CN114085348B - Block copolymer, preparation method and application thereof - Google Patents
Block copolymer, preparation method and application thereof Download PDFInfo
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- CN114085348B CN114085348B CN202111448703.7A CN202111448703A CN114085348B CN 114085348 B CN114085348 B CN 114085348B CN 202111448703 A CN202111448703 A CN 202111448703A CN 114085348 B CN114085348 B CN 114085348B
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- 229920001400 block copolymer Polymers 0.000 title claims abstract description 26
- 238000002360 preparation method Methods 0.000 title claims abstract description 10
- 210000000988 bone and bone Anatomy 0.000 claims abstract description 23
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 60
- 239000000243 solution Substances 0.000 claims description 56
- 229920000520 poly(3-hydroxybutyrate-co-3-hydroxyvalerate) Polymers 0.000 claims description 39
- RRAMGCGOFNQTLD-UHFFFAOYSA-N hexamethylene diisocyanate Chemical compound O=C=NCCCCCCN=C=O RRAMGCGOFNQTLD-UHFFFAOYSA-N 0.000 claims description 35
- 239000002202 Polyethylene glycol Substances 0.000 claims description 34
- 229920001223 polyethylene glycol Polymers 0.000 claims description 34
- 239000005057 Hexamethylene diisocyanate Substances 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 18
- 238000002156 mixing Methods 0.000 claims description 13
- 239000011259 mixed solution Substances 0.000 claims description 12
- 239000000463 material Substances 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 230000035484 reaction time Effects 0.000 claims description 4
- 230000008439 repair process Effects 0.000 claims description 3
- 239000002994 raw material Substances 0.000 claims 1
- 230000035876 healing Effects 0.000 abstract description 15
- 230000015556 catabolic process Effects 0.000 abstract description 3
- 238000006731 degradation reaction Methods 0.000 abstract description 3
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- 229920000642 polymer Polymers 0.000 description 12
- 229910052757 nitrogen Inorganic materials 0.000 description 9
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- 238000010586 diagram Methods 0.000 description 8
- 238000001228 spectrum Methods 0.000 description 8
- 239000012043 crude product Substances 0.000 description 7
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- REKYPYSUBKSCAT-UHFFFAOYSA-N 3-hydroxypentanoic acid Chemical compound CCC(O)CC(O)=O REKYPYSUBKSCAT-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- 238000002329 infrared spectrum Methods 0.000 description 4
- 229920001427 mPEG Polymers 0.000 description 4
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
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- 238000005406 washing Methods 0.000 description 3
- WHBMMWSBFZVSSR-UHFFFAOYSA-M 3-hydroxybutyrate Chemical compound CC(O)CC([O-])=O WHBMMWSBFZVSSR-UHFFFAOYSA-M 0.000 description 2
- WHBMMWSBFZVSSR-UHFFFAOYSA-N R3HBA Natural products CC(O)CC(O)=O WHBMMWSBFZVSSR-UHFFFAOYSA-N 0.000 description 2
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 2
- 229920001577 copolymer Polymers 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
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- 238000007490 hematoxylin and eosin (H&E) staining Methods 0.000 description 2
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- 210000000963 osteoblast Anatomy 0.000 description 2
- 230000001737 promoting effect Effects 0.000 description 2
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- RGCKGOZRHPZPFP-UHFFFAOYSA-N alizarin Chemical compound C1=CC=C2C(=O)C3=C(O)C(O)=CC=C3C(=O)C2=C1 RGCKGOZRHPZPFP-UHFFFAOYSA-N 0.000 description 1
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- 239000010936 titanium Substances 0.000 description 1
- 238000002604 ultrasonography Methods 0.000 description 1
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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
- C08G18/48—Polyethers
- C08G18/4833—Polyethers containing oxyethylene units
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/14—Macromolecular materials
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
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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
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- C08G18/40—High-molecular-weight compounds
- C08G18/4009—Two or more macromolecular compounds not provided for in one single group of groups C08G18/42 - C08G18/64
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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
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- 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
- C08G18/4283—Hydroxycarboxylic acid or ester
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Abstract
The application relates to a block copolymer, a preparation method and application thereof, belonging to the technical field of high polymer materials. The structural formula of the block copolymer is shown as the following formula:
wherein n is 100-500. The block copolymer has good hydrophilicity and faster degradation speed, and can improve the bone healing speed.
Description
Technical Field
The application relates to the technical field of solar cell preparation, in particular to a block copolymer, a preparation method and application thereof.
Background
The copolymer (PHBV) of 3-hydroxybutyrate and 3-hydroxyvalerate as a piezoelectric material is a high molecular organic matter and has been applied in the fields of orthopedics and other medical disciplines for many years. The high molecular organic matter has certain biodegradability, biocompatibility and piezoelectric performance similar to that of human bone, and may be used in modifying the surface of titanium alloy rack.
The piezoelectric property of PHBV provides a negatively charged surface potential at the surface of the material, and recent studies indicate that the negative potential at the surface of the material is favorable for mineralization and osteogenic differentiation of cells.
However, it has problems such as slow degradation rate and poor hydrophilicity, and the effect of promoting bone healing is desired to be improved.
Disclosure of Invention
In view of the deficiencies of the prior art, the embodiments of the present application aim to provide a block copolymer, a preparation method and applications thereof, which have good hydrophilicity and can improve the bone healing speed.
In a first aspect, embodiments herein provide a block copolymer having a structural formula shown in the following formula:
wherein n is 100-500.
In some embodiments herein, the block copolymer comprises the following starting materials: polyethylene glycol, PHBV and hexamethylene diisocyanate.
In some examples of the present application, the HV mass fraction was 10% to 20% based on the total mass of PHBV.
In some embodiments of the present application, the polyethylene glycol has an average molecular weight of 5000 to 20000.
In a second aspect, the present application provides a method for preparing a block copolymer, comprising the steps of: firstly, mixing a hexamethylene diisocyanate solution and a polyethylene glycol solution, and carrying out a first-step reaction to obtain a first mixed solution. Then adding the PHBV solution into the first mixed solution, mixing and carrying out the second step reaction.
In some examples of the present application, both the first and second reactions are carried out at room temperature in the absence of light.
In some embodiments of the present application, the first step reaction time is 1h or more; the time of the second step reaction is1 day or more.
In some embodiments of the present application, the mass ratio of polyethylene glycol to PHBV is1 (1-2); the mass volume ratio of the polyethylene glycol to the hexamethylene diisocyanate is (5-10) and 100 g/mu L.
In some examples herein, hexamethylene diisocyanate was mixed with methylene chloride to give a hexamethylene diisocyanate solution; mixing polyethylene glycol and dichloromethane to obtain a polyethylene glycol solution; dripping a polyethylene glycol solution into a hexamethylene diisocyanate solution at the speed of 0.5-1.5mL/min under the stirring condition, and reacting at room temperature in a dark place for 4 hours or more to obtain a first mixed solution; mixing PHBV with dichloromethane to obtain a PHBV solution; dropping the PHBV solution into the first mixed solution at the speed of 2-10mL/min, and reacting at room temperature in the dark for 2 days or more.
In a third aspect, the present application provides a use of the above block copolymer in the preparation of a bone repair material.
The block copolymer, the preparation method and the application thereof provided by the embodiment of the application have the beneficial effects that: the hexamethylene diisocyanate is used for connecting the polyethylene glycol and the PHBV to form a block polymer, and the block polymer has good hydrophilicity and can improve the bone healing speed.
Drawings
To more clearly illustrate the technical solutions of the embodiments of the present application, the drawings needed in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present application and therefore should not be considered as limiting the scope, and those skilled in the art can also obtain other related drawings based on the drawings without inventive efforts.
FIG. 1 is a flow diagram of a process for preparing block copolymers provided herein;
FIG. 2 is an IR spectrum of PHBV-PEG20k provided in example 1 of the present application;
FIG. 3 is an IR spectrum of PHBV-PEG5k provided in example 2 of the present application;
FIG. 4 is a C13 spectrum of PHBV-PEG20k provided in example 1 of the present application;
FIG. 5 is a C13 spectrum of PHBV-PEG5k provided in example 2 of the present application;
FIG. 6 is a spectrum of H1 of PHBV-PEG20k provided in example 1 of the present application;
FIG. 7 is a H1 spectrum of PHBV-PEG5k provided in example 2 herein;
FIG. 8 is a nuclear magnetic resonance image of PHBV-PEG20k provided in example 1 of the present application;
FIG. 9 is a nuclear magnetic resonance image of PHBV-PEG5k provided in example 2 of the present application;
FIG. 10 is a schematic diagram of the water contact angle of PHBV-PEG20k provided in example 1 of the present application;
FIG. 11 is a schematic diagram showing the water contact angle of PHBV-PEG5k provided in example 2 herein;
FIG. 12 is a piezoelectric test characterization plot of a polymer;
FIG. 13 is a first schematic representation of the bone healing function of a polymer;
FIG. 14 is a second schematic illustration of the bone healing function of the polymer;
FIG. 15 is a third schematic representation of the bone healing function of the polymer;
fig. 16 is a fourth schematic of the bone healing function of the polymer.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present application more apparent, the technical solutions of the present application are described below clearly and completely.
In the prior art, PHBV can promote osteogenic differentiation of cells to a certain extent, but the degradation speed is low, the hydrophilicity is poor, and the effect of promoting bone healing is poor.
In order to solve the above problems, the present application provides a block copolymer which has good hydrophilicity, can increase the speed of bone healing, and can be used to prepare a bone repair material.
FIG. 1 is a flow chart of a process for preparing a block copolymer as provided herein, referring to FIG. 1, the preparation method comprises the following steps:
s110, preparing a hexamethylene diisocyanate (HMDI) solution: mixing hexamethylene diisocyanate with a solvent to obtain a hexamethylene diisocyanate solution. Alternatively, the hexamethylene diisocyanate is transferred to a nitrogen-protected vessel, and a solvent (e.g., dry methylene chloride) is added and mixed to obtain a hexamethylene diisocyanate solution.
Alternatively, the volume concentration of the hexamethylene diisocyanate solution is 4-6. Mu.L/mL. For example: the volume concentration of the hexamethylene diisocyanate solution was 4. Mu.L/mL, 5. Mu.L/mL, or 6. Mu.L/mL.
In other embodiments, the solvent may also be benzene, toluene, chlorobenzene, etc., which is not limited in this application.
S120, preparing a polyethylene glycol (PEG) solution: mixing polyethylene glycol with a solvent to obtain a polyethylene glycol solution. Alternatively, polyethylene glycol is placed in a container, an air exhaust valve is added, vacuum is pumped for 2 hours while heating at 80 ℃, and then nitrogen is filled until the temperature is cooled to room temperature. After cooling, the solvent (e.g., dry dichloromethane) is transferred to a vessel and dissolved with shaking until ready for use.
Alternatively, the polyethylene glycol has an average molecular weight of from 5000 to 20000. For example: the polyethylene glycol has an average molecular weight of 5000, 10000, 15000 or 20000. The mass volume concentration of the polyethylene glycol solution is 0.1-0.4g/mL. For example: the mass volume concentration of the polyethylene glycol solution is 0.1g/mL, 0.2g/mL, 0.3g/mL or 0.4g/mL.
S130, mixing the hexamethylene diisocyanate solution with the polyethylene glycol solution, and carrying out the first-step reaction to obtain a first mixed solution. Wherein the first-step reaction is carried out at room temperature in a dark condition, and the time of the first-step reaction is 1h or more.
Optionally, the polyethylene glycol solution obtained in step S120 is transferred to a constant pressure dropping funnel, is kept under nitrogen protection, is dropped into the hexamethylene diisocyanate solution obtained in step S110 at a speed of 0.5-1.5mL/min under stirring, and is reacted at room temperature in a dark place for 4 hours or more, so as to obtain a first mixed solution.
Illustratively, the stirring speed is 600rpm, 700rpm, 800rpm, or 1000rpm; the dropping speed of the polyethylene glycol solution is 0.5mL/min, 0.8mL/min, 1.0mL/min, 1.2mL/min or 1.5mL/min; the reaction time is 4h, 5h, 6h, 8h or 10h in a dark place.
Alternatively, the mass-to-volume ratio of polyethylene glycol to hexamethylene diisocyanate is (5-10): 100 g/. Mu.L. For example, the mass volume ratio of polyethylene glycol to hexamethylene diisocyanate is 5g, 100. Mu.L, 6 g.
S140, preparing a PHBV (copolymer of 3-hydroxybutyrate and 3-hydroxyvalerate) solution: mixing the PHBV with a solvent to obtain a PHBV solution. Alternatively, PHBV was placed in a container, equipped with a bleed valve, heated at 80 ℃ while evacuating for 5h, then purged with nitrogen until cooled to room temperature. After cooling, the solvent (e.g., dry dichloromethane) is transferred to the solvent and dissolved with shaking until ready for use.
Optionally, the HV mass fraction is 10% to 20% based on the total mass of PHBV. For example: HV accounts for 10%, 12%, 14%, 16%, 18% or 20% by mass. The mass volume concentration of the PHBV solution is 0.1-0.4g/mL. For example: the mass volume concentration of the PHBV solution is 0.1g/mL, 0.2g/mL, 0.3g/mL or 0.4g/mL.
S150, adding the PHBV solution into the first mixed solution, mixing and carrying out the second-step reaction. Wherein the second step reaction is carried out under the condition of room temperature and light shielding, and the time of the second step reaction is1 day or more.
Optionally, the PHBV solution obtained in the step S140 is transferred to a constant pressure dropping funnel, the PHBV solution is dropped into the first mixed solution at a speed of 2-10mL/min, and the mixture is reacted at room temperature in a dark place for 2 days or more.
Illustratively, the stirring speed is 600rpm, 700rpm, 800rpm, or 1000rpm; the dropping speed of the PHBV solution is 2mL/min, 4mL/min, 6mL/min, 8mL/min or 10mL/min; the reaction time is 2 days, 3 days, 4 days or 5 days in a dark place.
Optionally, the mass ratio of the polyethylene glycol to the PHBV is1 (1-2). For example, the mass ratio of the polyethylene glycol to the PHBV is 1.
And S160, after the reaction is finished, removing the solvent to obtain a crude product, dissolving the precipitate to obtain a refined product, and washing to obtain the block copolymer.
Alternatively, after the reaction is completed, methylene chloride is removed by rotary evaporation to obtain a crude product, the crude product is dissolved in 80mL of tetrahydrofuran, then 1L of distilled water is dropwise added into the solution while stirring to obtain a refined product, the refined product is filtered, washed with distilled water for 3 times, and dried in vacuum at 50 ℃ overnight to obtain the block copolymer.
The structural formula of the block copolymer is shown as the following formula:
wherein n is 100-500. It should be noted that the value of n is consistent with the polymerization degree of polyethylene glycol, and x and y are consistent with the structural formula of PHBV. The block copolymer has good hydrophilicity, and can improve the bone healing speed.
In order to make the objects, technical solutions and advantages of the embodiments of the present application clearer, the technical solutions in the embodiments of the present application will be clearly and completely described below. The examples, in which specific conditions are not specified, were carried out according to conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are conventional products which are not indicated by manufacturers and are commercially available.
Example 1
A method for preparing a block copolymer, comprising the steps of:
(1) Placing 8.0g of mPEG-20k (manufacturer: solarbio, product number: 25322-68-3) in a 50mL round-bottom flask, adding an air suction valve, heating at 80 ℃ while vacuumizing for 2h, and then filling nitrogen until the temperature is cooled to room temperature; after cooling, 40mL of dry dichloromethane were transferred to a round-bottom flask, dissolved with shaking and subsequently transferred to an isobaric dropping funnel, protected with nitrogen, until needed.
(2) mu.L of hexamethylene diisocyanate (HMDI, manufactured by BENZE, cat. No. 822-06-0) was transferred to a nitrogen-protected round-bottomed flask, and 20mL of dried methylene chloride was added and mixed to obtain a HMDI solution.
(3) Dropping a dichloromethane solution of mPEG-20k into the HMDI solution at the speed of 1mL/min under the stirring of 800rpm, and reacting for 6 hours at room temperature in a dark place to obtain mPEG 20k -NCO。
(4) 13.3g of PHBV (manufacturer: ningbo Tianan biomaterial Co., ltd., product number: 80181-31-3) is placed in a 100mL round-bottom flask, an air exhaust valve is added, heating is carried out at 80 ℃ while vacuumizing is carried out for 5h, and then nitrogen is filled until the temperature is cooled to room temperature; after cooling, 80mL of dry dichloromethane were transferred to a round bottom flask, dissolved with shaking and then transferred to a constant pressure dropping funnel.
(5) Dropping mPEG at a rate of 5mL/min 20k in-NCO solution, react for 3 days at room temperature in the dark.
(6) And after the reaction is finished, removing dichloromethane by rotary evaporation to obtain a crude product, dissolving the crude product by using 80mL of tetrahydrofuran, dropwise adding 1L of distilled water into the solution while stirring to obtain a refined product, filtering, washing by using distilled water for 3 times, and performing vacuum drying at 50 ℃ overnight to obtain the PHBV-PEG20k.
Example 2
A method for preparing a block copolymer, comprising the steps of:
(1) 2.5g of mPEG-5k (manufacturer: sigma, cat # 31961-02-1) is placed in a 50mL round-bottom flask, an air exhaust valve is added, heating is carried out at 80 ℃, vacuum pumping is carried out for 2 hours, and then nitrogen is filled until the temperature is cooled to room temperature; after cooling, 40mL of dry dichloromethane were transferred to a round-bottom flask, dissolved with shaking and subsequently transferred to a dropping funnel under constant pressure, protected with nitrogen, until used.
(2) 130. Mu.L of hexamethylene diisocyanate (HMDI, manufactured by BENZE, cat. No. 822-06-0) was transferred to a nitrogen-protected round-bottomed flask, and 20mL of dried methylene chloride was added and mixed to obtain a HMDI solution.
(3) Dropping the dichloromethane solution of mPEG-5k into the HMDI solution at the speed of 1mL/min under the stirring of 800rpm, and reacting for 6 hours at room temperature in a dark place to obtain mPEG 5k -NCO。
(4) Placing 10g of PHBV (manufacturer: ningbo Tianan biomaterial Co., ltd., product number: 80181-31-3) into a 100mL round-bottom flask, adding an air exhaust throttle, heating at 80 ℃ and vacuumizing for 5 hours, and then filling nitrogen until the temperature is cooled to room temperature; after cooling, 80mL of dry dichloromethane were transferred to a round-bottom flask, dissolved by shaking and then transferred to a dropping funnel with constant pressure.
(5) Dropping mPEG at a rate of 5mL/min 5k in-NCO solution, react for 3 days at room temperature in the dark.
(6) And after the reaction is finished, removing dichloromethane by rotary evaporation to obtain a crude product, dissolving the crude product by using 80mL of tetrahydrofuran, dropwise adding 1L of distilled water into the solution while stirring to obtain a refined product, filtering, washing by using distilled water for 3 times, and performing vacuum drying at 50 ℃ overnight to obtain PHBV-PEG5k.
Test example 1
FIG. 2 iS a graph showing a Si 10 FT-IR spectrometer in example 1 of the present application, in which the wave number iS 400 to 4000cm -1 PHBV-PEG20k infrared spectrum with spectrometer resolution; FIG. 3 is an IR spectrum of PHBV-PEG5k (Experimental condition: 4cm, nygaku Co., ltd.) provided in example 2 of the present application -1 The signal-to-noise ratio is 50000. ) (ii) a FIG. 4 is a C13 spectrum of PHBV-PEG20k provided in example 1 of the present application; FIG. 5 is a C13 spectrum of PHBV-PEG5k provided in example 2 of the present application; FIG. 6 is a spectrum of H1 of PHBV-PEG20k provided in example 1 of the present application; FIG. 7 is a spectrum of H1 of PHBV-PEG5k provided in example 2 of the present application; FIG. 8 is the NMR chart of PHBV-PEG20k provided in example 1 of the present application; FIG. 9 is the NMR chart of PHBV-PEG5k provided in example 2 of the present application.
As can be seen from fig. 2, 4, 6 and 8, the structural formula of PHBV-PEG20k provided in example 1 is:
wherein n is 456, HV accounts for 12% by mass and BV accounts for 88% by mass based on the total mass of PHBV.
As can be seen from fig. 3, 5, 7 and 9, the structural formula of PHBV-PEG5k provided in example 2 is:
wherein n is 114, the HV mass ratio is 12 percent and the BV mass ratio is 88 percent based on the total mass of the PHBV.
Test example 2
FIG. 10 is a schematic diagram of the water contact angle of PHBV-PEG20k provided in example 1 of the present application; FIG. 11 is a schematic diagram of the water contact angle of PHBV-PEG5k provided in example 2 of the present application (experimental conditions: test by water contact tester). The water contact angle of PHBV is 65-70 degrees, and comparing with FIG. 10 and FIG. 11, it can be seen that the block copolymer provided in the examples of the present application has a smaller water contact angle and better hydrophilicity than PHBV.
FIG. 12 shows the piezoelectric test characteristics of the polymer (experimental conditions: detection on a piezoelectric detector). As can be seen from FIG. 12, the negative potential of PHBV-PEG20k provided by the present application is more obvious, and is more favorable for osteogenic differentiation of cells.
Test example 3
After staining cytoskeletal protein beta actin with immunofluorescence, pictures were taken by a confocal laser microscope to obtain fig. 13, and fig. 13 is a first schematic diagram of the bone healing function of the polymer. As can be seen from FIG. 13, the PHBV-PEG20k material has good cell ductility after being co-cultured with the backbone protein compared with the traditional PHBV material, and has no obvious difference with the control group.
After 2h/d of ultrasonic stimulation with the frequency of 1MHz and the intensity of 30mW/cm < 2 >, the alizarin red is stained after 30d of osteoblast culture to obtain a graph 14, and as can be seen from the graph 14, the osteogenic capacity of the histiocyte co-cultured by the PHBV-PEG20k and the osteoblast is obviously enhanced.
After a rat is made into a tibial bone defect model, corresponding materials are implanted, ultrasonic stimulation is given, and after 3 months, a specimen is taken out to be subjected to computer test to obtain a graph 15, wherein the graph 15 is a third schematic diagram of the bone healing function of the polymer. As can be seen from FIG. 16, the MicroCT results in the rat bone defect model show that the PHBV-PEG20k endophyte group has a significantly better bone formation ability than the Ti endophyte group even when the same ultrasonic stimulation is given.
After the rat is made into a tibial bone defect model, the corresponding material is implanted, ultrasonic stimulation is given, a specimen section is taken after 3 months, the density of the trabecular bone is observed by HE staining to obtain a figure 16, and the figure 16 is a fourth schematic diagram of the bone healing function of the polymer. As can be seen in fig. 16, HE staining results showed that PHBV-PEG20k metaphyseal trabecular density and trabecular strength were optimal under ultrasound stimulation.
In conclusion, the block polymer provided by the embodiment of the application has better hydrophilicity, is easier to degrade and has better bone healing function.
The embodiments described above are some, but not all embodiments of the present application. The detailed description of the embodiments of the present application is not intended to limit the scope of the claimed application, but is merely representative of selected embodiments of the application. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present application.
Claims (6)
1. The application of a block copolymer in preparing a bone repair material is characterized in that the structural formula of the block copolymer is shown as the following formula:
wherein n is 100-500;
the block copolymer comprises the following raw materials: polyethylene glycol, PHBV and hexamethylene diisocyanate; based on the total mass of PHBV, the mass proportion of HV is 10-20%;
the mass ratio of the polyethylene glycol to the PHBV is1 (1-2); the mass volume ratio of the polyethylene glycol to the hexamethylene diisocyanate is (5-10): 100 g/mu L.
2. Use according to claim 1, wherein the polyethylene glycol has an average molecular weight of 5000-20000.
3. Use according to claim 1 or 2, characterized in that the preparation of the block copolymer comprises the following steps:
firstly, mixing a hexamethylene diisocyanate solution and a polyethylene glycol solution, and carrying out a first-step reaction to obtain a first mixed solution;
then adding the PHBV solution into the first mixed solution, mixing and carrying out the second step reaction.
4. The use according to claim 3, wherein the first and second reactions are carried out at room temperature in the absence of light.
5. The use of claim 4, wherein the reaction time of the first step is 1h or more; the time of the second step reaction is1 day or more.
6. Use according to claim 3, characterized in that hexamethylene diisocyanate is mixed with methylene chloride to obtain a hexamethylene diisocyanate solution;
mixing polyethylene glycol and dichloromethane to obtain a polyethylene glycol solution;
dripping the polyethylene glycol solution into the hexamethylene diisocyanate solution at the speed of 0.5-1.5mL/min under the stirring condition, and reacting for 4 hours or more at room temperature in a dark place to obtain a first mixed solution;
mixing PHBV with dichloromethane to obtain a PHBV solution;
dropping the PHBV solution into the first mixed solution at the speed of 2-10mL/min, and reacting at room temperature in a dark place for 2 days or more.
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Inventor after: Zhang Weilin Inventor after: Zhang Zhiyu Inventor after: Zhao Wei Inventor after: Zhao Duoyi Inventor before: Zhang Zhiyu Inventor before: Zhang Weilin Inventor before: Zhao Wei Inventor before: Zhao Duoyi |
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Effective date of registration: 20231019 Address after: 524001 South 57, people's Road South, Xiashan District, Zhanjiang, Guangdong Patentee after: AFFILIATED HOSPITAL OF GUANGDONG MEDICAL University Address before: 110033 1-2, No. 4-32, Chongshan East Road, Huanggu District, Shenyang City, Liaoning Province Patentee before: Zhang Weilin |