In-situ compatibilization method of polylactic acid / polycaprolactone composite material and application thereof

Abstract

The invention discloses an in-situ compatibilization method of a polylactic acid / polycaprolactone composite material and application of the polylactic acid / polycaprolactone composite material, and belongs to the field of polymer biomedical materials. The preparation method comprises the following steps: preparing polycaprolactone from caprolactone and tetraphenyltin; then polycaprolactone is subjected to end capping with dimethyl carbonate, then the polycaprolactone subjected to end capping is compounded with polylactic acid, and the polylactic acid / polycaprolactone composite material is prepared. Polycaprolactone is terminated by non-toxic dimethyl carbonate with good biocompatibility, and in-situ compatibilization with polylactic acid can be realized by high reactivity of a terminal carbonate group under strong shearing action, so that in a compatibilization-free system, the mechanical property of the polylactic acid / polycaprolactone composite material is optimized, cell proliferation and growth are promoted, and the polylactic acid / polycaprolactone composite material has good biocompatibility. The biocompatibility reduction and the mechanical property loss of a composite material in a non-compatibilization system caused by the addition of a small-molecule blending compatibilizer can be avoided, and the composite material can be well applied to the field of medical materials such as biomedical sutures.

Description

Technical Field

[0001] The invention belongs to the field of polymer biomedical materials, and in particular relates to an in-situ volume expansion method of a polylactic acid / polycaprolactone medical polymer material and its application in the field of absorbable sutures. Background Art

[0002] Medical sutures are essential medical devices in clinical surgery, and have important functions such as suturing larger wounds and promoting tissue closure. However, the non-absorbability of traditional medical sutures also makes patients vulnerable to secondary injuries. With the development of polymer materials with good biocompatibility and the interaction between biological science and material science, new synthetic fibers such as polylactic acid, polyglycolic acid, polycaprolactone, polytrimethylene carbonate and other absorbable sutures have gradually become good substitutes for traditional non-absorbable sutures such as nylon and polypropylene.

[0003] Polylactic acid is a typical type of biodegradable polyester. It can be made from biomass renewable resources such as corn and straw through hydrolysis, enzymolysis, saccharification, fermentation, polymerization and other steps. It has excellent mechanical strength, biocompatibility and degradability. It has become the preferred material for absorbable medical sutures. However, due to the presence of side chain methylene, the strong molecular rigidity of polylactic acid leads to poor ductility during fiberization and a long degradation cycle, making it difficult to perfectly meet the industry requirements for absorbable medical sutures. Based on this, when polylactic acid is compounded with high molecular materials such as polytrimethylene carbonate and polycaprolactone that have excellent ductility, biocompatibility and faster degradation rate, the ductility of the composite material can be optimized while shortening its degradation cycle, thereby expanding the application of polylactic acid-based composite materials.

[0004] However, due to the existence of phase separation phenomenon, when polylactic acid and degradable materials such as polycaprolactone are directly compounded, there will be problems such as significant decrease in mechanical properties, which is difficult to be fully promoted. Therefore, it is usually necessary to mix maleic anhydride (CN117328162), styrene-acrylonitrile (CN 115322543) and other compatibilizers with polylactic acid and polycaprolactone together and then put them into a twin screw to prepare a composite material. Although the use of the above-mentioned compatibilizer can achieve the optimization of composite material performance, the addition of the compatibilizer will cause the biocompatibility of polylactic acid / polycaprolactone composite material to decrease, thereby reducing the application of polylactic acid / polycaprolactone in the field of biomedical materials.

[0005] Therefore, how to ensure the compatibility of the two phases of the polylactic acid / polycaprolactone composite material without reducing its biocompatibility has become a key technical issue for the widespread application of polylactic acid / polycaprolactone polymer composite materials in the field of absorbable medical sutures. Summary of the invention

[0006] The first purpose of the present invention is to provide an in-situ volume expansion method for a polylactic acid / polycaprolactone composite material, which can effectively solve the disadvantage that the mechanical properties of traditional polylactic acid and polycaprolactone are significantly reduced when they are compounded.

[0007] The second object of the present invention is to provide a polylactic acid / polycaprolactone composite material without adding a compatibilizer, which can effectively avoid the addition of a compatibilizer that will cause the biocompatibility of the polylactic acid / polycaprolactone composite material to decrease.

[0008] The third purpose of the present invention is to propose an application of a polylactic acid / polycaprolactone composite material in a biomedical suture, which can promote cell proliferation and growth without losing the mechanical properties of the material.

[0009] In order to solve the above problems, the technical solution adopted by the present invention is as follows:

[0010] The invention discloses an in-situ volume expansion method for a polylactic acid / polycaprolactone composite material, comprising the steps of capping polycaprolactone with dimethyl carbonate, mixing the capped polycaprolactone with polylactic acid, extruding the mixture by a temperature-controlled twin-screw extruder, and performing subsequent treatment to prepare the polylactic acid / polycaprolactone composite material.

[0011] Furthermore, the polycaprolactone is prepared by reaction with caprolactone as a raw material under the catalysis of tetraphenyltin; the amount of the tetraphenyltin used is 0.01-1000ppm of the mass of the caprolactone.

[0012] Furthermore, the temperature required for preparing polycaprolactone from caprolactone and tetraphenyltin is 160° C. to 200° C., and the time required is 8 to 12 hours.

[0013] Furthermore, the molar ratio of the polycaprolactone to dimethyl carbonate is 1:0.1-0.5.

[0014] Furthermore, the temperature required for the dimethyl carbonate to cap the polycaprolactone is 150-190° C., and the time required is 15-20 hours.

[0015] Furthermore, the amount of the blocked polycaprolactone is 1:0.1 to 100 of the mass of the polylactic acid.

[0016] Furthermore, the in-situ volume expansion method of any of the above-mentioned polylactic acid / polycaprolactone composite materials comprises the following steps:

[0017] (1) heating caprolactone and tetraphenyltin to 160-200° C. under nitrogen protection and reacting for 8-12 hours to prepare polycaprolactone;

[0018] (2) adding dimethyl carbonate to the polycaprolactone prepared in step (1), and reacting under reflux at 150-190° C. for 15-20 hours, discharging excess unreacted dimethyl carbonate from a polycondensation pipeline, and granulating and drying the obtained carbonate-terminated polycaprolactone for later use;

[0019] (3) The carbonate-terminated polycaprolactone obtained in step (2) and granulated and dried is mixed with polylactic acid in a mass ratio of 1:0.1 to 100, and then added into a twin-screw, processed at 190 to 210° C., and then water-cooled, granulated, and dried to obtain a polylactic acid / polycaprolactone composite material.

[0020] Furthermore, the polylactic acid / polycaprolactone composite material prepared by any of the above methods has the following molecular structure:

[0021]

[0022] Wherein, X represents the degree of polymerization of polycaprolactone, ranging from 100 to 1000; Y represents the degree of polymerization of polylactic acid, ranging from 100 to 2500.

[0023] Furthermore, the polylactic acid / polycaprolactone composite material is used in medical materials.

[0024] Furthermore, the medical material is a biomedical suture.

[0025] Compared with the prior art, the advantages of the present invention are as follows:

[0026] 1) The present invention introduces dimethyl carbonate, which is almost non-toxic and has excellent biocompatibility, into the polylactic acid / polycaprolactone composite material, which can further improve the macroscopic properties of the polylactic acid / polycaprolactone composite material while still maintaining its original good biocompatibility, thereby avoiding the problem of the composite material being limited in the field of absorbable medical sutures due to the use of small molecule expanders.

[0027] 2) The polylactic acid / polycaprolactone composite material prepared by the present invention can well solve the disadvantage that the mechanical properties of traditional polylactic acid and polycaprolactone will be significantly reduced when they are compounded. On the premise of retaining the original mechanical properties, it can greatly improve the cell survival rate, and the cell survival rate can reach up to 109.6%.

[0028] 3) The present invention uses dimethyl carbonate to end-cap polycaprolactone, and utilizes the high reactivity and structural similarity of the carbonate group to achieve in-situ compatibility of carbonate-end-capped polycaprolactone and polylactic acid, which can effectively avoid the addition of a compatibilizer that will lead to a decrease in the biocompatibility of the polylactic acid / polycaprolactone composite material. BRIEF DESCRIPTION OF THE DRAWINGS

[0029] Figure 1 The molecular structure diagram of the polylactic acid / polycaprolactone composite material with in-situ volume expansion effect of the present invention;

[0030] Wherein, X represents the degree of polymerization of polycaprolactone, ranging from 100 to 1000; Y represents the degree of polymerization of polylactic acid, ranging from 100 to 2500. DETAILED DESCRIPTION

[0031] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with specific embodiments.

[0032] The polylactic acid used in the following examples and comparative examples is a commercially available product, model number Natureworks 4032D; other raw materials, reagents, instruments and equipment used, unless otherwise specified, are commercially available products or obtained according to the prior art.

[0033] The test method is as follows:

[0034] Mechanical properties test: The mechanical properties test standard of polylactic acid / polycaprolactone composite materials is tested in accordance with ISO 527-2019.

[0035] Cytotoxicity test: The cytotoxicity test standard of polylactic acid / polycaprolactone composite materials is tested in accordance with ISO20993-5-2009 standard.

[0036] Example 1

[0037] An in-situ volume expansion method for a polylactic acid / polycaprolactone composite material, comprising the following steps:

[0038] (1) 3 kg of caprolactone and 1.5 g of tetraphenyltin were placed in a 5 L polymerization reactor protected by nitrogen, the temperature was raised to 200° C., and the reaction was carried out for 10 hours to prepare polycaprolactone;

[0039] (2) adding 0.5 kg of dimethyl carbonate to the polymerization kettle of the polycaprolactone prepared in step (1), and reacting under reflux at 180° C. for 20 h, discharging the excess unreacted dimethyl carbonate from the polycondensation pipeline, and granulating and drying the obtained carbonate-terminated polycaprolactone for later use;

[0040] (3) After being granulated and dried, 0.3 kg of carbonate-terminated polycaprolactone and 0.7 kg of polylactic acid obtained in step (2) are fully mixed and added into a twin-screw, processed at 200° C., and then water-cooled, granulated, and dried to obtain white particles, namely, polylactic acid / polycaprolactone composite materials.

[0041] The prepared polylactic acid / polycaprolactone composite material was subjected to mechanical property tests and cytotoxicity tests, and the test results are shown in Table 1.

[0042] Example 2

[0043] An in-situ volume expansion method for a polylactic acid / polycaprolactone composite material, comprising the following steps:

[0044] (1) 3 kg of caprolactone and 0.3 g of tetraphenyltin were placed in a 5 L polymerization reactor protected by nitrogen, the temperature was raised to 200° C., and the reaction was carried out for 10 hours to prepare polycaprolactone;

[0045] (2) adding 0.7 kg of dimethyl carbonate to the polymerization kettle of the polycaprolactone prepared in step (1), and subjecting the mixture to reflux reaction at 180° C. for 15 h, discharging the excess unreacted dimethyl carbonate from the polycondensation pipeline, and granulating and drying the obtained carbonate-terminated polycaprolactone for later use;

[0046] (3) After being granulated and dried, 0.2 kg of carbonate-terminated polycaprolactone obtained in step (2) and 0.8 kg of polylactic acid are fully mixed, added into a twin-screw, processed at 200° C., and then water-cooled, granulated, and dried to obtain white particles, namely, polylactic acid / polycaprolactone composite materials.

[0047] The prepared polylactic acid / polycaprolactone composite material was subjected to mechanical property tests and cytotoxicity tests, and the test results are shown in Table 1.

[0048] Comparative Example 1

[0049] A method for preparing a polylactic acid / polycaprolactone composite material, comprising the following steps:

[0050] (1) 3 kg of caprolactone and 1.5 g of tetraphenyltin were placed in a 5 L polymerization reactor protected by nitrogen, the temperature was raised to 200° C., and the reaction was carried out for 10 hours to prepare polycaprolactone;

[0051] (2) 0.3 kg of polycaprolactone and 0.7 kg of polylactic acid which have not been end-capped, granulated and dried in step (1) are fully mixed and added into a twin-screw extruder, processed at 200° C., and then water-cooled, granulated and dried to obtain white particles, namely the polylactic acid / polycaprolactone composite material.

[0052] The prepared polylactic acid / polycaprolactone composite material was subjected to mechanical property tests and cytotoxicity tests, and the test results are shown in Table 1.

[0053] Comparative Example 2

[0054] A method for preparing a polylactic acid / polycaprolactone composite material, comprising the following steps:

[0055] (1) 3 kg of caprolactone and 1.5 g of tetraphenyltin were placed in a 5 L polymerization reactor protected by nitrogen, the temperature was raised to 200° C., and the reaction was carried out for 10 hours to prepare polycaprolactone;

[0056] (2) 0.3 kg of polycaprolactone, 0.7 kg of polylactic acid and 0.01 kg of Joncryl ADR 4370S type compatibilizer which are not end-capped, granulated and dried in step (1) are fully mixed and added into a twin-screw extruder, processed at 200° C., and then water-cooled, granulated and dried to obtain white particles, namely the polylactic acid / polycaprolactone composite material.

[0057] The prepared polylactic acid / polycaprolactone composite material was subjected to mechanical property tests and cytotoxicity tests, and the test results are shown in Table 1.

[0058] Comparative Example 3

[0059] A method for preparing a polylactic acid / polycaprolactone composite material, comprising the following steps:

[0060] (1) 3 kg of caprolactone and 1.5 g of tetraphenyltin were placed in a 5 L polymerization reactor protected by nitrogen, the temperature was raised to 200° C., and the reaction was carried out for 10 hours to prepare polycaprolactone;

[0061] (2) 0.3 kg of polycaprolactone, 0.7 kg of polylactic acid and 0.01 kg of POSSepoxy 8 type extender which are not end-capped, granulated and dried in step (1) are fully mixed and added into a twin screw, processed at 200° C., and then water-cooled, granulated and dried to obtain white particles, namely the polylactic acid / polycaprolactone composite material.

[0062] The prepared polylactic acid / polycaprolactone composite material was subjected to mechanical property tests and cytotoxicity tests, and the test results are shown in Table 1.

[0063] Comparative Example 4

[0064] A method for preparing a polylactic acid / polycaprolactone composite material, comprising the following steps:

[0065] (1) 3 kg of caprolactone and 1.5 g of tetraphenyltin were placed in a 5 L polymerization reactor protected by nitrogen, the temperature was raised to 200° C., and the reaction was carried out for 10 hours to prepare polycaprolactone;

[0066] (2) 0.3 kg of polycaprolactone, 0.7 kg of polylactic acid and 0.01 kg of maleic anhydride type compatibilizer which are not end-capped, granulated and dried in step (1) are fully mixed and added into a twin screw, processed at 200° C., and then water-cooled, granulated and dried to obtain white particles, namely the polylactic acid / polycaprolactone composite material.

[0067] The prepared polylactic acid / polycaprolactone composite material was subjected to mechanical property tests and cytotoxicity tests, and the test results are shown in Table 1.

[0068] Table 1 Comparison of the performance test results of the polylactic acid / polycaprolactone composite materials prepared in Examples 1 to 2 and Comparative Examples 1 to 4

[0069] Tensile strength at break MPa Elongation at break % Cell survival rate% Example 1 37.5 19.9 109.6 Example 2 39.3 16.0 108.1 Comparative Example 1 24.6 7.7 104.5 Comparative Example 2 38.4 23.1 84.8 Comparative Example 3 37.5 17.3 90.1 Comparative Example 4 34.3 35.2 47.2

[0070] It can be seen from the data in Table 1 that, compared with Comparative Examples 1 to 4, when Examples 1 to 2 use non-toxic and biocompatible dimethyl carbonate to end-cap polycaprolactone, the high reactivity of the terminal carbonate group can achieve in-situ volume expansion with polylactic acid under strong shearing action, thereby optimizing the mechanical properties of the polylactic acid / polycaprolactone composite material in a non-volatilized system, and promoting cell proliferation and growth, which can avoid the problems of decreased biocompatibility caused by the addition of small molecule blending expanders and loss of mechanical properties of the composite material in a non-volatilized system.

[0071] The polylactic acid / polycaprolactone composite material prepared by the present invention can well solve the disadvantage that the mechanical properties will be significantly reduced when the traditional polylactic acid and polycaprolactone are compounded. On the premise of retaining the original mechanical properties, it can greatly improve the cell survival rate, and the cell survival rate can be as high as 109.6%. It can be used in biomedical sutures among medical materials and has good biocompatibility.

[0072] The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. An in-situ volume expansion method for a polylactic acid / polycaprolactone composite material, characterized in that: The polycaprolactone is end-capped with dimethyl carbonate, and then the end-capped polycaprolactone is mixed with polylactic acid, extruded by a temperature-controlled twin-screw extruder, and subjected to subsequent treatment to prepare a polylactic acid / polycaprolactone composite material.

2. The in-situ volume expansion method of the polylactic acid / polycaprolactone composite material according to claim 1, characterized in that: The polycaprolactone is prepared by reaction with caprolactone as raw material under the catalysis of tetraphenyltin; the amount of the tetraphenyltin is 0.01-1000ppm of the mass of the caprolactone.

3. The in-situ volume expansion method of the polylactic acid / polycaprolactone composite material according to claim 2, characterized in that: The temperature required for preparing polycaprolactone from caprolactone and tetraphenyltin is 160° C. to 200° C., and the time required is 8 to 12 hours.

4. The in-situ volume expansion method of the polylactic acid / polycaprolactone composite material according to claim 1, characterized in that: The molar ratio of the polycaprolactone to dimethyl carbonate is 1:0.1-0.

5.

5. The in-situ volume expansion method of the polylactic acid / polycaprolactone composite material according to claim 1, characterized in that: The temperature required for the dimethyl carbonate to cap the polycaprolactone is 150-190° C. and the time required is 15-20 hours.

6. The in-situ volume expansion method of the polylactic acid / polycaprolactone composite material according to claim 1, characterized in that: The amount of the blocked polycaprolactone is 1:0.1 to 100 of the mass of the polylactic acid.

7. The in-situ volume expansion method of the polylactic acid / polycaprolactone composite material according to any one of claims 1 to 6, characterized in that: Here are the steps: (1) heating caprolactone and tetraphenyltin to 160-200° C. under nitrogen protection and reacting for 8-12 hours to prepare polycaprolactone; (2) adding dimethyl carbonate to the polycaprolactone prepared in step (1), and reacting under reflux at 150-190° C. for 15-20 hours, discharging excess unreacted dimethyl carbonate from a polycondensation pipeline, and granulating and drying the obtained carbonate-terminated polycaprolactone for later use; (3) The carbonate-terminated polycaprolactone obtained in step (2) and granulated and dried is mixed with polylactic acid in a mass ratio of 1:0.1 to 100, and then added into a twin-screw, processed at 190 to 210° C., and then water-cooled, granulated, and dried to obtain a polylactic acid / polycaprolactone composite material.

8. A polylactic acid / polycaprolactone composite material prepared by the method according to any one of claims 1 to 7, characterized in that: The molecular structure is as follows: Wherein, X represents the degree of polymerization of polycaprolactone, ranging from 100 to 1000; Y represents the degree of polymerization of polylactic acid, ranging from 100 to 2500.

9. Use of the polylactic acid / polycaprolactone composite material according to claim 8 in medical materials.

10. The use according to claim 9, characterized in that: The medical material is a biomedical suture.

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