Degradable material and preparation method thereof

Abstract

The application provides a degradable material, which comprises poly(lactic acid-amino acid) / polycaprolactone microspheres; the poly(lactic acid-amino acid) / polycaprolactone microspheres are prepared by blending poly(lactic acid-amino acid) and polycaprolactone; the proportion of poly(lactic acid-amino acid) and polycaprolactone in the poly(lactic acid-amino acid) / polycaprolactone microspheres is (1-10):(1-10); the polymerization monomers of the poly(lactic acid-amino acid) comprise lactide and amino acid, and the proportion of the lactide and the amino acid is (2-10):1; the median particle size D50 of the poly(lactic acid-amino acid) / polycaprolactone microspheres is 30-300 mu m, and the particle size distribution is less than 1.0. The poly(lactic acid-amino acid) / polycaprolactone microspheres provided by the application solve the problems of slow degradation rate, poor hydrophilicity and mechanical property of the existing degradable material by introducing the hydrolysis bond group in the amino acid, and have good degradation performance and stability.

Description

Technical Field

[0001] This invention relates to the field of preparation and modification technology of biodegradable materials, specifically to a biodegradable material and its preparation method. Background Technology

[0002] The severity of marine pollution has drawn significant attention from humanity. "White pollution" from non-degradable plastics has driven countless marine species to the brink of extinction and severely damaged marine ecosystems. Degradable materials, in seawater, do not exhibit the same degradation rate and efficiency as in ordinary environments; some even fail to degrade at all in seawater.

[0003] Polylactic acid (PLA) is a plant starch-based biodegradable polymer with good biocompatibility and degradation properties, widely used in tissue engineering, cell engineering, artificial scaffolds, and packaging materials. However, PLA suffers from low mechanical strength and poor hydrophilicity; these properties can be improved by altering its crystal structure or through composite modification. Polycaprolactone (PCL) is a polyester-based biodegradable polymer with excellent shape memory and biocompatibility, making it highly sought after in the biomedical and shape memory materials fields. Due to its slow degradation rate, poor hydrophilicity, and poor mechanical properties, many studies have modified PCL through blending or copolymerization.

[0004] Currently, with the increasing awareness of environmental protection, the problem of seawater degradation needs further solutions. Traditional solidification methods for preparing polymer microspheres typically involve adding the dispersed phase to the continuous phase using a dropwise addition method, adjusting the rotation speed and type of emulsifier to prepare the microspheres. Microspheres obtained using this method are often uneven in size, have large widths, and are prone to aggregation and adhesion, severely impacting their application.

[0005] Therefore, there is an urgent need for a biodegradable material with advantages such as large specific surface area, porous structure, smooth and round surface, good uniformity, and regular and non-adhesive particles to address this problem. Summary of the Invention

[0006] To address the shortcomings of the prior art, the present invention provides a porous biodegradable material with a high degradation rate.

[0007] The technical problem to be solved by the present invention is achieved through the following technical solution:

[0008] This invention provides a biodegradable material comprising poly(lactic acid-amino acid) / polycaprolactone microspheres; the poly(lactic acid-amino acid) / polycaprolactone microspheres are prepared by blending poly(lactic acid-amino acid) and polycaprolactone.

[0009] The mass ratio of poly(lactic acid-amino acid) to polycaprolactone in the poly(lactic acid-amino acid) / polycaprolactone microspheres is (1-10):(1-10); the polymer monomers of the poly(lactic acid-amino acid) include lactide and amino acids, and the mass ratio of lactide and amino acids is (2-10):1; the median particle size D50 of the poly(lactic acid-amino acid) / polycaprolactone microspheres is 30-300 μm, and the particle size distribution is <1.0.

[0010] Furthermore, the median particle size D50 of the poly(lactic acid-amino acid) / polycaprolactone microspheres is 180-300 μm.

[0011] A method for preparing the above-mentioned biodegradable material, the method comprising the following steps:

[0012] Step 1: Take amino acids and lactide and put them into a reaction tube, and pass in an inert gas for exchange. Under vacuum conditions, place the reaction tube in an oil bath and stir for a certain period of time to obtain a reaction mixture. After the reaction is completed, put the reaction tube into ice water and dissolve the obtained reaction mixture in an organic solvent to obtain mixed solution 1. The mixed solution 1 is reprecipitated in a mixed solvent of ethanol / water. The precipitate is filtered and dried to obtain poly(lactic acid-amino acid) copolymer.

[0013] Step 2: Dissolve the poly(lactic acid-amino acid) copolymer obtained in Step 1 in an organic solvent to obtain mixed solution 2;

[0014] Step 3: Dissolve the polyvinyl alcohol solution in deionized water and add a co-emulsifier to obtain mixed solution 3. Disperse the poly(lactic acid-amino acid) mixed solution 2 obtained in step 2 and polycaprolactone in mixed solution 3 to obtain a mixed liquid.

[0015] Step 4: Disperse the mixture from Step 3 in distilled water and stir. After evaporating the organic solvent, a precipitate is obtained. Filter, wash and dry the precipitate to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres.

[0016] Further, in step one, the mass ratio of the amino acid to lactide is 1:(2-10); the reaction mixture is obtained by stirring in an oil bath under vacuum for a certain period of time, the vacuum condition is 30-50 Pa, the oil bath temperature is 140-160℃, and the stirring time is 12-48 hours.

[0017] Further, the precipitate obtained after reprecipitation in step one is dried under vacuum at 28-32°C for 22-24 hours to obtain a poly(lactic acid-amino acid) copolymer;

[0018] Furthermore, the organic solvent in step two is selected from any one or more of dichloromethane, trichloromethane, carbon tetrachloride, and tetrahydrofuran.

[0019] Furthermore, the polyvinyl alcohol solution in step three has a solubility of 0.5% to 2% in deionized water.

[0020] Furthermore, in step three, the polyvinyl alcohol solution is dissolved in deionized water and stirred to obtain mixed solution 3. The stirring speed is 700-800 rpm and the stirring time is 0.5-2 hours.

[0021] Further, in step four, the mixture is dispersed in distilled water and stirred at a speed of 600-1000 rpm for 0.1-2 hours; in step four, the precipitate is filtered, washed, and dried at a temperature of 10-40°C for 12-24 hours.

[0022] Furthermore, the amino acid in step one is any one or more of lysine, aspartic acid, or alanine.

[0023] This invention provides poly(lactic acid-amino acid) / polycaprolactone microspheres, which address the problems of slow degradation rate, poor hydrophilicity, and poor mechanical properties of existing degradable materials by introducing hydrolytic bonding groups from amino acids, resulting in better degradation performance and stability. This invention also provides a simple method for preparing poly(lactic acid-amino acid) / polycaprolactone microspheres, yielding porous, smooth, round, and uniform poly(lactic acid-amino acid) / polycaprolactone microspheres. Detailed Implementation

[0024] It should be noted that, unless otherwise specified, the embodiments and features described in this application can be combined with each other.

[0025] It should be noted that the following detailed descriptions are illustrative and intended to provide further explanation of this application. Unless otherwise specified, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this application pertains.

[0026] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the exemplary embodiments according to this application. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0027] The present invention will now be described in detail with reference to the embodiments.

[0028] Biodegradable polylactic acid / polycaprolactone (PCLA) microspheres possess advantages such as large specific surface area, smooth and rounded particle surface, and good micropore shape and uniformity, making them a hot research topic in seawater degradation treatment. This degradation method belongs to biodegradation. Biodegradation generally involves three steps: First, microorganisms adsorb onto the material, and through microbial growth and metabolism, they exert a certain physical degradation effect on the material; then, extracellular depolymerases produced by microbial metabolism act on the polymer material, causing the polymer chains to undergo hydrolysis and enzymatic degradation into small soluble molecules; finally, the soluble small molecules are absorbed by the microorganisms, and under the action of intracellular depolymerases and other metabolic processes, they are ultimately completely decomposed into water, carbon dioxide, and other biomass, which are then excreted from the body. Biodegradation is essentially an enzymatic hydrolysis reaction of polyester under the action of enzymes secreted by microorganisms. The degree and rate of material degradation are affected by many factors, including environmental factors such as water content, temperature, humidity, pH value, mineral content, oxygen concentration, microbial species and concentration, and material-related factors such as the composition, molecular weight, functional groups, hydrogen bonds, substituents, spatial structure and crystal structure of the polymer material.

[0029] Therefore, biodegradable polymeric materials with a large number of hydrolytic bonds such as amide bonds, ester groups, enamines, amino groups, and amide groups can be introduced as basic materials. At the same time, the materials have a large number of hydrolytic bonds, more linear molecular chains, fewer molecular side chains, lower molecular cross-linking degree, fewer internal hydrogen bonds, better molecular flexibility, and lower molecular crystallinity.

[0030] A biodegradable material comprising poly(lactic acid-amino acid) / polycaprolactone microspheres; wherein the median particle size D50 of the poly(lactic acid-amino acid) / polycaprolactone microspheres is 30-300 μm and the particle size distribution (D90-D10 / D50) < 1.0.

[0031] Specifically, the biodegradable material includes poly(lactic acid-amino acid) / polycaprolactone microspheres. It should be noted that the poly(lactic acid-amino acid) / polycaprolactone microspheres refer to microspheres prepared from a blend of poly(lactic acid-amino acid) and polycaprolactone using an oil-in-water (o / w) emulsification solvent evaporation method. The median particle size D50 of the poly(lactic acid-amino acid) / polycaprolactone microspheres is 30-300 μm, and the particle size distribution (D90-D10 / D50) of the poly(lactic acid-amino acid) / polycaprolactone microspheres is <1.0. Preferably, the median particle size D50 of the poly(lactic acid-amino acid) / polycaprolactone microspheres is 180-300 μm.

[0032] Furthermore, the poly(lactic acid-amino acid) / polycaprolactone microspheres are prepared by blending poly(lactic acid-amino acid) and polycaprolactone.

[0033] The mass ratio of poly(lactic acid-amino acid) to polycaprolactone in the poly(lactic acid-amino acid) / polycaprolactone microspheres is (1-10):(1-10).

[0034] The mass ratio of lactide (lactic acid) to amino acid in the polymer monomer of the poly(lactic acid-amino acid) is (2-10):1.

[0035] Specifically, in poly(lactic acid-amino acid) / polycaprolactone microspheres, considering both degradation rate and structural uniformity, the mass ratio of poly(lactic acid-amino acid) / polycaprolactone is (1-10):(1-10). Poly(lactic acid-amino acid) is a crystalline polyester. When the poly(lactic acid-amino acid) / polycaprolactone ratio exceeds 10:1, the heat resistance and mechanical properties of the poly(lactic acid-amino acid) / polycaprolactone microspheres are poor, resulting in poor toughness and a longer degradation cycle, severely restricting their application. Polycaprolactone has good flexibility, processability, and thermal stability. If the poly(lactic acid-amino acid) / polycaprolactone ratio is less than 1:10, the excessively high polycaprolactone content will cause the poly(lactic acid-amino acid) / polycaprolactone microspheres to stick together, leading to a poorer degradation effect.

[0036] Specifically, considering degradability and microsphere formation, the preferred mass ratio of lactide to amino acids in the poly(lactic acid-amino acid) monomer is (2-10):1. When the ratio of lactide to amino acids is less than 2:1, the amino acid content is too high, resulting in a higher alkalinity of the solution during the polymerization of poly(lactic acid-amino acid), leading to a more pronounced racemization of the resulting polymer, which is not conducive to obtaining the desired bulk. Conversely, when the ratio of lactide to amino acids exceeds 10:1, the final degradation effect will be worse.

[0037] Specifically, porous biodegradable materials are more conducive to microbial attachment, thereby improving the biodegradation rate. As polymer-formed microspheres gradually degrade on their surface, numerous micropores appear. These pores come into contact with the external environment, continuously adsorbing biodegradable microorganisms. The number of pores on the biodegradable microspheres determines their surface area and degradation rate; both factors jointly influence the adsorption of seawater microorganisms, thus achieving a better degradation effect.

[0038] A method for preparing the above-mentioned biodegradable material, the method comprising the following steps:

[0039] Step 1: Place amino acids and lactide into a reaction tube and pass an inert gas through it for exchange. Stir the reaction in an oil bath under vacuum for a certain period of time to obtain a reaction mixture. After the reaction is completed, place the reaction tube into ice water and dissolve the obtained reaction mixture in an organic solvent to obtain mixed solution 1. The mixed solution 1 is redetermined in a mixed solvent of ethanol / water at room temperature. The precipitate is filtered and dried to obtain poly(lactic acid-amino acid) copolymer.

[0040] Step 2: Dissolve the poly(lactic acid-amino acid) copolymer obtained in Step 1 in an organic solvent to obtain mixed solution 2;

[0041] Step 3: Dissolve the polyvinyl alcohol solution in deionized water and add a co-emulsifier to obtain mixed solution 3. Dissolve the poly(lactic acid-amino acid) mixed solution 2 obtained in step 2 and polycaprolactone in mixed solution 3 to obtain a mixed liquid.

[0042] Step 4: Disperse the mixture from Step 3 in distilled water and stir. After evaporating the organic solvent, a precipitate is obtained. Filter, wash and dry the precipitate to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres.

[0043] Further, in step one, the mass ratio of amino acids to lactide is 1:(2-10); the inert gas is argon, nitrogen, etc., and is used to remove oxygen from the reaction system. To ensure continuous flow of the inert gas to keep the system oxygen-free until the formed poly(lactic acid-amino acid) is removed from the reactor, the inert gas is preferably exchanged three times or more; the reaction mixture is obtained by stirring in an oil bath under vacuum conditions for a certain period of time. The vacuum conditions are 30-50 Pa. Insufficient vacuum will increase the oxygen content, causing lactide to oxidize and discolor, as well as coking and carbonization. The oil bath temperature is 140-160℃, and the stirring time is 12-48 hours. When the oil bath temperature is less than 140℃, the oligomers of lactic acid are not easy to form poly(lactic acid-amino acid) polymers; when the oil bath temperature exceeds 160℃, the lactic acid oligomers will decompose and oxidize, and the formed poly(lactic acid-amino acid) will coke. Stirring time of less than 12 hours results in incomplete reaction and lower molecular weight; stirring time exceeding 48 hours causes side reactions in the generated copolymer, leading to increased impurities and affecting subsequent reactions. This increases subsequent workload and cost.

[0044] The organic solvent in step one is selected from any one or more of dichloromethane, trichloromethane, carbon tetrachloride, and tetrahydrofuran, preferably tetrahydrofuran; the precipitate obtained after recrystallization in step one is dried under vacuum at 28-32°C for 22-24 hours to obtain a poly(lactic acid-amino acid) copolymer.

[0045] Furthermore, the organic solvent in step two is selected from any one or more of dichloromethane, trichloromethane, carbon tetrachloride, and tetrahydrofuran.

[0046] Further, in step three, the polyvinyl alcohol solution dissolved in deionized water has a solubility of 0.5%–2%. In step three, the polyvinyl alcohol solution is dissolved in deionized water, and a co-emulsifier is added and stirred to obtain mixed solution 3. The stirring speed is 700–800 rpm, and the stirring time is 0.5–2 hours. When the organic solvent evaporates from the droplet surface, the polymer concentration increases and then reaches a critical point, at which point the polymer concentration is greater than its solubility in the organic phase, and precipitation occurs to form microspheres. Increasing the amount of emulsifier leads to a smaller microsphere size, possibly because the droplets formed during emulsification become smaller with increasing emulsifier dosage. Excessive emulsifier can make the microspheres more brittle, thereby reducing their stability and affecting their size distribution. The addition of the co-emulsifier gives the emulsifier ultra-low surface tension; changes the curvature of the oil-water interface, forming smaller droplets; enhances the fluidity of the spheres; and reduces their rigidity. Preferably, the co-emulsifier is selected from any one of ethanol, polyisobutylene alcohol, and glycerin; more preferably, the solubility of the co-emulsifier in deionized water is 1% to 5%.

[0047] Further, in step four, the mixture is dispersed in distilled water and stirred at a speed of 600-1000 rpm for 0.5-2 hours. The precipitate is then filtered, washed, and dried at a temperature of 10-40°C for 12-24 hours. The stirring speed of the mixture in distilled water in step four affects the size distribution of the biodegradable microspheres. Increasing the dispersion and stirring time affects the size of the microspheres. Increasing the dispersion and stirring time in step four can reduce the size of the biodegradable microspheres, likely due to the contact time between the droplets and the continuous phase and the diffusion rate of dichloromethane into the atmosphere. The longer the droplets remain in the continuous phase, the more thoroughly the solvent evaporates, resulting in smaller microspheres.

[0048] Furthermore, the amino acid in step one is any one or more of lysine, aspartic acid, or alanine.

[0049] This invention provides poly(lactic acid-amino acid) / polycaprolactone microspheres, which address the problems of slow degradation rate, poor hydrophilicity, and poor mechanical properties of existing degradable materials by introducing hydrolytic bonding groups from amino acids, resulting in better degradation performance and stability. This invention also provides a simple method for preparing poly(lactic acid-amino acid) / polycaprolactone microspheres, yielding porous, smooth, round, and uniform poly(lactic acid-amino acid) / polycaprolactone microspheres.

[0050] Further explanation will be provided through specific examples:

[0051] Example 1:

[0052] Step 1: Place a small stir bar in the polymerization tube, add 1 part by weight of lysine and 5 parts by weight of lactide, and exchange the mixture with argon gas three times. Seal the tube under vacuum (40 Pa) and stir for 48 hours in an oil bath at 150°C using a magnetic stirrer. Then, place the polymerization tube in ice water to stop the reaction. Dissolve the obtained product in tetrahydrofuran and recrystallize it in a mixed solvent of ethanol / water at room temperature. After filtering the precipitate, dry it under vacuum at 30°C for 24 hours.

[0053] Step 2: Dissolve the poly(lactic acid-amino acid) copolymer obtained in Step 1 in tetrahydrofuran to obtain Solution 1;

[0054] Step 3: Dissolve the polyvinyl alcohol solution in deionized water and adjust its solubility to 0.5%; add ethanol as a co-emulsifier and adjust its solubility in deionized water to 2%. Stir with a magnetic stirrer at 700 rpm for 0.5 hours to obtain mixed solution 3. Take 6 parts by weight of poly(lactic acid-amino acid) and 4 parts by weight of polycaprolactone and disperse them in mixed solution 3 to obtain a mixed liquid.

[0055] Step 4: Disperse the mixture in 350 ml of distilled water at a speed of 900 rpm for 1 hour to allow the organic solvent to evaporate. Filter the formed microspheres, wash them with distilled water, and dry them in an oven at 40°C for 24 hours to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A1.

[0056] Example 2

[0057] The difference from Example 1 is as follows:

[0058] Step 1: Place a small stir bar in the polymerization tube, add 1 part aspartic acid and 5 parts lactide by weight, and exchange with argon three times. Seal the tube under vacuum (50 Pa) and stir for 24 hours in an oil bath at 140°C using a magnetic stirrer. Then, place the polymerization tube in ice water to stop the reaction. Dissolve the obtained product in tetrahydrofuran and recrystallize it in a mixed solvent of ethanol / water at room temperature. After filtering the precipitate, dry it under vacuum at 30°C for 24 hours.

[0059] Step 4: Disperse the mixture in 350 ml of distilled water and stir at 900 rpm for 1 hour to evaporate the organic solvent. Filter the formed microspheres, wash them with distilled water, and dry them in an oven at 10°C for 18 hours to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A2.

[0060] Example 3

[0061] The difference from Example 1 is as follows:

[0062] Step 1: Place a small stir bar in the polymerization tube, add 1 part alanine and 5 parts lactide by weight, and exchange the mixture with argon gas three times. Seal the tube under vacuum (30 Pa) and stir for 12 hours in an oil bath at 160°C using a magnetic stirrer. Then, place the polymerization tube in ice water to stop the reaction. Dissolve the obtained product in tetrahydrofuran and recrystallize it in a mixed solvent of ethanol / water at room temperature. After filtration, dry the precipitate under vacuum at 30°C for 24 hours.

[0063] Step 4: Disperse the mixture in 350 ml of distilled water and stir at 900 rpm for 1 hour to evaporate the organic solvent. Filter the formed microspheres, wash them with distilled water, and dry them in an oven at 30°C for 12 hours to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A3.

[0064] Example 4

[0065] The difference from Example 1 is as follows:

[0066] In step one, 1 part of amino acid and 2 parts of lactide are added to the polymerization tube by weight to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A4.

[0067] Example 5

[0068] The difference from Example 1 is as follows:

[0069] In step one, 1 part of amino acid and 10 parts of lactide are added to the polymerization tube by weight to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A5.

[0070] Example 6

[0071] The difference from Example 1 is as follows:

[0072] In step three, 1 part by weight of poly(lactic acid-amino acid) and 10 parts by weight of polycaprolactone are taken to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A6.

[0073] Example 7

[0074] The difference from Example 1 is as follows:

[0075] In step three, 10 parts by weight of poly(lactic acid-amino acid) and 1 part by weight of polycaprolactone are taken to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A7.

[0076] Example 8

[0077] The difference from Example 1 is as follows:

[0078] In step three, the polyvinyl alcohol solution is dissolved in deionized water and its concentration is adjusted to 1%. The mixture is stirred with a magnetic stirrer at a speed of 700 rpm for 1 hour to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A8.

[0079] Example 9

[0080] The difference from Example 1 is as follows:

[0081] In step three, the polyvinyl alcohol solution is dissolved in deionized water and its concentration is adjusted to 1.5%. The mixture is stirred with a magnetic stirrer at a speed of 800 rpm for 1 hour to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A9.

[0082] Example 10

[0083] The difference from Example 1 is as follows:

[0084] In step three, the polyvinyl alcohol solution is dissolved in deionized water and its concentration is adjusted to 2%. The mixture is stirred with a magnetic stirrer at a speed of 800 rpm for 2 hours to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A10.

[0085] Example 11

[0086] The difference from Example 1 is as follows:

[0087] In step three, the polyvinyl alcohol solution is dissolved in deionized water and its concentration is adjusted to 2%. The mixture is stirred with a magnetic stirrer at a speed of 900 rpm for 0.5 hours to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A11.

[0088] Example 12

[0089] The difference from Example 1 is as follows:

[0090] In step three, the polyvinyl alcohol solution is dissolved in deionized water and its concentration is adjusted to 3%. The mixture is stirred with a magnetic stirrer at a speed of 700 rpm for 0.5 hours to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A12.

[0091] Example 13

[0092] The difference from Example 1 is as follows:

[0093] In step three, the polyvinyl alcohol solution is dissolved in deionized water and its concentration is adjusted to 2%. The mixture is stirred with a magnetic stirrer at a speed of 700 rpm for 0.5 hours to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A13.

[0094] Example 14

[0095] The difference from Example 1 is as follows:

[0096] In step four, the mixing liquid is dispersed at a speed of 600 rpm for 2 hours, and the resulting poly(lactic acid-amino acid) / polycaprolactone microspheres are designated as A14.

[0097] Example 15

[0098] The difference from Example 1 is as follows:

[0099] In step four, the mixing liquid is dispersed at a speed of 1000 rpm for 0.5 hours, resulting in poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as A15.

[0100] Example 16

[0101] The difference from Example 1 is as follows:

[0102] In step four, the mixing liquid is dispersed at a speed of 500 rpm for 1 hour, and the resulting poly(lactic acid-amino acid) / polycaprolactone microspheres are designated as A16.

[0103] Example 17

[0104] The difference from Example 1 is as follows:

[0105] In step four, the mixing liquid is dispersed at a speed of 1200 rpm for 1 hour, and the resulting poly(lactic acid-amino acid) / polycaprolactone microspheres are designated as A17.

[0106] Example 18

[0107] The difference from Example 1 is as follows:

[0108] In step four, the mixing liquid is dispersed at a speed of 900 rpm for 3 hours, and the resulting poly(lactic acid-amino acid) / polycaprolactone microspheres are designated as A18.

[0109] Comparative Example 1

[0110] The difference from Example 1 is as follows:

[0111] In step one, 1 part by weight of amino acid and 1 part by weight of lactide are added to the polymerization tube to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as E1.

[0112] Comparative Example 2

[0113] The difference from Example 1 is as follows:

[0114] In step one, 1 part of amino acid and 15 parts of lactide are added to the polymerization tube by weight to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as E2.

[0115] Comparative Example 3

[0116] The difference from Example 1 is as follows:

[0117] In step three, 1 part by weight of poly(lactic acid-amino acid) and 15 parts by weight of polycaprolactone are taken to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as E3.

[0118] Comparative Example 4

[0119] The difference from Example 1 is as follows:

[0120] In step three, 15 parts by weight of poly(lactic acid-amino acid) and 1 part by weight of polycaprolactone are taken to obtain poly(lactic acid-amino acid) / polycaprolactone microspheres, denoted as E4.

[0121] The properties of the poly(lactic acid-amino acid) / polycaprolactone microspheres A1-18 and E1-4 prepared above were tested using the following methods:

[0122] Test method:

[0123] 1. Particle size test: The particle size is determined using a particle size analyzer (PSA).

[0124] 2. Porosity Test: The porosity is measured using a gravimetric method. It determines the pore volume of the material based on the change in weight before and after immersion in a suitable liquid (such as water). The skeletal volume of the material can be obtained from the density and dry weight of the raw materials. Therefore, the porosity of the porous material can be calculated using the following formula: p = v_1 / v_1 + v_2;

[0125] In the formula, v_1 ​​is the pore volume of the material, and v_2 is the skeleton volume of the material.

[0126] 3. Particle size distribution: Microspheres settle in liquid or gaseous media in order of particle size. The concentration of microspheres of different sizes in the light column is measured at a certain settling height h using a light transmission method, and the microsphere particle size distribution is calculated.

[0127] 4. Degradation rate in seawater: Imitating seawater conditions, the mass of the material after degradation was measured after 180 days. The biodegradation rate of the material was expressed as the ratio of the actual degraded mass to the original mass.

[0128] The measured experimental data are shown in Table 1:

[0129] Table 1

[0130]

[0131]

[0132] Based on the experimental data above, it can be seen that the degradation rates of the biodegradable materials in the examples are all superior to those of the biodegradable biomaterials prepared in the comparative examples. In Comparative Example 1, the ratio of lactide content to amino acid content is less than 2:1, and in Comparative Example 2, the ratio of lactide content to amino acid content is greater than 10:1. This shows that both excessively large and small ratios are detrimental to the degradation performance of the biodegradable materials. Data from Comparative Examples 3 and 4 indicate that when the ratio of poly(lactic acid-amino acid) to polycaprolactone exceeds (1-10):(1-10), the degradation cycle becomes longer, thus reducing degradation efficiency. The poly(lactic acid-amino acid) / polycaprolactone microsphere biodegradable material provided by this invention, by introducing a reasonable proportion of amino acids, utilizes the hydrolytic bond groups in amino acids to solve the problems of slow degradation rate, poor hydrophilicity, and poor mechanical properties of existing biodegradable materials, exhibiting better degradation performance and stability. This invention also provides a method for preparing poly(lactic acid-amino acid) / polycaprolactone microspheres, which is relatively simple and yields porous, uniform, and highly efficient poly(lactic acid-amino acid) / polycaprolactone microspheres.

[0133] The above are merely preferred embodiments of the present invention and are not intended to limit the present invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A degradable material, characterized in that, The degradable material comprises poly(lactic-amino acid) / polycaprolactone microspheres; the poly(lactic-amino acid) / polycaprolactone microspheres are prepared by blending poly(lactic-amino acid) and polycaprolactone; The mass ratio between the poly(lactic-amino acid) and the polycaprolactone in the poly(lactic-amino acid) / polycaprolactone microspheres is (1-10):(1-10); the polymerized monomers of the poly(lactic-amino acid) comprise lactide and amino acid, and the mass ratio between the lactide and the amino acid is (2-10):1; the median particle size D50 of the poly(lactic-amino acid) / polycaprolactone microspheres is 30-300 μm, and the particle size distribution (D90-D10) / D50 is less than 1.0; The preparation method of the degradable material comprises the following steps: Step one: place amino acid and lactide in a reaction tube, and exchange with inert gas, and then stir and react in an oil bath under vacuum for a period of time to obtain a reaction mixture; after the reaction is completed, the reaction tube is placed in ice water, and the obtained reaction mixture is dissolved in an organic solvent to obtain a mixed solution 1; the mixed solution 1 is re-precipitated in an ethanol / water mixed solvent; the precipitate is filtered and dried to obtain a poly(lactic-amino acid) copolymer; Step two: dissolve the poly(lactic-amino acid) copolymer obtained in step one in an organic solvent to obtain a mixed solution 2; Step three: dissolve a polyvinyl alcohol solution in deionized water, and add a co-emulsifier to obtain a mixed solution 3; disperse the poly(lactic-amino acid) mixed solution 2 and polycaprolactone obtained in step two in the mixed solution 3 to obtain a mixed liquid; Step four: disperse the mixed liquid in step three in distilled water and stir; after the organic solvent is evaporated, a precipitate is obtained; the formed precipitate is filtered, washed and dried to obtain poly(lactic-amino acid) / polycaprolactone microspheres.

2. The degradable material of claim 1, wherein, The median particle size D50 of the poly(lactic-amino acid) / polycaprolactone microspheres is 180-300 μm.

3. A method for producing the degradable material according to any one of claims 1 to 2, characterized by, The preparation method comprises the following steps: Step one: place amino acid and lactide in a reaction tube, and exchange with inert gas, and then stir and react in an oil bath under vacuum for a period of time to obtain a reaction mixture; after the reaction is completed, the reaction tube is placed in ice water, and the obtained reaction mixture is dissolved in an organic solvent to obtain a mixed solution 1; the mixed solution 1 is re-precipitated in an ethanol / water mixed solvent; the precipitate is filtered and dried to obtain a poly(lactic-amino acid) copolymer; Step two: dissolve the poly(lactic-amino acid) copolymer obtained in step one in an organic solvent to obtain a mixed solution 2; Step three: dissolve a polyvinyl alcohol solution in deionized water, and add a co-emulsifier to obtain a mixed solution 3; disperse the poly(lactic-amino acid) mixed solution 2 and polycaprolactone obtained in step two in the mixed solution 3 to obtain a mixed liquid; Step four: disperse the mixed liquid in step three in distilled water and stir; after the organic solvent is evaporated, a precipitate is obtained; the formed precipitate is filtered, washed and dried to obtain poly(lactic-amino acid) / polycaprolactone microspheres.

4. The production method according to claim 3, characterized by, The amino acid and lactide are mixed in a mass ratio of 1: (2-10) in step one; the reaction mixture is obtained by stirring in an oil bath under vacuum for a certain time, the vacuum condition is 30-50 Pa, the oil bath temperature is 140-160 ℃, and the stirring time is 12-48 hours.

5. The preparation method according to claim 3, characterized in that, The precipitate obtained after reprecipitation in step one is vacuum dried at 28-32 ℃ for 22-24 hours to obtain the poly (lactic acid-amino acid) copolymer.

6. The preparation method according to claim 3, characterized in that, The organic solvent in step two is selected from any one or more of dichloromethane, chloroform, carbon tetrachloride, and tetrahydrofuran.

7. The preparation method according to claim 3, characterized in that, The solubility of the polyvinyl alcohol solution in deionized water in step three is 0.5% to 2%.

8. The preparation method according to claim 3, characterized in that, The polyvinyl alcohol solution in deionized water in step three is stirred to obtain a mixed solution 3, the stirring speed is 700-800 rpm, and the stirring time is 0.5-2 hours.

9. The preparation method according to claim 3, characterized in that, In step four, the mixed solution is dispersed in distilled water and stirred, the stirring speed is 600-1000 rpm, and the stirring time is 0.1-2 hours; the precipitate is filtered, washed, and dried, the drying temperature is 10-40 ℃, and the drying time is 12-24 hours.

10. The preparation method according to claim 3, characterized in that, The amino acid in step one is any one or more of lysine, aspartic acid, or alanine.

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