CN102827367B

CN102827367B - Aliphatic polyester-polyamino acid block copolymer and preparation method thereof as well as hydrogel and preparation method thereof

Info

Publication number: CN102827367B
Application number: CN201210341827.XA
Authority: CN
Inventors: 陈学思; 韩锦东; 丁建勋; 庄秀丽; 尹静波
Original assignee: Changchun Institute of Applied Chemistry of CAS
Current assignee: Changzhou Institute Of Energy Storage Materials & Devices
Priority date: 2012-09-14
Filing date: 2012-09-14
Publication date: 2014-07-02
Anticipated expiration: 2032-09-14
Also published as: CN102827367A

Abstract

The invention provides an aliphatic polyester-polyamino acid block copolymer shown in formula I, wherein R1 is substituent group shown in formula II or formula III, R2 is substituent group shown in formula IV, formula V or formula VI, R3 is substituent group shown in formula VII or formula VIII, n is more than or equal to 10 and less than or equal to 500, q is more than or equal to 0 and less than or equal to 100, and p is more than or equal to 7 and less than or equal to 300. The aliphatic polyester-polyamino acid block copolymer shown in formula I is simple in preparation method and controllable in number-average molecular weight, and has good biodegradable property and biocompatibility. The invention also provides a preparation method of the aliphatic polyester-polyamino acid block copolymer, hydrogel containing the aliphatic polyester-polyamino acid block copolymer, and a preparation method of the hydrogel.

Description

A kind of aliphatic polyester-polyamino acid block copolymer and preparation method thereof and a kind of hydrogel and preparation method thereof

Technical field

The present invention relates to polymkeric substance preparation field, be specifically related to a kind of aliphatic polyester-polyamino acid block copolymer and preparation method thereof and and a kind of hydrogel and preparation method thereof.

Background technology

Polyamino acid, as the biodegradable macromole polypeptide of one, have good biological activity, tissue affinity, reduced immunogenicity, and its degraded product has no side effect.So polyamino acid is at biomedical sector, as the aspects such as bioseparation, organizational project, gene therapy and medicine control release are with a wide range of applications.Multiple polyamino acid has good side group modifiability simultaneously, can in gene and drug delivery system, introduce functional group, has great using value.But the deficiency of polyamino acid mechanical property has seriously limited its application in field of tissue engineering technology.

In polyamino acid segment, introducing block polymer prepared by other blocks is one of important channel of improving polyamino acid performance, by regulating the factor such as proportioning of multipolymer kind, molecular weight and each component can control the performance of multipolymer.Polyester material is as poly(lactic acid), and poly-(ξ-caprolactone), poly phosphate and poly (glycolide-lactide), have good biocompatibility, anticoagulant property, and the advantages such as nontoxic and hypoimmunity, are therefore widely used in biological medicine and field of tissue engineering technology.The Pitt of the U.S. and Schin days ler proposes the carrier discharging as medicine control with polyester material the beginning of the seventies, and its drug permeability and biological degradability have been carried out to systematic research.The research of nearly 30 years shows, polyester material and monomer whose all have good histocompatibility, and polyester material is hydrolyzable degraded in physiological environment, and low molecular weight fragments can be annexed and degrade in cell in scavenger cell.

Polyester-polyurethane base acid segmented copolymer has the common advantage of polyester and polyamino acid simultaneously.Wherein, linear polyoxyethylene glycol (monomethyl ether)-polyamino acid block and triblock copolymer is widely studied and is applied to biomedicine field.

Polymer(vol.46,005, and Journal of Polymer Science Part A:Polymer Chemistry(Vol.49 p653-659), 2011,3491-3498) preparation method of the segmented copolymer of a kind of polyglutamic acid and poly (glycolide-lactide) and poly-(6-caprolactone) is disclosed respectively, and studied its thermomechanical property and self-assembly behavior etc., show that it is a kind of biomedical material of having very much potentiality.Chinese patent 03121397.9(grant number) a kind of polyoxyethylene glycol-aliphatic polyester-polyamino acid terpolymer disclosed.But disclosed polyoxyethylene glycol (monomethyl ether)-polyamino acid block or triblock copolymer in above-mentioned paper and patent, preparation method is comparatively loaded down with trivial details.

Summary of the invention

The technical problem to be solved in the present invention is to provide a kind of preparation method simple, and number-average molecular weight is controlled, has the extremely preparation method of aliphatic polyester-polyamino acid block copolymer of good biodegradable and biocompatibility.

In order to solve above technical problem, the invention provides the aliphatic polyester-polyamino acid block copolymer shown in a kind of formula I,

Wherein, R ₁for the substituting group shown in formula II or formula III; R ₂for the substituting group shown in formula IV, formula V or formula VI; R ₃for the substituting group shown in formula VII or formula VIII; 10≤n≤500; 0≤q≤100; 7≤p≤300;

The present invention also provides the preparation method of the aliphatic polyester-polyamino acid block copolymer shown in a kind of formula I, it is characterized in that, comprises the following steps:

A) monomer of tertbutyloxycarbonyl carbonic anhydride, thanomin and fat group polyester is blended in organic solvent, carries out ring-opening polymerization, and remove tertbutyloxycarbonyl, obtain end with amino aliphatic polyester; The monomer of described aliphatic polyester is rac-Lactide, lactic acid or 6-caprolactone;

B) described end is blended in organic solvent with carboxylic acid anhydride in amino aliphatic polyester and γ-benzyl-amino acid-N-, polymerization reaction take place, obtains aliphatic polyester-polyamino acid benzyl ester block copolymer; In described γ-benzyl-amino acid-N-, carboxylic acid anhydride is carboxylic acid anhydride or the interior carboxylic acid anhydride of γ-benzyl-aspartic acid-N-in γ-benzyl-Pidolidone-N-;

C) described aliphatic polyester-polyamino acid benzyl ester block copolymer and hydrobromic glacial acetic acid solution are blended in organic solvent, substitution reaction occur and obtain aliphatic polyester-polyamino acid block copolymer;

Wherein, R ₁for the substituting group shown in formula II or formula III; R ₂for the substituting group shown in formula IV, formula V or formula VI; R ₃for the substituting group shown in formula VII or formula VIII; 10≤n≤500; Q=0; 7≤p≤300;

Preferably, described organic solvent is selected from the one in toluene, dimethyl sulfoxide (DMSO), dichloro acetic acid, methylene dichloride, tetrahydrofuran (THF), chloroform.

Preferably, step a) is specially:

A1) tertbutyloxycarbonyl carbonic anhydride, thanomin are blended in organic solvent, reaction obtains tertbutyloxycarbonyl and protects amino thanomin;

A2) protect the monomer of amino thanomin and aliphatic polyester to be blended in organic solvent described tertbutyloxycarbonyl, carry out ring-opening polymerization, obtain tertbutyloxycarbonyl and protect amino aliphatic polyester;

A3) protect amino aliphatic polyester and trifluoroacetic acid to be dissolved in organic solvent described tertbutyloxycarbonyl, slough tertbutyloxycarbonyl, obtain end with amino aliphatic polyester.

Preferably, also comprise step d):

D) aliphatic polyester-polyamino acid block copolymer step c) being obtained and properties-correcting agent react under the effect of condensing agent and catalyzer, obtain the polymkeric substance shown in formula I, and wherein q meets following condition 0<q≤100; Described properties-correcting agent is styryl carbinol, Hydroxyethyl acrylate or tonka bean camphor.

Preferably, described aliphatic polyester-polyamino acid block copolymer and properties-correcting agent are 20:1 ~ 3 in molar ratio.

The present invention also provides a kind of hydrogel, it is characterized in that, comprising:

Hydrogel prepared by aliphatic polyester-polyamino acid block copolymer claimed in claim 1 and solvent; Described hydrogel is that the polymkeric substance shown in formula I and glycols compound under the effect of catalyzer and condensing agent, crosslinking reaction occur and make;

In the amount of substance y of the amount of substance x of wherein said glycols compound, described catalyzer and described aliphatic polyester-polyamino acid block copolymer, the amount of substance z of hydroxyl meets the following x:z=1:10 of relation ~ 3:5, y:z=1:1 ~ 5; Amount of substance w and the z of condensing agent meet the following w:z=5 of relation ~ 15:1; The volume u of described solvent and the amount of substance z ' of described aliphatic polyester-polyamino acid block copolymer meet the following u:z of relation '=10 ~ 20:1.

Preferably, described glycols compound is selected from one or more in ethylene glycol, Diethylene Glycol, triethylene glycol and PEG400 (polyoxyethylene glycol that number-average molecular weight is 400).

Preferably, the degree of crosslinking of described hydrogel composition is 10% ~ 60%.

The present invention also provides a kind of preparation method of hydrogel, comprises the following steps:

M) according to mol ratio by described aliphatic polyester-polyamino acid block copolymer and glycols compound in solvent, under the effect of catalyzer and condensing agent, there is crosslinking reaction and obtain hydrogel.

The present invention protects amino thanomin as initiator take tertbutyloxycarbonyl; cause the ring-opening polymerizations such as caprolactone, rac-Lactide or lactic acid; then slough tertbutyloxycarbonyl with trifluoroacetic acid and protect amino group, further obtain aliphatic polyester-polyamino acid block copolymer take aliphatic polyester carboxylic acid anhydride ring-opening polymerization in macromole evocating agent causes amino acid-N-of end band amino.Be the number-average molecular weight of adjustable segmented copolymer by the mol ratio of controlling carboxylic acid anhydride in the mol ratio of initiator and esters monomer and amino acid-N-, the number-average molecular weight of described aliphatic polyester section is 2000-30000, and the number-average molecular weight of described polyamino acid section is 2000-40000.

The present invention also provides hydrogel prepared by a kind of aliphatic polyester-polyamino acid block copolymer and preparation method thereof, under the effect of condensing agent and catalyzer, be there is to crosslinking reaction in aliphatic polyester-polyamino acid block copolymer provided by the invention and glycols compound, make original linear polymer become three-dimensional polymer, and form hydrogel in solvent.Hydrogel provided by the invention is owing to having had the character of polyamino acid and two kinds of blocks of aliphatic polyester, and on described polyamino acid block, also has other substituted radical, the performance that can also increase for described hydrogel other, further expands the range of application of hydrogel.

Aliphatic polyester-polyamino acid block copolymer prepared by the present invention, can carry out chemically crosslinked with glycols compound condensation reaction, prepares good biocompatibility and can biodegradable aliphatic polyester-polyamino acid block copolymer hydrogel.

Accompanying drawing explanation

The tertbutyloxycarbonyl that Fig. 1 embodiment of the present invention 1 obtains is protected the nuclear magnetic resonance map of amino thanomin in chloroform;

The amino nuclear magnetic resonance map that gathers (6-caprolactone) of tertbutyloxycarbonyl protection that Fig. 2 embodiment of the present invention 2 obtains; Wherein being attributed to of each peak:

Fig. 3 embodiment of the present invention 6(1) poly-(6-caprolactone)-b-poly-(Pidolidone benzyl ester) of obtaining nuclear magnetic resonance map in trifluoroacetic acid;

Fig. 4 embodiment of the present invention 6(2) poly-(6-caprolactone)-b-PLGA of obtaining nuclear magnetic resonance map in trifluoroacetic acid;

The aliphatic polyester that Fig. 5 embodiment of the present invention 40 obtains-figure of the scanning electronic microscope of b-polyamino acid hydrogel.

Embodiment

In order further to understand the present invention, below in conjunction with embodiment, the preferred embodiments of the invention are described, but should be appreciated that these are described is the restriction for further illustrating the features and advantages of the present invention rather than patent of the present invention being required.

The invention provides a kind of aliphatic polyester-polyamino acid block copolymer, there is structure shown in formula I:

According to the present invention, polymkeric substance shown in formula I is owing to having aliphatic polyester block and polyamino acid block, described in it, polyester block is connected by amido linkage with polyamino acid block, so the polymkeric substance shown in formula I has good biocompatibility and biodegradable.In addition, the compound shown in formula I can have the selection of multiple molecular amount according to the difference of block quantity.According to the present invention, in the polymkeric substance shown in formula I, the number-average molecular weight of aliphatic polyester section is preferably 2000-30000, and the number-average molecular weight of described polyamino acid section is preferably 2000-40000.

The present invention also provides the preparation method of the aliphatic polyester-polyamino acid block copolymer shown in a kind of formula I, comprises the following steps:

B) described end is blended in organic solvent with carboxylic acid anhydride in amino aliphatic polyester and γ-benzyl-amino acid-N-, polymerization reaction take place, obtains aliphatic polyester-polyamino acid benzyl ester block copolymer; In described γ-benzyl-amino acid-N-, carboxylic acid anhydride is carboxylic acid anhydride or the interior carboxylic acid anhydride of γ-benzyl-aspartic acid-N-in γ-benzyl-Pidolidone-N-.

According to the present invention, in order to make the character of product more stable, productive rate is higher, and the present invention is optimized step a), and described step a) is specially:

According to the present invention, the organic solvent using in above-mentioned reaction process is preferably selected from the one in toluene, dimethyl sulfoxide (DMSO), dichloro acetic acid, methylene dichloride, tetrahydrofuran (THF), chloroform,

According to the present invention, step a1) be to protect amino thanomin in order to prepare tertbutyloxycarbonyl; Step a1) be specially:

Measure thanomin and add in round-bottomed flask, add 20 times to the tetrahydrofuran (THF) of thanomin volume, put into ice bath and stir; Take with the sodium bicarbonate of the molar masss such as thanomin and be dissolved in deionized water, add round-bottomed flask; The tert.-butoxy carbonic anhydride taking, the mol ratio of described tert.-butoxy carbonic anhydride and thanomin is 1:1 ~ 1.5, after dissolving, slowly adds in reaction system room temperature reaction 20 ~ 25h with constant pressure funnel with tetrahydrofuran (THF); With repeatedly extractive reaction product of ether, anhydrous sodium sulfate drying 10 ~ 15h for gained supernatant liquor, after filtering with G4 funnel, gained filtrate is removed ether wherein by rotary evaporation, obtains product tertbutyloxycarbonyl and protects amino thanomin;

Step a2) be to protect amino aliphatic polyester, step a2 in order to prepare tertbutyloxycarbonyl) be specially:

Take aliphatic polyester monomer, add in ampulla, then add toluene, volume of toluene (mL) consumption is 50 times of aliphatic polyester monomer weight (g), inject the toluene solution of 0.1 ~ 0.2mol/L stannous octoate with syringe, the mol ratio of described stannous octoate and described aliphatic polyester monomer is 1:800 ~ 1000, then the tertbutyloxycarbonyl of the 0.1 ~ 0.2mol/L adding is protected the toluene solution of amino thanomin, described tertbutyloxycarbonyl protect amino thanomin and esters monomer mole ratio be 1:500 ~ 1:10, put into 100 ~ 150 ℃ of oil baths and react 20 ~ 25h, after completion of the reaction, use ether sedimentation, ether is 8 ~ 15:1 with the ratio of the volumetric usage of toluene, Büchner funnel filters, products therefrom dissolves with chloroform again, use ether dissolution, Büchner funnel filters products therefrom dry 20 ~ 25h in vacuum, obtains tertbutyloxycarbonyl and protects amino aliphatic polyester again,

Step a3) be to have amino aliphatic polyester, step a3 in order to prepare end) be specially:

Take tertbutyloxycarbonyl and protect amino aliphatic polyester, dissolve with methylene dichloride, volume (mL) consumption of described methylene dichloride and the preferred mass (g) of aliphatic polyester are than being 5 ~ 10:1; Reaction unit is put in ice bath, slowly adds trifluoroacetic acid, the consumption of described trifluoroacetic acid and the volume ratio of methylene dichloride are preferably 1:1 ~ 2.After reaction 1 ~ 2h, by 5 times of reaction solution dilutions, saturated sodium bicarbonate is neutralized to neutrality, and deionized water wash then with saturated nacl aqueous solution washing, then is used deionized water wash; Anhydrous magnesium sulfate drying 10 ~ 15h for gained solution, after G4 funnel filters, after gained filtrate is concentrated, use ether sedimentation, after Büchner funnel filters, products therefrom dissolves with chloroform, use again ether sedimentation, Büchner funnel filters products therefrom at vacuum-drying 20 ~ 25h, obtains end with amino aliphatic polyester, deposits in moisture eliminator;

Step b) is that step b) is specially in order to prepare aliphatic polyester-polyamino acid benzyl ester block copolymer:

The end taking is with amino aliphatic polyester, add toluene solution, the volumetric usage (mL) of described toluene and the quality (g) of aliphatic polyester are than being preferably 45 ~ 55:1, immerse in the oil bath of 120 ~ 130 ℃, after azeotropic 1 ~ 2h, pick out toluene, residual toluene, being that system is cooling front with oil pump extraction, adds the interior carboxylic acid anhydride of amino acid-N-, and in described amino acid-N-, carboxylic acid anhydride and end are preferably 10 ~ 300 with the mol ratio of amino aliphatic polyester; Substitute nitrogen three times, add and heavily steam chloroform with syringe, in described amino acid-N-, the quality of carboxylic acid anhydride and the volume ratio of chloroform are 1:25 ~ 35, and then react 2 ~ 3 days in 20 ~ 30 ℃ of oil baths.After reaction finishes, use ether sedimentation, the volume ratio of described EC is preferably 10 ~ 15:1, Büchner funnel filters after the dissolving of filter products therefrom chloroform, use ether sedimentation, products therefrom is dry 20 ~ 25h under vacuum, obtains aliphatic polyester-polyamino acid benzyl ester block copolymer again;

Step c) is in order to prepare aliphatic polyester-polyamino acid block copolymer, the polymkeric substance shown in the formula I obtaining, and q=0.Step c) is specially:

Take aliphatic polyester-polyamino acid benzyl ester block copolymer, dissolve with dichloro acetic acid, the quality (g) of volume (mL) consumption of described dichloro acetic acid and aliphatic polyester-polyamino acid benzyl ester block copolymer is than being 10 ~ 15:1, be placed in ice bath, add Hydrogen bromide glacial acetic acid solution, the volume ratio of described Hydrogen bromide and Glacial acetic acid is preferably 1:2 ~ 4, the quality (g) of volume (mL) consumption of described Hydrogen bromide glacial acetic acid solution and aliphatic polyester-polyamino acid benzyl ester block copolymer is than electing 10 ~ 15:1 as, after reaction 2 ~ 3h, use ether sedimentation, G4 funnel filters, products therefrom N, dinethylformamide dissolves, pack dialysis tubing (MWCO:7000) into, in distilled water, dialyse 3 days.Product is put into beaker, and lyophilize obtains aliphatic polyester-polyamino acid block copolymer.

In order further to strengthen the functional of aliphatic polyester-polyamino acid provided by the invention, can also be on the carboxyl of described polyamino acid block the different functional group of grafting.Also comprise that aliphatic polyester-polyamino acid block copolymer and properties-correcting agent that step d) obtains step c) react under the effect of condensing agent and catalyzer, obtain the polymkeric substance shown in formula I, wherein q meets following condition 0<q≤100; Described properties-correcting agent is styryl carbinol, Hydroxyethyl acrylate or tonka bean camphor.

According to the present invention, the compound that described functionalized group is provided is Hydroxyethyl acrylate, styryl carbinol or tonka bean camphor.Described aliphatic polyester-polyamino acid block copolymer and properties-correcting agent are preferably 20:1 ~ 3 in molar ratio.Described catalyzer is preferably 4-dimethylamino pyrroles, and described condensing agent is preferably 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride.Within now aliphatic polyester-the polyamino acid of preparation is included in the scope of the polymkeric substance shown in formula I, just q meets 0<q≤100.

The preparation of aliphatic polyester-b-poly-(amino acid-co-amino acid-Hydroxyethyl acrylate)

Take aliphatic polyester-polyamino acid block copolymer, with dmso solution, volume (mL) consumption of described dimethyl sulfoxide (DMSO) and the weight (g) of aliphatic polyester-polyamino acid block copolymer are than being 80 ~ 120:1, then in described dimethyl sulfoxide (DMSO), add catalyzer DMAP, in the consumption of described DMAP and described segmented copolymer, the ratio of carboxyl mole is preferably 1 ~ 2:1 ~ 2, then add Hydroxyethyl acrylate, in described Hydroxyethyl acrylate and aliphatic polyester-polyamino acid block copolymer, the mol ratio of carboxyl total amount is preferably 1 ~ 3:20, add again condensing agent 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, the mol ratio of the consumption of described 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride consumption and DMAP is 10 ~ 15:1, be placed in the oil bath of 25 ~ 35 ℃, reaction 20 ~ 25h.After completion of the reaction, put into dialysis membrane (MWCO:3000), dialyse 3 days in distilled water, every 3h changes water once, and after dialysis finishes, lyophilize, obtains aliphatic polyester-b-polyamino acid-co-amino acid-Hydroxyethyl acrylate multipolymer.

The preparation of aliphatic polyester-b-polyamino acid-co-amino acid-styryl carbinol

Take aliphatic polyester-polyamino acid block copolymer, with dmso solution, volume (mL) consumption of described dimethyl sulfoxide (DMSO) and the weight (g) of aliphatic polyester-b-polyamino acid block copolymer are than being 80 ~ 120:1, then in described dimethyl sulfoxide (DMSO), add catalyzer DMAP, the ratio of the consumption of described DMAP and pre-reaction carboxyl mole is preferably 1 ~ 2:1 ~ 2, then the styryl carbinol adding, in described styryl carbinol and aliphatic polyester-polyamino acid block copolymer, the mol ratio of carboxyl total amount is preferably 1 ~ 3:20, (mol ratio of the consumption of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride consumption and DMAP is preferably 10 ~ 15:1 to add 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride again, be placed in the oil bath of 25 ~ 35 ℃, reaction 20 ~ 25h.After completion of the reaction, put into dialysis membrane (MWCO:3000), dialyse 3 days in distilled water, every 3h changes water once, and after dialysis finishes, lyophilize, obtains aliphatic polyester-b-poly-(amino acid-co-amino acid-styryl carbinol).

The preparation of aliphatic polyester-b-poly-(amino acid-co-amino acid-tonka bean camphor)

Take aliphatic polyester-polyamino acid block copolymer, with dmso solution, volume (mL) consumption of described dimethyl sulfoxide (DMSO) and the weight (g) of aliphatic polyester-polyamino acid block copolymer are than being 80 ~ 120:1, (ratio of the consumption of DMAP and pre-reaction carboxyl mole is 1 ~ 2:1 ~ 2 to add DMAP, then the tonka bean camphor adding, in described tonka bean camphor and aliphatic polyester-polyamino acid block copolymer, the mol ratio of carboxyl total amount is preferably 1 ~ 3:20), add again 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, the mol ratio of the consumption of described 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride consumption and DMAP is preferably 10 ~ 15:1, be placed in the oil bath of 25 ~ 35 ℃, reaction 20 ~ 25h.After completion of the reaction, put into dialysis membrane (MWCO:3000), dialyse 3 days in distilled water, every 3h changes water once, and after dialysis finishes, lyophilize, obtains aliphatic polyester-b-poly-(amino acid-co-amino acid-tonka bean camphor).

To gather, (6-caprolactone)-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate), as example, the equation of whole reaction is as follows below:

Above-mentioned 1 ~ 4 equation can illustrate, the raw material ratio that aliphatic polyester-polyamino acid block copolymer prepared by preparation method provided by the invention can react by control is determined the molecular weight of product.

The present invention protects amino thanomin as initiator take tertbutyloxycarbonyl; cause the ring-opening polymerizations such as caprolactone, rac-Lactide; then slough tertbutyloxycarbonyl with trifluoroacetic acid and protect amino group, further obtain aliphatic polyester-polyamino acid block copolymer take aliphatic polyester carboxylic acid anhydride ring-opening polymerization in macromole evocating agent causes amino acid-N-of end band amino.Be the number-average molecular weight of adjustable segmented copolymer by the mol ratio of controlling carboxylic acid anhydride in the mol ratio of initiator and esters monomer and amino acid-N-, the number-average molecular weight of described aliphatic polyester section is 2000-30000, and the number-average molecular weight of described polyamino acid section is 2000-40000.

Aliphatic polyester-polyamino acid block copolymer prepared by the present invention, can carry out chemically crosslinked with glycols compound condensation reaction, prepares good biocompatibility and can biodegradable aliphatic polyester-polyamino acid block copolymer hydrogel,

The present invention also provides a kind of hydrogel, comprising:

In the amount of substance y of the amount of substance x of wherein said glycols compound, described catalyzer and described aliphatic polyester-polyamino acid block copolymer, the amount of substance z of hydroxyl meets the following x:z=1:10 of relation ~ 3:5, and y:z=1:1 ~ 5 are preferably 1:1 ~ 2; Amount of substance w and the z of condensing agent meet the following w:z=5 of relation ~ 15:1; The volume u of described solvent and the amount of substance z ' of described aliphatic polyester-polyamino acid block copolymer meet the following u:z of relation '=10 ~ 20:1.

According to the present invention, described glycols compound plays the effect of linking agent, can with aliphatic polyester-polyamino acid in unreacted carboxyl groups react, described glycols compound is selected from one or more in ethylene glycol, Diethylene Glycol, triethylene glycol and PEG400.Catalyzer provided by the invention is preferably 4-dimethylamino pyrroles, there is good catalytic activity, can catalytic esterification, and described condensing agent is preferably 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, there is very strong activated carboxylic ability, can cause crosslinking reaction.Be preferably dimethyl sulfoxide (DMSO) or water according to solvent of the present invention.The degree of crosslinking of described hydrogel composition is preferably 10% ~ 60%.

M) in molar ratio by described aliphatic polyester-polyamino acid block copolymer and glycols compound in solvent, under the effect of catalyzer and condensing agent, there is crosslinking reaction and obtain hydrogel.

Described catalyzer is preferably 4-dimethylamino pyrroles, there is good catalytic activity, can catalytic esterification, and described condensing agent is preferably 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, there is very strong activated carboxylic ability, impel the generation of condensation reaction.Described solvent is preferably water or dimethyl sulfoxide (DMSO).

Step m is specially:

Aliphatic polyester-polyamino acid block copolymer claimed in claim 2 of getting, in dimethyl sulfoxide (DMSO), dissolve, the volumetric usage of dimethyl sulfoxide (DMSO) is 15 times of aliphatic polyester-polyamino acid block copolymer quality, the volume unit of dimethyl sulfoxide (DMSO) is mL, the mass unit of aliphatic polyester-polyamino acid block copolymer is g, then the glycols compound adding, wherein, in glycols chemicals and aliphatic polyester-polyamino acid block copolymer, in polyamino acid block, the mol ratio of carboxyl is 1:10 ~ 3:5, add DMAP, the consumption of DMAP and pre-reaction carboxyl mole ratio be 1:2, add again 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, the mol ratio of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride and DMAP is 10:1, normal-temperature reaction 24h, the gained gel 3d that dialyses in deionized water, every 3h changes water once, obtain aliphatic polyester-polyamino acid block copolymer hydrogel.

Be below the specific embodiment of the invention, elaborate the present invention program.

Embodiment 1: tertbutyloxycarbonyl is protected the preparation of amino thanomin

Measure 12mL thanomin and add in the round-bottomed flask of 1L, add 200mL tetrahydrofuran (THF), put into ice bath and stir.Take 16.8g sodium bicarbonate and be dissolved in 200mL water, add round-bottomed flask.After taking 48g tert.-butoxy carbonic anhydride 100mL tetrahydrofuran (THF) and dissolving, slowly add in reaction system room temperature reaction 24h with constant pressure funnel.With repeatedly extractive reaction product of ether, gained supernatant liquor anhydrous sodium sulfate drying 12h, after filtering with G4 funnel, gained filtrate is removed ether wherein by rotary evaporation, obtains product tertbutyloxycarbonyl and protects amino thanomin.

The product obtaining is carried out to nuclear magnetic scanning, the collection of illustrative plates obtaining as shown in Figure 1, being wherein attributed to of each peak:

1.4ppm（s,9H,(CH ₃) ₃O-C(O)）;

3.3ppm（t,2H,(CH ₃) ₃OC(O)NHCH ₂-）；

3.7ppm（t,2H,(CH ₃) ₃OC(O)-NHCH ₂CH ₂OH）。

Proof tertbutyloxycarbonyl protects the success of amino thanomin synthetic.

Embodiment 2: the amino preparation that gathers (6-caprolactone) of tertbutyloxycarbonyl protection of different number-average molecular weights

Take 4 parts of 11.4g(0.1mol) ξ-caprolactone put into ampulla; add respectively toluene 60mL; inject respectively the toluene solution of 1mL 0.1mol/L stannous octoate with syringe; then add respectively the 0.1mol/L tertbutyloxycarbonyl of 5.56mL, 1mL, 0.67mL, 0.4mL to protect the toluene solution of amino thanomin, put into 120 ℃ of oil baths and react 24h.After completion of the reaction; with the sedimentation of 600mL ether; Büchner funnel filters; products therefrom dissolves with 50mL chloroform again; use again 500mL ether dissolution; Büchner funnel filters products therefrom dry 24h in vacuum, obtains amino poly-(6-caprolactone) of tertbutyloxycarbonyl protection of different number-average molecular weights.

Number-average molecular weight and the reaction yield of gathering (6-caprolactone) that the protection of table 1 gained tertbutyloxycarbonyl is amino

Sample title	Number-average molecular weight Mn	Reaction yield (%)
			1	2100	92.7
2	11400	94.7
			3	30700	93.7

In upper table, number-average molecular weight Mn is the number-average molecular weight of the product tertbutyloxycarbonyl protection after deprotection amino poly-(6-caprolactone), by ¹h NMR measures and obtains.

The product obtaining is carried out to nuclear magnetic scanning, the collection of illustrative plates obtaining as shown in Figure 2, being wherein attributed to of each peak: 1.4ppm:

（t,(9+2n)H,(CH ₃)3OC(O)NHCH ₂CH ₂OC(O)CH ₂CH ₂CH ₂CH ₂CH ₂O）;

1.55ppm（t,4nH,C(O)CH ₂CH ₂CH ₂CH ₂CH ₂O）；

2.25ppm（t,2nH,C(O)CH ₂CH ₂CH ₂CH ₂CH ₂O）；

4.05ppm（t,2nH,C(O)CH ₂CH ₂CH ₂CH ₂CH ₂O）。Proof tertbutyloxycarbonyl protects the success of poly-(6-caprolactone) of amino thanomin to synthesize.

Embodiment 3: the tertbutyloxycarbonyl of different number-average molecular weights is protected the preparation of amino poly(lactic acid)

Take 4 parts of 7.2g(0.1mol) rac-Lactide put into ampulla; add respectively toluene 60mL; inject respectively the toluene solution of 1mL 0.1mol/L stannous octoate with syringe; then add respectively the 0.1mol/L tertbutyloxycarbonyl of 5.56mL, 1mL, 0.33mL, 0.2mL to protect the toluene solution of amino thanomin, put into 120 ℃ of oil baths and react 24h.After completion of the reaction, with the sedimentation of 600mL ether, Büchner funnel filters; products therefrom dissolves with 50mL chloroform again; use 500mL ether dissolution, Büchner funnel filters products therefrom dry 24h in vacuum again, and the tertbutyloxycarbonyl that obtains different number-average molecular weights is protected amino poly(lactic acid).

Table 2 gained tertbutyloxycarbonyl is protected number-average molecular weight and the reaction yield of amino poly(lactic acid)

Sample title	Number-average molecular weight Mn	Reaction yield (%)
			1	1400	90.1
2	7200	90.4
			3	21000	91.6
4	34200	90.7

In upper table, number-average molecular weight Mn is the number-average molecular weight that the product tertbutyloxycarbonyl after deprotection is protected amino poly(lactic acid), by ¹h NMR measures and obtains.

Embodiment 4: the amino deprotection that gathers (6-caprolactone) of different number-average molecular weight tertbutyloxycarbonyl protections

Amino poly-(ε-caprolactone) the each 2.0g of tertbutyloxycarbonyl protection that takes different number-average molecular weights in embodiment 2, adds 15mL methylene dichloride, and reaction unit is put in ice bath, slowly adds 7.5mL trifluoroacetic acid.After reaction 2h, by 5 times of reaction solution dilutions, saturated sodium bicarbonate is neutralized to neutrality, and 100mL deionized water wash then with the washing of 100mL saturated nacl aqueous solution, then is used 100mL deionized water wash.Gained solution anhydrous magnesium sulfate drying 12h, after G4 funnel filters, ether sedimentation after gained filtrate is concentrated, after Büchner funnel filters, products therefrom dissolves with chloroform, use ether sedimentation, Büchner funnel filters again, and products therefrom is after vacuum-drying 24h, obtain poly-(6-caprolactone) of the end band amino of different number-average molecular weights, deposit in moisture eliminator.

Number-average molecular weight and the reaction yield of poly-(6-caprolactone) of table 3 products therefrom end band amino

Sample title	Number-average molecular weight Mn	Reaction yield (%)
			1	2100	86.7
2	12200	85.1
			3	29700	89.7

In upper table, Mn is the number-average molecular weight of poly-(6-caprolactone) of the product end band amino after deprotection, by ¹h NMR measures and obtains.

Embodiment 5: different number-average molecular weight tertbutyloxycarbonyls are protected the deprotection of amino poly(lactic acid)

Take the different number-average molecular weight tertbutyloxycarbonyls of embodiment 3 and protect the each 2.0g of amino poly(lactic acid), add 15mL methylene dichloride, reaction unit is put in ice bath, slowly add 7.5mL trifluoroacetic acid.After reaction 2h, by 5 times of reaction solution dilutions, saturated sodium bicarbonate is neutralized to neutrality, and deionized water 100mL washing then with saturated nacl aqueous solution 100mL washing, then is used 100mL deionized water wash.Gained solution anhydrous magnesium sulfate drying 12h, after G4 funnel filters, ether sedimentation after gained filtrate is concentrated, after Büchner funnel filters, products therefrom dissolves with chloroform, use ether sedimentation, Büchner funnel filters again, and products therefrom is after vacuum-drying 24h, obtain the poly(lactic acid) of the end band amino of different number-average molecular weights, deposit in moisture eliminator.

Number-average molecular weight and the reaction yield of the poly(lactic acid) of table 4 products therefrom end band amino

Sample title	Number-average molecular weight Mn	Reaction yield (%)
			1	1300	85.7
2	6900	87.4

3	20800	87.6
			4	34100	88.7

In upper table, Mn is the number-average molecular weight of the poly(lactic acid) of the product end band amino after deprotection, by ¹h NMR measures and obtains.

Embodiment 6: prepare poly-(6-caprolactone)-PLGA segmented copolymer of different molecular weight as initiator to gather (6-caprolactone)

(1) take 0.5g(0.243mmol) poly-(6-caprolactone) of the number-average molecular weight end band amino that is 2166, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly being extracted out with oil pump for system is cooling, add respectively carboxylic acid anhydride monomer in 1.148g (4.38mmol), 3.19g (12.17mmol), 6.379g (24.3mmol) γ-phenmethyl-Pidolidone ester-N-, substitute N ₂three times, then add respectively 34.5mL, 95.7mL, 191mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 350mL, 957mL, the sedimentation of 1.91L ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly-(6-caprolactone)-polyamino acid multipolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 5 products therefrom and reaction yield

Sample number into spectrum	Number-average molecular weight Mn ₁	Number-average molecular weight Mn2	Reaction yield (%)
				1	1900	3700	86.2
2	1900	10700	84.1
				3	1900	21200	84.4

Mn in upper table ₁for the number-average molecular weight of poly-(6-caprolactone) section in poly-(6-caprolactone)-poly-(Pidolidone benzyl ester) segmented copolymer, Mn ₂for the number-average molecular weight of poly-(Pidolidone benzyl ester) section in poly-(6-caprolactone)-poly-(Pidolidone benzyl ester) segmented copolymer, by ¹h NMR measures and obtains.

The product obtaining is carried out to nuclear magnetic scanning, the collection of illustrative plates obtaining as shown in Figure 3, being wherein attributed to of each peak: 1.25ppm(t, 2mH, C (O) CH ₂cH ₂cH ₂cH ₂cH ₂o); 1.51ppm(t, 4mH, C (O) CH ₂cH ₂cH ₂cH ₂cH ₂o),

1.8ppm and 2.0ppm(2nH, NHCH (CH ₂cH ₂c (O) OCH ₂ph) C (O));

2.3ppm(t,2(m+n)H,C(O)CH ₂CH ₂CH ₂CH ₂CH ₂O, NHCH(CH ₂CH ₂C(O)OCH ₂Ph)C(O));

4.05ppm(t,2mH,C(O)CH ₂CH ₂CH ₂CH ₂CH ₂O);

4.55ppm(s,nH,NHCH(CH ₂CH ₂C(O)OCH ₂Ph)C(O));

4.95ppm(t,2nH,NHCH(CH ₂CH ₂C(O)OCH ₂Ph)C(O));

7.1ppm(m,5nH,NHCH(CH ₂CH ₂C(O)OCH ₂Ph)C(O))。

The success that proves poly-(6-caprolactone)-b-poly-(Pidolidone benzyl ester) is synthetic.

(2) take respectively the segmented copolymer of different block ratios in 1g the present embodiment, add 10mL dichloro acetic acid, be stirred to dissolving, be placed in ice bath, add the Hydrogen bromide glacial acetic acid solution of 3mL 33%, after reaction 2h, use ether sedimentation, G4 funnel filters, products therefrom 20mLN, dinethylformamide dissolves, and packs dialysis tubing (molecular weight cut-off is 7000) into, dialyses 3 days in distilled water.Dialyzate is proceeded in beaker, and lyophilize obtains poly-(6-caprolactone)-PLGA segmented copolymer of different block ratios.

Table 6 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	1900	2200	81.7
2	1900	6200	83.4
				3	1900	12200	85.2

Mn in upper table ₁for the number-average molecular weight of poly-(6-caprolactone) section in poly-(6-caprolactone)-PLGA segmented copolymer, Mn ₂for the number-average molecular weight of PLGA section in poly-(6-caprolactone)-PLGA segmented copolymer, by ¹h NMR measures and obtains.

The product obtaining is carried out to nuclear magnetic scanning, the collection of illustrative plates obtaining as shown in Figure 4, wherein, being attributed to of each peak: 1.25ppm(t, 2mH, C (O) CH ₂cH ₂cH ₂cH ₂cH ₂o);

1.51ppm（t,4mH,C(O)CH ₂CH ₂CH ₂CH ₂CH ₂O），

1.8ppm and 2.0pp, 2nH, NHCH (CH ₂cH ₂c (O) OCH ₂ph) C (O));

2.3ppm(t,2mH,C(O)CH ₂CH ₂CH ₂CH ₂CH ₂O);

2.45ppm(t,2nH,NHCH(CH ₂CH ₂C(O)OCH ₂Ph)C(O));

4.05ppm(t,2mH,C(O)CH ₂CH ₂CH ₂CH ₂CH ₂O);

4.65ppm(s,nH,NHCH(CH ₂CH ₂C(O)OCH ₂Ph)C(O))。

The success that proves poly-(6-caprolactone)-b-PLGA is synthetic.

Embodiment 7: gather (6-caprolactone)-PLGA segmented copolymer for what initiator was prepared different molecular weight take poly-(6-caprolactone) of end band amino

(1) take 0.5g(0.044mmol) poly-(6-caprolactone) of the number-average molecular weight end band amino that is 12198, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.576g (2.2mmol), 1.153g (4.4mmol), 2.305g(8.8mmol) the interior carboxylic acid anhydride monomer of γ-phenmethyl-Pidolidone ester-N-, substitute N ₂three times, then add respectively 17mL, 34.6mL, 69mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 170mL, 346mL, the sedimentation of 690mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly-(6-caprolactone)-polyamino acid multipolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 7 products therefrom and reaction yield

Sample number into spectrum	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	10900	10700	87.2
2	10900	21200	88.4
				4	10900	41800	85.9

Table 8 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₁	Reaction yield (%)
				1	10900	6200	81.7

2	10900	12400	83.4
				3	10900	24600	85.2

Embodiment 8: gather (6-caprolactone)-PLGA segmented copolymer for what initiator was prepared different molecular weight take poly-(6-caprolactone) of end band amino

(1) take 5 parts of 1.0g(0.035mmol) poly-(6-caprolactone) of the number-average molecular weight end band amino that is 29700, add 100mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.458g (1.75mmol), 1.375g (5.25mmol), 2.751g(10.5mmol) the interior carboxylic acid anhydride monomer of γ-phenmethyl-Pidolidone ester-N-, substitute N ₂three times, then add respectively 13.8mL, 41.2mL, 82.5mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 138mL, 412mL, the sedimentation of 825mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly-(6-caprolactone)-polyamino acid multipolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 9 products therefrom and reaction yield

Sample number into spectrum	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	27400	10500	81.7
2	27400	30800	81.4
				3	27400	63300	81.6

Table 10 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	27400	6200	81.7
2	27400	18300	83.4
				3	27400	37500	85.2

Embodiment 9: poly(lactic acid)-PLGA segmented copolymer of preparing different molecular weight take the poly(lactic acid) of end band amino as initiator

(1) take 0.5g(0.386mmol) poly(lactic acid) of the number-average molecular weight end band amino that is 1283, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly being extracted out with oil pump for system is cooling, add respectively the interior carboxylic acid anhydride monomer of γ-phenmethyl-Pidolidone ester-N-of 1.82g (6.948mmol), 5.056g (19.3mmol), 10.113g (38.6mmol), substitute N ₂three times, then add respectively 54.6mL, 151.6mL, 303mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 546mL, 1516mL, the sedimentation of 3.03L ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly(lactic acid)-polyamino acid multipolymer of different block ratios.

Number-average molecular weight and the reaction yield of the molecular weight of table 11 products therefrom poly(lactic acid)-poly-(Pidolidone benzyl ester)

Sample number into spectrum	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	1200	3700	85.2
2	1200	10700	86.1
				3	1200	21200	85.4

Mn in upper table ₁for the number-average molecular weight of poly(lactic acid) section in poly(lactic acid)-poly-(Pidolidone benzyl ester) segmented copolymer, Mn ₂for the number-average molecular weight of poly-(Pidolidone benzyl ester) section in poly(lactic acid)-poly-(Pidolidone benzyl ester) segmented copolymer, by ¹h NMR measures and obtains.

Table 12 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	1200	2200	81.7
2	1200	6200	83.4
				3	1200	12200	85.2

Mn in upper table ₁for the number-average molecular weight of poly(lactic acid) section in poly(lactic acid)-PLGA segmented copolymer, Mn ₂for the number-average molecular weight of PLGA section in poly(lactic acid)-PLGA segmented copolymer, by ¹h NMR measures and obtains.

Embodiment 10: poly(lactic acid)-PLGA segmented copolymer of preparing different molecular weight take the poly(lactic acid) of end band amino as initiator

(1) take 0.5g(0.069mmol) poly(lactic acid) of the number-average molecular weight end band amino that is 6971, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.909g (3.47mmol), 1.807g (6.9mmol), 2.711g (10.35mmol), 3.615g(13.8mmol) the interior carboxylic acid anhydride monomer of γ-phenmethyl-Pidolidone ester-N-, substitute N ₂three times, then add respectively 27.3mL, 54.2mL, 81.3mL, 108mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 273mL, 542mL, 813mL, the sedimentation of 1.08mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly(lactic acid)-polyamino acid multipolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 13 products therefrom and reaction yield

Sample number into spectrum	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	7000	10300	83.4
2	7000	21000	85.1

3	7000	30800	86.3
				4	7000	42200	85.7

Table 14 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	7000	6200	82.7
2	7000	12400	82.4
				3	7000	18960	84.2
4	7000	24600	85.1

Embodiment 11: poly(lactic acid)-PLGA segmented copolymer of preparing different molecular weight take the poly(lactic acid) of end band amino as initiator

(1) take 1g(0.046mmol) poly(lactic acid) of the number-average molecular weight end band amino that is 20867, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.606g (2.31mmol), 1.205g (4.6mmol), 1.807g (6.9mmol), 2.41g(9.2mmol) the interior carboxylic acid anhydride monomer of γ-phenmethyl-Pidolidone ester-N-, substitute N ₂three times, then add respectively 18.2mL, 36.1mL, 54.2mL, 72.3mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 182mL, 361mL, 542mL, the sedimentation of 723mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly(lactic acid)-PLGA segmented copolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 15 products therefrom and reaction yield

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	20800	10500	81.2
2	20800	20600	83.1
				3	20800	32000	82.7
4	20800	41100	82.3

Table 16 reacts number-average molecular weight and the reaction yield of gained poly(lactic acid)-PLGA segmented copolymer

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	20800	6000	82.7
2	20800	12400	82.4
				3	20800	18400	83.2
	20800	25000	84.2

Embodiment 12: poly(lactic acid)-PLGA segmented copolymer of preparing different molecular weight take the poly(lactic acid) of end band amino as initiator

(1) take 1g(0.028mmol) poly(lactic acid) of the number-average molecular weight end band amino that is 34115, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.367g (1.4mmol), 0.733g (2.8mmol), 1.1g (4.2mmol), 1.467g(5.6mmol) the interior carboxylic acid anhydride monomer of γ-phenmethyl-Pidolidone ester-N-, substitute N ₂three times, then add respectively 11mL, 22mL, 33mL, 44mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 137mL, 412mL, 542mL, the sedimentation of 550mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly-breast-PLGA segmented copolymer of different block ratios.

Number-average molecular weight and the reaction yield of table 17 gained poly(lactic acid)-b-poly-(Pidolidone benzyl ester)

Sample number into spectrum	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₁	Reaction yield (%)
				1	34700	10500	83.2
2	34700	20600	87.1
				3	34700	32000	84.1
4	34700	41100	85.3

Table 18 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	34700	6000	83.7
2	34700	12400	83.2
				3	34700	18400	84.2

4

34700

25000

82.8

Embodiment 13: prepare poly-(6-caprolactone) of different molecular weight-gather (L-Aspartic acid) segmented copolymer for initiator take poly-(6-caprolactone) of end band amino

(1) take 0.5g(0.243mmol) poly-(6-caprolactone) of the number-average molecular weight end band amino that is 2166, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly being extracted out with oil pump for system is cooling, add respectively carboxylic acid anhydride in 1.09g (4.38mmol), 3.03g (12.17mmol), 6.05g (24.3mmol) γ-phenmethyl-L-Aspartic acid-N-, substitute N ₂three times, then add respectively 32.7mL, 90.9mL, 181mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 327mL, 909mL, the sedimentation of 1.81L ether, Büchner funnel filters after the dissolving of products therefrom chloroform, use again ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly-(6-caprolactone)-poly-(L-Aspartic acid benzyl ester) segmented copolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 19 products therefrom and reaction yield

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	1900	3500	83.8
2	1900	10200	84.1
				3	1900	19800	85.4

Mn in upper table ₁for the number-average molecular weight of poly-(6-caprolactone) section in poly-(6-caprolactone)-poly-(L-Aspartic acid benzyl ester) segmented copolymer, Mn ₂for the number-average molecular weight of poly-(L-Aspartic acid benzyl ester) section in poly-(6-caprolactone)-poly-(L-Aspartic acid benzyl ester) segmented copolymer, by ¹h NMR measures and obtains.

Table 20 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	1900	1900	81.7
2	1900	5500	83.4
				3	1900	11100	85.2

Mn in upper table ₁for the number-average molecular weight of poly-(6-caprolactone) section in poly-(6-caprolactone)-poly-(L-Aspartic acid) segmented copolymer, Mn ₂for the number-average molecular weight of poly-(L-Aspartic acid) section in poly-(6-caprolactone)-poly-(L-Aspartic acid) segmented copolymer, by ¹h NMR measures and obtains.

Embodiment 14: prepare poly-(6-caprolactone) of different molecular weight-gather (L-Aspartic acid) segmented copolymer for initiator take poly-(6-caprolactone) of end band amino

Take 0.5g(0.044mmol) poly-(6-caprolactone) of the number-average molecular weight end band amino that is 12198, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.547g (2.2mmol), 1.095g (4.4mmol), 2.166g (8.7mmol), 3.286g(13.2mmol) the interior carboxylic acid anhydride of γ-phenmethyl-L-Aspartic acid-N-, substitute N ₂three times, then add respectively 16.4mL, 32.8mL, 65mL, 98.6mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 164mL, 328mL, 650mL, the sedimentation of 986mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, use again ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly-(6-caprolactone)-poly-(L-Aspartic acid) segmented copolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 21 products therefrom and reaction yield

Sample number into spectrum	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	10900	10200	87.5
2	10900	19800	87.4
				3	10900	39100	84.8
4	10900	59600	83.9

Table 22 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample number into spectrum	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	10900	5500	82.7
2	10900	11100	83.1
				3	10900	22000	83.4
4	10900	33300	82.9

Embodiment 15: prepare poly-(6-caprolactone) of different molecular weight-gather (L-Aspartic acid) segmented copolymer for initiator take poly-(6-caprolactone) of end band amino

(1) take 1.0g(0.035mmol) poly-(6-caprolactone) of the number-average molecular weight end band amino that is 29754, add 100mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.435g (1.75mmol), 0.87g (3.5mmol), 1.307g (5.25mmol), 2.614g(10.5mmol) the interior carboxylic acid anhydride of γ-phenmethyl-L-Aspartic acid-N-, substitute N ₂three times, then add respectively 13mL, 26.1mL, 39.2mL, 78.4mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 130mL, 261mL, 392mL, the sedimentation of 784mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, use again ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly-(6-caprolactone)-poly-(L-Aspartic acid) segmented copolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 23 products therefrom and reaction yield

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	27400	9800	83.6
2	27400	19800	83.2
				3	27400	29100	83.4
4	27400	60000	82.7

Table 24 reacts number-average molecular weight and the reaction yield of gained poly-(6-caprolactone)-poly-(L-Aspartic acid) segmented copolymer

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	27400	5500	81.7
2	27400	11100	83.4
				3	27400	22000	85.2
4	27400	33300	84.3

Embodiment 16: poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer of preparing different molecular weight take the poly(lactic acid) of end band amino as initiator

(1) take 0.5g(0.386mmol) poly(lactic acid) of the number-average molecular weight end band amino that is 1283, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly being extracted out with oil pump for system is cooling, add respectively the interior carboxylic acid anhydride of γ-phenmethyl-L-Aspartic acid-N-of 1.718g (6.9mmol), 4.8g (19.3mmol), 9.611g (38.6mmol), substitute N ₂three times, then add respectively 51.5mL, 144mL, 288mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 515mL, 1.44L, the sedimentation of 2.88L ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 25 products therefrom and reaction yield

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	1200	3500	84.2
2	1200	9800	85.6
				3	1200	19000	84.8

Table 26 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	1200	1900	81.7
2	1200	5400	83.4

3

1200

11100

85.2

Embodiment 17: poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer of preparing different molecular weight take the poly(lactic acid) of end band amino as initiator

(1) take 0.5g(0.069mmol) poly(lactic acid) of the number-average molecular weight end band amino that is 6971, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.864g (3.47mmol), 1.718g (6.9mmol), 2.577g (10.35mmol), 3.436g(13.8mmol) the interior carboxylic acid anhydride of γ-phenmethyl-L-Aspartic acid-N-, substitute N ₂three times, then add respectively 25.9mL, 51.5mL, 77.3mL, 103mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 259mL, 515mL, 773mL, the sedimentation of 1.03mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, use again ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 27 products therefrom and reaction yield

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	11000	10200	82.2
2	11000	19800	83.7
				3	11000	39100	84.5
4	11000	59600	83.3

Table 28 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	11000	5500	81.7
2	11000	11100	83.4
				3	11000	22000	85.2
	11000	33300

Embodiment 18: poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer of preparing different molecular weight take the poly(lactic acid) of end band amino as initiator

Take 1g(0.046mmol) poly(lactic acid) of the number-average molecular weight end band amino that is 20867, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.575g (2.31mmol), 1.145g (4.6mmol), 1.718g (6.9mmol), 2.29g(9.2mmol) the interior carboxylic acid anhydride of γ-phenmethyl-L-Aspartic acid-N-, substitute N ₂three times, then add respectively 17.2mL, 34.3mL, 51.5mL, 68.7mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 172mL, 343mL, 515mL, the sedimentation of 687mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 29 products therefrom and reaction yield

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	21000	9800	84.2
2	21000	19800	85.4

3	21000	29000	83.7
				4	21000	39100	85.4

Table 30 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	21000	5400	81.7
2	21000	10800	83.4
				3	21000	16200	85.2
4	21000	22300	83.7

Embodiment 19: poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer of preparing different molecular weight take the poly(lactic acid) of end band amino as initiator

Take 1g(0.028mmol) poly(lactic acid) of the number-average molecular weight end band amino that is 34115, add 60mL toluene, immerse in the oil bath of 125 ℃, after azeotropic 2h, pick out toluene, residual toluene is frontly extracted out with oil pump system is cooling, add respectively 0.348g (1.4mmol), 0.697g (2.8mmol), 1.045g (4.2mmol), 1.394g(5.6mmol) the interior carboxylic acid anhydride monomer of γ-phenmethyl-Pidolidone ester-N-, substitute N ₂three times, then add respectively 10.4mL, 20.9mL, 31.3mL, 41.8mL heavily to steam chloroform with syringe, in 25 ℃ of oil baths, react 3 days.After reaction finishes, use respectively 104mL, 209mL, 313mL, the sedimentation of 418mL ether, Büchner funnel filters after the dissolving of products therefrom chloroform, then uses ether sedimentation, products therefrom is dry 24h under vacuum, obtains poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer of different block ratios.

The number-average molecular weight of the molecular weight of table 31 products therefrom and reaction yield

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	35000	9800	83.2
2	35000	19800	87.1
				3	35000	29000	84.1
4	35000	39100	85.3

Table 32 reacts number-average molecular weight and the reaction yield of poly-(the 6-caprolactone)-PLGA segmented copolymer of gained

Sample title	Number-average molecular weight Mn ₁	Number-average molecular weight Mn ₂	Reaction yield (%)
				1	35000	5400	83.7
2	35000	10800	84.2
				3	35000	16200	83.2
4	35000	22300	83.5

Embodiment 20: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-L-glutamic acid Hydroxyethyl acrylate)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=1900, Mn ₂=2200), use respectively 20mL dmso solution, add respectively 0.01g4-Dimethylamino pyridine, then add respectively the Hydroxyethyl acrylate of 0.0095g, 0.0191g, 0.0286g, add again 0.1572g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-glutamic acid Hydroxyethyl acrylate).

Table 33 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	90.7
2	0.2	0.18	91.2
				3	0.3	0.29	90.9

In upper table, N ₁: N ₂for theoretical percentage of grafting, n ₁: n ₂for actual percentage of grafting, actual percentage of grafting by ¹h NMR measures and obtains.

Embodiment 21: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=1900, Mn ₂=6200), use respectively 20mL dmso solution, add respectively 0.0144g DMAP, then add respectively the Hydroxyethyl acrylate of 0.0137g, 0.0274g, 0.0411g, add again 0.2262g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate).

Table 34 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.1	91.7
2	0.2	0.19	92.2
				3	0.3	0.28	91.9

In upper table, N ₁: N ₂for theoretical percentage of grafting, n ₁: n ₂for actual percentage of grafting, actual percentage of grafting by ¹h NMR measures and obtains

Embodiment 22: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=1900, Mn ₂=12200), use respectively 20mL dmso solution, add respectively 0.0163g DMAP, then add respectively the Hydroxyethyl acrylate of 0.0155g, 0.031g, 0.0466g, add again 0.2569g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate).

Table 35 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.1	90.5
2	0.2	0.18	89.8
				3	0.3	0.29	90.3

Embodiment 23: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=10900, Mn ₂=6200), use respectively 20mL dmso solution, add respectively 0.0068g DMAP, then add respectively the Hydroxyethyl acrylate of 0.0065g, 0.013g, 0.0195g, add again 0.1074g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-glutamic acid Hydroxyethyl acrylate).

Table 36 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	91.5
2	0.2	0.18	89.6
				3	0.3	0.28	91.3

Embodiment 24: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=10900, Mn ₂=12400), use respectively 20mL dmso solution, add respectively 0.01g DMAP, then add respectively the Hydroxyethyl acrylate of 0.0095g, 0.019g, 0.0285g, add again 0.1572g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-glutamic acid Hydroxyethyl acrylate).

Table 37 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.1	92.5

2	0.2	0.18	90.6
				3	0.3	0.27	90.3

Embodiment 25: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=10900, Mn ₂=24600), use respectively 20mL dmso solution, add respectively 0.0131g4-Dimethylamino pyridine, then add respectively the Hydroxyethyl acrylate of 0.0125g, 0.025g, 0.0374g, add again 0.205g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate).

Table 38 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	91.5
2	0.2	0.2	91.6
				3	0.3	0.28	92.3

Embodiment 26: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=27400, Mn ₂=6200), use respectively 20mL dmso solution, add respectively 0.0035g DMAP, then add respectively the Hydroxyethyl acrylate of 0.0033g, 0.0066g, 0.0099g, add again 0.0546g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-glutamic acid Hydroxyethyl acrylate).

Table 39 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.08	90.7
2	0.2	0.19	92.6
				3	0.3	0.29	93.3

Embodiment 27: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=27400, Mn ₂=18300), use respectively 20mL dmso solution, add respectively 0.0049g DMAP, then add respectively the Hydroxyethyl acrylate of 0.0046g, 0.0093g, 0.0139g, add again 0.0767g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate).

Table 40 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	91.5
2	0.2	0.19	91.8
				3	0.3	0.28	92.3

Embodiment 28: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=27400, Mn ₂=37500), use respectively 20mL dmso solution, add respectively 0.0109g DMAP, then add respectively the Hydroxyethyl acrylate of 0.0103g, 0.0206g, 0.031g, add again 0.1706g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate).

Table 41 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	92.5
2	0.2	0.18	91.6
				3	0.3	0.29	90.3

Embodiment 29: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-styryl carbinol)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=1900, Mn ₂=2200), use respectively 20mL dmso solution, add respectively 0.01g4-Dimethylamino pyridine, then add respectively the styryl carbinol of 0.0109g, 0.022g, 0.033g, add again 0.1572g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-L-L-glutamic acid-styryl carbinol).

Table 42 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-L-glutamic acid-styryl carbinol)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	92.7
2	0.2	0.18	93.2
				3	0.3	0.29	93.8

Embodiment 30: the preparation of poly-(6-caprolactone)-b-poly-(Pidolidone-co-L-tonka bean camphor)

Take poly-(the 6-caprolactone)-PLGA segmented copolymer (Mn of 3 parts of 0.2g ₁=1900, Mn ₂=2200), use respectively 20mL dmso solution, add respectively 0.01g4-Dimethylamino pyridine, then add respectively the tonka bean camphor of 0.012g, 0.024g, 0.036g, add again 0.1572g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), dialyse 3 days in distilled water, every 3h changes water once, after dialysis finishes, and lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-tonka bean camphor).

Table 43 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-tonka bean camphor)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.08	93.7
2	0.2	0.18	92.4
				3	0.3	0.28	91.8

The preparation of embodiment 31: poly(lactic acid)-b-poly-(Pidolidone-co-L-L-glutamic acid-Hydroxyethyl acrylate)

Take 3 parts of 0.2g poly(lactic acid)-PLGA segmented copolymer (Mn ₁=1200, Mn ₂=2200), use respectively 20mL dmso solution, add respectively 0.0121g4-Dimethylamino pyridine, then add respectively the Hydroxyethyl acrylate of 0.0115g, 0.0231g, 0.0346g, add again 0.1898g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), dialyse 3 days in distilled water, every 3h changes water once, after dialysis finishes, and lyophilize, the poly(lactic acid)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-Hydroxyethyl acrylate).

Table 44 reacts percentage of grafting and the reaction yield of gained poly(lactic acid)-b-poly-(Pidolidone-co-L-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	92.1
2	0.2	0.19	91.8
				3	0.3	0.29	93.4

The preparation of embodiment 32: poly(lactic acid)-b-poly-(Pidolidone-co-L-L-glutamic acid-styryl carbinol)

Take 3 parts of 0.2g poly(lactic acid)-PLGA segmented copolymer (Mn ₁=1200, Mn ₂=2200), use respectively 20mL dmso solution, add respectively 0.0121g4-Dimethylamino pyridine, then add respectively the styryl carbinol of 0.0132g, 0.0265g, 0.0398g, add again 0.1898g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), dialyse 3 days in distilled water, every 3h changes water once, after dialysis finishes, and lyophilize, the poly(lactic acid)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-styryl carbinol).

Table 45 reacts percentage of grafting and the reaction yield of gained poly(lactic acid)-b-poly-(Pidolidone-co-L-styryl carbinol)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	90.7
2	0.2	0.18	92.2
				3	0.3	0.28	91.8

The preparation of embodiment 33: poly(lactic acid)-b-poly-(Pidolidone-co-L-L-glutamic acid-tonka bean camphor)

Take 3 parts of 0.2g poly(lactic acid)-PLGA segmented copolymer (Mn ₁=1200, Mn ₂=2200), use respectively 20mL dmso solution, add respectively 0.0121g4-Dimethylamino pyridine, then add respectively the tonka bean camphor of 0.0145g, 0.029g, 0.0434g, add again 0.1898g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), dialyse 3 days in distilled water, every 3h changes water once, after dialysis finishes, and lyophilize, the poly(lactic acid)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-tonka bean camphor).

Table 46 reacts percentage of grafting and the reaction yield of gained poly(lactic acid)-b-poly-(Pidolidone-co-L-tonka bean camphor)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.08	91.7
2	0.2	0.18	91.3
				3	0.3	0.28	92.7

Embodiment 34: the preparation of poly-(6-caprolactone)-b-poly-(L-Aspartic acid-co-L-aspartic acid-Hydroxyethyl acrylate)

Take 3 parts of 0.2g poly-(6-caprolactone)-poly-(L-Aspartic acid) segmented copolymer (Mn ₁=1900, Mn ₂=1900), use respectively 20mL dmso solution, add respectively 0.0095g DMAP, then add respectively the Hydroxyethyl acrylate of 0.009g, 0.0181g, 0.0271g, add again 0.1495g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-aspartic acid-Hydroxyethyl acrylate).

Table 47 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-aspartic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	90.7
2	0.2	0.19	92.9
				3	0.3	0.29	93.2

Embodiment 35: the preparation of poly-(6-caprolactone)-b-poly-(L-Aspartic acid-co-L-aspartic acid-styryl carbinol)

Take 3 parts of 0.2g poly-(6-caprolactone)-poly-(L-Aspartic acid) segmented copolymer (Mn ₁=1900, Mn ₂=1900), use respectively 20mL dmso solution, add respectively 0.0095g DMAP, then add respectively the styryl carbinol of 0.0105g, 0.021g, 0.0314g, add again 0.1495g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-aspartic acid-styryl carbinol).

Table 48 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-aspartic acid-styryl carbinol)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.08	92.4
2	0.2	0.18	91.5
				3	0.3	0.29	92.8

Embodiment 36: the preparation of poly-(6-caprolactone)-b-poly-(L-Aspartic acid-co-L-aspartic acid-tonka bean camphor)

Take 3 parts of 0.2g poly-(6-caprolactone)-poly-(L-Aspartic acid) segmented copolymer (Mn ₁=1900, Mn ₂=1900), use respectively 20mL dmso solution, add respectively 0.0095g DMAP, then add respectively the tonka bean camphor of 0.0105g, 0.021g, 0.0314g, add again 0.1495g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, poly-(the 6-caprolactone)-b-that obtains different percentage of grafting gathers (Pidolidone-co-L-aspartic acid-tonka bean camphor).

Table 49 reacts percentage of grafting and the reaction yield of poly-(the 6-caprolactone)-b-of gained poly-(Pidolidone-co-L-aspartic acid-tonka bean camphor)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.1	92.7
2	0.2	0.18	93.2
				3	0.3	0.28	93.8

The preparation of embodiment 37: poly(lactic acid)-b-poly-(L-Aspartic acid-co-L-aspartic acid-Hydroxyethyl acrylate)

Take 3 parts of 0.2g poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer (Mn ₁=1200, Mn ₂=1900), use respectively 20mL dmso solution, add respectively 0.0116g DMAP, then add respectively the Hydroxyethyl acrylate of 0.011g, 0.022g, 0.033g, add again 0.1821g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), in distilled water, dialyse 3 days, every 3h changes water once, after dialysis finishes, lyophilize, the poly(lactic acid)-b-that obtains different percentage of grafting gathers (L-Aspartic acid-co-L-aspartic acid-Hydroxyethyl acrylate).

Table 50 reacts percentage of grafting and the reaction yield of gained poly(lactic acid)-b-poly-(L-Aspartic acid-co-L-aspartic acid-Hydroxyethyl acrylate)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.08	91.6
2	0.2	0.18	93.4
				3	0.3	0.29	93.6

The preparation of embodiment 38: poly(lactic acid)-b-poly-(L-Aspartic acid-co-L-aspartic acid-styryl carbinol)

Take 3 parts of 0.2g poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer (Mn ₁=1200, Mn ₂=1900), use respectively 20mL dmso solution, add respectively 0.0116g DMAP, then add respectively the styryl carbinol of 0.0127g, 0.0255g, 0.0382g, add again 0.1821g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), dialyse 3 days in distilled water, every 3h changes water once, after dialysis finishes, and lyophilize, the poly(lactic acid)-b-that obtains different percentage of grafting gathers (L-Aspartic acid-co-L-aspartic acid-styryl carbinol).

Table 51 reacts percentage of grafting and the reaction yield of gained poly(lactic acid)-b-poly-(L-Aspartic acid-co-L-aspartic acid-styryl carbinol)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.1	93.7
2	0.2	0.19	91.2
				3	0.3	0.29	93.3

The preparation of embodiment 39: poly(lactic acid)-b-poly-(L-Aspartic acid-co-L-aspartic acid-tonka bean camphor)

Take 3 parts of 0.2g poly(lactic acid)-poly-(L-Aspartic acid) segmented copolymer (Mn ₁=1200, Mn ₂=1900), use respectively 20mL dmso solution, add respectively 0.0116g DMAP, then add respectively the tonka bean camphor of 0.0127g, 0.0255g, 0.0382g, add again 0.1821g 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride, be placed in the oil bath of 30 ℃, reaction 24h.After completion of the reaction, put into dialysis membrane (molecular weight cut-off is 3000), dialyse 3 days in distilled water, every 3h changes water once, after dialysis finishes, and lyophilize, the poly(lactic acid)-b-that obtains different percentage of grafting gathers (L-Aspartic acid-co-L-aspartic acid-tonka bean camphor).

Table 52 reacts percentage of grafting and the reaction yield of gained poly(lactic acid)-b-poly-(L-Aspartic acid-co-L-aspartic acid-tonka bean camphor)

Reaction numbering	N ₁:N ₂	n ₁:n ₂	Reaction yield (%)
				1	0.1	0.09	92.9
2	0.2	0.19	92.1
				3	0.3	0.27	93.6

The above is only the preferred embodiment of the present invention; it should be pointed out that for those skilled in the art, under the premise without departing from the principles of the invention; can also make some improvements and modifications, these improvements and modifications also should be considered as protection scope of the present invention.

Embodiment 40: the preparation of hydrogel

Take embodiment 6(2) in poly-(6-caprolactone)-PLGA segmented copolymer (Mn of sample title 2 ₁=1900, Mn ₂=6200) tri-parts of 80mg, use respectively 1mL dmso solution, then add respectively the dimethyl sulphoxide solution 36 μ L of the ethylene glycol of 20mg:mL, 110 μ L, 219 μ L, after mixing, add the dimethyl sulphoxide solution 48 μ L of 60mg:mL DMAP, 144 μ L, 288 μ L, add again respectively 878 μ L, 526 μ L, the dimethyl sulfoxide (DMSO) of 0 μ L, the dimethyl sulphoxide solution 91 μ L of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride of 0.5g:mL, 273 μ L, 546 μ L, room temperature reaction 24h, the deionized water 3d that dialyses for gained gel, every 3h changes deionized water once, obtain theoretical degree of crosslinking and be respectively 10%, 30%, 60% hydrogel.

Fig. 5 is the electron microscope picture of the hydrogel prepared of the present embodiment, from figure we can see aliphatic polyester-three-dimensional porous structure of b-polyamino acid hydrogel.

Embodiment 41: the preparation of hydrogel

Take embodiment 6(2) in poly-(6-caprolactone)-PLGA segmented copolymer (Mn of sample title 2 ₁=1900, Mn ₂=6200) tri-parts of 80mg, use respectively 1mL dmso solution, then add respectively the dimethyl sulphoxide solution 36 μ L of the Diethylene Glycol of 34mg:mL, 110 μ L, 219 μ L, after mixing, add the dimethyl sulphoxide solution 48 μ L of 60mg:mL DMAP, 144 μ L, 288 μ L, add again respectively 878 μ L, 526 μ L, the dimethyl sulfoxide (DMSO) of 0 μ L, the dimethyl sulphoxide solution 91 μ L of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride of 0.5g:mL, 273 μ L, 546 μ L, room temperature reaction 24h, the deionized water 3d that dialyses for gained gel, every 3h changes deionized water once, obtain theoretical degree of crosslinking and be respectively 10%, 30%, 60% hydrogel.

Embodiment 42: the preparation of hydrogel

Take embodiment 6(2) in poly-(6-caprolactone)-PLGA segmented copolymer (Mn of sample title 2 ₁=1900, Mn ₂=6200) tri-parts of 80mg, use respectively 1mL dmso solution, then add respectively the dimethyl sulphoxide solution 36 μ L of the triethylene glycol of 48mg:mL, 110 μ L, 219 μ L, after mixing, add the dimethyl sulphoxide solution 48 μ L of 60mg:mL DMAP, 144 μ L, 288 μ L, add again respectively 878 μ L, 526 μ L, the dimethyl sulfoxide (DMSO) of 10 μ L, the dimethyl sulphoxide solution 91 μ L of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride of 0.5g:mL, 273 μ L, 546 μ L, room temperature reaction 24h, the deionized water 3d that dialyses for gained gel, every 3h changes deionized water once, obtain theoretical degree of crosslinking and be respectively 10%, 30%, 60% hydrogel.

Embodiment 43: the preparation of hydrogel

Take embodiment 6(2) in poly-(6-caprolactone)-PLGA segmented copolymer (Mn of sample title 2 ₁=1900, Mn ₂=6200) tri-parts of 80mg, use respectively 1mL dmso solution, then add respectively the dimethyl sulphoxide solution 36 μ L of the PEG400 of 130mg:mL, 110 μ L, 219 μ L, after mixing, add the dimethyl sulphoxide solution 48 μ L of 60mg:mL DMAP, 144 μ L, 288 μ L, add again respectively 878 μ L, 526 μ L, the dimethyl sulfoxide (DMSO) of 0 μ L, the dimethyl sulphoxide solution 91 μ L of 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride of 0.5g:mL, 273 μ L, 546 μ L, room temperature reaction 24h, the deionized water 3d that dialyses for gained gel, every 3h changes deionized water once, obtain theoretical degree of crosslinking and be respectively 10%, 30%, 60% hydrogel.

Above to a kind of aliphatic polyester-polyamino acid block copolymer provided by the invention and preparation method thereof and a kind of hydrogel and preparation method thereof be described in detail, having applied specific case herein sets forth principle of the present invention and embodiment, the explanation of above embodiment is just for helping to understand method of the present invention and core concept thereof, should be understood that, for those skilled in the art, under the premise without departing from the principles of the invention, can also carry out some improvement and modification to the present invention, these improvement and modification also fall in the protection domain of the claims in the present invention.

Claims

1. aliphatic polyester-the polyamino acid block copolymer shown in formula I,

I

2. a preparation method for the aliphatic polyester-polyamino acid block copolymer shown in formula I, is characterized in that, comprises the following steps:

A) monomer of tertbutyloxycarbonyl carbonic anhydride, thanomin and aliphatic polyester is blended in organic solvent, carries out ring-opening polymerization, and remove tertbutyloxycarbonyl, obtain end with amino aliphatic polyester; The monomer of described aliphatic polyester is rac-Lactide, lactic acid or 6-caprolactone;

I

3. preparation method according to claim 2, is characterized in that, described organic solvent is selected from the one in toluene, dimethyl sulfoxide (DMSO), dichloro acetic acid, methylene dichloride, tetrahydrofuran (THF), chloroform.

4. preparation method according to claim 2, is characterized in that, step a) is specially:

5. preparation method according to claim 2, is characterized in that, also comprises step d):

D) aliphatic polyester-polyamino acid block copolymer step c) being obtained and properties-correcting agent react under the effect of condensing agent and catalyzer, obtain the polymkeric substance shown in formula I, and wherein q meets following condition 0<q≤100; Described properties-correcting agent is styryl carbinol, Hydroxyethyl acrylate or tonka bean camphor; Described catalyzer is 4-dimethylamino pyrroles, and described condensing agent is 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride.

6. preparation method according to claim 5, is characterized in that, described aliphatic polyester-polyamino acid block copolymer and properties-correcting agent are 20:1～3 in molar ratio.

7. a hydrogel, is characterized in that, comprising:

Wherein, in the amount of substance y of the amount of substance x of described glycols compound, described catalyzer and described aliphatic polyester-polyamino acid block copolymer, the amount of substance z of hydroxyl meets the following x:z=1:10 of relation～3:5, y:z=1:1～5; Amount of substance w and the z of condensing agent meet the following w:z=5 of relation～15:1; The volume u of described solvent and the amount of substance z' of described aliphatic polyester-polyamino acid block copolymer meet the following u:z'=10 of relation～20:1.

8. hydrogel according to claim 7, is characterized in that, described glycols compound is selected from one or more in ethylene glycol, Diethylene Glycol, triethylene glycol and PEG400.

9. hydrogel composition according to claim 7, is characterized in that, the degree of crosslinking of described hydrogel composition is 10%～60%.

10. a preparation method for hydrogel, is characterized in that, comprises the following steps:

In solvent, under the effect of catalyzer and condensing agent, there is described aliphatic polyester-polyamino acid block copolymer and glycols compound crosslinking reaction and obtain hydrogel in the mol ratio m) providing according to claim 7; Described catalyzer is 4-dimethylamino pyrroles, and described condensing agent is 1-ethyl-(3-dimethylaminopropyl) carbodiimide hydrochloride.