Preparation method of polylactic acid antibacterial material for medical stent

Abstract

The invention relates to the technical field of polylactic acid, and discloses a preparation method of a polylactic acid antibacterial material for medical scaffolds.According to the preparation method, polylactic acid, a polyurethane elastomer and a quaternary ammonium salt polymer antibacterial agent are subjected to melt extrusion, and the polylactic acid antibacterial material for the medical scaffoldsis obtained. The quaternary ammonium salt polymer antibacterial agent provided by the invention contains a polyester structural unit similar to polylactic acid and a carbamate group identical to polyurethane, so that the quaternary ammonium salt polymer antibacterial agent can play a role of a compatilizer, the compatibility between polylactic acid and a polyurethane elastomer is improved, the polyurethane elastomer plays a better toughening role, and the service life of the polyurethane elastomer is prolonged. The elongation at break and the impact strength of polylactic acid are obviously improved, and higher tensile strength is kept. The obtained polylactic acid material has good practical application in the fields of medical supplies such as stents, biological tissue engineering and the like.

Description

Technical Field

[0001] The invention relates to the technical field of polylactic acid, in particular to a method for preparing a polylactic acid antibacterial material for a medical stent. Background Art

[0002] Polylactic acid is a new type of biodegradable material. Its raw materials are cheap and easy to obtain, the preparation method is simple, it has high mechanical strength and good biocompatibility. It is widely used in tableware, packaging, medical supplies, biological tissue engineering and other fields. Traditional polylactic acid has the problem of poor toughness, and toughening and modifying it is a research hotspot. At present, rubber, polyurethane, POE elastomer, poly(propylene glycol adipate) and the like are mainly used to toughen and modify polylactic acid.

[0003] Polyurethane and its elastomer are materials with good toughness, high mechanical strength and high heat resistance, and are widely used in polymer materials such as polylactic acid, epoxy resin, polypropylene, and polyvinyl chloride. The Chinese invention patent with announcement number CN110358097B discloses a PLA-based compatibilizer with excellent performance, its preparation method and application. The compatibilizer prepared with polylactic acid, glycidyl methacrylate and diisopropylbenzene peroxide as raw materials can solve the compatibility problem between PLA and TPU, thereby improving the comprehensive performance of the composite material. However, the patent does not reflect the good antibacterial properties of polylactic acid, which is not conducive to the practical application of polylactic acid in the fields of medical supplies, biological tissue engineering, etc. Summary of the invention

[0004] Technical problem to be solved: The present invention provides a polylactic acid antibacterial material for medical stents with antibacterial properties and high toughness.

[0005] Technical solution: A method for preparing a polylactic acid antibacterial material for medical stents, comprising:

[0006] Step A: In an ice bath, add diacyl chloride monomer, dihydroxy quaternary ammonium salt monomer and triethylamine in a ratio of 1 mol:(1-1.1) mol:(1-1.2) mol to N,N-dimethylformamide, and then stir and react at room temperature for 18-24 hours. Pour the solution into ethanol, filter, wash with water and ethanol, and dry to obtain a quaternary ammonium salt polymer antibacterial agent.

[0007] Step B: adding polylactic acid, polyurethane elastomer, quaternary ammonium salt polymer antibacterial agent and antioxidant in a ratio of (70-95) g: (5-30) g: (1.2-5) g into a twin-screw extruder for melt extrusion to obtain a polylactic acid antibacterial material for medical stents.

[0008] Further, the structural formula of the diacyl chloride is n is any integer value from 1 to 4.

[0009] Furthermore, in step B, the extrusion temperature is 180-190° C. and the screw speed is 15-30 r / min.

[0010] Further, the preparation method of the dihydroxy quaternary ammonium salt monomer is:

[0011] (1) Add hexamethylene diisocyanate and 4-bromomethylbenzyl alcohol in a ratio of 1 mol:(1-1.2) mol to tetrahydrofuran, heat to 65-70°C in a nitrogen atmosphere, condense and reflux for 4-6 hours, rotary evaporate, wash with petroleum ether, and recrystallize the product in ethyl acetate to obtain a dibromo intermediate.

[0012] (2) Add 1 mol:(1-1.4) mol of dibromo intermediate and 3-dimethylamino-1-propanol to the solvent, heat to 75-85° C., condense and reflux for 24-36 hours, rotary evaporate, wash with petroleum ether, and recrystallize the product in ethanol to obtain a dihydroxy quaternary ammonium salt monomer.

[0013] Furthermore, the solvent in (2) is ethanol or acetonitrile.

[0014] (III) Technical effect: The present invention uses hexamethylene diisocyanate, 4-bromomethylbenzyl alcohol, 3-dimethylamino-1-propanol and other raw materials to react to obtain a new type of dihydroxy quaternary ammonium salt monomer, which is then polymerized with a diacyl chloride compound to obtain a quaternary ammonium salt polymer antibacterial agent, and then the polylactic acid is filled and modified with a polyurethane elastomer toughening agent to obtain a polylactic acid antibacterial material for medical stents.

[0015] The quaternary ammonium salt polymer antibacterial agent of the invention contains polyester structural units, has good compatibility with the polyester molecular chain of polylactic acid, and has little effect on the mechanical properties of polylactic acid. Meanwhile, the polymer main chain of the antibacterial agent contains a large number of quaternary ammonium salt antibacterial groups, which endows the polylactic acid with good antibacterial rate and antibacterial performance.

[0016] The quaternary ammonium salt polymer antibacterial agent of the present invention contains a polyester structural unit similar to polylactic acid and a carbamate group identical to polyurethane, so that the quaternary ammonium salt polymer antibacterial agent can play the role of a compatilizer, improve the compatibility between polylactic acid and polyurethane elastomer, make polyurethane elastomer play a better toughening effect, the elongation at break and the impact strength of polylactic acid are obviously improved, and higher tensile strength is maintained. The obtained polylactic acid material has good practical application in fields such as medical supplies such as stents and biological tissue engineering. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1 It is the reaction formula for preparing dihydroxy quaternary ammonium salt monomer.

[0018] Figure 2 It is the reaction formula of quaternary ammonium polymer antibacterial agent. DETAILED DESCRIPTION

[0019] The embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only used to illustrate the present invention and should not be construed as limiting the scope of the present invention.

[0020] Polylactic acid, CAS No. 26023-30-3, Hubei Xingyan New Material Technology Co., Ltd.

[0021] Polyurethane elastomer, model BASF TPU C95A, Dongguan Canhui New Material Technology Co., Ltd.

[0022] Embodiment 1:

[0023] (1) Add 40 mmol hexamethylene diisocyanate and 40 mmol 4-bromomethylbenzyl alcohol to 80 mL tetrahydrofuran, heat to 70°C in a nitrogen atmosphere, reflux for 4 h, rotary evaporate, wash with petroleum ether, and recrystallize the product from ethyl acetate to obtain a dibromo intermediate.

[0024] (2) Add 40 mmol of the dibromo intermediate and 56 mmol of 3-dimethylamino-1-propanol to 300 mL of acetonitrile solvent, heat to 85° C., condense and reflux for 24 hours, rotary evaporate, wash with petroleum ether, and recrystallize the product in ethanol to obtain a dihydroxy quaternary ammonium salt monomer.

[0025] (3) In an ice bath, add 60 mmol glutaryl chloride, 60 mol dihydroxy quaternary ammonium salt monomer, and 66 mmol triethylamine to 800 mL N,N-dimethylformamide, and then stir and react at room temperature for 24 h. Pour the solution into ethanol, filter, wash with water and ethanol, and dry to obtain a quaternary ammonium salt polymer antibacterial agent.

[0026] (4) Add 950 g of polylactic acid, 50 g of polyurethane elastomer, 12 g of quaternary ammonium salt polymer antibacterial agent, and 7 g of antioxidant 1010 into a twin-screw extruder for melt extrusion at an extrusion temperature of 185° C. and a screw speed of 15 r / min to obtain a polylactic acid antibacterial material for medical stents.

[0027] Embodiment 2:

[0028] (1) Add 40 mmol hexamethylene diisocyanate and 48 mmol 4-bromomethylbenzyl alcohol to 100 mL tetrahydrofuran, heat to 65°C in a nitrogen atmosphere, condense and reflux for 6 h, rotary evaporate, wash with petroleum ether, and recrystallize the product in ethyl acetate to obtain a dibromo intermediate.

[0029] (2) Add 40 mmol of the dibromo intermediate and 40 mmol of 3-dimethylamino-1-propanol to 300 mL of ethanol solvent, heat to 75° C., condense and reflux for 36 hours, rotary evaporate, wash with petroleum ether, and recrystallize the product in ethanol to obtain a dihydroxy quaternary ammonium salt monomer.

[0030] (3) In an ice bath, add 60 mmol malonyl chloride, 66 mol dihydroxy quaternary ammonium salt monomer, and 66 mmol triethylamine to 900 mL N,N-dimethylformamide, and then stir and react at room temperature for 18 h. Pour the solution into ethanol, filter, wash with water and ethanol, and dry to obtain a quaternary ammonium salt polymer antibacterial agent.

[0031] (4) Add 900 g of polylactic acid, 100 g of polyurethane elastomer, 25 g of quaternary ammonium salt polymer antibacterial agent, and 6 g of antioxidant 1010 into a twin-screw extruder for melt extrusion at an extrusion temperature of 180° C. and a screw speed of 30 r / min to obtain a polylactic acid antibacterial material for medical stents.

[0032] Embodiment 3:

[0033] (1) In an ice bath, add 60 mmol adipoyl chloride, 60 mol dihydroxy quaternary ammonium salt monomer (prepared in the same manner as in Example 1), and 60 mmol triethylamine to 800 mL N,N-dimethylformamide, and then stir at room temperature for 24 h. Pour the solution into ethanol, filter, wash with water and ethanol, and dry to obtain a quaternary ammonium salt polymer antibacterial agent.

[0034] (2) Add 800 g of polylactic acid, 200 g of polyurethane elastomer, 38 g of quaternary ammonium polymer antibacterial agent, and 4 g of antioxidant 1010 into a twin-screw extruder for melt extrusion at an extrusion temperature of 190° C. and a screw speed of 15 r / min to obtain a polylactic acid antibacterial material for medical stents.

[0035] Embodiment 4:

[0036] (1) In an ice bath, add 60 mmol succinyl chloride, 66 mol dihydroxy quaternary ammonium salt monomer (prepared in the same manner as in Example 1), and 72 mmol triethylamine to 900 mL N,N-dimethylformamide, and then stir and react at room temperature for 18 h. Pour the solution into ethanol, filter, wash with water and ethanol, and dry to obtain a quaternary ammonium salt polymer antibacterial agent.

[0037] (2) Add 700 g of polylactic acid, 300 g of polyurethane elastomer, 50 g of quaternary ammonium salt polymer antibacterial agent, and 4 g of antioxidant 1010 into a twin-screw extruder for melt extrusion at an extrusion temperature of 190° C. and a screw speed of 30 r / min to obtain a polylactic acid antibacterial material for medical stents.

[0038] Comparative Example 1:

[0039] (1) Add 950 g of polylactic acid and 7 g of antioxidant 1010 into a twin-screw extruder for melt extrusion at an extrusion temperature of 185° C. and a screw speed of 15 r / min to obtain a polylactic acid material for medical stents.

[0040] Comparative Example 2:

[0041] (1) Add 950 g of polylactic acid, 12 g of a quaternary ammonium salt polymer antibacterial agent (prepared in the same manner as in Example 1), and 7 g of antioxidant 1010 into a twin-screw extruder for melt extrusion at an extrusion temperature of 185° C. and a screw speed of 15 r / min to obtain a polylactic acid antibacterial material for medical stents.

[0042] Comparative Example 3:

[0043] (1) Add 950 g of polylactic acid, 50 g of polyurethane elastomer, and 7 g of antioxidant 1010 into a twin-screw extruder for melt extrusion at an extrusion temperature of 185° C. and a screw speed of 15 r / min to obtain a polylactic acid material for medical stents.

[0044] Comparative Example 4

[0045] (1) Add 40 mmol of 1,4-di(bromomethyl)benzene and 56 mmol of 3-dimethylamino-1-propanol to 300 mL of acetonitrile solvent, heat to 85°C, condense and reflux for 24 hours, rotary evaporate, wash with petroleum ether, and recrystallize the product in ethanol to obtain a dihydroxy quaternary ammonium salt monomer. The structural formula is:

[0046]

[0047] (2) In an ice bath, add 60 mmol glutaryl chloride, 60 mol dihydroxy quaternary ammonium salt monomer, and 66 mmol triethylamine to 800 mL N,N-dimethylformamide, and then stir and react at room temperature for 24 h. Pour the solution into ethanol, filter, wash with water and ethanol, and dry to obtain a quaternary ammonium salt polymer antibacterial agent.

[0048] (3) Add 950 g of polylactic acid, 50 g of polyurethane elastomer, 12 g of quaternary ammonium polymer antibacterial agent, and 7 g of antioxidant 1010 into a twin-screw extruder for melt extrusion at an extrusion temperature of 185° C. and a screw speed of 15 r / min to obtain a polylactic acid antibacterial material for medical stents.

[0049] The polylactic acid antibacterial material was injected into a specimen by an injection molding machine at a temperature of 200°C. The tensile properties were tested according to GB / T1040.1-2018. The impact properties were tested according to GB / T 1043.1-2008.

[0050] The antibacterial performance was tested according to QB / T 2591-2003 standard. Antibacterial rate = (BC) / B×100%. B is the average number of recovered bacteria (cfu / piece) of the blank control sample, and the polylactic acid material of comparative example 1 was used as the blank control sample. A is the average number of recovered bacteria (cfu / piece) of the antibacterial plastic sample, and the polylactic acid materials of Examples 1-4 and Comparative Examples 2-4 were used as the antibacterial plastic samples.

[0051] Table 1: Effect test

[0052]

[0053] As shown in Table 1, the elongation at break of the polylactic acid material of Comparative Example 1 is only 8.4%, and the impact strength is only 1.94 kJ / m 2 , poor toughness.

[0054] Comparative Example 2 adds a quaternary ammonium salt polymer antibacterial agent, which contains a polyester structural unit and has good compatibility with the polyester molecular chain of polylactic acid. It has little effect on the mechanical properties of polylactic acid, and the tensile strength, elongation at break and impact strength are very similar to those of Comparative Example 1. At the same time, it gives polylactic acid good antibacterial rate and antibacterial properties.

[0055] In Comparative Example 3, polyurethane elastomer was added, and the elongation at break and impact strength of the polylactic acid material were improved to a certain extent, and the toughness was improved, but the tensile strength was reduced, and it had almost no antibacterial property.

[0056] Embodiment 1-4 has added quaternary ammonium salt polymer antibacterial agent and polyurethane elastomer, quaternary ammonium salt polymer antibacterial agent contains the polyester structural unit similar to polylactic acid, and the carbamate group identical with polyurethane, makes quaternary ammonium salt polymer antibacterial agent can play the effect of compatilizer, improves the compatibility between polylactic acid and polyurethane elastomer, makes polyurethane elastomer play better toughening effect, elongation at break and impact strength obviously improve, and keeps higher tensile strength.Quaternary ammonium salt polymer antibacterial agent gives polylactic acid excellent antibacterial property simultaneously.

[0057] Comparative Example 4 uses 1,4-bis(bromomethyl)benzene and 3-dimethylamino-1-propanol to react to obtain a dihydroxy quaternary ammonium salt monomer, which is then polymerized with glutaryl chloride to obtain a quaternary ammonium salt polymer antibacterial agent that does not contain a carbamate group and cannot act as a compatibilizer. It cannot improve the compatibility between polylactic acid and polyurethane elastomer, resulting in poor toughening effect of the polyurethane elastomer, and the elongation at break and impact strength of the polylactic acid material are lower than those of the embodiments, and the tensile strength is reduced.

[0058] It can be understood that the above specific description of the present invention is only used to illustrate the present invention and is not limited to the technical solutions described in the embodiments of the present invention. Those skilled in the art should understand that the present invention can still be modified or replaced by equivalents to achieve the same technical effects; as long as the use requirements are met, they are within the protection scope of the present invention.

Claims

1. A method for preparing a polylactic acid antibacterial material for medical stents, characterized in that: The preparation method comprises the following steps: Step A: In an ice bath, add diacyl chloride monomer having a structural formula of dihydroxy quaternary ammonium salt monomer and triethylamine, and then stirred at room temperature for 18-24 hours, the solution was poured into ethanol, filtered, washed with water and ethanol, and dried to obtain a quaternary ammonium salt polymer antibacterial agent; Step B: adding polylactic acid, polyurethane elastomer, quaternary ammonium salt polymer antibacterial agent and antioxidant into a twin-screw extruder for melt extrusion to obtain polylactic acid antibacterial material for medical stent.

2. The method for preparing the polylactic acid antibacterial material for medical stent according to claim 1, characterized in that: In the step A, the ratio of the diacyl chloride monomer, the dihydroxy quaternary ammonium salt monomer, and the triethylamine is 1 mol: (1-1.1) mol: (1-1.2) mol.

3. The method for preparing the polylactic acid antibacterial material for medical stent according to claim 2, characterized in that: The structural formula of the diacyl chloride is n is any integer value from 1 to 4.

4. The method for preparing the polylactic acid antibacterial material for medical stent according to claim 1, characterized in that: In the step B, the ratio of polylactic acid, polyurethane elastomer and quaternary ammonium salt polymer antibacterial agent is (70-95) g: (5-30) g: (1.2-5) g.

5. The method for preparing the polylactic acid antibacterial material for medical stent according to claim 1, characterized in that: In step B, the extrusion temperature is 180-190° C., and the screw speed is 15-30 r / min.

6. The method for preparing the polylactic acid antibacterial material for medical stent according to claim 2, characterized in that: The preparation method of the dihydroxy quaternary ammonium salt monomer is: (1) Add hexamethylene diisocyanate and 4-bromomethylbenzyl alcohol to tetrahydrofuran, heat to 65-70° C. in a nitrogen atmosphere, reflux under condensation for 4-6 hours, rotary evaporate, wash with petroleum ether, and recrystallize the product in ethyl acetate to obtain a dibromo intermediate; (2) Add the dibromo intermediate and 3-dimethylamino-1-propanol to the solvent, heat to 75-85° C., condense and reflux for 24-36 hours, rotary evaporate, wash with petroleum ether, and recrystallize the product in ethanol to obtain a dihydroxy quaternary ammonium salt monomer.

7. The method for preparing the polylactic acid antibacterial material for medical stent according to claim 6, characterized in that: The ratio of hexamethylene diisocyanate to 4-bromomethylbenzyl alcohol in (1) is 1 mol:(1-1.2) mol.

8. The method for preparing the polylactic acid antibacterial material for medical stent according to claim 6, characterized in that: The solvent in (2) is ethanol or acetonitrile.

9. The method for preparing the polylactic acid antibacterial material for medical stent according to claim 6, characterized in that: The ratio of the dibromo intermediate to 3-dimethylamino-1-propanol in (2) is 1 mol:(1-1.4) mol.

10. A polylactic acid antibacterial material for medical stents prepared by the preparation method according to any one of claims 1 to 9.

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