CN108485280A - Rgd peptide grafting is poly-（Malaysia acyl hexamethylene diamine acid-D, Pfansteihl）The preparation method of/β-TCP composite materials - Google Patents
Rgd peptide grafting is poly-（Malaysia acyl hexamethylene diamine acid-D, Pfansteihl）The preparation method of/β-TCP composite materials Download PDFInfo
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- A61L27/00—Materials for grafts or prostheses or for coating grafts or prostheses
- A61L27/40—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material
- A61L27/44—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix
- A61L27/46—Composite materials, i.e. containing one material dispersed in a matrix of the same or different material having a macromolecular matrix with phosphorus-containing inorganic fillers
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- 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
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- 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
- A61L27/54—Biologically active materials, e.g. therapeutic substances
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- 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
- A61L27/56—Porous materials, e.g. foams or sponges
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- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F283/00—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G
- C08F283/02—Macromolecular compounds obtained by polymerising monomers on to polymers provided for in subclass C08G on to polycarbonates or saturated polyesters
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- C08G81/00—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers
- C08G81/02—Macromolecular compounds obtained by interreacting polymers in the absence of monomers, e.g. block polymers at least one of the polymers being obtained by reactions involving only carbon-to-carbon unsaturated bonds
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/20—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices containing or releasing organic materials
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- A61L2300/00—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices
- A61L2300/60—Biologically active materials used in bandages, wound dressings, absorbent pads or medical devices characterised by a special physical form
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- A61L2300/604—Biodegradation
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- C08J2387/00—Characterised by the use of unspecified macromolecular compounds, obtained otherwise than by polymerisation reactions only involving unsaturated carbon-to-carbon bonds
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- C08K3/00—Use of inorganic substances as compounding ingredients
- C08K3/32—Phosphorus-containing compounds
- C08K2003/321—Phosphates
- C08K2003/325—Calcium, strontium or barium phosphate
Abstract
The present invention relates to rgd peptide grafting is poly-（Malaysia acyl hexamethylene diamine acid D, L lactic acid）The preparation method of/β TCP composite materials.The present invention makes it be conducive to the growth of the adhesion of cell using Malaysia acyl hexamethylene diamine acid, rgd peptide polydactyl acid, for improving its cellular affinity；Hexamethylene diamine acts on the accumulation primarily to acid in control degradation process, prevents implanting tissue aseptic necrosis；First synthesis Malaysia acyl hexamethylene diamine acid is introduced into polylactic acid side chain again, can reduce polylactic acid reaction times and avoid the reduction of its molecular weight, ensure the mechanical property of composite material；For nanometer β TCP as a kind of good biodegradation material of biocompatibility, the degrade calcium generated, phosphonium ion are also the necessary material of the growths such as bone tissue, neuron.
Description
Technical field
The present invention relates to biomedical material technologies, and in particular to a kind of RGD can be used for Repair of tissue defect is more
Peptide is grafted the preparation method of poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)/composite porous β-TCP.
Background technology
Peripheral nerve injury is common disease clinically, and it is always clinically urgently to be resolved hurrily to find suitable repair materials
Problem.Degradable high molecular material is increasingly taken seriously, such as polylactic acid (PLA), polyurethane (PU), polyamide (PA)
Deng wherein more commonly used is polylactic acid and its copolymer with other materials.Polylactic acid by FDA standards because its
Catabolite is mostly small molecule and carbon dioxide, non-toxic, can be absorbed by the body or be excreted by metabolism, in addition by
It is widely used in organizational project, CO2 laser weld, field of medicine release in its good biocompatibility, biological degradability.
However simple poly-lactic acid material can not meet the needs of organizational project, this is because on polylactic acid main chain only
A small amount of carboxyl and hydroxyl lacks active reactive group, causes material surface is seriously hydrophobic to be unfavorable for cell adhesion, gathers breast in addition
Sour material degradation is in acidity.Therefore how to increase polylactic acid surface active groups, introduce the cells growth activity factor, alleviate part
Acidity is excessively high to seem most important.
Rgd peptide has been proved to that the tactophily of cell can be promoted, and is conducive to proliferation, the differentiation of cell.β-TCP tools
There are good bioactivity and biocompatibility, similar to body bone tissue ingredient, β-TCP can also neutralize alleviation in alkalinity and gather
The acidity of lactic acid degradation.Therefore rgd peptide is introduced into polylactic acid side chain and is one suitable with the compound porous materials that prepare of β-TCP
Selection.
Find that prior art polydactyl acid common practice is first by the published research data of a large amount of reading analysis
Active group (such as hydroxyl, carbon-carbon double bond) is introduced on polylactic acid side chain, then will be had by bridge of above-mentioned active group
Chemistry or the molecule such as starch, chitosan of bioactivity, which are connected on main chain, forms entirety.In addition to this also by simple total
The mixed method that polylactic acid is modified.It is more by the general molecular weight and molecular weight of modified product after chemical modification, lose matrix
The original mechanical strength of material；And blending and modifying product due to mixing it is uneven so that material performance differs everywhere.Pertinent literature is joined
See a Wu Fei, Li Yaming, soldier, wait the polypeptide grafted poly-/polylactic acid of novel nano-materials lactic-co-glycolic acid-L-lysine/
Nanometer hydroxyapatite/valproic acid nerve trachea promotes research [J] the China experimental surgery magazine of peripheral nerve regeneration of rats,
2015,32(7):The modification of 1595-1598., b Luo Yan phoenix poly- (D, L-lactic acid) and external degradation and cytocompatibility Journal of Sex Research
[D] University Of Chongqing, 2003., the bone tissue engineer host materials of poly- (D, Pfansteihl) the base bionic extracellular matrixes of c Niu Xufeng grinds
Study carefully [D] University Of Chongqing, 2006., the preparation of the handsome .PRGD/PDLLA/ β-TCP/NGF composite nerve conduits of the tight fine jades of d and its around
Application [D] Wuhan University of Technologys in CO2 laser weld, 2008., e Li Juan .RGD be grafted poly- (hydroxyacetic acid-L-lysine-breast
Acid) research [D] the Wuhan University of Technology of/PDLLA/ β-TCP composite materials for peripheral nerve defection reparation, 2008..
The present invention mainly seeks a kind of first individually react the small molecule with chemistry, bioactivity and monomer is made, and closes
The activity of its functional group is not affected during at monomer, and monomer is only then grafted to polylactic acid master by single step reaction
On the side chain of chain, the above problem is effectively overcome.
Invention content
It is an object of the invention to solve the above problem existing for existing peripheral nerve injury repair materials, one kind is provided
It is composite porous and preparation method thereof that rgd peptide is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)/β-TCP, the composite wood
Material by by rgd peptide introduce polylactic acid side chain and with β-TCP are compound obtains, preparation method is specific as follows：
(a) under the conditions of triethylamine (TEA) is existing, maleic anhydride (MAH) and hexamethylene diamine (HMD) react in the solution
To Malaysia acyl hexamethylene diamine acid；
(b) under cumyl peroxide (DCP) existence condition, Malaysia acyl hexamethylene diamine acid and Poly D,L-lactide
(PDLLA) polylactic acid (BMPLA) that Malaysia acyl hexamethylene diamine acid is modified is obtained by the reaction in the solution；
(c) under polypeptide condensing agent existence condition, polylactic acid and rgd peptide that Malaysia acyl hexamethylene diamine acid is modified are in the solution
Rgd peptide is obtained by the reaction and is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)；
(d) rgd peptide is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) to be uniformly mixed in the solution with β-TCP, is done
It is dry to obtain rgd peptide to be grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)/β-TCP composite porous.
Further, maleic anhydride in step (a), hexamethylene diamine, triethylamine mole are 1:(1.2-2):(1-1.2), institute
The organic solvent used is dichloromethane.
Further, Poly D,L-lactide in step (b), Malaysia acyl hexamethylene diamine acid, cumyl peroxide mass ratio
It is 1:0.1:0.005, used organic solvent is tetrahydrofuran (THF) and ethanol solution.
Further, polylactic acid, the quality of rgd peptide that polypeptide condensing agent, Malaysia acyl hexamethylene diamine acid are modified in step (c)
Than being 0.3:1:0.01, used organic solvent is tetrahydrofuran and n,N-Dimethylformamide (DMF).
Further, rgd peptide is grafted the quality of poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) and β-TCP in step (d)
Than being 1:(0.05-0.15), used solvent are the mixture of dioxane, water, the wherein volume ratio of dioxane and water
It is 100:(0-20).
Further, step (a) detailed process is as follows：Hexamethylene diamine is dissolved in the dichloromethane solution of triethylamine protection,
Maleic anhydride is dissolved in dichloromethane solution, at room temperature by two kinds of solution hybrid reactions, is co-precipitated using THF- absolute ethyl alcohols
The isolated Malaysia acyl hexamethylene diamine acid of method.
Further, step (b) detailed process is as follows：Dried Poly D,L-lactide is dissolved in tetrahydrofuran, it will
Malaysia acyl hexamethylene diamine acid is dissolved in the ethanol solution that volume fraction is 90%, and peroxidating diisopropyl is added after two kinds of solution are mixed
Benzene is sufficiently stirred and is dried in vacuo 48h or more at room temperature, 150 DEG C of reactions is then heated under protective atmosphere, using THF-
H2The polylactic acid that the isolated Malaysia acyl hexamethylene diamine acid of O coprecipitations is modified.
Further, step (c) detailed process is as follows：The polylactic acid that Malaysia acyl hexamethylene diamine acid is modified is dissolved in tetrahydrofuran
In and with triethanolamine adjust pH to neutrality, be subsequently added into polypeptide condensing agent and adjust pH value of solution to 7-8, acquired solution is placed in
A period of time is activated in ice-water bath, rgd peptide is dissolved in n,N-Dimethylformamide, and two kinds of solution are mixed, are not being surpassed
5-10h is reacted in the environment of crossing 4 DEG C, excessive distilled water is added after the completion of reaction, and the film for collecting surface is dried under vacuum to constant weight, obtains
It is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) to rgd peptide.
Further, step (d) detailed process is as follows：Rgd peptide is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)
It is dissolved in the mixed solution of dioxane and water, then addition nanometer β-TCP and ultrasonic disperse make it be uniformly mixed thereto, then
Mixed solution is placed in freezing 12h or more in -80 DEG C to 0 DEG C of refrigerator, it is dry that the sample after later curing frost is put into freezing
Solvent is fully dried and removed in dry machine, it is porous multiple to obtain poly- (Malaysia acyl hexamethylene diamine acid-D, the Pfansteihl)/β-TCP of rgd peptide grafting
Condensation material.
Further, the polypeptide condensing agent is 1- ethyls-(3- dimethylaminopropyls) carbodiimide hydrochloride
(EDCI) mass ratio of the mixed liquor formed with I-hydroxybenzotriazole (HOBT), wherein EDCI and HOBT are 1:1.
The present invention improves its cellular affinity, is conducive to using Malaysia acyl hexamethylene diamine acid, rgd peptide polydactyl acid
The adhesion of cell is grown；Being introduced into for hexamethylene diamine can more effectively control acid in degradation process than simple composite hydroxylapatite
The accumulation of property, prevents implanting tissue aseptic necrosis.First by maleic anhydride and hexamethylene diamine synthesis Malaysia acyl hexamethylene diamine acid, then by its
Polylactic acid side chain is introduced, the number that polylactic acid participates in reaction is reduced, effectively avoids its molecular weight during the reaction
It reduces, improves the mechanical property of composite material.Compound nanometer β-TCP be it is a kind of have good biocompatibility biology drop
Material is solved, the degrade calcium generated, phosphonium ion are also the necessary material of the growths such as bone tissue, neuron.
Compared with prior art, the invention has the advantages that：(1) present invention process is relatively simple, reaction and production
Object is controllable；(2) modifying process of Poly D,L-lactide is simple, can effectively reduce the damage of raw material molecular weight during the reaction
It loses；(3) the aperture structure shapes and sizes of timbering material can be adjusted by the concentration and solution pre-freezing temperature of polymer solution
Section.
Description of the drawings
Fig. 1 is the infrared spectrogram of 1 intermediate product Malaysia acyl hexamethylene diamine acid of the embodiment of the present invention；
Fig. 2 is the infrared spectrogram for the polylactic acid that 1 intermediate product Malaysia acyl hexamethylene diamine acid of the embodiment of the present invention is modified；Fig. 3
The contact angle test result of poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) is grafted for 1 intermediate product rgd peptide of the embodiment of the present invention
Figure；
Fig. 4 is that 1 target product rgd peptide of the embodiment of the present invention is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)/β-
SEM figures composite porous TCP.
Specific implementation mode
To make those of ordinary skill in the art fully understand technical scheme of the present invention and advantageous effect, below in conjunction with specific
Embodiment is further described.
Embodiment 1
1) 2.335g hexamethylene diamines are dissolved in 10mL dichloromethane first, add 6.106mL triethylamines and stirred evenly；
1.6335g maleic anhydrides are dissolved in 5mL dichloromethane.Under the conditions of being stirred at room temperature, by the dichloromethane of maleic anhydride in 0.5h
Alkane solution is added drop-wise in the dichloromethane solution of hexamethylene diamine, the reaction was continued at room temperature after being added dropwise to complete 2h.After the completion of reaction, institute
It obtains mixed solution and uses the isolated Malaysia acyl hexamethylene diamine acid monomers of THF- absolute ethyl alcohol coprecipitations, be dried in vacuo standby
With.The THF- absolute ethyl alcohols coprecipitation concrete operations are as follows：Substance after reaction is dissolved in appropriate THF, then to mixed
It closes and instills excessive absolute ethyl alcohol in solution, collect precipitation.
The infrared spectrogram of intermediate product Malaysia acyl hexamethylene diamine acid monomers is as shown in Figure 1, from monomer made from the step
FTIR collection of illustrative plates can be seen that in 1674cm-1There is the characteristic absorption peak of C=O in amido bond in position, in 1524cm-1There is acyl at place
The bending vibration absorption peak of N-H in amine key, in 3375cm-1Place display absorption peak may be in amido bond N- replace secondary amide and
N-H stretching vibration peaks in primary amine.This, which is absolutely proved, successfully synthesizes subject monomers.
2) 5g Poly D,L-lactide is dissolved in appropriate tetrahydrofuran, the Malaysias 0.504g acyl hexamethylene diamine acid is dissolved in volume point
Number is in 90% ethanol solution.Under agitation, the ethanol solution of Malaysia acyl hexamethylene diamine acid is instilled into Poly D,L-lactide
Tetrahydrofuran solution in, continue stir a period of time after add 0.026g cumyl peroxides, object to be mixed fully stirs
48h or more is dried in vacuo after mixing at room temperature fully to remove solvent.Mixture is finally placed in 150 DEG C under nitrogen protection
2h is reacted in oil bath, products therefrom is dissolved in appropriate tetrahydrofuran, instills the film that excessive distilled water collects surface thereto
The polylactic acid that (THF-H2O coprecipitations) is modified to get product Malaysia acyl hexamethylene diamine acid.
The infrared spectrogram for the polylactic acid that acyl hexamethylene diamine acid in intermediate product Malaysia made from the step is modified is as shown in Figure 2.
1647cm is can be seen that from the FTIR collection of illustrative plates of polydactyl acid-1There is the characteristic absorption peak of-CO-N- amido bonds in position, then
In 1558cm-1The appearance of-NH- flexural vibrations peaks after having amino to react at wave band, this illustrates that the monomer in step (1) is successfully grafted
In polylactic acid.
3) polylactic acid that the Malaysias 1g acyl hexamethylene diamine acid is modified is dissolved in the tetrahydrofuran of 50mL, is adjusted with triethanolamine
Polypeptide condensing agent is then added to neutrality in the pH of solution thereto, waits for that mixture is placed in ice-water bath by its dissolving after mixing
Half an hour is activated in (being less than 4 DEG C), adjusts the pH to 7-8 of solution.The polypeptide condensing agent is by 0.15g 1- ethyls-(3- diformazans
Base aminopropyl) carbodiimide hydrochloride (EDCI) and 0.15g I-hydroxybenzotriazoles (HOBT) composition.10mg RGD is more
Peptide is dissolved in 5mL n,N-Dimethylformamide (DMF), mixture rgd peptide-DMF solution being added drop-wise to after ice-water bath
In, less than 4 DEG C reaction 5h of control temperature then instill excessive distilled water into mixture, collect the film on surface, its vacuum is done
It is dry to obtain rgd peptide to constant weight and be grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) material.
It is tested by Static water contact angles, the hydrophily of composite material obtained by this step significantly improves (Fig. 3).
4) 1g rgd peptides poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) material is grafted to be dissolved in 10mL dioxane,
0.05g β-TCP and ultrasonic disperse 2h is added thereto under agitation, mixed solution is then placed in ice in 0 DEG C of refrigerator
Freeze 12h or more, mixed solution is finally transferred to vacuum freeze drying in -50 DEG C of environment and removes solvent, obtains rgd peptide grafting
Poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)/β-TCP are composite porous.
By SEM it has been observed that obtaining composite porous aperture in 100um or so, and arranged regular (Fig. 4).
Embodiment 2
1) 2.365g hexamethylene diamines are dissolved in 10mL dichloromethane first, add 4.64mL triethylamines and stirred evenly；
1.25g maleic anhydrides are dissolved in 5mL dichloromethane.Under the conditions of being stirred at room temperature, by the dichloromethane of maleic anhydride in 0.5h
Solution is added drop-wise in the dichloromethane solution of hexamethylene diamine, the reaction was continued at room temperature after being added dropwise to complete 2h.After the completion of reaction, gained
Mixed solution uses the isolated Malaysia acyl hexamethylene diamine acid monomers of THF- absolute ethyl alcohol coprecipitations, is dried in vacuo spare.
2) 5g Poly D,L-lactide is dissolved in appropriate tetrahydrofuran, the Malaysias 0.504g acyl hexamethylene diamine acid is dissolved in volume point
Number is in 90% ethanol solution.Under agitation, the ethanol solution of Malaysia acyl hexamethylene diamine acid is instilled into Poly D,L-lactide
Tetrahydrofuran solution in, continue stir a period of time after add 0.026g cumyl peroxides, object to be mixed fully stirs
48h or more is dried in vacuo after mixing at room temperature fully to remove solvent.Mixture is finally placed in 150 DEG C under nitrogen protection
2h is reacted in oil bath, products therefrom is dissolved in appropriate tetrahydrofuran, instills the film that excessive distilled water collects surface thereto, i.e.,
Obtain the polylactic acid that product Malaysia acyl hexamethylene diamine acid is modified.
3) polylactic acid that the Malaysias 1g acyl hexamethylene diamine acid is modified is dissolved in the tetrahydrofuran of 50mL, is adjusted with triethanolamine
Polypeptide condensing agent is then added to neutrality in the pH of solution thereto, waits for that mixture is placed in ice-water bath by its dissolving after mixing
Half an hour is activated in (being less than 4 DEG C), adjusts the pH to 7-8 of solution.The polypeptide condensing agent is by 0.15g 1- ethyls-(3- diformazans
Base aminopropyl) carbodiimide hydrochloride (EDCI) and 0.15g I-hydroxybenzotriazoles (HOBT) composition.10mg RGD is more
Peptide is dissolved in 5mL n,N-Dimethylformamide (DMF), mixture rgd peptide-DMF solution being added drop-wise to after ice-water bath
In, less than 4 DEG C reaction 6h of control temperature then instill excessive distilled water into mixture, collect the film on surface, its vacuum is done
It is dry to obtain rgd peptide to constant weight and be grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) material.
4) 1g rgd peptides are grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) material and are dissolved in 10mL dioxane/water
(the two volume ratio is 100 to system:10) in, 0.05g β-TCP and ultrasonic disperse 2h is added thereto under agitation, then
Mixed solution is placed in frost 12h or more in -20 DEG C of refrigerator, it is cold that mixed solution is finally transferred to vacuum in -50 DEG C of environment
Jelly dries and removes solvent, and it is composite porous to obtain poly- (Malaysia acyl hexamethylene diamine acid-D, the Pfansteihl)/β-TCP of rgd peptide grafting.
Embodiment 3
1) 2.5g hexamethylene diamines are dissolved in 10mL dichloromethane first, add 5.9mL triethylamines and stirred evenly；It will
1.32g maleic anhydrides are dissolved in 5mL dichloromethane.It is in 0.5h that the dichloromethane of maleic anhydride is molten under the conditions of being stirred at room temperature
Drop is added in the dichloromethane solution of hexamethylene diamine, the reaction was continued at room temperature after being added dropwise to complete 2h.After the completion of reaction, gained is mixed
It closes solution and uses the isolated Malaysia acyl hexamethylene diamine acid monomers of THF- absolute ethyl alcohol coprecipitations, be dried in vacuo spare.
2) 5g Poly D,L-lactide is dissolved in appropriate tetrahydrofuran, the Malaysias 0.504g acyl hexamethylene diamine acid is dissolved in volume point
Number is in 90% ethanol solution.Under agitation, the ethanol solution of Malaysia acyl hexamethylene diamine acid is instilled into Poly D,L-lactide
Tetrahydrofuran solution in, continue stir a period of time after add 0.026g cumyl peroxides, object to be mixed fully stirs
48h or more is dried in vacuo after mixing at room temperature fully to remove solvent.Mixture is finally placed in 150 DEG C under nitrogen protection
2h is reacted in oil bath, products therefrom is dissolved in appropriate tetrahydrofuran, instills the film that excessive distilled water collects surface thereto, i.e.,
Obtain the polylactic acid that product Malaysia acyl hexamethylene diamine acid is modified.
3) polylactic acid that the Malaysias 1g acyl hexamethylene diamine acid is modified is dissolved in the tetrahydrofuran of 50mL, is adjusted with triethanolamine
Polypeptide condensing agent is then added to neutrality in the pH of solution thereto, waits for that mixture is placed in ice-water bath by its dissolving after mixing
Half an hour is activated in (being less than 4 DEG C), adjusts the pH to 7-8 of solution.The polypeptide condensing agent is by 0.15g 1- ethyls-(3- diformazans
Base aminopropyl) carbodiimide hydrochloride (EDCI) and 0.15g I-hydroxybenzotriazoles (HOBT) composition.10mg RGD is more
Peptide is dissolved in 5mL n,N-Dimethylformamide (DMF), mixture rgd peptide-DMF solution being added drop-wise to after ice-water bath
In, less than 4 DEG C reaction 8h of control temperature then instill excessive distilled water into mixture, collect the film on surface, its vacuum is done
It is dry to obtain rgd peptide to constant weight and be grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) material.
4) by 1.5g rgd peptides be grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) material be dissolved in 10mL dioxane/
(the two volume ratio is 100 to aqueous systems；10) in, 0.10g β-TCP and ultrasonic disperse 2h is added thereto under agitation, so
Mixed solution is placed in frost 12h or more in -20 DEG C of refrigerator afterwards, mixed solution is finally transferred to vacuum in -50 DEG C of environment
Freeze-drying removes solvent, obtains rgd peptide and is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, the Pfansteihl)/porous composite woods of β-TCP
Material.
Embodiment 4
1) 2.5g hexamethylene diamines are dissolved in 10mL dichloromethane first, add 4.7mL triethylamines and stirred evenly；It will
1.05g maleic anhydrides are dissolved in 5mL dichloromethane.It is in 0.5h that the dichloromethane of maleic anhydride is molten under the conditions of being stirred at room temperature
Drop is added in the dichloromethane solution of hexamethylene diamine, the reaction was continued at room temperature after being added dropwise to complete 2h.After the completion of reaction, gained is mixed
It closes solution and uses the isolated Malaysia acyl hexamethylene diamine acid monomers of THF- absolute ethyl alcohol coprecipitations, be dried in vacuo spare.
2) 5g Poly D,L-lactide is dissolved in appropriate tetrahydrofuran, the Malaysias 0.504g acyl hexamethylene diamine acid is dissolved in volume point
Number is in 90% ethanol solution.Under agitation, the ethanol solution of Malaysia acyl hexamethylene diamine acid is instilled into Poly D,L-lactide
Tetrahydrofuran solution in, continue stir a period of time after add 0.026g cumyl peroxides, object to be mixed fully stirs
48h or more is dried in vacuo after mixing at room temperature fully to remove solvent.Mixture is finally placed in 150 DEG C under nitrogen protection
2h is reacted in oil bath, products therefrom is dissolved in appropriate tetrahydrofuran, instills the film that excessive distilled water collects surface thereto, i.e.,
Obtain the polylactic acid that product Malaysia acyl hexamethylene diamine acid is modified.
3) polylactic acid that the Malaysias 1g acyl hexamethylene diamine acid is modified is dissolved in the tetrahydrofuran of 50mL, is adjusted with triethanolamine
Polypeptide condensing agent is then added to neutrality in the pH of solution thereto, waits for that mixture is placed in ice-water bath by its dissolving after mixing
Half an hour is activated in (being less than 4 DEG C), adjusts the pH to 7-8 of solution.The polypeptide condensing agent is by 0.15g 1- ethyls-(3- diformazans
Base aminopropyl) carbodiimide hydrochloride (EDCI) and 0.15g I-hydroxybenzotriazoles (HOBT) composition.10mg RGD is more
Peptide is dissolved in 5mL n,N-Dimethylformamide (DMF), mixture rgd peptide-DMF solution being added drop-wise to after ice-water bath
In, less than 4 DEG C reaction 10h of control temperature then instill excessive distilled water into mixture, the film on surface are collected, by its vacuum
Drying to constant weight obtains rgd peptide and is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) material.
4) by 1.5g rgd peptides be grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) material be dissolved in 10mL dioxane/
(the two volume ratio is 100 to aqueous systems:20) in, 0.225g β-TCP and ultrasonic disperse 2h is added thereto under agitation, so
Mixed solution is placed in frost 12h or more in -70 DEG C of refrigerator afterwards, mixed solution is finally transferred to vacuum in -50 DEG C of environment
Freeze-drying removes solvent, obtains rgd peptide and is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, the Pfansteihl)/porous composite woods of β-TCP
Material.
Claims (10)
- The preparation method of 1.RGD polypeptide grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)/composite porous β-TCP, it is special Sign is, includes the following steps：(a) existing for triethylamine under the conditions of, Malaysia acyl hexamethylene diamine acid is obtained by the reaction in maleic anhydride and hexamethylene diamine in the solution；(b) under cumyl peroxide existence condition, Malaysia acyl hexamethylene diamine acid reacts in the solution with Poly D,L-lactide The polylactic acid being modified to Malaysia acyl hexamethylene diamine acid；(c) under polypeptide condensing agent existence condition, the polylactic acid that Malaysia acyl hexamethylene diamine acid is modified is reacted in the solution with rgd peptide It obtains rgd peptide and is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)；(d) rgd peptide poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) is grafted to be uniformly mixed in the solution with β-TCP, dry It is composite porous it to be grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl)/β-TCP to rgd peptide.
- 2. preparation method as described in claim 1, it is characterised in that：Maleic anhydride in step (a), hexamethylene diamine, triethylamine Mole be 1:(1.2-2):(1-1.2), used organic solvent are dichloromethane.
- 3. preparation method as described in claim 1, it is characterised in that：Poly- D in step (b), L- lactides, Malaysia acyl hexamethylene diamine Sour, cumyl peroxide mass ratio is 1:0.1:0.005, used organic solvent is tetrahydrofuran and ethanol solution.
- 4. preparation method as described in claim 1, it is characterised in that：Polypeptide condensing agent, Malaysia acyl hexamethylene diamine acid in step (c) The mass ratio of modified polylactic acid, rgd peptide is 0.3:1:0.01, used organic solvent is tetrahydrofuran and N, N- diformazans Base formamide.
- 5. preparation method as described in claim 1, it is characterised in that：In step (d) rgd peptide grafting it is poly- (Malaysia acyl oneself two Amino acid-D, Pfansteihl) with the mass ratio of β-TCP it is 1:(0.05-0.15), used solvent are the mixing of dioxane, water The volume ratio of object, wherein dioxane and water is 100:(0-20).
- 6. preparation method as described in claim 1, it is characterised in that：Step (a) detailed process is as follows：Hexamethylene diamine is dissolved in three In the dichloromethane solution of ethamine protection, maleic anhydride is dissolved in dichloromethane solution, is at room temperature mixed two kinds of solution anti- It answers, using the isolated Malaysia acyl hexamethylene diamine acid of THF- absolute ethyl alcohol coprecipitations.
- 7. preparation method as described in claim 1, it is characterised in that：Step (b) detailed process is as follows：By dried poly- D, L- lactides are dissolved in tetrahydrofuran, Malaysia acyl hexamethylene diamine acid are dissolved in the ethanol solution that volume fraction is 90%, by two kinds Cumyl peroxide is added after solution mixing, 48h or more is sufficiently stirred and is dried in vacuo at room temperature, then under protective atmosphere 150 DEG C of reactions are heated to, using THF-H2The polylactic acid that the isolated Malaysia acyl hexamethylene diamine acid of O coprecipitations is modified.
- 8. preparation method as described in claim 1, it is characterised in that：Step (c) detailed process is as follows：By Malaysia acyl hexamethylene diamine The modified polylactic acid of acid is dissolved in tetrahydrofuran and adjusts pH to neutrality with triethanolamine, is subsequently added into polypeptide condensing agent and adjusts Acquired solution is placed in ice-water bath to 7-8 and activates a period of time, rgd peptide is dissolved in N, N- dimethyl formyls by pH value of solution In amine, two kinds of solution are mixed, 5-10h is reacted in the environment of no more than 4 DEG C, excessive distilled water is added after the completion of reaction, receives The film on collection surface is dried under vacuum to constant weight, is obtained rgd peptide and is grafted poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl).
- 9. preparation method as described in claim 1, it is characterised in that：Step (d) detailed process is as follows：Rgd peptide is grafted Poly- (Malaysia acyl hexamethylene diamine acid-D, Pfansteihl) is dissolved in the mixed solution of dioxane and water, then nanometer β-TCP are added thereto And ultrasonic disperse makes it be uniformly mixed, and mixed solution is then placed in freezing 12h or more in -80 DEG C to 0 DEG C of refrigerator, later will Sample after frost solidification is put into freeze drier and fully dries and removes solvent, obtain rgd peptide grafting it is poly- (Malaysia acyl oneself two Amino acid-D, Pfansteihl)/β-TCP are composite porous.
- 10. the preparation method as described in claim 1,4 or 8, it is characterised in that：The polypeptide condensing agent is 1- ethyls-(3- bis- Dimethylaminopropyl) carbodiimide hydrochloride and I-hydroxybenzotriazole composition mixed liquor, the mass ratio of the two is 1:1.
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| CN201810257579.8A CN108485280A (en) | 2018-03-27 | 2018-03-27 | Rgd peptide grafting is poly-（Malaysia acyl hexamethylene diamine acid-D, Pfansteihl）The preparation method of/β-TCP composite materials |
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Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008093341A3 (en) * | 2007-01-31 | 2009-06-18 | Technion Res & Dev Foundation | Electrospun scaffolds and methods of generating and using same |
| CN104910410A (en) * | 2015-06-05 | 2015-09-16 | 武汉理工大学 | Preparation method of RGD polypeptide grafted poly(maleic anhydride-hexamethylendiamine-DL-lactic acid)/modified hydroxyapatite porous composite material |
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2018
- 2018-03-27 CN CN201810257579.8A patent/CN108485280A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2008093341A3 (en) * | 2007-01-31 | 2009-06-18 | Technion Res & Dev Foundation | Electrospun scaffolds and methods of generating and using same |
| CN104910410A (en) * | 2015-06-05 | 2015-09-16 | 武汉理工大学 | Preparation method of RGD polypeptide grafted poly(maleic anhydride-hexamethylendiamine-DL-lactic acid)/modified hydroxyapatite porous composite material |
Non-Patent Citations (3)
| Title |
|---|
| TONG QIU ET AL.: ""PDLLA/PRGD/β-TCPconduits build the neurotrophin-rich microenvironment suppressing the oxidative stress and promoting the sciatic nerve regeneration"", 《SOCIETY FOR BIOMATERIALS》 * |
| 吕丽永: ""PLLA_TCP纳米复合支架的制备及性能研究"", 《中国优秀硕士学位论文全文数据库 工程科技Ⅰ辑》 * |
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