heat the die from top to bottom. Continue until the cleaning material is smoothly and smoothly extruded.

[0077] After the extruded material is free of impurities, set the temperature of each temperature zone again, i.e. set the temperature of Zone 1 to 150±3℃, the temperature of Zone 2 to 170℃±3℃, and the temperature of Zone 3 to 168±3℃, and let the temperature stabilize for about 10 minutes.

[0078] When there is no material in the screw from the hopper, add 1kg of P34HB particles to the hopper. This time, the material is used as the formal stretching material, and the P34HB particles are sequentially melted and extruded through Zone 1, Zone 2, and Zone 3 of the single-screw extruder to produce a single filament.

[0079] Step (2): The monofilament extruded from the extruder is drawn to the first drawing roller of the drawing machine at a speed of about 8 m / s.

[0080] The monofilament with a length of about 40 cm is completely immersed in the hot water of the temperature-controlled water tank by adjusting the fixed roller of the temperature-controlled water tank, and the immersion depth is about 1-3 cm below the water surface, to obtain the pre-crystallized monofilament.

[0081] Step (3): The drawing machine is opened and the speed and draw ratio of the first drawing roller, the second drawing roller and the third drawing roller are set as shown in Table 3 below, so that the pre-crystallized monofilament is drawn through the first drawing roller and the second drawing roller, and then further drawn through the second drawing roller and the third drawing roller, and the drawn monofilament is obtained after the target draw ratio is drawn. The pre-crystallized monofilament after passing through the temperature-controlled water tank enters the drawing machine from the first drawing roller on the right side of the drawing machine and exits the drawing machine from the third drawing roller. The draw ratio of the monofilament is in the debugging stage, which is not drawn into the winder and is manually drawn to the ground from the third drawing roller.

[0082] Table 3

[0083] Primary draw ratio 1 times Secondary draw ratio 1 times First draw roll speed 8 m / s Second draw roll speed 8 m / s Third draw roll speed 8 m / s

[0084] The speed and draw ratio of the first drawing roller, the second drawing roller and the third drawing roller are continuously adjusted as shown in Tables 4 and 5 below, so that the pre-crystallized monofilament is drawn through the first drawing roller and the second drawing roller, and then further drawn through the second drawing roller and the third drawing roller, and the monofilament is stably drawn for 15 s.

[0085] Table 4

[0086] First draw roll speed 8 m / s Second draw roll speed 16 m / s Third draw roll speed 72 m / s

[0087] Step (4): The laser diameter measuring tension winder is opened and the winding line speed is set to 6 m / min. The monofilament stably drawn for 15 s is drawn into the winder for winding. When 1 kg of material is completely extruded (i.e. no material is extruded from the extruder), the winder is closed. The plastic nut is rotated counterclockwise and the spool is removed, completing the spool winding, to obtain the medical polyhydroxyalkanoate monofilament product.

[0088] III. Yield calculation:

[0089] The weight m1 of the empty spool is weighed using a high-precision electronic scale. The weight m2 of the wound spool is weighed using a high-precision electronic scale.

[0090] The yield and material loss rate are obtained according to the following formula, and the experimental data are shown in Table 5 below.

[0091]

[0092] Loss rate x = (1-y)*100%

[0093] IV. Post-processing:

[0094] Turn off the power of the winding machine.

[0095] Turn off the power of the stretching machine and close the air pipe.

[0096] Turn off the power of the heating rod and take it out of the water tank.

[0097] After confirming that all materials are extruded from the extruder, turn off the power of the extruder.

[0098] V. Equipment cleaning:

[0099] Clean the sanitation.

[0100] Clean the scattered granular materials and garbage around the extruder.

[0101] Clean the waste materials in the die head of the extruder and the water tank below.

[0102] Open the drain switch and drain the water in the water tank.

[0103] Clean the waste silk on the stretching machine, the winding machine and the ground.

[0104] Clean the sanitation around the equipment.

[0105] Test Example 1

[0106] In this test example, the breaking strength, maximum load, linear density and breaking elongation of the medical polyhydroxyalkanoate filaments obtained in Examples 1-17 were measured by using the conventional methods in the art, and the experimental results are shown in Table 5.

[0107] Table 5

[0108]

[0109]

[0110] As can be seen from the above Table 5, the medical polyhydroxyalkanoate filaments provided by Examples 1-17 of the present application have high strength and high toughness, and the components of the medical polyhydroxyalkanoate filaments only have a single PHA without any auxiliary agent and additive, and the problem of complex and long-term clinical research does not occur, and the medical polyhydroxyalkanoate filaments can be truly applied to the clinic.

[0111] Test Example 2

[0112] The test example first knits the medical polyhydroxyalkanoate monofilament obtained in Example 1 of the application into warp-knitted patches by using the existing conventional warp-knitting method in the art, and two batches of warp-knitted patches, i.e., 0818 batch and 0825 batch, are knitted, wherein the knitting structure of the 0818 batch is relatively loose, and the knitting density of the 0825 batch is increased, the loop structure is more regular, and the knitting structure is relatively tight. Then, the two batches of warp-knitted patches are heat-pressed and shaped by using a setting machine, wherein the temperature of heat-pressing and shaping is 90°C, the time is 72h, and the weight of the weight used is 25kg. The effect pictures of the 0818 batch of warp-knitted patches before and after heat-pressing and shaping are shown in Figure 2a and Figure 2b respectively, and the effect pictures of the 0825 batch of warp-knitted patches before and after heat-pressing and shaping are shown in Figure 2c and Figure 2d respectively.

[0113] It can be seen from Figure 2a and Figure 2c that the 0818 batch of warp-knitted patches and the 0825 batch of warp-knitted patches before heat-pressing and shaping all have problems of different degrees of edge curling, rolling and cutting off residues. By comparing Figure 2a and Figure 2b and Figure 2c and Figure 2d it can be found that after the warp-knitted patches are heat-pressed and shaped, the edge curling phenomenon is significantly improved, and the cutting off residue phenomenon is also improved.

[0114] The existing conventional test method in the art is used to measure the load, tensile strength and elongation and other performance parameters of the 0818 batch of warp-knitted patches before heat-pressing and shaping and the 0825 batch of warp-knitted patches before and after heat-pressing and shaping, respectively, wherein the experimental results of the 0818 batch of warp-knitted patches and the 0825 batch of warp-knitted patches are shown in Tables 6 and 7 respectively.

[0115] Table 6

[0116]

[0117] Table 7

[0118]

[0119] By comparing the experimental data in Tables 6 and 7, it can be known that the tensile load of the 0818 batch of warp-knitted patch samples fluctuates too much, and the maximum elongation at break is too high, while the tensile strength of the 0825 batch of warp-knitted patch samples fluctuates less, and the elongation is significantly improved.

[0120] It can be known from the experimental data in Table 7 that heat-pressing treatment can improve the tensile strength of the patch.

[0121] YY / T_1816-2022_Surgical Implants-Synthetic Nonabsorbable Mesh-Dural (Spinal) Patch The industry standard stipulates that the tensile strength should be ≥4MPa, the suture strength should be ≥15N, and the elongation at break should be ≥30%. From the experimental data in Table 7, it can be seen that the 0825 batch of warp-knitted patches after hot pressing meet the requirements of the industry standard.

[0122] YY / T_1814-2022_Surgical Implants-Synthetic Nonabsorbable Mesh-Hernia Repair Patch The industry standard stipulates that the longitudinal and transverse tensile strength should be ≥16N / cm (the tensile force that the patch unit width or length can withstand), and the suture strength / tear strength should be ≥16N. According to the calculation of the experimental data in Table 7, the longitudinal tensile strength of the 0825 batch of samples after hot pressing is 20.49N / cm, which meets the requirements of the industry standard.

[0123] In summary, the medical polyhydroxyalkanoate monofilament prepared by the medical polyhydroxyalkanoate single raw material provided by the embodiment of the present application only has a single PHA, without any auxiliary agent and additive, and the monofilament has high strength and high toughness. The medical polyhydroxyalkanoate monofilament provided by the embodiment of the present application can maintain a certain strength for a long time during clinical use, which is beneficial to tissue repair. In addition, the degradation time of the medical polyhydroxyalkanoate monofilament provided by the embodiment of the present application is consistent with the tissue repair time, so that it has a wide application prospect in the field of tissue repair.

[0124] The embodiment of the present application overcomes the problem that the prior art can only use a multi-component raw material mixture to make the strength and toughness of the obtained monofilament meet the requirements, successfully realizes drawing of a single medical PHA material, so that the obtained monofilament only has a single PHA, and can maintain corresponding strength and toughness, thereby laying a solid foundation for clinical conversion and application of the monofilament.

[0125] Those skilled in the art can understand that the features described in various embodiments and / or claims of the present application can be combined or / and combined, even if such combination or combination is not explicitly described in the present application. In particular, the features described in various embodiments and / or claims of the present application can be combined and / or combined in various combinations without departing from the spirit and teachings of the present application. All these combinations and / or combinations fall within the scope of the present application.

[0126] The embodiments of the present invention have been described above. However, these embodiments are merely illustrative and not intended to limit the scope of the invention. Although various embodiments have been described above, this does not mean that the measures in the various embodiments cannot be used advantageously in combination. The scope of the invention is defined by the appended claims and their equivalents. Various substitutions and modifications can be made by those skilled in the art without departing from the scope of the invention, and all such substitutions and modifications should fall within the scope of the invention.

Claims

1. A method for producing a medical polyhydroxyalkanoate filament, characterized by, The preparation method comprises: Step (1): preparing monofilament by melt extrusion method with medical polyhydroxyalkanoate as raw material; Step (2): immersing the monofilament into hot water at 40-60℃ to obtain pre-crystallized monofilament; Step (3): drawing the pre-crystallized monofilament by 5-20 times to obtain drawn monofilament; Step (4): winding the drawn monofilament to obtain medical polyhydroxyalkanoate monofilament product.

2. The production method according to claim 1, characterized by, The medical polyhydroxyalkanoate has a molecular weight ranging from 50,000 to 1,000,000.

3. The production method according to claim 1 or 2, characterized by, The medical polyhydroxyalkanoate comprises PHB, P34HB or PHBHHX, preferably P34HB.

4. The production method according to claim 1 or 2, characterized by, Step (1) specifically comprises: melt extruding the medical polyhydroxyalkanoate raw material through the barrel 1 zone, the barrel 2 zone and the barrel 3 zone of the single screw extruder in sequence to obtain monofilament; The temperatures of the barrel 1 zone, the barrel 2 zone and the barrel 3 zone are different, and the temperature ranges are all 145-200℃.

5. The preparation method according to claim 1, characterized in that, In step (2), the water entry length of the monofilament ranges from 40cm to 120cm during the immersion process.

6. The production method according to claim 1 or 5, characterized by, In step (2), the water entry depth of the monofilament ranges from 1cm to 3cm during the immersion process.

7. The preparation method according to claim 1, characterized in that, In step (3), the drawing is two-stage drawing, wherein the speed of the first drawing roller is 5-20m / s, the speed of the second drawing roller is 5-20m / s, and the speed of the third drawing roller is 5-20m / s.

8. The production method according to claim 1 or 7, characterized by, In step (3), the drawing multiple of the first-stage drawing is 1-4 times, and the drawing multiple of the second-stage drawing is 2-5 times.

9. The production method according to claim 1 or 2, characterized by, In step (4), the linear speed of the winding is 2-20m / min.

10. A medical polyhydroxyalkanoate monofilament prepared by the preparation method of the medical polyhydroxyalkanoate monofilament according to any one of claims 1-9.

11. Use of the medical polyhydroxyalkanoate monofilament according to claim 10 as base wire in preparing medical devices.

12. Use according to claim 11, characterized in that, The medical devices comprise absorbable surgical sutures, hernia patches, artificial blood vessels, artificial esophagi or embolism springs.

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