CN101445607A - Copolymer of fibroin and poly D,L-lactic acid, preparation method and application thereof - Google Patents
Copolymer of fibroin and poly D,L-lactic acid, preparation method and application thereof Download PDFInfo
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Abstract
The invention discloses a copolymer of fibroin and a poly D,L-lactic acid. The molecular weight of the copolymer having the structure is 5,000 to 180,000, and the mass ratio of the fibroin chain segment and the poly L-lactic acid chain segment is 0.5/99.5-99/0.5. The invention also discloses a solid phase polymerization preparation method thereof, the application thereof in biomedical materials, nano material thereof and a preparation method of nano materials. Copolymer of fibroin and poly D,L-lactic acid is prepared by adopting melt ring opening polymerization, and solvent is not used in the synthesis technique; therefore, the invention has the advantages that the process is simple, and the product cost is low. Through the invention, copolymer of fibroin and poly D,L-lactic acid with different number average molecular weight can be prepared. Copolymer of fibroin and poly D,L-lactic acid prepared by the invention can improve the hydrophilicity, the biocompatibility and the cellualar affinity of lactic acid material and control the degradation speed of the material.
Description
Technical field:
The invention belongs to technical field of polymer materials, be specifically related to a kind of fibroin and poly-D, multipolymer of L-lactic acid and its production and application.
Background technology:
Poly(lactic acid) (PLA) is the good biodegradable absorption macromolecular material of a kind of biocompatibility, product with good biocompatibility, degraded can participate in metabolism, the low toxin of human body, has been widely used in organizational project and other biological field of medicaments.But also there is performance deficiency in poly(lactic acid), as fragility is big, mechanical strength is lower and degradation cycle is restive etc.In addition, PLA is hydrophobic polymer, and the adhesivity of pair cell is relatively poor.Pure poly(lactic acid) can cause the inflammatory reaction that some are gentle after as tissue engineering material implantable bioartificial body.Therefore, in order to improve poly-lactic acid material mechanical property, biodegradability and biocompatibility, must carry out modification to poly-lactic acid material.The normal method of modifying that adopts comprises modification by copolymerization method, plasma surface treatment, finishing method etc.Wherein, modification by copolymerization is the important molecular engineering mode of poly(lactic acid), wetting ability, crystallinity by can changing material with the copolymerization of other monomers or oligopolymer etc., the degradation speed of polymkeric substance can be controlled according to the molecular weight of multipolymer and comonomer or oligopolymer kind and proportioning etc., thereby realizes the widespread use of poly-lactic acid material aspect organizational project.
The modification by copolymerization operational path of poly(lactic acid) comprises two kinds of the copolycondensations of the ring-opening polymerization of rac-Lactide/comonomer and lactic acid/comonomer.Hydrophilic polymer segment is introduced in copolymerization such as rac-Lactide or lactic acid and hydrophilic monomer or polymkeric substance such as polyoxyethylene glycol, amino acid, poly-peptide and polyose in hydrophobic polylactic acid chain segment, can improve the biocompatibility of material, regulates its degradation rate.
Polyamino acid has a plurality of active function groups, can the immobilizing biologically active molecule, and as protein, carbohydrate, polypeptide etc., its side chain can be connected with little peptide, medicine or linking agent etc., promotes the adhesion and the growth of cell.Polyamino acid itself also has excellent biological compatibility and biodegradable, and its degraded product amino acid is to human body toxicological harmless effect.The polyamino acid segment is introduced poly(lactic acid), can reduce degree of crystallinity, adjusting degradation property, the raising wetting ability of poly(lactic acid).The reactive functional of multipolymer side chain can adsorbed proteins, carbohydrate, polypeptide etc., makes whole multipolymer macromolecular chain obtain specific amino-acid sequence so that cell recognition, thereby the effective immobilizing biologically active factor improves the affinity of poly(lactic acid) and cell.
Lactic acid-amino acid copolymer generally prepares by the ring opening copolymer of rac-Lactide and amino acid cyclic derivatives, and wherein the copolymerization of lactic acid/Methionin system research at most.Barrera etc. then synthesize earlier and contain lactic acid structural unit and the unitary cyclic dimer of amino protected Methionin, obtain containing the lactic acid-Methionin multipolymer of Methionin unit 2.6% again with rac-Lactide positively charged ion ring-opening copolymerization.But the amino coupling small peptide of this multipolymer is given its better biological activity, can effectively improve bonding strength (J.Am.Chem.Soc., 2004,115 (23): 11010-11011) of its pair cell.Jin etc. have synthesized the unitary cyclic dimer of amino protected Serine earlier, then with rac-Lactide reaction, have synthesized the lactic acid that contains Serine 2% and multipolymer (Polymer, 1998,39 (21): 5155-5162) of Serine.Elisseeff and Kimura etc. prepare the alternating copolymer of lactic acid and glycine, Methionin by designing new ring, and these materials are good carriers of cell cultures and organizational project.Aminoacids content has remarkably influenced to its performance in the multipolymer, and its second-order transition temperature, fusing point, degree of crystallinity all are lower than poly (l-lactic acid) (PLLA), and its degradation speed is slightly faster than PLLA.Aminoacids content is high more in the multipolymer, and degradation speed is fast more.By changing Modulatory character (Elisseeff, Macromolecules, 1997,30 (7): 2182～2184 that aminoacids content can be realized the degradation speed of polylactic acid-based material in the multipolymer.Kimura，Macromolecules，2006，21(11)：3338～3340)。Chinese patent ZL03135454.8 discloses a kind of poly(lactic acid)-amino acid ester blend and preparation method thereof, adopt the solution blended process polydactyl acid, obtain the blend of poly(lactic acid)/amino acid ester, this blend material has good biocompatibility and interface compatibility, can be used as tissue stent material.But amino acid whose preparation and polymerization cost height, complex process, and the content of amino acid segment is lower in the multipolymer, has influenced the improvement of material property.
Fibroin (SF) is a kind of natural amino acid multipolymer, has good mechanical property and biocompatibility.Contain 18 seed amino acids in the fibroin protein, wherein glycine (36%), L-Ala (28%), Serine (14%) and tyrosine (10%) content are more.Some amino acid of fibroin extensively are present in people and the vertebrate tissue, and human body cell is had affinity.Fibroin can be made as various ways such as fiber, powder, gel, silk peptide powder and fibroin membrane according to different research purposes and preparation condition, can be used as makeup base material, foodstuff additive and medical material etc.In recent years, the gel of fibroin and porous material have been developed as drug release carrier, three-dimensional cell substratum, artificial skin, anticoagulant material and dialysis membrane etc., but the regenerated silk protein material remains in mechanical property and the unmanageable problem of degradation speed.And pure fibroin membrane dissolve-loss ratio is very high, can not directly use, and after the insoluble processing, intensity is bigger, but elongation is very little, and Tg surpasses 200 ℃, and film is not only hard but also crisp, is difficult to use in vivo, uses so must just can be used as medical material later on through modification.Domestic having mixed fibroin and poly(lactic acid), the research report of the preparation bio-medical material that cell adhesion is good, degradation property is good.Chen Jianyong, Zhang Jiazhong etc. carry out modification with poly (l-lactic acid) to fibroin membrane, and the mechanical property of co-blended film obviously improves, and vapour permeability also increases, (chemical industry journal, 2008,3 (59): 773～777 but water vapour permeability slightly descends; Functional materials, 2007,12 (38): 2048～2051).Zhou Yan, Liu Yang etc. utilize fibroin protein solution and poly(lactic acid) solution thorough mixing to make blend film.Change the structure properties effect of fibroin, preparation Biodegradable films (silk monthly magazine, 2007,4:16～18).
Poly(lactic acid) has good performance as biodegradable material.Fibroin can carry out acid or alkali catalyzed hydrolysis, generates the fibroin than small molecular weight.Can obtain the water miscible fibroin (SF) of desired molecule amount by the concentration, hydrolysis time, temperature etc. of control silk fibroin solution.Therefore, on the basis of taking all factors into consideration these two kinds of material properties of fibroin and poly(lactic acid), utilize fibroin, carry out ring opening copolymer with rac-Lactide as hydrophilic radical, can synthetic segmented copolymer.But this respect does not still have the research report at present both at home and abroad.
The serious scarcity of China's oil resource has restricted expanding economy, and China has the Biological resources of abundant lactic acid class, can substitute petroleum chemicals.Simultaneously, China is silk big country in the world, and waste silk in the production and waste cocoon can prepare the fibroin peptide chain.Fibroin/polylactic acid modified material all is with a wide range of applications in fields such as bio-medical material, textile materials, plastics and coating.
Summary of the invention:
Technical problem to be solved by this invention provides a kind of fibroin and poly-D, and the multipolymer of L-lactic acid is with wetting ability, biocompatibility, the cellular affinity that improves poly-lactic acid material, the degradation speed of control material.
The technical problem that the present invention also will solve provides the preparation method of above-mentioned multipolymer.
Another technical problem that the present invention also will solve provides a kind of fibroin and poly-D, the nano material of the multipolymer of L-lactic acid.
The technical problem again that the present invention also will solve provides above-mentioned preparation of nanomaterials.
Last technical problem that the present invention also will solve provides above-mentioned fibroin and poly-D, the application of the multipolymer of L-lactic acid.
For solving the problems of the technologies described above, the technical solution used in the present invention is as follows:
A kind of fibroin and poly-D, the multipolymer of L-lactic acid, this multipolymer has following structure:
Wherein, X is 1～2500 a integer, and Y is 1～970 a integer, and R is: H ,-CH
3,-CH
2OH ,-CH
2SH ,-CH (HO) CH
3,-CH (CH
3)
2,-CH
2CH (CH
3)
2,-CH (CH
3) CH
2CH
3,-CH
2CH
2SCH
3,-CH
2COOH ,-CH
2CH
2CONH
2,-CH
2CH
2CH
2CH
2NH
2,-CH
2CH
2CH
2CH
2NH
2,
In any one;
This molecular weight of copolymer is 5000～180000, fibroin segment and poly-D, and L-lactic acid segmental mass ratio is 0.5/99.5～99.5/0.5.
Above-mentioned fibroin and poly-D, the preparation method of the multipolymer of L-lactic acid comprises the steps:
(1) the fusion ring-opening polymerization prepares fibroin and poly-D, the multipolymer of L-lactic acid (PDLLASF):
With catalyst system, D, the silk fibroin powder after L-rac-Lactide and the dehydration adds in the polymeric kettle, under 0～30 mmhg pressure, under 140～200 ℃, reacts 2～40 hours; Described catalyst body is tin compound and organic acid compound system, and wherein the molar content of tin compound accounts for 1～99% of whole catalyst system; The consumption of tin compound is D in the catalyst system, 0.01～6.0wt% of L-rac-Lactide quality, and fibroin and D, the mass ratio of L-rac-Lactide are 1/99～99/1;
(2) fibroin peptide chain and poly-D, the purifying of the multipolymer of L-lactic acid (PDLLASF):
The multipolymer that step (1) is obtained is dissolved in ethyl acetate, and filtration is also used ether sedimentation, and the throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 10～16 hours.At PDLLASF multipolymer shown in Figure 1
13On the C-NMR nuclear magnetic resonance spectrum, fibroin segmental charateristic avsorption band is 44.8ppm, 50.6ppm, 166.6ppm and 169.6ppm, poly (l-lactic acid) segmental charateristic avsorption band is positioned at 69.2ppm, 169.48ppm, and the poly (l-lactic acid) segment absorption peak 66-72ppm place that copolymerization is connected with fibroin, promptly this multipolymer is made up of polylactic acid chain segment and fibroin peptide segment.
The relative molecular mass of the described fibroin of step (1) is 1000～100000.The molecular weight of fibroin has tangible influence equally to the structure and the performance of multipolymer, can obtain the silk peptide segment of different chain lengths by the hydrolysising condition of fibroin, and the molecular weight of the used fibroin of the present invention is 1000～100000.
The described catalyst body of step (1) is tin compound and organic acid compound system, and so-called compound system is about to the system that above-mentioned two kinds of materials mix formation.Tin compound is SnCl
2, SnCl
22H
2O, SnCl
4, SnCl
42H
2The mixture of any one in O, stannous octoate and the tributyl methoxyl group tin or two or more arbitrary proportions; Organic acid is the mixture of any one or two or more arbitrary proportions in acetate, sad, halogenated carboxylic acid, fluosulfonic acid, Phenylsulfonic acid, tosic acid, naphthene sulfonic acid, naphthalene disulfonic acid and Phenylsulfonic acid, naphthene sulfonic acid and the naphthalene disulfonic acid that contains methyl, dimethyl, trimethylammonium, methylol, ethyl, diethyl, propyl group or sec.-propyl.The preferred SnCl of described catalyst system
2/ acetate, SnCl
22H
2O/ is sad, stannous octoate/sad etc., SnCl
2/ Phenylsulfonic acid, SnCl
4/ Phenylsulfonic acid, SnCl
2/ p-methyl benzenesulfonic acid, SnCl
2/ naphthene sulfonic acid, SnCl
2The mixture of any one in/naphthalene disulfonic acid, stannous octoate/naphthene sulfonic acid, the stannous octoate/naphthalene disulfonic acid or two or more arbitrary proportions.When the fusion ring-opening polymerization, can select different catalyst systems for use, the microstructure of control multipolymer, synthetic multipolymer with different molecular weight and molecular weight distribution.Table 1 and table 2 are the intrinsic viscosities of PSFLA under the different catalysts proportioning.
The intrinsic viscosity of PSFLA under the table 1 different catalysts proportioning
Reaction conditions: rac-Lactide: fibroin=10:1 (mass ratio), reaction times 6h, 170 ℃ of temperature of reaction, SnCl
2Consumption 0.5wt%.
Catalyst proportion: A:SnCl
2/ naphthalene disulfonic acid=2:1 (mol ratio); B:SnCl
2/ naphthalene disulfonic acid=1:1 (mol ratio);
C:SnCl
2/ naphthalene disulfonic acid=1:2 (mol ratio).
The intrinsic viscosity of PSFLA under the table 2 different catalysts proportioning
Reaction conditions: rac-Lactide: fibroin=6:1 (mass ratio), reaction times 6h, 170 ℃ of temperature of reaction, SnCl
2Consumption 0.5wt%.
Catalyst proportion: A:SnCl
2/ naphthalene disulfonic acid=2:1 (mol ratio); B:SnCl
2/ naphthalene disulfonic acid=1:1 (mol ratio); C:SnCl
2/ naphthalene disulfonic acid=1:2 (mol ratio).
D, the L-rac-Lactide is by D, and L-lactic acid cyclisation dimerization forms, and major impurity is residual lactic acid, water, and oligopolymer, their contained-OH are to D, the ring-opening polymerization of L-rac-Lactide influence is very big, can make catalyzer lose catalytic activity, in addition-OH can participate in chain initiation, shift, stop, therefore be difficult to obtain high molecular weight polylactic acid, so rough D, the L-rac-Lactide must just can be used for the preparation of homopolymer and multipolymer through refining.Recrystallization D, the fusing point of L-rac-Lactide are 125.0 ℃, and melting range is in 1.0 ℃, and the D of this purity, L-rac-Lactide just can make polymerization single polymerization monomer and use.
Fibroin protein absorbs water easily, and minor amount of water may cause D, the hydrolysis of L-rac-Lactide, thus influence the smooth implementation of ring-opening polymerization.Therefore the used fibroin protein of the present invention needs to use through 40～70 ℃ of vacuum hydro-extraction 8-10 hours ability, and the main purpose of dehydration is the moisture of removing in the raw material, suppresses D, the hydrolysis reaction of L-rac-Lactide.
D, the L-rac-Lactide can carry out ring-opening polymerization with a spot of active group under the condition that catalyzer exists.The carboxyl end groups of fibroin and amino end group all have higher activity, under the effect of catalyzer, can with D, the ring-opening polymerization of L-rac-Lactide, reactional equation is as shown below:
A kind of fibroin and poly-D, the nano material of the multipolymer of L-lactic acid, this multipolymer has following structure:
Wherein, X is 1～2000 a integer, and Y is 1～2000 a integer, and R is: H ,-CH
3,-CH
2OH ,-CH
2SH ,-CH (HO) CH
3,-CH (CH
3)
2,-CH
2CH (CH
3)
2,-CH (CH
3) CH
2CH
3,-CH
2CH
2SCH
3,-CH
2COOH ,-CH
2CH
2CONH
2,-CH
2CH
2CH
2CH
2NH
2,-CH
2CH
2CH
2CH
2NH
2,
In any one;
Molecular weight of copolymer is 5000～180000, fibroin segment and poly-D, and L-lactic acid segmental mass ratio is 0.5/99.5～99.5/0.5, its thickness of thin layer 20～80 nanometers.
Above-mentioned fibroin and poly-D, the preparation of nanomaterials of the multipolymer of L-lactic acid is: with fibroin behind the purifying and poly-D, the multipolymer of L-lactic acid is dissolved in the good solvent, form the solution of concentration 0.1～5g/100mL, precipitate as precipitation agent with poor solvent, the volumetric usage of precipitation agent is 0.5～20.0 times a good solvent volume again, and throw out was 65 ℃ of following vacuum-dryings 10～16 hours, obtain fibroin and poly-D, the nano material of the multipolymer of L-lactic acid.
Wherein, described good solvent is the mixture of any one or two or more arbitrary proportions in chloroform, tetrahydrofuran (THF), ethyl acetate, monochloroethane and the trifluoroacetic acid; Described poor solvent is the mixture of any one or two or more arbitrary proportions in toluene, methyl alcohol, ethanol, acetone and the ether.Preferably with in chloroform/ether, chloroform/methanol or the chloroform/acetone any one as solvent/precipitation agent system.
Above-mentioned fibroin and poly-D, the multipolymer of L-lactic acid can be in the widespread use of biomedical materials field such as suture, medicine sustained release, artificial organ and tissue engineering material, also can be in the widespread use in suture, medicine sustained release, artificial organ and tissue engineering material field, and develop it and using in fields such as textile materials, plastics and coating.
The present invention is by changing the proportioning of rac-Lactide and fibroin, and poly(lactic acid)-fibroin multipolymer that preparation has different degradation rates and mechanical property satisfies different purposes.The molecular weight of multipolymer, fusing point, second-order transition temperature, degree of crystallinity and degradation rate all change and change along with monomeric ratio.The result of X-ray diffraction shows, with SnCl
2When/naphthalene disulfonic acid (two component mol ratios are 1:1) was catalyzer, when the mass ratio of rac-Lactide/fibroin was 10/1, the PDLLASF sample had partial crystallization attitude structure.And the mass ratio of rac-Lactide/fibroin is 6/1 o'clock, and the PDLLAS sample has amorphous state structure (see figure 2).Low-molecular-weight PDLLASF can be used for pharmaceutical auxiliary agent, pharmaceutical carrier, protein release vehicle and vaccine adjuvant etc., and high-molecular weight PDLLASF then can be used to prepare film, wet-spinning and tissue engineering material.
Beneficial effect: the present invention adopts the fusion ring-opening polymerization to prepare fibroin and poly-D, and the multipolymer of L-lactic acid does not use solvent in synthesis technique, thereby technology is simple, and product cost is low.The present invention can prepare the fibroin and the poly-D of different number-average molecular weights, and the multipolymer of L-lactic acid, molecular weight are 5000～180000.The fibroin and the poly-D of the present invention preparation, the multipolymer of L-lactic acid can improve wetting ability, biocompatibility, the cellular affinity of poly-lactic acid material, the degradation speed of control material.
Description of drawings
Fig. 1 is fibroin and poly-D, the multipolymer of L-lactic acid
13The C-NMR spectrogram.
Fig. 2 is the X-diffraction spectrogram of the PSFLA of different catalysts proportioning.Polymeric reaction condition: monomeric mass ratio is rac-Lactide: fibroin=8:1, reaction times 6h, 170 ℃ of temperature of reaction, SnCl
2Consumption 0.5wt%; The mole proportioning of catalyst system is: A:SnCl
2/ naphthalene disulfonic acid=2:1; B:SnCl
2/ naphthalene disulfonic acid=1:1; C:SnCl
2/ naphthalene disulfonic acid=1:2.
Fig. 3 is fibroin and poly-D, the SEM photo of the nano material of the multipolymer of L-lactic acid.Reaction conditions: monomeric mass ratio is rac-Lactide: fibroin=8:1, reaction times 6h, and 170 ℃ of temperature of reaction, catalyzer is SnCl
2/ naphthalene disulfonic acid system, SnCl
2Consumption 0.75wt%, catalyst molar ratio 1:1.
Fig. 4 is fibroin and poly-D, the SEM photo of the nano material of the multipolymer of L-lactic acid.Reaction conditions: monomeric mass ratio is rac-Lactide: fibroin=6:1, reaction times 6h, and 170 ℃ of temperature of reaction, catalyzer is SnCl
2With naphthalene disulfonic acid catalyst system, SnCl
2Consumption 0.75wt%, the mole proportioning 1:1 of catalyzer.
Embodiment:
According to following embodiment, the present invention may be better understood.Yet, those skilled in the art will readily understand that the described concrete material proportion of embodiment, processing condition and result thereof only are used to illustrate the present invention, and should also can not limit the present invention described in detail in claims.
Embodiment 1:
With D, silk fibroin powder (number average relative molecular mass 3000), SnCl after L-rac-Lactide, the dehydration
2/ Catalyzed by p-Toluenesulfonic Acid agent system (SnCl
2Molar content account for whole catalyst system 50%) add in the polymeric kettle.SnCl
2Consumption be D, the 0.5wt% of L-rac-Lactide, D, L-rac-Lactide and fibroin quality are than being 4:1.The pressure of system progressively is reduced to the sealing of 0 mmhg (pressure warning unit reading) back, and temperature of reaction is 170 ℃, and the reaction times is 10 hours.Polymerization is dissolved in ethyl acetate with the multipolymer that obtains after finishing, and filtration is also used ether sedimentation, and the throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 16 hours.Be yellow powder behind this multipolymer purifying, molecular weight 1.20 ten thousand, yield are 75%, no fusing point.
Embodiment 2:
With D, L-rac-Lactide, fibroin protein powder (the number average relative molecular mass is 3000), SnCl
2/ naphthene sulfonic acid catalyst system (SnCl
2Molar content account for whole catalyst system 50%) add in the polymeric kettle.SnCl
2Consumption be D, the 0.5wt% of L-rac-Lactide, D, the mass ratio of L-rac-Lactide and fibroin are 10:1.Seal after the pressure of system progressively is reduced to 10 mmhg, temperature of reaction is 170 ℃, and the reaction times is 10 hours.Polymerization is dissolved in ethyl acetate with the multipolymer that obtains after finishing, and filters and use ether sedimentation.The throw out that leaches obtains the poly(lactic acid) and the fibroin protein peptide chain multipolymer of purifying 65 ℃ of following vacuum-dryings 16 hours.Be yellow powder behind this multipolymer purifying, molecular weight 1.63 ten thousand, yield are 73%, 120 ℃ of fusing points.
Embodiment 3:
With D, L-rac-Lactide, fibroin protein powder (the number average relative molecular mass is 1000), stannous octoate/naphthene sulfonic acid catalyst system (molar content of stannous octoate account for whole catalyst system 50%) add in the polymeric kettle.The consumption of stannous octoate is D, the 0.5wt% of L-rac-Lactide, and D, the mass ratio of L-rac-Lactide and fibroin are 10:1.Seal after the pressure of system progressively is reduced to 2 mmhg, temperature of reaction is 170 ℃, and the reaction times is 15 hours.Polymerization is dissolved in ethyl acetate with the multipolymer that obtains after finishing, and filters and use ether sedimentation.The throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 10 hours.Be yellow powder behind this multipolymer purifying, molecular weight 1.8 ten thousand, yield are 76%, 130 ℃ of fusing points.
Embodiment 4:
With D, L-rac-Lactide, fibroin protein powder (the number average relative molecular mass is 1000), SnCl
4/ Phenylsulfonic acid catalyst system (SnCl
4Molar content account for whole catalyst system 50%) add in the polymeric kettle.SnCl
4Consumption be D, the 0.5wt% of L-rac-Lactide, D, the mass ratio of L-rac-Lactide and fibroin are 2:1.The pressure of system progressively is reduced to the sealing of back below 1 mmhg, and temperature of reaction is 170 ℃, and the reaction times is 15 hours.Polymerization is dissolved in ethyl acetate with the multipolymer that obtains after finishing, and filters and use ether sedimentation.The throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 16 hours.Be yellow powder behind this multipolymer purifying, molecular weight 5.0 ten thousand, no fusing point belongs to amorphous polymer, and yield is 69%.
Embodiment 5:
With D, L-rac-Lactide, fibroin protein powder (the number average relative molecular mass is 1000), SnCl
2/ tosic acid/naphthalene disulfonic acid catalyst system (SnCl
2Molar content account for 50% of whole catalyst system, the mol ratio 1/1 of tosic acid and naphthalene disulfonic acid) add in the polymeric kettle.SnCl
2Consumption be D, the 0.5wt% of L-rac-Lactide, D, the mass ratio of L-rac-Lactide and fibroin are 99:1.The pressure of system progressively is reduced to the sealing of back below 1 mmhg, and temperature of reaction is 200 ℃, and the reaction times is 4 hours.Polymerization is dissolved in ethyl acetate with the multipolymer that obtains after finishing, and filters and use ether sedimentation.The throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 16 hours.Be yellow powder behind this multipolymer purifying, molecular weight 1.1 ten thousand, 130.0 ℃ of fusing points, yield are 69%.
Embodiment 6:
With D, L-rac-Lactide, fibroin protein powder (the number average relative molecular mass is 1000000), SnCl
2/ acetic acid catalyst system (SnCl
2Molar content account for whole catalyst system 99%) add in the polymeric kettle.SnCl
2Consumption be D, the 6.0wt% of L-rac-Lactide, D, the mass ratio of L-rac-Lactide and fibroin are 1:99.The pressure of system progressively is reduced to the sealing of back below 1 mmhg, and temperature of reaction is 140 ℃, and the reaction times is 40 hours.Polymerization is dissolved in ethyl acetate with the multipolymer that obtains after finishing, and filters and use ether sedimentation.The throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 16 hours.Be yellow powder behind this multipolymer purifying, molecular weight 11.0 ten thousand, no fusing point, yield are 65%.
Embodiment 7:
With D, silk fibroin powder (number average relative molecular mass 3000), SnCl after L-rac-Lactide, the dehydration
2/ Catalyzed by p-Toluenesulfonic Acid agent system (SnCl
2Molar content account for whole catalyst system 50%) add in the polymeric kettle.SnCl
2Consumption be D, the 0.5wt% of L-rac-Lactide, D, L-rac-Lactide and fibroin quality are than being 4:1.The pressure of system progressively is reduced to the sealing of 0 mmhg (pressure warning unit reading) back, and temperature of reaction is 170 ℃, and the reaction times is 2 hours.Polymerization is dissolved in ethyl acetate with the multipolymer that obtains after finishing, and filtration is also used ether sedimentation, and the throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 16 hours.Be yellow powder behind this multipolymer purifying, molecular weight 5000, yield are 45%, no fusing point.
Embodiment 8:
With D, L-rac-Lactide, fibroin protein powder (number average relative molecular mass 3000), SnCl
2/ naphthalene disulfonic acid catalyst system (SnCl
2Molar content account for whole catalyst system 1%) add in the polymeric kettle.SnCl
2Consumption be D, the 0.05wt% of L-rac-Lactide, D, the mass ratio of L-rac-Lactide and fibroin are 2:1.The pressure of system progressively is reduced to the sealing of back below 2 mmhg, and temperature of reaction is 170 ℃, and the reaction times is 6 hours.Polymerization is dissolved in ethyl acetate with the multipolymer that obtains after finishing, and filters and use ether sedimentation.The throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 16 hours.This molecular weight of copolymer 2.0 ten thousand, yield are 75%.
This multipolymer is dissolved in chloroform, 50 milliliters of the solution of preparation 0.5g/100mL, and under agitation slowly drip 200 milliliters of ether.Behind the gained solution Air drying,, obtain the nano thin-layer material (as shown in Figure 3) of multipolymer again 65 ℃ of following vacuum-dryings 16 hours.
Embodiment 9:
With D, L-rac-Lactide, fibroin protein powder (number average relative molecular mass 3000), SnCl
2/ naphthalene disulfonic acid catalyst system (SnCl
2Molar content account for whole catalyst system 60%) add in the polymeric kettle.SnCl
2Consumption be D, the 0.5wt% of L-rac-Lactide, D, the mass ratio of L-rac-Lactide and fibroin are 50:1.Seal after the pressure of system progressively is reduced to 30 mmhg, temperature of reaction is 170 ℃, and the reaction times is 10 hours.Polymerization is dissolved in ethyl acetate with the multipolymer that obtains after finishing, and filters and use ether sedimentation.The throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 16 hours.This molecular weight of copolymer 1.48 ten thousand, yield is 53%.
This multipolymer is dissolved in chloroform, 50 milliliters of the solution of preparation 1g/100mL, and under agitation slowly drip 400 ml methanol.Behind the gained solution Air drying,, obtain the nano thin-layer material (as shown in Figure 4) of multipolymer again 65 ℃ of following vacuum-dryings 12 hours.
Claims (10)
1, a kind of fibroin and poly-D, the multipolymer of L-lactic acid is characterized in that this multipolymer has following structure:
Wherein, X is 1～2000 a integer, and Y is 1～2000 a integer, and R is: H ,-CH
3,-CH
2OH ,-CH
2SH ,-CH (HO) CH
3,-CH (CH
3)
2,-CH
2CH (CH
3)
2,-CH (CH
3) CH
2CH
3,-CH
2CH
2SCH
3,-CH
2COOH ,-CH
2CH
2CONH
2,-CH
2CH
2CH
2CH
2NH
2,-CH
2CH
2CH
2CH
2NH
2,
In any one;
This molecular weight of copolymer is 5000～180000, fibroin segment and poly-D, and L-lactic acid segmental mass ratio is 0.5/99.5～99.5/0.5.
2, described fibroin of claim 1 and poly-D, the preparation method of the multipolymer of L-lactic acid is characterized in that this method comprises the steps:
(1) the fusion ring-opening polymerization prepares fibroin and poly-D, the multipolymer of L-lactic acid:
With catalyst system, D, the silk fibroin powder after L-rac-Lactide and the dehydration adds in the polymeric kettle, under 0～30 mmhg pressure, under 140～200 ℃, reacts 2～40 hours; Described catalyst body is tin compound and organic acid compound system, and wherein the molar content of tin compound accounts for 1～99% of whole catalyst system; The consumption of tin compound is D in the catalyst system, 0.01～6.0wt% of L-rac-Lactide quality, and fibroin and D, the mass ratio of L-rac-Lactide are 1/99～99/1;
(2) fibroin and poly-D, the purifying of the multipolymer of L-lactic acid:
The multipolymer that step (1) is obtained is dissolved in ethyl acetate, and filtration is also used ether sedimentation, and the throw out that leaches obtains the fibroin and the poly-D of purifying, the multipolymer of L-lactic acid 65 ℃ of following vacuum-dryings 10～16 hours.
3, fibroin according to claim 2 and poly-D, the preparation method of the multipolymer of L-lactic acid is characterized in that the relative molecular mass of the described fibroin of step (1) is 1000～100000.
4, fibroin according to claim 2 and poly-D, the preparation method of the multipolymer of L-lactic acid is characterized in that the described catalyst system of step (1), tin compound is SnCl
2, SnCl
22H
2O, SnCl
4, SnCl
42H
2The mixture of any one in O, stannous octoate and the tributyl methoxyl group tin or two or more arbitrary proportions; Organic acid is the mixture of any one or two or more arbitrary proportions in acetate, sad, halogenated carboxylic acid, fluosulfonic acid, Phenylsulfonic acid, tosic acid, naphthene sulfonic acid, naphthalene disulfonic acid and Phenylsulfonic acid, naphthene sulfonic acid and the naphthalene disulfonic acid that contains methyl, dimethyl, trimethylammonium, methylol, ethyl, diethyl, propyl group or sec.-propyl.
5, fibroin peptide chain according to claim 4 and poly-D, the preparation method of the multipolymer of L-lactic acid is characterized in that described catalyst body is SnCl
2/ acetate, SnCl
2/ sad, stannous octoate/sad, SnCl
2/ Phenylsulfonic acid, SnCl
4/ Phenylsulfonic acid, SnCl
2/ p-methyl benzenesulfonic acid, SnCl
2/ naphthene sulfonic acid, SnCl
2The mixture of any one in/naphthalene disulfonic acid, stannous octoate/naphthene sulfonic acid, the stannous octoate/naphthalene disulfonic acid or two or more arbitrary proportions.
6, a kind of fibroin and poly-D, the nano material of the multipolymer of L-lactic acid is characterized in that this multipolymer has following structure:
Wherein, X is 1～2000 a integer, and Y is 1～2000 a integer, and R is: H ,-CH
3,-CH
2OH ,-CH
2SH ,-CH (HO) CH
3,-CH (CH
3)
2,-CH
2CH (CH
3)
2,-CH (CH
3) CH
2CH
3,-CH
2CH
2SCH
3,-CH
2COOH ,-CH
2CH
2CONH
2,-CH
2CH
2CH
2CH
2NH
2,-CH
2CH
2CH
2CH
2NH
2,
In any one;
Molecular weight of copolymer is 5000～180000, fibroin segment and poly-D, and L-lactic acid segmental mass ratio is 0.5/99.5～99.5/0.5, its thickness of thin layer 20～80 nanometers.
7, described fibroin of claim 6 and poly-D, the preparation of nanomaterials of the multipolymer of L-lactic acid, it is characterized in that this method is with fibroin behind the purifying and poly-D, the multipolymer of L-lactic acid is dissolved in the good solvent, forming concentration is the solution of 0.1～5g/100mL, precipitate as precipitation agent with poor solvent again, the volumetric usage of precipitation agent is 0.5～20 times a good solvent volume, throw out was 65 ℃ of following vacuum-dryings 10～16 hours, obtain fibroin and poly-D, the nano material of the multipolymer of L-lactic acid.
8, fibroin according to claim 7 and poly-D, the preparation of nanomaterials of the multipolymer of L-lactic acid is characterized in that described good solvent is the mixture of any one or two or more arbitrary proportions in chloroform, tetrahydrofuran (THF), ethyl acetate, monochloroethane and the trifluoroacetic acid; Described poor solvent is the mixture of any one or two or more arbitrary proportions in toluene, methyl alcohol, ethanol, acetone and the ether.
9, fibroin according to claim 8 and poly-D, the preparation of nanomaterials of the multipolymer of L-lactic acid is characterized in that with in chloroform/ether, chloroform/methanol or the chloroform/acetone any one as solvent/precipitation agent system.
10, described fibroin of claim 1 and poly-D, the application of the multipolymer of L-lactic acid in bio-medical material.
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Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104530670A (en) * | 2014-12-22 | 2015-04-22 | 南京林业大学 | Fibroin/polylactic acid blend material and melt-blending preparation method thereof |
| CN105133117A (en) * | 2015-07-07 | 2015-12-09 | 宁波武田纺织有限公司 | Method for preparing high-elastic wrap yarn |
| CN107880254A (en) * | 2017-12-21 | 2018-04-06 | 南京林业大学 | A kind of poly (l-lactic acid) cyclodextrin copolymers material and preparation method thereof |
| CN110016133A (en) * | 2019-04-26 | 2019-07-16 | 安徽农业大学 | A kind of macromole nucleating agent and its application method for quickly crystallizing polylactic acid |
| CN110511359A (en) * | 2018-05-22 | 2019-11-29 | 南京林业大学 | A kind of poly- D-ALPHA-Hydroxypropionic acid cyclodextrin copolymers material and its melt polymerization preparation method |
Family Cites Families (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101053670B (en) * | 2007-04-03 | 2011-02-02 | 浙江理工大学 | Silk fibroin and polymeric lactic acid compound film and its preparation method |
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2008
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104530670A (en) * | 2014-12-22 | 2015-04-22 | 南京林业大学 | Fibroin/polylactic acid blend material and melt-blending preparation method thereof |
| CN105133117A (en) * | 2015-07-07 | 2015-12-09 | 宁波武田纺织有限公司 | Method for preparing high-elastic wrap yarn |
| CN105133117B (en) * | 2015-07-07 | 2017-10-24 | 宁波武田纺织有限公司 | A kind of preparation method of high resiliency wrap yarn |
| CN107880254A (en) * | 2017-12-21 | 2018-04-06 | 南京林业大学 | A kind of poly (l-lactic acid) cyclodextrin copolymers material and preparation method thereof |
| CN107880254B (en) * | 2017-12-21 | 2021-04-27 | 南京林业大学 | Poly L-lactic acid cyclodextrin copolymer material and preparation method thereof |
| CN110511359A (en) * | 2018-05-22 | 2019-11-29 | 南京林业大学 | A kind of poly- D-ALPHA-Hydroxypropionic acid cyclodextrin copolymers material and its melt polymerization preparation method |
| CN110016133A (en) * | 2019-04-26 | 2019-07-16 | 安徽农业大学 | A kind of macromole nucleating agent and its application method for quickly crystallizing polylactic acid |
| CN110016133B (en) * | 2019-04-26 | 2021-10-26 | 安徽农业大学 | Macromolecular nucleating agent for rapid crystallization of polylactic acid and use method thereof |
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