阅读说明：本技术 一种聚乳酸高强度高抗菌医用缝合线及其制备方法 (Polylactic acid high-strength high-antibacterial medical suture and preparation method thereof ) 是由 朱晓肸 朱坤福 于 2020-05-26 设计创作，主要内容包括：本发明涉及一种聚乳酸高强度高抗菌医用缝合线及其制备方法,由以下质量分的各组分组成：聚乳酸纳米材料110-130份,脱乙酰化壳聚糖20-25份,聚乙二醇单甲醚3-5份,茶树油1-2份,桂皮油2-3份,山梨醇1-2份,甘露醇1-2份；其中,聚乳酸纳米材料制备方法为：L-丙交酯、正十八胺改性的氧化石墨烯、催化剂、表面活性剂和抗菌药物在超临界二氧化碳中反应得到原位包裹抗菌药物的聚乳酸纳米材料。本发明方法制备的聚乳酸高强度高抗菌医用缝合线拉力强度高、打结牢固、生物相容性好,抗菌能力强。本发明制备聚乳酸纳米材料的方法无毒无污染,是一种经济实用、绿色环保的制备方法。(The invention relates to a polylactic acid high-strength high-antibacterial medical suture and a preparation method thereof, wherein the polylactic acid high-strength high-antibacterial medical suture comprises the following components in parts by mass: 130 parts of polylactic acid nano material, 20-25 parts of deacetylated chitosan, 3-5 parts of polyethylene glycol monomethyl ether, 1-2 parts of tea tree oil, 2-3 parts of cassia oil, 1-2 parts of sorbitol and 1-2 parts of mannitol; the preparation method of the polylactic acid nano material comprises the following steps: l-lactide, n-octadecylamine modified graphene oxide, a catalyst, a surfactant and an antibacterial agent react in supercritical carbon dioxide to obtain the polylactic acid nano material in which the antibacterial agent is wrapped in situ. The polylactic acid medical suture line with high strength and high antibacterial property prepared by the method has the advantages of high tensile strength, firm knotting, good biocompatibility and strong antibacterial capability. The method for preparing the polylactic acid nano material is non-toxic and pollution-free, and is an economical, practical, green and environment-friendly preparation method.)

1. A polylactic acid high-strength high-antibacterial medical suture and a preparation method thereof are characterized by comprising the following components by mass: 130 parts of polylactic acid nano material, 20-25 parts of deacetylated chitosan, 3-5 parts of polyethylene glycol monomethyl ether, 1-2 parts of tea tree oil, 2-3 parts of cassia oil, 1-2 parts of sorbitol and 1-2 parts of mannitol; the preparation method of the polylactic acid nano material comprises the following steps: (1) adding L-lactide, n-octadecylamine modified graphene oxide, a surfactant and an antibacterial drug into a pre-dried reaction kettle, and performing vacuum drying for 2-3 hours at 65-85 ℃ by using an oil pump; (2) adding a catalyst under the protection of argon, heating to 130-150 ℃, and adding carbon dioxide gas of 25-30 MPa; (3) reacting for 15-20 hours under stirring, then cooling to room temperature under stirring, discharging carbon dioxide gas, opening the reaction kettle and collecting a sample, namely the polylactic acid nano material.

2. The polylactic acid medical suture with high strength and high antibacterial property and the preparation method thereof as claimed in claim 1, wherein the deacetylated chitosan is 75-85% deacetylated chitosan.

3. The polylactic acid medical suture line with high strength and high antibacterial property and the preparation method thereof as claimed in claim 1, wherein the species of the polyethylene glycol monomethyl ether in the step (1) is one or more of polyethylene glycol 8000 monomethyl ether, polyethylene glycol 9000 monomethyl ether and polyethylene glycol 10000 monomethyl ether.

4. The polylactic acid high-strength high-antibacterial medical suture line and the preparation method thereof as claimed in claim 1, wherein the graphene oxide in step (1) is one or more of single-layer graphene oxide, double-layer graphene oxide and three-layer graphene oxide.

5. The polylactic acid medical suture line with high strength and high antibacterial property and the preparation method thereof as claimed in claim 1, wherein the graphene oxide in step (1) is prepared by using Staudenmaier method.

6. The polylactic acid medical suture line with high strength and high antibacterial property and the preparation method thereof as claimed in claim 1, wherein the preparation method of the n-octadecylamine modified graphene oxide in the step (1) is as follows: graphene oxide is ultrasonically dispersed in DMF, oxalyl chloride is added at the temperature of-5 ℃ and the mixture is treated and reacted at the temperature of 80-85 ℃ for 12-14 hours. And after the reaction is finished, washing the reaction product by using dichloromethane, and carrying out forced air drying at the temperature of 50-60 ℃ for 10-12 hours to obtain the graphene oxide functionalized by the acyl chloride group. And ultrasonically dispersing the graphene oxide functionalized by acyl chloride groups in DMF (dimethyl formamide), adding triethylamine and n-octadecylamine, and reacting the mixture for 10-15 hours at the temperature of 100-110 ℃. And filtering the black product, washing with a small amount of ethanol, and carrying out forced air drying at 70-80 ℃ for 8-10 hours to obtain the n-octadecylamine modified graphene oxide.

7. The polylactic acid medical suture with high strength and high antibacterial property and the preparation method thereof as claimed in claim 1, wherein the surfactant in step (1) is one or two of polyoxyethylene octylphenol ether and polyoxyethylene nonylphenol ether.

8. The polylactic acid medical suture with high strength and high antibacterial property and the preparation method thereof as claimed in claim 1, wherein the antibacterial drug in step (1) is one or two of penicillin and erythromycin.

9. The polylactic acid high-strength high-antibacterial medical suture line and the preparation method thereof as claimed in claim 1, wherein the catalyst in step (2) is one or more of stannous lactate, aluminum lactate and zinc lactate.

10. The polylactic acid medical suture line with high strength and high antibacterial property and the preparation method thereof as claimed in claim 1, wherein the mass fractions of the L-lactide, the n-octadecylamine modified graphene oxide, the surfactant, the antibacterial agent and the catalyst in the steps (1) and (2) are (100) 120, (5-8) 2-3, (1-2) 2-3.

11. The polylactic acid high-strength high-antibacterial medical suture line and the preparation method thereof as claimed in claims 1 to 10, characterized by comprising the following steps:

(1) preparing suture fibers: uniformly mixing polylactic acid nano material, deacetylated chitosan, polyethylene glycol monomethyl ether, tea tree oil, cassia oil, sorbitol and mannitol, heating to 75-85 ℃, stirring at the speed of 200-300r/min for 5-8h, heating to 125 ℃, extruding by using a double-screw extruder, cooling by water, air-drying, and granulating to obtain master batches; heating to 190-220 ℃ to melt and defoam the master batch, and obtaining primary fiber through a spinneret plate; stretching the primary fiber in a water bath at 50-60 ℃ to obtain suture fiber;

(2) drying and sterilizing: and (3) further drying and sterilizing the suture fiber by using ethylene oxide to obtain the dried polylactic acid high-strength high-antibacterial suture.

12. The polylactic acid medical suture with high strength and high antibacterial property and the preparation method thereof as claimed in claim 11, wherein the ethylene oxide sterilization concentration in the step (2) is 250mg/L-350 mg/L.

13. The polylactic acid medical suture with high strength and high antibacterial property and the preparation method thereof as claimed in claim 11, wherein the ethylene oxide sterilization time in the step (2) is 4h-5 h.

Technical Field

The invention relates to a polylactic acid high-strength high-antibacterial medical suture and a preparation method thereof, belonging to the technical field of nano medical suture processing.

Background

The polylactic acid medical suture is generally used in operations and plays an important role in promoting wound healing. However, in the prior art, the strength of the suture thread for polylactic acid is far lower than that of a non-absorbable suture thread, a good antibacterial effect can be achieved only by processing with a special antibacterial agent, and the antibacterial effect is not lasting, so that the prepared high-strength high-antibacterial suture thread for polylactic acid has high tensile strength, firm knotting, good biocompatibility, no adverse reaction in a human body, and long-lasting antibacterial performance, and has important significance.

There are three conventional methods for synthesizing polylactic acid, which are direct condensation polymerization of lactic acid, Ring Opening Polymerization (ROP) of lactide, and azeotropic dehydration condensation polymerization of lactic acid. The lactic acid condensation polymerization reaction is a method for generating polylactic acid from lactic acid through bulk condensation polymerization reaction, but water is generated in the lactic acid condensation polymerization process, and the presence of water is not beneficial to forward reaction, so that the molecular chain of the obtained product is short. Lactic acid azeotropic dehydration condensation polymerization is a method for preparing polylactic acid with higher molecular weight by azeotropic dehydration of lactic acid and a catalyst in a refluxing high-boiling-point aprotic solvent under reduced pressure, but the reaction conditions are severe, the production cost is high and the process is complex. Compared with the two synthesis methods, no byproduct is generated in the ROP reaction process, and polylactic acid with higher molecular weight can be obtained, but the traditional lactide ring-opening polymerization reaction usually uses an organic solvent such as toluene, so that the cost is increased, and the toxic and side effects are improved. Therefore, an economical, practical, green and environment-friendly method for preparing polylactic acid is needed.

The tensile modulus of graphene oxide is 1.01TPa, the ultimate strength is 116GPa, the graphene oxide is a nano material with high strength and high toughness, n-octadecylamine modified graphene oxide and an antibacterial are added into an L-lactide monomer, a reaction method of in-situ polymerization is utilized to synthesize a polylactic acid nano material wrapping the antibacterial, the polylactic acid and the n-octadecylamine modified graphene oxide are combined through pi-pi stacking effect, pores of a polymer are filled, acting force between polymer chain segments is enhanced, the polylactic acid and the n-octadecylamine modified graphene oxide are crosslinked to form a chemical bond through chemical reaction, the strength of a polylactic acid medical suture line is improved, the sharp edge of the modified graphene oxide can be cut, mechanically wrapped, peroxidized and phospholipid molecules are extracted to break the structural and functional integrity of bacteria and fungi, and the oxygen-containing functional group on the graphene oxide sheet layer and the sugar or protein of cells in the bacteria and fungi form a hydrogen bond The method comprises the following steps of (1) blocking the material exchange of bacteria and fungi so as to cause the bacteria and the fungi to lack nutrient substances to die, (5) combining polylactic acid synthesis, n-octadecylamine modified graphene oxide and antibacterial drugs, and simultaneously realizing the in-situ synthesis of polylactic acid nano materials and the in-situ wrapping of the antibacterial drugs, and is an important idea for developing the polylactic acid medical suture which has the advantages of high tensile strength, firm knot, good biocompatibility, no adverse reaction in a human body and improved lasting antibacterial performance.

The supercritical carbon dioxide technology is a novel technology with great development potential in the field of green chemistry. The technology takes carbon dioxide as a medium for chemical synthesis or processing, has the characteristics of stable chemical property, no toxicity, no corrosion, no flammability, no explosion, easy realization of critical state (304K, 73.8bar) and the like, simultaneously has high dissolving capacity of liquid and high diffusivity of gas, and is an important idea for replacing the traditional organic solvent for synthesizing polylactic acid.

Disclosure of Invention

The invention relates to a polylactic acid high-strength high-antibacterial medical suture and a preparation method thereof, wherein the polylactic acid high-strength high-antibacterial medical suture comprises the following components in parts by mass: 130 parts of polylactic acid nano material, 20-25 parts of deacetylated chitosan, 3-5 parts of polyethylene glycol monomethyl ether, 1-2 parts of tea tree oil, 2-3 parts of cassia oil, 1-2 parts of sorbitol and 1-2 parts of mannitol; the preparation method of the polylactic acid nano material comprises the following steps: (1) adding L-lactide, n-octadecylamine modified graphene oxide, a surfactant and an antibacterial drug into a pre-dried reaction kettle, and performing vacuum drying for 2-3 hours at 65-85 ℃ by using an oil pump; (2) adding a catalyst under the protection of argon, heating to 130-150 ℃, and adding carbon dioxide gas of 25-30 MPa; (3) reacting for 15-20 hours under stirring, then cooling to room temperature under stirring, discharging carbon dioxide gas, opening the reaction kettle and collecting a sample, namely the polylactic acid nano material.

The chitosan according to the scheme is deacetylated 60-80%.

According to the scheme, the polyethylene glycol monomethyl ether in the step (1) is one or more of polyethylene glycol 8000 monomethyl ether, polyethylene glycol 9000 monomethyl ether and polyethylene glycol 10000 monomethyl ether.

According to the scheme, the graphene oxide type in the step (1) is one or more of single-layer graphene oxide, double-layer graphene oxide and three-layer graphene oxide.

According to the scheme, the graphene oxide in the step (1) is prepared by using a Staudenmaier method.

According to the scheme, the preparation method of the n-octadecylamine modified graphene oxide in the step (1) comprises the following steps: graphene oxide is ultrasonically dispersed in DMF, oxalyl chloride is added at the temperature of-5 ℃ and the mixture is treated and reacted at the temperature of 80-85 ℃ for 12-14 hours. And after the reaction is finished, washing the reaction product by using dichloromethane, and carrying out forced air drying at the temperature of 50-60 ℃ for 10-12 hours to obtain the graphene oxide functionalized by the acyl chloride group. And ultrasonically dispersing the graphene oxide functionalized by acyl chloride groups in DMF (dimethyl formamide), adding triethylamine and n-octadecylamine, and reacting the mixture for 10-15 hours at the temperature of 100-110 ℃. And filtering the black product, washing with a small amount of ethanol, and carrying out forced air drying at 70-80 ℃ for 8-10 hours to obtain the n-octadecylamine modified graphene oxide.

According to the scheme, the surfactant in the step (1) is one or two of polyoxyethylene octylphenol ether and polyoxyethylene nonylphenol ether.

According to the scheme, the antibacterial agent in the step (1) is one or two of penicillin and erythromycin.

According to the scheme, the catalyst in the step (2) is one or more of stannous lactate, aluminum lactate and zinc lactate.

According to the scheme, the mass fractions of the L-lactide, the n-octadecylamine modified graphene oxide, the surfactant, the antibacterial agent and the catalyst in the steps (1) and (2) are (100-120), (5-8), (2-3), (1-2) and (2-3).

According to the scheme, the polylactic acid high-strength high-antibacterial medical suture and the preparation method thereof are characterized by comprising the following steps:

(1) preparing suture fibers: uniformly mixing polylactic acid nano material, deacetylated chitosan, polyethylene glycol monomethyl ether, tea tree oil, cassia oil, sorbitol and mannitol, heating to 75-85 ℃, stirring at the speed of 200-300r/min for 5-8h, heating to 125 ℃, extruding by using a double-screw extruder, cooling by water, air-drying, and granulating to obtain master batches; heating to 190-220 ℃ to melt and defoam the master batch, and obtaining primary fiber through a spinneret plate; stretching the primary fiber in a water bath at 50-60 ℃ to obtain suture fiber;

(2) drying and sterilizing: and (3) further drying and sterilizing the suture fiber by using ethylene oxide to obtain the dried polylactic acid high-strength high-antibacterial suture. The sterilization concentration of the ethylene oxide is 250g/L-350mg/L, and the sterilization time of the ethylene oxide is 4h-5 h.

The invention has the beneficial effects that:

according to the invention, polylactic acid synthesis, modified graphene oxide and antibacterial agent are combined, in-situ synthesis of a polylactic acid nano material and in-situ wrapping of the antibacterial agent are realized simultaneously, and the polylactic acid is combined with the modified n-octadecylamine modified graphene oxide through pi-pi accumulation, so that the pores of the polymer are filled, and the acting force between polymer chain segments is enhanced; polylactic acid and n-octadecylamine modified graphene oxide are crosslinked to form a chemical bond through a chemical reaction, so that the strength of the polylactic acid medical suture is improved; the n-octadecylamine modified graphene oxide has good affinity to fungi and bacteria, keeps sharp edges, and can cut, mechanically wrap, peroxide and extract phospholipid molecules to break the structural and functional integrity of the bacteria and the fungi; the oxygen-containing functional groups on the n-octadecylamine-modified graphene oxide sheets form hydrogen bonds with sugars or proteins of cells in bacteria and fungi to block material exchange of the bacteria and fungi, thereby causing the bacteria and fungi to die of nutrient-deficient substances. The poly-p-dioxanone medical suture line which has high tensile strength, firm knot, good biocompatibility, no adverse reaction in human body and improved lasting antibacterial property is developed. The polylactic acid nano material coated with the antibacterial agent in situ is synthesized by adopting a supercritical carbon dioxide technology, and the synthesis method is economical, practical, green and environment-friendly.

Detailed Description

The following is a further description with reference to specific examples.