CN106674486A - Polyester type polyurethane material with side chain containing phosphorylcholine group and preparation method thereof - Google Patents
Polyester type polyurethane material with side chain containing phosphorylcholine group and preparation method thereof Download PDFInfo
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- CN106674486A CN106674486A CN201611235863.2A CN201611235863A CN106674486A CN 106674486 A CN106674486 A CN 106674486A CN 201611235863 A CN201611235863 A CN 201611235863A CN 106674486 A CN106674486 A CN 106674486A
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/70—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the isocyanates or isothiocyanates used
- C08G18/72—Polyisocyanates or polyisothiocyanates
- C08G18/80—Masked polyisocyanates
- C08G18/8003—Masked polyisocyanates masked with compounds having at least two groups containing active hydrogen
- C08G18/8006—Masked polyisocyanates masked with compounds having at least two groups containing active hydrogen with compounds of C08G18/32
- C08G18/8009—Masked polyisocyanates masked with compounds having at least two groups containing active hydrogen with compounds of C08G18/32 with compounds of C08G18/3203
- C08G18/8012—Masked polyisocyanates masked with compounds having at least two groups containing active hydrogen with compounds of C08G18/32 with compounds of C08G18/3203 with diols
- C08G18/8016—Masked aliphatic or cycloaliphatic polyisocyanates
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
- A61L27/18—Macromolecular materials obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/50—Materials characterised by their function or physical properties, e.g. injectable or lubricating compositions, shape-memory materials, surface modified materials
- A61L27/58—Materials at least partially resorbable by the body
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/08—Processes
- C08G18/10—Prepolymer processes involving reaction of isocyanates or isothiocyanates with compounds having active hydrogen in a first reaction step
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
- C08G18/4269—Lactones
- C08G18/4277—Caprolactone and/or substituted caprolactone
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- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G18/00—Polymeric products of isocyanates or isothiocyanates
- C08G18/06—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen
- C08G18/28—Polymeric products of isocyanates or isothiocyanates with compounds having active hydrogen characterised by the compounds used containing active hydrogen
- C08G18/40—High-molecular-weight compounds
- C08G18/42—Polycondensates having carboxylic or carbonic ester groups in the main chain
- C08G18/4266—Polycondensates having carboxylic or carbonic ester groups in the main chain prepared from hydroxycarboxylic acids and/or lactones
- C08G18/428—Lactides
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G2230/00—Compositions for preparing biodegradable polymers
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Abstract
The invention relates to a polyester type polyurethane material with a side chain containing a phosphorylcholine group and a preparation method thereof. The preparation method comprises the following steps of: (1) causing polyester glycol react with excessive diisocyanate, thereby acquiring a double-end isocyanate group prepolymer; and (2) adopting a phosphorylcholine compound containing two amino groups for expanding the chain of the double-end isocyanate group prepolymer, thereby acquiring a biodegradable polyurethane material with the side chain containing the phosphorylcholine group. The phosphorylcholine group in the polyurethane material is located on the side chain of the polymer, so that the biocompatibility of the material can be effectively promoted under the condition of low content of the phosphorylcholine group. Soft segments of the material are all made from polyester; the degree of crystallinity is higher; the higher mechanical strength of the material is guaranteed; the main chain is fully hydrophobic; the degradation velocity is low; the polyurethane material, which is used as a tissue engineering repairing holder material, and the like, can be long-term applied to organism; after the material acts, the material can be gradually degraded into non-toxic products and then absorbed by the organism, so that the injury of the second operation can be avoided.
Description
Technical field
The invention belongs to can medical macromolecular materials field, and in particular to a kind of side chain group containing Phosphorylcholine polyester-type gathers
Urethane material and preparation method thereof.
Background technology
Since Bayer AG's invention, from medical catheter to artificial heart, polyurethane (PU) has in medical instruments field
It is widely used.Polyurethane has unique performance, such as relatively excellent biocompatibility, chemical characteristic, remarkable power
Performance and processing characteristics etc. are learned, becomes the ideal chose of numerous medical product raw materials, particularly when simultaneously selected materials will be solved
When certainly complicated mechanical property and biocompatibility issues, for example prepare interposing catheter, intervention device coating, hemodialysis membrane,
The contacting blood device such as artificial heart and making assisted circulation of ventriculus cordis system, medical polyurethane is typically the optimum selection of raw material.At present,
Thrombosis, calcification and bacterium infection are including the major complications faced for contacting blood material including medical polyurethane.When
Medical material is entered in human body, and tissue and main and material the surface of blood contact, therefore understands that the table with control material
Surface properties are the keys for eliminating complication.
Phosphoryl choline polymer has-CH2NO5The compound of P+ groups, comprising polytype, common are two Laurels
Acyl group lecithin (DLPC) (as shown in Equation 1), dimyristoyl phosphatidyl choline (DMPC) (as shown in Equation 2), two Palmic acid phosphorus
Phosphatidylcholine (DPPC) (as shown in Equation 3), distearoyl phosphatidylcholine (DSPC) (as shown in Equation 4), poly- 2- methacryls
Epoxide ethylphosphocholine (PMPC) (as shown in Equation 5) etc..Its interaction very little with various biotic components in blood, i.e. phosphorus
Phatidylcholine group is able to maintain that the normal conformation of biotic component in blood makes the outer surface of hemocyte cell membrane have good blood
Liquid phase capacitive, therefore critical role is accounted in outer cell membrane, he directly affects how biological cell has an effect with the external world.
Based on imitative membrane structure set out design synthesis phosphoryl choline polymer enjoy pass because it has good biocompatibility
Note.By the construction for imitating extracellular Lipid bilayer membranes, the material rich in Phosphorylcholine group is disguised it as in vivo
The natural component of surrounding so as to which, with excellent biocompatibility, surface is difficult the biofoulings such as adsorbed proteins, platelet,
Thrombosiss are prevented, so as to many problems that surface smut causes can be eliminated.The birds of the same feather flock together exploitation of compound of Phosphorylcholine is sought for people
Biocompatible materialses are looked for open new approach.
Phosphorylcholine can be widely used in the modified field to polyurethane material.The Phosphorylcholine modification polyurethane of early stage
Method be by after 2- methylacryoyloxyethyl Phosphorylcholines (MPC) and methacrylic acid -2- Octyl Nitrite copolymerization by copolymerization
Thing is blended with block polyurethane, and develops semi-intercrossing network technology on this basis.Developed with azo two again later
Isobutyl is fine for initiator, and MPC is prepared for butyl methacrylate, the copolymerization of first Isooctyl acrylate monomer using radical polymerization
Thing.Although the Phosphorylcholine group of the polymer for preparing is located at side chain, the table for being gathered in material is can be very good under water environment
Face, plays a part of to increase biocompatibility, but the phosphoryl choline polymer degradation property of free-radical polymerized preparation is very poor, and
And blending method causes the mechanical performance of material to reduce, application is very restricted.
Another kind of Phosphorylcholine method of modifying is the surface that Phosphorylcholine group is grafted to polyurethane material, with 2- methyl
Acrylyl oxy-ethyl Phosphorylcholine (MPC) and choline glycerophosphatide (GPC) derivant provide compound for PC groups, and with surface
Coupling MPC methods, surface coupling aldehyde radical Phosphorylcholine method and surface grafting GPC derivative methods, by PC groups covalence graft to poly- carbon
Acid esters type polyurethane surface.The Phosphorylcholine modified biological material that the method is obtained has higher biocompatibility.Although material
Material surface grafting Phosphorylcholine group can effectively improve the biocompatibility of material, but this method has technique very multiple
It is miscellaneous, it is relatively costly, and it is only applicable to the material of surface comparison rule so as to the problems such as commercialization becomes extremely difficult.
There is a kind of Phosphorylcholine method of modifying to be both-end hydroxy compounds of the synthesis containing Phosphorylcholine group at present, so
Carry out chain extension using diisocyanate afterwards and prepare the polyurethane that main chain contains Phosphorylcholine group.This preparation method resulting materials
With good biocompatibility, but the Phosphorylcholine group contained in the material is fully located on main chain, in the use of material
During substantial portion of choline group be embedded in material internal, it is difficult to be enriched in the surface of material, therefore the material has life
Thing limited compatibility, the both-end hydroxy compounds of synthesis Phosphorylcholine group cause the material using the aldehydes matter containing phenyl ring
Material is the shortcomings of poisonous mass degradation is had out during long-term use.
The content of the invention
According to above the deficiencies in the prior art, it is an object of the present invention to provide a kind of side chain contains Phosphorylcholine group
Polyester type polyurethane material, the polyurethane material Phosphorylcholine group is located on side chain, can effectively platelet and albumen
The deposition of matter and the generation of thrombosis is avoided, with higher biocompatibility, while the soft section of polyurethane material is crystallization
Polyester, hard section has ordered structure and contains carbamate groups so that material has higher mechanical strength, and main chain
Completely the characteristic of hydrophobic is met as degradation speed slower needed for organizational project renovating bracket material, and soft section catabolite is little
Carboxylic acids, hard section catabolite are fatty amine and aminoacid, and after materials serve effect non-toxic products quilt can be gradually degraded to
Organism absorbs, it is to avoid the injury of second operation, can with prolonged application in organism.
Another object of the present invention is to provide the preparation that a kind of side chain contains the polyester type polyurethane material of Phosphorylcholine group
Method, the preparation process is simple, the diisocyanate of selection is the aliphatic diisocyanate containing multiple amido formates, drop
Solution product can be absorbed by organism, can for a long time be applied to organism as biomaterial etc..By prepared by this preparation method gathering
Ester type polyurethane material for it is complete synthesis, without potential animal derived, while with excellent biocompatibility and mechanical performance, and
With biological degradability, catabolite is nontoxic, can be absorbed by organism.
To achieve these goals, the present invention is adopted the following technical scheme that：
The invention provides a kind of side chain contains the polyester type polyurethane material of Phosphorylcholine group, molecular weight is more than 1.8
×105, membrane material fracture strength more than 42Mpa, elongation at break more than 600%, the adsorbance of protein be less than 2.5 μ g/cm2、
Degradation time is in 105-120d.
Present invention also offers a kind of preparation method of side chain group containing Phosphorylcholine polyester type polyurethane material, including with
Lower step：
(1) polyester-diol reacts with excess diisocyanate, obtains both-end isocyanate group prepolymer；
(2) chain extension is carried out to both-end isocyanate group prepolymer with the Phosphorylcholine compound of double amino, obtains side chain phosphorous
The polyurethane material of phatidylcholine group.
Preferably, the polyester-diol in step (1) be PGA, PLLA, PDLLA or poly- ε-oneself
Lactone, molecular weight is 400~5000, and preferred molecular weight is 500~3000.
Preferably, the diisocyanate in step (1) be 1,6- hexamethylene diisocyanates-BDO -1,6-
Hexamethylene diisocyanate (HDI-BDO-HDI), Isosorbide-5-Nitrae-tetramethylene diisocyanate-BDO-methylene of Isosorbide-5-Nitrae-four
Group diisocyanate (BDI-BDO-BDI).
Preferably, the concrete preparation method of HDI-BDO-HDI/BDI-BDO-HDI is different with BDO (BDO) and two
Cyanate is raw material, and molar ratio is：n-OH：N-NCO=1:4-30, reaction temperature 70-100 DEG C, response time 1-5h is closed
Into HDI-BDO-HDI.
Preferably, BDO and 1,6- hexamethylene diisocyanate (HDI) mol ratio are 1:12, under a dry nitrogen atmosphere
Reaction system in 4 hours response time, is cooled to room temperature by reaction, 80 DEG C of reaction temperature, obtains white solid, normal 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) mol ratio are 1:14, it is anti-under dry nitrogen atmosphere
Should, 80 DEG C of reaction temperature, response time 3h cools to room temperature and forms white solid, and normal hexane washs three times and removes excess
BDI, normal-temperature vacuum it is dry BDI-BDO-BDI.
Preferably, the addition of the excess diisocyanate described in step (1) is-NCO and-OH mol ratios are 2.0, plus
Enter mode and be dissolved in dimethyl sulfoxide (10g/30mL) for diisocyanate, mix with polyester-diol at normal temperatures
Preferably, reaction temperature is 80~100 DEG C in step (1), and the response time is 2.5~6.0h.
Preferably, the Phosphorylcholine compound of the double amino described in step (2) is Lys-PC (such as the institute of formula 6 for concrete structure
Show) or Lys-EG-PC (as shown in Equation 7).
Preferably, the addition of double amino Phosphorylcholine compounds is in step (2)：-NH2:- NCO=1:2 (mole
Than), reaction temperature is 10~20 DEG C, and the response time is 1.0~2.0h.
Preferably, preparation method includes the purification step to the phosphorous phatidylcholine group polyurethane material of side chain：With dichloromethane
Alkane or dioxane dissolve, the sedimentation of ice ether, sucking filtration, and normal-temperature vacuum drying is to constant weight.
Preferably, polyurethane material of the side chain obtained in step (2) containing Phosphorylcholine group is dissolved in benign organic molten
In agent, the solution that concentration is 4~7% (g/mL) is made into, Jing solvents volatilization film forming prepares polyurethane film material.
Preferably, good solvent is one kind or wherein several of chloroform, dichloromethane, chloroform, acetone or dioxane
The mixed solvent planted.Solvent volatilization temperature is 15~25 DEG C, normal pressure 60~90h of volatilization, is dried by normal-temperature vacuum, obtains membrane material
Material.
Preferably, the thickness of gained polyurethane film material membrane is 0.18~0.22mm.
Preferably, the polyurethane material can make the various dosage forms required for organism, particularly film, sponge, cartilage
Dosage form.
Preferably, the polyurethane material as organizational project renovating bracket material medical domain application.
Beneficial effects of the present invention
1. the soft section of material prepared by the present invention is the polyester of crystallization, and hard section has ordered structure and contains carbamate
Base and urine base, can form substantial amounts of hydrogen bond so that material has higher mechanical strength between hard section and between hard section and soft section,
And the complete hydrophobic of main chain, meets as degradation speed slower needed for organizational project renovating bracket material.The polyurethane material
Soft section catabolite be small carboxylic acid molecules, hard section catabolite be fatty amine and aminoacid, can be by after materials serve effect
Gradually it is degraded to non-toxic products to be absorbed by organism, it is to avoid the injury of second operation, can with prolonged application in organism.
2. the material Phosphorylcholine group that prepared by the present invention is located at the side chain of polymer, with higher hydrophilic, is giving birth to
The surface of material can be gathered in object under water environment, not only will not be adsorbed and precipitating proteins, will not also cause platelet to swash
Work cause the untoward reaction such as blood coagulation, it is to avoid thrombosis generation, with high biocompatibility.
3. preparation process is simple of the present invention, conventional method can meet to prepare and require, and can be prepared into various dosage forms, have
Higher commercialization prospect.
Description of the drawings
The shape need of Fig. 1, national regulations measuring mechanical property PU films.
The platelet viscosity SEM photograph of Fig. 2, sample A6.
Specific embodiment
With reference to specific embodiment, the invention will be further described.
Embodiment 1
By 0.01mol PLLA (PLLA, Mn=2000) (it is dissolved in dimethyl sulfoxide with 0.02mol HDI-BDO-HDI
In：10g/30mL) it is placed in there-necked flask, drying nitrogen protection, mechanical agitation, is warming up to 80 DEG C, after reaction 4.0h, is cooled to
18 DEG C, 0.01mol Lys-PC, stirring is added when system viscosity becomes cannot normally be stirred greatly, dichloromethane to be added in right amount, stirred
After mixing 1h, add dichloromethane to concentration about 15wt%, ice ether sedimentation, sucking filtration, normal-temperature vacuum drying obtains side chain and contain to constant weight
The polyurethane material A1 of Phosphorylcholine group.
The preparation of membrane material：A1 is dissolved in organic solvent dioxane, concentration is made into for the molten of 6.5% (g/mL)
Liquid, using Teflon mould in 25 DEG C of normal pressures volatilization 80h, after film is removed from mould Jing normal-temperature vacuums it is dry membrane material
Material, the thickness of the membrane material of gained is 0.20mm.
Embodiment 2
By 0.01mol poly-epsilon-caprolactone (PCL, Mn=2000) (it is dissolved in dimethyl sulfoxide with 0.02mol HDI-BDO-HDI
In：10g/30mL) it is placed in there-necked flask, drying nitrogen protection, mechanical agitation, is warming up to 85 DEG C, after reaction 3.5h, is cooled to
18 DEG C, 0.01mol Lys-PC, stirring is added when system viscosity becomes cannot normally be stirred greatly, dichloromethane to be added in right amount, stirred
After mixing 1h, add dichloromethane to concentration about 15wt%, ice ether sedimentation, sucking filtration, normal-temperature vacuum drying obtains side chain and contain to constant weight
The polyurethane material A2 of Phosphorylcholine group.
The preparation of membrane material：A2 is dissolved in organic solvent chloroform, concentration is made into for the molten of 5.5% (g/mL)
Liquid, using Teflon mould in 24 DEG C of normal pressures volatilization 90h, after film is removed from mould Jing normal-temperature vacuums it is dry membrane material
Material, the thickness of the membrane material of gained is 0.19mm.
Embodiment 3
By 0.01mol poly-epsilon-caprolactone (PCL, Mn=1500) (it is dissolved in dimethyl sulfoxide with 0.02mol HDI-BDO-HDI
In：10g/30mL) it is placed in there-necked flask, drying nitrogen protection, mechanical agitation, is warming up to 85 DEG C, after reaction 3.5h, is cooled to
18 DEG C, 0.01mol Lys-PC, stirring is added when system viscosity becomes cannot normally be stirred greatly, dichloromethane to be added in right amount, stirred
After mixing 1.5h, add dichloromethane to concentration about 15wt%, ice ether sedimentation, sucking filtration, normal-temperature vacuum drying obtains side chain to constant weight
Polyurethane material A3 containing Phosphorylcholine group.
The preparation of membrane material：A3 is dissolved in organic solvent chloroform, the solution that concentration is 4% (g/mL) is made into,
Using Teflon mould in 15 DEG C of normal pressures volatilization 60h, after film is removed from mould Jing normal-temperature vacuums it is dry membrane material,
The thickness of the membrane material of gained is 0.18mm.
Embodiment 4
By 0.01mol poly-epsilon-caprolactone (PCL, Mn=1000) (it is dissolved in dimethyl sulfoxide with 0.02mol BDI-BDO-BDI
In：10g/30mL) it is placed in there-necked flask, drying nitrogen protection, mechanical agitation, is warming up to 85 DEG C, after reaction 3.5h, is cooled to
18 DEG C, 0.01mol Lys-PC, stirring is added when system viscosity becomes cannot normally be stirred greatly, dichloromethane to be added in right amount, stirred
After mixing 1.5h, add dichloromethane to concentration about 15wt%, ice ether sedimentation, sucking filtration, normal-temperature vacuum drying obtains side chain to constant weight
Polyurethane material A4 containing Phosphorylcholine group.
The preparation of membrane material：A4 is dissolved in organic solvent dichloromethane, the solution that concentration is 5% (g/mL) is made into,
Using Teflon mould in 20 DEG C of normal pressures volatilization 65h, after film is removed from mould Jing normal-temperature vacuums it is dry membrane material,
The thickness of the membrane material of gained is 0.20mm.
Embodiment 5
By 0.01mol poly (l-lactic acid) (PLLA, Mn=1000) (be dissolved in dimethyl sulfoxide with 0.02mol BDI-BDO-BDI：
10g/30mL) it is placed in there-necked flask, drying nitrogen protection, mechanical agitation, is warming up to 80 DEG C, after reaction 4.0h, is cooled to 20
DEG C, add 0.01mol Lys-PC, stirring when system viscosity becomes cannot normally be stirred greatly, dichloromethane to be added in right amount, stirred
After 1.5h, add dichloromethane to concentration about 15wt%, ice ether sedimentation, sucking filtration, normal-temperature vacuum drying obtains side chain and contain to constant weight
Phosphorylcholine group can polyurethane material A5.
The preparation of membrane material：A5 is dissolved in organic solvent dichloromethane, the solution that concentration is 5% (g/mL) is made into,
Using Teflon mould in 20 DEG C of normal pressures volatilization 60h, after film is removed from mould Jing normal-temperature vacuums it is dry membrane material,
The thickness of the membrane material of gained is 0.21mm.
Embodiment 6
By 0.01mol poly-L-lactic acid (PLLA, Mn=1000) (be dissolved in dimethyl sulfoxide with 0.02mol BDI-BDO-BDI：
10g/30mL) it is placed in there-necked flask, drying nitrogen protection, mechanical agitation, is warming up to 80 DEG C, after reaction 4.0h, is cooled to 18
DEG C, add 0.01mol Lys-EG-PC, stirring when system viscosity becomes cannot normally be stirred greatly, dichloromethane to be added in right amount,
After stirring 1.5h, add dichloromethane to concentration about 15wt%, ice ether sedimentation, sucking filtration, normal-temperature vacuum drying obtains side to constant weight
Polyurethane material A6 of the chain containing Phosphorylcholine group.
The preparation of membrane material：A6 is dissolved in organic solvent dioxane, concentration is made into for the molten of 5.5% (g/mL)
Liquid, using Teflon mould in 22 DEG C of normal pressures volatilization 80h, after film is removed from mould Jing normal-temperature vacuums it is dry membrane material
Material, the thickness of the membrane material of gained is 0.22mm.
Embodiment 7
By the poly- D of 0.01mol, Pfansteihl (PDLLA, Mn=1000) (it is dissolved in dimethyl sulfoxide with 0.02mol BDI-BDO-BDI
In：10g/30mL) it is placed in there-necked flask, drying nitrogen protection, mechanical agitation, is warming up to 90 DEG C, after reaction 4.0h, is cooled to
18 DEG C, 0.01mol Lys-EG-PC, stirring is added when system viscosity becomes cannot normally be stirred greatly, dichloromethane to be added in right amount
Alkane, after stirring 1.5h, adds dichloromethane to concentration about 15wt%, the sedimentation of ice ether, sucking filtration, normal-temperature vacuum drying to constant weight,
Obtain polyurethane material A7 of the side chain containing Phosphorylcholine group.
The preparation of membrane material：A7 is dissolved in organic solvent-acetone, the solution that concentration is 5.5% (g/mL) is made into, is made
With Teflon mould in 25 DEG C of normal pressures volatilization 75h, after film is removed from mould Jing normal-temperature vacuums it is dry membrane material, institute
The thickness of the membrane material for obtaining is 0.20mm.
Embodiment 8
By 0.01mol polylactide (PGA, Mn=1000) (be dissolved in dimethyl sulfoxide with 0.02mol HDI-BDO-HDI：
10g/30mL) it is placed in there-necked flask, drying nitrogen protection, mechanical agitation, is warming up to 80 DEG C, after reaction 4.0h, is cooled to 18
DEG C, add 0.01mol Lys-PC, stirring when system viscosity becomes cannot normally be stirred greatly, dichloromethane to be added in right amount, stirred
After 2h, add dichloromethane to concentration about 15wt%, ice ether sedimentation, sucking filtration, normal-temperature vacuum drying obtains side chain phosphorous to constant weight
The polyurethane material A8 of phatidylcholine group.
The preparation of membrane material：A8 is dissolved in organic solvents, chloroform, the solution that concentration is 6% (g/mL) is made into, is used
Teflon mould in 23 DEG C of normal pressures volatilization 80h, by normal-temperature vacuum it is dry membrane material, film is removed from mould gained
Membrane material thickness be 0.22mm.
Analysis method
Analysis below method is used for all of embodiment, unless otherwise indicated.
Molecular weight and molecular weight distribution：Poly- ammonia is determined using Alpha type gel permeation chrommatographs (GPC) of Water companies of the U.S.
The molecular weight and molecualr weight distribution of ester, 4mg samples are dissolved in 2mL tetrahydrofurans, and with 0.4 μm of filtering head special chromatogram bottle is filled into
In, mobile phase speed is 0.5mL/min, and chromatograph box temperature is set to 35 DEG C, and standard specimen is monodisperse polystyrene.
Degradation property：In the membrane material immersion normal saline circular by a diameter of 10mm is cut into, 37 DEG C of constant temperature are maintained, with one
It is the state that the cycle observes membrane material, when membrane material produces fragment, loses mechanical performance, it is believed that degraded is completed, it is determined as degraded
Time.
Mechanical performance：The tensile property of the polyurethane film synthesized for test, using Dongguan, Guangdong Heng Yu Instrument Ltd.
The computermatic single-column tensile testing machine of HY939C types determine the tensile strength and elongation at break of film.Before on-test, first by sample
Product soak 3min in normal saline, then make dumbbell shape model, and the method specified according to GB GB/T1040.2-2006 is entered
Row is determined, as shown in Figure 1.
Water contact angle measurement：Water contact angle test is carried out in thin film with air contact one side, distilled water (droplet size:2μ
L), temperature:25 DEG C, contact angle numerical value of the water drop contact surface in about 1min is determined, take 5 points and make meansigma methodss.
Protein adsorbance:The polymeric film of 1cm × 1cm is soaked in the phosphate buffer of pH=7.4 (PBS) and is filled
Divide swelling equilibrium, during the bovine serum albumen solution (BSA) that concentration is 0.6g/L is placed on after taking-up, in 37 DEG C of water bath with thermostatic control
Middle immersion 2h.Polymeric film is taken out after end, with the abundant drip washing of PBS buffer solution 3 times.Then with the SDS solution of 1% (w/w)
(PBS solution) is cleaned by ultrasonic 20min, accurately pipettes same volume cleanout fluid in tool plug test tube, adds Micro-BcATMEgg
(PierceInc., Rockford, 23235), are sufficiently mixed white matter detection kit working solution, sealing, 60 DEG C of constant temperature water bath 1h.
Finally naturally cool to room temperature, using ultraviolet-visible spectrophotometer at 562nm wavelength mensuration absorbance, according to standard
Curve calculates adsorbance, takes the meansigma methodss of 3 samples.
Platelet adhesion reaction is tested：Fresh blood is extracted from healthy rabbit hearts, the citric acid that mass fraction is 3.8% is added
Sodium solution is 9 as the ratio of anticoagulant, whole blood and anticoagulant:1, the whole blood for adding anticoagulant is put in centrifuge, just
It is 1400r/min that secondary centrifugation arranges rotating speed, and 10min is centrifuged；Then supernatant recentrifuge is drawn, arranging rotating speed is still
1400r/min, is centrifuged 15min, and the supernatant is platelet poor plasma (PRP), draws about 3/4 supernatant and discards, and residue is
For PRP；By modified polyurethane film (1.0 × 1.0cm2) 24 orifice plates are positioned over, first it is immersed in the PBS bufferings of PH=7.4
4h in solution, then under 37 DEG C of constant temperature, in PRP solution 1h is incubated.Take the film out, with PBS buffer solution 3 times are rinsed repeatedly
To remove unadsorbed platelet, then film is immersed in again the blood of 30min fixation surfaces in 2.5% glutaraldehyde PBS solution
Platelet.And then by film be sequentially placed in the ethanol water of variable concentrations gradient (50,60,70,80,90,100%) carry out by
Level dehydration, soaks 30min in the solution of every kind of concentration, is finally dried at room temperature, metal spraying, using S-4800 types SEM (Japan
Hitachi, Ltd) observation film surface platelet adhesion reaction situation.
The performance of polyurethane film material of the side chain containing Phosphorylcholine group is as shown in table 1 in embodiment 1-8.
The platelet adhesion stereoscan photograph of polyurethane film material (A6) of the side chain containing Phosphorylcholine group in embodiment 6
As shown in Figure 1.
The biological assessment test of polyurethane film material of the side chain containing Phosphorylcholine group is as shown in table 2 in embodiment 1-8.
The side chain of table 1 contains mechanical performance, surface hydrophilicity and the protein adsorbance of the polyurethane film of Phosphorylcholine group
As shown in Table 1, the poly- ammonia material of side chain prepared by this patent is provided method containing Phosphorylcholine group have compared with
High molecular weight, its corresponding membrane material has very high fracture strength, meets bio-tissue engineering renovating bracket material
Demand.With the increase of hard section (segment of amido-containing acid ester base and urine base) content, fracture strength increases.The degraded of membrane material
Time is all higher than 15 weeks, up to 17 weeks, examine prepared by film it is relatively thin, specific surface area is larger, if prepared by dosage form
Shape into required for organizational project renovating bracket material, its degradation time can be greatly increased.The degradation time Phosphorylcholine of film
Content and urethane raw species it is relevant, modified polyurethane material degree of crystallinity is higher, degrade it is slower.Its water contact angle and egg
The rule of white matter adsorbance is consistent, i.e., contact angle is less, and surface hydrophilicity is higher, and protein adsorbance is less.With phosphinylidyne
The increase of choline group content, the Phosphorylcholine group of side chain forms hydrophilic interface due to the mutual aggressiveness of hydrophilic in water,
Simultaneously because the high biocompatibility of Phosphorylcholine group, its adsorbance to protein is also reduced, greatly improved medical
The biocompatibility of polyurethane material.The adsorbance of the protein of the sample in this patent embodiment is less than 2.2 μ g/cm2, or even
Less than 1.5 μ g/cm2, show that the material shows splendid biocompatibility, organism can be long-term used in.
It will be noted from fig. 1 that the platelet counts of Phosphorylcholine modified polyurethane film surface adhesion are seldom, and big portion
Point platelet is not assembled, and remains in that original pattern.Show that the material has excellent low platelet Adhesion property.
Test biology of polyurethane film material (sample A1-A8) of the side chain of table 2. containing Phosphorylcholine group
| Antibacterial is tested | It is aseptic | GB/T14233.2-2005 chapter 2 |
| Cytotoxicity | <I levels | GB/T14233.2-2005 |
| Intradermal zest | Stimulate without Intradermal | 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 the membrane material prepared by embodiment of the present invention 1-8 shows each reality
Applying example can obtain nontoxic, non-stimulated, good biocompatibility and meet the material of Clinical practice requirement.
Although giving detailed description to the specific embodiment of the present invention above and illustrating, it should be noted that
We can carry out various equivalent changes and modification to above-mentioned embodiment according to the conception of the present invention, and the function produced by it is made
With still without departing from description and accompanying drawing covered it is spiritual when, all should be within protection scope of the present invention.
Claims (10)
1. a kind of side chain contains Phosphorylcholine group polyester type polyurethane material, it is characterised in that：Described PAUR
Material soft section is the polyester of crystallization, and hard section contains carbamate groups, and polyurethane material molecular weight is more than 1.8 × 105, membrane material
Material fracture strength is less than 2.2 μ g/cm more than 42Mpa, elongation at break more than the adsorbance of 600%, protein2, degradation time
In 105-120d.
2. a kind of preparation method of side chain group containing Phosphorylcholine polyester type polyurethane material, it is characterised in that：
Comprise the following steps：
(1) polyester-diol reacts 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 side chain containing phosphinylidyne
The polyurethane material of choline group.
3. preparation method according to claim 2, it is characterised in that：Polyester-diol described in step (1) is the friendship of poly- second
Ester, PLLA, PDLLA or poly-epsilon-caprolactone, described polyester-diol molecular weight is 400~5000, preferably
Molecular weight is 500~3000.
4. preparation method according to claim 2, it is characterised in that：Described diisocyanate in step (1) is 1,
6- hexamethylene diisocyanates-BDO -1,6- hexamethylene diisocyanates, the Carbimide. of Isosorbide-5-Nitrae-tetramethylene two
Ester -1,4- butanediol -1,4- tetramethylene diisocyanates.
5. preparation method according to claim 2, it is characterised in that：Excess diisocyanate described in step (1)
Addition is-NCO and-OH mol ratios are 2.0, and reaction temperature is 80~100 DEG C, and the response time is 2.5~6.0h.
6. preparation method according to claim 2, it is characterised in that：The Phosphorylcholine of the double amino described in step (2)
Compound is that concrete structure is Lys-PC (as shown in Equation 6) or Lys-EG-PC (as shown in Equation 7), Phosphorylcholine compound addition
For：-NH2It is 1 with-NCO mol ratios:2, reaction temperature is 10~20 DEG C, and the response time is 1.0~2.0h,
7. preparation method according to claim 2, it is characterised in that：Described preparation method is included to the step (2)
The purification step of side chain group containing Phosphorylcholine polyurethane material：Dissolved with dichloromethane or dioxane, the sedimentation of ice ether is taken out
Filter, normal-temperature vacuum drying is to constant weight.
8. preparation method according to claim 2, it is characterised in that：The side chain obtained in step (2) is contained into Phosphorylcholine
The polyurethane material of group is dissolved in organic solvent, is made into the solution that concentration is 4~7% (g/mL), Jing solvents volatilization film forming
Polyurethane film material is prepared, described good solvent is chloroform, dichloromethane, chloroform, acetone or dioxane
A kind of or wherein several mixed solvent, solvent volatilization temperature is 15~25 DEG C, normal pressure 60~90h of volatilization, by normal-temperature vacuum
It is dried, obtains polyurethane film material, the thickness of the membrane material of gained is 0.18~0.22mm.
9. according to the arbitrary described preparation method of claim 2-8, it is characterised in that：Preparing gained polyurethane material can make
Various dosage forms required for organism, particularly film, sponge, cartilage dosage form.
10. polyester type polyurethane material of the side chain according to claim 1 containing Phosphorylcholine group makees organizational project reparation
Application of the timbering material in medical domain.
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| CN107216435A (en) * | 2017-06-26 | 2017-09-29 | 山东师范大学 | A kind of new side chain is the poly- of phosphatide polyethylene glycol（Urethane urea）And preparation method thereof |
| CN109054485A (en) * | 2018-06-27 | 2018-12-21 | 佛山市博新生物科技有限公司 | A kind of antibacterial coating liquid and its preparation method and application |
| CN111234170A (en) * | 2020-01-15 | 2020-06-05 | 中国科学院长春应用化学研究所 | Polyurethane material, preparation method thereof and application of polyurethane material in artificial meniscus material |
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| 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 |
| CN114213615A (en) * | 2021-12-29 | 2022-03-22 | 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 |
| CN115417963A (en) * | 2022-09-19 | 2022-12-02 | 苏州百孝医疗科技有限公司 | Biocompatible polycarbonate polyurethane, preparation method and application |
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| WO2021254348A1 (en) * | 2020-06-16 | 2021-12-23 | 杭州启明医疗器械股份有限公司 | Super-lubricative coating for interventional valve delivery system and preparation method therefor |
| 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 |
| CN114213615A (en) * | 2021-12-29 | 2022-03-22 | 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 |
| 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 |
| CN115417963A (en) * | 2022-09-19 | 2022-12-02 | 苏州百孝医疗科技有限公司 | Biocompatible polycarbonate polyurethane, preparation method and application |
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