CN106674486A - Polyester type polyurethane material with side chain containing phosphorylcholine group and preparation method thereof - Google Patents

Abstract

The invention relates to a side chain phosphorylcholine group-containing polyester polyurethane material and a preparation method thereof. The preparation method comprises the following steps: (1) reacting polyester diol with excess diisocyanate to obtain double-terminal isocyanate (2) using a diamino phosphorylcholine compound to extend the chain of the double-terminal isocyanate-based prepolymer to obtain a biodegradable polyurethane material containing phosphorylcholine groups in the side chain. The phosphorylcholine group in the polyurethane material is located at the side chain of the polymer, so a small amount of phosphorylcholine group content can well improve the biocompatibility of the material. The soft segment of the material is homopolyester, which has a high degree of crystallinity, which ensures that the material has high mechanical strength, and the main chain is completely hydrophobic, and the degradation speed is slow. It can be used as a tissue engineering repair scaffold material for long-term application in biological After the material plays a role, it can gradually degrade into non-toxic products and be absorbed by the organism, avoiding the damage of secondary surgery.

Description

A side chain phosphorylcholine group-containing polyester polyurethane material and preparation method thereof

technical field

The invention belongs to the field of medical polymer materials, and specifically relates to a side chain phosphorylcholine group-containing polyester polyurethane material and a preparation method thereof.

Background technique

Since Bayer's invention, polyurethane (PU) has been widely used in the field of medical devices, from medical catheters to artificial hearts. Polyurethane has unique properties, such as relatively excellent biocompatibility, chemical properties, excellent mechanical properties and processing properties, etc., and has become an ideal choice for many medical product raw materials, especially when the selected material must simultaneously solve complex mechanical properties and When biocompatibility issues, such as the preparation of blood contact devices such as interventional catheters, interventional device coatings, hemodialysis membranes, artificial hearts and ventricular assist circulatory systems, medical polyurethane is usually the best choice of raw materials. Currently, thrombus, calcification and bacterial infection are the main complications faced by blood contact materials including medical polyurethane. When medical materials enter the human body, human tissue and blood are mainly in contact with the surface of the material, so understanding and controlling the surface properties of the material is the key to eliminating complications.

Phosphorylcholine polymers are compounds with -CH ₂ NO ₅ P+ groups, including various types, common ones are dilauroyl lecithin (DLPC) (as shown in formula 1), dimyristoylphosphatidylcholine base (DMPC) (as shown in formula 2), dipalmitoylphosphatidylcholine (DPPC) (as shown in formula 3), distearoylphosphatidylcholine (DSPC) (as shown in formula 4), poly 2-methacryloyloxyethyl phosphorylcholine (PMPC) (as shown in formula 5) and the like. It has very little interaction with various biological components in the blood, that is, the phosphorylcholine group can maintain the normal conformation of the biological components in the blood, so that the outer surface of the blood cell membrane has good blood compatibility, so it occupies a large amount in the outer cell membrane. Important position, he directly affects how the cells of the organism interact with the outside world. Phosphorylcholine polymers designed and synthesized based on imitating cell membrane structures have attracted much attention because of their good biocompatibility. By imitating the structure of the extracellular phospholipid bilayer membrane, the material rich in phosphorylcholine groups disguises it as the surrounding natural components in the organism, making it have excellent biocompatibility, and the surface is not easy to adsorb proteins, platelets, etc. Biofouling, prevents the formation of blood clots, thereby eliminating many problems caused by surface fouling. The development of phosphorylcholine polymers has opened up a new way for people to find biocompatible materials.

Phosphorylcholine can be widely used in the field of modification of polyurethane materials. The early phosphorylcholine modified polyurethane method was to copolymerize 2-methacryloyloxyethylphosphorylcholine (MPC) with 2-ethylhexyl methacrylate and then copolymerize the copolymer with block polyurethane. Mixed, and on this basis to develop a semi-interpenetrating network technology. Later, azobisisobutyronitrile was developed as an initiator, and a copolymer of MPC, butyl methacrylate, and isooctyl methacrylate was prepared by free radical polymerization. Although the phosphorylcholine group of the prepared polymer is located in the side chain, it can be well aggregated on the surface of the material in an aqueous environment and play a role in increasing biocompatibility, but the phosphorylcholine prepared by free radical copolymerization The degradation performance of the polymer is very poor, and the blending method leads to a reduction in the mechanical properties of the material, and the application is greatly limited.

Another phosphorylcholine modification method is to graft phosphorylcholine groups to the surface of polyurethane materials, and use 2-methacryloyloxyethylphosphorylcholine (MPC) and glycerophosphorylcholine (GPC) ) derivatives provide compounds for the PC group, and the PC group is covalently grafted to the surface of polycarbonate polyurethane by surface coupling MPC method, surface coupling formyl phosphorylcholine method and surface grafting GPC derivative method. . The phosphorylcholine modified biological material obtained by the method has high biocompatibility. Although grafting phosphorylcholine groups on the surface of materials can effectively improve the biocompatibility of materials, this method has a very complicated process, high cost, and is only suitable for materials with relatively regular surfaces, making it difficult to commercialize. very difficult issues.

At present, there is another phosphorylcholine modification method, which is to synthesize double-terminal hydroxyl compounds containing phosphorylcholine groups, and then use diisocyanate for chain extension to prepare polyurethanes containing phosphorylcholine groups in the main chain. The material obtained by this preparation method has good biocompatibility, but the phosphorylcholine group contained in the material is completely located on the main chain, and a considerable part of the choline group is embedded in the material during the use of the material. Inside, it is difficult to enrich on the surface of the material, so the material has limited biocompatibility, and the double-terminal hydroxyl compound of the synthetic phosphorylcholine group uses a phenolic substance containing a benzene ring, which leads to the long-term use of the material There will be disadvantages such as degradation of toxic substances.

Contents of the invention

According to the above deficiencies in the prior art, an object of the present invention is to provide a polyester polyurethane material with a side chain containing a phosphorylcholine group, the polyurethane material phosphorylcholine group is located on the side chain, which can effectively prevent The deposition of platelets and proteins and avoiding the formation of thrombus have high biocompatibility. At the same time, the soft segment of the polyurethane material is crystalline polyester, and the hard segment has an ordered structure and contains carbamate groups, making the material It has high mechanical strength, and the main chain is completely hydrophobic to meet the slow degradation rate required as a tissue engineering repair scaffold material. The degradation products of the soft segment are small molecular carboxylic acids, and the degradation products of the hard segment are fatty amines and amino acids. After the material functions, it can be gradually degraded into non-toxic products and absorbed by the organism, avoiding the damage of the secondary operation, and can be applied to the organism for a long time.

Another object of the present invention is to provide a method for preparing a polyester polyurethane material containing phosphorylcholine groups in the side chain. The preparation process is simple, and the diisocyanate selected is aliphatic di Isocyanates, degradation products can be absorbed by organisms, and can be used as biomaterials for long-term application in organisms. The polyester polyurethane material prepared by this preparation method is fully synthetic, has no potential animal origin, has excellent biocompatibility and mechanical properties, and is biodegradable, and the degradation products are non-toxic and can be absorbed by organisms.

In order to achieve the above object, the present invention adopts the following technical solutions:

The invention provides a polyester polyurethane material with a side chain containing phosphorylcholine groups, the molecular weight is greater than 1.8×10 ⁵ , the breaking strength of the membrane material is greater than 42 MPa, the elongation at break is greater than 600%, and the adsorption amount of protein is less than 2.5 μg/cm ² , the degradation time is 105-120d.

The present invention also provides a method for preparing a side chain phosphorylcholine group-containing polyester polyurethane material, comprising the following steps:

(1) Polyester diol reacts with excess diisocyanate to obtain a double-ended isocyanate group prepolymer;

(2) Extending the double-terminal isocyanate group prepolymer with a diamino phosphorylcholine compound to obtain a polyurethane material containing a phosphorylcholine group in the side chain.

Preferably, the polyester diol in step (1) is polyglycolide, poly L-lactide, poly D,L-lactide or polyε-caprolactone, with a molecular weight of 400-5000, preferably 500-3000.

Preferably, the diisocyanate in step (1) is 1,6-hexamethylene diisocyanate-1,4-butanediol-1,6-hexamethylene diisocyanate (HDI-BDO-HDI), 1 , 4-tetramethylene diisocyanate-1,4-butanediol-1,4-tetramethylene diisocyanate (BDI-BDO-BDI).

Preferably, the specific preparation method of HDI-BDO-HDI/BDI-BDO-HDI is to use 1,4-butanediol (BDO) and diisocyanate as raw materials, and the molar ratio of feeding is: n-OH:n-NCO=1 : 4-30, reaction temperature 70-100 ℃, reaction time 1-5h, synthetic HDI-BDO-HDI.

Preferably, the molar ratio of BDO to 1,6-hexamethylene diisocyanate (HDI) is 1:12, react under a dry nitrogen atmosphere, the reaction temperature is 80°C, the reaction time is 4 hours, and the reaction system is cooled to room temperature to obtain The white solid was washed three times with n-hexane to remove excess HDI, and dried under vacuum at room temperature to obtain HDI-BDO-HDI.

Preferably, the molar ratio of BDO and 1,4-tetramethylene diisocyanate (BDI) is 1:14, react under a dry nitrogen atmosphere, the reaction temperature is 80°C, the reaction time is 3h, cool down to room temperature to form a white solid, n-hexane Wash three times to remove excess BDI, and vacuum dry at room temperature to obtain BDI-BDO-BDI.

Preferably, the addition of excess diisocyanate described in step (1) is that the molar ratio of -NCO to -OH is 2.0, and the addition method is that diisocyanate is dissolved in dimethyl sulfoxide (10g/30mL), and mixed with Polyester diol blend

Preferably, the reaction temperature in step (1) is 80-100° C., and the reaction time is 2.5-6.0 h.

Preferably, the bisamino phosphorylcholine compound described in step (2) has a specific structure of Lys-PC (as shown in formula 6) or Lys-EG-PC (as shown in formula 7).

Preferably, the amount of bisamidophosphorylcholine compound added in step (2) is: -NH ₂ :-NCO=1:2 (molar ratio), the reaction temperature is 10-20°C, and the reaction time is 1.0-2.0h .

Preferably, the preparation method includes a step of purifying the side chain phosphorylcholine group-containing polyurethane material: dissolving in dichloromethane or dioxane, settling with glacial ether, suctioning, and drying in vacuum at room temperature to constant weight.

Preferably, the polyurethane material containing the phosphorylcholine group in the side chain obtained in step (2) is dissolved in a benign organic solvent to form a solution with a concentration of 4 to 7% (g/mL), which is volatilized by the solvent to form Membrane, the polyurethane membrane material is prepared.

Preferably, the benign solvent is one or a mixed solvent of chloroform, dichloromethane, chloroform, acetone or dioxane. The solvent volatilization temperature is 15-25°C, volatilizes at normal pressure for 60-90 hours, and then vacuum-dries at normal temperature to obtain the membrane material.

Preferably, the obtained polyurethane film material film has a thickness of 0.18-0.22 mm.

Preferably, the polyurethane material can be made into various dosage forms required by organisms, especially membrane, sponge and cartilage dosage forms.

Preferably, the polyurethane material is used as a scaffold material for tissue engineering repair in the medical field.

Beneficial effects of the present invention

1. The soft segment of the material prepared by the present invention is crystalline polyester, the hard segment has an ordered structure and contains carbamate and urea groups, and a large amount of hydrogen can be formed between the hard segment and between the hard segment and the soft segment bonds, so that the material has high mechanical strength, and the main chain is completely hydrophobic, which meets the slow degradation rate required as a scaffold material for tissue engineering repair. The degradation products of the soft segment of the polyurethane material are small molecular carboxylic acids, and the degradation products of the hard segment are fatty amines and amino acids, which can be gradually degraded into non-toxic products and absorbed by organisms after the material functions, avoiding the damage of secondary surgery, and can long-term application in living organisms.

2. The phosphorylcholine group of the material prepared by the present invention is located in the side chain of the polymer, has high hydrophilicity, and will gather on the surface of the material in the water environment of the organism, not only will not adsorb and precipitate proteins, but also It will not cause adverse reactions such as platelet activation and coagulation, and avoid the formation of thrombus, and has extremely high biocompatibility.

3. The preparation process of the present invention is simple, conventional methods can meet the preparation requirements, and can be prepared into various dosage forms, which has a high commercialization prospect.

Description of drawings

Figure 1. The national standard stipulates the shape requirements of the PU film for mechanical performance testing.

Fig. 2. SEM photo of platelet viscosity of sample A6.

detailed description

The present invention will be further described below in conjunction with specific embodiments.

Example 1

Put 0.01mol poly-L-lactide (PLLA, M _n = 2000) and 0.02mol HDI-BDO-HDI (dissolved in dimethyl sulfoxide: 10g/30mL) in a three-necked flask, protected by dry nitrogen, and mechanically stirred , heat up to 80°C, after 4.0 hours of reaction, cool down to 18°C, add 0.01mol Lys-PC, stir, when the viscosity of the system becomes too high to stir normally, add an appropriate amount of dichloromethane, stir for 1 hour, then add dichloromethane When the concentration was about 15 wt%, settled with glacial ether, filtered with suction, and vacuum-dried at room temperature to constant weight to obtain polyurethane material A1 containing phosphorylcholine groups in the side chain.

Preparation of film material: Dissolve A1 in the organic solvent dioxane to make a solution with a concentration of 6.5% (g/mL), use a polytetrafluoroethylene mold to volatilize at 25°C under normal pressure for 80 hours, and remove the film from the mold After taking it off, dry it under normal temperature and vacuum to obtain a membrane material, and the thickness of the obtained membrane material is 0.20 mm.

Example 2

Put 0.01mol polyε-caprolactone (PCL, M _n = 2000) and 0.02mol HDI-BDO-HDI (dissolved in dimethyl sulfoxide: 10g/30mL) in a three-necked flask, protected by dry nitrogen, and mechanically stirred , heat up to 85°C, react for 3.5 hours, cool down to 18°C, add 0.01mol Lys-PC, stir, when the viscosity of the system becomes too high to stir normally, add an appropriate amount of dichloromethane, stir for 1 hour, then add dichloromethane When the concentration is about 15 wt%, settle with glacial ether, filter with suction, and vacuum-dry at room temperature to constant weight to obtain polyurethane material A2 containing phosphorylcholine groups in the side chain.

Preparation of film material: Dissolve A2 in the organic solvent chloroform to make a solution with a concentration of 5.5% (g/mL), use a polytetrafluoroethylene mold to volatilize at 24°C under normal pressure for 90 hours, and take the film from the mold After drying under normal temperature and vacuum to obtain a film material, the thickness of the obtained film material is 0.19mm.

Example 3

Put 0.01mol polyε-caprolactone (PCL, M _n = 1500) and 0.02mol HDI-BDO-HDI (dissolved in dimethyl sulfoxide: 10g/30mL) in a three-necked flask, protected by dry nitrogen, and mechanically stirred , heat up to 85°C, react for 3.5 hours, cool down to 18°C, add 0.01mol Lys-PC, stir, when the viscosity of the system becomes too high to stir normally, add an appropriate amount of dichloromethane, stir for 1.5h, add dichloromethane Methane to a concentration of about 15 wt%, settled with glacial ether, filtered with suction, and vacuum-dried at room temperature to constant weight to obtain polyurethane material A3 containing phosphorylcholine groups in the side chain.

Preparation of film material: Dissolve A3 in the organic solvent chloroform to make a solution with a concentration of 4% (g/mL), use a polytetrafluoroethylene mold to volatilize at 15°C under normal pressure for 60 hours, and take the film from the mold The membrane material is obtained by vacuum drying at normal temperature after exposure, and the thickness of the obtained membrane material is 0.18mm.

Example 4

Put 0.01mol polyε-caprolactone (PCL, M _n = 1000) and 0.02mol BDI-BDO-BDI (dissolved in dimethyl sulfoxide: 10g/30mL) in a three-necked flask, protected by dry nitrogen, and mechanically stirred , heat up to 85°C, react for 3.5 hours, cool down to 18°C, add 0.01mol Lys-PC, stir, when the viscosity of the system becomes too high to stir normally, add an appropriate amount of dichloromethane, stir for 1.5h, add dichloromethane Methane to a concentration of about 15 wt%, settled with glacial ether, filtered with suction, and vacuum-dried at room temperature to constant weight to obtain polyurethane material A4 containing phosphorylcholine groups in the side chain.

Preparation of membrane material: Dissolve A4 in the organic solvent dichloromethane to make a solution with a concentration of 5% (g/mL), use a polytetrafluoroethylene mold to volatilize at 20°C under normal pressure for 65 hours, and take the membrane out of the mold After drying under normal temperature and vacuum to obtain a film material, the thickness of the obtained film material is 0.20mm.

Example 5

Put 0.01mol poly-L-lactic acid (PLLA, M _n = 1000) and 0.02mol BDI-BDO-BDI (dissolved in dimethyl sulfoxide: 10g/30mL) in a three-necked flask, protect it with dry nitrogen, stir mechanically, and raise the temperature to 80°C, react for 4.0 hours, then cool down to 20°C, add 0.01mol Lys-PC, stir, when the viscosity of the system becomes too high to stir normally, add an appropriate amount of dichloromethane, stir for 1.5h, then add dichloromethane to The concentration is about 15 wt%, settled with glacial ether, filtered with suction, and vacuum-dried at room temperature to constant weight to obtain polyurethane material A5 containing phosphorylcholine groups in the side chain.

Preparation of membrane material: Dissolve A5 in the organic solvent dichloromethane to make a solution with a concentration of 5% (g/mL), use a polytetrafluoroethylene mold to volatilize at 20°C under normal pressure for 60 hours, and take the membrane out of the mold The membrane material was obtained by vacuum drying at normal temperature after exposure, and the thickness of the obtained membrane material was 0.21 mm.

Example 6

Put 0.01mol poly-L-lactic acid (PLLA, M _n =1000) and 0.02mol BDI-BDO-BDI (dissolved in dimethyl sulfoxide: 10g/30mL) in a three-necked flask, protect it with dry nitrogen, stir it mechanically, and raise the temperature to 80°C, after reacting for 4.0 hours, cool down to 18°C, add 0.01mol Lys-EG-PC, stir, when the viscosity of the system becomes too high and cannot be stirred normally, add an appropriate amount of dichloromethane, stir for 1.5h, then add dichloromethane When the concentration is about 15 wt%, settle with glacial ether, filter with suction, and vacuum-dry at room temperature to constant weight to obtain polyurethane material A6 containing phosphorylcholine groups in the side chain.

Preparation of film material: Dissolve A6 in the organic solvent dioxane to make a solution with a concentration of 5.5% (g/mL), use a polytetrafluoroethylene mold to volatilize at 22°C under normal pressure for 80 hours, and remove the film from the mold After taking it off, vacuum-dry at normal temperature to obtain a membrane material, and the thickness of the obtained membrane material is 0.22mm.

Example 7

Put 0.01mol poly D,L-lactic acid (PDLLA, M _n =1000) and 0.02mol BDI-BDO-BDI (dissolved in dimethyl sulfoxide: 10g/30mL) in a three-necked flask, protected by dry nitrogen, and mechanically stirred , heat up to 90°C, react for 4.0 hours, cool down to 18°C, add 0.01mol Lys-EG-PC, stir, when the viscosity of the system becomes too high to stir normally, add an appropriate amount of dichloromethane, stir for 1.5h, add dichloromethane to a concentration of about 15 wt%, settled with glacial ether, suction filtered, and vacuum-dried at room temperature to constant weight to obtain polyurethane material A7 containing phosphorylcholine groups in the side chain.

Preparation of membrane material: Dissolve A7 in organic solvent acetone to make a solution with a concentration of 5.5% (g/mL), use a polytetrafluoroethylene mold to volatilize at 25°C under normal pressure for 75 hours, and remove the membrane from the mold Vacuum drying at normal temperature to obtain a membrane material, the thickness of the obtained membrane material is 0.20mm.

Example 8

Put 0.01mol polylactide (PGA, M _n =1000) and 0.02mol HDI-BDO-HDI (dissolved in dimethyl sulfoxide: 10g/30mL) in a three-necked flask, protected by dry nitrogen, stirred mechanically, and raised the temperature to 80°C, after reacting for 4.0 hours, cool down to 18°C, add 0.01mol Lys-PC, and stir. When the viscosity of the system becomes too high and cannot be stirred normally, add an appropriate amount of dichloromethane. After stirring for 2 hours, add dichloromethane to a concentration of about 15 wt%, settled with glacial ether, filtered with suction, and vacuum-dried at room temperature to constant weight to obtain polyurethane material A8 containing phosphorylcholine groups in the side chain.

Preparation of membrane material: Dissolve A8 in the organic solvent chloroform to make a solution with a concentration of 6% (g/mL), use a polytetrafluoroethylene mold to volatilize at 23°C under normal pressure for 80 hours, and then dry it in vacuum at normal temperature to obtain a membrane material , The thickness of the film material obtained by removing the film from the mold was 0.22 mm.

Analytical method

The following analytical methods were used for all examples unless otherwise stated.

Molecular weight and molecular weight distribution: use the Alpha type gel chromatography (GPC) of American Water company to measure the molecular weight and molecular weight distribution of polyurethane, 4mg sample is dissolved in 2mL tetrahydrofuran, filter in the special chromatographic bottle with 0.4μm filter tip, mobile phase velocity is 0.5mL/min, the temperature of the chromatographic column oven is set to 35°C, and the standard sample is monodisperse polystyrene.

Degradation performance: Soak the membrane material cut into a circle with a diameter of 10mm in normal saline, maintain a constant temperature of 37°C, and observe the state of the membrane material on a daily basis. When the membrane material produces fragments and loses its mechanical properties, it is considered that the degradation is complete. Degradation time.

Mechanical properties: In order to test the tensile properties of the synthesized polyurethane film, the tensile strength and elongation at break of the film were measured using a HY939C computerized single-column tensile testing machine from Guangdong Dongguan Hengyu Instrument Co., Ltd. Before the test starts, soak the sample in physiological saline for 3 minutes, then make a dumbbell-shaped model, and measure it according to the method stipulated in the national standard GB/T1040.2-2006, as shown in Figure 1.

Water contact angle measurement: The water contact angle test is carried out on the side of the film in contact with the air, distilled water (drop volume: 2μL), temperature: 25°C, measure the contact angle value of the water drop contact surface at about 1min, take 5 points as an average value.

Protein adsorption: Soak a 1cm×1cm polymer film in phosphate buffered saline (PBS) with pH=7.4 to fully swell and balance it, take it out and place it in bovine serum albumin solution (BSA) with a concentration of 0.6g/L Soak in a constant temperature water bath at 37°C for 2 hours. After the end, the polymer membrane was taken out and fully rinsed with PBS buffer solution 3 times. Then use 1% (w/w) SDS solution (PBS solution) to ultrasonically clean for 20min, accurately pipette the same volume of cleaning solution into a stoppered test tube, and then add Micro-BcA ^TM protein detection kit working solution (Pierce Inc., Rockford , 23235), fully mixed, sealed, 60 ℃ water bath constant temperature 1h. Finally, it was naturally cooled to room temperature, and the absorbance was measured at a wavelength of 562 nm using a UV-visible spectrophotometer, and the adsorption amount was calculated according to the standard curve, and the average value of three samples was taken.

Platelet adhesion test: extract fresh blood from the heart of healthy rabbits, add sodium citrate solution with a mass fraction of 3.8% as an anticoagulant, the ratio of whole blood to anticoagulant is 9:1, and add the whole blood with anticoagulant Put it into a centrifuge, set the speed of centrifugation at 1400r/min for the first time, and centrifuge for 10min; then absorb the supernatant and centrifuge again, set the speed at 1400r/min, centrifuge for 15min, the supernatant is platelet-poor plasma (PRP), absorb about 3/4 of the supernatant was discarded, and the rest was PRP; the modified polyurethane membrane (1.0×1.0cm ² ) was placed in a 24-well plate, first immersed in PBS buffer solution with pH=7.4 for 4 hours, and then in At a constant temperature of 37°C, incubate in PRP solution for 1 h. The membrane was taken out, washed repeatedly with PBS buffer solution 3 times to remove unadsorbed platelets, and then soaked in 2.5% glutaraldehyde PBS solution for 30min to fix the platelets on the surface. Immediately afterwards, the membrane was sequentially put into ethanol aqueous solutions with different concentration gradients (50, 60, 70, 80, 90, 100%) for step-by-step dehydration, soaked in each concentration solution for 30min, and finally dried at room temperature, sprayed Jin, S-4800 SEM (Hitachi, Japan) was used to observe the adhesion of platelets on the membrane surface.

The properties of the polyurethane film materials with phosphorylcholine groups in the side chains in Examples 1-8 are shown in Table 1.

The platelet adhesion scanning electron micrograph of the polyurethane membrane material (A6) containing phosphorylcholine groups in the side chain in Example 6 is shown in FIG. 1 .

Table 2 shows the biological evaluation tests of the polyurethane membrane materials containing phosphorylcholine groups in the side chains in Examples 1-8.

Table 1 Mechanical properties, surface hydrophilicity and protein adsorption capacity of polyurethane membranes containing phosphorylcholine groups in side chains

It can be seen from Table 1 that the polyurethane material containing phosphorylcholine groups in the side chain prepared by the method provided by this patent has a relatively high molecular weight, and its corresponding membrane material has a very high breaking strength, which meets the requirements of biological tissue engineering repair. Scaffold material requirements. As the content of hard segment (segment containing carbamate group and urea group) increases, the breaking strength increases. The degradation time of membrane materials is more than 15 weeks, and the longest is 17 weeks. It is considered that the prepared membrane is thinner and has a larger specific surface area. If the dosage form is prepared into the shape required for tissue engineering repair scaffold materials, the degradation time will increase greatly. The degradation time of the film is related to the content of phosphorylcholine and the type of polyurethane raw material. The higher the crystallinity of the modified polyurethane material, the slower the degradation. Its water contact angle is consistent with the law of protein adsorption, that is, the smaller the contact angle, the higher the surface hydrophilicity and the smaller the protein adsorption. As the content of phosphorylcholine groups increases, the phosphorylcholine groups in the side chains in the water will form a hydrophilic interface due to the hydrophilic interpolymerization, and at the same time, due to the high biocompatibility of the phosphorylcholine groups It also reduces the amount of protein adsorption, which greatly improves the biocompatibility of medical polyurethane materials. The protein adsorption amount of the samples in the examples of this patent is less than 2.2 μg/cm ² , even less than 1.5 μg/cm ² , indicating that the material exhibits excellent biocompatibility and can be used in organisms for a long time.

It can be seen from Figure 1 that the number of platelets adhered to the surface of the phosphorylcholine-modified polyurethane membrane was very small, and most of the platelets did not aggregate, and still maintained their original morphology. It shows that the material has excellent low platelet adhesion properties.

Table 2. Biological tests of polyurethane membrane materials (sample A1-A8) containing phosphorylcholine groups in the side chain

bacteria test sterile Chapter Two of GB/T14233.2-2005 Cytotoxicity <Level I GB/T14233.2-2005 Intradermal irritation No skin irritation GB/T14233.10-2005 Sensitization non-allergenic GB/T14233.10-2005 acute systemic toxicity no significant difference GB/T14233.11-2011

It can be seen from Table 2 that the test results of the biological properties of the membrane materials prepared in Examples 1-8 of the present invention show that each example can obtain materials that are non-toxic, non-irritating, and have good biocompatibility and meet the requirements for clinical use.

Although the specific embodiments of the present invention have been described and illustrated in detail above, it should be pointed out that we can make various equivalent changes and modifications to the above-mentioned embodiments according to the concept of the present invention, and the functional effects produced by it are still the same. Anything beyond the spirit contained in the specification and drawings shall fall within the protection scope of the present invention.

Claims (10)

1. a kind of side chain contains phosphoryl choline group polyester type polyurethane material, it is characterized in that: described polyester type polyurethane material soft segment is the polyester of crystallization, and hard segment contains carbamate group, polyurethane The molecular weight of the material is greater than 1.8×10 ⁵ , the breaking strength of the membrane material is greater than 42Mpa, the elongation at break is greater than 600%, the protein adsorption is less than 2.2μg/cm ² , and the degradation time is 105-120d. 2. a kind of preparation method of side chain containing phosphorylcholine group polyester polyurethane material, it is characterized in that: Include the following steps: (1) Polyester diol reacts with excess diisocyanate to obtain a double-ended isocyanate-based prepolymer, (2) Using a diamino phosphorylcholine compound to extend the chain of the double-terminal isocyanate-based prepolymer to obtain a polyurethane material containing phosphorylcholine groups in the side chain. 3. preparation method according to claim 2, is characterized in that: the polyester diol described in step (1) is polyglycolide, poly L-lactide, poly D, L-lactide or Polyε-caprolactone, the molecular weight of the polyester diol is 400-5000, preferably 500-3000. 4. The preparation method according to claim 2, characterized in that: the diisocyanate described in step (1) is 1,6-hexamethylene diisocyanate-1,4-butanediol-1,6 - hexamethylene diisocyanate, 1,4-tetramethylene diisocyanate -1,4-butanediol-1,4-tetramethylene diisocyanate. 5. The preparation method according to claim 2, characterized in that: the added amount of the excess diisocyanate described in step (1) is that the molar ratio of -NCO to -OH is 2.0, and the reaction temperature is 80 to 100°C. The time is 2.5～6.0h. 6. The preparation method according to claim 2, characterized in that: the phosphorylcholine compound of the bisamino group described in step (2) is that the specific structure is Lys-PC (as shown in formula 6) or Lys-EG- PC (as shown in Formula 7), the amount of phosphorylcholine compound added is: the molar ratio of _-NH2 to -NCO is 1:2, the reaction temperature is 10-20°C, the reaction time is 1.0-2.0h, 7. preparation method according to claim 2, is characterized in that: described preparation method comprises the purification step to described step (2) side chain containing phosphorylcholine group polyurethane material: with dichloromethane or dichloromethane The oxyhexane was dissolved, settled with glacial ether, filtered with suction, and dried under vacuum at room temperature until constant weight. 8. The preparation method according to claim 2, characterized in that: the polyurethane material containing phosphorylcholine groups in the side chain obtained in step (2) is dissolved in an organic solvent, and the concentration is 4 to 7%. (g/mL) solution, the polyurethane film material is prepared through solvent volatilization and film formation, and the good solvent is one of chloroform, dichloromethane, chloroform, acetone or dioxane or a mixture of several of them Solvent, solvent volatilization temperature is 15-25°C, volatilization at normal pressure for 60-90h, and then vacuum drying at normal temperature to obtain polyurethane film material, the thickness of the obtained film material is 0.18-0.22mm. 9. The preparation method according to any one of claims 2-8, characterized in that: the prepared polyurethane material can be made into various dosage forms required by organisms, especially membrane, sponge and cartilage dosage forms. 10. The application of the polyester polyurethane material containing phosphorylcholine groups in the side chain according to claim 1 as a tissue engineering repair scaffold material in the medical field.