CN102731762A - Poly(DL-lactic acid) material modified based on 24 peptides in E domain of mechano-growth factor (MGF) and diamine, and preparation method and application thereof - Google Patents
Poly(DL-lactic acid) material modified based on 24 peptides in E domain of mechano-growth factor (MGF) and diamine, and preparation method and application thereof Download PDFInfo
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Abstract
The invention relates to a poly(DL-lactic acid) material modified based on 24 peptides in E domain of MGF and diamine. The molecular formula of the poly(DL-lactic acid) material is represented by I. A preparation method for the poly(DL-lactic acid) material is as follows: diamine reacts with maleic anhydride modified poly(DL-lactic acid) to produce diamine-maleic anhydride modified poly(DL-lactic acid); diamine-maleic anhydride modified poly(DL-lactic acid) and the 24 peptides in the E domain of MGF are used as raw materials, one selected from the group consisting of DCC, EDC and a mixture is used as a condensing agent, then the raw materials and the condensing agent are subjected to a reaction at a temperature of 0 to 50 DEG C for 8 to 48 h, an obtained reaction solution is added into an excess aqueous medium, a membrane-like precipitate is collected, and the membrane-like precipitate is the poly(DL-lactic acid) material modified based on the 24 peptides in the E domain of MGF and diamine. The invention also discloses application of the poly(DL-lactic acid) material modified based on the 24 peptides in the E domain of MGF and diamine in preparation of bioactive bionic materials. The material provided in the invention has better hydrophilicity, cellular affinity and biodegradability and is expected to mitigate related problems caused by understressing during the process of tissue repair or regeneration treatment.
Description
Technical field
The invention belongs to technical field of biological material, particularly the polypeptide modified polylactic acid material.
Background technology
(mechano growth factor is the alternative splicing variant of growth factor-1 (IGF-1) MGF) to growth factor, has stress stimulation susceptibility, is receiving the muscle of stress stimulation, bone, and in the muscle, nervous tissue of damage higher expression is arranged.Further discover; MGF carboxyl terminal E structural domain 24 peptides (tyrosine-Stimulina-proline(Pro)-proline(Pro)-serine-threonine-l-asparagine-Methionin-l-asparagine-Threonine-Methionin-Serine-Stimulina-l-arginine-l-arginine-LYS-GLY-serine-threonine-Phe-Glu-Glu-Histidine-Methionin) have the function that promotes the bone defect repair. but single polypeptide because in vivo the transformation period short, in the bone defect repair, can not reach the ideal effect.Therefore a kind of stable, economical and reliable is delivered mounting system and is seemed particularly important.In in the past 10 years, various material as the extracellular support be used for the bone defect repair as, POLYACTIC ACID, Win 40350, polyoxyethylene glycol, calcium phosphate, collagen etc.POLYACTIC ACID [poly (DL-lactic acid) wherein; PDLLA] because have good biocompatibility, biological degradability and degraded product nontoxic, be prone to advantage such as machine-shaping; Become bone and transplant the focus of research field, the basic requirement of satisfying as the bone tissue engineer cell epimatrix material in bone defect repair field.But single poly-lactic acid material hydrophobicity is strong, lack the reactive group of further modification and the site of specific cell identification, and acid product is prone to cause inflammatory reaction in the body after the degraded, has therefore limited POLYACTIC ACID in bone defect repair Application for Field.This team once carried out modification with tetramethylenediamine, maleic anhydride to POLYACTIC ACID, in the POLYACTIC ACID skeleton, had introduced abundant-NH
2With-COOH reactive group, improved the wetting ability of this material, phenomenon falls in pH suddenly that overcome in the POLYACTIC ACID degradation process, and has improved scleroblast sticking on this modified polylactic acid material.But this polydactyl acid lacks the site of cell-specific identification, not biologically active.
The present invention is directed to above problem, the POLYACTIC ACID that utilizes Mechano growth factor E structural domain 24 peptide modification diamines and maleic anhydride to modify prepares a kind of novel organizational project biomimetic scaffolds and medical material, and Shang Weijian has other report.
Summary of the invention
One of the object of the invention is to provide a kind of biomaterial, and this material of this biomaterial has excellent biological compatibility and biological degradability, is applicable to field of tissue engineering technology and medical field.
The implementation of above-mentioned purpose is:
A kind of POLYACTIC ACID based on Mechano growth factor E structural domain 24 peptides and diamines modification, its molecular formula such as I:
Wherein A is D-lactic acid, L-lactic acid and D, and among arbitrary in the L-lactic acid, n=100-20000, m=2-6, said Ct24E-MGF are that its aminoacid sequence is shown in SEQ ID NO:1 based on Mechano growth factor E structural domain 24 peptides.
Further, said A is D, L-lactic acid, n=100-20000, m=2-6.
Two of the object of the invention is to provide the preparation method of said POLYACTIC ACID based on Mechano growth factor E structural domain 24 peptides and diamines modification, and this method is simple to operate, is applicable to scale operation.
The implementation of above-mentioned technical purpose is:
The preparation method of described POLYACTIC ACID based on Mechano growth factor E structural domain 24 peptides and diamines modification, concrete steps are:
The preparation of A diamines and maleic anhydride modified POLYACTIC ACID
With diamines, molecular formula the maleic anhydride modified POLYACTIC ACID reaction as III shown in of molecular formula, generate diamines and the maleic anhydride modified POLYACTIC ACID of molecular formula such as IV like II:
B is based on the preparation of the POLYACTIC ACID of Mechano growth factor E structural domain 24 peptides and diamines modification
Diamines and maleic anhydride modified POLYACTIC ACID with molecular formula such as IV; With Mechano growth factor E structural domain 24 peptides shown in SEQ ID NO:1 be raw material; With arbitrary in DCC, EDC or the mixture be condensing agent, reaction is 8-48 hour under 0-50 ℃ of condition, said reaction solution adds in the water medium; Collect membranaceous throw out, said membranaceous throw out is the POLYACTIC ACID based on Mechano growth factor E structural domain 24 peptides and diamines modification of molecular formula such as I; Wherein mixture is for being that 1: 1 EDC and NHS mixes with mass ratio; DCC is meant N; N '-NSC 57182; EDC is meant 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide, and NHS is meant 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide and N-hydroxy-succinamide; A is D-lactic acid, L-lactic acid and D among the I, among arbitrary in the L-lactic acid, and n=100-20000
Further, specifically may further comprise the steps:
1) said maleic anhydride modified POLYACTIC ACID is dissolved in the organic solvent, adds said growth factor E structural domain 24 peptides, stir, reaction solution A, said organic solvent be in THF, DMSO 99.8MIN., the methylene dichloride any;
2) condensing agent is added in the above-mentioned reaction solution, reaction is 8-48 hour under 0-50 ℃ of condition, gets reaction solution B;
3) reaction solution B is added dropwise in the zero(ppm) water, collects membranaceous throw out, said membranaceous throw out is the POLYACTIC ACID based on Mechano growth factor E structural domain 24 peptides and diamines modification;
In the above-mentioned reaction system, said maleic anhydride and diamine modified poly-latic acid concentration are/10 milliliters of 50 milligrams-3 grams, and Mechano growth factor E structural domain 24 peptide concentrations are 5-30 milligram/10 milliliter, and said condensing agent concentration is 45-75 milligram/10 milliliter.
Preferably, with the membranaceous throw out lyophilize of gained.
Preferably; The preparation method of said maleic anhydride modified POLYACTIC ACID is: with toxilic acid acyl and POLYACTIC ACID, generate maleic anhydride modified POLYACTIC ACID through free radical reaction, the initiator in the reaction is tert-butyl peroxide or peroxo-phenyl-diformyl; Reaction times is 40-150 ℃; Said toxilic acid acyl is 0.5%-20% by weight percentage, and initiator uses weight percent to be 0.1%-10%, and surplus is a POLYACTIC ACID; Reaction product is dissolved in THF or methylene dichloride, splashes in ether or the ethanol, collecting precipitation saidly is precipitated as maleic anhydride modified POLYACTIC ACID.
Preferably, splash in the excessive ether after said pale brown look maleic anhydride modified POLYACTIC ACID is dissolved in methylene dichloride, collecting precipitation will precipitate vacuum-drying at room temperature.
Preferably, the weight ratio of said maleic anhydride modified POLYACTIC ACID and said Mechano growth factor E structural domain 24 peptides is 50: 1, and the molar weight of said condensing agent is more than or equal to the molar weight of carboxyl in the poly-lactic acid material of said modification.
Three of the object of the invention is to provide the new application based on the POLYACTIC ACID of Mechano growth factor E structural domain 24 peptides and diamines modification, and this is applied as preparation biological activity bionic material new approaches are provided.
The technical scheme that realizes above-mentioned purpose is:
The application of said poly-lactic acid material in preparation biological activity bionic material.
Further, said biological activity bionic material is the biological activity bionic material that osteanagenesis reparation, revascularization are repaired.
Beneficial effect of the present invention is: (the Luo YF that reports with respect to existing literature based on the POLYACTIC ACID of Mechano growth factor E structural domain 24 peptides and diamines modification of the present invention; Wang YL; Niu XF; Et al.Synthesis, characterization and biodegradation of butanediamine grafted poly (DL-lactic acid) [J] .Eur Polym J, 2007; 43:3856-64.) have better wetting ability and cellular affinity and biological degradability, and be expected to improve the associated problem that cause understressing to cause in tissue repair or the regenerative therapy process.
Description of drawings
Fig. 1 is based on the POLYACTIC ACID purification liquid high-efficient liquid phase chromatogram of Mechano growth factor E structural domain 24 peptides and diamines modification.
Fig. 2 is the propagation situation analysis figure of scleroblast after glass, DPLA, MGF-t24E-DPLA material surface are cultivated 1 day, 3 days, 5 days, 7 days.
Embodiment
In order to make the object of the invention, technical scheme and a bit clearer, will combine accompanying drawing that the preferred embodiments of the present invention are carried out detailed description below.
Mechano growth factor E structural domain 24 peptides (Ct24E-MGF) that use in the present invention prepare with reference to " expression and the activation analysis of Mechano growth factor in intestinal bacteria " literature methods such as Zhang Bingbing.
The preparation of embodiment 1 maleic anhydride modified POLYACTIC ACID
5.0 grams are gathered D, and L-lactic acid and 0.5 gram maleic anhydride, 10 milligrams of tert-butyl peroxides mix, and vacuum fusion is sealed in 50 milliliters the round-bottomed flask.50 ℃ of reactions got pale brown look maleic anhydride modified POLYACTIC ACID in 24 hours.Splash in the excessive ether collecting precipitation after product is dissolved in methylene dichloride.Redissolve deposition three times.To precipitate at room temperature, vacuum got the brown maleic anhydride modified POLYACTIC ACID of 3.8 grams in irritated 48 hours; Molecular formula as:
wherein A is D, L-lactic acid.Other is through parallel test: when A is D-lactic acid or L-lactic acid, all can realize.
The preparation of embodiment 2 maleic anhydride modified POLYACTIC ACIDs
5.0 grams are gathered (D, L-lactic acid) and 0.5 gram maleic anhydride, 20 milligrams of tert-butyl peroxides mix, and vacuum fusion is sealed in 50 milliliters the round-bottomed flask.50 ℃ of reactions got pale brown look maleic anhydride modified POLYACTIC ACID in 24 hours.Splash in the excessive ether collecting precipitation after product is dissolved in methylene dichloride.Redissolve deposition three times.To precipitate at room temperature, vacuum got the brown maleic anhydride modified POLYACTIC ACID of 3.5 grams in irritated 48 hours; Molecular formula like
wherein A be D, L-lactic acid.Other is through parallel test: when A is D-lactic acid or L-lactic acid, all can realize.
The preparation of embodiment 3 maleic anhydride modified POLYACTIC ACIDs
5.0 grams are gathered (D, L-lactic acid) and 0.5 gram maleic anhydride, 30 milligrams of tert-butyl peroxides mix, and vacuum fusion is sealed in 50 milliliters the round-bottomed flask.50 ℃ of reactions got pale brown look maleic anhydride modified POLYACTIC ACID in 24 hours.Splash in the excessive ether collecting precipitation after product is dissolved in methylene dichloride.Redissolve deposition three times.To precipitate at room temperature, vacuum got the brown maleic anhydride modified POLYACTIC ACID of 4.2 grams in irritated 48 hours; Molecular formula as:
wherein A is D, L-lactic acid.Other is through parallel test: when A is D-lactic acid or L-lactic acid, all can realize.
Embodiment 4 diamines and maleic anhydride modified POLYACTIC ACID
0.25 diamines of restraining oneself is dissolved in 10 milliliters of THFs, repeats three parts; The maleic anhydride modified POLYACTIC ACID of getting 5 gram embodiment 1-3 gained respectively is dissolved in 100 milliliters of THFs.Then under the condition of room temperature (room temperature among the embodiment with reference to " explanation in the Chinese pharmacopoeia) magnetic agitation, the tetrahydrofuran solution of hexanediamine dropwise is added drop-wise in the tetrahydrofuran solution of maleic anhydride modified POLYACTIC ACID, drip afterreaction and continued 30 minutes.Product solution is dripped as in the excessive zero(ppm) water collecting precipitation, redissolve deposition three times.To precipitate at room temperature vacuum irritated 48 hours; Molecular formula is two parts of m=2 wherein like
, n=100; Another part m=2, n=2000 obtains 3.2 grams.
Embodiment 5 diamines and maleic anhydride modified POLYACTIC ACID
0.25 diamines of restraining oneself is dissolved in 10 milliliters of THFs, repeats three parts; The maleic anhydride modified POLYACTIC ACID of getting 5 gram embodiment 1-3 gained is dissolved in 100 milliliters of THFs.Then under the condition of room temperature magnetic agitation, the tetrahydrofuran solution of hexanediamine dropwise is added drop-wise in the tetrahydrofuran solution of maleic anhydride modified POLYACTIC ACID, drip afterreaction and continued 30 minutes.Product solution is dripped as in the excessive zero(ppm) water collecting precipitation, redissolve deposition three times.To precipitate at room temperature vacuum irritated 48 hours.To precipitate at room temperature vacuum irritated 48 hours; Molecular formula is two parts of m=4 wherein like
, n=100; Another part m=4, n=2000 obtains 2.8 grams.
0.25 diamines of restraining oneself is dissolved in 10 milliliters of THFs, and the maleic anhydride modified POLYACTIC ACID of 5 grams is dissolved in 100 milliliters of THFs.And then under the condition of room temperature magnetic agitation, the tetrahydrofuran solution of hexanediamine dropwise is added drop-wise in the tetrahydrofuran solution of maleic anhydride modified POLYACTIC ACID, drip afterreaction and continued 30 minutes.Product solution is dripped as in the excessive zero(ppm) water collecting precipitation, redissolve deposition three times.To precipitate at room temperature vacuum irritated 48 hours 3.5 grams diamines and maleic anhydride modified POLYACTIC ACID.To precipitate at room temperature vacuum irritated 48 hours; Molecular formula is two parts of m=6 wherein like
; N=100; Obtain, obtain 3.5 grams; Another part m=6, n=2000.
1 gram maleic anhydride and diamine modified poly-latic acid are dissolved in 10 milliliters of THFs, add 20 milligrams of Mechano growth factor E structural domain 24 peptides (aminoacid sequence is shown in SEQ ID NO:1), the room temperature lower magnetic force stirs the two is mixed; Again with 75 milligrams of N; N '-NSC 57182 adds in the above-mentioned reactant, and stirring reaction 24h under the room temperature removes by filter the insolubles N that reaction generates; N '-NSC 30023 (DCU); Filtrating is splashed in the excessive zero(ppm) water the membranaceous throw out in the collection system, redissolve deposition three times.To precipitate lyophilize and get 0.753 gram force growth factor E structural domain, 24 peptide polydactyl acids in 24 hours; Its molecular formula like
wherein A be D; In the L-lactic acid; N=100; M=6, said Ct24E-MGF are that its aminoacid sequence is shown in SEQ ID NO:1 based on Mechano growth factor E structural domain 24 peptides.
1 gram maleic anhydride and diamine modified poly-latic acid are dissolved in 10 milliliters of THFs; Add 20 milligrams of Mechano growth factor E structural domain 24 peptides (aminoacid sequence is shown in SEQ ID NO:1); The room temperature lower magnetic force stirs the two is mixed; With in 1-(3-dimethylaminopropyl)-above-mentioned reactant of 3-ethyl carbodiimide (EDC) adding of 45 milligrams, stirring reaction milligram 24h under the room temperature splashes into reaction soln in the excessive zero(ppm) water again; Membranaceous throw out in the collection system, redissolve deposition three times.To precipitate lyophilize and get 0.705 gram force growth factor E structural domain, 24 peptide polydactyl acids in 24 hours; Its molecular formula like
wherein A be D; In the L-lactic acid; N=20000; M=2, said Ct24E-MGF are that its aminoacid sequence is shown in SEQ ID NO:1 based on Mechano growth factor E structural domain 24 peptides.
Embodiment 9 is based on the preparation of the POLYACTIC ACID of Mechano growth factor E structural domain 24 peptides and diamines modification
1 gram maleic anhydride and diamine modified poly-latic acid are dissolved in 10 milliliters of THFs; Add 20 milligrams of Mechano growth factor E structural domain 24 peptides (its aminoacid sequence such as SEQ ID NO:1), the room temperature lower magnetic force stirs the two is mixed, and 60 milligrams of EDC and 60 milligrams of NHS is added in the above-mentioned reactant again; Stirring reaction 24h under the room temperature; Reacted solution is splashed in the excessive zero(ppm) water the membranaceous throw out in the collection system, redissolve deposition three times.To precipitate lyophilize and get 0.727 gram force growth factor E structural domain, 24 peptide polydactyl acids in 24 hours; Its molecular formula like
wherein A be D; In the L-lactic acid; N=2000; M=4, said Ct24E-MGF are that its aminoacid sequence is shown in SEQ ID NO:1 based on Mechano growth factor E structural domain 24 peptides.
Get detecting through the HPLC analytical column based on Mechano growth factor E structural domain 24 peptides (MGF-Ct24E) reference liquid with in the purification liquid of the POLYACTIC ACID (MGF-Ct24E-DPLA) of Mechano growth factor E structural domain 24 peptides and diamines modification of embodiment 9, the result is as shown in Figure 1.The peak of MGF-Ct24E occurred at the 15th minute, wherein a peak belongs to the MGF-Ct24E peak in the MGF-Ct24E reference liquid, and peak area is 43217144.000mAu*sec; The b peak belongs to the MGF-Ct24E peak in the MGF-Ct24E-DPLA purification liquid, and peak area is 347448.625mAu*sec.The total amount of considering the purification liquid of collection is 112ml; Is 0.738mg by peak area value according to the content that equation of linear regression calculates MGF-Ct24E in the purification liquid, and this has proved that MGF-Ct24E successfully is grafted in the diamine modified poly-latic acid (DPLA) to calculate the MGF-Ct24E that is grafted among the DPLA thus and be 0.92 μ mol/g..
Table 1 is the result of MGF-Ct24E-DPLA material amino acid analysis.The result shows that MGF-Ct24E successfully is grafted among the DPLA.The consumption of considering MGF-Ct24E is 1% (mass ratio) of DPLA, and molecular weight is 2849g/mol, and the average content of MGF-Ct24E in the DPLA material is 0.87 μ mol/g, and grafting efficiency is 24.7%.
The result of table 1MGF-Ct24E-DPLA material amino acid analysis
Embodiment 11 is based on the functional performance of the POLYACTIC ACID of Mechano growth factor E structural domain 24 peptides and diamines modification
One osteoblastic proliferation situation
TP: scleroblast is with 1 * 10
4/ cm
2Density be inoculated into the propagation situation after glass, DPLA, MGF-Ct24E-DPLA material surface are cultivated 1d, 3d, 5d, 7d,, adopt mtt assay to be detected as the proliferation activity of osteocyte on polymeric film respectively, the result sees Fig. 2 for details.The high more proliferation activity that shows of OD value is high more, and vice versa.
As can be seen from Figure 2, along with the prolongation of incubation time, the cell number on three groups of materials all has obvious increase, and when cultivating the 7th day, each organizes the surperficial cell proliferation vigor difference of substrate material highly significant.At one time, scleroblast is followed successively by in the proliferation activity size on three kinds of substrate material surfaces: MGF-Ct24E-DPLA material group>blank control group>DPLA group, the introducing of this explanation MGF-Ct24E can improve osteoblastic multiplication capacity.
The detection of two Static Water contact angles and water-intake rate
TP: take drip method to measure the Static Water contact angle.Immobilization material film on slide glass keeps material smooth, on contact angle instrument, detects then.Measuring temperature is 25 ℃.Each sample surfaces detects 6 points, and calculating mean value, and the result sees table 1 for details.Record source recording starting materials film weight is W
0, then material film is placed 37 ℃ zero(ppm) water successive soaking 24h, wipe the free-water of material surface away with filter paper, weighing is W
1Change calculations water-intake rate according to film weight before and after the suction.Water-intake rate=(W
2-W
1)/W
1* 100%.Each sample parallel testing 6 times is averaged.The result sees table 1 for details.
The Static Water contact angle and the water-intake rate of table 2 maleic anhydride and diamine modified poly-latic acid, Mechano growth factor E structural domain 24 peptide polydactyl acids.The Static Water contact angle minimum (40.4 °) of this table explanation of force growth factor E structural domain 24 peptide polydactyl acids, water-intake rate the highest (3.05%), wetting ability is best.
The Static Water contact angle and the suction of table 2DPLA and MGF-Ct24E-DPLA material
Explanation is at last; Above embodiment is only unrestricted in order to technical scheme of the present invention to be described; Although with reference to preferred embodiment the present invention is specified, those of ordinary skill in the art should be appreciated that and can make amendment or be equal to replacement technical scheme of the present invention; And not breaking away from the aim and the scope of technical scheme of the present invention, it all should be encompassed in the middle of the claim scope of the present invention.
Claims (10)
1. one kind based on Mechano growth factor E structural domain 24 peptides and diamines and maleic anhydride modified POLYACTIC ACID, it is characterized in that, said molecular formula such as I based on Mechano growth factor E structural domain 24 peptides and diamines and maleic anhydride modified POLYACTIC ACID:
Wherein A is D-lactic acid, L-lactic acid and D, and among arbitrary in the L-lactic acid, n=100-20000, m=2-6, said Ct24E-MGF are that its aminoacid sequence is shown in SEQ ID NO:1 based on Mechano growth factor E structural domain 24 peptides.
2. the POLYACTIC ACID based on Mechano growth factor E structural domain 24 peptides and diamines modification according to claim 1 is characterized in that said A is D, L-lactic acid, n=100-2000, m=2-6.
3. the preparation method of claim 1 or 2 described POLYACTIC ACIDs based on Mechano growth factor E structural domain 24 peptides and diamines modification is characterized in that concrete steps are:
The preparation of A diamines and maleic anhydride modified POLYACTIC ACID
With diamines, molecular formula the maleic anhydride modified POLYACTIC ACID reaction as III shown in of molecular formula, generate diamines and the maleic anhydride modified POLYACTIC ACID of molecular formula such as IV like II:
B is based on the preparation of the POLYACTIC ACID of Mechano growth factor E structural domain 24 peptides and diamines modification
Diamines and maleic anhydride modified POLYACTIC ACID with molecular formula such as IV; With Mechano growth factor E structural domain 24 peptides shown in SEQ ID NO:1 be raw material; With arbitrary in DCC, EDC or the mixture be condensing agent, reaction is 8-48 hour under 0-50 ℃ of condition, said reaction solution adds in the water medium; Produce membranaceous throw out, said membranaceous throw out is the POLYACTIC ACID based on Mechano growth factor E structural domain 24 peptides and diamines modification of molecular formula such as I; Wherein mixture is for being that 1: 1 EDC and NHS mixes with mass ratio; DCC is meant N; N '-NSC 57182; EDC is meant 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide, and NHS is meant 1-(3-dimethylaminopropyl)-3-ethyl carbodiimide and N-hydroxy-succinamide; A is D-lactic acid, L-lactic acid and D among the I, among arbitrary in the L-lactic acid, and n=100-20000, m=2-6,
4. preparation method according to claim 3 is characterized in that, specifically may further comprise the steps:
1) said maleic anhydride modified POLYACTIC ACID is dissolved in the organic solvent, adds said growth factor E structural domain 24 peptides, stir, reaction solution A, said organic solvent be in THF, DMSO 99.8MIN., the methylene dichloride any;
2) condensing agent is added among the above-mentioned reaction solution A, reaction is 8-48 hour under 0-50 ℃ of condition, gets reaction solution B;
3) reaction solution B is added dropwise in the zero(ppm) water, collects membranaceous throw out, said membranaceous throw out is the POLYACTIC ACID based on Mechano growth factor E structural domain 24 peptides and diamines modification;
In the above-mentioned reaction system, said maleic anhydride and diamine modified poly-latic acid concentration are/10 milliliters of 0.5 gram-3 grams, and Mechano growth factor E structural domain 24 peptide concentrations are 5-30 milligram/10 milliliter, and said condensing agent concentration is 45-75 milligram/10 milliliter.
5. preparation method according to claim 3 is characterized in that, with the membranaceous throw out lyophilize of gained.
6. preparation method according to claim 3 is characterized in that, the preparation method of maleic anhydride modified POLYACTIC ACID described in the steps A is: with toxilic acid acyl and POLYACTIC ACID; Generate maleic anhydride modified POLYACTIC ACID through free radical reaction; Initiator in the reaction is tert-butyl peroxide or peroxo-phenyl-diformyl, and the reaction times is 40-150 ℃, and said toxilic acid acyl is 0.5%-20% by weight percentage; Initiator uses weight percent to be 0.1%-10%, and surplus is a POLYACTIC ACID; Reaction product is dissolved in THF or methylene dichloride, splashes in ether or the ethanol, collecting precipitation saidly is precipitated as maleic anhydride modified POLYACTIC ACID.
7. preparation method according to claim 6 is characterized in that, splashes in the excessive ether after said maleic anhydride modified POLYACTIC ACID is dissolved in methylene dichloride, and collecting precipitation will be deposited in vacuum-drying.
8. preparation method according to claim 4 is characterized in that, the weight ratio of said maleic anhydride and diamine modified poly-latic acid and said Mechano growth factor E structural domain 24 peptides is 50: 1.
9. claim 1 or the 2 said application of POLYACTIC ACID in preparation biological activity bionic material based on Mechano growth factor E structural domain 24 peptides and diamines modification.
10. application according to claim 9 is characterized in that: said biological activity bionic material is the biological activity bionic material that osteanagenesis reparation, revascularization are repaired.
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CN103520769A (en) * | 2013-09-04 | 2014-01-22 | 重庆大学 | Macrophage growth factor (MGF) or E peptide modified tissue engineering scaffold material and preparation method thereof |
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 |
CN108929439A (en) * | 2017-05-22 | 2018-12-04 | 四川理工学院 | Multifunctional polymer and its preparation method and application |
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廖保强: "力生长因子E肽促进骨愈合及含E肽生物活性材料的研究", 《中国优秀硕士学位论文全文数据库医药卫生科技辑》 * |
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CN103316600B (en) * | 2013-05-14 | 2015-03-25 | 中国科学院宁波材料技术与工程研究所 | Method for fixing heparin on polylactic acid hemodialysis membrane surface |
CN103520769A (en) * | 2013-09-04 | 2014-01-22 | 重庆大学 | Macrophage growth factor (MGF) or E peptide modified tissue engineering scaffold material and preparation method thereof |
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 |
CN108929439A (en) * | 2017-05-22 | 2018-12-04 | 四川理工学院 | Multifunctional polymer and its preparation method and application |
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