CN100465209C - Preparation method of degradable polymer material for stent in shape memory pipe cavity - Google Patents
Preparation method of degradable polymer material for stent in shape memory pipe cavity Download PDFInfo
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- CN100465209C CN100465209C CNB2006100301593A CN200610030159A CN100465209C CN 100465209 C CN100465209 C CN 100465209C CN B2006100301593 A CNB2006100301593 A CN B2006100301593A CN 200610030159 A CN200610030159 A CN 200610030159A CN 100465209 C CN100465209 C CN 100465209C
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Abstract
The present invention belongs to the field of polymer technology, and is especially preparation process of degradable polymer for rack inside shape memory tube. Lactide, glycolide or caprolactone, biodegradable polyester and diisocyanate as materials are first bulk melt polymerized to prepare the degradable polymer with thermal deformation transforming temperature (Ttrns) of about 37 deg.c. The obtained material is processed at temperature over melting temperature (Tm) so as to shape into spiral rack, applied with stress at temperature higher than Ttrans to form shape easily operational handling and frozen to eliminate stress into the product. The rack inside shape memory tube has excellent biocompatibility, can provide temporary support on the stenotic lumen and is degradable without need of post-operational taking out. In addition, the rack may be also used as medicine carrier.
Description
Technical field
The invention belongs to technical field of polymer materials, be specifically related to a class and can be used for treating the degradable high polymer material that is used for stent in shape memory pipe cavity (Biodegradable Shape-Memory Endoluminal Stent, preparation method BSMES) of luminal stenosis disease.
Background technology
Luminal stenosis is clinical common disease, endoluminal stent (endoluminal stent, ES) implantation is to be used for the treatment of the luminal stenosis venereal disease at present to become one of method the most efficiently and effectively, but owing to combine not tight between ES and wall of the lumen, there is rimala, due to leak around the ES be common complication, the shape memory alloy of development in recent years (shape-memory alloys, SMAs) support has effectively been alleviated this problem, but through metal is because of its thrombus source, that implants is permanent, the finiteness of appendix medicine, restenosis and because of long-term compressing cause in the film atrophy cause aneurysma to form or tube wall perforation etc. uses it still to have certain limitation.Many scholars have taken all factors into consideration the short-term of the potential complication of through metal and actual needs, develop support of new generation---and the Biodegradable polymer support (biodegradable polymer stents, BPS).
Generally occur in 8 hours based on stripping off of interventional therapy postoperative inner membrance with acute obturation, and the tube chamber restenosis mainly occurred in postoperative 3～6 months, take all factors into consideration the short-term of the potential complication of through metal and actual needs, Stack equal to take the lead in having developed in 1988 Biodegradable scaffold (biodegradable stents, BDS).Than through metal, the BPS support has: 1. have excellent biological compatibility, particularly blood compatibility.2. become nontoxic product and first immunogenicity by biological degradation.3. provide temporary supporting role to narrow tube chamber, and do not have secular complication.4. can be used as carrier and carry the medicine of antithrombotic and anti-intimal hyperplasia, and need not to carry out superiority such as secular whole body anti-freezing.In recent years, BDS is very fast in the development and the application in narrow disease therapeutic field.Tamai etc. have reported that human coronary is implanted into degradable poly lactic acid (PLLA) support in the recent period and 6 months result, and preliminary result shows, to implant for the mankind be feasible, safety and effectively to the PLLA support in the coronary artery.The dog test of Petas shows, places BDS and common stainless steel support in urethra, follows up a case by regular visits to respectively 6～12 months, and the BDS group all is far smaller than the stainless steel stent group of contrast in aspect indexs such as proliferation of fibrous tissue, chronic inflammatory reaction and oedema as a result.Korpela has carried out BDS and the through metal effectiveness study for the rabbit airway constriction, and the result is BDS group and through metal group therapeutic equivalence, but the short-term that BDS had retains and the characteristics of degraded automatically then are that through metal is incomparable.German scholar Lendlein proposed biodegradable shape memory polymers (biodegradable shape-memory polymers first on " Science " in 2002, BSMPs) notion, and reported with ethylene glycol to be initiator, obtain hydroxy-end capped PPDO and polycaprolactone through ring-opening polymerization, and then by 2,2,4-tri-methyl hexamethylene isocyanic ester carries out coupling, obtain the method for the shape-memory material of heat deformation point of inversion about 40 ℃, and be applied to operating sutures, obtained good effect, showed that biodegradable shape memory polymers is in the tempting prospect of biomedical materials field.Lendlein seminar has carried out a series of researchs to biodegradable shape memory polymers (BSMPs) subsequently, and report has synthesized the different polymkeric substance of a series of heat deformation point of inversion temperature, and studies its bio-toxicity and biocompatibility.The United States Patent (USP) of applications such as Langer " BIODEGRADABLE SHAPEMEMORYPOLYMERS " (US 6160084) is though include to some extent the polymkeric substance that the present invention relates to, but the preparation method of its macromolecular material adopts solution polymerization process, and the reaction times reached more than 10 days.In sum, with rac-Lactide (LA), glycollide (GL), caprolactone (CL) copolymerization or homopolymer and linear polyesters (LPE) is raw material, with vulcabond (DI) is coupling agent, by body melt polymerization process biodegradable shape memory polymers (BSMPs) and be applied to endoluminal stent, the research for the treatment of various narrow property diseases aspect has not yet to see relevant report.
Summary of the invention
The object of the present invention is to provide a kind of preparation method who is used for the degradable high polymer material of stent in shape memory pipe cavity.
The preparation method of the degradable high polymer material that is used for stent in shape memory pipe cavity that the present invention proposes, ring-opening polymerization takes place in the wantonly two kinds of monomers in rac-Lactide, glycollide or the caprolactone, makes hydroxy-end capped oligopolymer; Hydroxy-end capped oligopolymer of gained and linear polyesters are passed through the body melt polymerization, make degradable high polymer material, the material that obtains is melt extruded, machine-shaping promptly gets product, and actual conditions is:
(1) ring-opening polymerization:
With the wantonly two kinds of monomers in rac-Lactide, glycollide or the caprolactone, under catalyzer and the effect of small molecules dibasic alcohol, at N
2Under the atmosphere, cause ring-opening polymerization, polymerization temperature is 140～180 ℃, and the time is 12～20 hours, pressure is 50～70Pa, and reaction finishes the back and adds dissolution with solvents, adds precipitation agent then with polymer precipitation, purified product, vacuum-drying obtains hydroxy-end capped oligopolymer;
(2) melt polymerization:
With hydroxy-end capped oligopolymer and the linear polyesters that obtains in the step (1), under the effect of coupling agent vulcabond, under N2 atmosphere, by the body melt polymerization, linked reaction takes place, melt temperature is 150～180 ℃, time is 30～40 minutes, pressure is 50～70Pa, and reaction finishes the back and adds dissolution with solvents, adds precipitation agent then with polymer precipitation, purified product, vacuum-drying obtains the white powder degradable high polymer material, and the mol ratio that reactant is formed is:
A, when adopting rac-Lactide and two kinds of monomer ring-opening polymerizations of glycollide, rac-Lactide: the mol ratio of glycollide is 1:6～6; 1, hydroxy-end capped oligopolymer: the mol ratio of linear polyesters is 1:3～3:1;
B, when adopting rac-Lactide and two kinds of monomer ring-opening polymerizations of caprolactone, rac-Lactide: the mol ratio of caprolactone is 1:4～4:1, hydroxy-end capped oligopolymer: the mol ratio of linear polyesters is 1:2～2:1;
C, when adopting glycollide and two kinds of monomer ring-opening polymerizations of caprolactone, glycollide: the mol ratio of caprolactone is 1:2～2:1, hydroxy-end capped oligopolymer: the mol ratio of linear polyesters is 3:7～7:3.
Among the present invention, rac-Lactide, glycollide or caprolactone are made with extra care purification before carrying out polyreaction.
Among the present invention, catalyzer is stannous octoate, aluminum isopropylate or tetrabutyl titanate described in the step (1), and perhaps for being a kind of of the inner complex that forms of coordination center with tin, antimony, germanium, aluminium element, the catalyzer add-on is 0.05～0.1wt% of monomer total amount.
Among the present invention, described small molecules dibasic alcohol is an ethylene glycol, 1, ammediol or 1, and 4-butyleneglycol a kind of, the mol ratio of small molecules dibasic alcohol and monomer total amount is 1:20～1:30.
Among the present invention, linear polyesters (LPE) is dibasic alcohol and dicarboxylic acid or dicarboxylic anhydride polycondensation product, and it has following structure (I):
Wherein, m, q are respectively 2～10 integer.
Among the present invention, vulcabond is hexamethylene diisocyanate or lysinediisocyanate, and the mol ratio of the add-on of vulcabond and hydroxy-end capped oligopolymer and linear polyesters summation is 1:2～2:1.
Among the present invention, it is tetrahydrofuran (THF), chloroform, methylene dichloride, dioxane or N that polymerization finishes the solvent that the back adds, dinethylformamide a kind of.
Among the present invention, the precipitation agent that polymerization finishes the back adding is a kind of of methyl alcohol or ethanol.
Among the present invention, the material that obtains is melt extruded, extrusion temperature is 160～200 ℃, and on the hot rotary drum of syncmotor, be wound into spirrillum, and the hot rotary drum temperature T of syncmotor m is 140～200 ℃, rotating speed is 20～35 rev/mins, obtain the support of different diameter and pitch, helical stent is immersed cooling in the cryosel bath, eliminate stress, promptly get product.
The present invention is the heat deformation temperature inversion that the prepares degradable high polymer material o'clock about 37 ℃, with the material that obtains at melt temperature (T
m) process, figuration is made into and is used for different intraluminal helix supports, at last greater than material deformation temperature inversion point (T
Trans) under the temperature processing be fixed to the shape of being convenient to operation technique, promptly get product.
Use when treating the luminal stenosis disease according to the degradable high polymer material stent in shape memory pipe cavity that the inventive method obtains.
Advantage of the present invention: this Biodegradable shape-memory endoluminal stent (BSMES) has good shape memory, and being convenient to machine-shaping is the shape that is easy to operation technique, after implanting, returns to original shape automatically under the body temperature effect; Has excellent biological compatibility, particularly blood compatibility; Provide temporary supporting role to narrow tube chamber, not need not to take out and have secular complication and postoperative, finally in vivo fully degraded back metabolism discharge; Can be used as carrier and carry the medicine of antithrombotic and anti-intimal hyperplasia, and need not to carry out superiority such as secular whole body anti-freezing.
Description of drawings
Fig. 1 is a shape synoptic diagram before and after biodegradable stent in shape memory pipe cavity (BSMES) is implanted.Wherein, (a) be the shape before implanting, (b) for implanting the shape of back for some time.
Embodiment
Embodiment 1
With the refined L-rac-Lactide of ethyl alcohol recrystallization method (LLA), glycollide (GL), ethylene glycol, stannous octoate is a raw material, the mol ratio of L-rac-Lactide (LLA), glycollide (GL) is 1:6, ethylene glycol and L-rac-Lactide (LLA) and glycollide (GL) molar weight and ratio be 1:20, add the inferior tin of octoate catalyst (0.05wt% is in LLA and GL total mass) at 140 ℃ and N
2Under the protection, pressure is reduced to 50Pa, melt polymerization 12 hours.After reaction finishes, add the tetrahydrofuran (THF) dissolving, add the methanol extraction purified product then, it is standby that vacuum-drying obtains the hydroxy-end capped PLGA of white powder; More than the step makes hydroxy-end capped PLGA, number-average molecular weight (Mn) is 2000 hydroxy-end capped linear polyesters poly butylene succinate (PBS), hexamethylene diisocyanate (HDI) is a raw material, the mol ratio of PLGA, poly butylene succinate (PBS) is 1:3, hexamethylene diisocyanate (HDI) and PLGA and PBS molar weight and ratio be 1:2, at 150 ℃ and N
2Under the protection, pressure is reduced to 50Pa, and frit reaction 30 minutes after reaction finishes, adds the chloroform dissolving, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains white powder.
Above-mentioned macromolecular material is melt extruded 170 ℃ of hot rotary drum temperature, rotating speed 30r/min under 200 ℃, coiling and molding immerses rapidly in the cryosel bath, and the support of typing is slowly stretching with it at 50 ℃ of following stress applications, immerse cooling in the cryosel bath, remove stress, promptly get product.
Embodiment 2
With the refined D of ethyl alcohol recrystallization method, L-rac-Lactide (DLLA), glycollide (GL), 1,3-propylene glycol, tin protochloride are raw material, D, the mol ratio of L-rac-Lactide (DLLA), glycollide (GL) is 1:1, ethylene glycol and D, L-rac-Lactide (DLLA) and glycollide (GL) molar weight and ratio be 1:25, add catalyzer tin protochloride (0.1wt% is in DLLA and GL total mass) at 160 ℃ and N
2Under the protection, pressure is reduced to 65Pa, melt polymerization 18 hours.After reaction finishes, add the tetrahydrofuran (THF) dissolving, add the methanol extraction purified product then, it is standby that vacuum-drying obtains the hydroxy-end capped PLGA of white powder; More than the step makes hydroxy-end capped PLGA, number-average molecular weight (Mn) is 2000 hydroxy-end capped linear polyesters poly adipate succinic acid ester (PBA), hexamethylene diisocyanate (HDI) is a raw material, the mol ratio of PLGA, poly adipate succinic acid ester (PBA) is 1:1, hexamethylene diisocyanate (HDI) and PLGA and PBA molar weight and ratio be 1:1, at 160 ℃ and N
2Under the protection, pressure is reduced to 65Pa, and frit reaction 35 minutes after reaction finishes, adds the chloroform dissolving, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains white powder.
Above-mentioned macromolecular material is melt extruded 150 ℃ of hot rotary drum temperature, rotating speed 30r/min under 170 ℃, coiling and molding immerses rapidly in the cryosel bath, and the support of typing is slowly stretching with it at 60 ℃ of following stress applications, immerse cooling in the cryosel bath, remove stress, promptly get product.
Embodiment 3
With the refined D of ethyl alcohol recrystallization method, L-rac-Lactide (DLLA), glycollide (GL), 1,4-butyleneglycol, stannous octoate are raw material, D, the mol ratio of L-rac-Lactide (DLLA), glycollide (GL) is 6:1, ethylene glycol and D, L-rac-Lactide (DLLA) and glycollide (GL) molar weight and ratio be 1:30, add the inferior tin of octoate catalyst (0.1wt% is in DLLA and GL total mass) at 180 ℃ and N
2Under the protection, pressure is reduced to 70Pa, melt polymerization 20 hours.After reaction finishes, add the tetrahydrofuran (THF) dissolving, add the methanol extraction purified product then, it is standby that vacuum-drying obtains the hydroxy-end capped PLGA of white powder; More than the step makes hydroxy-end capped PLGA, number-average molecular weight (Mn) is 2000 the poly-hexanodioic acid hexylene glycol ester (PHA) of hydroxy-end capped linear polyesters, lysinediisocyanate (LDI) is a raw material, the mol ratio of PLGA, poly-hexanodioic acid hexylene glycol ester (PHA) is 3:1, lysinediisocyanate (LDI) and PLGA and PHA molar weight and ratio be 2:1, at 180 ℃ and N
2Under the protection, pressure is reduced to 70Pa, and frit reaction 40 minutes after reaction finishes, adds the chloroform dissolving, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains white powder.
Above-mentioned macromolecular material is melt extruded 140 ℃ of hot rotary drum temperature, rotating speed 30r/min under 165 ℃, coiling and molding immerses rapidly in the cryosel bath, and the support of typing is slowly stretching with it at 45 ℃ of following stress applications, immerse cooling in the cryosel bath, remove stress, promptly get product.
Embodiment 4
With the refined L-rac-Lactide of ethyl alcohol recrystallization method (LLA), caprolactone (CL), ethylene glycol, tin protochloride is a raw material, the mol ratio of L-rac-Lactide (LLA), caprolactone (CL) is 1:4, ethylene glycol and L-rac-Lactide (LLA) and caprolactone (CL) molar weight and ratio be 1:20, add catalyzer tin protochloride (0.1wt% is in LLA and CL total mass) at 140 ℃ and N
2Under the protection, pressure is reduced to 70Pa, melt polymerization 20 hours.After reaction finishes, add N, dinethylformamide dissolves, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains the hydroxy-end capped PCLA of white powder; More than the step makes hydroxy-end capped PCLA, number-average molecular weight (Mn) is 2000 hydroxy-end capped linear polyesters poly adipate succinic acid ester (PBA), hexamethylene diisocyanate (HDI) is a raw material, the mol ratio of PCLA, poly adipate succinic acid ester (PBA) is 1:2, hexamethylene diisocyanate (HDI) and PCLA and PBA molar weight and ratio be 1:1, at 150 ℃ and N
2Under the protection, pressure is reduced to 70Pa, and frit reaction 30 minutes after reaction finishes, adds the chloroform dissolving, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains white powder.
Above-mentioned macromolecular material is melt extruded 150 ℃ of hot rotary drum temperature, rotating speed 25r/min under 160 ℃, coiling and molding immerses rapidly in the cryosel bath, and the support of typing is slowly stretching with it at 50 ℃ of following stress applications, immerse cooling in the cryosel bath, remove stress, promptly get product.
Embodiment 5
With the refined D-rac-Lactide of ethyl alcohol recrystallization method (DLA), caprolactone (CL), 1,4-butyleneglycol, germanium chloride is a raw material, the mol ratio of D-rac-Lactide (DLA), caprolactone (CL) is 1:1, ethylene glycol and D-rac-Lactide (DLA) and caprolactone (CL) molar weight and ratio be 1:25, add catalyzer germanium chloride (0.05wt% is in DLA and CL total mass) at 160 ℃ and N
2Under the protection, pressure is reduced to 60Pa, melt polymerization 18 hours.After reaction finishes, add N, dinethylformamide dissolves, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains the hydroxy-end capped PCLA of white powder; More than the step makes hydroxy-end capped PCLA, number-average molecular weight (Mn) is 2000 hydroxy-end capped linear polyesters poly butylene succinate (PBS), lysinediisocyanate (LDI) is a raw material, the mol ratio of PCLA, poly butylene succinate (PBS) is 1:1, lysinediisocyanate (LDI) and PCLA and PBS molar weight and ratio be 1:2, at 165 ℃ and N
2Under the protection, pressure is reduced to 60Pa, and frit reaction 35 minutes after reaction finishes, adds the chloroform dissolving, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains white powder.
Above-mentioned macromolecular material is melt extruded 150 ℃ of hot rotary drum temperature, rotating speed 20r/min under 170 ℃, coiling and molding immerses rapidly in the cryosel bath, and the support of typing is slowly stretching with it at 40 ℃ of following stress applications, immerse cooling in the cryosel bath, remove stress, promptly get product.
Embodiment 6
With the refined D of ethyl alcohol recrystallization method, L-rac-Lactide (DLLA), caprolactone (CL), 1,3-propylene glycol, tetrabutyl titanate is a raw material, and the mol ratio of L-rac-Lactide (DLLA), caprolactone (CL) is 4:1, ethylene glycol and L-rac-Lactide (DLLA) and caprolactone (CL) molar weight and ratio be 1:30, add catalyzer metatitanic acid four butyl esters (0.1wt% is in DLLA and CL total mass) at 180 ℃ and N
2Under the protection, pressure is reduced to 50Pa, melt polymerization 12 hours.After reaction finishes, add N, dinethylformamide dissolves, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains the hydroxy-end capped PCLA of white powder; More than the step makes hydroxy-end capped PCLA, number-average molecular weight (Mn) is 2000 the poly-hexanodioic acid hexylene glycol ester (PHA) of hydroxy-end capped linear polyesters, lysinediisocyanate (LDI) is a raw material, the mol ratio of PCLA, the poly-hexanodioic acid hexylene glycol ester (PHA) of polyester is 2:1, lysinediisocyanate (LDI) and PCLA and PHA molar weight and ratio be 2:1, at 180 ℃ and N
2Under the protection, pressure is reduced to 50Pa, and frit reaction 40 minutes after reaction finishes, adds the chloroform dissolving, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains white powder.
Above-mentioned macromolecular material is melt extruded 150 ℃ of hot rotary drum temperature, rotating speed 20r/min under 165 ℃, coiling and molding immerses rapidly in the cryosel bath, and the support of typing is slowly stretching with it at 40 ℃ of following stress applications, immerse cooling in the cryosel bath, remove stress, promptly get product.
Embodiment 7
With the refined glycollide of ethyl alcohol recrystallization method (GL), caprolactone (CL), ethylene glycol, stannous octoate is a raw material, the mol ratio of glycollide (GL), caprolactone (CL) is 1:2, ethylene glycol and glycollide (GL) and caprolactone (CL) molar weight and ratio be 1:20, add the inferior tin of octoate catalyst (0.1wt% is in LLA and CL total mass) at 140 ℃ and N
2Under the protection, pressure is reduced to 70Pa, melt polymerization 20 hours.After reaction finishes, add the tetrahydrofuran (THF) dissolving, add the methanol extraction purified product then, it is standby that vacuum-drying obtains the hydroxy-end capped PGCL of white powder; More than the step makes hydroxy-end capped PGCL, number-average molecular weight (Mn) is 2000 hydroxy-end capped linear polyesters poly adipate succinic acid ester (PBA), hexamethylene diisocyanate (HDI) is a raw material, the mol ratio of PGCL, poly adipate succinic acid ester (PBA) is 3:7, hexamethylene diisocyanate (HDI) and PGCL and PBA molar weight and ratio be 1:1, at 150 ℃ and N
2Under the protection, pressure is reduced to 50Pa, and frit reaction 30 minutes after reaction finishes, adds the chloroform dissolving, adds the methanol extraction purified product then, and it is standby that vacuum-drying obtains white powder.
Above-mentioned macromolecular material is melt extruded 150 ℃ of hot rotary drum temperature, rotating speed 35r/min under 160 ℃, coiling and molding immerses rapidly in the cryosel bath, and the support of typing is slowly stretching with it at 45 ℃ of following stress applications, immerse cooling in the cryosel bath, remove stress, promptly get product.
Embodiment 8
With the refined glycollide of ethyl alcohol recrystallization method (GL), caprolactone (CL), ethylene glycol, stannous octoate is a raw material, the mol ratio of glycollide (GL), caprolactone (CL) is 1:1, ethylene glycol and glycollide (GL) and caprolactone (CL) molar weight and ratio be 1:25, add the inferior tin of octoate catalyst (0.05wt% is in LLA and CL total mass) at 160 ℃ and N
2Under the protection, pressure is reduced to 60Pa, melt polymerization 18 hours.After reaction finishes, add the tetrahydrofuran (THF) dissolving, add the methanol extraction purified product then, it is standby that vacuum-drying obtains the hydroxy-end capped PGCL of white powder; More than the step makes hydroxy-end capped PGCL, number-average molecular weight (Mn) is 2000 hydroxy-end capped linear polyesters poly butylene succinate (PBS), lysinediisocyanate (LDI) is a raw material, the mol ratio of PGCL, poly butylene succinate (PBS) is 1:1, lysinediisocyanate (LDI) and PGCL and PBS molar weight and ratio be 2:1, at 165 ℃ and N
2Under the protection, pressure is reduced to 60Pa, and frit reaction 35 minutes after reaction finishes, adds the dioxane dissolving, adds the ethanol sedimentation purified product then, and it is standby that vacuum-drying obtains white powder.
Above-mentioned macromolecular material is melt extruded 150 ℃ of hot rotary drum temperature, rotating speed 35r/min under 160 ℃, coiling and molding immerses rapidly in the cryosel bath, and the support of typing is slowly stretching with it at 45 ℃ of following stress applications, immerse cooling in the cryosel bath, remove stress, promptly get product.
Embodiment 9
With the refined glycollide of ethyl alcohol recrystallization method (GL), caprolactone (CL), ethylene glycol, tin protochloride is a raw material, the mol ratio of glycollide (GL), caprolactone (CL) is 2:1, ethylene glycol and glycollide (GL) and caprolactone (CL) molar weight and ratio be 1:30, add catalyzer tin protochloride (0.1wt% is in LLA and CL total mass) at 180 ℃ and N
2Under the protection, pressure is reduced to 50Pa, melt polymerization 12 hours.After reaction finishes, add the tetrahydrofuran (THF) dissolving, add the methanol extraction purified product then, it is standby that vacuum-drying obtains the hydroxy-end capped PGCL of white powder; More than the step makes hydroxy-end capped PGCL, number-average molecular weight (Mn) is 2000 the poly-hexanodioic acid hexylene glycol ester (PHA) of hydroxy-end capped linear polyesters, lysinediisocyanate (LDI) is a raw material, the mol ratio of PGCL, poly-hexanodioic acid hexylene glycol ester (PHA) is 7:3, lysinediisocyanate (LDI) and PGCL and PHA molar weight and ratio be 1:2, at 180 ℃ and N
2Under the protection, pressure is reduced to 50Pa, and frit reaction 40 minutes after reaction finishes, adds the methylene dichloride dissolving, adds the ethanol sedimentation purified product then, and it is standby that vacuum-drying obtains white powder.
Above-mentioned macromolecular material is melt extruded 150 ℃ of hot rotary drum temperature, rotating speed 35r/min under 160 ℃, coiling and molding immerses rapidly in the cryosel bath, and the support of typing is slowly stretching with it at 45 ℃ of following stress applications, immerse cooling in the cryosel bath, remove stress, promptly get product.
Claims (7)
1, a kind of preparation method who is used for the degradable high polymer material of stent in shape memory pipe cavity is characterized in that the wantonly two kinds of monomers in rac-Lactide, glycollide or the caprolactone, and ring-opening polymerization takes place, and makes hydroxy-end capped oligopolymer; Hydroxy-end capped oligopolymer of gained and linear polyesters are passed through the body melt polymerization, make degradable high polymer material, the material that obtains is melt extruded, machine-shaping promptly gets product, and actual conditions is:
(1) ring-opening polymerization:
With the wantonly two kinds of monomers in rac-Lactide, glycollide or the caprolactone, under catalyzer and the effect of small molecules dibasic alcohol, at N
2Under the atmosphere, cause ring-opening polymerization, polymerization temperature is 140～180 ℃, and the time is 12～20 hours, pressure is 50～70Pa, and reaction finishes the back and adds dissolution with solvents, adds precipitation agent then with polymer precipitation, purified product, vacuum-drying obtains hydroxy-end capped oligopolymer;
(2) melt polymerization:
With hydroxy-end capped oligopolymer and the linear polyesters that obtains in the step (1), under the effect of coupling agent vulcabond, at N
2Under the atmosphere, by the body melt polymerization, linked reaction takes place, melt temperature is 150～180 ℃, time is 30～40 minutes, pressure is 50～70Pa, and reaction finishes the back and adds dissolution with solvents, adds precipitation agent then with polymer precipitation, purified product, vacuum-drying obtains the white powder degradable high polymer material, and the mol ratio that reactant is formed is:
A, when adopting rac-Lactide and two kinds of monomer ring-opening polymerizations of glycollide, rac-Lactide: the mol ratio of glycollide is 1:6～6:1, hydroxy-end capped oligopolymer: the mol ratio of linear polyesters is 1:3～3:1;
B, when adopting rac-Lactide and two kinds of monomer ring-opening polymerizations of caprolactone, rac-Lactide: the mol ratio of caprolactone is 1:4～4:1, hydroxy-end capped oligopolymer: the mol ratio of linear polyesters is 1:2～2:1;
C, when adopting glycollide and two kinds of monomer ring-opening polymerizations of caprolactone, glycollide: the mol ratio of caprolactone is 1:2～2:1, hydroxy-end capped oligopolymer: the mol ratio of linear polyesters is 3:7～7:3;
Linear polyesters is dibasic alcohol and dicarboxylic acid or dicarboxylic anhydride polycondensation product, and it has following structure (I):
Wherein, m, q are respectively 2～10 integer;
Described small molecules dibasic alcohol is an ethylene glycol, 1, ammediol or 1, and 4-butyleneglycol a kind of, the mol ratio of small molecules dibasic alcohol and monomer total amount is 1:20～1:30.
2,, it is characterized in that monomer rac-Lactide, glycollide or caprolactone adopt the ethyl alcohol recrystallization method to make with extra care purification before carrying out polyreaction according to the preparation method of the described macromolecular material of claim 1.
3, according to the preparation method of the described macromolecular material of claim 1, it is characterized in that catalyzer is stannous octoate, aluminum isopropylate or tetrabutyl titanate described in the step (1), perhaps for being a kind of of the inner complex that forms of coordination center with tin, antimony, germanium, aluminium element, the catalyzer add-on is 0.05～0.1wt% of monomer total amount.
4, according to the preparation method of the described macromolecular material of claim 1, it is characterized in that vulcabond is hexamethylene diisocyanate or lysinediisocyanate, the mol ratio of the add-on of vulcabond and hydroxy-end capped oligopolymer and linear polyesters summation is 1:2～2:1.
5,, it is characterized in that it is tetrahydrofuran (THF), chloroform, methylene dichloride, dioxane or N that polymerization finishes the solvent that the back adds, dinethylformamide a kind of according to the preparation method of the described macromolecular material of claim 1.
6,, it is characterized in that the precipitation agent that adds after polymerization finishes is a kind of of methyl alcohol or ethanol according to the preparation method of the described macromolecular material of claim 1.
7, according to the preparation method of the described macromolecular material of claim 1, it is characterized in that the material that will obtain melt extrudes, extrusion temperature is 160～200 ℃, be wound into spirrillum on the hot rotary drum of syncmotor, the hot rotary drum temperature T of syncmotor m is 140～200 ℃, and rotating speed is 20～35 rev/mins, obtain the support of different diameter and pitch, helical stent is immersed cooling in the cryosel bath, eliminate stress, promptly get product.
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| CN101730551B (en) * | 2007-04-19 | 2016-01-27 | 史密夫和内修有限公司 | Orientated polymeric devices |
| CN102764168A (en) * | 2011-05-03 | 2012-11-07 | 上海理工大学 | Elastic shape memory recyclable bracket and manufacturing method and using method thereof |
| US9102782B2 (en) | 2011-08-12 | 2015-08-11 | China Petroleum & Chemical Corporation | Transparent copolyester, preparing method thereof and articles made from the same |
| CN102327652A (en) * | 2011-09-28 | 2012-01-25 | 微创医疗器械(上海)有限公司 | Biodegradable stent and preparation method thereof |
| CN102488931A (en) * | 2011-12-08 | 2012-06-13 | 张自强 | Spiral urethral stent and production method thereof |
| CN102675858A (en) * | 2012-05-22 | 2012-09-19 | 同济大学 | Method for preparing degradable tear duct embolisms having shape memory function |
| CN105771003B (en) * | 2016-04-15 | 2019-04-16 | 同济大学 | A method of biodegradable polymer self-expanding type blood vessel dilator is prepared based on 3D printing technique |
| CN112386747B (en) * | 2017-06-02 | 2022-04-12 | 天津工业大学 | Ureteral stent tube with shape memory function and preparation method and application thereof |
| CN107868645A (en) * | 2017-11-02 | 2018-04-03 | 上海纳米技术及应用国家工程研究中心有限公司 | Thermal-induced deformation plastic sheeting and preparation of sections method and products thereof and application |
| CN108853609A (en) * | 2018-07-20 | 2018-11-23 | 童红霞 | A kind of rhinitis prevention and treatment nasal cavity medicine controlled release treatment bracket |
| CN110016214B (en) * | 2019-04-11 | 2021-04-30 | 林元钦 | PLA blending modified material for 3D printing and preparation method thereof |
| CN110452374B (en) * | 2019-08-30 | 2021-09-28 | 苏州大学 | Three-dimensional spherical alpha-helical cationic polypeptide with efficient gene delivery capacity and preparation method and application thereof |
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