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:
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;
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:
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;
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:
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.
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:
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, 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%.
The present invention also provides a kind of preparation method of hydrogel, comprises the following steps:
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 |
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.
(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 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 |
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.
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 |
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.
(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 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 |
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.
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.
(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 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 |
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.
(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 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 |
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 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 |
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.
(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 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 |
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 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 |
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.
(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 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 |
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 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.
(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 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 |
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.
(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 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 |
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 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 |
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.
(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 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 |
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 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 |
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.
(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 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 |
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 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 |
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.
(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 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 |
|
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 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 |
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.
(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 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 |
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 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 |
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.
(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 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 |
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 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 |
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 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 |
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 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 |
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 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 |
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 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 |
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 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 |
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 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 |
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 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 |
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 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 |
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
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 |
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
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 |
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
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 |
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 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 |
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 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 |
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 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 |
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
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 |
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
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 |
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
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 |
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
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.