Low-irritation modified poly-L-lactic acid capable of promoting tissue regeneration and application of modified poly-L-lactic acid in medical beauty injection reagent

Abstract

The invention provides modified poly-L-lactic acid and application thereof in a medical beauty injection reagent. According to the invention, a binary composite catalyst MnO2 / Cr2O3 and a ternary composite catalyst TiO2 / ZnO / SnO2 are synthesized. The two catalysts are relatively stable in performance as inorganic catalysts and have no biotoxicity. MnO2 / Cr2O3 is used for synthesizing lactide from lactic acid, so that the yield of L-lactide can be greatly improved. In addition, under the action of a TiO2 / ZnO / SnO2 catalyst, the L-polylactic acid which is modified by chitosan and is easily metabolized by a human body is synthesized through a microwave method. Optical isomers of the polylactic acid comprise L-polylactic acid, D-polylactic acid and racemic polylactic acid. Only dehydrogenase capable of metabolizing L-lactic acid exists in a human body, and the synthesized modified L-polylactic acid can be applied to medical beauty injection reagents.

Description

Technical Field

[0001] The present invention belongs to the field of biomedical materials and relates to a modified L-polylactic acid, and in particular to a modified L-polylactic acid and its application in medical beauty injection reagents. Background Art

[0002] Poly-L-lactic acid (PLLA) is a new type of injectable skin filler material that can slowly degrade into carbon dioxide and water in soft tissue, activating fibroblasts to stimulate collagen formation. Recent studies have found that even if PLLA has been degraded in the body in the long term, the proliferating collagen fibers can still play a filling role, with long-term effectiveness and safety. PLLA filling can be used for facial rejuvenation in dermatology and medical cosmetology to treat facial volume tissue loss and reduce facial wrinkles, and has broad development and application potential.

[0003] From the perspective of mechanical properties, the main disadvantages of polylactic acid are hardness, brittleness, and poor impact strength. It is difficult to meet the requirements of certain medical repairs of human parts, which restricts its use. At present, the main application field is biomedical materials. Due to the slow degradation rate of PLLA, the long-term presence of undegraded parts produces side effects, and sometimes produces aseptic inflammation locally. Under natural conditions, it degrades slowly, and the controlled release system of polymer drugs requires different degradation rates for different drugs. PLLA has better biocompatibility, and is also a material with extremely strong rigidity and lack of toughness, which is difficult to meet the requirements of use. Therefore, in recent years, the modification of polylactic acid has become a hot topic of research. At present, there are several methods for modifying polylactic acid at home and abroad, such as blending, copolymerization, and making composite materials. The hardness and brittleness of polylactic acid materials are its significant disadvantages. In order to improve this mechanical property, the commonly used modification method is blending. The slow crystallization rate of polylactic acid and the low softening temperature limit its application field. People shorten the setting time in material molding and improve the heat resistance of the material by adding nucleating agents. The degradation and aging process of polylactic acid is affected by factors such as the product's shape, crystallinity, thermal history of the manufacturing process, and monomer copolymerization ratio. In order to control the specific degradation rate and residual strength of polylactic acid, the copolymerization method mainly includes copolymerization of left-handed monomers with a small amount of racemates. In addition, nanomaterials are also used to modify polylactic acid. Nanoparticles, as crystallization nucleating agents, increase the crystallization rate and crystallinity of polylactic acid, reduce the grain size, and improve the mechanical properties.

[0004] In view of the defects and shortcomings of the tin catalyst stannous octoate, the present invention synthesizes a binary composite catalyst MnO2 / Cr2O3 and a ternary composite catalyst TiO2 / ZnO / SnO2. The MnO2 / Cr2O3 binary catalyst is applied to the lactic acid synthesis lactide reaction to improve the yield of L-lactide. Then, under the action of the TiO2 / ZnO / SnO2 catalyst, chitosan-modified L-polylactic acid is synthesized by microwave method. The modified L-polylactic acid synthesized by the present invention can be used in medical beauty injection reagents. Summary of the invention

[0005] In view of the above problems, the present invention provides a chitosan-modified L-polylactic acid. A binary composite catalyst MnO2 / Cr2O3 and a ternary composite catalyst TiO2 / ZnO / SnO2 are synthesized. These two catalysts are relatively stable as inorganic catalysts and do not have the biological toxicity of the commonly used catalyst stannous octoate.

[0006] The present invention provides a modified L-polylactic acid and its application in medical beauty injection reagents. The specific preparation steps are as follows: S1. Weigh 2.8-3.6 g of dried MnO2 and 0.6-0.9 g of Cr2O3, grind them evenly with a mortar and put them into a corundum boat. Then place the corundum boat in the center of the tube furnace tube, pass nitrogen for 30 min, heat it to 150-200°C at 2-4°C / min, and keep it for 1-2h. Then heat it to 350-400°C at 4-5°C / min, and keep it for 1-2h. Finally, heat it to 550-600°C at 2-4°C / min, and keep it for 5-6 h. After the reaction is completed, the rod-shaped binary composite catalyst MnO2 / Cr2O3 can be obtained after cooling to room temperature. In this step, the addition of Cr2O3 changes the structure of manganese dioxide from flake to rod-shaped. This rod-shaped structure increases the specific surface area and particle dispersion of the MnO2 material, allowing the material to fully contact the reactants, thereby greatly improving the catalytic performance of the material.

[0007] S2. Add 100-150 mL of lactic acid and 0.5-1 g of zeolite to a 500 mL single-necked flask, and add 2-3 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1. Heat the mixture at a vacuum degree of 450-500 Pa and a temperature of 90-100 °C for 3-4 h, then raise the temperature to 120-140 °C and continue heating for 4-5 h. Adjust the vacuum degree to 600-700 Pa, raise the temperature to 220-250 °C for 1-2 h, then lower the temperature to 80 °C to obtain crude lactide. Stir the crude lactide and ethyl acetate at a mass volume ratio of 1 g:6 mL at 55 °C until the lactide is completely dissolved. Let stand to room temperature, then put the mixture in a refrigerator for cooling and crystallization for 8-10 h. After complete crystallization, filter the mixture and vacuum dry it at 60-80 °C to constant weight. Recrystallize 3-4 times and dry in a vacuum drying oven at 60-80°C to constant weight to obtain L-lactide. In this step, the binary catalyst prepared in step S1 is applied to the reaction of synthesizing lactide from lactic acid to increase the yield of L-lactide.

[0008] S3, weigh 8-10 ml of tetrabutyl titanate, 2-4 mg of tin nitrate powder, and 4-8 mg of zinc acetate powder, mix and add to 60-70 mL of aqueous solution, mix evenly and transfer to a 150 mL reactor, react at 160-200°C for 20-24 hours, let it cool naturally to room temperature, then filter with distilled water and anhydrous ethanol in turn, wash and collect the samples, and then dry them in a constant temperature drying oven at 60-80°C for 12-20 hours to obtain a thin film morphology of the ternary composite catalyst TiO2 / ZnO / SnO2. In this step, TiO2 has good stability and reducibility, as well as the advantages of high catalytic efficiency. ZnO and SnO2 have similar properties to TiO2, and are all semiconductors. The ternary composite catalyst TiO2 / ZnO / SnO2 synthesized by the three is relatively stable as an inorganic catalyst.

[0009] S4, dissolving 100-120 mg of the L-lactide prepared in step S2 into 10-15 mL of chloroform, dissolving 10-15 mg of chitosan into 8-10 mL of 1% acetic acid aqueous solution, and ultrasonically dispersing 1-3 mg of the ternary composite catalyst TiO2 / ZnO / SnO2 prepared in step S3 into 5-8 mL of ethanol, then adding the above solutions into a 200 mL flask and mixing evenly, preheating in an oil bath at 100-120°C, and putting into a microwave reactor after mixing evenly, setting the power to 200-300 W, the temperature to 100-120°C, and the reaction time to 10-20 min, to obtain crude chitosan-modified L-polylactic acid, and then dissolving the crude chitosan-modified L-polylactic acid into chloroform, and precipitating with anhydrous ethanol to obtain pure chitosan-modified L-polylactic acid. As a polymer material, L-polylactic acid can be slowly degraded into carbon dioxide and water in soft tissues, activating fibroblasts to stimulate the formation of collagen, and it has high mechanical strength, is non-toxic, non-irritating, and has good biocompatibility. In this step, chitosan-modified L-polylactic acid is synthesized by microwaves. The L-polylactic acid molecule contains a large number of active groups such as hydroxyl (-OH) and carboxyl (-COOH), and chitosan contains hydroxyl (-OH) and amino (-NH2). The two can be combined in various forms such as hydrogen bonds, ester bonds, amine bonds, and ionic bonds, so that the modified polylactic acid has good performance and can be used as an injection reagent to become a commonly used medical beauty material in clinical practice.

[0010] Preferably: MnO2, Cr2O3 and lactic acid are purchased from Wuhan Proloff Biotechnology Co., Ltd., ethyl acetate, tetrabutyl titanate, tin nitrate powder and zinc acetate are purchased from Shanxi Zhongnuo Biotechnology Co., Ltd., and chitosan and chloroform are purchased from Shanxi Lake Biotechnology Co., Ltd.

[0011] Preferably: in step S1, 2.8 g of MnO2 and 0.6 g of Cr2O3 after drying are weighed, ground evenly with a mortar, and then placed in a corundum boat; Preferably: in step S1, the corundum boat is placed in the center of the tube furnace, nitrogen is passed through for 30 min, the temperature is increased to 150° C. at 2° C. / min, and maintained for 1 h; Preferably: in step S2, 100 mL of lactic acid is added to a 500 mL single-necked flask; Preferably: 2 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1 is added in step S2; Preferably: in step S3, 8 ml of tetrabutyl titanate, 2 mg of tin nitrate powder, and 4 mg of zinc acetate powder are weighed, mixed, and added to 60 mL of aqueous solution; Preferably: in step S3, the sample is reacted at 160°C for 20 h and then naturally cooled to room temperature; Preferably: in the step S4, 100 mg of the L-lactide prepared in the step S2 is dissolved in 10 mL of chloroform; Preferably, in step S4, the mixture is preheated in a 100°C oil bath, mixed evenly and then placed in a microwave reactor, with the power set to 200W and the temperature set to 100°C.

[0012] Due to the adoption of the above technical solution, the technical progress achieved by the present invention is: 1. The present invention synthesizes a binary composite catalyst MnO2 / Cr2O3 and a ternary composite catalyst TiO2 / ZnO / SnO2. These two catalysts are relatively stable as inorganic catalysts and do not have the biological toxicity of the commonly used catalyst stannous octoate.

[0013] 2. Using MnO2 / Cr2O3 in the synthesis of lactide from lactic acid can increase the yield of L-lactide.

[0014] 3. The optical isomers of polylactic acid include left-handed polylactic acid, right-handed polylactic acid and racemic polylactic acid. Human body only has dehydrogenase that can metabolize left-handed lactic acid. The present invention synthesizes chitosan modified left-handed polylactic acid by microwave method. The left-handed polylactic acid molecule contains a large amount of active groups such as hydroxyl (-OH) and carboxyl (-COOH), and chitosan contains hydroxyl (-OH) and amino (-NH2). Under the action of TiO2 / ZnO / SnO2 catalyst, the two can be combined in various forms such as hydrogen bond, ester bond, amine bond, ionic bond, so that the modified polylactic acid has good performance. BRIEF DESCRIPTION OF THE DRAWINGS

[0015] In order to more clearly illustrate the technical solutions in the embodiments of the present invention, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative labor.

[0016] Figure 1 This is a scanning electron microscope image of the catalyst prepared in step S1 of Example 1 of the present invention.

[0017] Figure 2 It is a scanning electron microscope image of the catalyst prepared in step S1 of comparative example 1 of the present invention.

[0018] Figure 3 This is a scanning electron microscope image of the catalyst prepared in step S3 of Example 3 of the present invention.

[0019] Figure 4 It is a scanning electron microscope image of the catalyst prepared in step S3 of comparative example 5 of the present invention.

[0020] Figure 5 It is a scanning electron microscope image of the catalyst prepared in step S3 of comparative example 6 of the present invention.

[0021] Figure 6 It is a scanning electron microscope image of the catalyst prepared in step S3 of comparative example 7 of the present invention.

[0022] Figure 7 It is a scanning electron microscope image of the modified L-polylactic acid prepared in Example 4 of the present invention.

[0023] Figure 8 It is a scanning electron microscope image of L-polylactic acid prepared in Comparative Example 8 of the present invention. DETAILED DESCRIPTION

[0024] In order to make the technical problems, technical solutions and beneficial effects to be solved by the present invention more clearly understood, the present invention is further described in detail below in conjunction with the accompanying drawings and embodiments. It should be understood that the specific embodiments described herein are only used to explain the content of the present invention and are not used to limit the present invention.

[0025] Example 1

[0026] The present invention provides a modified L-polylactic acid and its application in medical beauty injection reagents. The specific preparation steps are as follows: S1. Weigh 2.8 g of dried MnO2 and 0.6 g of Cr2O3, grind them evenly with a mortar and put them into a corundum boat. Then place the corundum boat in the center of the tube furnace tube, pass nitrogen for 30 min, heat it to 150°C at 2°C / min, and keep it for 1h. Then heat it to 350°C at 4°C / min and keep it for 1h. Finally, heat it to 550°C at 2°C / min and keep it for 5h. After the reaction is completed, the rod-shaped binary composite catalyst MnO2 / Cr2O3 can be obtained after cooling to room temperature. In this step, the addition of Cr2O3 changes the structure of manganese dioxide from flake to rod-shaped. This rod-shaped structure increases the specific surface area and particle dispersion of the MnO2 material, allowing the material to fully contact the reactants, thereby greatly improving the catalytic performance of the material.

[0027] S2. Add 100 mL of lactic acid and 0.5 g of zeolite to a 500 mL single-necked flask, and add 2 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1. Heat at a vacuum degree of 450 Pa and a temperature of 90 ° C for 3 h, then heat to 120 ° C, and continue heating for 4 h. Adjust the vacuum degree to 600 Pa, heat to 220 ° C for 1 h, and then reduce the temperature to 80 ° C to obtain crude lactide. Stir the crude lactide and ethyl acetate at a mass volume ratio of 1g:6mL at 55 ° C until the lactide is completely dissolved. After standing to room temperature, put it in a refrigerator for cooling and crystallization for 8 h. After complete crystallization, filter it and vacuum dry it at 60 ° C to constant weight. Recrystallize it 3 times and dry it in a vacuum drying oven at 60 ° C to constant weight to obtain left-handed lactide. The binary catalyst prepared in step S1 is used in the reaction of synthesizing lactide from lactic acid to increase the yield of left-handed lactide.

[0028] S3, weigh 8 ml of tetrabutyl titanate, 2 mg of tin nitrate powder, and 4 mg of zinc acetate powder, mix and add to 60 mL of aqueous solution, mix evenly and transfer to a 150 mL reactor, react at 160 ° C for 20 h, let it cool naturally to room temperature, then filter with distilled water and anhydrous ethanol in turn, wash and collect the samples, and then dry them in a constant temperature drying oven at 60 ° C for 12 h to obtain a thin film morphology of the ternary composite catalyst TiO2 / ZnO / SnO2. In this step, TiO2 has good stability and reducibility, as well as the advantages of high catalytic efficiency. ZnO and SnO2 have similar properties to TiO2, and are all semiconductors. The ternary composite catalyst TiO2 / ZnO / SnO2 synthesized by the three is relatively stable as an inorganic catalyst.

[0029] S4, dissolving 100 mg of L-lactide prepared in step S2 into 10 mL of chloroform, dissolving 10 mg of chitosan into 8 mL of 1% acetic acid aqueous solution, and ultrasonically dispersing 1 mg of the ternary composite catalyst TiO2 / ZnO / SnO2 prepared in step S3 into 5 mL of ethanol, then adding the above solution into a 200 mL flask and mixing evenly, preheating in a 100°C oil bath, and putting into a microwave reactor after mixing evenly, setting the power to 200 W, the temperature to 100°C, and the reaction time to 10 min, to obtain crude chitosan-modified L-polylactic acid, and then dissolving the crude chitosan-modified L-polylactic acid into chloroform, and precipitating with anhydrous ethanol to obtain pure chitosan-modified L-polylactic acid. As a polymer material, L-polylactic acid can be slowly degraded into carbon dioxide and water in soft tissues, activating fibroblasts to stimulate the formation of collagen, and it has high mechanical strength, is non-toxic, non-irritating, and has good biocompatibility. In this step, chitosan-modified L-polylactic acid is synthesized by microwave. The L-polylactic acid molecule contains a large number of active groups such as hydroxyl (-OH) and carboxyl (-COOH), and chitosan contains hydroxyl (-OH) and amino (-NH2). The two can be combined in various forms such as hydrogen bonds, ester bonds, amine bonds, and ionic bonds. The modified polylactic acid has good performance and can be used as an injectable agent to become a commonly used medical beauty material in clinical practice.

[0030] Comparative Example 1: Except that Cr2O3 is not added in step S1, the rest is the same as Example 1.

[0031] Figure 1 and Figure 2 The scanning electron microscope images of the catalyst prepared in step S1 of Example 1 and Comparative Example 1 are shown respectively. Figure 1 and Figure 2 It can be seen that the sample morphology obtained when Cr2O3 is not added is nano-flake, and the particle dispersion is poor, while the sample with Cr2O3 presents a rod-like structure, and its length is about 0.5~2 μm on average, and most of the product particles can be well dispersed, and agglomeration occurs in a small amount. The existence of Cr2O3 makes the structure of nano manganese dioxide change from sheet to rod-like, and the nano rod-like structure formed is more regular and has a more uniform size. This rod-like structure increases the specific surface area of ​​MnO2 material and the dispersion of particles, so that the material can be fully contacted with reactants, thereby greatly improving the catalytic performance of the material. Therefore, the binary composite catalyst MnO2 / Cr2O3 prepared by Example 1 has advantages in the reaction of synthesizing lactide from lactic acid.

[0032] Example 2

[0033] S1. Weigh 3 g of dried MnO2 and 0.7 g of Cr2O3, grind them evenly with a mortar and put them into a corundum boat. Then place the corundum boat in the center of the tube furnace tube, pass nitrogen for 30 min, heat to 160°C at 3°C / min, and keep for 1h. Then heat to 360°C at 4°C / min and keep for 1h. Finally, heat to 560°C at 2°C / min and keep for 5h. After the reaction is completed, the rod-shaped binary composite catalyst MnO2 / Cr2O3 can be obtained after cooling to room temperature. In this step, the addition of Cr2O3 changes the structure of manganese dioxide from flake to rod-shaped. This rod-shaped structure increases the specific surface area and particle dispersion of the MnO2 material, allowing the material to fully contact the reactants, thereby greatly improving the catalytic performance of the material.

[0034] S2. Add 110 mL of lactic acid and 0.6 g of zeolite to a 500 mL single-necked flask, and add 2 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1. Heat at a vacuum degree of 460 Pa and a temperature of 92 °C for 3 h, then heat to 125 °C, and continue heating for 4 h. Adjust the vacuum degree to 620 Pa, heat to 230 °C for 1 h, and then reduce the temperature to 80 °C to obtain crude lactide. Stir the crude lactide and ethyl acetate at a mass volume ratio of 1g:6mL at 55 °C until the lactide is completely dissolved. After standing to room temperature, put it in a refrigerator for cooling and crystallization for 90 h. After complete crystallization, filter it and vacuum dry it at 65 °C to constant weight. Recrystallize it 3 times and dry it in a vacuum drying oven at 65 °C to constant weight to obtain left-handed lactide. The binary catalyst prepared in step S1 is used in the reaction of synthesizing lactide from lactic acid to increase the yield of left-handed lactide.

[0035] S3, weigh 9 ml of tetrabutyl titanate, 3 mg of tin nitrate powder, and 5 mg of zinc acetate powder, mix and add to 62 mL of aqueous solution, mix well and transfer to a 150 mL reactor, react at 170°C for 21 h, let it cool naturally to room temperature, then filter with distilled water and anhydrous ethanol in turn, wash and collect the samples, and then dry them in a constant temperature drying oven at 65°C for 14 h to obtain a thin film morphology of the ternary composite catalyst TiO2 / ZnO / SnO2. In this step, TiO2 has good stability and reducibility, as well as the advantages of high catalytic efficiency. ZnO and SnO2 have similar properties to TiO2, and are all semiconductors. The ternary composite catalyst TiO2 / ZnO / SnO2 synthesized by the three is relatively stable as an inorganic catalyst.

[0036] S4, dissolve 105 mg of L-lactide prepared in step S2 in 11 mL of chloroform, dissolve 11 mg of chitosan in 9 mL of 1% acetic acid aqueous solution, and ultrasonically disperse 2 mg of the ternary composite catalyst TiO2 / ZnO / SnO2 prepared in step S3 in 6 mL of ethanol, then add the above solution to a 200 mL flask and mix evenly, preheat in a 105°C oil bath, mix evenly and put into a microwave reactor, set the power to 220 W, the temperature to 105°C, and the reaction time to 14 min, to obtain crude chitosan-modified L-polylactic acid, then dissolve the crude chitosan-modified L-polylactic acid in chloroform, and precipitate with anhydrous ethanol to obtain pure chitosan-modified L-polylactic acid. As a polymer material, L-polylactic acid can be slowly degraded into carbon dioxide and water in soft tissues, activate fibroblasts to stimulate the formation of collagen, and has high mechanical strength, non-toxicity, non-irritation and good biocompatibility. In this step, chitosan-modified L-polylactic acid is synthesized by microwave. The L-polylactic acid molecule contains a large number of active groups such as hydroxyl (-OH) and carboxyl (-COOH), and chitosan contains hydroxyl (-OH) and amino (-NH2). The two can be combined in various forms such as hydrogen bonds, ester bonds, amine bonds, and ionic bonds. The modified polylactic acid has good performance and can be used as an injectable agent to become a commonly used medical beauty material in clinical practice.

[0037] Comparative Example 2: Except for replacing the binary composite catalyst MnO2 / Cr2O3 in step S2 with Sn(Oct)2, the rest is the same as Example 2.

[0038] Comparative Example 3: Except for adding 0.5 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in Step S1 in Step S2, the rest is the same as Example 2.

[0039] Comparative Example 4: Except for adding 4 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in Step S1 in Step S2, the rest is the same as Example 2.

[0040] The reaction of lactic acid to lactide is as follows: 2C3H6O3→C6H8O4+2H2O. The volume of lactic acid is 110 mL and the density of lactic acid is 1.2 g / mL. The lactic acid m1 is calculated to be 132 g. The molar mass of each compound is known. m2 is the theoretical mass of crude lactide produced, and m' is the actual mass of lactide produced. m2=(m1×144.125) / (2×90.08), and the crude yield of lactide=m' / m2. Table 1 shows the effect of the catalyst in step S2 of Example 2 and Comparative Examples 2 to 4 on the crude yield of lactide.

[0041] Table 1 project Example 2 Comparative Example 2 Comparative Example 3 Comparative Example 4 Actual crude lactide yield m' (g) 102.6±0.1 72.0±0.1 54.68±0.2 64.53±0.1 Actual crude lactide yield (%) 97.14 68.22 51.74 61.08 The data in Table 1 show that the crude yield and crude yield of lactide obtained after using different types or different amounts of catalysts are different. The binary catalyst prepared in step S1 of Example 2 of the present invention is used in the reaction of synthesizing lactide from lactic acid to improve the yield of left-handed lactide. However, the actual crude yield and crude yield of lactide obtained by replacing the commonly used catalyst Sn(Oct)2 in Comparative Example 2 and changing the amount of binary composite catalyst MnO2 / Cr2O3 in Comparative Examples 3 to 4 are reduced. Therefore, adding an appropriate MnO2 / Cr2O3 catalyst in the reaction of synthesizing lactide from lactic acid increases the crude yield of lactide.

[0042] Example 3

[0043] S1. Weigh 3.2 g of dried MnO2 and 0.8 g of Cr2O3, grind them evenly with a mortar and put them into a corundum boat. Then place the corundum boat in the center of the tube furnace tube, pass nitrogen for 30 min, heat to 180°C at 3°C / min, and keep for 2h. Then heat to 390°C at 5°C / min and keep for 2h. Finally, heat to 580°C at 3°C / min and keep for 6h. After the reaction is completed, the rod-shaped binary composite catalyst MnO2 / Cr2O3 can be obtained after cooling to room temperature. In this step, the addition of Cr2O3 changes the structure of manganese dioxide from flake to rod-shaped. This rod-shaped structure increases the specific surface area and particle dispersion of the MnO2 material, allowing the material to fully contact the reactants, thereby greatly improving the catalytic performance of the material.

[0044] S2. Add 120 mL of lactic acid and 0.7 g of zeolite to a 500 mL single-necked flask, and add 3 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1. Heat at a vacuum degree of 480 Pa and a temperature of 98 ° C for 4 h, then heat to 135 ° C, and continue heating for 5 h. Adjust the vacuum degree to 680 Pa, heat to 240 ° C for 2 h, and then reduce the temperature to 80 ° C to obtain crude lactide. Stir the crude lactide and ethyl acetate at a mass volume ratio of 1g:6mL at 55 ° C until the lactide is completely dissolved. After standing to room temperature, put it in a refrigerator for cooling and crystallization for 9 h. After complete crystallization, filter it and vacuum dry it at 75 ° C to constant weight. Recrystallize it 4 times and dry it in a vacuum drying oven at 70 ° C to constant weight to obtain left-handed lactide. The binary catalyst prepared in step S1 is used in the reaction of synthesizing lactide from lactic acid to increase the yield of left-handed lactide.

[0045] S3, weigh 9 ml of tetrabutyl titanate, 3 mg of tin nitrate powder, and 7 mg of zinc acetate powder, mix and add to 68 mL of aqueous solution, mix evenly and transfer to a 150 mL reactor, react at 180°C for 23 h, let it cool naturally to room temperature, then filter with distilled water and anhydrous ethanol in turn, wash and collect the samples, and then dry them in a constant temperature drying oven at 70°C for 18 h to obtain a thin film morphology of the ternary composite catalyst TiO2 / ZnO / SnO2. In this step, TiO2 has good stability and reducibility, as well as the advantages of high catalytic efficiency. ZnO and SnO2 have similar properties to TiO2, and are all semiconductors. The ternary composite catalyst TiO2 / ZnO / SnO2 synthesized by the three is relatively stable as an inorganic catalyst.

[0046] S4, dissolve 115 mg of L-lactide prepared in step S2 in 12 mL of chloroform, dissolve 14 mg of chitosan in 9 mL of 1% acetic acid aqueous solution, and ultrasonically disperse 2 mg of the ternary composite catalyst TiO2 / ZnO / SnO2 prepared in step S3 in 9 mL of ethanol, then add the above solution to a 200 mL flask and mix evenly, preheat in a 115°C oil bath, mix evenly and put into a microwave reactor, set the power to 280 W, the temperature to 115°C, and the reaction time to 18 min, to obtain crude chitosan-modified L-polylactic acid, then dissolve the crude chitosan-modified L-polylactic acid in chloroform, and precipitate with anhydrous ethanol to obtain pure chitosan-modified L-polylactic acid. As a polymer material, L-polylactic acid can be slowly degraded into carbon dioxide and water in soft tissues, activate fibroblasts to stimulate the formation of collagen, and has high mechanical strength, non-toxicity, non-irritation and good biocompatibility. In this step, chitosan-modified L-polylactic acid is synthesized by microwave. The L-polylactic acid molecule contains a large number of active groups such as hydroxyl (-OH) and carboxyl (-COOH), and chitosan contains hydroxyl (-OH) and amino (-NH2). The two can be combined in various forms such as hydrogen bonds, ester bonds, amine bonds, and ionic bonds. The modified polylactic acid has good performance and can be used as an injectable agent to become a commonly used medical beauty material in clinical practice.

[0047] Comparative Example 5: Except that tetrabutyl titanate is not weighed in step S3, the rest is the same as Example 3.

[0048] Comparative Example 6: Except for weighing 2 ml of tetrabutyl titanate in step S3, the rest is the same as Example 3.

[0049] Comparative Example 7: Except for weighing 12 ml of tetrabutyl titanate in step S3, the rest is the same as Example 3.

[0050] Figures 3 to 6The scanning electron microscope images of the catalyst prepared in step S3 of Example 3 of the present invention and Comparative Examples 5 to 7 are shown. Figures 3 to 6 It can be seen that the overall composite is relatively uniform, and the various substances are closely combined with each other. The composite powder with tetrabutyl titanate added ( Figure 3 and Figures 5 and 6 ) is significantly higher than that without adding tetrabutyl titanate ( Figure 4 ) is well composited, because the powder material with tetrabutyl titanate added has a significant enlargement phenomenon. However, the catalyst powder particles synthesized in Comparative Examples 5 to 7 with tetrabutyl titanate added are uneven, and there is a significant agglomeration phenomenon, which affects the catalytic performance of the composite system. The ternary composite catalyst TiO2 / ZnO / SnO2 prepared in Example 3 appears in an obvious film after adding an appropriate amount of tetrabutyl titanate, but the composite materials in Comparative Example 5 without adding tetrabutyl titanate and Comparative Examples 6 to 7 with changing the amount of tetrabutyl titanate added do not show such a film. It can be seen that the ternary composite catalyst TiO2 / ZnO / SnO2 prepared in Example 3 is the best composited, and such a catalyst is conducive to the synthesis of left-handed polylactic acid.

[0051] Example 4

[0052] S1. Weigh 2.7 g of dried MnO2 and 0.8 g of Cr2O3, grind them evenly with a mortar and put them into a corundum boat. Then place the corundum boat in the center of the tube furnace tube, pass nitrogen for 30 min, heat it to 190℃ at 2~4℃ / min, and keep it for 2h. Then heat it to 390℃ at 5℃ / min and keep it for 2h. Finally, heat it to 590℃ at 4℃ / min and keep it for 6h. After the reaction is completed, the rod-shaped binary composite catalyst MnO2 / Cr2O3 can be obtained after cooling to room temperature. In this step, the addition of Cr2O3 changes the structure of manganese dioxide from flake to rod-shaped. This rod-shaped structure increases the specific surface area and particle dispersion of the MnO2 material, allowing the material to fully contact the reactants, thereby greatly improving the catalytic performance of the material.

[0053] S2. Add 140 mL of lactic acid and 0.9 g of zeolite to a 500 mL single-necked flask, and add 3 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1. Heat at a vacuum degree of 490 Pa and a temperature of 98°C for 4 h, then heat to 138°C, and continue heating for 5 h. Adjust the vacuum degree to 690 Pa, heat to 240°C for 2 h, and then reduce the temperature to 80°C to obtain crude lactide. Stir the crude lactide and ethyl acetate at a mass volume ratio of 1g:6mL at 55°C until the lactide is completely dissolved. After standing to room temperature, put it in a refrigerator for cooling and crystallization for 9 h. After complete crystallization, filter it and vacuum dry it at 75°C to constant weight. Recrystallize it 4 times and dry it in a vacuum drying oven at 78°C to constant weight to obtain left-handed lactide. In this step, the binary catalyst prepared in step S1 is applied to the reaction of synthesizing lactide from lactic acid to increase the yield of left-handed lactide.

[0054] S3, weigh 9 ml of tetrabutyl titanate, 4 mg of tin nitrate powder, and 7 mg of zinc acetate powder, mix and add to 68 mL of aqueous solution, mix well and transfer to a 150 mL reactor, react at 188°C for 23 h, let it cool naturally to room temperature, then filter with distilled water and anhydrous ethanol in turn, wash and collect the samples, and then dry them in a constant temperature drying oven at 78°C for 18 h to obtain a thin film morphology of the ternary composite catalyst TiO2 / ZnO / SnO2. In this step, TiO2 has good stability and reducibility, as well as the advantages of high catalytic efficiency. ZnO and SnO2 have similar properties to TiO2, and are all semiconductors. The ternary composite catalyst TiO2 / ZnO / SnO2 synthesized by the three is relatively stable as an inorganic catalyst.

[0055] S4, dissolve 110 mg of L-lactide prepared in step S2 in 14 mL of chloroform, dissolve 14 mg of chitosan in 10 mL of 1% acetic acid aqueous solution, and ultrasonically disperse 3 mg of the ternary composite catalyst TiO2 / ZnO / SnO2 prepared in step S3 in 8 mL of ethanol, then add the above solution to a 200 mL flask and mix evenly, preheat in a 119°C oil bath, mix evenly and put into a microwave reactor, set the power to 290 W, the temperature to 115°C, and the reaction time to 19 min, to obtain crude chitosan-modified L-polylactic acid, then dissolve the crude chitosan-modified L-polylactic acid in chloroform, and precipitate with anhydrous ethanol to obtain pure chitosan-modified L-polylactic acid. As a polymer material, L-polylactic acid can be slowly degraded into carbon dioxide and water in soft tissues, activate fibroblasts to stimulate the formation of collagen, and has high mechanical strength, non-toxicity, non-irritation and good biocompatibility. In this step, chitosan-modified L-polylactic acid is synthesized by microwave. The L-polylactic acid molecule contains a large number of active groups such as hydroxyl (-OH) and carboxyl (-COOH), and chitosan contains hydroxyl (-OH) and amino (-NH2). The two can be combined in various forms such as hydrogen bonds, ester bonds, amine bonds, and ionic bonds. The modified polylactic acid has good performance and can be used as an injectable agent to become a commonly used medical beauty material in clinical practice.

[0056] Comparative Example 8: Except that chitosan is not added in step S4, the rest is the same as Example 4.

[0057] Figure 7-8 They are scanning electron microscope images of L-polylactic acid of Example 4 and Comparative Example 8. As shown in the figure, the morphology of L-polylactic acid before and after modification does not change much. The L-polylactic acid is spherical with a smooth surface and a particle size range of 20-60 μm. This particle size range is conducive to injection and is not easily captured and removed by capillary walls or immune cells, and is suitable for in vivo implantation applications.

[0058] 200 mg of the poly(L-lactic acid) of Example 4, 200 mg of the poly(L-lactic acid) of Comparative Example 8 and 200 mg of the city were respectively added with 122 mg of sodium carboxymethyl cellulose and 165.8 mg of mannitol, and then were uniformly dispersed in 1000 ml of deionized water and freeze-dried to obtain the poly(L-lactic acid) subcutaneous filler.

[0059] The experimental animals were female rabbits with a body weight of about 2 kg, purchased from Chengdu Enswell Biotechnology Co., Ltd. According to literature reports, new collagen can be observed 3 months after L-polylactic acid is implanted in the body. The experiment performed Masson's trichrome staining on tissue sections at 4, 6 and 9 months after implantation to evaluate the effect of the chitosan-modified L-polylactic acid prepared by the present invention on stimulating collagen regeneration. Table 2 shows the Masson's trichrome staining phenomenon of rabbit subcutaneous tissue at different time points after implantation of the L-polylactic acid filler of the present invention.

[0060] Table 2 project Example 4 Comparative Example 8 Commercially available poly(L-lactic acid) April A darker blue part appears A light blue part appears A darker blue part appears June The blue part increases The blue part does not change much The blue part increases September Collagen fibers were observed surrounding No collagen fiber surrounding was observed Collagen fibers were observed surrounding As shown in Table 2, the Masson's trichrome staining photos 4 months after implantation show that there is a darker blue part around the left-handed polylactic acid, indicating new collagen tissue; at the 6th month, the surrounding blue part increases, indicating that more collagen has been regenerated; at the 9th month, collagen fibers can also be observed surrounding the fiber capsules formed by fibroblasts. This is similar to the phenomenon of commercially available left-handed polylactic acid, indicating that the modified left-handed polylactic acid of the present invention can stimulate collagen regeneration. However, there is no obvious collagen production and fiber capsule formation in Comparative Example 8, indicating that the biocompatibility and regeneration-promoting effect of unmodified left-handed polylactic acid are poor. Therefore, chitosan has good biocompatibility, can reduce the host's immune response to foreign materials, and thus promote tissue healing and regeneration.

[0061] Example 5

[0062] S1. Weigh 3.6 g of dried MnO2 and 0.9 g of Cr2O3, grind them evenly with a mortar and put them into a corundum boat. Then place the corundum boat in the center of the tube furnace tube, pass nitrogen for 30 min, heat to 200°C at 4°C / min, and keep for 2h. Then heat to 400°C at 5°C / min and keep for 2h. Finally, heat to 600°C at 4°C / min and keep for 6 h. After the reaction is completed, the rod-shaped binary composite catalyst MnO2 / Cr2O3 can be obtained after cooling to room temperature. In this step, the addition of Cr2O3 changes the structure of manganese dioxide from flake to rod-shaped. This rod-shaped structure increases the specific surface area of ​​the MnO2 material and the dispersion of the particles, allowing the material to fully contact the reactants, thereby greatly improving the catalytic performance of the material.

[0063] S2. Add 150 mL of lactic acid and 1 g of zeolite to a 500 mL single-necked flask, and add 3 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1. Heat at a vacuum degree of 500 Pa and a temperature of 100 ° C for 4 h, then heat to 140 ° C, and continue heating for 5 h. Adjust the vacuum degree to 700 Pa, heat to 250 ° C for 2 h, and then reduce the temperature to 80 ° C to obtain crude lactide. Stir the crude lactide and ethyl acetate at a mass volume ratio of 1 g: 6 mL at 55 ° C until the lactide is completely dissolved. After standing to room temperature, put it in a refrigerator for cooling and crystallization for 10 h. After complete crystallization, filter it and vacuum dry it at 80 ° C to constant weight. Recrystallize it 4 times and dry it in a vacuum drying oven at 80 ° C to constant weight to obtain left-handed lactide. The binary catalyst prepared in step S1 is used in the reaction of synthesizing lactide from lactic acid to increase the yield of left-handed lactide.

[0064] S3, weigh 10 ml of tetrabutyl titanate, 4 mg of tin nitrate powder, and 8 mg of zinc acetate powder, mix and add to 70 mL of aqueous solution, mix evenly and transfer to a 150 mL reactor, react at 200 ° C for 24 h, let it cool naturally to room temperature, then filter with distilled water and anhydrous ethanol in turn, wash and collect the samples, and then dry them in a constant temperature drying oven at 80 ° C for 20 h to obtain a thin film morphology of the ternary composite catalyst TiO2 / ZnO / SnO2. In this step, TiO2 has good stability and reducibility, as well as the advantages of high catalytic efficiency. ZnO and SnO2 have similar properties to TiO2, and are all semiconductors. The ternary composite catalyst TiO2 / ZnO / SnO2 synthesized by the three is relatively stable as an inorganic catalyst.

[0065] S4, 120 mg of L-lactide prepared in step S2 was dissolved in 15 mL of chloroform, 15 mg of chitosan was dissolved in 10 mL of 1% acetic acid aqueous solution, 3 mg of the ternary composite catalyst TiO2 / ZnO / SnO2 prepared in step S3 was ultrasonically dispersed in 8 mL of ethanol, and then the above solution was added to a 200 mL flask and mixed evenly, preheated in a 120°C oil bath, and put into a microwave reactor after mixing evenly, and the power was set to 300 W, the temperature was set to 120°C, and the reaction time was 20 min, so as to obtain crude chitosan-modified L-polylactic acid, and then the crude chitosan-modified L-polylactic acid was dissolved in chloroform, and pure chitosan-modified L-polylactic acid was obtained by precipitation with anhydrous ethanol. L-polylactic acid, as a polymer material, can be slowly degraded into carbon dioxide and water in soft tissues, activate fibroblasts to stimulate the formation of collagen, and has high mechanical strength, non-toxicity, non-irritation and good biocompatibility. In this step, chitosan-modified L-polylactic acid is synthesized by microwave. The L-polylactic acid molecule contains a large number of active groups such as hydroxyl (-OH) and carboxyl (-COOH), and chitosan contains hydroxyl (-OH) and amino (-NH2). The two can be combined in various forms such as hydrogen bonds, ester bonds, amine bonds, and ionic bonds. The modified polylactic acid has good performance and can be used as an injectable agent to become a commonly used medical beauty material in clinical practice.

[0066] Comparative Example 9: Except that the ternary composite catalyst TiO2 / ZnO / SnO2 in step S4 is replaced by Sn(Oct)2, the rest is the same as Example 5 Comparative Example 10: Except that chitosan is not added in step S4, the rest is the same as Example 5.

[0067] Comparative Example 11: Except that Cr2O3 is not added in step S1, the rest is the same as Example 5.

[0068] Comparative Example 12: Except for replacing the binary composite catalyst MnO2 / Cr2O3 in step S2 with Sn(Oct)2, the rest is the same as Example 5.

[0069] Comparative Example 13: Except for adding 0.5 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1 in step S2, the rest is the same as Example 5.

[0070] Comparative Example 14: Except that 4 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1 was added in step S2 and no nano-Ca(CO3)2 was added, the rest was the same as Example 5.

[0071] Comparative Example 15: Except that tetrabutyl titanate is not weighed in step S3, the rest is the same as Example 5.

[0072] Comparative Example 16: Except for weighing 2 ml of tetrabutyl titanate in step S3, the rest is the same as Example 5.

[0073] Comparative Example 17: Except for weighing 12 ml of tetrabutyl titanate in step S3, the rest is the same as Example 5.

[0074] The modified L-polylactic acid prepared in Example 5 and Comparative Examples 9 to 17 was added to pure water, and stirred at room temperature by a magnetic stirrer at 360 rpm to obtain a uniform viscous dispersion system with a concentration of 20% (w / v). The method for preparing microneedles is as follows: the polydimethylsiloxane template after thorough cleaning is placed on a vacuum operating table, dust is removed with tape, a vacuum pump is turned on to evacuate, excess liquid is removed with tape, the above dispersion system is scraped with a special iron plate and iron sheet, and the residual solution left on the edge of the mold is peeled off by using a blade, and then the vacuum is continued for 2 hours, and finally the template is removed and placed in a fume hood to dry overnight, and then demolded with a polymethyl methacrylate organic glass sheet. Thus, L-polylactic acid microneedles can be obtained.

[0075] Levorotatory polylactic acid microneedle mouse epidermal penetration experiment: mice were selected as models to simulate microneedle penetration experiments of living animals. Female mice weighing 20±2 g were selected as experimental animals for animal experiments for in vivo experiments. Before starting the animal experiment, two weeks of feeding time were required to adapt the animals to laboratory conditions to ensure that the experimental conditions of each mouse remained uniform. The experimental process of the animal experiment was: the mice were anesthetized using a special inhalation anesthesia machine for small animals, and the mice were anesthetized with 2.5% isoflurane. Next, the hair on the back of the mouse at the experimental site required for the experiment was removed with an electric shaver, and the back skin was kept clean with a depilatory cream. Then, the completely dried Example 5, the Levorotatory polylactic acid prepared by comparative examples 9 to 17 Levorotatory polylactic acid were manually inserted into the depilatory treated part of the mouse back skin, and the needle was removed after ensuring that the microneedle was completely dissolved in the subcutaneous tissue after 5 minutes. A handheld digital microscope was used to observe the penetration of microneedles on the surface of the mouse skin, photograph the pinholes and expansion, and the changes in the mouse epidermis as the microneedles penetrated and dissolved. Table 3 shows the changes in the skin surface of the microneedles prepared in Example 5 and Comparative Examples 9 to 17 of the present invention over time after the microneedles were inserted into the mouse skin.

[0076] Table 3 project Example 5 Comparative Example 9 Comparative Example 10 Comparative Example 11 Comparative Example 12 Comparative Example 13 Comparative Example 14 Comparative Example 15 Comparative Example 16 Comparative Example 17 1h Expansion Expansion Expansion Expansion Expansion Expansion Expansion Expansion Expansion Expansion 24h The expansion is spreading A small amount of redness and swelling Extensive redness and swelling A small amount of redness and swelling A small amount of redness and swelling A small amount of redness and swelling A small amount of redness and swelling A small amount of redness and swelling A small amount of redness and swelling A small amount of redness and swelling 72h Swelling disappears Slow reduction of erythema and swelling No reduction in erythema or swelling Slow reduction of erythema and swelling Slow reduction of erythema and swelling Slow reduction of erythema and swelling Slow reduction of erythema and swelling Slow reduction of erythema and swelling Slow reduction of erythema and swelling Slow reduction of erythema and swelling Table 3 shows the changes in the skin over time after the microneedles were inserted into the mouse skin. The microneedles in Example 5 and Comparative Examples 9 to 17 were able to be inserted into the mouse skin, indicating that they all had sufficient insertion ability and could pierce the mouse epidermis to exert their effects. In Example 5, within the first hour after the microneedle was inserted into the experiment, the surface of the microneedle pinhole expanded, and the surface expansion reached the maximum value. At 24 hours, the microneedle expansion showed a diffusion trend, indicating that the chitosan-modified L-polylactic acid migrated and degraded in the mouse body. After 72 hours, the mouse epidermis swelled and disappeared, and no erythema or redness appeared during the period. However, after the microneedles in Examples 9 to 17 were inserted into the mouse epidermis, erythema and redness appeared on the surface of the microneedle pinhole over time. It shows that the chitosan-modified L-polylactic acid prepared by the present invention has excellent catalytic activity, and the L-polylactic acid modified by chitosan can be degraded. Therefore, the modified L-polylactic acid prepared by the present invention not only does not cause skin damage, but also degrades rapidly, and has application potential in medical beauty injection reagents.

[0077] The embodiments described above are merely descriptions of the preparation process of the present invention, and are not intended to limit the scope of the present invention. Without departing from the design spirit of the present invention, various modifications and improvements made to the technical solution of the present invention by ordinary technicians in this field should all fall within the protection scope determined by the claims of the present invention.

Claims

1. A method for preparing modified L-polylactic acid, characterized in that: The MnO2 / Cr2O3 binary catalyst was used in the reaction of synthesizing lactide from lactic acid to increase the yield of L-lactide. Then, chitosan-modified L-polylactic acid was synthesized by microwave method under the action of TiO2 / ZnO / SnO2 catalyst.

2. The method for preparing the modified L-polylactic acid according to claim 1, characterized in that: The specific preparation steps are as follows: S1, preparing binary composite catalyst MnO2 / Cr2O3; S2, preparing L-lactide; S3, preparing a ternary composite catalyst TiO2 / ZnO / SnO2 with a thin film morphology; S4. Prepare chitosan-modified L-polylactic acid.

3. The modified L-polylactic acid according to claim 2, characterized in that: S1. Weigh the dried MnO2 and Cr2O3, grind them evenly, pass nitrogen for 30 min, heat them to 150-200°C at 2-4°C / min, keep them for 1-2h, then heat them to 350-400°C at 4-5°C / min, keep them for 1-2h, and finally heat them to 550-600°C at 2-4°C / min, keep them for 5-6h, to obtain the binary composite catalyst MnO2 / Cr2O3; S2, adding lactic acid and zeolite, and adding the binary composite catalyst MnO2 / Cr2O3 prepared in step S1, heating for 3-4 h under the conditions of vacuum degree of 450-500 Pa and temperature of 90-100 ° C, then heating to 120-140 ° C, and continuing heating for 4-5 h, adjusting the vacuum degree to 600-700 Pa, heating to 220-250 ° C for 1-2 h, and then reducing the temperature to 80 ° C, to obtain crude lactide, stirring the crude lactide and ethyl acetate until the lactide is completely dissolved, letting it stand to room temperature, and cooling and crystallizing in a refrigerator, filtering, vacuum drying to constant weight, recrystallizing several times, and drying to constant weight, to obtain L-lactide; S3, weighing tetrabutyl titanate, tin nitrate powder, and zinc acetate powder, mixing them, adding them to the aqueous solution, mixing them evenly, reacting them at 160-200°C for 20-24 hours, allowing them to cool naturally to room temperature, and then filtering them with distilled water and anhydrous ethanol in turn, washing and collecting the samples, and then obtaining a ternary composite catalyst TiO2 / ZnO / SnO2 with a film-like morphology; S4, dissolving the L-lactide prepared in step S2 into chloroform, dissolving chitosan into 1% acetic acid aqueous solution, ultrasonically dispersing the ternary composite catalyst TiO2 / ZnO / SnO2 prepared in step S3 into ethanol, and then mixing the above solutions evenly, preheating them in an oil bath at 100-120°C, and putting them into a microwave reactor after mixing evenly, setting the power to 200-300 W, the temperature to 100-120°C, the reaction time to 10-20 min, and cooling to obtain crude chitosan-modified L-polylactic acid, which is then purified.

4. The method for preparing the modified L-polylactic acid according to claim 2 or 3, characterized in that: The S1, weighing 2.8-3.6 g of dried MnO2 and 0.6-0.9 g of Cr2O3, grinding them evenly with a mortar and putting them into a corundum boat, then placing the corundum boat in the center of the tube furnace tube, passing nitrogen for 30 min, heating to 150-200°C at 2-4°C / min, keeping for 1-2h, then heating to 350-400°C at 4-5°C / min, keeping for 1-2h, and finally heating to 550-600°C at 2-4°C / min, keeping for 5-6h, to obtain the binary composite catalyst MnO2 / Cr2O3.

5. The method for preparing the modified L-polylactic acid according to claim 2 or 3, characterized in that: S2: add 100-150 mL of lactic acid and 0.5-1 g of zeolite to a 500 mL single-necked flask, and add 2-3 mg of the binary composite catalyst MnO2 / Cr2O3 prepared in step S1, heat for 3-4 h at a vacuum degree of 450-500 Pa and a temperature of 90-100 ° C, then heat to 120-140 ° C, and continue heating for 4-5 h, adjust the vacuum degree to 600-700 Pa, heat to 220-250 ° C for 1-2 h, and then reduce the temperature to 80 ℃, crude lactide can be obtained, crude lactide and ethyl acetate are stirred at 55℃ at a mass volume ratio of 1g:6mL until lactide is completely dissolved, let it stand to room temperature, put it in a refrigerator to cool and crystallize for 8-10h, after complete crystallization, filter it, vacuum dry it at 60-80℃ to constant weight, recrystallize it 3-4 times, and dry it in a vacuum drying oven at 60-80℃ to constant weight to obtain l-lactide.

6. The method for preparing the modified L-polylactic acid according to claim 2 or 3, characterized in that: The S3, weighing 8-10 ml of tetrabutyl titanate, 2-4 mg of tin nitrate powder, and 4-8 mg of zinc acetate powder, adding the mixture to 60-70 mL of aqueous solution, mixing them evenly, and transferring them into a 150 mL reactor, reacting them at 160-200° C. for 20-24 hours, allowing them to cool naturally to room temperature, and then filtering them with distilled water and anhydrous ethanol in turn, washing and collecting the samples, and then drying them in a constant temperature drying oven at 60-80° C. for 12-20 hours to obtain a thin film-like ternary composite catalyst TiO2 / ZnO / SnO2; The method for preparing the modified L-polylactic acid according to claim 2 or 3, It is characterized by.

7. The above S4, dissolving 100-120 mg of the L-lactide prepared in step S2 into 10-15 mL of chloroform, dissolving 10-15 mg of chitosan into 8-10 mL of 1% acetic acid aqueous solution, and ultrasonically dispersing 1-3 mg of the ternary composite catalyst TiO2 / ZnO / SnO2 prepared in step S3 into 5-8 mL of ethanol, and then adding the above solution to a 200 mL flask and mixing evenly, preheating in an oil bath at 100-120°C, and putting it into a microwave reactor after mixing evenly, setting the power to 200-300 W, the temperature to 100-120°C, the reaction time to 10-20 min, and taking out the sample after cooling to obtain crude chitosan-modified L-polylactic acid, and then dissolving the crude chitosan-modified L-polylactic acid in chloroform, and precipitating it with anhydrous ethanol to obtain pure chitosan-modified L-polylactic acid.

8. The modified L-polylactic acid prepared by the method for preparing the modified L-polylactic acid according to any one of claims 1 to 7.

9. Use of the modified L-polylactic acid described in claim 8 in medical cosmetic injection reagents.

10. Use of the modified L-polylactic acid according to claim 8 in promoting tissue healing and regeneration medicine.

Images