CN106674484B - A kind of side chain group containing Phosphorylcholine polyether polyurethane material and preparation method thereof - Google Patents
A kind of side chain group containing Phosphorylcholine polyether polyurethane material and preparation method thereof Download PDFInfo
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- 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
- C08G18/78—Nitrogen
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- C08G18/7843—Nitrogen containing -N-C=0 groups containing urethane groups
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- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
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- C08G18/10—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
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- 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
- C08G18/48—Polyethers
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- 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
- C08G18/48—Polyethers
- C08G18/4833—Polyethers containing oxyethylene units
- C08G18/4837—Polyethers containing oxyethylene units and other oxyalkylene units
- C08G18/4845—Polyethers containing oxyethylene units and other oxyalkylene units containing oxypropylene or higher oxyalkylene end groups
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- 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
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- C08G18/00—Polymeric products of isocyanates or isothiocyanates
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- C08G18/6666—Compounds of group C08G18/48 or C08G18/52
- C08G18/667—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38
- C08G18/6681—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/32 or C08G18/3271 and/or polyamines of C08G18/38
- C08G18/6685—Compounds of group C08G18/48 or C08G18/52 with compounds of group C08G18/32 or polyamines of C08G18/38 with compounds of group C08G18/32 or C08G18/3271 and/or polyamines of C08G18/38 with compounds of group C08G18/3225 or polyamines of C08G18/38
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Abstract
The present invention relates to a kind of side chains to contain Phosphorylcholine polyether polyurethane material and preparation method thereof, and preparation method obtains both-end isocyanate group prepolymer the following steps are included: (1) polyetherdiol is reacted with excess diisocyanate；(2) using the Phosphorylcholine compound of double amino as chain extender, chain extension is carried out to both-end isocyanate group prepolymer, obtains Phosphorylcholine modified polyurethane.This is simple for process, and Phosphorylcholine group is located at the side chain of polymer, and the surface of material can be gathered in when applying in vivo, greatly improves the biocompatibility of material, very low to the adsorbance of protein and blood platelet in blood.Film prepared by the material has good mechanical strength and flexibility, and used diisocyanate is the aliphatic diisocyanate containing multiple amidocarbonic acid ester groups, and catabolite is nontoxic to be absorbed by organism.
Description
Technical field
The invention belongs to can medical macromolecular materials field, and in particular to a kind of side chain contains Phosphorylcholine group polyether-type
Polyurethane material and preparation method thereof.
Background technique
Polyurethane has high design method multiplicity, good biocompatibility, mechanical strength, wear-resisting, endurance, high resiliency, easy
Processing and nontoxic easily the advantages that being absorbed by the body, be a kind of environmentally friendly functional material, at present in artificial organ, imitative
The biological medicines Material Fields such as biological skin, medical sponge, postoperative suture, slow-released system matrix have a wide range of applications.So
And although the man-made organ made from polyurethane or there is preferable biocompatibility with the medical instrument of human contact,
It is found in clinical use, when touching blood using the surface of such as artificial blood vessel of man-made organ obtained by polyurethane material, blood
Slurry albumen will be adsorbed onto material surface first, then cause the activation of blood platelet and stick, finally result in blood coagulation phenomenon, lead to blood
Pipe restenosis etc..
Phosphorylcholine is the main component of biological cell outer membrane, that is, has-CH2NO5P+The compound of group, comprising more
Seed type common are dilauroyl lecithin (DLPC) (as shown in Equation 1), dimyristoyl phosphatidyl choline (DMPC)
(as shown in Equation 2), dipalmitoylphosphatidylcholine (DPPC) (as shown in Equation 3), Distearoyl Phosphatidylcholine (DSPC) are (such as formula
Shown in 4), poly- 2- methacryloxyethyl Phosphorylcholine (PMPC) (as shown in Equation 5) etc..
Phosphorylcholine is made of, biological function is main as a kind of amphiphatic molecule hydrophilic head and hydrophobic tail portion
It is the component part as cell membrane, plays an important role during the growth metabolism of biology.It under certain condition include phosphinylidyne
The polymer of choline group can form the bilayer of similar biomembrane, the high molecular material rich in the effective group of Phosphorylcholine
The natural component for the surrounding that disguises oneself as in vivo, improves the biocompatibility of material, and surface is not easy adsorbed proteins, blood
Platelet etc., so as to eliminate many problems of surface smut bring.To reduce the formation of thrombus, inflammation significantly, in cell
The reaction such as poison.
Therefore, Phosphorylcholine group is introduced on polyurethane matrix, reduces polyurethane material and is used for as man-made organ
The immune response of human body bring, has widened it in the application range of medical field.The Phosphorylcholine surface developed in recent years changes
Property polyurethane processing method it is more, mainly have polyurethane material surface access Phosphorylcholine group, Phosphorylcholine base will be contained
The polymer of group is blended with polyurethane material, having synthesized the both-end hydroxy compounds containing Phosphorylcholine group, chain extension is prepared for again
Main chain contains the methods of the polyurethane of Phosphorylcholine group.
Wherein on polyurethane material surface, the access group modified method of Phosphorylcholine is that polyurethane film is immersed in containing phosphorus
Reaction is carried out in the solvent of phatidylcholine makes surface first introduce primary amine groups, but its Phosphorylcholine group for being accessed is unstable is easy
It falls off under external condition, and method complexity, higher cost, is difficult to industrialized production；By the polymerization containing Phosphorylcholine group
Though the method for modifying that object is blended with polyurethane material improves the biocompatibility of original polyurethane material but discovery contains phosphinylidyne
When the polymer volume of choline group is more, it may appear that the mechanical performance of material reduces problem；It has synthesized and has contained Phosphorylcholine base
Chain extension is prepared for containing in the method for modifying material for the polyurethane that main chain contains Phosphorylcholine group the both-end hydroxy compounds of group again
Some Phosphorylcholine groups are fully located on main chain, and substantial portion of choline group is embedded in material in the use process of material
Material is internal, is difficult to be enriched in the surface of material, and the utilization rate of Phosphorylcholine group reduces, and the biocompatibility of the material is caused to mention
The problems such as height is limited, and prepares difficulty, higher cost.
Summary of the invention
According to the above-mentioned deficiencies of the prior art, it is an object of the present invention to provide a kind of side chains to contain Phosphorylcholine group
Polyether polyurethane material, which is located on side chain, hinders blood platelet and protein
Deposition, avoids the generation of thrombus, biocompatibility with higher.The soft segment of polyurethane material is polyether segment simultaneously, firmly
Containing carbamate groups and urea groups, polyurethane material molecular weight with higher in section, catabolite can be absorbed by organism,
Corresponding membrane material breaking strength with higher and elongation at break, not only flexible but also not easy to break, met biomaterial
Demand.
Another object of the present invention is to provide a kind of preparation of polyether polyurethane material that side chain contains Phosphorylcholine group
Method, the preparation process is simple, and the diisocyanate of selection is the aliphatic diisocyanate containing multiple amidocarbonic acid ester groups,
Catabolite can be absorbed by organism, be can be used as biomaterial etc. and be applied to organism for a long time.It is prepared by this preparation method
Polyether polyurethane material be it is fully synthetic, without biocompatibility and mechanical performance potential animal derived, while that have high, and
With biological degradability, catabolite is nontoxic, can be absorbed by organism.
To achieve the goals above, the present invention adopts the following technical scheme:
A kind of side chain contains Phosphorylcholine group polyether polyurethane material, and the polyether polyurethane material soft segment is poly-
Ether segment, carbamate groups and urea groups are contained in hard section, and polyurethane material molecular weight is greater than 1.1 × 105, membrane material fracture is by force
Degree is greater than 22Mpa, elongation at break is greater than the adsorbance of 750%, protein less than 2.3 μ g/cm2。
The present invention also provides the preparation methods that a kind of side chain contains the polyether polyurethane material of Phosphorylcholine, including with
Lower step:
(1) polyetherdiol is reacted with excess diisocyanate, obtains both-end isocyanate-based prepolymers；
(2) chain extension is carried out to both-end isocyanate-based prepolymers with the Phosphorylcholine compound of double amino, obtains phosphinylidyne gallbladder
Alkali modification polyurethane.
Preferably, the polyetherdiol in step (1) be polyoxyethylene oxypropylene block copolymer (poloxamer Px),
Polypropylene oxide (PPO), polytetrahydrofuran (PTMG), more preferable molecular weight are 1000-5000.
Preferably, poloxamer is polypropylene oxide-polyethylene oxide-polypropylene oxide (PPO-PEO-PPO) three block
Polymer, wherein content of the polyethylene oxide in poloxamer is 15wt%-30wt%.
Preferably, the diisocyanate in step (1) is 1,6- hexamethylene diisocyanate -1,4-butanediol -1,6-
Hexamethylene diisocyanate (HDI-BDO-HDI), Isosorbide-5-Nitrae-tetramethylene diisocyanate-- four methylene of 1,4-butanediol-Isosorbide-5-Nitrae
Group diisocyanate (BDI-BDO-BDI).
Preferably, the specific preparation method of HDI-BDO-HDI and BDI-BDO-HDI is with 1,4-butanediol (BDO) and two
Isocyanates is raw material, molar ratio are as follows: n-OH:n-NCO=1:4-30,70-100 DEG C of reaction temperature, reaction time 1-5h,
Synthesize HDI-BDO-HDI.
Preferably, BDO and 1,6- hexamethylene diisocyanate (HDI) molar ratio are 1:12, under a dry nitrogen atmosphere
Reaction, the reaction time 4 hours, is cooled to room temperature for reaction system by 80 DEG C of reaction temperature, obtains white solid, n-hexane washing three
Secondary removing excess HDI, normal-temperature vacuum it is dry HDI-BDO-HDI.
Preferably, BDO and Isosorbide-5-Nitrae-tetramethylene diisocyanate (BDI) molar ratio are 1:14, anti-under dry nitrogen atmosphere
It answers, 80 DEG C of reaction temperature, reaction time 3h, cools to room temperature and form white solid, n-hexane washing removes excessive three times
BDI, normal-temperature vacuum it is dry BDI-BDO-BDI.
Preferably, it is 2.0 that the additional amount of excess diisocyanate, which is-NCO:-OH molar ratio, in step (1), adding manner
It is dissolved in dimethyl sulfoxide (10g/30mL) for diisocyanate, is mixed at normal temperature with polyetherdiol.
Preferably, reaction temperature is 60-95 DEG C in step (1), reaction time 2-6h.
Preferably, double amino Phosphorylcholine compounds (DAPC) described in step (2) are that specific structure is as shown in Equation 6:
Preferably, in step (2) double amino Phosphorylcholine compounds additional amount are as follows:-NH2It is 1:2 with-NCO molar ratio.
Reaction temperature is 10-20 DEG C, reaction time 1.0-2.0h, until infrared detection-NCO absorption peak completely disappears.
Preferably, the preparation method includes the purification step to the phosphorous phatidylcholine group polyurethane material of side chain: with
Methylene chloride dissolution, the sedimentation of ice ether, normal-temperature vacuum are dry to constant weight.
Preferably, Phosphorylcholine modified polyurethane material obtained in step (2) is dissolved in benign organic solvent, is made into
Concentration is the solution of 3-7% (g/mL), volatilizees and forms a film through solvent, polyurethane film material is prepared.
Preferably, good solvent is chloroform, methylene chloride, acetone or dioxane, and solvent volatilization temperature is 15-30
DEG C, normal pressure volatilization 48-96h, normal-temperature vacuum drying to constant weight.
Preferably, gained polyurethane film material membrane with a thickness of 0.18-0.22mm.
Preferably, which can be made various dosage forms, especially film, sponge, cartilage required for organism
Dosage form.
Preferably, the polyurethane material as biomaterial medical domain application.
Beneficial effects of the present invention
1. polyurethane soft segment prepared by the present invention is polyether segment, ensure that as drawing higher needed for biomaterial
Ability and flexibility are stretched, contains more carbamate groups and urea groups in hard section, finer and close hydrogen can be formed in the material
Key ensure that material has good mechanical strength.
2. material Phosphorylcholine group prepared by the present invention is located at the side chain of polymer, can assemble in application in vivo
It on the surface of material, plays a protective role to material, during which applies in vivo, hinders blood platelet and protein
Deposition, avoids the generation of thrombus, to improve biocompatibility.The diisocyanate of the materials'use is to contain multiple amine
The aliphatic diisocyanate of carbamate base, avoiding catabolite is fatty amine, can be absorbed by organism, can be used as biological drop
It solves material and is applied to organism.
3. preparation process of the present invention is simple, conventional method can meet preparation and require, and can be prepared into a variety of dosage forms, have
Higher commercialization prospect.
Detailed description of the invention
The blood platelet viscosity SEM photograph of Fig. 1, sample P 5.
Specific embodiment
It is next combined with specific embodiments below that the invention will be further described.
Embodiment 1
By 15g (0.01mol) PLURONICS F87 (Mn=1500, PEOwt%=20%) and 8.52g (0.02mol) HDI-
BDO-HDI (being dissolved in dimethyl sulfoxide: 10g/30mL) is placed in three-necked flask, drying nitrogen protection, and mechanical stirring is warming up to 80
DEG C, after reacting 4h, 20 DEG C are cooled to, 3.61g (0.01mol) DAPC is added, stirring can not be stirred normally when system viscosity becomes larger
When, methylene chloride is added in right amount, after stirring 1h, methylene chloride is added to concentration about 15wt%, the sedimentation of ice ether filters, room temperature
It is dried under vacuum to constant weight, obtains Phosphorylcholine modified polyurethane P1.
The preparation of membrane material: P1 is dissolved in organic solvent dioxane, and being made into concentration is the molten of 6.5% (g/mL)
Liquid volatilizees 80h in 25 DEG C of normal pressures, by normal-temperature vacuum it is dry membrane material, resulting membrane material with a thickness of 0.2mm.
Embodiment 2
By 15g (0.01mol) PLURONICS F87 (Mn=1500, PEOwt%=20%) and 7.40g (0.02mol) BDI-
BDO-BDI (being dissolved in dimethyl sulfoxide: 10g/30mL) is placed in three-necked flask, drying nitrogen protection, and mechanical stirring is warming up to 80
DEG C, after reacting 3h, 18 DEG C are cooled to, 3.61g (0.01mol) DAPC is added, stirring can not be stirred normally when system viscosity becomes larger
When, methylene chloride is added in right amount, after stirring 1h, methylene chloride is added to concentration about 15wt%, the sedimentation of ice ether filters, room temperature
It is dried under vacuum to constant weight, obtains Phosphorylcholine modified polyurethane P2.
The preparation of membrane material: P2 is dissolved in organic solvent chloroform, and being made into concentration is the molten of 5.5% (g/mL)
Liquid volatilizees 90h in 24 DEG C of normal pressures, by normal-temperature vacuum it is dry membrane material, resulting membrane material with a thickness of 0.19mm.
Embodiment 3
By 10g (0.01mol) polypropylene oxide (PPO, Mn=1000) and 8.52g (0.02mol) HDI-BDO-HDI is (molten
In dimethyl sulfoxide: 10g/30mL) it is placed in three-necked flask, drying nitrogen protection, mechanical stirring, 85 DEG C are warming up to, 3h is reacted
Afterwards, 20 DEG C are cooled to, 3.61g (0.01mol) DAPC is added, stirring is appropriate to mend when system viscosity, which becomes larger, normally to be stirred
It adds methylene chloride, after stirring 1.5h, methylene chloride is added to concentration about 15wt%, the sedimentation of ice ether filters, and normal-temperature vacuum is dry
To constant weight, Phosphorylcholine modified polyurethane P3 is obtained.
The preparation of membrane material: P3 is dissolved in organic solvent chloroform, is made into the solution that concentration is 4% (g/mL),
Volatilized 60h using Teflon mould in 15 DEG C of normal pressures, after film is removed from the mold through normal-temperature vacuum it is dry membrane material,
Resulting membrane material with a thickness of 0.18mm.
Embodiment 4
By 20g (0.01mol) polypropylene oxide (PPO, Mn=2000) and 7.40g (0.02mol) BDI-BDO-BDI is (molten
In dimethyl sulfoxide: 10g/30mL) it is placed in three-necked flask, drying nitrogen protection, mechanical stirring, 80 DEG C are warming up to, reaction
After 3.5h, 20 DEG C are cooled to, 3.61g (0.01mol) DAPC is added, stirring is fitted when system viscosity, which becomes larger, normally to be stirred
Amount adds methylene chloride, after stirring 1.5h, methylene chloride is added to concentration about 15wt%, the sedimentation of ice ether filters, normal-temperature vacuum
Drying obtains Phosphorylcholine modified polyurethane P4 to constant weight.
The preparation of membrane material: P4 is dissolved in organic solvent dichloromethane, is made into the solution that concentration is 5% (g/mL),
Volatilized 65h using Teflon mould in 20 DEG C of normal pressures, after film is removed from the mold through normal-temperature vacuum it is dry membrane material,
Resulting membrane material with a thickness of 0.20mm.
Embodiment 5
By 15g (0.01mol) polytetrahydrofuran (PTMG, Mn=1500) and 8.52g (0.02mol) HDI-BDO-HDI is (molten
In dimethyl sulfoxide: 10g/30mL) it is placed in three-necked flask, drying nitrogen protection, mechanical stirring, 80 DEG C are warming up to, reaction
After 3.5h, 15 DEG C are cooled to, 3.61g (0.01mol) DAPC is added, stirring is fitted when system viscosity, which becomes larger, normally to be stirred
Amount adds methylene chloride, after stirring 1.5h, methylene chloride is added to concentration about 15wt%, the sedimentation of ice ether filters, normal-temperature vacuum
Drying obtains Phosphorylcholine modified polyurethane P5 to constant weight.
The preparation of membrane material: P5 is dissolved in organic solvent dichloromethane, is made into the solution that concentration is 5% (g/mL),
Volatilized 60h using Teflon mould in 20 DEG C of normal pressures, after film is removed from the mold through normal-temperature vacuum it is dry membrane material,
Resulting membrane material with a thickness of 0.22mm.
Embodiment 6
By 20g (0.01mol) polytetrahydrofuran (PTMG, Mn=2000) and 7.40g (0.02mol) BDI-BDO-BDI is (molten
In dimethyl sulfoxide: 10g/30mL) it is placed in three-necked flask, drying nitrogen protection, mechanical stirring, 75 DEG C are warming up to, 3h is reacted
Afterwards, 15 DEG C are cooled to, 3.61g (0.01mol) DAPC is added, stirring is appropriate to mend when system viscosity, which becomes larger, normally to be stirred
It adds methylene chloride, after stirring 1h, methylene chloride is added to concentration about 15wt%, the sedimentation of ice ether filters, and normal-temperature vacuum is dry extremely
Constant weight obtains Phosphorylcholine modified polyurethane P6.
The preparation of membrane material: P6 is dissolved in organic solvent dioxane, and being made into concentration is the molten of 5.5% (g/mL)
Liquid is volatilized 80h using Teflon mould in 22 DEG C of normal pressures, after film is removed from the mold through normal-temperature vacuum it is dry membrane material
Material, resulting membrane material with a thickness of 0.2mm.
Embodiment 7
By 20g (0.01mol) Pluronic/Lutrol F 108 (Px338, Mn=2000, PEOwt%=15%) and 7.40g
(0.02mol) BDI-BDO-BDI (being dissolved in dimethyl sulfoxide: 10g/30mL) is placed in three-necked flask, drying nitrogen protection, mechanical
Stirring is warming up to 75 DEG C, after reacting 3h, is cooled to 18 DEG C, and 3.61g (0.01mol) DAPC, stirring, when system viscosity becomes is added
When can not normally stir greatly, methylene chloride is added in right amount, and after stirring 1h, methylene chloride is added to concentration about 15wt%, ice ether
Sedimentation filters, and normal-temperature vacuum is dry to constant weight, obtains Phosphorylcholine modified polyurethane P7.
The preparation of membrane material: P7 is dissolved in organic solvent-acetone, is made into the solution that concentration is 7% (g/mL), is used
Teflon mould volatilizees 75h in 25 DEG C of normal pressures, after film is removed from the mold through normal-temperature vacuum it is dry membrane material, gained
Membrane material with a thickness of 0.20mm.
Embodiment 8
By 15g (0.01mol) Pluronic/Lutrol F 108 (Px338, Mn=1500, PEOwt%=15%) and 8.52g
(0.02mol) HDI-BDO-HDI (being dissolved in dimethyl sulfoxide: 10g/30mL) is placed in three-necked flask, drying nitrogen protection, mechanical
Stirring is warming up to 85 DEG C, after reacting 4h, is cooled to 20 DEG C, and 3.61g (0.01mol) DAPC, stirring, when system viscosity becomes is added
When can not normally stir greatly, methylene chloride is added in right amount, and after stirring 1h, methylene chloride is added to concentration about 15wt%, ice ether
Sedimentation filters, and normal-temperature vacuum is dry to constant weight, obtains Phosphorylcholine modified polyurethane P8.
The preparation of membrane material: P8 is dissolved in organic solvents, chloroform, is made into the solution that concentration is 6% (g/mL), is used
Teflon mould volatilizees 80h in 23 DEG C of normal pressures, by normal-temperature vacuum it is dry membrane material, film is removed from the mold into gained
Membrane material with a thickness of 0.22mm.
Analysis method
Following analysis method is used for all embodiments, unless otherwise stated.
Molecular weight: using Water company, the U.S. Alpha type gel permeation chrommatograph (GPC) measurement polyurethane molecular weight and
Molecular weight distribution, solvent are tetrahydrofuran, and standard specimen is monodisperse polystyrene.
Mechanical performance: it is surveyed using the computermatic single-column tensile testing machine of the HY939C type of Dongguan, Guangdong Heng Yu Instrument Ltd.
Determine the tensile strength and elongation at break of film.Before on-test, sample is first impregnated into 3min in physiological saline, is then made mute
Bell pattern type, is measured according to method as defined in national standard GB13022-91.
Water contact angle measurement: water contact angle test contacts one side with air in film and carries out, distilled water (droplet size: 2 μ
), L temperature: 25 DEG C, contact angle numerical value of the water drop contact surface in about 1min is measured, 5 points is taken to make average value.
Protein adsorbance: the polymer film of 1cm × 1cm is soaked in the phosphate buffer (PBS) of pH=7.4 and is filled
Divide swelling equilibrium, is placed it in after taking-up in the bovine serum albumen solution (BSA) that concentration is 0.6g/L, in 37 DEG C of water bath with thermostatic control
Middle immersion 2h.After take out polymer film, sufficiently eluted 3 times with PBS buffer solution.Then with the SDS solution of 1% (w/w)
(PBS solution) is cleaned by ultrasonic 20min, accurately pipettes same volume cleaning solution in tool plug test tube, adds Micro-BcATMEgg
White matter detection kit working solution (PierceInc., Rockford, 23235), is sufficiently mixed, sealing, 60 DEG C of constant temperature water bath lh.
Room temperature is finally naturally cooled to, absorbance is measured at 562nm wavelength using ultraviolet-visible spectrophotometer, according to standard
Curve calculates to obtain adsorbance, takes the average value of 3 samples.
Platelet adhesion reaction experiment: extracting new blood from healthy rabbit hearts, and the citric acid that mass fraction is 3.8% is added
For sodium solution as anti-coagulants, the ratio of whole blood and anti-coagulants is 9:1, the whole blood that anticoagulant is added is put into a centrifuge, just
Secondary centrifugation setting revolving speed is 1400r/min, is centrifuged 10min；Then it draws supernatant liquor to be centrifuged again, setting revolving speed is still
1400r/min is centrifuged 15min, and supernatant liquor is platelet poor plasma (PRP), draws about 3/4 supernatant and discards, residue is
For PRP；By modified polyurethane film (1.0 × 1.0cm2) be placed in 24 orifice plates, first it is immersed in the PBS buffering of pH=7.4
4h in solution is incubated for 1h in PRP solution then under 37 DEG C of constant temperature.It takes the film out, with PBS buffer solution repeated flushing 3 times
To remove unadsorbed blood platelet, then film is immersed in the blood of 30min fixation surface in 2.5% glutaraldehyde PBS solution again
Platelet.And then film is sequentially placed into the ethanol water of various concentration gradient (50,60,70,80,90,100%) carry out by
Grade dehydration, 30min is impregnated in the solution of every kind of concentration, is finally dried at room temperature, metal spraying, using S-4800 type SEM (Japan
Hitachi, Ltd) observation film surface platelet adhesion reaction situation.
The performance of Phosphorylcholine modified polyurethane membrane material is as shown in table 1 in embodiment 1-8.
The stereoscan photograph of the platelet adhesion reaction of polyurethane film material is as shown in Figure 1 in embodiment 5.
The biological assessment test of polyurethane film material is as shown in table 2 in embodiment 1-8.
Mechanical system's energy, hydrophily and the protein adsorbance of 1 Phosphorylcholine modified polyurethane film of table
As shown in Table 1, the Phosphorylcholine modified polyurethane molecular weight with higher of the preparation of method provided by this patent,
Its corresponding membrane material breaking strength with higher and elongation at break, not only flexible but also not easy to break, met biomaterial
Demand.With the increase of hard segment content, breaking strength increases；With the increase of content of soft segmer, elongation at break increases.Contact
The size at angle reacts hydrophilic size, and contact angle is bigger, and hydrophily is poorer, on the contrary.Contact angle shown in table shows this kind
Material has preferable hydrophily, and hydrophily is better, fewer to the absorption of protein.The albumen of sample in this patent embodiment
The adsorbance of matter is less than 2.3 μ g/cm2, even less than 1.5 μ g/cm2, show that the material shows splendid biocompatibility, it can
It is long-term used in organism.
It will be noted from fig. 1 that the platelet counts that Phosphorylcholine modified polyurethane film surface is sticked are seldom, and big portion
Divide blood platelet there is no aggregation, still maintains original pattern.Show that the material has excellent antiplatelet Adhesion property.
The biology of 2 Phosphorylcholine modified polyurethane membrane material (sample P 1-P8) of table is tested
| Bacterium test | It is sterile | GB/T14233.2-2005 chapter 2 |
| Cytotoxicity | < I grades | GB/T14233.2-2005 |
| Intradermal irritation | Without intradermal stimulation | GB/T14233.10-2005 |
| Sensitization | Without sensitization | GB/T14233.10-2005 |
| Acute systemic toxicity | No significant difference | GB/T14233.11-2011 |
As shown in Table 2, the biology performance testing result of membrane material prepared by 1-8 of the embodiment of the present invention shows each reality
Apply the material that example can obtain nontoxic, non-stimulated, good biocompatibility and meet clinical use requirement.
Although the detailed description and description of the specific embodiments of the present invention are given above, it should be noted that
We can carry out various equivalent changes and modification to above embodiment according to the concept of the present invention, and generated function is made
It, should all be within protection scope of the present invention when with the spirit still covered without departing from specification and attached drawing.
Claims (5)
1. a kind of side chain contains Phosphorylcholine group polyether polyurethane material, it is characterised in that: the polyurethane material is soft
Section is polyether segment, and carbamate groups and urea groups are contained in hard section, and polyurethane material molecular weight is greater than 1.1 × 105, membrane material
Breaking strength is greater than 22MPa, elongation at break is greater than the adsorbance of 750%, protein less than 2.3 μ g/cm2；
Wherein, the polyurethane material is prepared via a method which to obtain:
(1) polyetherdiol is reacted with excess diisocyanate, obtains both-end isocyanate-based prepolymers；
(2) chain extension is carried out to both-end isocyanate-based prepolymers with double amino Phosphorylcholine compounds, it is modified obtains Phosphorylcholine
Polyurethane；
Phosphorylcholine modified polyurethane material obtained in step (2) is dissolved in organic solvent, being made into concentration is 3-7%g/
The solution of mL is volatilized into film preparation through solvent and obtains polyurethane film material；
Wherein, polyetherdiol described in step (1) can be poloxamer, polypropylene oxide or polytetrahydrofuran, and described is poly-
Ether glycol molecular weight is 1000-5000, and content of the polyethylene oxide in poloxamer is 15wt%-30wt%；
Wherein, diisocyanate described in step (1) is 1,6- hexamethylene diisocyanate -1,4-butanediol -1,6- six
Methylene diisocyanate, Isosorbide-5-Nitrae-tetramethylene diisocyanate -1,4-butanediol-Isosorbide-5-Nitrae-tetramethylene diisocyanate, mistake
The additional amount of amount diisocyanate is-NCO and-OH molar ratio is 2.0, and adding manner is that diisocyanate is dissolved in dimethyl sulfoxide
10g/30mL is mixed with polyetherdiol at normal temperature, and polyetherdiol and di-isocyanate reaction temperature are 60-95 DEG C, when reaction
Between be 2-6h；
Double amino Phosphorylcholine compounds described in step (2) are that specific structure is double amino Phosphorylcholine chemical combination as shown in Equation 6
The additional amount of object is-NH2It is 1:2 with-NCO molar ratio, reaction temperature is 10-20 DEG C, reaction time 1.0-2.0h, until infrared
Detection-NCO absorption peak completely disappears；
2. polyurethane material according to claim 1, it is characterised in that: the preparation method includes to the phosphorous acyl of side chain
The purification step of choline group polyurethane material: being dissolved with methylene chloride, the sedimentation of ice ether, and normal-temperature vacuum is dry to constant weight.
3. polyurethane material according to claim 1, it is characterised in that: the organic solvent is chloroform, dichloro
Methane, chloroform, acetone or dioxane one kind or in which several mixed solvents, solvent volatilization temperature is 15-25 DEG C, normal pressure
Volatilize 60-90h, by normal-temperature vacuum it is dry membrane material, resulting membrane material with a thickness of 0.18-0.22mm.
4. polyurethane material according to claim 1 to 3, it is characterised in that: the modified poly- ammonia of preparation gained Phosphorylcholine
Ester material can be made various dosage forms, especially film or sponge dosage form required for organism.
It is being cured 5. side chain according to claim 1 contains Phosphorylcholine group polyether polyurethane material as biomaterial
The application in field.
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| CN107216435B (en) * | 2017-06-26 | 2020-01-31 | 山东师范大学 | poly (urethane-urea) with side chain of phosphatide polyethylene glycol and preparation method thereof |
| CN109054485B (en) * | 2018-06-27 | 2020-06-05 | 佛山市博新生物科技有限公司 | Antibacterial coating liquid and preparation method and application thereof |
| CN110483740B (en) * | 2019-08-12 | 2021-08-27 | 山东师范大学 | Polymer, pH-sensitive nano-vesicle, preparation method and application |
| CN113388147A (en) * | 2021-06-29 | 2021-09-14 | 杨欣 | Preparation method of biomaterial phosphorylcholine modified polyurethane |
| CN113956437A (en) * | 2021-10-28 | 2022-01-21 | 赛克赛斯生物科技股份有限公司 | Polyurethane sponge and preparation method and application thereof |
| CN114213615B (en) * | 2021-12-29 | 2022-09-16 | 广东粤港澳大湾区黄埔材料研究院 | Swelling-resistant phosphorylcholine modified polyurethane material and preparation method thereof |
| CN114380969B (en) * | 2021-12-30 | 2023-05-26 | 广东粤港澳大湾区黄埔材料研究院 | Hydrophilic modified additive and preparation method thereof |
| CN115073699B (en) * | 2022-06-14 | 2024-01-26 | 杭州柏医健康科技有限公司 | Temperature-insensitive polyurethane polymer and application thereof |
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