CN114524913B - High-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer, and preparation method and application thereof - Google Patents

High-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer, and preparation method and application thereof Download PDF

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CN114524913B
CN114524913B CN202210200194.4A CN202210200194A CN114524913B CN 114524913 B CN114524913 B CN 114524913B CN 202210200194 A CN202210200194 A CN 202210200194A CN 114524913 B CN114524913 B CN 114524913B
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polyurethane elastomer
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CN114524913A (en
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陈思翀
王曼
吴刚
王玉忠
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Sichuan University
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Abstract

The invention discloses a high-flexibility high-elasticity degradable and adjustable absorbable polyurethane elastomer, a preparation method and application thereof; the method comprises the following steps: step 1: adding the aliphatic random copolyester dihydric alcohol prepolymer and the aliphatic polyester dihydric alcohol prepolymer into a reactor, and heating to a temperature above the melting point of the prepolymers for melting and mixing; step 2: adding diisocyanate into the mixture, and reacting to obtain an isocyanate-terminated prepolymer; and step 3: adding a chain extender, and obtaining the required absorbable polyurethane elastomer after the reaction is finished; the polyurethane obtained by the invention has the advantages of good biocompatibility, high flexibility, high elasticity, adjustable and controllable degradation, absorbability and the like, and can resist the corrosion action of various proteases, so that the polyurethane elastomer can be used for preparing digestive tract anastomosis medical equipment, biodegradable coatings for repairing stents, soft tissue regeneration and repair medical products, degradable packaging materials, degradable sealing materials and degradable battery packaging materials.

Description

High-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer, and preparation method and application thereof
Technical Field
The invention relates to the technical field of polyurethane elastomers, in particular to a high-flexibility high-elasticity degradable and adjustable absorbable polyurethane elastomer, a preparation method and application thereof.
Background
Polyurethane is a new organic polymer material and is known as the fifth major plastic. The main part of raw materials for synthesizing the polyurethane are polyisocyanate and hydroxyl-terminated compound, and due to different reaction conditions, different types of diisocyanate, different proportions of diisocyanate and hydroxyl-terminated compound, different types of hydroxyl-terminated compound and different relative molecular weight masses of hydroxyl-terminated compound, the structure and performance of the polyurethane have great difference, so that the polyurethane material can be widely applied to the fields of coating, adhesive, thermoplastic elastomer, foam material and the like. The polyurethane prepared by using the biodegradable polymer precursor as the raw material has excellent mechanical property and processability, certain biodegradability and good biocompatibility, and has important application prospect in the fields of disposable environment-friendly materials, biomedical materials and the like. For example, CN102675855A causes active degradation of polyurethane by adding phosphorus pentoxide with strong oxidizing effect to the polyurethane; for example, CN10297730A adopts a blend of liquefied biomass and starch as a polyol material to synthesize polyurethane, so as to improve the degradation performance of the polyurethane; for example, CN103910846A adopts polypropylene carbonate polyol, polyester diol, polyether diol, diisocyanate, catalyst, chain extender, and organic solvent to prepare a polyurethane material with good storage stability, excellent coating film performance, and good degradation performance. For example, CN104387553A adopts propylene glycol fumarate, isocyanate and a chain extender as raw materials to prepare biodegradable polyurethane; for example, CN108409938A adopts selective coupling reaction between aliphatic polyester diol and diisocyanate-terminated hydrophilic polyether or between aliphatic polyester diol and diisocyanate-terminated aliphatic polyester block to obtain degradable polyurethane with alternate blocks.
However, the existing biodegradable polyurethane has the defects that the degradation rate is not adjustable, the retention time of mechanical properties and the in vivo retention time are difficult to be considered simultaneously, and the like, and the application of the existing biodegradable polyurethane in vivo implanted materials, especially in complex biological enzyme environments, is severely limited. Taking the digestive tract anastomosis operation (such as pancreatico-enterostomy, gastrointestinal anastomosis, cholangio-enterostomy and the like) as an example, drainage of digestive juice (pancreatic juice, gastric juice, bile and the like) is of great importance to the success of the anastomosis operation. For example, the pancreas intestine anastomosis drainage is to arrange a drainage tube in a pancreas catheter of a pancreas section, introduce the pancreatic juice of the residual pancreas into small intestine or outside the body, reduce the accumulation of pancreatin at an anastomotic stoma, relieve the pressure bearing of the anastomotic stoma, and play a positive role in slowing down and preventing the occurrence of pancreas fistula. At present, the support tubes mainly used for external drainage are all made of elastomer materials which can not be degraded in vivo, such as silica gel, organic silicon composite materials and the like. In the later period, the patient has complications such as puncture of the digestive tract by the residual drainage tube, blockage of the pancreatic duct and the bile duct, secondary pain is caused to the patient, serious complications such as intra-abdominal infection and intra-abdominal bleeding can be further caused, and the life of the patient is threatened. On one hand, the complete healing of the tissues at the anastomotic site requires 25 to 40 days, and on the other hand, the digestive juice contains various digestive enzymes such as protease, lipase, amylase and the like, so that the digestive juice can cause stronger corrosion to most of the degradable high molecular materials in vivo in clinical application at present. Therefore, it is often difficult for the existing degradable and absorbable polymer materials to satisfy the clinical requirements of maintaining sufficient support strength and integrity in the above time range.
For example, CN203777107U, CN214017682U, CN111493961A, CN111493960A, CN212699007U, CN201469862U use silica gel, translucent silica gel or polyethylene to prepare the supporting tube for pancreaticotomy, which is simple and effective in relieving anastomotic pressure and promoting the healing of fistula, but these materials are not degradable, and need to be removed by a secondary operation, thus causing secondary pain to patients. For example, CN104174072A is a cross-linking type medical polyurethane pancreas and intestine anastomat material prepared by a prepolymer prepared by a certain mass fraction of polyisocyanate and polymer polyol, a chain extender, a defoaming agent, an antibacterial agent and a reinforcing agent, and has the advantages of high ductility, high tear strength, high flexibility and excellent medium resistance, and can be widely applied to the medical field. But the preparation process is more complex, and a chemical crosslinking structure is introduced, so that the biodegradability and absorbability of the material have certain problems. For example, CN1823688A utilizes polyglycolic acid to make a pancreas intestine anastomat, which can greatly simplify the operation steps, reduce the operation intensity and greatly shorten the operation time. However, simple polyglycolic acid materials cannot resist the corrosive action of various proteases in pancreatic juice, and thus are difficult to meet the use requirement of long healing time. For example, CN108992116A utilizes absorbable materials such as polycaprolactone, polypropylene or polylactic acid-glycolic acid copolymer to prepare a pancreatico-intestinal anastomosis supporting barb tube, and solves the problem of difficult suturing in the pancreatico-intestinal anastomosis operation. However, the above materials all have different problems: the polypropylene has nondegradable property; the polylactic acid-glycolic acid copolymer is not resistant to the corrosion of pancreatic juice; although polycaprolactone can resist pancreatic juice corrosion, the retention time in vivo (more than 1 to 2 years for complete degradation) is long. Meanwhile, the degradation rate of the polycaprolactone material cannot be effectively adjusted according to the wound healing time of a patient, and the polycaprolactone material is high in crystallinity, so that the mechanical strength of the material reaches about 20MPa, the hardness reaches about 75HA, the polycaprolactone material is not suitable for soft tissues, and tissue damage to a certain degree can be caused after the polycaprolactone material is implanted.
The polyurethane can freely and flexibly regulate and control the hardness and hardness degree and the mechanical property of the material by introducing the polyols with different molecular weights and molecular structures, so that the polyurethane meets the use requirements of the material, but the effective regulation and control of the retention time of the mechanical property in vivo and the retention time in vivo of the polyurethane are still very difficult to realize. In addition, the organism contains various biological enzymes such as protease, lipase, amylase and the like, the environment is very complex, the difficulty of regulating and controlling the biodegradation performance of the material is further increased, and the application of the material is further limited. Therefore, the preparation of the absorbable polyurethane elastomer with the physical property meeting the requirement and the adjustable and controllable degradation property has important application significance in the fields of in-vivo implanted devices and degradable disposable universal materials.
Disclosure of Invention
The invention provides a high-flexibility, high-elasticity, degradation-controllable and absorbable polyurethane elastomer, a preparation method and application aiming at the problems in the prior art.
The technical scheme adopted by the invention is as follows: a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer has the following structure:
Figure GDA0003897629120000031
wherein: u is diisocyanate residue-CO-HN-R-NH-CO-; s is a flexible chain segment, C is a crystalline chain segment, and D is a straight-chain dihydric alcohol residue; x and y are any integers of 10-100.
Further, the flexible chain segment is the residue of aliphatic random copolyester diol prepolymer; the crystalline segment is the residue of an aliphatic polyester diol prepolymer having semi-crystallinity; the linear diol residue is provided for a linear diol.
Further, the aliphatic random copolyester dihydric alcohol prepolymer is obtained by polymerization reaction of one or more than two monomers of dioxanone, lactide, glycolide, epsilon-caprolactone, gamma-butyrolactone, delta-valerolactone, delta-caprolactone, delta-octalactone, delta-decalactone and delta-dodecalactone.
Further, the aliphatic polyester diol prepolymer is one of polydioxanone, poly epsilon-lactone and poly delta-valerolactone.
Further, the diisocyanate residue is formed by reacting diisocyanate with prepolymers corresponding to the flexible chain segment and the crystalline chain segment, and the diisocyanate is one or two or more of 4,4' -dimethyl methane diisocyanate, 1, 6-hexamethylene diisocyanate, L-lysine diisocyanate and isophorone diisocyanate.
Further, the aliphatic random copolymerized diol prepolymer has a number average molecular weight of 1 to 10kg/mol, and the aliphatic polyester diol prepolymer has a number average molecular weight of 1 to 10kg/mol.
A preparation method of a high-flexibility, high-elasticity, degradation-controllable and absorbable polyurethane elastomer comprises the following steps:
step 1: adding the aliphatic random copolyester diol prepolymer and the aliphatic polyester diol prepolymer into a reactor, dewatering and drying under constant temperature and vacuum conditions, and after dewatering is finished, heating to a temperature higher than the melting point of the prepolymer in a protective atmosphere to melt and mix;
and 2, step: under a protective atmosphere, adding diisocyanate into the mixture obtained in the step 1, and fully reacting to obtain an isocyanate-terminated prepolymer;
and 3, step 3: and (3) under a protective atmosphere, adding a chain extender into the isocyanate-terminated prepolymer obtained in the step (2), and after the reaction is finished, obtaining the required absorbable polyurethane elastomer.
Further, the mass ratio of the aliphatic random copolyester glycol prepolymer to the aliphatic polyester glycol prepolymer is 1; diol prepolymer: diisocyanate: the molar ratio of the chain extender is 0.5-1; the dihydric alcohol prepolymer is aliphatic random copolyester dihydric alcohol prepolymer and aliphatic polyester dihydric alcohol prepolymer.
Furthermore, the chain extender is straight-chain dihydric alcohol and is composed of one or two or more of 1, 4-butanediol, 1, 6-hexanediol, 1, 5-pentanediol, 1, 7-heptanediol and 1, 8-octanediol.
The application of the absorbable polyurethane elastomer with high flexibility, high elasticity and adjustable and controllable degradation is characterized in that the polyurethane elastomer can be used for digestive tract anastomosis medical equipment, biodegradable coatings of repair brackets, soft tissue regeneration repair medical products, degradable packaging materials, degradable sealing materials and degradable battery packaging materials.
The beneficial effects of the invention are:
(1) The invention is a three-section polyurethane structure, S is a flexible chain segment formed by aliphatic random copolyester diol prepolymer; c is a semi-crystalline chain segment formed by aliphatic polyester diol prepolymer; d is a hard segment formed by reacting straight-chain dihydric alcohol with diisocyanate; a large number of intermolecular hydrogen bonding may be formed. The soft chain segment can endow the material with excellent flexibility, so that the mechanical property of the material is matched with that of a soft pancreatic and intestinal tissue, and the semi-crystalline chain segment can effectively improve the strength and toughness of the material and keep the material with sufficient supporting effect; the hard segments can form a physical network based on intermolecular hydrogen bonding through a large number of urethane bonds, so that the material is endowed with excellent elasticity;
(2) The absorbable polyurethane elastomer disclosed by the invention can meet the requirements of digestive tract tissues such as pancreas and biliary tract on good biocompatibility, and various physical and chemical properties, and can resist the corrosion action of protease, lipase and amylase in digestive juice such as pancreatic juice and bile, so that the absorbable polyurethane elastomer can be used for digestive tract anastomosis medical equipment, biodegradable coatings of repair stents, soft tissue regeneration repair medical products, degradable packaging materials, degradable sealing materials, degradable battery packaging materials and the like.
(3) The invention effectively regulates and controls the degradation speed and the in-vivo retention time of the material by adjusting the random copolymerization composition, meets the requirement of adjusting different degradation rates according to different time periods of healing of an anastomotic stoma of a patient, and meets the requirement of controllably adjusting the mechanical property retention time and the in-vivo complete degradation time.
Drawings
FIG. 1 is a tensile test curve of the polyurethane elastomers obtained in examples 1 to 4 of the present invention.
FIG. 2 is a curve of the elastic cycle test at 50%, 100%, 200% deformation for the polyurethane elastomer obtained in example 1 of the present invention.
Detailed Description
A high-flexibility, high-elasticity, degradation-controllable and absorbable polyurethane elastomer has the following structure:
Figure GDA0003897629120000041
wherein: u is diisocyanate residue-CO-HN-R-NH-CO-; s is a flexible chain segment, C is a crystalline chain segment, and D is a straight-chain dihydric alcohol residue; x and y are any integers of 10-100.
Wherein the flexible chain segment is the residue of aliphatic random copolyester diol prepolymer; the crystalline segment is the residue of an aliphatic polyester diol prepolymer having semi-crystallinity; the linear diol residue is provided as a linear diol.
The aliphatic random copolyester dihydric alcohol prepolymer is obtained by polymerization reaction of one or more than two monomers of dioxanone (PDO), lactide (LA), glycolide (GA), epsilon-caprolactone (epsilon-CL), gamma-butyrolactone (gamma-BL), delta-valerolactone (delta-VL), delta-caprolactone (delta-HL), delta-octalactone (delta-OL), delta-decalactone (delta-DoL) and delta-dodecalactone (delta-Del). The copolymerization proportion is controlled to be 30-50 percent. Preferably, the dioxanone (PDO) is polymerized with one of epsilon-caprolactone (epsilon-CL), delta-valerolactone (delta-VL), delta-caprolactone (delta-HL), delta-octalactone (delta-OL) and delta-decalactone (delta-DoL). The number average molecular weight of the aliphatic random copolyester dihydric alcohol prepolymer is 1-10 kg/mol.
The aliphatic polyester diol prepolymer is one of polydioxanone (PPDO), poly epsilon-lactone (PCL) and poly delta-valerolactone (P delta VL). The number average molecular weight of the aliphatic polyester diol prepolymer is 1-10 kg/mol.
The diisocyanate residue is formed by the reaction of diisocyanate and prepolymer corresponding to the flexible chain segment and the crystalline chain segment, and the diisocyanate is one or more than two of 4,4' -dimethyl Methane Diisocyanate (MDI), 1, 6-Hexamethylene Diisocyanate (HDI), L-Lysine Diisocyanate (LDI) and isophorone diisocyanate (IPDI).
A preparation method of a high-flexibility, high-elasticity, degradation-controllable and absorbable polyurethane elastomer comprises the following steps:
step 1: adding the aliphatic random copolyester dihydric alcohol prepolymer and the aliphatic polyester dihydric alcohol prepolymer into a reactor, and dehydrating and drying under the conditions of constant temperature and vacuum; keeping the temperature constant by adopting an oil bath, wherein the dewatering temperature is 30-60 ℃; the vacuum degree is kept between 0.06 and 0.12MPa; the water removal time is usually 3 to 8 hours. After the water removal is finished, heating to be above the melting point of the prepolymer under a protective atmosphere, and melting and mixing. The protective atmosphere is selected from inert gases, which can be high purity nitrogen or helium.
Step 2: under a protective atmosphere, adding diisocyanate into the mixture obtained in the step 1, and after full reaction, obtaining an isocyanate-terminated prepolymer, wherein the reaction time is 1-3 h.
And 3, step 3: and (3) adding a chain extender into the isocyanate-terminated prepolymer obtained in the step (2) in a protective atmosphere, and obtaining the required absorbable polyurethane elastomer after the reaction is finished, wherein the reaction time is 1-3 h.
The reaction temperature in step 2 and step 3 is selected according to the melting temperature of the S-stage and C-stage materials, and is usually 60 to 125 ℃.
The mass ratio of the aliphatic random copolyester diol prepolymer to the aliphatic polyester diol prepolymer is 1; diol prepolymer: diisocyanate: the molar ratio of the chain extender is 0.5-1; the dihydric alcohol prepolymer is aliphatic random copolyester dihydric alcohol prepolymer and aliphatic polyester dihydric alcohol prepolymer. The chain extender is straight chain diol, and is one or more of 1, 4-butanediol, 1, 6-hexanediol, 1, 5-pentanediol, 1, 7-heptanediol and 1, 8-octanediol. The medical polyurethane elastomer prepared by the method HAs the breaking strength of 2-60 MPa, the breaking elongation of about 100-4000 percent and the Shore hardness of 30-88 HA.
The application of the absorbable polyurethane elastomer with high flexibility, high elasticity and controllable degradation is characterized in that the mechanical property of the absorbable polyurethane elastomer is matched with biological soft tissues, the absorbable polyurethane elastomer has the advantages of high flexibility, high elasticity, controllable degradation, absorbability and the like, can resist the corrosion of various proteases such as pancreatic juice and bile, and can be maintained for 10-40 days in pancreatic juice media, so that the absorbable polyurethane elastomer can be used for digestive tract anastomosis medical equipment, biodegradable coatings for repairing stents, medical products for regenerating and repairing soft tissues, degradable packaging materials, degradable sealing materials, degradable battery packaging materials and the like.
The invention is further illustrated by the following specific examples; the following tensile test curves were obtained for the static tensile test.
Static tensile test: using a dumbbell cutter to cut the films of different samples into tensile sample strips with the thickness of 25 multiplied by 4 multiplied by 0.5cm, and using an electronic universal tester (Instron 3366, instron corporation, USA) to carry out tensile property test according to the method of GB/T1040.3-2006, wherein the tensile rate is 10mm/min and the room temperature is 25 ℃; the sensor is subjected to mechanical property test by 1 KN.
The cyclic tensile test method is as follows: the test instrument and the sample band preparation method are the same as those of a tensile test, and the elastic behavior of the polymer is characterized by a tensile cycle mode of a universal testing machine.
The following hardness is measured by using a Shore A hardness test method, and the specific method is as follows: a sample of 50 multiplied by 25 multiplied by 6mm is prepared by a polytetrafluoroethylene die, a hardness test is carried out by a Shore A durometer (Victoria LXD-A) according to the national standard GB/T531-1999 "indentation hardness test method of rubber pocket durometer", and the test conditions are as follows: at room temperature 25 ℃, each sample was measured in parallel at least 3 times, and the mean and variance values were determined.
Example 1
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (DO-c-delta VL) with number average molecular weight of 10.0kg/mol 50％ ) -OH) and a polycaprolactone prepolymer (HO-PCL-OH) having a number average molecular weight of 1.4kg/mol, in a mass ratio of 5:1 adding the prepolymer into a reactor, dehydrating the prepolymer in vacuum for 5 hours at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa, and melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen after the dehydration is finished;
step 2: under the protection of nitrogen, 1, 6-hexamethylene diisocyanate with the molar weight of hydroxyl groups of 1.85/1 was added into the mixture obtained in the step 1, and the mixture was reacted in an oil bath at 80 ℃ for 3 hours to obtain an isocyanate-terminated prepolymer.
And step 3: under the protection of nitrogen, chain extender 1, 4-butanediol with the molar weight of hydroxyl groups of 0.85/1 is added into the isocyanate-terminated prepolymer obtained in the step 2, and the reaction is stopped after the reaction is carried out for 3 hours in an oil bath at the temperature of 80 ℃. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 2
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (DO-c-delta VL) with number average molecular weight of 1.0kg/mol 42％ ) OH) and a number average molecular weight of 1.4kg/mol of a polypentanolide prepolymer (HO-PVL-OH) in a mass ratio of 1:10, adding the prepolymer into a reactor, carrying out vacuum dehydration for 5 hours at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa, and after the dehydration is finished, melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen;
step 2: under the protection of nitrogen, adding L-lysine diisocyanate with the molar weight of hydroxyl groups being 4/1 into the mixture obtained in the step 1. After 3h of reaction in an oil bath at 80 ℃ an isocyanate-terminated prepolymer was obtained.
And 3, step 3: under the protection of nitrogen, adding chain extender 1, 7-heptanediol with the molar weight of terminal hydroxyl of 3/1 into the isocyanate-terminated prepolymer obtained in the step 2, reacting in an oil bath at 80 ℃ for 3h, and stopping the reaction. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with glacial methanol to obtain the required absorbable polyurethane elastomer.
Example 3
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (DO-c-delta VL) with the number average molecular weight of 1.0kg/mol 36％ ) -OH) and a number average molecular weight of 10.0kg/mol of a polypentanolide prepolymer (HO-PVL-OH) in a mass ratio of 10:1, adding the prepolymer into a reactor, dehydrating for 5 hours in vacuum at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa, and melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen after the dehydration is finished.
Step 2: under the protection of nitrogen, L-lysine diisocyanate with the molar weight of the terminal hydroxyl of 3.1/1 is added into the mixture obtained in the step 1. After 3h of reaction in an oil bath at 80 ℃ an isocyanate-terminated prepolymer was obtained.
And 3, step 3: under the protection of nitrogen, chain extender 1, 5-pentanediol with the molar weight of hydroxyl groups of 2.1/1 is added into the isocyanate-terminated prepolymer obtained in the step 2, and the reaction is stopped after the reaction is carried out in an oil bath at 80 ℃ for 3h. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 4
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (DO-c) with number average molecular weight of 10.0kg/mol-δHL 31％ ) OH) and a number average molecular weight of 1.1kg/mol of a polypentanolide prepolymer (HO-PVL-OH) in a mass ratio of 1:1, adding the prepolymer into a reactor, dehydrating the prepolymer in vacuum for 5 hours at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa, and melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen after the dehydration is finished.
Step 2: adding isophorone diisocyanate with the molar weight of hydroxyl groups of 1.5/1 into the mixture obtained in the step 1 under the protection of nitrogen, and reacting in an oil bath at 80 ℃ for 3 hours to obtain an isocyanate-terminated prepolymer.
And step 3: under the protection of nitrogen, chain extender 1, 6-hexanediol with the molar weight of hydroxyl groups of 0.5/1 is added into the isocyanate-terminated prepolymer obtained in the step 2, and the reaction is stopped after the reaction is carried out in an oil bath at 80 ℃ for 3h. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 5
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (DO-c-delta Del) with the number average molecular weight of 4.5kg/mol 45％ ) OH) and a poly delta-valerolactone prepolymer (HO-PVL-OH) having a number average molecular weight of 2.0kg/mol in a mass ratio of 5:1 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen.
Step 2: adding isophorone diisocyanate with the molar weight of hydroxyl at the end of 5/1 into the mixture obtained in the step 1 under the protection of nitrogen, and reacting in an oil bath at the temperature of 80 ℃ for 3 hours to obtain an isocyanate-terminated prepolymer.
And 3, step 3: under the protection of nitrogen, chain extender 1,7 hepta-hexanediol with the molar weight of terminal hydroxyl of 4/1 is added into the isocyanate-terminated prepolymer obtained in the step 2, and the reaction is stopped after reacting in an oil bath at 80 ℃ for 3h. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 6
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (DO-c-delta Del) with the number average molecular weight of 9.0kg/mol 49％ ) OH) and a poly delta-valerolactone prepolymer (HO-PVL-OH) with a number average molecular weight of 2.0kg/mol in a mass ratio of 7:1 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen.
Step 2: adding isophorone diisocyanate with the molar weight of hydroxyl at the end of 2.1/1 into the mixture obtained in the step 1 under the protection of nitrogen, and reacting in an oil bath at the temperature of 80 ℃ for 3 hours to obtain an isocyanate-terminated prepolymer.
And 3, step 3: under the protection of nitrogen, chain extender 1, 5-pentanediol with the molar weight of terminal hydroxyl groups of 1.1/1 is added into the isocyanate-terminated prepolymer obtained in the step 2, and the reaction is stopped after the reaction is carried out for 3 hours in an oil bath at the temperature of 80 ℃. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 7
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (DO-c-delta OL) with number average molecular weight of 1.0kg/mol 35％ ) -OH) and a polydioxanone prepolymer (HO-PPDO-OH) having a number average molecular weight of 9.0kg/mol in a mass ratio of 9:1 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 125 ℃ under the protection of nitrogen.
And 2, step: under the protection of nitrogen, adding L-lysine diisocyanate with the molar weight of hydroxyl groups being 4/1 into the mixture obtained in the step 1. After 3h of reaction in an oil bath at 125 ℃ an isocyanate-terminated prepolymer was obtained.
And 3, step 3: under the protection of nitrogen, chain extender 1, 5-pentanediol with the molar weight of hydroxyl group being 3/1 is added into the isocyanate-terminated prepolymer obtained in the step 2, and the reaction is stopped after the reaction is carried out for 3 hours in an oil bath at 125 ℃. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 8
A preparation method of a high-flexibility, high-elasticity, degradation-controllable and absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (DO-c-delta OL) with number average molecular weight of 6.0kg/mol 37％ ) -OH) and a polydioxanone prepolymer (HO-PPDO-OH) having a number average molecular weight of 1.0kg/mol in a mass ratio of 2:1 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 125 ℃ under the protection of nitrogen.
Step 2: under the protection of nitrogen, L-lysine diisocyanate with the molar weight of 2.8/1 of hydroxyl groups is added into the mixture obtained in the step 1. After 3h of reaction in an oil bath at 125 ℃ an isocyanate-terminated prepolymer was obtained.
And step 3: under the protection of nitrogen, chain extender 1, 8-octanediol with the molar weight of terminal hydroxyl groups of 1.8/1 was added to the isocyanate terminated prepolymer obtained in step 2, and the reaction was stopped after reacting in an oil bath at 125 ℃ for 3 hours. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 9
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (DO-c-delta OL) with number average molecular weight of 6.0kg/mol 48％ ) -OH) and a polydioxanone prepolymer (HO-PPDO-OH) having a number average molecular weight of 2.0kg/mol, in a mass ratio of 5:1 adding into a reactor; in an oil bath at 60 DEG CAnd (3) dehydrating under vacuum for 5 hours under the condition, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in an oil bath at 125 ℃ under the protection of nitrogen.
And 2, step: under the protection of nitrogen, 4' -dimethylmethane diisocyanate with a molar amount of 0.5/1 of terminal hydroxyl groups was added to the mixture obtained in step 1. After reaction in an oil bath at 125 ℃ for 3h, an isocyanate-terminated prepolymer was obtained.
And step 3: under the protection of nitrogen, chain extender 1, 6-hexanediol with the molar weight of hydroxyl groups of 0.5/1 is added into the isocyanate-terminated prepolymer obtained in the step 2, and the reaction is stopped after the reaction is carried out in an oil bath at 125 ℃ for 3h. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 10
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (CL-c-delta VL) with the number average molecular weight of 8.0kg/mol 40％ ) -OH) and a number average molecular weight of 6.0kg/mol of a polypentanolide prepolymer (HO-PVL-OH) in a mass ratio of 4:1 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen.
Step 2: under the protection of nitrogen, L-lysine diisocyanate with the molar weight of the terminal hydroxyl of 2.5/1 is added into the mixture obtained in the step 1. After 3h of reaction in an oil bath at 125 ℃ an isocyanate-terminated prepolymer was obtained.
And step 3: under the protection of nitrogen, chain extender 1, 7-heptanediol with the molar weight of hydroxyl groups of 1.5/1 was added to the isocyanate terminated prepolymer obtained in step 2, and the reaction was stopped after reacting for 3 hours in an oil bath at 80 ℃. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
The polyurethane elastomers obtained in examples 1 to 9 were subjected to tensile property test and hardness test, and the results are shown in table 1.
TABLE 1 results of the Performance test of examples 1 to 9
Figure GDA0003897629120000101
The static tensile test of example 1 shows that the polyurethane elastomer has an elongation at break of 993%, a stress at break of 7.3MPa and an elastic modulus of 2.9MPa, and the results are shown in FIG. 1, which indicates that the polyurethane elastomer has excellent mechanical properties. The polyurethane elastomer samples obtained in example 1 were subjected to a cyclic tensile test, and elastic recovery tests were performed for 10 cyclic tensile cycles at deformations of 50%, 100%, and 200%, respectively, and the results are shown in fig. 2, and specific data are shown in table 2. The samples all exhibited significant hysteresis loss during the first cycle of the elastic cycle. This is due to hysteresis effects caused by factors such as microstructure destruction, hydrogen bond dissociation, etc. after the material is stretched, and this phenomenon is typical of the marins effect. Meanwhile, in the following 9 cycle stretching periods, the loading curve almost completely coincides with the unloading curve of the previous period, and the hysteresis loss is gradually reduced, which indicates that the sample has excellent elastic recovery performance.
Table 2 shows the elastic recovery under different deformations of example 1
Figure GDA0003897629120000102
Example 11
A preparation method of a high-flexibility, high-elasticity, degradation-controllable and absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (CL-c-delta VL) with number average molecular weight of 6.0kg/mol 43％ ) -OH) and a poly delta-valerolactone prepolymer (HO-PVL-OH) having a number average molecular weight of 2.0kg/mol in a mass ratio of 7:1 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen.
Step 2: 4,4' -dimethylmethane diisocyanate with the molar amount of hydroxyl at the terminal of 4.3/1 was added to the mixture obtained in step 1 under the protection of nitrogen, and the mixture was reacted in an oil bath at 80 ℃ for 3 hours to obtain an isocyanate terminated prepolymer.
And step 3: under the protection of nitrogen, chain extender 1, 7-heptanediol with the molar weight of hydroxyl groups of 3.3/1 was added to the isocyanate terminated prepolymer obtained in step 2, and the reaction was stopped after reacting for 3 hours in an oil bath at 80 ℃. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 12
A preparation method of a high-flexibility, high-elasticity, degradation-controllable and absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (CL-c-delta VL) with number average molecular weight of 2.0kg/mol 37％ ) -OH) and a poly delta-valerolactone prepolymer (HO-PVL-OH) having a number average molecular weight of 1.0kg/mol in a mass ratio of 1:10 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen.
Step 2: under the protection of nitrogen, L-lysine diisocyanate with the molar weight of 5.1/1 of hydroxyl is added into the mixture obtained in the step 1, and the mixture is reacted in an oil bath at the temperature of 80 ℃ for 3 hours to obtain an isocyanate-terminated prepolymer.
And 3, step 3: under the protection of nitrogen, chain extender 1, 8-octanediol with the molar weight of hydroxyl groups of 4.1/1 was added to the isocyanate terminated prepolymer obtained in step 2, and the reaction was stopped after reacting in an oil bath at 80 ℃ for 3 hours. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 13
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: number average molecular weight2.0kg/mol of aliphatic random copolyester diol prepolymer (HO-P (DO-c-delta Del) 42％ ) -OH) and a poly delta-valerolactone prepolymer (HO-PVL-OH) having a number average molecular weight of 2.0kg/mol in a mass ratio of 3:1 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen.
And 2, step: under the protection of nitrogen, adding L-lysine diisocyanate with the molar weight of hydroxyl of 1/0.5 into the mixture obtained in the step 1, and reacting in an oil bath at 80 ℃ for 3 hours to obtain an isocyanate-terminated prepolymer.
And 3, step 3: under the protection of nitrogen, chain extender 1, 7-heptanediol with the molar weight of terminal hydroxyl groups of 0.5/1 was added to the isocyanate terminated prepolymer obtained in step 2, and the reaction was stopped after reacting in an oil bath at 80 ℃ for 3 hours. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 14
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (CL-c-delta VL) with the number average molecular weight of 8.0kg/mol 45％ ) OH) and a poly delta-valerolactone prepolymer (HO-PVL-OH) having a number average molecular weight of 2.0kg/mol in a mass ratio of 6:2 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen.
And 2, step: adding isophorone diisocyanate with the molar weight of terminal hydroxyl of 2.9/1 into the mixture obtained in the step 1 under the protection of nitrogen, and reacting in an oil bath at 80 ℃ for 3 hours to obtain an isocyanate-terminated prepolymer.
And step 3: under the protection of nitrogen, chain extender 1, 5-pentanediol with the molar weight of terminal hydroxyl groups of 1.9/1 is added into the isocyanate-terminated prepolymer obtained in the step 2, and the reaction is stopped after the reaction is carried out for 3 hours in an oil bath at the temperature of 80 ℃. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 15
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (CL-c-delta VL) with number average molecular weight of 2.0kg/mol 50％ ) -OH) and poly delta-valerolactone prepolymer (HO-PVL-OH) having a number average molecular weight of 3.0kg/mol in a mass ratio of 7:3 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen.
Step 2: under the protection of nitrogen, 4' -dimethylmethane diisocyanate with the molar weight of 3.2/1 of hydroxyl groups was added into the mixture obtained in step 1, and the mixture was reacted in an oil bath at 80 ℃ for 3 hours to obtain an isocyanate-terminated prepolymer.
And step 3: under the protection of nitrogen, chain extender 1, 6-hexanediol with the molar weight of 2.2/1 of hydroxyl groups is added into the isocyanate-terminated prepolymer obtained in the step 2, and the reaction is stopped after the reaction is carried out in an oil bath at 80 ℃ for 3h. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
Example 16
A preparation method of a high-flexibility high-elasticity degradation-controllable absorbable polyurethane elastomer comprises the following steps:
step 1: aliphatic random copolyester diol prepolymer (HO-P (CL-c-delta VL) with the number average molecular weight of 2.0kg/mol 38％ ) -OH) and poly delta-valerolactone prepolymer (HO-PCL-OH) having a number average molecular weight of 3.0kg/mol in a mass ratio of 7:3 adding into a reactor; and (3) dehydrating under vacuum for 5h at the temperature of 60 ℃ in an oil bath, keeping the vacuum degree at 100Pa to remove water, and then melting and mixing the prepolymer in the oil bath at the temperature of 80 ℃ under the protection of nitrogen.
Step 2: under the protection of nitrogen, 4' -dimethylmethane diisocyanate with the molar weight of 5/1 of hydroxyl is added into the mixture obtained in the step 1 and reacts in an oil bath at the temperature of 80 ℃ for 3 hours to obtain an isocyanate-terminated prepolymer.
And 3, step 3: under the protection of nitrogen, chain extender 1, 6-octanediol with the molar weight of hydroxyl groups of 4/1 was added to the isocyanate terminated prepolymer obtained in step 2, and the reaction was stopped after reacting for 3 hours in an oil bath at 80 ℃. And after the temperature of the reaction bottle is cooled to room temperature, adding trichloromethane, standing and dissolving overnight, and precipitating with methanol to obtain the required absorbable polyurethane elastomer.
The invention is a three-section polyurethane structure, S is a flexible chain segment formed by aliphatic random copolyester diol prepolymer; c is a semi-crystalline chain segment formed by aliphatic polyester diol prepolymer; d is a hard segment formed by reacting straight-chain dihydric alcohol with diisocyanate; a large number of intermolecular hydrogen bonding may be formed. The soft chain segment can endow the material with excellent flexibility, so that the mechanical property of the material is matched with that of a soft pancreatic and intestinal tissue, and the semi-crystalline chain segment can effectively improve the strength and toughness of the material and keep the material with sufficient supporting effect; the hard segments can form a physical network based on intermolecular hydrogen bonding through a large number of urethane bonds, thereby endowing the material with excellent elasticity. The polyurethane obtained by the invention has the advantages of good biocompatibility, high flexibility, high elasticity, controllable degradation, absorbability and the like, and can resist the corrosion action of various proteases such as pancreatic juice, bile and the like.
The degradation speed and the in-vivo retention time of the material are effectively regulated and controlled by regulating the random copolymerization composition, the requirements of regulating different degradation rates according to different time periods of healing of an anastomotic stoma of a patient are met, and the requirements of controllably regulating the mechanical property retention time and the in-vivo complete degradation time are met
Compared with the traditional polyurethane synthesis, the preparation method of the invention has the advantages that the synthesis is carried out under the condition of not adding any organic solvent or catalyst, the reaction raw materials are all high boiling point substances with the boiling point of more than 250 ℃, and the polyurethane basically does not contain volatile organic compounds. In the preparation process of the polyurethane, no vulcanizing agent or reinforcing agent is added, a high-temperature vulcanizing process is not needed, and the preparation process is simple and practical. The used raw materials are relatively low in price and have practical application value. The obtained polyurethane elastomer has high elasticity, high flexibility, good biocompatibility, controllable degradation, absorbability and resistance to corrosion of various proteases such as pancreatic juice, bile and the like, so that the material can be used for digestive tract anastomosis medical equipment, biodegradable coatings of repair stents, soft tissue regeneration repair medical products, degradable packaging materials, degradable sealing materials, degradable battery packaging materials and the like.

Claims (4)

1. A high-flexibility high-elasticity degradable and controllable absorbable polyurethane elastomer, which is characterized in that,
the preparation method comprises the following steps:
step 1: adding aliphatic random copolyester dihydric alcohol prepolymer and aliphatic polyester dihydric alcohol prepolymer into a reactor
Keeping constant temperature, dewatering and drying under vacuum condition, heating to above melting point of prepolymer in protective atmosphere after dewatering, and melting
Mixing; the aliphatic random copolyester dihydric alcohol prepolymer is obtained by the polymerization reaction of p-dioxanone and epsilon-caprolactone, delta-valerolactone, delta-octalactone or delta-dodecalactone; the aliphatic polyester diol prepolymer is one of polydioxanone, poly epsilon-lactone and poly delta-valerolactone;
step 2: under protective atmosphere, adding diisocyanate into the mixture obtained in the step 1, and fully reacting to obtain the product
To isocyanate terminated prepolymers;
and step 3: adding a chain extender into the isocyanate-terminated prepolymer obtained in the step 2 under the condition of protective atmosphere, and reacting
After finishing, the required polyurethane elastomer can be obtained;
the mass ratio of the aliphatic random copolyester diol prepolymer to the aliphatic polyester diol prepolymer is 1; diol prepolymer: diisocyanate: the molar ratio of the chain extender is 0.5-1; the dihydric alcohol prepolymer is aliphatic random copolyester dihydric alcohol prepolymer and aliphatic polyester dihydric alcohol prepolymer; the chain extender is one or more than two of 1, 4-butanediol, 1, 6-hexanediol, 1, 5-pentanediol, 1, 7-heptanediol and 1, 8-octanediol;
the flexible chain segment in the polyurethane elastomer is the residue of aliphatic random copolyester diol prepolymer; crystalline chain segment of
A residue of a semi-crystalline aliphatic polyester diol prepolymer; the linear diol residue is provided as a linear diol.
2. The absorbable polyurethane elastomer with high flexibility, elasticity and controllable degradation as claimed in claim 1, wherein the diisocyanate is one or more selected from 4,4' -dimethylmethane diisocyanate, 1, 6-hexamethylene diisocyanate, L-lysine diisocyanate and isophorone diisocyanate.
3. The absorbable polyurethane elastomer with high flexibility, high elasticity and controllable degradation as claimed in claim 1, wherein the aliphatic random copolyester glycol prepolymer has a number average molecular weight of 1-10 kg/mol, and the aliphatic polyester glycol prepolymer has a number average molecular weight of 1-10 kg/mol.
4. The application of the absorbable polyurethane elastomer with high flexibility, high elasticity and controllable degradation as claimed in any one of claims 1 to 3, wherein the polyurethane elastomer can be used for preparing medical devices for digestive tract anastomosis, preparing biodegradable coatings for repairing stents, preparing medical products for soft tissue regeneration and repair, preparing degradable packaging materials, preparing degradable sealing materials and preparing degradable battery packaging materials.
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