CN108276556B - Medical polyurethane material, preparation method thereof and repair stent - Google Patents
Medical polyurethane material, preparation method thereof and repair stent Download PDFInfo
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- CN108276556B CN108276556B CN201810120073.2A CN201810120073A CN108276556B CN 108276556 B CN108276556 B CN 108276556B CN 201810120073 A CN201810120073 A CN 201810120073A CN 108276556 B CN108276556 B CN 108276556B
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
- C08G18/428—Lactides
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/08—Processes
- C08G18/10—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/77—Polyisocyanates or polyisothiocyanates having heteroatoms in addition to the isocyanate or isothiocyanate nitrogen and oxygen or sulfur
- C08G18/771—Polyisocyanates or polyisothiocyanates having heteroatoms in addition to the isocyanate or isothiocyanate nitrogen and oxygen or sulfur oxygen
Abstract
The invention provides a medical polyurethane material, a preparation method thereof and a repair bracket, and relates to the technical field of medical materials. The medical polyurethane material provided by the invention comprises gastrodin, the mechanical property is greatly improved, and the application range is wider. And the composition has good biocompatibility, blood compatibility and biological stability, can effectively avoid side effects such as rejection reaction and the like when being applied in a body, and is better, stable and safe. The preparation method of the medical polyurethane material provided by the invention is simple and convenient to operate, can be used for industrial large-scale production, and is suitable for popularization and application. The repair scaffold provided by the invention has excellent mechanical property, is not easy to damage, has wide applicability, and can be used for repairing bones, blood vessels or nerves and the like. In addition, the repair bracket provided by the invention can effectively avoid side effects such as rejection and the like, and is more stable and safe.
Description
Technical Field
The invention relates to the technical field of medical materials, in particular to a medical polyurethane material, a preparation method thereof and a repair bracket.
Background
Tissue engineering is an emerging discipline established and developed in the eighties of the last century, and relates to a plurality of disciplines such as life science, biology, material science and the like. The basic principle and the method are that after being cultured and expanded in vitro, cells are implanted into a high polymer material bracket which can be degraded and absorbed in a human body, a three-dimensional space for propagation and regeneration is provided for the cells, the cells can grow on the three-dimensional bracket according to a prefabricated form after obtaining nutrient substances, and then the bracket is implanted into a damaged part of the human body, so that the implanted cells can be continuously propagated to form new tissues and organs with original special functions and forms, and simultaneously, the bracket can be degraded and absorbed, thereby achieving the treatment purposes of repairing wounds and reconstructing functions, and avoiding the risk of secondary operations.
The traditional bone grafting materials used in clinic are mainly divided into autogenous bone, allogeneic bone, specially processed xenogeneic bone, artificial bone material and the like, and the methods have the defects of applicability, complications and the like. The bone tissue cultured in vitro by means of tissue engineering is used as a repair material, so that various defects of other means are avoided, and an ideal effect can be achieved.
Polyurethane (PU) is a block polymer composed of hard segments and soft segments, and different physical and chemical properties and degradation properties can be obtained by selecting different soft segments or adjusting the proportion of the soft segments and the soft segments according to different requirements, and the Polyurethane has been widely paid attention in the field of tissue engineering because of the advantages of good biocompatibility, blood compatibility, flexible regulation and control of properties, and the like. On the basis, the slow release polyurethane stent which can meet the mechanical property requirement and can load functional drugs is particularly important.
However, the existing drug carriers have small pores or poor mechanical properties, and are difficult to provide effective sustained release amount and three-dimensional support, thus being unattractive.
Therefore, the development of the high-performance stent material which not only has good biocompatibility and flexibly adjustable physical and chemical properties, mechanical properties and degradation properties, but also can load functional drugs so as to meet the requirements of clinical repair on the high-performance stent material is particularly important. In view of the above, the present invention is particularly proposed.
Disclosure of Invention
The first purpose of the present invention is to provide a medical polyurethane material to alleviate the technical problem that the mechanical properties of the polyurethane sustained-release material in the prior art are difficult to meet the requirements in various aspects.
The second objective of the present invention is to provide a preparation method of the medical polyurethane material, so as to alleviate the technical problems of the preparation method of the medical polyurethane material in the prior art, such as complicated operation, complex process and incapability of combining gastrodin.
The third purpose of the invention is to provide a repair bracket which comprises the medical polyurethane material.
The invention provides a medical polyurethane material, which comprises gastrodin.
Further, the medical polyurethane material is a degradable block polyurethane material.
The invention also provides a preparation method of the medical polyurethane material, which comprises the following steps:
adding gastrodin into the medical polyurethane prepolymer to prepare the medical polyurethane material.
Further, adding a curing agent into oligomer polyol, and reacting to obtain the medical polyurethane prepolymer;
preferably, the oligomer polyol is one or more of polycaprolactone diol, polyethylene glycol, polyethylene adipate glycol, polylactic acid-glycolic acid copolymer or polyhexamethylene adipate glycol, and more preferably is polylactic acid-glycolic acid copolymer;
preferably, the curing agent is isocyanate, preferably diisocyanate, more preferably one or more of toluene diisocyanate, isophorone diisocyanate, diphenylmethane diisocyanate, dicyclohexylmethane diisocyanate, hexamethylene diisocyanate or lysine diisocyanate, and further preferably lysine diisocyanate;
preferably, a catalyst is also associated with the reaction of the oligomeric polyol with the curing agent.
Further, 5-10g of curing agent is added into every 20-40g of oligomer polyol, 0.1-0.3mL of catalyst is added after the reaction is carried out for 1-3h at the temperature of 60-80 ℃, and the medical polyurethane prepolymer is obtained after the reaction is stirred for 1-3 h.
Further, adding gastrodin into the medical polyurethane prepolymer for reaction, then adding a foaming agent for continuous reaction to obtain a reactant, and drying the reactant at high temperature to obtain the medical polyurethane material;
preferably, 2.5-4g of gastrodin is added into 25-50g of medical polyurethane prepolymer, 1-3mL of foaming agent is added after reaction for 1-3h to continue reaction for 0.1-1h to obtain a reactant, and the reactant is dried at the high temperature of 120 ℃ for 24h at 100 ℃ to prepare the medical polyurethane material.
Further, adding a curing agent and an organic solvent into oligomer polyol, and reacting to obtain the medical polyurethane prepolymer;
preferably, the oligomer polyol is one or more of polycaprolactone diol, polyethylene glycol, polyethylene adipate glycol, polylactic acid-glycolic acid copolymer or polyhexamethylene adipate glycol, and more preferably is polylactic acid-glycolic acid copolymer;
preferably, the curing agent is isocyanate, preferably diisocyanate, more preferably one or more of toluene diisocyanate, isophorone diisocyanate, diphenylmethane diisocyanate, dicyclohexylmethane diisocyanate, hexamethylene diisocyanate or lysine diisocyanate, and further preferably lysine diisocyanate;
preferably, the organic solvent is dimethyl sulfoxide.
Further, 3-4g of curing agent and 30-50mL of organic solvent are added into 10-20g of oligomer polyol, and the mixture is stirred at 40-60 ℃ in the dark for 4-7 days to prepare the medical polyurethane prepolymer.
Further, adding gastrodin into the medical polyurethane prepolymer under a low-temperature condition, and drying to obtain the medical polyurethane material;
preferably, 1-6.5g of gastrodin is added into 43-74g of medical polyurethane prepolymer at 25-40 ℃, and vacuum drying is carried out for 2-48h at 40-60 ℃ to prepare the medical polyurethane material.
In addition, the invention also provides a repair stent which comprises the medical polyurethane material or the medical polyurethane material prepared by the preparation method of the medical polyurethane material.
The medical polyurethane material provided by the invention comprises gastrodin. The invention combines the gastrodin with the polyurethane material for the first time to obtain the medical polyurethane material loaded with the gastrodin, and perfectly combines the polyhydroxy functionality, the hydrophilicity and the pharmaceutical activity of the gastrodin. The crosslinking degree of the gastrodin and the polyurethane material is increased by utilizing the chemical structure of the gastrodin with multiple functional groups, the mechanical property is greatly improved, and the application range is wider. In addition, as the gastrodin is a natural plant extract, the gastrodin can resist oxidative stress, promote osteogenic differentiation of stem cells, effectively improve dynamic balance of a microenvironment, and the medical polyurethane material loaded with the gastrodin has good biocompatibility, blood compatibility and biological stability, can effectively avoid side effects such as rejection and the like when being applied in a body, and is better, stable and safe.
The preparation method of the medical polyurethane material provided by the invention is simple and convenient to operate, and the medical polyurethane material with excellent mechanical property, biocompatibility, blood compatibility and biostability can be prepared by adding gastrodin into the medical polyurethane prepolymer, so that the medical polyurethane material can be industrially produced in a large scale and is suitable for popularization and application.
The repair bracket provided by the invention comprises the medical polyurethane material or the medical polyurethane material prepared by the preparation method of the medical polyurethane material. The repair scaffold has excellent mechanical property, is not easy to damage, has wide applicability, and can be used for repairing bones, blood vessels, nerves and the like. In addition, the repair scaffold provided by the invention can effectively avoid side effects such as rejection and the like, is more stable and safe, and the degradation product can resist apoptosis, improve the microenvironment in vivo and has a wide application prospect.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings in the following description are some embodiments of the present invention, and other drawings can be obtained by those skilled in the art without creative efforts.
FIG. 1A is a graph showing the results of initial modulus provided in Experimental example 1 of the present invention;
FIG. 1B is a graph showing the results of the maximum elongation to break coefficient provided in Experimental example 1 of the present invention;
FIG. 2 is a Scanning Electron Microscope (SEM) microscopic view of a cross section of a bone repair scaffold provided in Experimental example 2 of the present invention;
FIG. 3 is a graph showing the results of IR spectroscopy characterization of a bone repair scaffold according to Experimental example 3 of the present invention;
FIG. 4A is a Scanning Electron Microscope (SEM) microscopic image of the bone repair scaffold provided in Experimental example 4 of the present invention after co-culturing with bone marrow stromal stem cells for 4 days;
fig. 4B is a Scanning Electron Microscope (SEM) microscopic image of the bone repair scaffold provided in inventive experimental example 4 co-cultured with bone marrow stromal stem cells for 10 days.
Detailed Description
The technical solutions of the present invention will be described clearly and completely with reference to the following embodiments, and it should be understood that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The invention provides a medical polyurethane material, which comprises gastrodin.
The gastrodin is extracted from dried root block of Gastrodia elata Blume of Orchidaceae, is a main ingredient with pharmacological action of Gastrodia elata Blume of Yunnan, has convenient source and safe application, is helpful for improving effective compliance of patients, and is a natural polyhydroxy glucopyranoside. Has good tranquilizing and sleep improving effects, and can be used for relieving neurasthenia, insomnia, and headache. The Chinese medicinal material rhizoma Gastrodiae can be used for treating pain, giddiness, numbness of limbs, convulsion, and convulsion. The Chinese medicinal composition is generally applied to treating vertebrobasilar artery insufficiency, vestibular neuronitis, vertigo and the like in clinic. Meanwhile, clinical application also shows that the gastrodin has the effect of enhancing the activity of antioxidant enzyme, can resist oxidative stress and apoptosis, promotes osteogenic differentiation of stem cells, slows down the process of bone resorption, and effectively improves the dynamic balance of bone microenvironment.
The medical polyurethane material provided by the invention combines gastrodin with a polyurethane material for the first time to obtain the gastrodin-loaded medical polyurethane material, and on the basis that the gastrodin is usually used as a medicament for treating nervous diseases such as dizziness, convulsion and the like, the medical polyurethane material utilizes the chemical structure of multiple functional groups of the gastrodin, so that the crosslinking degree of the gastrodin and the polyurethane material is increased, the mechanical property is greatly improved, and the application range is wider. In addition, as the gastrodin is a natural plant extract, the medical polyurethane material loaded with the gastrodin has good biocompatibility, blood compatibility and biological stability, can effectively avoid side effects such as rejection reaction and the like when being applied in a body, and is better, stable and safe.
In a preferred embodiment, the medical polyurethane material is a degradable segmented polyurethane material.
The degradable block polyurethane material has good biocompatibility, can effectively avoid adverse reaction with organisms, has small side effect, is biodegradable, can be automatically decomposed after entering a human body, and is non-toxic and harmless to the human body.
The invention also provides a preparation method of the medical polyurethane material, which comprises the following steps:
adding gastrodin into the medical polyurethane prepolymer to prepare the medical polyurethane material.
The preparation method of the medical polyurethane material provided by the invention is simple and convenient to operate, and the medical polyurethane material with excellent mechanical property, biocompatibility, blood compatibility and biostability can be prepared by adding gastrodin into the medical polyurethane prepolymer, so that the medical polyurethane material can be industrially produced in a large scale and is suitable for popularization and application.
In a preferred embodiment, a curing agent is added to the oligomer polyol and reacted to obtain a medical polyurethane prepolymer.
Preferably, the oligomer polyol is one or more of polycaprolactone diol, polyethylene glycol, polyethylene adipate glycol, polylactic acid-glycolic acid copolymer or polyhexamethylene adipate glycol, more preferably polylactic acid-glycolic acid copolymer.
The polylactic acid-glycolic acid copolymer is formed by random polymerization of two monomers, namely lactic acid and glycolic acid, is a degradable functional polymer organic compound, and has good biocompatibility, no toxicity and good encapsulation and film forming performances. The medical polyurethane prepolymer provided by the invention is prepared by using the polylactic acid-glycolic acid copolymer as a raw material, and has the advantages of higher degradation rate, better biocompatibility, blood compatibility and biostability.
Preferably, the curing agent is an isocyanate, preferably a diisocyanate, more preferably one or more of toluene diisocyanate, isophorone diisocyanate, diphenylmethane diisocyanate, dicyclohexylmethane diisocyanate, hexamethylene diisocyanate or lysine diisocyanate, and further preferably lysine diisocyanate.
The lysine diisocyanate is used as a curing agent to be combined with the oligomer polyol, so that the water resistance, the stretchability and the interface bonding performance of the prepared medical polyurethane prepolymer can be improved to a greater extent, and the applicability of the medical polyurethane prepolymer is enhanced.
Preferably, a catalyst is also associated with the reaction of the oligomeric polyol with the curing agent. More preferably, the catalyst is stannous octoate.
The catalyst is added in the reaction process, so that the reaction can be accelerated, and the time and cost are saved.
In a preferred embodiment, 5-10g of curing agent is added into 20-40g of oligomer polyol, 0.1-0.3mL of catalyst is added after reaction for 1-3h at 60-80 ℃, and the mixture is stirred for 1-3h to obtain the medical polyurethane prepolymer.
Wherein, the oligomer polyol can be, for example, but not limited to, 20g, 25g, 30g, 35g, or 40 g; the curing agent may be, for example, but is not limited to, 5g, 6g, 7g, 8g, 9g, or 10 g; the reaction temperature may be, for example, but not limited to, 60 ℃, 65 ℃, 70 ℃, 75 ℃, or 80 ℃; the reaction time may be, for example, but is not limited to, 1h, 1.5h, 2h, 2.5h, or 3 h; the catalyst may be, for example, but is not limited to, 0.1mL, 0.2mL, or 0.3 mL; the stirring time may be, for example, but is not limited to, 1h, 2h, or 3 h.
In a preferred embodiment, gastrodin is added into the medical polyurethane prepolymer for reaction, then a foaming agent is added for continuous reaction to obtain a reactant, and the reactant is dried at high temperature to obtain the medical polyurethane material.
Preferably, 2.5-4g of gastrodin is added into 25-50g of medical polyurethane prepolymer, 1-3mL of foaming agent is added after reaction for 1-3h to continue reaction for 0.1-1h to obtain a reactant, and the reactant is dried at the high temperature of 120 ℃ for 24h at 100 ℃ to prepare the medical polyurethane material.
The medical polyurethane prepolymer can be, but is not limited to, 25g, 30g, 35g, 40g, 45g or 50 g; gastrodine may be, for example, but is not limited to, 2.5g, 3g, 3.5g, or 4 g; the reaction time may be, for example, but is not limited to, 1h, 2h, or 3 h; the blowing agent may be, for example, but is not limited to, 1mL, 2mL, or 3 mL; the time for continuing the reaction may be, for example, but not limited to, 0.1h, 0.5h, or 1 h; the high temperature drying temperature can be, for example, but not limited to, 100 ℃, 105 ℃, 110 ℃, 115 ℃ or 120 ℃.
In a preferred embodiment, a curing agent and an organic solvent are added to the oligomer polyol and reacted to obtain a medical polyurethane prepolymer.
Preferably, the oligomer polyol is one or more of polycaprolactone diol, polyethylene glycol, polyethylene adipate glycol, polylactic acid-glycolic acid copolymer or polyhexamethylene adipate glycol, more preferably polylactic acid-glycolic acid copolymer.
The polylactic acid-glycolic acid copolymer is formed by random polymerization of two monomers, namely lactic acid and glycolic acid, is a degradable functional polymer organic compound, and has good biocompatibility, no toxicity and good encapsulation and film forming performances. The medical polyurethane prepolymer provided by the invention is prepared by using the polylactic acid-glycolic acid copolymer as a raw material, and has the advantages of higher degradation rate, better biocompatibility, blood compatibility and biostability.
Preferably, the curing agent is an isocyanate, preferably a diisocyanate, more preferably one or more of toluene diisocyanate, isophorone diisocyanate, diphenylmethane diisocyanate, dicyclohexylmethane diisocyanate, hexamethylene diisocyanate or lysine diisocyanate, and further preferably lysine diisocyanate.
The lysine diisocyanate is used as a curing agent to be combined with the oligomer polyol, so that the water resistance, the stretchability and the interface bonding performance of the prepared medical polyurethane prepolymer can be improved to a greater extent, and the applicability of the medical polyurethane prepolymer is enhanced.
Preferably, the organic solvent is dimethyl sulfoxide.
Dimethyl sulfoxide can be dissolved with medical polyurethane prepolymer and gastrodin simultaneously, and dimethyl sulfoxide is added in the reaction process, so that the medical polyurethane prepolymer and gastrodin have higher compatibility, and the prepared medical polyurethane material has more excellent mechanical properties.
In a preferred embodiment, 3-4g of curing agent and 30-50mL of organic solvent are added to 10-20g of oligomer polyol, and the mixture is stirred at 40-60 ℃ in the dark for 4-7 days to prepare a medical polyurethane prepolymer.
Wherein the oligomer polyol may be, for example, but not limited to, 10g, 15g, or 20 g; the curing agent may be, for example, but is not limited to, 3g, 3.5g, or 4 g; the organic solvent may be, for example, but is not limited to, 30mL, 35mL, 40mL, 45mL, or 50 mL; the reaction temperature may be, for example, but not limited to, 40 ℃, 45 ℃, 50 ℃, 55 ℃ or 60 ℃; the reaction time may be, for example, but not limited to, 4 days, 5 days, 6 days, or 7 days.
In a preferred embodiment, gastrodin is added into the medical polyurethane prepolymer under the low temperature condition, and the medical polyurethane material is prepared after drying.
Adding gastrodin at low temperature is favorable for maintaining medicinal activity of gastrodin and reducing side reaction product.
Preferably, 1-6.5g of gastrodin is added into 43-74g of medical polyurethane prepolymer at the temperature of 25-40 ℃, and vacuum drying is carried out for 2-48h at the temperature of 40-60 ℃ to prepare the medical polyurethane material.
The reaction temperature may be, for example, but not limited to, 25 ℃, 30 ℃, 35 ℃ or 40 ℃; the medical polyurethane prepolymer can be, but is not limited to, 43g, 50g, 55g, 60g, 65g, 70g or 74 g; gastrodine can be, for example, but is not limited to, 1g, 1.5g, 2g, 2.5g, 3g, 3.5g, 4g, 4.5g, 5g, 5.5g, 6g, or 6.5 g; the temperature of the vacuum drying may be, for example, but not limited to, 40 ℃, 45 ℃, 50 ℃, 55 ℃ or 60 ℃; the time for vacuum drying may be, for example, but not limited to, 2h, 5h, 10h, 15h, 20h, 25h, 30h, 35h, 40h, 45h, or 48 h.
In addition, the invention also provides a repair stent which comprises the medical polyurethane material or the medical polyurethane material prepared by the preparation method of the medical polyurethane material.
The repairing bracket provided by the invention has excellent mechanical property, is not easy to damage and has wide applicability, can be prepared into a degradable block polyurethane bone repairing bracket loaded with a traditional Chinese medicine component gastrodin, a degradable block polyurethane blood vessel repairing bracket loaded with a traditional Chinese medicine component gastrodin, a degradable block polyurethane nerve repairing bracket loaded with a traditional Chinese medicine component gastrodin, and the like, and is used for repairing bones, blood vessels, nerves, and the like.
The medical polyurethane material with good biocompatibility and bioactivity, and flexibly adjustable physical and chemical properties, mechanical properties and degradation properties is used for preparing the polyurethane porous bone repair scaffold with gastrodin loading, and the excellent biological properties and degradation properties of the material, the high porosity of the scaffold and the pharmaceutical activity of gastrodin are perfectly combined, so that the requirement of clinical bone repair on the high-performance porous scaffold material is met, and the application prospect is wide.
The biodegradable elastomer polyurethane with good mechanical property and cell tissue compatibility is loaded with gastrodin, so that the peripheral vascular resistance can be effectively reduced, the blood pressure is reduced, the arterial vascular compliance is increased, the vascular endothelial injury is obviously improved, and the functionalization and bionic construction of the artificial vascular stent are facilitated.
Similarly, by adjusting the proportions of the oligomer polyol, the curing agent and the gastrodin, an elastomer with high anti-kink performance can be obtained. Based on the bionic preparation of the bioactive polyurethane, the loading of the gastrodin is beneficial to improving the mechanical property of the material, and the degradation rate of the polyurethane is controlled by regulating the proportion amount of the gastrodin, so that the gastrodin is continuously and gradually released in local, the nerve protection effect of the gastrodin can be fully exerted, the directional differentiation of Schwann cells and nerve cells is accelerated, and the targeted nerve repair effect is further realized.
In addition, the repair bracket provided by the invention can effectively avoid side effects such as rejection and the like, and is more stable and safe.
The present invention will be further described with reference to specific examples and comparative examples.
Example 1
The embodiment provides a medical polyurethane material, which is prepared by the following preparation method:
(a) adding 20.0g of polylactic acid-glycolic acid (molecular weight 2000) copolymer into a three-neck flask filled with nitrogen, slowly adding 10g of lysine diisocyanate (molecular weight 226), and reacting at 60 ℃ for 3 hours to obtain a medical polyurethane prepolymer;
(b) adding 2.5g of gastrodin into the medical polyurethane prepolymer obtained in the step (a) and reacting for 3 hours;
(c) adding 1mL of water into the product obtained in the step (b) and continuing to react for 1 h;
(d) and collecting a sample, and placing the sample in a 100 ℃ oven for curing and drying for 24 hours to obtain the medical polyurethane material.
Example 2
The embodiment provides a medical polyurethane material, which is prepared by the following preparation method:
(a) adding 40.0g of polylactic acid-glycolic acid copolymer (molecular weight 4000) into a three-neck flask filled with nitrogen, slowly adding 5g of lysine diisocyanate, and reacting at 80 ℃ for 1h to obtain a medical polyurethane prepolymer;
(b) adding 4g of gastrodin into the medical polyurethane prepolymer obtained in the step (a), and reacting for 1 h;
(c) adding 3mL of water into the product obtained in the step (b) and continuing to react for 0.1 h;
(d) and collecting a sample, and placing the sample in a 120 ℃ oven for curing and drying for 24 hours to obtain the medical polyurethane material.
Example 3
The embodiment provides a medical polyurethane material, which is prepared by the following preparation method:
(a) adding 30.0g of polylactic acid-glycolic acid copolymer into a three-neck flask filled with nitrogen, slowly adding 7.9g of lysine diisocyanate, and reacting at 70 ℃ for 2 hours to obtain a medical polyurethane prepolymer;
(b) adding 3.4g of gastrodin into the medical polyurethane prepolymer obtained in the step (a) and reacting for 2 hours;
(c) adding 2mL of water into the product obtained in the step (b) and continuing to react for 0.5 h;
(d) and collecting a sample, and placing the sample in a 110 ℃ oven for curing and drying for 24h to obtain the medical polyurethane material.
Example 4
The embodiment provides a medical polyurethane material, which is prepared by the following preparation method:
(a) adding 30.0g of polylactic acid-glycolic acid copolymer into a three-neck flask filled with nitrogen, slowly adding 7.9g of lysine diisocyanate, and reacting for 2 hours at 70 ℃;
(b) adding 0.2mL of stannous octoate into the product obtained in the step (a), and stirring for 2h to obtain a medical polyurethane prepolymer;
(c) adding 3.4g of gastrodin into the medical polyurethane prepolymer obtained in the step (b), and reacting for 2 hours;
(d) adding 2mL of water into the product obtained in the step (c) and continuously reacting for 0.5 h;
(e) and collecting a sample, and placing the sample in a 110 ℃ oven for curing and drying for 24h to obtain the medical polyurethane material.
Example 5
The embodiment provides a medical polyurethane material, which is prepared by the following preparation method:
(a) adding 30.0g of polycaprolactone diol into a three-neck flask filled with nitrogen, slowly adding 7.8g of isophorone diisocyanate, and reacting for 2 hours at 70 ℃;
(b) adding 0.2mL of stannous octoate into the product obtained in the step (a), and stirring for 2h to obtain a medical polyurethane prepolymer;
(c) adding 3.4g of gastrodin into the medical polyurethane prepolymer obtained in the step (b), and reacting for 2 hours;
(d) adding 2mL of water into the product obtained in the step (c) and continuously reacting for 0.5 h;
(e) and collecting a sample, and placing the sample in a 110 ℃ oven for curing and drying for 24h to obtain the medical polyurethane material.
Example 6
The embodiment provides a medical polyurethane material, which is prepared by the following preparation method:
(a) adding 10.0g of polylactic acid-glycolic acid copolymer into a three-neck flask filled with nitrogen, simultaneously adding 4.0g of lysine diisocyanate and 30mL of DMSO, and stirring at 60 ℃ in a dark place for 4 days to generate a medical polyurethane prepolymer;
(b) adding 2.5g of gastrodin into the medical polyurethane prepolymer under the low-temperature condition;
(c) and vacuum drying at 40 ℃ to obtain the medical polyurethane material.
Example 7
The embodiment provides a medical polyurethane material, which is prepared by the following preparation method:
(a) adding 20.0g of polylactic acid-glycolic acid copolymer into a three-neck flask filled with nitrogen, simultaneously adding 3.0g of lysine diisocyanate and 50mL of DMSO, and stirring at 40 ℃ in a dark place for 6 days to generate a medical polyurethane prepolymer;
(b) adding 1g of gastrodin into the medical polyurethane prepolymer under the low-temperature condition;
(c) and vacuum drying at 60 ℃ to obtain the medical polyurethane material.
Example 8
The embodiment provides a medical polyurethane material, which is prepared by the following preparation method:
(a) adding 16.0g of polylactic acid-glycolic acid copolymer into a three-neck flask filled with nitrogen, simultaneously adding 3.60g of lysine diisocyanate and 40mL of DMSO, and stirring at 50 ℃ in a dark place for 5 days to generate a medical polyurethane prepolymer;
(b) adding 1.83g of gastrodin into the medical polyurethane prepolymer under the low-temperature condition;
(c) and vacuum drying at 50 ℃ to obtain the medical polyurethane material.
Example 9
The embodiment provides a medical polyurethane material, which is prepared by the following preparation method:
(a) adding 16.0g of polycaprolactone diol into a three-neck flask filled with nitrogen, simultaneously adding 3.60g of isophorone diisocyanate and 40mL of DMSO, and stirring at 50 ℃ in a dark place for 5 days to generate a medical polyurethane prepolymer;
(b) adding 1.83g of gastrodin into the medical polyurethane prepolymer under the low-temperature condition;
(c) and vacuum drying at 50 ℃ to obtain the medical polyurethane material.
Comparative example 1
The comparative example provides a medical polyurethane material prepared by applying the following preparation method:
(a) adding 15.0g of polylactic acid-glycolic acid copolymer into a three-neck flask filled with nitrogen, slowly adding 15g of lysine diisocyanate, and reacting for 4 hours at 50 ℃;
(b) adding 0.05mL of stannous octoate into the product obtained in the step (a), and stirring for 4 hours to obtain a medical polyurethane prepolymer;
(c) adding 3.4g of gastrodin into the medical polyurethane prepolymer obtained in the step (b), and reacting for 0.5 h;
(d) adding 4mL of water into the product obtained in the step (c) and continuing to react for 0.05 h;
(e) and collecting a sample, and placing the sample in a 130 ℃ oven for curing and drying for 24 hours to obtain the medical polyurethane material.
Comparative example 2
The comparative example provides a medical polyurethane material prepared by applying the following preparation method:
(a) adding 22.0g of polylactic acid-glycolic acid copolymer into a three-neck flask filled with nitrogen, simultaneously adding 2.0g of lysine diisocyanate and 55mL of DMSO, and stirring at 30 ℃ in the dark for 7 days to generate a medical polyurethane prepolymer;
(b) adding 1.83g of gastrodin into the medical polyurethane prepolymer under the low-temperature condition;
(c) and vacuum drying at 30 ℃ to obtain the medical polyurethane material.
Comparative example 3
This comparative example provides a medical polyurethane material, which is different from example 4 in that the amount of gastrodin added is 1.7 g.
Comparative example 4
This comparative example provides a medical polyurethane material, which is different from example 4 in that 0.85g of gastrodin was added.
Comparative example 5
This comparative example provides a medical polyurethane material, which is different from example 4 in that gastrodin is added in an amount of 0.425 g.
Comparative example 6
This comparative example provides a medical polyurethane material, which is different from example 4 in that gastrodin is not added.
Experimental example 1
The medical polyurethane materials provided in examples 1 to 9 and comparative examples 1 to 6 were used to prepare bone repair scaffolds, respectively. The prepared bone repair scaffold is subjected to mechanical property and degradation period detection, and the results are shown in the following table:
as can be seen from the results in the above table, the bone repair scaffolds prepared from the medical polyurethane materials provided in examples 1 to 9 of the present invention have higher maximum tensile strength and higher maximum elongation at break than the bone repair scaffolds prepared from the medical polyurethane materials provided in comparative examples 1 to 6. The medical polyurethane material prepared by the preparation method provided by the invention has excellent mechanical property, is not easy to damage and has wide applicability.
Examples 1 to 5 employ a preparation method provided by the present invention to prepare a medical polyurethane material. The difference between example 1 and example 4 is that the maximum tensile strength and the maximum elongation-to-break coefficient of the medical polyurethane material prepared in example 4 are higher due to the addition of the catalyst, which indicates that the medical polyurethane material prepared by the reaction with the addition of the catalyst has stronger mechanical properties. Moreover, as can be seen from comparison between examples 1 to 4 and example 5, the medical polyurethane material prepared from the preferred raw materials provided by the invention has a faster degradation rate, can reduce the retention time of foreign substances in vivo, and is safer. Further, example 4 is a medical polyurethane material prepared under the preferred conditions of the present invention, which has the highest maximum tensile strength and the highest maximum elongation-to-break coefficient, and thus shows that the medical polyurethane material prepared under the preferred conditions of the present invention has stronger mechanical properties.
Examples 6 to 9 another preparation method provided by the present invention was applied to prepare a medical polyurethane material. As can be seen from the comparison between examples 6 to 8 and example 9, the medical polyurethane material prepared from the preferred raw materials provided by the invention has a faster degradation rate, can reduce the retention time of foreign substances in vivo, and is safer. Further, example 8 shows that the maximum tensile strength and the maximum elongation-to-break coefficient of the medical polyurethane material prepared under the preferred conditions of the present invention are the highest, which indicates that the medical polyurethane material prepared under the preferred conditions of the present invention has stronger mechanical properties.
In order to further illustrate the beneficial effects brought by loading gastrodin in the medical polyurethane material, the medical polyurethane materials provided in example 5 and comparative examples 3 to 6 were tested, and the test results are shown in fig. 1A and 1B. As can be seen from the figure, the initial modulus of the scaffold is obviously increased and the elongation at break is reduced with the increase of the gastrodin proportion, which shows that the polyhydroxy structure of the gastrodin is helpful for increasing the crosslinking degree of the polymer, thereby improving the mechanical property of the polymer.
Experimental example 2
In order to save the experimental cost, the cross section of the bone repair scaffold prepared from the medical polyurethane material provided in application example 4 is subjected to scanning electron microscope detection, and the result is shown in fig. 2. As can be seen from figure 2, the scaffold is a through porous structure and can simulate natural bone tissues.
Experimental example 3
In order to save experimental cost, infrared spectroscopy characterization is performed on the bone repair scaffold prepared from the medical polyurethane material provided in application example 4, and the result is shown in fig. 3. It can be seen from fig. 3 that the hydroxyl peak of polyurethane is significantly weakened, which indicates that the hydroxyl of gastrodin reacts with IPDI, effectively loading gastrodin.
Experimental example 4
In order to save experimental cost, the bone marrow stromal cells and the bone repair scaffold prepared from the medical polyurethane material provided in application example 4 were co-cultured. The results of observation on a scanning electron microscope at the time of co-cultivation for 4 days are shown in FIG. 4A. As can be seen in FIG. 4A, cells grew adherently on the surface of the scaffold. The results of observation on a scanning electron microscope at 10 days of co-cultivation are shown in FIG. 4B. From fig. 4B, it can be seen that the cells proliferated significantly, producing a large amount of pseudopodia, indicating that the porous scaffold has good biocompatibility.
Finally, it should be noted that: the above embodiments are only used to illustrate the technical solution of the present invention, and not to limit the same; while the invention has been described in detail and with reference to the foregoing embodiments, it will be understood by those skilled in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some or all of the technical features may be equivalently replaced; and the modifications or the substitutions do not make the essence of the corresponding technical solutions depart from the scope of the technical solutions of the embodiments of the present invention.
Claims (2)
1. The medical polyurethane material is characterized by being prepared by the following preparation method:
(a) adding 30.0g of polylactic acid-glycolic acid copolymer into a three-neck flask filled with nitrogen, slowly adding 7.9g of lysine diisocyanate, and reacting for 2 hours at 70 ℃;
(b) adding 0.2mL of stannous octoate into the product obtained in the step (a), and stirring for 2h to obtain a medical polyurethane prepolymer;
(c) adding 3.4g of gastrodin into the medical polyurethane prepolymer obtained in the step (b), and reacting for 2 hours;
(d) adding 2mL of water into the product obtained in the step (c) and continuously reacting for 0.5 h;
(e) and collecting a sample, and placing the sample in a 110 ℃ oven for curing and drying for 24h to obtain the medical polyurethane material.
2. A prosthetic stent comprising the medical polyurethane material of claim 1.
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| CN111467582A (en) * | 2020-03-03 | 2020-07-31 | 昆明医科大学 | Intravascular stent and preparation method thereof |
| CN111909343B (en) * | 2020-08-11 | 2022-04-08 | 丽水学院 | Elastic polyurethane antibacterial material and preparation method thereof |
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| WO2006055261A2 (en) * | 2004-11-05 | 2006-05-26 | Carnegie Mellon University | Degradable polyurethane foams |
| WO2007123536A1 (en) * | 2006-04-24 | 2007-11-01 | Carnegie Mellon University | Biodegradable polyurethanes |
| CN104356345A (en) * | 2014-12-01 | 2015-02-18 | 四川大学 | Fluorescent graft degradable block polyurethane, bone repair material and preparation method thereof |
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| EP1592728A2 (en) * | 2003-01-16 | 2005-11-09 | Carnegie-Mellon University | Biodegradable polyurethanes and use thereof |
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| WO2000067813A1 (en) * | 1999-05-07 | 2000-11-16 | Salviac Limited | Biostable polyurethane products |
| WO2006055261A2 (en) * | 2004-11-05 | 2006-05-26 | Carnegie Mellon University | Degradable polyurethane foams |
| WO2007123536A1 (en) * | 2006-04-24 | 2007-11-01 | Carnegie Mellon University | Biodegradable polyurethanes |
| CN104356345A (en) * | 2014-12-01 | 2015-02-18 | 四川大学 | Fluorescent graft degradable block polyurethane, bone repair material and preparation method thereof |
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