A basic magnesium sulfate whisker-reinforced polylactide composite and a preparation method and application thereof

Abstract

This invention belongs to the field of biodegradable material modification, specifically relating to a basic magnesium sulfate whisker-reinforced polylactide composite, its preparation method, and its applications. The basic magnesium sulfate whisker-reinforced polylactide composite of this invention comprises the following components by mass fraction: 80-97.5% gluconolactone-modified polylactide and 2.5-20% basic magnesium sulfate whiskers. The basic magnesium sulfate whisker-reinforced polylactide composite provided by this invention possesses high modulus and rigidity, exhibiting early defect support and ligation fixation functions. It gradually degrades and is absorbed and replaced by tissue. The degradation components provide various organic components that promote tissue regeneration, enhancing tissue regeneration and reconstruction. Its degradation rate can be controlled according to the composition to match tissue regeneration and reconstruction. During use, it reduces surgical infections caused by bacterial infection and inflammation, such as redness and swelling, and exudation. It has wide applications in surgical ligation fixation, defect repair, short-term fixation, and isolation.

Description

Technical Field

[0001] This invention belongs to the field of biodegradable material modification, specifically relating to a basic magnesium sulfate whisker-reinforced polylactide composite, its preparation method, and its application. Background Technology

[0002] Human soft tissues require repair and functional restoration after surgery or trauma. Unlike hard tissues such as bone, soft tissues like muscles and blood vessels have a shorter repair cycle. Non-degradable or difficult-to-degrade materials are unsuitable for wound isolation and fixation. Materials with high initial strength and stiffness, and capable of complete degradation within a short period, are needed for various ligation and fixation methods. Currently, polylactic acid (PLA), poly-1,4-dioxanone (PPDO), and polyamino acids are the main materials used in this field.

[0003] Polylactide, also known as polylactic acid (PLA), is a polymer obtained by polymerization of lactic acid or lactide as the main raw material. The raw materials are abundant and renewable. The production process of polylactide is pollution-free, and the product is biodegradable, achieving recycling in nature, making it an ideal green polymer material. Currently, it is widely used in clothing, packaging, construction, and the pharmaceutical and medical device fields. For example, anti-adhesion membranes are widely used clinically as isolation and bridging repair materials. Polylactide anti-adhesion membranes effectively isolate surgical wounds from adjacent organs and tissues, preventing adverse adhesions between the wound and surrounding tissues. This isolates surgical wounds and reinforces weak areas of soft tissue, preventing postoperative adhesions in surgeries such as those for herniated discs, gallstones, appendicitis, and uterine fibroids. The lactic acid component of polylactide has the same structure and chemical composition as lactic acid produced in the human body. Its degradation and metabolism follow the same pathway as human lactic acid metabolism, with the final metabolic product being water dioxide, which does not accumulate in the body and is harmless to humans. However, polylactide produces acidic byproducts during its degradation in vivo, leading to an excessively low pH at the implantation site. This causes an inflammatory response, and the acidity further accelerates the degradation of lactic acid, resulting in a persistently acidic environment that affects tissue healing and growth recovery. This is one of the problems that urgently needs to be solved.

[0004] On the other hand, polylactide has a tensile strength of 20-60 MPa and an elongation at break of 4-10%; although its elastic modulus can reach 3000-4000 MPa, its flexural modulus is only 100-150 MPa, and its degradation period varies depending on its structure. For example, DL-polylactide has a degradation period of 12-16 months, while L-polylactide has a degradation period of more than 24 months. As a medical material, polylactide has the following performance issues:

[0005] (1) If it is a fixed material, its flexural modulus needs to be increased, its rigidity and resistance to flexural deformation under stress conditions need to be improved.

[0006] (2) The degradation cycle is too long, 12-24 months, which does not match the repair and recovery cycle of the soft and hard tissues. It is necessary to improve the degradation speed and shorten the degradation cycle.

[0007] (3) Polylactide has an elongation at break of only 4-10% and poor toughness, which needs to be improved.

[0008] Especially when used as a support structure, such as for temporary support and fixation of bone injuries, or for ligation of blood vessels and bile ducts, it requires higher rigidity and the ability to degrade in a short period of time after it has completed its support, fixation, and ligation functions, such as complete degradation in 4 to 12 weeks, so that tissue function can be fully restored.

[0009] Because polylactide (PL) is a fully biodegradable material, ordinary glass fibers, carbon fibers, quartz fibers, and basalt fibers are unsuitable as reinforcing materials due to their non-degradability. While natural fibers such as velvet fiber have high strength, their rigidity is insufficient, making them unsuitable as reinforcement for PLA. Therefore, inorganic fibers or whiskers are necessary for reinforcing PLA. Considering the interaction between medical PLA and tissues, the reinforcing material used must be non-toxic and safe, with inorganic whiskers preferred for pharmaceutical applications. Inorganic whiskers possess the reinforcing function of fibers and have high rigidity and flexural modulus. When used for ligation and fixation, the reinforcing whiskers gradually degrade and are absorbed and metabolized during the gradual degradation of PLA. Therefore, when selecting inorganic whiskers, their composition must be considered first. The metal ions should be those found in human tissues, such as sodium, potassium, calcium, and magnesium, or small amounts of trace elements such as strontium and zinc. The inorganic components of the whiskers should be readily metabolized and safe and non-toxic, such as sulfate, chloride, and phosphate ions.

[0010] Therefore, there is an unmet need in the field for inorganic whisker-reinforced polylactide materials suitable for medical applications. Summary of the Invention

[0011] Considering the above factors, this invention selects basic magnesium sulfate whiskers, with commonly used clinical therapeutic drugs magnesium sulfate and magnesium hydroxide as the main components, as the reinforcing component of polylactide. These whiskers can be metabolized in vivo, have good biocompatibility with tissues, and provide beneficial effects and functions for tissue regeneration and functional recovery. Moreover, as a reinforcing component, it requires a small amount, enhances the rigidity and strength of polylactide, and maintains other properties of polylactide unchanged. The properties, uses, and production process of basic magnesium sulfate whiskers are as follows: Chemical properties: White powder, relative density 2.3, apparent density <0.1 g / cm³. 3 Specific surface area <10m² 2With an oil absorption of 500 ml / 100 g, fiber diameter < 1 μm, fiber length 10–100 μm, aspect ratio 50–100, and needle-like or fibrous crystalline shape, it possesses excellent electrical properties and affinity for water and organic solvents. Due to the presence of water of crystallization, its operating temperature is lower than other whiskers, mostly below 250°C. The presence of water of crystallization also gives the whiskers excellent flame retardancy. Applications include excellent reinforcing effects on plastics, and its effect on improving flexural modulus is better than glass fiber and talc. Furthermore, as a medical material, in addition to its reinforcing effect, the biocompatibility of basic magnesium sulfate whiskers must be considered; therefore, this invention also prepares medical-grade basic magnesium sulfate whiskers.

[0012] Specifically, in one aspect, the present invention provides a basic magnesium sulfate whisker-reinforced polylactide composite comprising the following components in mass fractions: 80-97.5% gluconolactone-modified polylactide and 2.5-20% basic magnesium sulfate whiskers.

[0013] Furthermore, the gluconic acid lactone-modified polylactide is copolymerized from lactide and gluconic acid lactone, wherein the content of lactide is 80-99 mol% and the content of gluconic acid lactone is 1-20 mol%.

[0014] Further, the gluconic acid lactone includes at least one of glucono-δ-lactone, glucono-γ-lactone, D-mannose-1,4-lactone, and L-mannose-1,4-lactone.

[0015] Furthermore, the basic magnesium sulfate whiskers are at least one of type 152 and type 150 basic magnesium sulfate whiskers.

[0016] In another aspect, the present invention provides a method for preparing a basic magnesium sulfate whisker-reinforced polylactide composite as described herein, comprising the following steps:

[0017] (1) Preparation of basic magnesium sulfate whiskers: Mix an aqueous solution of a weakly alkaline organic magnesium salt with an aqueous solution of magnesium sulfate, and then add an aqueous solution of an alkaline amino acid under stirring. The mixed solution is subjected to a hydrothermal reaction. The reaction product is collected by filtration, washed and dried to obtain basic magnesium sulfate whiskers.

[0018] (2) Preparation of polylactide modified with gluconolactone: under the protection of nitrogen or inert gas, lactide and gluconolactone and catalyst are added to the reactor and reacted at 120-180℃ for 6-50 hours to obtain gluconolactone modified polylactide.

[0019] (3) Preparation of basic magnesium sulfate whisker-reinforced polylactide composite: The basic magnesium sulfate whiskers prepared in step (1) and the gluconic acid lactone-modified polylactide prepared in step (2) are melt-extruded together in the required mass ratio to obtain the basic magnesium sulfate whisker-reinforced polylactide composite.

[0020] Furthermore, the molar ratio of the weakly alkaline organic magnesium salt to magnesium sulfate is 1.0:3.0-6.0.

[0021] Furthermore, the molar ratio of basic amino acids to magnesium sulfate is 1.0:1.0-2.0.

[0022] Furthermore, the weakly alkaline organic magnesium salt includes at least one of magnesium acetate, magnesium propionate, and magnesium butyrate.

[0023] Furthermore, the basic amino acid includes at least one of lysine, histidine, and arginine.

[0024] Furthermore, the hydrothermal reaction is carried out under conditions of 0.4-1.0 mPa and 140-200 °C.

[0025] Furthermore, the basic magnesium sulfate whiskers are type 152 basic magnesium sulfate whiskers.

[0026] Further, the type 152 basic magnesium sulfate whiskers are dried at 240-250°C for 2-10 hours to obtain type 150 basic magnesium sulfate whiskers.

[0027] Furthermore, the catalyst comprises zinc amino acid and / or tin, as well as titanate ester.

[0028] Furthermore, the amino acid in the zinc and / or tin amino acids includes at least one of phenylalanine, arginine, lysine, and histidine.

[0029] Furthermore, the amino acid in the zinc and / or tin amino acids is preferably phenylalanine.

[0030] Furthermore, the amino acid in the zinc and / or tin amino acids is a combination of phenylalanine and other amino acids.

[0031] Furthermore, the amino acid zinc and / or tin is prepared as follows: a zinc or tin complex of the amino acid is prepared using amino acids and zinc or tin salts as raw materials.

[0032] Furthermore, the zinc salt is zinc chloride or zinc sulfate, and the tin salt is stannous chloride.

[0033] Further, the zinc and / or tin complex of the amino acid is prepared as follows: under the protection of nitrogen or an inert gas, the amino acid is reacted with an inorganic guanidine salt in a solvent at 50-80°C to generate an organic guanidine salt of phenylalanine, and then an aqueous and / or alcoholic solution of zinc and / or tin salt is added, and the reaction is carried out at 50-80°C for 3-8 hours to obtain the zinc and / or tin complex of the amino acid.

[0034] Furthermore, the ratio of the total amount of amino acids to the solvent is 1 (mol): 1-2 (L).

[0035] Furthermore, the molar ratio of amino acids to inorganic guanidine salts is 1:0.5-1.2.

[0036] Furthermore, the molar ratio of amino acids to zinc salts and / or tin salts is 2:1.

[0037] Furthermore, the solvent is at least one selected from water, methanol, ethanol, tetrahydrofuran, and dioxane.

[0038] Furthermore, the inorganic guanidine salt is guanidine carbonate.

[0039] Furthermore, it also includes filtering, collecting, washing, and drying the zinc and / or tin complexes of the obtained amino acids.

[0040] Furthermore, the titanate includes at least one of tetrabutyl titanate and tetrabutyl zirconate.

[0041] Furthermore, step (2) is carried out in an anhydrous and oxygen-free environment.

[0042] Furthermore, the reactor is evacuated before the heating reaction in step (2).

[0043] Furthermore, the reaction in step (2) is preferably carried out at 130-140°C, and the reaction time is preferably 16-32 hours.

[0044] Furthermore, the reaction includes reacting at 120-150°C for 2-4 hours, and then raising the temperature to 130-160°C for 5-15 hours.

[0045] Furthermore, step (2) also includes adding an aprotic solvent to the reactor to dissolve the harvested aminolactam and gluconic acid lactone modified lactide polymer, and then using a polar solvent to precipitate, wash and dry the polymer.

[0046] Furthermore, the melt extrusion in step (3) is carried out under nitrogen or inert gas protection, and the outlet of the melt extrusion is protected with nitrogen or dry ice to prevent the polylactide composite reinforced with basic magnesium sulfate whiskers from being oxidized by air or absorbing water.

[0047] In other respects, the present invention also provides for the medical use of basic magnesium sulfate whisker-reinforced polylactide composites prepared as described herein or by the methods described herein.

[0048] Furthermore, the application includes its use in soft tissue repair.

[0049] The beneficial effects of this invention are:

[0050] This invention enhances the strength and rigidity of polylactide (PLD) by introducing basic magnesium sulfate whiskers, while reducing its acidity and avoiding the irritation of tissues by degradation acid products. This allows PLA to be used for fixation such as ligation. The introduction of gluconic acid lactone units increases the polarity and degradation rate of PLA, adapting it to the tissue repair cycle. The use of titanate and zinc phenylalanine catalysts instead of catalysts like stannous octoate avoids the toxicity of tin. The basic magnesium sulfate whisker-reinforced PLA composite provided by this invention has high modulus and rigidity, providing early defect support and ligation fixation. It gradually degrades and is absorbed and replaced by tissue, with the degradation components providing various organic components that promote tissue regeneration, improving tissue regeneration and reconstruction. Its degradation rate can be controlled according to the composition, matching the tissue regeneration and reconstruction process. During use, it reduces surgical infections caused by bacterial infection and inflammation, such as redness and swelling, and exudation. It has wide applications in surgical ligation fixation, defect repair, short-term fixation, and isolation. Detailed Implementation

[0051] This invention will implement the preparation and application of basic magnesium sulfate whisker-reinforced polylactide composites through the following specific technical route.

[0052] The schematic formula of the polylactide composite reinforced with basic magnesium sulfate whiskers of the present invention is as follows:

[0053]

[0054] In Formula I, m1 and m2 are the mass fractions of basic magnesium sulfate whiskers and polylactide, m1 + m2 = 100, m1 ≤ 20. That is, in the composite composition, the content of basic magnesium sulfate whiskers is no higher than 20 wt%, which allows for adjustment of the composite's acidity, strength, and stiffness while maintaining the basic properties of polylactide. n is the degree of polymerization of polylactide, i.e., the number of repeating units in one polylactide molecule; n ≥ 1000, meaning the molecular weight (weight average) of polylactide is at least greater than 150,000. x, y, and z are the molar ratios of Mg(OH)2, MgSO4, and H2O in the basic magnesium sulfate whisker composition. Currently discovered types include 138, 165, 435, 115, 152, 153, 157, 158, 150, 212, 213, and 311 (the first, second, and third digits of each of the aforementioned types represent the values ​​of x, y, and z, respectively). Among them, type 152 basic magnesium sulfate whiskers are characterized by high strength, high rigidity, high elastic modulus, and low density, while also possessing mechanical properties such as flame retardancy, heat resistance, and wear resistance, making them the most widely studied type. In this invention, type 152 basic magnesium sulfate whiskers are primarily used as reinforcing whiskers for polylactide composites reinforced with basic magnesium sulfate whiskers, i.e., x = 1, y = 5, z = 2; type 150 is used as a supplement, i.e., x = 1, y = 5, z = 0.

[0055] Currently, the main methods for preparing basic magnesium sulfate whiskers are: using MgSO4 and Mg(OH)2 as raw materials to prepare whiskers via hydrothermal synthesis, but this method has a low conversion rate because Mg(OH)2 is slightly soluble in water, which affects the reaction rate; using MgSO4 and MgO as raw materials to prepare whiskers via hydrothermal synthesis, but this method has a more complex reaction process; some researchers have also used MgSO4 and NaOH as raw materials to prepare type 152 basic magnesium sulfate whiskers, but this requires the addition of seed crystals during the preparation process, resulting in lower product purity.

[0056] This invention utilizes a hydrothermal method involving the hydrolysis of magnesium sulfate to prepare medical-grade basic magnesium sulfate whiskers. Instead of using water-insoluble basic magnesium compounds such as magnesium hydroxide and magnesium oxide, it employs weakly basic organic magnesium salts, such as magnesium acetate [(pH 7.95 (1mM solution); 8.23 ​​(10mM solution); 8.41 (100mM solution); 8.78 (1000mM solution))], magnesium propionate, and magnesium butyrate. It avoids using sodium hydroxide, potassium hydroxide, lithium hydroxide, or amines such as ammonia or triethylamine to adjust the pH. Instead, it uses basic amino acids to adjust the pH, thereby producing ultrapure basic magnesium sulfate whiskers with few metal ion impurities and no ammonia residue. The specific implementation method is as follows: magnesium sulfate is prepared into a 0.5-2.0M solution using deionized water; magnesium acetate (magnesium propionate or magnesium butyrate) is prepared into a 0.5-2.0M solution; and basic amino acids are prepared into… Prepare a 0.5-2.0 M solution; further, add a magnesium acetate (magnesium propionate or magnesium butyrate) solution to the magnesium sulfate solution, and add an alkaline amino acid solution while stirring to form a white suspension slurry, which is then left to stand for a period of time. The slurry is then transferred to a hydrothermal reactor and subjected to a hydrothermal reaction at 0.4-1.0 mPa and 140-200℃ for 5-20 hours. After the reaction, cool to room temperature, filter the product, and wash it 6 times with deionized water (g / 10-20 ml). Then, vacuum dry at 100-120℃ for 10-20 hours to obtain type 152 fibrous basic magnesium sulfate whiskers. The ratio (mol) of magnesium acetate to magnesium sulfate is 1.0:3.0-6.0. The pH adjuster used is selected from the following amino acid monomers: Lysine,

[0057] Histidine, Arginine. The ratio of amino acids to magnesium sulfate is 1.0:1.0-2.0 (mol). Further, the obtained type 152 basic magnesium sulfate whiskers are dehydrated and dried at 240-250℃ for 2-10 hours to obtain type 150 basic magnesium sulfate whiskers.

[0058] To synthesize high molecular weight polylactide with a suitable degradation cycle, based on the tissue wound recovery cycle, the provided polylactide should be largely degraded (i.e., more than 80%) within 4 months. This allows sufficient space and time for tissue repair and reconstruction. Too slow degradation hinders tissue repair and functional recovery in vivo, while too rapid degradation fails to achieve the goals of ligation, fixation, and isolation. Therefore, this invention introduces gluconate-δ-lactone while ensuring the molecular weight of the polylactide. Glucono-γ-lactone D-mannose-1,4-lactone and L-mannose-1,4-lactone These are used as components to regulate the degradation rate. These gluconic lactones possess a lactone structure and multiple hydroxyl groups, allowing them to act as initiating monomers for lactide polymerization and enhance the polarity and hydrophilicity of polylactide. This promotes the surface interaction between polylactide and tissue fluid, thereby increasing the degradation rate. After high-vacuum drying, the selected gluconic lactones are polymerized together with lactide monomers to obtain high-molecular-weight polylactide with a suitable degradation cycle. Due to the introduction of gluconic lactones, m2 in Formula I above can be expressed as: In Formula II, A represents lactide, m1 represents the number of lactide monomers, m1≥8, and B represents gluconic acid lactone, including gluconic acid-δ-lactone, gluconic acid-γ-lactone, D-mannose-1,4-lactone and L-mannose-1,4-lactone. The molar fraction of gluconic acid lactone is less than or equal to 20, that is, not exceeding 20% ​​molar, with 2.5-10.0% molar being preferred.

[0059] Therefore, the above equation I can be expressed as

[0060] Furthermore, due to the strong neurotoxicity of tin ions, this invention selects a non-tin catalyst as the polymerization catalyst. Since obtaining high molecular weight PLA requires a highly efficient catalyst, and commonly used tin compounds such as stannous octoate are highly toxic and difficult to separate from the polymer, this invention requires a non-toxic, tissue-friendly catalyst.

[0061] Furthermore, the present invention selects tetrabutyl titanate. Tetrabutyl zirconate Amino acid zinc catalysts, such as zinc phenylalanine, and amino acid tin catalysts, such as tin phenylalanine, are used as catalysts in the synthesis of polylactide. To reduce the amount of tin used, this invention employs a combination catalyst, combining two or more of the above catalysts for polymerization catalysis. Examples include combinations of tetrabutyl titanate and zinc phenylalanine, tetrabutyl titanate and tin phenylalanine, and tetrabutyl titanate, zinc phenylalanine, and tin phenylalanine, etc., aiming to synthesize high molecular weight polylactide with minimal or no tin. Furthermore, the catalyst can also catalyze the ring-opening of the gluconic acid lactone component and copolymerize with lactide to form high molecular weight polylactide. The ratio of titanate to amino acid zinc (amino acid tin) is 1.0:1.0-2.0 (wt). The catalyst dosage is 0.1-1.0 wt% of the total monomer content. The amino acid zinc and amino acid tin can be prepared as described in this invention. Specifically, phenylalanine is added to a reactor equipped with heating, stirring, and nitrogen protection. Solvents such as water, methanol, ethanol, tetrahydrofuran, and dioxane are added, with the total amino acid to solvent ratio being 1 (mol):1-2 L. Then, guanidine carbonate is added, with a guanidine carbonate to amino acid molar ratio of 0.5-1.0:1. The mixture is then heated to 50-80°C under nitrogen protection, and a clear solution is formed after approximately 30 minutes. Further, zinc chloride or zinc sulfate is prepared as an aqueous or methanol solution and added to the above solution. The mixture is reacted at 50-80°C under nitrogen protection for 3-8 hours, then cooled to room temperature, and filtered to obtain the zinc complex of phenylalanine. After washing twice with methanol, ethanol, tetrahydrofuran, or dioxane, it is dried in a vacuum oven at 60°C for 12-24 hours. When synthesizing tin amino acids, stannous chloride is used instead of zinc chloride or zinc sulfate. The ratio of zinc chloride or zinc sulfate (stannous chloride) to phenylalanine is 0.45-0.55:1.0 (mol).

[0062] Furthermore, lactide polymerization typically uses alcohols as initiators, such as benzyl alcohol and cyclohexyl alcohol. These initiators are highly efficient at initiating ring-opening polymerization, but they need to be removed after polymerization if mixed in the polymer, otherwise they will affect the polymer's properties. However, the polymer is sensitive to water and cannot be washed with water. Using other solvents for washing increases both the process and cost. Therefore, gluconolactone is chosen as the initiator, as it can act as both an initiator and a monomer, increasing the polymer's hydrophilicity and polarity. This accelerates the degradation rate of the polymer in aqueous solutions such as blood and tissue fluid, and the presence of comonomers also increases its toughness.

[0063] Furthermore, another key technology provided by this invention is the polymerization process route for active gluconic acid lactone (GAL) polymers. The polymerization reaction requires a vacuum, anhydrous, and oxygen-free environment, and the polymer container needs to be dehydrated and deoxygenated. In this invention, a continuously vacuum-capable reactor with a ceramic liner can be used. The reactor, equipped with heating and a ceramic liner, can have an outlet for high-purity nitrogen or argon gas, a vacuum port (T-port, which closes when the required vacuum level is reached and opens when needed), a thermocouple temperature display for online monitoring of the reaction temperature, and a magnetic stirrer for stirring in the liquid state to ensure uniform material distribution in the liquid system. Specifically, before adding raw materials and catalysts, the heated reactor with a ceramic liner can be purged with high-purity nitrogen and heated to 120°C, with high-purity nitrogen continuously purging at this temperature for 15 minutes. Then, the T-port is closed to stop the nitrogen flow. The temperature is lowered to 30-50℃, then lactide, gluconolactone, basic magnesium sulfate whiskers, and tetrabutyl titanate-zinc (tin) phenylalanine complex are added through the feed port, followed by sealing the feed port. Nitrogen gas is then restarted, and the T-port is opened, allowing nitrogen to flow for 15 minutes. Next, the T-port is closed, nitrogen gas is shut off, and a vacuum is created. When the vacuum level is less than 50 Pa, the T-port is closed, and heating begins. Heating is stopped when the temperature reaches 120-150℃, and stirring is started for 20 minutes. The reaction is then carried out at 120-150℃ for 2-6 hours, followed by increasing the temperature to 130-160℃ and reacting for 5-15 hours.

[0064] Furthermore, after polymerization, the polymer is dissolved and purified using aprotic solvents such as 1,2-dichloroethane, chloroform, and dichloromethane, at a dosage of 1 g (polymer) / 5-10 ml (solvent). After polymerization, once the polymer has cooled to room temperature, the solvent is injected into the reactor. After complete dissolution, the polymer solution is discharged from the discharge port. Then, polar solvents such as methanol, ethanol, tetrahydrofuran, and dioxane are added to precipitate the polymer. After washing 5-8 times with the solvent, the polymer is placed in a high-vacuum oven for drying at 60-80°C for 6-18 hours, preferably 8-12 hours.

[0065] Further, basic magnesium sulfate whiskers and synthesized polylactide are mixed and extruded in a molten state using a twin-screw extruder to form a basic magnesium sulfate whisker-reinforced polylactide composite. Before extrusion, the synthesized polylactide and basic magnesium sulfate whiskers are thoroughly dried in a vacuum oven. The extrusion hopper is dried with nitrogen, and the polylactide and basic magnesium sulfate whiskers are added to the hopper under nitrogen protection. The outlet of the twin-screw extruder is protected with nitrogen or dry ice to prevent the basic magnesium sulfate whisker polylactide composite from being oxidized by air or absorbing moisture. After obtaining the basic magnesium sulfate whisker-reinforced polylactide composite granules at the outlet, they are sealed and stored. This process prepares basic magnesium sulfate whisker polylactide composites with a coverage of 2.5wt%-20wt% basic magnesium sulfate whiskers.

[0066] Furthermore, the prepared basic magnesium sulfate whisker polylactide composite was processed into samples such as strips, films, and ligation clips for mechanical, degradation, and biological evaluation.

[0067] Furthermore, the dried polymer was micro-injected into mechanical specimens at 180-200℃ using a Hacker rheometer.

[0068] Molecular weight test: The intrinsic viscosity was measured at 37±0.1℃, using the following formula: η=[2(η sp –lnηr)] 1 / 2 / C. C is the polymer solution viscosity (g / L); η r For relative viscosity, dilute solution = t / t0; η sp To increase specific viscosity, η sp =η r -1. η=KMα, calculate the viscosity-average molecular weight of polylactide (where K=1.04×10-4, α=0.75); molecular weight distribution was measured using GPC, and the solvent was THF.

[0069] (1) Determination of molecular weight: The molecular weight of polylactide (PLA) was determined by the viscosity method. A certain amount of product (approximately 0.080-0.1009 g) was accurately weighed, dissolved in THF in a 100 mL volumetric flask, and left overnight with shaking. The eluent time t was measured using an Ubbelohde viscometer with a capillary diameter of 0.46 mm in a constant temperature water bath at 37 °C. The eluent time to of the pure solvent was also measured. The intrinsic viscosity of PLA was determined using the one-point method. (2) Determination of molecular weight distribution: The molecular weight distribution was determined using a Water410 gel permeation chromatography analyzer. The solvent was THF, the mobile phase eluent flow rate was 1.00 mL / min, and the temperature was 35 °C.

[0070] Thermal performance testing: The melting point (Tm) of the PLA product was determined using a Perkin-Elemer DEC-7 differential scanning calorimeter (DSC). The initial temperature was set at 20℃, the heating rate was 10℃ / min, and the atmosphere was nitrogen.

[0071] Mechanical property testing: Tensile strength and flexural modulus were measured according to GB13022-91 method.

[0072] Degradation test method: The injection-molded material was subjected to degradation test in PBS solution. The PBS preparation method is as follows: Accurately weigh KH2PO4 (0.544g), Na2HPO4·12H2O (7.16g), NaCl (16g) and KCl (0.402g) and dissolve them in 2L of deionized water. Make up to volume with a volumetric flask, and determine the pH range between 7.2 and 7.4. Place the sample in a centrifuge tube and add a certain amount of PBS solution. The volume ratio of PBS solution to sample mass is 1g / 30mL. Then place the centrifuge tube containing the sample in a constant temperature shaking incubator at 37℃ and 80rpm / min. Remove the sample and change the solution at 1 (1D), 1w, 4w and 12w days. Rinse the surface of the sample with deionized water, vacuum dry and weigh it, and calculate the weight loss rate. The total weight loss rate over 12 weeks is used as the standard. Three control groups are set up for each sample.

[0073] pH measurement: The supernatant of the sample was measured using a pH meter, and the PBS was replaced every 7 days.

[0074] Cytotoxicity and cell proliferation rate tests: Extracts were prepared according to the provisions of T16886 concerning biological materials, and the proliferation rate was calculated by comparing the standard extract with the blank.

[0075] The present invention will be further illustrated below with reference to specific embodiments, but the embodiments do not limit the present invention in any way. Unless otherwise specified, the reagents, methods, and equipment used in the present invention are conventional reagents, methods, and equipment in this technical field.

[0076] Example 1:

[0077] (1) Preparation of basic magnesium sulfate whiskers: 246.5 g of magnesium sulfate heptahydrate (MgSO4·7H2O) was added to 500 ml of deionized water and dissolved completely. Then, another 500 mL of deionized water was added and the mixture was stirred until homogeneous, yielding a 1 L, 1 M magnesium sulfate solution. 155.4 g of magnesium acetate (C4H6O4Mg) was added to 500 ml of deionized water and dissolved completely. Then, another 500 mL of deionized water was added and the mixture was stirred until homogeneous, yielding a 1 L, 1 M magnesium acetate solution. 330.0 g of arginine was dissolved in 100 ml of deionized water and dissolved completely. Then, another 100 mL of deionized water was added and the mixture was stirred until homogeneous, yielding a 2 L, 1 M arginine solution.

[0078] 200 ml of 1M magnesium acetate solution was added to 1 L of 1M magnesium sulfate solution, and 1.5 L of 1M arginine solution was added while stirring to form a white suspension slurry, which was left to stand for 2 hours. The slurry was then transferred to a 10 L stainless steel hydrothermal reactor and reacted at 0.6 MPa and 150 °C for 6 hours, followed by a hydrothermal reaction at 0.9 MPa and 190 °C for 10 hours. After the reaction, the mixture was cooled to room temperature. The resulting product was filtered and washed 6 times with deionized water (g product / 10-20 ml). It was then vacuum dried at 110 °C for 12 hours to obtain 138 g of fibrous type 152 basic magnesium sulfate whiskers.

[0079] (2) Catalyst preparation:

[0080] 1) Synthesis of arginine / L-phenylalanine zinc: Arginine (17.5 g, about 0.1 mol), L-phenylalanine (16.5 g, about 0.1 mol), and methanol (300 ml) were added to a 1 L three-necked flask and stirred in a 60 °C water bath for 20 min. Guanidine carbonate (24 g, about 0.2 mol) was added, followed by 50 ml of deionized water. After complete dissolution, nitrogen gas was bubbled into the solution for 10 min to remove oxygen from the solution and the reaction flask. Then, 100 ml of a zinc chloride methanol-water solution (methanol / water = 80 ml / 20 ml) (13.6 g, about 0.1 mol) was added dropwise over 30 minutes. The reaction was carried out at 60 °C for 5 hours, cooled to room temperature, filtered, and the precipitate was washed four times with ethanol. The product was dried in a 60 °C vacuum oven for 24 hours to obtain 38 g; the moisture content after drying was less than 0.01%.

[0081] 2) Tetrabutyl titanate was dried with anhydrous magnesium sulfate baked at 500℃.

[0082] (3) Preparation of polylactide polymers:

[0083] A 10L ceramic-lined reactor with a heated inner liner was purged with high-purity nitrogen and heated to 120°C. High-purity nitrogen was continuously purged at this temperature for 15 minutes. Then, the T-port was closed, and nitrogen purging was stopped. The temperature was lowered to 30°C, and then dried L-lactide (702g), 45g D-mannose-1,4-lactone, and arginine / L-phenylalanine zinc (2.5g) and tetrabutyl titanate prepared in step (2) were added through the feed port. The feed port was then closed. Nitrogen was restarted, the T-port was opened, and nitrogen was purged for 15 minutes. Then, the T-port was closed, nitrogen was stopped, and a vacuum was started. When the vacuum level was less than 50Pa, the T-port was closed, and the temperature was raised. When the temperature reached 130°C, the heating was stopped, and stirring was started. Stirring was stopped after 20 minutes. The reaction was then carried out at 130°C for 6 hours, followed by a reaction at 140°C for 12 hours. The vacuum level was less than 50Pa throughout the polymerization process. Then, the solution was cooled to room temperature, and 6 L of chloroform was added. After complete dissolution, the polymer solution was transferred to a 25 L stainless steel container, and 12 L of methanol was added to precipitate the polymer. After filtration, the polymer was washed five times with ethanol and then dried in an 80 °C high vacuum oven for 12 hours to obtain 738 g of product (polylactide).

[0084] (4) Take 5g of basic magnesium sulfate whiskers prepared in step (1) and 195g of polylactide prepared in step (3), and use a Hacker micro twin-screw extruder to mix and extrude at 195°C to obtain a basic magnesium sulfate polylactide composite; wherein, the operating table is protected by nitrogen and the extrusion is completed in a nitrogen environment; then use a Hacker micro injection molding machine to injection mold the polylactide obtained in step (3) and the basic magnesium sulfate polylactide composite obtained in step (4) into tensile and bending strips respectively.

[0085] Product Testing Analysis

[0086] According to the method in a specific embodiment of the present invention, the product is subjected to the following tests:

[0087] (1) Diameter and length of basic magnesium sulfate whiskers were observed by SEM magnification of 200x; (2) Polylactide molecular weight test (viscosity method and GPC); (3) Melting point (°C) test (DSC); (4) Mechanical property test of basic magnesium sulfate polylactide composite: tensile strength (MPa) and flexural modulus (MPa); (5) Degradation performance test (degradation cycle, percentage of degradation in 12w; pH change); (6) Cytotoxicity test (0-5 grade), proliferation rate (%).

[0088] Test results:

[0089] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0090] (2) The weight-average molecular weight of polylactide is 21.5000, and the molecular weight distribution coefficient is 1.21.

[0091] (3) Melting point (°C): 169

[0092] (4) Tensile strength (MPa): 39, flexural modulus (MPa): 1200

[0093] (5) 12w degradation percentage (wt%): 87; pH: 6.0-6.5

[0094] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 109%.

[0095] Example 2 (same as Example 1, except that the content of D-mannose-1,4-lactone is different from that in Example 1)

[0096] The other steps are the same as in Example 1, except for step (3):

[0097] (3) A 10L ceramic-lined reactor with a heating element was purged with high-purity nitrogen and heated to 120°C. High-purity nitrogen was continuously purged at this temperature for 15 minutes. Then the T-port was closed and the nitrogen purging was stopped. The temperature was lowered to 30°C. Then, dried L-lactide (685g), D-mannose-1,4-lactone (89g), and zinc arginine / L-phenylalanine (2.5g) and tetrabutyl titanate (2.5g) were added by opening the feed port. Then the feed port was closed. The nitrogen was reopened, the T-port was opened, and nitrogen was purged for 15 minutes. Then, the T-port was closed, the nitrogen was turned off, and a vacuum was started. When the vacuum degree was less than 50Pa, the T-port was closed, and the temperature was started. When the temperature reached 130°C, the temperature was stopped, and the stirring was started. The stirring was stopped after 20 minutes. The reaction was then carried out at 130°C for 6 hours, and then the temperature was increased to 140°C and the reaction was carried out for 12 hours. The entire polymerization process was carried out under a vacuum of less than 50 Pa. The solution was then cooled to room temperature, and 6 L of chloroform was added. After complete dissolution, the polymer solution was transferred to a 25 L stainless steel container, and 12 L of methanol was added to precipitate the polymer. After filtration, the polymer was washed five times with ethanol and then dried in an 80 °C high-vacuum oven for 12 hours to obtain 739 g of product.

[0098] Test results:

[0099] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0100] (2) The weight-average molecular weight of polylactide is 19.8000, and the molecular weight distribution coefficient is 1.33.

[0101] (3) Melting point (°C): 168

[0102] (4) Tensile strength (MPa): 37, flexural modulus (MPa): 1100

[0103] (5) 12w degradation percentage (wt%): 88; pH: 6.0-6.5

[0104] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 109%.

[0105] Example 3 (same as Example 1, except that the polymerization catalyst used is tetrabutyl titanate and tin phenylalanine)

[0106] The other steps are the same as in Example 1, except for step (2) which involves the synthesis of tin-substituted arginine / L-phenylalanine zinc, and step (3) which are different:

[0107] (3) Preparation of polylactide polymer: A 10L reactor with a heated ceramic inner liner was purged with high-purity nitrogen and heated to 120°C. High-purity nitrogen was continuously purged at this temperature for 15 minutes. Then the T-port was closed and the nitrogen purging was stopped. The temperature was lowered to 30°C, and then dried L-lactide (702g), 45g D-mannose-1,4-lactone, and L-phenylalanine tin (2.5g) and tetrabutyl titanate (2.5g) were added by opening the feed port. Then the feed port was closed. The nitrogen was reopened, the T-port was opened, and nitrogen was purged for 15 minutes. Then the T-port was closed, the nitrogen was turned off, and a vacuum was started. When the vacuum degree was less than 50Pa, the T-port was closed, and the temperature was started. When the temperature reached 130°C, the temperature was stopped, and stirring was started. Stirring was stopped after 20 minutes. Then the reaction was carried out at 130°C for 6 hours, and then the temperature was raised to 140°C for 12 hours. The entire polymerization process was carried out under a vacuum of less than 50 Pa. The solution was then cooled to room temperature, and 6 L of chloroform was added. After complete dissolution, the polymer solution was transferred to a 25 L stainless steel container, and 12 L of methanol was added to precipitate the polymer. After filtration, the polymer was washed five times with ethanol and then dried in an 80 °C high-vacuum oven for 12 hours to obtain 738 g of product.

[0108] Test results:

[0109] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0110] (2) The weight-average molecular weight of polylactide is 29.6000, and the molecular weight distribution coefficient is 1.26.

[0111] (3) Melting point (°C): 169

[0112] (4) Tensile strength (MPa): 45, flexural modulus (MPa): 1300

[0113] (5) 12w degradation percentage (wt%): 85; pH: 6.2-6.8

[0114] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 101%.

[0115] Example 4 (same as Example 1, except that gluconate-γ-lactone is used instead of D-mannose-1,4-lactone)

[0116] Test results:

[0117] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0118] (2) The weight-average molecular weight of polylactide is 21.5000, and the molecular weight distribution coefficient is 1.21.

[0119] (3) Melting point (°C): 169

[0120] (4) Tensile strength (MPa): 39, flexural modulus (MPa): 1200

[0121] (5) 12w degradation percentage (wt%): 87; pH: 6.0-6.5

[0122] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 111%.

[0123] Example 5 (same as Example 1, except that basic magnesium sulfate whiskers and lactide are polymerized together)

[0124] (1)-(2) Same as Example 1.

[0125] (3) Preparation of a composite by copolymerization of magnesium sulfate whiskers and polylactide. A 10L reactor with a heated ceramic inner liner was purged with high-purity nitrogen and heated to 120°C. High-purity nitrogen was continuously purged at this temperature for 15 minutes. Then the T-port was closed and the nitrogen purging was stopped. The temperature was lowered to 30°C. Then, by opening the feed port, dried L-lactide (702g), 45g D-mannose-1,4-lactone, and zinc arginine / L-phenylalanine (2.5g) prepared in (2), as well as 2.5g tetrabutyl titanate, were added. Finally, 20.0g of basic magnesium sulfate whiskers prepared in (1) were added, and then the feed port was closed. The nitrogen was reopened, the T-port was opened, and nitrogen was purged for 15 minutes. Then, the T-port was closed, the nitrogen was turned off, and a vacuum was started. When the vacuum degree was less than 50Pa, the T-port was closed, and the temperature was started. When the temperature reached 130°C, the temperature was stopped, and stirring was started. Stirring was stopped after 20 minutes. The reaction was then carried out at 130℃ for 6 hours, followed by a further increase to 140℃ for 12 hours. The vacuum level was less than 50 Pa throughout the polymerization process. The mixture was then cooled to room temperature, and 6 L of chloroform was added. After complete dissolution, the polymer solution was transferred to a 25 L stainless steel container, and 12 L of methanol was added to precipitate the polymer. After filtration, the polymer was washed five times with ethanol and then dried in an 80℃ high-vacuum oven for 12 hours to obtain 758 g of product.

[0126] (4)-(5) Same as Example 1

[0127] Test results:

[0128] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0129] (2) Melt index of the composite (200℃, g / 10min): 52

[0130] (3) Melting point (°C): 169

[0131] (4) Tensile strength (MPa): 39, flexural modulus (MPa): 1200

[0132] (5) 12w degradation percentage (wt%): 91%; pH: 6.3-6.8

[0133] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 112%.

[0134] Example 6 (same as Example 1, except that the content of basic magnesium sulfate whiskers is increased to 7.5%)

[0135] The other steps are the same as in Example 1, except for step (4):

[0136] (4) 15g of the obtained basic magnesium sulfate whiskers and 185g of the polylactide prepared in step (3) were mixed and extruded at 190°C using a Hacker micro twin-screw extruder. The operating table was protected by nitrogen. After the extrusion was completed in a nitrogen environment, the polylactide and basic magnesium sulfate polylactide composite obtained in (3) and (4) were injection molded into tensile and bending strips using a Hacker micro injection molding machine.

[0137] Test results:

[0138] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0139] (2) The weight-average molecular weight of polylactide is 21.5000, and the molecular weight distribution coefficient is 1.21.

[0140] (3) Melting point (°C): 169

[0141] (4) Tensile strength (MPa): 45, flexural modulus (MPa): 1500

[0142] (5) 12w degradation percentage (wt%): 82; pH: 7.0-7.1

[0143] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 115%.

[0144] Example 7 (same as Example 1, except that the content of basic magnesium sulfate whiskers is increased to 10.0%)

[0145] (1)-(3) are the same as in Example 1.

[0146] (4) 20g of basic magnesium sulfate whiskers and (3) 180g of polylactide were prepared and extruded by mixing at 190°C using a Hacker micro twin-screw extruder. The operating table was protected by nitrogen. After the extrusion was completed in a nitrogen environment, the polylactide and basic magnesium sulfate polylactide composite obtained in (3) and (4) were injection molded into tensile and bending strips using a Hacker micro injection molding machine.

[0147] Test results:

[0148] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0149] (2) The weight-average molecular weight of polylactide is 21.5000, and the molecular weight distribution coefficient is 1.21.

[0150] (3) Melting point (°C): 170

[0151] (4) Tensile strength (MPa): 49, flexural modulus (MPa): 1700

[0152] (5) 12w degradation percentage (wt%): 83; pH: 7.1-7.2

[0153] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 112%.

[0154] Example 8 (same as Example 1, except that the content of basic magnesium sulfate whiskers is increased to 15%)

[0155] (1)-(3) are the same as in Example 1.

[0156] (4) 30 g of basic magnesium sulfate whiskers and (3) 170 g of polylactide were prepared and extruded by mixing at 190°C using a Hacker micro twin-screw extruder. The operating table was protected by nitrogen. After the extrusion was completed in a nitrogen environment, the polylactide and basic magnesium sulfate polylactide composite obtained in (3) and (4) were injection molded into tensile and bending strips using a Hacker micro injection molding machine.

[0157] Test results:

[0158] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0159] (2) The weight-average molecular weight of polylactide is 21.5000, and the molecular weight distribution coefficient is 1.21.

[0160] (3) Melting point (°C): 169

[0161] (4) Tensile strength (MPa): 50, flexural modulus (MPa): 1900

[0162] (5) 12w degradation percentage (wt%): 81; pH: 7.1-7.3

[0163] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 113%.

[0164] Example 9 (Same as Example 1, except that the content of basic magnesium sulfate whiskers is increased to 20.0%)

[0165] (1)-(3) are the same as in Example 1.

[0166] (4) 40g of basic magnesium sulfate whiskers and (3) 160g of polylactide were prepared and extruded by mixing at 190°C using a Hacker micro twin-screw extruder. The operating table was protected by nitrogen. After the extrusion was completed in a nitrogen environment, the polylactide and basic magnesium sulfate polylactide composite obtained in (3) and (4) were injection molded into tensile and bending strips using a Hacker micro injection molding machine.

[0167] Test results:

[0168] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0169] (2) The weight-average molecular weight of polylactide is 21.5000, and the molecular weight distribution coefficient is 1.21.

[0170] (3) Melting point (°C): 169

[0171] (4) Tensile strength (MPa): 55, flexural modulus (MPa): 2100

[0172] (5) 12w degradation percentage (wt%): 81; pH: 7.0-7.3

[0173] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 117%.

[0174] Example 10 (same as Example 1, except that type 150 basic magnesium sulfate whiskers are used instead of type 152).

[0175] (1) Preparation of basic magnesium sulfate whiskers: 246.5g of magnesium sulfate heptahydrate (MgSO4·7H2O) was added to 500ml of deionized water and dissolved completely. Then, another 500mL of deionized water was added and stirred until homogeneous, yielding a 1L, 1M magnesium sulfate solution. 155.4g of magnesium acetate (C4H6O4Mg) was added to 500ml of deionized water and dissolved completely. Then, another 500mL of deionized water was added and stirred until homogeneous, yielding a 1L, 1M magnesium acetate solution. 330.0g of arginine was dissolved in 100ml of deionized water and dissolved completely. Then, another 100mL of deionized water was added and stirred until homogeneous, yielding a 2L, 1M arginine solution. 200ml of the 1M magnesium acetate solution was added to the 1L, 1M magnesium sulfate solution, and while stirring, 1.5L of the 1M arginine solution was added to form a white suspension slurry, which was left to stand for 2 hours. The slurry was then transferred to a 10L stainless steel hydrothermal reactor and reacted at 0.6MPa and 150℃ for 6 hours, followed by a hydrothermal reaction at 0.9MPa and 190℃ for 10 hours. After the reaction, the mixture was cooled to room temperature. The resulting product was filtered and washed six times with deionized water (g / 10-20ml). It was then vacuum dried at 110℃ for 12 hours to obtain 138g of fibrous type 152 basic magnesium sulfate whiskers.

[0176] The obtained type 152 basic magnesium sulfate whiskers were dried under vacuum at 260°C for 12 hours to remove the water of crystallization.

[0177] (2)-(5) Same as Example 1.

[0178] Test results:

[0179] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.5-0.8μm, length: 80-110μm.

[0180] (2) The weight-average molecular weight of polylactide is 21.5000, and the molecular weight distribution coefficient is 1.21.

[0181] (3) Melting point (°C): 169

[0182] (4) Tensile strength (MPa): 409, flexural modulus (MPa): 1300

[0183] (5) 12w degradation percentage (wt%): 87; pH: 6.3-6.6

[0184] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 110%.

[0185] Comparative Example 1: Synthesis and Performance of Traditional PLA

[0186] A 10L ceramic-lined reactor with a heated inner liner was purged with high-purity nitrogen and heated to 120°C. High-purity nitrogen was continuously purged at this temperature for 15 minutes. The T-port was then closed, and nitrogen purging was stopped. The temperature was lowered to 50°C, and then dried L-lactide (1000g) and stannous octoate (5g) were added through the feed port. The feed port was then closed. Nitrogen was reopened, and the T-port was opened, purging nitrogen for 15 minutes. Next, the T-port was closed, nitrogen purging was stopped, and a vacuum was initiated. When the vacuum level was less than 50Pa, the T-port was closed, and heating began. When the temperature reached 130°C, heating was stopped, and stirring was started and stopped after 20 minutes. The reaction was then carried out at 130°C for 6 hours, followed by a reaction at 140°C for 12 hours. The vacuum level remained less than 50Pa throughout the polymerization process. The mixture was then cooled to room temperature, and 6L of chloroform was added. After complete dissolution, the polymer solution was transferred to a 25L stainless steel container, and 12L of methanol was added to precipitate the polymer. After filtration, the polymer was washed five times with ethanol and then dried in an 80℃ high vacuum oven for 12 hours to obtain 829g of product.

[0187] The test was conducted in the same manner as in Example 1.

[0188] Test results:

[0189] (1) The weight-average molecular weight is 55.3000, and the molecular weight distribution coefficient is 1.32.

[0190] (2) Melting point (°C): 175

[0191] (3) Tensile strength (MPa): 50 and elongation at break (%) 4.5; flexural modulus 231 MPa

[0192] (4) Degradation cycle (w): 60; pH: 2.5-4.5

[0193] (5) Cytotoxicity: Grade 1, cell proliferation rate: 65%.

[0194] It has high molecular weight and high strength, but poor toughness, low modulus and poor rigidity; it has a long degradation cycle and low pH during degradation, which is not conducive to tissue growth.

[0195] Comparative Example 2: Same as Example 1, except that basic magnesium sulfate whiskers were not added, but d-mannonic acid 1-4 lactone was added.

[0196] Test results:

[0197] (1) The weight-average molecular weight of polylactide is 21.5000, and the molecular weight distribution coefficient is 1.21.

[0198] (2) Melting point (°C): 169

[0199] (3) Tensile strength (MPa): 40, flexural modulus (MPa): 182

[0200] (4) 12w degradation percentage (wt%): 87; pH: 2.3-4.6

[0201] (5) Cytotoxicity: Grade 1, cell proliferation rate: 65%.

[0202] It has poor toughness and a low pH during degradation, which is not conducive to tissue growth.

[0203] Comparative Example 3: Same as Example 1, except that basic magnesium sulfate whiskers were added, and d-mannonic acid 1-4 lactone was removed during the polymerization process. Test results:

[0204] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0205] (2) The weight-average molecular weight of polylactide is 23.3000, and the molecular weight distribution coefficient is 1.25.

[0206] (3) Melting point (°C): 171

[0207] (4) Tensile strength (MPa): 43, flexural modulus (MPa): 1300

[0208] (5) 12w degradation percentage (wt%): 65; pH: 6.0-6.5

[0209] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 111%.

[0210] Compared with Example 1, the degradation is slower and the degradation cycle is longer, which does not match the tissue repair and recovery cycle.

[0211] Compared with Example 1, the degradation is slower, the degradation cycle is longer, and the toughness is reduced.

[0212] Comparative Example 4: Same as Example 1, except that only tetrabutyl titanate was used as the catalyst, and zinc phenylalanine was removed.

[0213] Test results:

[0214] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0215] (2) The weight-average molecular weight of polylactide is 12.6000, and the molecular weight distribution coefficient is 1.39.

[0216] (3) Melting point (°C): 169

[0217] (4) Tensile strength (MPa): 35, flexural modulus (MPa): 900

[0218] (5) 12w degradation percentage (wt%): 93; pH: 6.0-6.5

[0219] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 105%.

[0220] Compared with Example 1, the copolymer has a lower molecular weight, faster degradation, and lower tensile strength and flexural modulus.

[0221] Comparative Example 5: Same as Example 1, except that only zinc phenylalanine was used as the catalyst, and tetrabutyl titanate was removed.

[0222] Test results:

[0223] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0224] (2) The weight-average molecular weight of polylactide is 11.3000, and the molecular weight distribution coefficient is 1.41.

[0225] (3) Melting point (°C): 167

[0226] (4) Tensile strength (MPa): 33, flexural modulus (MPa): 830

[0227] (5) 12w degradation percentage (wt%): 95; pH: 6.0-6.5

[0228] (6) Cytotoxicity: Grade 0, Cell proliferation rate: 102%.

[0229] Compared with Example 1, the copolymer has a lower molecular weight, faster degradation, and lower tensile strength and flexural modulus.

[0230] Comparative Example 6: Same as Example 1, except that stannous octoate was used as the catalyst instead of the combined catalyst in Example 1. Test results:

[0231] (1) Diameter and length of basic magnesium sulfate whiskers: diameter 0.3-0.5μm, length: 75-105μm.

[0232] (2) The weight-average molecular weight of polylactide is 60.1000, and the molecular weight distribution coefficient is 1.28.

[0233] (3) Melting point (°C): 173

[0234] (4) Tensile strength (MPa): 55, flexural modulus (MPa): 1.3

[0235] (5) 12w degradation percentage (wt%): 82; pH: 6.0-6.5

[0236] (6) Cytotoxicity: Grade 1, cell proliferation rate: 68%.

[0237] Stannous octoate has high catalytic efficiency and can obtain higher molecular weight aggregates. However, compared with zinc catalysts, tin catalysts are more toxic to cells and require further washing and replacement to remove residual tin from polylactide.

[0238] It should be noted that while the specification provides preferred embodiments of the present invention, the invention can be implemented in many different forms and is not limited to the embodiments described herein. These embodiments are not intended to impose additional limitations on the scope of the invention; their purpose is to provide a more thorough and comprehensive understanding of the disclosure. Furthermore, the above-described technical features can be combined with each other to form various embodiments not listed above, all of which are considered to fall within the scope of the specification. Moreover, those skilled in the art can make improvements or modifications based on the above description, and all such improvements and modifications should fall within the protection scope of the appended claims.

Claims

1. A process for the preparation of a poly-L-lactide composite reinforced with magnesium hydroxide sulfate whiskers, characterized in that, Includes the following steps: (1) Preparation of basic magnesium sulfate whiskers: Mix an aqueous solution of a weakly alkaline organic magnesium salt with an aqueous solution of magnesium sulfate, and then add an aqueous solution of an alkaline amino acid under stirring. The mixed solution is subjected to a hydrothermal reaction. The reaction product is collected by filtration, washed and dried to obtain basic magnesium sulfate whiskers. (2) Preparation of polylactide modified with gluconolactone: under the protection of inert gas, lactide and gluconolactone and catalyst are added to the reactor and reacted at 120-180℃ for 6-50 hours to obtain gluconolactone modified polylactide. (3) Preparation of basic magnesium sulfate whisker-reinforced polylactide composite: The basic magnesium sulfate whiskers prepared in step (1) and the gluconic acid lactone-modified polylactide prepared in step (2) are melt-extruded together in the required mass ratio to obtain the basic magnesium sulfate whisker-reinforced polylactide composite.

2. The production method according to claim 1, characterized by, The polylactide complex comprises the following components in the indicated mass fractions: 80-97.5% gluconolactone-modified polylactide and 2.5-20% basic magnesium sulfate whiskers.

3. The production method according to claim 1, characterized by, The polylactide modified with gluconolactone contains 80-99 mol of lactide and 1-20 mol of gluconolactone.

4. The method of claim 1, wherein, The gluconic acid lactone includes at least one of glucono-δ-lactone, glucono-γ-lactone, D-mannose-1,4-lactone and L-mannose-1,4-lactone.

5. The preparation method according to claim 1, characterized in that, The basic magnesium sulfate whiskers are at least one of type 152 and type 150 basic magnesium sulfate whiskers, wherein the molar ratio of Mg(OH)2, MgSO4 and H2O in the composition of type 152 basic magnesium sulfate whiskers is 1:5:2, and the molar ratio of Mg(OH)2, MgSO4 and H2O in the composition of type 150 basic magnesium sulfate whiskers is 1:5:

0.

6. The preparation method according to claim 1, characterized in that, The molar ratio of weakly alkaline organic magnesium salts to magnesium sulfate is 1.0:3.0-6.

0.

7. The preparation method according to claim 1, characterized in that, The molar ratio of basic amino acids to magnesium sulfate is 1.0:1.0-2.

0.

8. The preparation method according to claim 1, characterized in that, The weakly alkaline organic magnesium salt includes at least one of magnesium acetate, magnesium propionate, and magnesium butyrate.

9. The preparation method according to claim 1, characterized in that, The basic amino acid includes at least one of lysine, histidine, and arginine.

10. The preparation method according to claim 1, characterized in that, The hydrothermal reaction is carried out under conditions of 0.4-1.0 MPa and 140-200℃.

11. The preparation method according to claim 5, characterized in that, The basic magnesium sulfate whiskers are type 152 basic magnesium sulfate whiskers.

12. The preparation method according to claim 11, characterized in that, The 152 type basic magnesium sulfate whiskers are dried at 240-250℃ for 2-10 hours to obtain the 150 type basic magnesium sulfate whiskers.

13. The preparation method according to claim 1, characterized in that, The catalyst contains zinc amino acids and / or tin, as well as titanate esters.

14. The preparation method according to claim 13, characterized in that, The amino acids in zinc and / or tin include at least one of phenylalanine, arginine, lysine, and histidine.

15. The preparation method according to claim 13, characterized in that, The amino acid zinc and / or tin complex is prepared as follows: using amino acids and zinc or tin salts as raw materials, a zinc or tin complex of the amino acid is prepared.

16. The preparation method according to claim 15, characterized in that, The zinc salt is zinc chloride or zinc sulfate, and the tin salt is stannous chloride.

17. The preparation method according to claim 13, characterized in that, The amino acid zinc and / or tin complex is prepared as follows: under the protection of an inert gas, the amino acid is reacted with an inorganic guanidine salt in a solvent at 50-80°C to generate an organic guanidine salt of the amino acid. Then, an aqueous and / or alcoholic solution of zinc salt and / or tin salt is added, and the reaction is carried out at 50-80°C for 3-8 hours to obtain the zinc and / or tin complex of the amino acid.

18. The preparation method according to claim 17, characterized in that, The ratio of the total amount of amino acids to the solvent is 1 mol: 1-2 L.

19. The preparation method according to claim 17, characterized in that, The molar ratio of amino acids to inorganic guanidine salts is 1:0.5-1.

2.

20. The preparation method according to claim 17, characterized in that, The molar ratio of amino acids to zinc salts and / or tin salts is 2:

1.

21. The preparation method according to claim 17, characterized in that, The solvent is at least one of water, methanol, ethanol, tetrahydrofuran, and dioxane.

22. The preparation method according to claim 17, characterized in that, The inorganic guanidine salt is guanidine carbonate.

23. The preparation method according to claim 17, characterized in that, It also includes filtering, collecting, washing, and drying the zinc and / or tin complexes of the obtained amino acids.

24. The preparation method according to claim 13, characterized in that, The titanate includes tetrabutyl titanate.

25. The preparation method according to claim 1, characterized in that, Step (2) is carried out in an anhydrous and oxygen-free environment.

26. The preparation method according to claim 1, characterized in that, Before the heating reaction in step (2), the reactor is evacuated.

27. The preparation method according to claim 1, characterized in that, The reaction in step (2) is carried out at 130-140°C for 16-32 hours.

28. The preparation method according to claim 1, characterized in that, The reaction described in step (2) involves reacting at 120-150°C for 2-6 hours, and then raising the temperature to 130-160°C for 5-15 hours.

29. The preparation method according to claim 1, characterized in that, Step (2) also includes adding an aprotic solvent to the reactor to dissolve the harvested gluconic acid lactone-modified polylactide, then precipitating, washing and drying the polymer with a polar solvent.

30. The preparation method according to claim 1, characterized in that, The melt extrusion described in step (3) is carried out under inert gas protection, and the outlet of the melt extrusion is protected with nitrogen or dry ice to prevent the polylactide composite reinforced with basic magnesium sulfate whiskers from being oxidized by air or absorbing water.

31. The use of a basic magnesium sulfate whisker-reinforced polylactide composite prepared by any one of claims 1-30 in the preparation of medical products.

32. The application according to claim 31, characterized in that, The medical product is used for soft tissue repair.

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