阅读说明：本技术 一种聚对二氧杂环己酮高强度高抗菌缝合线及制备方法 (High-strength and high-antibacterial poly (p-dioxanone) suture and preparation method thereof ) 是由 朱俊辉 朱志腾 薛飞 于 2020-05-26 设计创作，主要内容包括：本发明涉及一种聚对二氧杂环己酮高强度高抗菌缝合线及制备方法,由以下质量分的各组分组成：聚对二氧杂环己酮纳米材料80-100份,壳聚糖15-25份,聚乙二醇单甲醚3-5份,桂皮油2-3份,甘露醇1-2份；其中,聚对二氧杂环己酮纳米材料制备方法为：二氧杂环环己酮、聚乙二醇改性的氧化石墨烯、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的聚对二氧杂环己酮纳米材料。本发明方法制备的聚对二氧杂环己酮高强度高抗菌缝合线拉力强度高、打结牢固、生物相容性好、抗菌能力强。本发明制备聚对二氧杂环己酮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 high-strength and high-antibacterial poly (p-dioxanone) suture and a preparation method thereof, wherein the suture comprises the following components in parts by mass: 80-100 parts of poly-p-dioxanone nano material, 15-25 parts of chitosan, 3-5 parts of polyethylene glycol monomethyl ether, 2-3 parts of cassia oil and 1-2 parts of mannitol; wherein the preparation method of the poly-p-dioxanone nano material comprises the following steps: the dioxanone, the polyethylene glycol modified graphene oxide, the catalyst, the surfactant and the antibacterial agent react in supercritical carbon dioxide to obtain the poly-p-dioxanone nano material in which the antibacterial agent is wrapped in situ. The high-strength and high-antibacterial poly-p-dioxanone suture prepared by the method has the advantages of high tensile strength, firm knot, good biocompatibility and strong antibacterial capability. The method for preparing the poly-p-dioxanone nano material is non-toxic and pollution-free, and is an economical, practical, green and environment-friendly preparation method.)

1. The high-strength and high-antibacterial poly (p-dioxanone) suture line and the preparation method are characterized by comprising the following components in parts by mass: 80-100 parts of poly-p-dioxanone nano material, 15-25 parts of chitosan, 3-5 parts of polyethylene glycol monomethyl ether, 2-3 parts of cassia oil and 1-2 parts of mannitol; wherein the preparation method of the poly-p-dioxanone nano material comprises the following steps: (1) adding dioxanone, polyethylene glycol modified graphene oxide, a surfactant and an antibacterial drug into a pre-dried reaction kettle, and performing vacuum drying for 2-3 hours at the temperature of 60-80 ℃ by using an oil pump; (2) adding a catalyst under the protection of argon, heating to 90-110 ℃, and adding carbon dioxide gas with the pressure of 28-32 MPa; (3) reacting for 25-35 hours under stirring, then cooling to room temperature under stirring, discharging carbon dioxide gas, opening the reaction kettle and collecting a sample, namely the poly-p-dioxanone nano material.

2. The poly-p-dioxanone high-strength high-antibacterial suture line and the preparation method thereof as claimed in claim 1, wherein the chitosan is deacetylated 60-80% chitosan.

3. The high-strength and high-antibacterial poly (p-dioxanone) suture line and the preparation method thereof according to claim 1, wherein 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 poly-p-dioxanone high-strength high-antibacterial suture line and the preparation method thereof according to claim 1, wherein the graphene oxide in the step (1) is one or more of single-layer graphene oxide, double-layer graphene oxide and three-layer graphene oxide.

5. The high-strength high-antibacterial poly (p-dioxanone) suture line and the preparation method thereof according to claim 1, wherein the graphene oxide in the step (1) is prepared by a Hummers method.

6. The high-strength high-antibacterial-property poly (p-dioxanone) suture line and the preparation method thereof according to claim 1, wherein the high-strength high-antibacterial-property absorbable suture line in the step (1) is prepared by the following steps: graphene oxide is dispersed in DMF, oxalyl chloride is added at 0-5 ℃ to react for 8-9 hours at 60 ℃. And after the reaction is finished, washing the reaction product by using dichloromethane, and carrying out forced air drying at the temperature of 40-50 ℃ for 8-10 hours to obtain the graphene oxide functionalized by the acyl chloride group. And dispersing the graphene oxide functionalized by acyl chloride groups in DMF, adding triethylamine and polyethylene glycol, and refluxing the mixture for 4-5 hours. And filtering the black product, and performing forced air drying on the black product for 8 to 10 hours at the temperature of between 50 and 60 ℃ by using a small amount of methanol to obtain the polyethylene glycol modified graphene oxide.

7. The high-strength high-antibacterial poly (p-dioxanone) suture line 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 high-strength high-antibacterial poly (p-dioxanone) suture line and the preparation method thereof according to claim 1, wherein the antibacterial drug in the step (1) is one or more of levofloxacin, mupirocin, ciprofloxacin and amikacin.

9. The poly-p-dioxanone high-strength high-antibacterial suture line and the preparation method thereof according to claim 1, wherein the catalyst in the step (2) is one or more of stannous octoate, triethyl aluminum and triethyl zinc.

10. The high-strength high-antibacterial poly (p-dioxanone) suture line and the preparation method thereof as claimed in claim 1, wherein the mass fractions of the poly (p-dioxanone) in the steps (1) and (2), the polyethylene glycol-modified graphene oxide, the surfactant, the ***e local anesthetic catalyst and the catalyst are (80-100), (5-10), (2-3), (1-2) and (3-5).

11. The poly-p-dioxanone high-strength high-antibacterial suture line and the preparation method thereof according to claims 1 to 10, which comprises the following steps:

(1) preparing suture fibers: uniformly mixing poly-p-dioxanone nano material, chitosan, polyethylene glycol monomethyl ether, cassia oil and mannitol, heating to 50-60 ℃, stirring at the speed of 300-400r/min for 8-10h, heating to 75-85 ℃, extruding by a double-screw extruder, cooling by water, air-drying, and granulating to obtain master batches; heating to 120-160 ℃ 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: the suture fiber is further dried and sterilized by using ethylene oxide to obtain the dried poly-p-dioxanone high-strength high-antibacterial suture.

12. The poly-p-dioxanone high-strength high-antibacterial suture line and the preparation method thereof according to claim 11, wherein the ethylene oxide sterilization concentration in the step (2) is 300mg/L-500 mg/L.

13. The poly-p-dioxanone high-strength high-antibacterial suture and the preparation method thereof according to claim 11, wherein the ethylene oxide sterilization time in the step (2) is 3h to 5 h.

Technical Field

The invention relates to a high-strength and high-antibacterial poly (p-dioxanone) suture and a preparation method thereof, belonging to the technical field of nano medical suture processing.

Background

The poly-p-dioxanone 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 poly-p-dioxanone medical suture is far lower than that of a non-absorbable suture, the degradation behavior is discontinuous, the probability of anaphylactic reaction in a human body is high, a good antibacterial effect can be achieved only by treating the poly-p-dioxanone medical suture with a special antibacterial agent, the antibacterial effect is not durable, and the anti-bacterial agent is easy to cause rejection reaction with the human body after entering the human body. Therefore, the preparation of the high-strength high-antibacterial poly-p-dioxanone suture line with high tensile strength, firm knot, good biocompatibility, no adverse reaction in human body and durable antibacterial performance has important significance.

The poly-p-dioxanone is prepared by ring-opening polymerization of p-dioxanone monomer. The existing synthesis method of poly-p-dioxanone has the balance of polymerization and depolymerization of dioxanone monomers, long polymerization time, low monomer conversion rate, poor quality controllability of polymerization products, generally needs to use organic solvents, and has larger pollution, so that an economical, practical, green and environment-friendly preparation method of poly-p-dioxanone is needed.

The modified graphene oxide and the antibacterial agent are added into a dioxanone monomer, the poly-p-dioxanone nano material coated with the antibacterial agent is synthesized by an in-situ polymerization reaction method, (1) the poly-p-dioxanone is combined with the polyethylene glycol modified graphene oxide through pi-pi accumulation effect, pores of polymers are filled, acting force between polymer chain segments is enhanced, (2) the poly-p-dioxanone and the polyethylene glycol modified graphene oxide are crosslinked to form a chemical bond through chemical reaction, the strength of a medical poly-p-dioxanone suture line is improved, (3) the modified graphene oxide keeps sharp edges, and the structural and functional integrity of bacteria and fungi can be cut, mechanically coated and extracted by phospholipid molecules, (4) oxygen-containing functional groups on the graphene oxide sheet layer, the bacteria and the fungi can be cut, and the integrity of the structures and the functions of the bacteria and the fungi can be broken and extracted The method is characterized in that saccharides or proteins of cells in bacteria form hydrogen bonds to block the material exchange of bacteria and fungi, so that the bacteria and the fungi lack nutrient substances to die (5) the synthesis of poly-p-dioxanone, the modified graphene oxide and the antibacterial drug are combined, and the in-situ synthesis of poly-p-dioxanone nano materials and the in-situ coating of the antibacterial drug are realized simultaneously, so that the important idea for developing the poly-p-dioxanone medical suture line which has high tensile strength, firm knot, good biocompatibility, no adverse reaction in a human body and improved lasting antibacterial performance is provided.

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 no toxicity, nonflammability, low price and the like, and the supercritical condition is easy to reach, so that the technology is an important idea for realizing economic, practical, green and environment-friendly synthesis of the poly-p-dioxanone.

Disclosure of Invention

The invention relates to a high-strength and high-antibacterial poly (p-dioxanone) suture and a preparation method thereof, wherein the high-strength and high-antibacterial poly (p-dioxanone) suture consists of the following components in parts by mass: 80-100 parts of poly-p-dioxanone nano material, 15-25 parts of chitosan, 3-5 parts of polyethylene glycol monomethyl ether, 2-3 parts of cassia oil and 1-2 parts of mannitol; wherein the preparation method of the poly-p-dioxanone nano material comprises the following steps: (1) adding polydioxanone, polyethylene glycol modified graphene oxide, a surfactant and an antibacterial drug into a pre-dried reaction kettle, and performing vacuum drying for 2-3 hours at 60-80 ℃ by using an oil pump; (2) adding a catalyst under the protection of argon, heating to 90-110 ℃, and adding carbon dioxide gas with the pressure of 28-32 MPa; (3) reacting for 25-35 hours under stirring, then cooling to room temperature under stirring, discharging carbon dioxide gas, opening the reaction kettle and collecting a sample, namely the poly-p-dioxanone 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 Hummers method.

According to the scheme, the preparation method of the polyethylene glycol modified graphene oxide in the step (1) comprises the following steps: graphene oxide is dispersed in DMF, oxalyl chloride is added at 0-5 ℃ to react for 8-9 hours at 60 ℃. And after the reaction is finished, washing the reaction product by using dichloromethane, and carrying out forced air drying at the temperature of 40-50 ℃ for 8-10 hours to obtain the graphene oxide functionalized by the acyl chloride group. And dispersing the graphene oxide functionalized by acyl chloride groups in DMF, adding triethylamine and polyethylene glycol, and refluxing the mixture for 4-5 hours. And filtering the black product, and performing forced air drying on the black product for 8 to 10 hours at the temperature of between 50 and 60 ℃ by using a small amount of methanol to obtain the polyethylene glycol 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 drugs in the step (1) are one or more of levofloxacin, mupirocin, ciprofloxacin and amikacin.

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

According to the scheme, the polydioxanone, the polyethylene glycol modified graphene oxide, the surfactant, the antibacterial agent and the catalyst in the steps (1) and (2) have the mass fractions of (80-100), (5-10), (2-3), (1-2) and (3-5).

According to the scheme, the high-strength and high-antibacterial poly (p-dioxanone) suture and the preparation method are characterized by comprising the following steps of:

(1) preparing suture fibers: uniformly mixing poly-p-dioxanone nano material, chitosan, polyethylene glycol monomethyl ether, cassia oil and mannitol, heating to 50-60 ℃, stirring at the speed of 300-400r/min for 8-10h, heating to 75-85 ℃, extruding by a double-screw extruder, cooling by water, air-drying, and granulating to obtain master batches; heating to 120-160 ℃ 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: the suture fiber is further dried and sterilized by using ethylene oxide to obtain the dried poly-p-dioxanone high-strength high-antibacterial suture. The sterilization concentration of the ethylene oxide is 300mg/L-500mg/L, and the sterilization time of the ethylene oxide is 3h-5 h.

The invention has the beneficial effects that:

according to the invention, the synthesis of the poly-p-dioxanone, the modified graphene oxide and the antibacterial agent are combined, the in-situ synthesis of the poly-p-dioxanone nano material and the in-situ wrapping of the local anesthetic are realized simultaneously, the poly-p-dioxanone and the polyethylene glycol modified graphene oxide are combined through the pi-pi stacking effect, the pores of the polymer are filled, and the acting force between polymer chain segments is enhanced; the poly-p-dioxanone and the modified graphene oxide are crosslinked to form a chemical bond through a chemical reaction, so that the strength of the poly-p-dioxanone medical suture is improved; the modified graphene oxide keeps sharp edges capable of cutting, mechanically wrapping, peroxidating and extracting phospholipid molecules to break the structural and functional integrity of bacteria and fungi; the oxygen-containing functional group on the modified graphene oxide lamella and the sugar or protein of cells in bacteria and fungi form hydrogen bonds to block the material exchange of the bacteria and the fungi, so that the bacteria and the fungi lack nutrient substances to die, and the poly-p-dioxanone medical suture which has high tensile strength, firm knot, good biocompatibility, no adverse reaction in human body and improved lasting antibacterial performance is developed. The poly-p-dioxanone 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.