CN112336917A - Degradable implantation type blood vessel support - Google Patents
Degradable implantation type blood vessel support Download PDFInfo
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- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
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- A—HUMAN NECESSITIES
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/04—Macromolecular materials
- A61L31/06—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61L31/00—Materials for other surgical articles, e.g. stents, stent-grafts, shunts, surgical drapes, guide wires, materials for adhesion prevention, occluding devices, surgical gloves, tissue fixation devices
- A61L31/14—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L31/148—Materials at least partially resorbable by the body
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- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
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- D—TEXTILES; PAPER
- D01—NATURAL OR MAN-MADE THREADS OR FIBRES; SPINNING
- D01F—CHEMICAL FEATURES IN THE MANUFACTURE OF ARTIFICIAL FILAMENTS, THREADS, FIBRES, BRISTLES OR RIBBONS; APPARATUS SPECIALLY ADAPTED FOR THE MANUFACTURE OF CARBON FILAMENTS
- D01F8/00—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof
- D01F8/18—Conjugated, i.e. bi- or multicomponent, artificial filaments or the like; Manufacture thereof from other substances
Abstract
The invention discloses a degradable implanted vascular stent, and a preparation method of a vascular stent material adopted by the degradable implanted vascular stent comprises the following steps: preparing chloromaleimide end group polycaprolactone, (II) preparing copolymer, (III) modifying chitosan copolymer, (IV) synthesizing furyl polyester polycondensate, and (V) forming the bracket. The preparation method of the intravascular stent material disclosed by the invention is simple and feasible, and the preparation cost is low; the prepared intravascular stent material has good biocompatibility, excellent mechanical property and degradability, and safe and reliable use.
Description
Technical Field
The invention belongs to the technical field of three types of medical instruments, relates to an expandable implant prosthesis, and particularly relates to a vascular stent and a preparation method thereof.
Background
At present, stent intervention is one of the main means for treating cardiovascular diseases, and is mainly applied to vascular lumen stenosis or embolism treatment caused by vascular diseases, so that blood circulation is improved, and the purpose of improving or treating the diseases is achieved. The therapeutic effect of stent intervention depends on the choice of the vascular stent material. The intravascular stent material with ideal performance is a powerful guarantee for improving the success rate and the treatment effect of the operation and relieving the pain of the patient.
The stent materials commonly used in the prior art mainly comprise non-degradable vascular stent materials and degradable vascular stent materials. The non-degradable blood vessel stent material mainly comprises stainless steel, cobalt, tantalum and nickel-titanium alloy, the metal stent material is not degradable in a human body, the metal stent material needs to be permanently kept in the human body, the risk degree of inducing restenosis is increased, the injury of a blood vessel wall is easily caused, and thrombosis is easily caused. The degradable blood vessel stent material has no stimulation to a human body, can reduce the risk of restenosis in a stent at a later period, does not influence the subsequent treatment of pathological changes, does not generate tail shadow, greatly lightens the psychological pressure of a patient on an implant, and shortens the applicable time of an antiplatelet medicament. However, the degradable vascular stent material in the prior art has insufficient mechanical properties, poor strength, oxidation resistance and toughness, too fast degradation speed in vivo, no contribution to vascular recovery and certain inflammatory reaction in the degradation process.
Therefore, the development of a vascular stent material which has mechanical properties, good degradability, excellent biocompatibility, safe and reliable use is imperative.
Disclosure of Invention
In order to overcome the defects in the prior art, the invention aims to provide a vascular stent material which has good biocompatibility, excellent mechanical property and degradability and is safe and reliable to use, so as to effectively solve the technical problems of insufficient mechanical property, poor strength, oxidation resistance and toughness, too fast degradation speed in vivo, inconvenience for vascular recovery and certain inflammatory reaction generated in the degradation process of the traditional degradable vascular stent material, and also provides a preparation method thereof.
The invention is realized by the following scheme: a preparation method of a blood vessel stent material comprises the following steps:
dissolving maleimide end group polycaprolactone and (E, Z) -1, 4-dichloro-1, 3-butadiene in a high boiling point solvent to react to prepare chloromaleimide end group polycaprolactone;
II, adding chloromaleimide end group polycaprolactone, D-gluconic acid 2-propylene-1-ester, 2-allyl methyl lactate and an initiator into N-methyl pyrrolidone for reaction to obtain a copolymer;
III modifying the copolymer with chitosan in acetic acid solution;
IV, adding 2, 5-furandicarboxylic acid and ethylene glycol into dimethyl sulfoxide, and reacting with dicyclohexylcarbodiimide and 4-dimethylaminopyridine to synthesize a furyl polyester polycondensate;
v, forming of a bracket: and dissolving the chitosan modified copolymer and the furan-based polyester polycondensate in a mixed solvent, and then carrying out electrostatic spinning to obtain the vascular stent material.
Furthermore, the preparation method of the vascular stent material comprises the following steps:
i, preparation of chloromaleimide terminated polycaprolactone: dissolving maleimide end group polycaprolactone and (E, Z) -1, 4-dichloro-1, 3-butadiene in a high boiling point solvent to form a solution in the atmosphere of nitrogen or inert gas, then adding the solution into a three-neck flask provided with a reflux condenser tube and an electric stirrer, carrying out reflux stirring reaction for 10-12 hours at the temperature of 120-130 ℃, and then carrying out rotary evaporation to remove the solvent to obtain chloromaleimide end group polycaprolactone;
II preparation of copolymer: adding the chloromaleimide end group polycaprolactone prepared in the step I, D-gluconic acid 2-propylene-1-ester, 2-allyl methyl lactate and an initiator into N-methylpyrrolidone, stirring and reacting for 4-6 hours at 70-80 ℃ in the atmosphere of nitrogen or inert gas, then precipitating in acetone, and placing the precipitated polymer in a vacuum drying oven at 70-80 ℃ to dry to constant weight to obtain a copolymer;
III Chitosan-modified copolymer: adding the copolymer prepared in the step II and chitosan into an acetic acid solution with the mass fraction of 5-10%, stirring and reacting for 8-10 hours at 50-60 ℃, then adding ammonia water, adjusting the solution to be neutral, then performing rotary evaporation to remove the solvent, washing the crude product with ethanol for 3-5 times, and finally placing the crude product in a vacuum drying oven at 90-100 ℃ to be dried to constant weight to obtain a chitosan modified copolymer;
IV Synthesis of a polycondensate of furyl polyester type: adding 2, 5-furandicarboxylic acid and ethylene glycol into dimethyl sulfoxide, adding dicyclohexylcarbodiimide and 4-dimethylaminopyridine into the dimethyl sulfoxide, stirring for 1-2 hours under the condition of ice-water bath in the nitrogen atmosphere, stirring for reacting for 18-22 hours at the temperature of 150 ℃ and 170 ℃, precipitating in acetone after the reaction is finished, and drying the precipitated polymer for 15-20 hours at the temperature of 70-80 ℃ in a vacuum drying oven to obtain the furyl polyester polycondensate;
v, forming of a bracket: and (3) dissolving the chitosan modified copolymer prepared in the step (III) and the furyl polyester polycondensate prepared in the step (IV) in a mixed solvent, heating to 150-180 ℃, stirring and refluxing for 20-30 minutes, cooling to room temperature to obtain a mixed solution, and performing electrostatic spinning on the mixed solution to obtain the vascular stent material.
Preferably, the mass ratio of the maleimide end group polycaprolactone, (E, Z) -1, 4-dichloro-1, 3-butadiene and the high boiling point solvent in the step I is 20:1 (40-50).
Preferably, the high boiling point solvent is selected from one or more of dimethyl sulfoxide, N-dimethylformamide and N-methylpyrrolidone.
Preferably, the mass ratio of the chloromaleimide end group polycaprolactone, the D-gluconic acid 2-propylene-1-ester, the 2-allyl methyl lactate, the initiator and the N-methylpyrrolidone in the step II is 2:1:1 (0.02-0.04): 20-25.
Preferably, the initiator is selected from at least one of azobisisobutyronitrile and azobisisoheptonitrile.
Preferably, the inert gas is selected from one of helium, neon and argon.
Preferably, the mass ratio of the copolymer, the chitosan and the acetic acid solution in the step III is 1 (0.5-0.8) to (8-12).
Preferably, the mass ratio of the 2, 5-furandicarboxylic acid, the ethylene glycol, the dimethyl sulfoxide, the dicyclohexylcarbodiimide and the 4-dimethylaminopyridine in the step IV is 2.5:1 (15-20) to 0.4-0.6: 0.3.
Preferably, the mass ratio of the chitosan modified copolymer, the furyl polyester polycondensate and the mixed solvent in the step V is 1:2 (10-15).
Preferably, the mixed solvent is formed by mixing tetrahydrofuran, water and acetic acid according to the mass ratio of 5:5: 1.
Preferably, the parameters of said electrospinning are as follows: spinning voltage is 5-15KV, advancing speed is 0.5-2mL/h, and receiving distance is 15-35 cm.
An intravascular stent material is prepared by the preparation method of the intravascular stent material.
Adopt the produced beneficial effect of above-mentioned technical scheme to lie in:
1) the preparation method of the intravascular stent material provided by the invention is simple and easy to operate, mild in reaction condition, easy in raw material obtaining, low in price and good in clinical practicability.
2) The intravascular stent material provided by the invention effectively solves the technical problems that the traditional degradable intravascular stent material has more or less insufficient mechanical properties, poor strength, oxidation resistance and toughness, too fast degradation speed in vivo, is not beneficial to vascular recovery, and can generate certain inflammatory reaction in the degradation process, and has the advantages of good biocompatibility, excellent mechanical properties and degradability, and safe and reliable use.
3) The intravascular stent material provided by the invention is prepared by blending and spinning the addition polymer and the condensation polymer, has the advantages of the two polymers, has good compatibility, maintains proper void ratio, and enhances the possibility and success rate of the intravascular stent material in practical application due to good mechanical properties of the addition polymer and the condensation polymer.
4) The intravascular stent material provided by the invention combines the advantages of chitosan, polycaprolactone and glycol which are good in biocompatibility and biodegradable materials, shows a lower hemolytic index, enhances safety, effectively reduces the limitation of high immunogenicity reaction in clinical application, reduces the failure of transplantation, and increases the stability of the material because all structures are connected by chemical bonds; the furan and maleic acid structures are introduced, so that the mechanical property of the material is improved, the components and the structures have synergistic effect, and the comprehensive performance of the support material is improved.
Detailed Description
In order to make the technical solutions of the present invention better understood and make the above features, objects, and advantages of the present invention more comprehensible, the present invention is further described with reference to the following examples. The examples are intended to illustrate the invention only and are not intended to limit the scope of the invention.
The maleimide-terminated polycaprolactone described in the following examples of the invention was prepared in advance, the preparation method referring to: zhang, m.j.; liu, h.h.; shao, w.; miao, k.; zhao, y.l. synthesis and properties of multiclearable ampiphilic polymeric compositions and topoothbrisk polymeric compositions compatible alteration PEG and PCL grafts, macromolecules,2013,46,1325 and 1336; other materials are from Shanghai spring Xin import and export trade company Limited.
Example 1
A preparation method of a blood vessel stent material comprises the following steps:
i, preparation of chloromaleimide terminated polycaprolactone: dissolving 20g of maleimide terminal group polycaprolactone and 1g of (E, Z) -1, 4-dichloro-1, 3-butadiene in 40g of dimethyl sulfoxide to form a solution in a nitrogen atmosphere, adding the solution into a three-neck flask provided with a reflux condenser tube and an electric stirrer, carrying out reflux stirring reaction for 10 hours at 120 ℃, and then carrying out rotary evaporation to remove the solvent to obtain chloromaleimide terminal group polycaprolactone;
II preparation of copolymer: adding 10g of chloromaleimide end group polycaprolactone prepared in the step I, 5g of D-gluconic acid 2-propylene-1-ester, 5g of 2-methyl allyl lactate and 0.1g of azodiisobutyronitrile into 100g of N-methyl pyrrolidone, stirring and reacting for 4 hours at 70 ℃ in a nitrogen atmosphere, then precipitating in acetone, and placing the precipitated polymer in a vacuum drying oven at 70 ℃ to be dried to constant weight to obtain a copolymer;
III Chitosan-modified copolymer: adding 10g of the copolymer prepared in the step II and 5g of chitosan into 80g of acetic acid solution with the mass fraction of 5%, stirring and reacting for 8 hours at 50 ℃, then adding ammonia water, adjusting the solution to be neutral, then performing rotary evaporation to remove the solvent, washing the crude product with ethanol for 3 times, and finally placing the crude product in a vacuum drying oven at 90 ℃ to be dried to constant weight to obtain a chitosan modified copolymer;
IV Synthesis of a polycondensate of furyl polyester type: adding 25g of 2, 5-furandicarboxylic acid and 10g of ethylene glycol into 150g of dimethyl sulfoxide, adding 4g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the dimethyl sulfoxide, stirring the mixture for 1 hour under the condition of ice-water bath in a nitrogen atmosphere, stirring the mixture for reacting for 18 hours at 150 ℃, precipitating the mixture in acetone after the reaction is finished, and drying the precipitated polymer in a vacuum drying oven at 70 ℃ for 15 hours to obtain a furyl polyester polycondensate;
v, forming of a bracket: and (3) dissolving 10g of the chitosan modified copolymer prepared in the step (III) and 20g of the furyl polyester polycondensate prepared in the step (IV) in 100g of a mixed solvent, heating to 150 ℃, stirring and refluxing for 20 minutes, cooling to room temperature to obtain a mixed solution, and performing electrostatic spinning on the mixed solution to obtain the intravascular stent material.
The mixed solvent is formed by mixing tetrahydrofuran, water and acetic acid according to the mass ratio of 5:5: 1.
The parameters of the electrostatic spinning are as follows: the spinning voltage is 5KV, the advancing speed is 0.5mL/h, and the receiving distance is 15 cm.
An intravascular stent material is prepared by the preparation method of the intravascular stent material.
Example 2
A preparation method of a blood vessel stent material comprises the following steps:
i, preparation of chloromaleimide terminated polycaprolactone: under helium atmosphere, dissolving 20g of maleimide terminal group polycaprolactone and 1g of (E, Z) -1, 4-dichloro-1, 3-butadiene in 42g of N, N-dimethylformamide to form a solution, then adding the solution into a three-neck flask provided with a reflux condenser tube and an electric stirrer, carrying out reflux stirring reaction for 10.5 hours at 123 ℃, and then carrying out rotary evaporation to remove the solvent to obtain chloromaleimide terminal group polycaprolactone;
II preparation of copolymer: adding 10g of chloromaleimide end group polycaprolactone prepared in the step I, 5g of D-gluconic acid 2-propylene-1-ester, 5g of 2-allyl methyl lactate and 0.13g of azodiisoheptanonitrile into 105g of N-methylpyrrolidone, stirring and reacting for 4.5 hours at 72 ℃ in a helium atmosphere, then precipitating in acetone, and placing the precipitated polymer in a vacuum drying oven at 73 ℃ to be dried to constant weight to obtain a copolymer;
III Chitosan-modified copolymer: adding 10g of the copolymer prepared in the step II and 6g of chitosan into 95g of acetic acid solution with the mass fraction of 6%, stirring and reacting for 8.5 hours at 53 ℃, then adding ammonia water, adjusting the solution to be neutral, then performing rotary evaporation to remove the solvent, washing the crude product with ethanol for 4 times, and finally placing the crude product in a vacuum drying oven at 93 ℃ to be dried to constant weight to obtain a chitosan modified copolymer;
IV Synthesis of a polycondensate of furyl polyester type: adding 25g of 2, 5-furandicarboxylic acid and 10g of ethylene glycol into 165g of dimethyl sulfoxide, adding 4.5g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the dimethyl sulfoxide, stirring the mixture for 1.3 hours under the condition of ice-water bath in a nitrogen atmosphere, stirring the mixture for reacting for 18.5 hours at 155 ℃, precipitating the mixture in acetone after the reaction is finished, and drying the precipitated polymer for 16.5 hours at 73 ℃ in a vacuum drying oven to obtain a furyl polyester polycondensate;
v, forming of a bracket: and (3) dissolving 10g of the chitosan modified copolymer prepared in the step (III) and 20g of the furyl polyester polycondensate prepared in the step (IV) in 125g of a mixed solvent, heating to 165 ℃, stirring and refluxing for 23 minutes, cooling to room temperature to obtain a mixed solution, and performing electrostatic spinning on the mixed solution to obtain the intravascular stent material.
The mixed solvent is formed by mixing tetrahydrofuran, water and acetic acid according to the mass ratio of 5:5: 1.
The parameters of the electrostatic spinning are as follows: the spinning voltage is 8KV, the advancing speed is 1mL/h, and the receiving distance is 20 cm.
An intravascular stent material is prepared by the preparation method of the intravascular stent material.
Example 3
A preparation method of a blood vessel stent material comprises the following steps:
i, preparation of chloromaleimide terminated polycaprolactone: dissolving 20g of maleimide end group polycaprolactone and 1g of (E, Z) -1, 4-dichloro-1, 3-butadiene in 45g of N-methyl pyrrolidone to form a solution in a neon atmosphere, adding the solution into a three-neck flask provided with a reflux condenser tube and an electric stirrer, carrying out reflux stirring reaction for 11 hours at 125 ℃, and then carrying out rotary evaporation to remove the solvent to obtain chloromaleimide end group polycaprolactone;
II preparation of copolymer: adding 20g of chloromaleimide end group polycaprolactone prepared in the step I, 10g of D-gluconic acid 2-propylene-1-ester, 10g of 2-allyl methyl lactate and 0.3g of azodiisobutyronitrile into 230g of N-methylpyrrolidone, stirring and reacting for 5 hours at 75 ℃ in a neon atmosphere, then precipitating in acetone, and placing the precipitated polymer in a vacuum drying oven at 75 ℃ to be dried to constant weight to obtain a copolymer;
III Chitosan-modified copolymer: adding 10g of the copolymer prepared in the step II and 6.5g of chitosan into 105g of acetic acid solution with the mass fraction of 7%, stirring and reacting at 56 ℃ for 9 hours, adding ammonia water, adjusting the solution to be neutral, performing rotary evaporation to remove the solvent, washing the crude product with ethanol for 4 times, and finally placing the crude product in a vacuum drying oven at 96 ℃ to be dried to constant weight to obtain a chitosan modified copolymer;
IV Synthesis of a polycondensate of furyl polyester type: adding 25g of 2, 5-furandicarboxylic acid and 10g of ethylene glycol into 180g of dimethyl sulfoxide, adding 5g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the dimethyl sulfoxide, stirring the mixture for 1.6 hours under the condition of ice-water bath in a nitrogen atmosphere, stirring the mixture for reaction for 20 hours at 160 ℃, precipitating the mixture in acetone after the reaction is finished, and drying the precipitated polymer in a vacuum drying oven at 75 ℃ for 18 hours to obtain a furyl polyester polycondensate;
v, forming of a bracket: and (3) dissolving 10g of the chitosan modified copolymer prepared in the step (III) and 20g of the furyl polyester polycondensate prepared in the step (IV) in 130g of a mixed solvent, heating to 170 ℃, stirring and refluxing for 26 minutes, cooling to room temperature to obtain a mixed solution, and performing electrostatic spinning on the mixed solution to obtain the intravascular stent material.
The mixed solvent is formed by mixing tetrahydrofuran, water and acetic acid according to the mass ratio of 5:5: 1.
The parameters of the electrostatic spinning are as follows: the spinning voltage is 10KV, the advancing speed is 1.2mL/h, and the receiving distance is 25 cm.
An intravascular stent material is prepared by the preparation method of the intravascular stent material.
Example 4
A preparation method of a blood vessel stent material comprises the following steps:
i, preparation of chloromaleimide terminated polycaprolactone: under argon atmosphere, dissolving 20g of maleimide end group polycaprolactone and 1g of (E, Z) -1, 4-dichloro-1, 3-butadiene in 48g of a high boiling point solvent to form a solution, then adding the solution into a three-neck flask provided with a reflux condenser tube and an electric stirrer, carrying out reflux stirring reaction at 128 ℃ for 11.5 hours, and then carrying out rotary evaporation to remove the solvent to obtain chloromaleimide end group polycaprolactone; the high-boiling-point solvent is a mixture formed by mixing dimethyl sulfoxide, N-dimethylformamide and N-methylpyrrolidone according to the mass ratio of 1:2: 1;
II preparation of copolymer: adding 20g of chloromaleimide end group polycaprolactone prepared in the step I, 10g of D-gluconic acid 2-propylene-1-ester, 10g of 2-allyl methyl lactate and 0.35g of initiator into 245g of N-methylpyrrolidone, stirring and reacting for 5.5 hours at 78 ℃ in an argon atmosphere, then precipitating in acetone, and placing the precipitated polymer in a vacuum drying oven at 78 ℃ to be dried to constant weight to obtain a copolymer; the initiator is formed by mixing azodiisobutyronitrile and azodiisoheptonitrile according to the mass ratio of 3: 5;
III Chitosan-modified copolymer: adding 10g of the copolymer prepared in the step II and 7.8g of chitosan into 115g of acetic acid solution with the mass fraction of 9%, stirring and reacting at 58 ℃ for 9.5 hours, adding ammonia water, adjusting the solution to be neutral, then performing rotary evaporation to remove the solvent, washing the crude product with ethanol for 5 times, and finally placing in a vacuum drying oven at 95 ℃ to be dried to constant weight to obtain a chitosan modified copolymer;
IV Synthesis of a polycondensate of furyl polyester type: adding 25g of 2, 5-furandicarboxylic acid and 10g of ethylene glycol into 194g of dimethyl sulfoxide, adding 5.8g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the dimethyl sulfoxide, stirring the mixture for 1.8 hours under the condition of ice-water bath in a nitrogen atmosphere, stirring the mixture for reaction for 21.5 hours at 168 ℃, precipitating the mixture in acetone after the reaction is finished, and drying the precipitated polymer in a vacuum drying oven at 79 ℃ for 19 hours to obtain a furyl polyester polycondensate;
v, forming of a bracket: and (3) dissolving 10g of the chitosan modified copolymer prepared in the step (III) and 20g of the furyl polyester polycondensate prepared in the step (IV) in 145g of a mixed solvent, heating to 178 ℃, stirring and refluxing for 29 minutes, cooling to room temperature to obtain a mixed solution, and performing electrostatic spinning on the mixed solution to obtain the intravascular stent material.
The mixed solvent is formed by mixing tetrahydrofuran, water and acetic acid according to the mass ratio of 5:5: 1.
The parameters of the electrostatic spinning are as follows: the spinning voltage is 13KV, the advancing speed is 1.8mL/h, and the receiving distance is 33 cm.
An intravascular stent material is prepared by the preparation method of the intravascular stent material.
Example 5
A preparation method of a blood vessel stent material comprises the following steps:
i, preparation of chloromaleimide terminated polycaprolactone: under the atmosphere of nitrogen, dissolving 20g of maleimide end group polycaprolactone and 1g of (E, Z) -1, 4-dichloro-1, 3-butadiene in 50g of N-methylpyrrolidone to form a solution, then adding the solution into a three-neck flask provided with a reflux condenser tube and an electric stirrer, carrying out reflux stirring reaction for 12 hours at 130 ℃, and then carrying out rotary evaporation to remove the solvent to obtain chloromaleimide end group polycaprolactone;
II preparation of copolymer: adding 10g of chloromaleimide end group polycaprolactone prepared in the step I, 5g of D-gluconic acid 2-propylene-1-ester, 5g of 2-allyl methyl lactate and 0.2g of azodiisoheptanonitrile into 125g of N-methylpyrrolidone, stirring and reacting for 6 hours at 80 ℃ in a nitrogen atmosphere, then precipitating in acetone, and placing the precipitated polymer in a vacuum drying oven to be dried to constant weight at 80 ℃ to obtain a copolymer;
III Chitosan-modified copolymer: adding 10g of the copolymer prepared in the step II and 8g of chitosan into 120g of acetic acid solution with the mass fraction of 10%, stirring and reacting for 10 hours at 60 ℃, then adding ammonia water, adjusting the solution to be neutral, then performing rotary evaporation to remove the solvent, washing the crude product with ethanol for 5 times, and finally placing the crude product in a vacuum drying oven at 100 ℃ to be dried to constant weight to obtain a chitosan modified copolymer;
IV Synthesis of a polycondensate of furyl polyester type: adding 25g of 2, 5-furandicarboxylic acid and 10g of ethylene glycol into 200g of dimethyl sulfoxide, adding 6g of dicyclohexylcarbodiimide and 3g of 4-dimethylaminopyridine into the dimethyl sulfoxide, stirring the mixture for 2 hours in an ice-water bath condition under a nitrogen atmosphere, stirring the mixture for reaction for 22 hours at 170 ℃, precipitating the mixture in acetone after the reaction is finished, and drying the precipitated polymer in a vacuum drying oven for 20 hours at 80 ℃ to obtain a furyl polyester polycondensate;
v, forming of a bracket: and (3) dissolving 10g of the chitosan modified copolymer prepared in the step (III) and 20g of the furyl polyester polycondensate prepared in the step (IV) in 150g of a mixed solvent, heating to 180 ℃, stirring and refluxing for 30 minutes, cooling to room temperature to obtain a mixed solution, and performing electrostatic spinning on the mixed solution to obtain the intravascular stent material.
The mixed solvent is formed by mixing tetrahydrofuran, water and acetic acid according to the mass ratio of 5:5: 1.
The parameters of the electrostatic spinning are as follows: the spinning voltage is 15KV, the advancing speed is 2mL/h, and the receiving distance is 35 cm.
An intravascular stent material is prepared by the preparation method of the intravascular stent material.
Comparative example
The main component of the commercially available intravascular stent material is polylactic acid, which is purchased from some company in Zhejiang.
The performance of the intravascular stent materials prepared in the examples 1 to 5 and the comparative example is tested, the test results are shown in the table 1, and the test method is as follows:
(1) biocompatible subcutaneous embedding test: the sample for slice observation was 10mmxl0mm membrane material. Taking out the membrane and the surrounding tissues together, placing the membrane and the surrounding tissues into formalin solution for fixation, carrying out paraffin section and hematoxylin-eosin staining, and observing the inflammatory reaction around the material under 40-fold and 100-fold optical microscopes respectively. The number of inflammatory cells per unit area of tissue surrounding the section of disc material in the field was counted randomly 3 times and averaged to give the number of inflammatory cells in the section.
(2) Tensile test for in vivo degradation: tensile testing was carried out using an Instron model 5565 static material tester from Instron, UK, with a sensor load of 500N. The sample was tested at 25 ℃ in an environment of 50% relative humidity with a set drawing speed of 5 mm/min.
(3) Hemolysis: the test was performed according to ISOTR 7405.
TABLE 1
| Test items | Inflammatory cell number after 200 days | Tensile strength | Hemolytic property |
| Unit of | ×103An | MPa | ％ |
| Example 1 | 1.0 | 45 | 0.05 |
| Example 2 | 0.9 | 47 | 0.05 |
| Example 3 | 0.8 | 49 | 0.04 |
| Example 4 | 0.8 | 50 | 0.03 |
| Example 5 | 0.6 | 52 | 0.02 |
| Comparative example | 3.5 | 25 | 0.45 |
As can be seen from Table 1, the intravascular stent material disclosed by the invention has more excellent mechanical properties, blood compatibility and biocompatibility.
The foregoing shows and describes the general principles, essential features, and advantages of the invention. It will be understood by those skilled in the art that the present invention is not limited to the embodiments described above, which are merely illustrative of the principles of the invention, but that various changes and modifications may be made without departing from the spirit and scope of the invention, which fall within the scope of the invention as claimed. The scope of the invention is defined by the appended claims and equivalents thereof.
Claims (9)
1. A degradable implantation type blood vessel bracket is characterized in that the preparation method of the blood vessel bracket material adopted by the implantation type blood vessel bracket comprises the following steps:
dissolving maleimide end group polycaprolactone and (E, Z) -1, 4-dichloro-1, 3-butadiene in a high boiling point solvent to react to prepare chloromaleimide end group polycaprolactone;
II, adding chloromaleimide end group polycaprolactone, D-gluconic acid 2-propylene-1-ester, 2-allyl methyl lactate and an initiator into N-methyl pyrrolidone for reaction to obtain a copolymer;
III modifying the copolymer with chitosan in acetic acid solution;
IV, adding 2, 5-furandicarboxylic acid and ethylene glycol into dimethyl sulfoxide, and reacting with dicyclohexylcarbodiimide and 4-dimethylaminopyridine to synthesize a furyl polyester polycondensate;
v, forming of a bracket: and dissolving the chitosan modified copolymer and the furan-based polyester polycondensate in a mixed solvent, and then carrying out electrostatic spinning to obtain the vascular stent material.
2. The degradable implantable vascular stent as claimed in claim 1, wherein the preparation method of the vascular stent material adopted by the implantable vascular stent comprises the following steps:
i, preparation of chloromaleimide terminated polycaprolactone: dissolving maleimide end group polycaprolactone and (E, Z) -1, 4-dichloro-1, 3-butadiene in a high boiling point solvent to form a solution in the atmosphere of nitrogen or inert gas, then adding the solution into a three-neck flask provided with a reflux condenser tube and an electric stirrer, carrying out reflux stirring reaction for 10-12 hours at the temperature of 120-130 ℃, and then carrying out rotary evaporation to remove the solvent to obtain chloromaleimide end group polycaprolactone;
II preparation of copolymer: adding the chloromaleimide end group polycaprolactone prepared in the step I, D-gluconic acid 2-propylene-1-ester, 2-allyl methyl lactate and an initiator into N-methylpyrrolidone, stirring and reacting for 4-6 hours at 70-80 ℃ in the atmosphere of nitrogen or inert gas, then precipitating in acetone, and placing the precipitated polymer in a vacuum drying oven at 70-80 ℃ to dry to constant weight to obtain a copolymer;
III Chitosan-modified copolymer: adding the copolymer prepared in the step II and chitosan into an acetic acid solution with the mass fraction of 5-10%, stirring and reacting for 8-10 hours at 50-60 ℃, then adding ammonia water, adjusting the solution to be neutral, then performing rotary evaporation to remove the solvent, washing the crude product with ethanol for 3-5 times, and finally placing the crude product in a vacuum drying oven at 90-100 ℃ to be dried to constant weight to obtain a chitosan modified copolymer;
IV Synthesis of a polycondensate of furyl polyester type: adding 2, 5-furandicarboxylic acid and ethylene glycol into dimethyl sulfoxide, adding dicyclohexylcarbodiimide and 4-dimethylaminopyridine into the dimethyl sulfoxide, stirring for 1-2 hours under the condition of ice-water bath in the nitrogen atmosphere, stirring for reacting for 18-22 hours at the temperature of 150 ℃ and 170 ℃, precipitating in acetone after the reaction is finished, and drying the precipitated polymer for 15-20 hours at the temperature of 70-80 ℃ in a vacuum drying oven to obtain the furyl polyester polycondensate;
v, forming of a bracket: and (3) dissolving the chitosan modified copolymer prepared in the step (III) and the furyl polyester polycondensate prepared in the step (IV) in a mixed solvent, heating to 150-180 ℃, stirring and refluxing for 20-30 minutes, cooling to room temperature to obtain a mixed solution, and performing electrostatic spinning on the mixed solution to obtain the vascular stent material.
3. The degradable implantable vascular stent of claim 2, wherein the weight ratio of the maleimide end group polycaprolactone, (E, Z) -1, 4-dichloro-1, 3-butadiene and the high boiling point solvent in step I is 20:1 (40-50); the high boiling point solvent is selected from one or more of dimethyl sulfoxide, N-dimethylformamide and N-methylpyrrolidone.
4. The degradable implantable vascular stent of claim 2, wherein the mass ratio of the chloromaleimide terminated polycaprolactone, the D-gluconic acid 2-propen-1-yl ester, the 2-allyl methyl lactate, the initiator and the N-methylpyrrolidone in the step II is 2:1:1 (0.02-0.04) to (20-25).
5. A degradable implantable vascular stent as defined in claim 2, wherein said initiator is selected from at least one of azobisisobutyronitrile, azobisisoheptonitrile; the inert gas is selected from helium, neon and argon.
6. A degradable implantable vascular stent as in claim 2, wherein the mass ratio of the copolymer, the chitosan and the acetic acid solution in the step III is 1 (0.5-0.8) to (8-12).
7. The degradable implantable vascular stent of claim 2, wherein the mass ratio of the 2, 5-furandicarboxylic acid, the ethylene glycol, the dimethyl sulfoxide, the dicyclohexylcarbodiimide and the 4-dimethylaminopyridine in the step IV is 2.5:1 (15-20) to 0.4-0.6: 0.3.
8. The degradable implantable vascular stent of claim 2, wherein the weight ratio of the chitosan modified copolymer, the furyl polyester polycondensate and the mixed solvent in step V is 1:2 (10-15); the mixed solvent is formed by mixing tetrahydrofuran, water and acetic acid according to the mass ratio of 5:5: 1.
9. A degradable implantable vascular stent according to claim 2, wherein the electrospinning parameters are as follows: spinning voltage is 5-15KV, advancing speed is 0.5-2mL/h, and receiving distance is 15-35 cm.
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| SG10201404111VA (en) * | 2013-07-16 | 2015-02-27 | Univ Nanyang Tech | Method for preparing a patterned substrate and use thereof in implants for tissue engineering |
| KR101449645B1 (en) * | 2014-04-08 | 2014-10-14 | 부산대학교 산학협력단 | POROUS ElECTROSPUN FIBER FOR POSSIBLE THICKNESS CONTROL, ITS MANUFACTURING METHOD, AND FOUR DIMENSIONAL SCAFFOLD FOR TISSUE REGENERATION USING THE SAME |
| CN105983134A (en) * | 2015-03-05 | 2016-10-05 | 刘畅 | Artificial blood vessel and preparation method thereof |
| CN105457101B (en) * | 2015-12-17 | 2019-04-09 | 华南理工大学 | A kind of preparation method of three-decker small-caliber vascular stent |
| CN106512087A (en) * | 2016-12-06 | 2017-03-22 | 北京航空航天大学 | Artificial blood vessel stent with aligned fibers and manufacturing method of artificial blood vessel stent |
| CN107419530B (en) * | 2017-07-26 | 2020-01-14 | 武汉理工大学 | Polycaprolactone electrostatic spinning stent and preparation method thereof |
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