Preparation method of ethylenediamine and RGD polypeptide modified MPLGA with high anhydride content

Abstract

The invention provides a preparation method of ethylenediamine and RGD polypeptide modified MPLGA with high anhydride content. With D,L-lactide, glycolide and maleic anhydride being raw materials, stannous octoate being a catalyst and benzoyl peroxide being an initiator, the maleic polylactide glycolide anhydride (MPLGA) with the high anhydride content is prepared through polymerization under vacuum conditions; a trichloromethane solution of ethylenediamine is added into a trichloromethane solution of MPLGA under stirring conditions, the mixture is kept warm for 5-10 minutes at the temperature lower than 10DEG C and reacts for 30-60 minutes at room temperature, the product is dropwise added into an excessive solvent to precipitate and be separated out, and polymer (EMPLGA) solids of ethylenediamine modified MPLGA are obtained; the EMPLGA is dissolved in tetrahydrofuran, a coupling agent, namely N,N-dicyclohexylcarbodiimide, is added, the pH value of the solution is adjusted to range from 8 to 9, stirring is carried out, a tetrahydrofuran solution of RGD is dropwise added, the mixture reacts for 24 hours at the temperature of 0 DEG C and then is filtered, and the polypeptide modified RGD-EMPLGA solids are obtained after the product is frozen and dried. The prepared product has better hydrophilia, cell affinity and a controllable degradation property.

Description

technical field

[0001] The invention relates to the technical field of production of degradable biomedical polymer materials, in particular to a preparation method of a polylactide-modified polymer rich in amino basic groups and biological signal molecules. Background technique

[0002] Polylactide (PLGA) is widely used in the fields of tissue engineering and sustained-release materials due to its good biocompatibility, easy-to-control degradation rate, and easy macroscopic shaping. However, the lack of clusters and biosignaling molecules and the accumulation of acidic degradation products in vivo limit its application.

[0003] The introduction of functional active groups or biological signal molecules by means of copolymerization modification, grafting, surface controllable aminolysis technology and other methods is one of the important methods to improve its performance. Our research group obtained maleic anhydride-grafted polylactide (MPLGA) by melt polymerization using...

Examples

Embodiment 1

[0027] Put 73 g of D,L-lactide, 27 g of glycolide and 5 g of maleic anhydride into an ampoule, then add 0.2 g of benzoyl peroxide (BPO) as an initiator, and 0.01 g of stannous octoate as a catalyst , vacuum dried for 12h. After drying, take it out, evacuate it with a diffusion pump for 1 h, seal the tube at a vacuum degree of 7.0 Pa, and react the sealed ampoule in a constant temperature drying oven at 130°C for 36 h. The crude product MPLGA was dissolved in chloroform and purified by precipitation with excess ethanol. The resulting MPLGA molecular weight M w =27850, M w / M n =1.65, the maleic anhydride graft rate is 9.2%.

[0028] Dissolve 5 g of purified MPLGA in 8 mL of chloroform to prepare a 30wt% MPLGA solution in chloroform, and mix equal volumes of ethylenediamine and chloroform to prepare a 38wt% ethylenediamine solution in chloroform. Add the chloroform of MPLGA into a three-necked flask equipped with a stirrer and a thermometer, add 2 mL of ethylenediamine in ...

Embodiment 2

[0031] Put 75 g of D,L-lactide, 25 g of glycolide and 8 g of maleic anhydride into an ampoule, then add 0.3 g of benzoyl peroxide (BPO) as an initiator, and 0.02 g of stannous octoate as a catalyst , vacuum dried for 12h. After drying, take it out, evacuate it with a diffusion pump for 1 h, seal the tube at a vacuum degree of 6.0 Pa, and react the sealed ampoule in a constant temperature drying oven at 140 °C for 48 h. The crude product MPLGA was dissolved in chloroform and purified by precipitation with excess ethanol. The resulting MPLGA molecular weight M w =30125, Mw / M n =1.60, maleic anhydride graft rate, 7.9%.

[0032] Dissolve 5g of MPLGA in 10mL of chloroform to prepare 25wt% MPLGA in chloroform, and mix equal volumes of ethylenediamine and chloroform to prepare 38wt% ethylenediamine in chloroform. Add the chloroform of MPLGA into a three-necked flask equipped with a stirrer and a thermometer, add 2 mL of ethylenediamine in chloroform solution dropwise under stir...

Embodiment 3

[0035] Put 70 g of D,L-lactide, 25 g of glycolide and 6 g of maleic anhydride into an ampoule, then add 0.2 g of benzoyl peroxide (BPO) as an initiator, and 0.03 g of stannous octoate as a catalyst , vacuum dried for 12h. After drying, take it out, evacuate it with a diffusion pump for 1 h, seal the tube at a vacuum degree of 8.0 Pa, and react the sealed ampoule in a constant temperature drying oven at 130°C for 60 h. The crude product MPLGA was dissolved in chloroform and purified by precipitation with excess ethanol. The resulting MPLGA molecular weight M w =28455, M w / M n =1.72, the maleic anhydride graft rate is 7.4%.

[0036] Dissolve 10g of MPLGA in 16mL of chloroform to prepare a 30wt% MPLGA solution in chloroform, and mix equal volumes of ethylenediamine and chloroform to prepare a 38wt% ethylenediamine solution in chloroform. Add the chloroform of MPLGA into a three-necked flask equipped with a stirrer and a thermometer, add 2 mL of ethylenediamine in chlorofor...

technical field

[0001] The invention relates to the technical field of production of degradable biomedical polymer materials, in particular to a preparation method of a polylactide-modified polymer rich in amino basic groups and biological signal molecules. Background technique

[0002] Polylactide (PLGA) is widely used in the fields of tissue engineering and sustained-release materials due to its good biocompatibility, easy-to-control degradation rate, and easy macroscopic shaping. However, the lack of clusters and biosignaling molecules and the accumulation of acidic degradation products in vivo limit its application.

[0003] The introduction of functional active groups or biological signal molecules by means of copolymerization modification, grafting, surface controllable aminolysis technology and other methods is one of the important methods to improve its performance. Our research group obtained maleic anhydride-grafted polylactide (MPLGA) by melt polymerization using...

Examples

Embodiment 1

[0027] Put 73 g of D,L-lactide, 27 g of glycolide and 5 g of maleic anhydride into an ampoule, then add 0.2 g of benzoyl peroxide (BPO) as an initiator, and 0.01 g of stannous octoate as a catalyst , vacuum dried for 12h. After drying, take it out, evacuate it with a diffusion pump for 1 h, seal the tube at a vacuum degree of 7.0 Pa, and react the sealed ampoule in a constant temperature drying oven at 130°C for 36 h. The crude product MPLGA was dissolved in chloroform and purified by precipitation with excess ethanol. The resulting MPLGA molecular weight M w =27850, M w / M n =1.65, the maleic anhydride graft rate is 9.2%.

[0028] Dissolve 5 g of purified MPLGA in 8 mL of chloroform to prepare a 30wt% MPLGA solution in chloroform, and mix equal volumes of ethylenediamine and chloroform to prepare a 38wt% ethylenediamine solution in chloroform. Add the chloroform of MPLGA into a three-necked flask equipped with a stirrer and a thermometer, add 2 mL of ethylenediamine in ...

Embodiment 2

[0031] Put 75 g of D,L-lactide, 25 g of glycolide and 8 g of maleic anhydride into an ampoule, then add 0.3 g of benzoyl peroxide (BPO) as an initiator, and 0.02 g of stannous octoate as a catalyst , vacuum dried for 12h. After drying, take it out, evacuate it with a diffusion pump for 1 h, seal the tube at a vacuum degree of 6.0 Pa, and react the sealed ampoule in a constant temperature drying oven at 140 °C for 48 h. The crude product MPLGA was dissolved in chloroform and purified by precipitation with excess ethanol. The resulting MPLGA molecular weight M w =30125, Mw / M n =1.60, maleic anhydride graft rate, 7.9%.

[0032] Dissolve 5g of MPLGA in 10mL of chloroform to prepare 25wt% MPLGA in chloroform, and mix equal volumes of ethylenediamine and chloroform to prepare 38wt% ethylenediamine in chloroform. Add the chloroform of MPLGA into a three-necked flask equipped with a stirrer and a thermometer, add 2 mL of ethylenediamine in chloroform solution dropwise under stir...

Embodiment 3

[0035] Put 70 g of D,L-lactide, 25 g of glycolide and 6 g of maleic anhydride into an ampoule, then add 0.2 g of benzoyl peroxide (BPO) as an initiator, and 0.03 g of stannous octoate as a catalyst , vacuum dried for 12h. After drying, take it out, evacuate it with a diffusion pump for 1 h, seal the tube at a vacuum degree of 8.0 Pa, and react the sealed ampoule in a constant temperature drying oven at 130°C for 60 h. The crude product MPLGA was dissolved in chloroform and purified by precipitation with excess ethanol. The resulting MPLGA molecular weight M w =28455, M w / M n =1.72, the maleic anhydride graft rate is 7.4%.

[0036] Dissolve 10g of MPLGA in 16mL of chloroform to prepare a 30wt% MPLGA solution in chloroform, and mix equal volumes of ethylenediamine and chloroform to prepare a 38wt% ethylenediamine solution in chloroform. Add the chloroform of MPLGA into a three-necked flask equipped with a stirrer and a thermometer, add 2 mL of ethylenediamine in chlorofor...

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