Process method for synthesizing lactic acid-lysine copolymer by catalytically opening loop and copolymerizing with acetic bicyclo-guanidine

A lysine copolymer and bicyclic guanidine catalyzed lactide technology, which is applied in the direction of medical preparations, drug combinations, and pharmaceutical formulations of non-active ingredients, can solve problems such as potential safety hazards and poor catalytic effects, and achieve rapid response , high biological safety, and high conversion rate of monomer

Active Publication Date: 2012-06-20
NANKAI UNIV
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  • Abstract
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  • Application Information

AI Technical Summary

Problems solved by technology

[0006] The purpose of the present invention is to solve the common use of lactone ring-opening catalysts in the synthesis of polylactide-lysine morpholine diketone by the current ring-opening copolymerization method---stannous octoate Sn(Oct) 2 Poor safety hazards and catalytic effects caused by the problem, to provide a high-efficiency, non-toxic, metal-free, biomimetic organic catalyst bicyclic guanidine acetate catalyzed ring-opening copolymerization synthesis of lactic acid-lysine copolymer with high biological safety Process method

Method used

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  • Process method for synthesizing lactic acid-lysine copolymer by catalytically opening loop and copolymerizing with acetic bicyclo-guanidine
  • Process method for synthesizing lactic acid-lysine copolymer by catalytically opening loop and copolymerizing with acetic bicyclo-guanidine
  • Process method for synthesizing lactic acid-lysine copolymer by catalytically opening loop and copolymerizing with acetic bicyclo-guanidine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0031] Add 1.000g (6.944mmol) of monomer L-lactide and 0.0473g (0.142mmol) of L-lactide lysine to the reaction kettle to control the molar ratio of L-lactide and morpholine lysine Be: 98 / 2; Add catalyst bicyclic guanidine acetate 0.0141g (0.071mmol), control the molar weight sum of comonomer lactide and lysine morpholine diketone and the ratio of the molar weight of catalyst bicyclic guanidine acetate is: 100 / 1. After three times of evacuation-argon operation, the reactor was heated to 130° C. for 5 minutes under vacuum, and then continued to react at 100° C. for 40 minutes.

[0032] 20ml of dichloromethane was used to dissolve the polymer in a pressure test tube. Then 5 ml of triethylsilane, 0.1 ml of triethylamine and 0.15 g of palladium dichloride were added. Reaction at room temperature for 72h to remove the protecting group O-benzyl. After the reaction, palladium dichloride was filtered off, and 5 ml of methanol was added to the filtrate to completely react with unreac...

Embodiment 2

[0035]Add 1.000g (6.944mmol) of monomer L-lactide and 0.1480g (0.443mmol) of L-lactide lysine to the reaction kettle to control the molar ratio of L-lactide and morpholine lysine Be: 94 / 6; Add catalyst bicyclic guanidine acetate 0.0147g (0.074mmol), control the molar weight sum of comonomer lactide and lysine morpholine diketone and the ratio of the molar weight of catalyst bicyclic guanidine acetate is: 100 / 1. After the reaction kettle was subjected to vacuum pumping and argon filling operations for three times, it was heated to 140° C. for 4 minutes under vacuum, and then continued to react at 120° C. for 30 minutes.

[0036] 20ml of dichloromethane was used to dissolve the polymer in a pressure test tube. Then 5 ml of triethylsilane, 0.1 ml of triethylamine and 0.15 g of palladium dichloride were added. Reaction at room temperature for 72h to remove the protecting group O-benzyl. After the reaction, palladium dichloride was filtered off, and 5 ml of methanol was added to...

Embodiment 3

[0039] Add 1.000g (6.944mmol) of monomer L-lactide and 0.2577g (0.772mmol) of L-lactide and 0.2577g (0.772mmol) of L-lactide to the reaction kettle to control the molar ratio of L-lactide and morpholine lysine Be: 90 / 10; Add catalyst bicyclic guanidine acetate 0.0154g (0.077mmol), control the molar weight sum of comonomer lactide and lysine morpholine diketone and the ratio of the molar weight of catalyst bicyclic guanidine acetate is: 100 / 1. After three times of evacuation-argon operation, the reactor was heated to 150° C. for 3 minutes under vacuum, and then continued to react at 130° C. for 20 minutes.

[0040] 20ml of dichloromethane was used to dissolve the polymer in a pressure test tube. Then 5 ml of triethylsilane, 0.1 ml of triethylamine and 0.15 g of palladium dichloride were added. Reaction at room temperature for 72h to remove the protecting group O-benzyl. After the reaction, palladium dichloride was filtered off, and 5 ml of methanol was added to the filtrate ...

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Abstract

The invention discloses a process method for synthesizing a lactic acid-lysine copolymer by catalytically opening a loop and copolymerizing with acetic bicyclo-guanidine (the molar content of diaminocaproic acid is 1-5 percent). The lactic acid-lysine copolymer is synthesized by taking acetic bicyclo-guanidine as a catalyst, taking lactide and lysine morpholine diketone as monomers, performing body loop opening copolymerization and undergoing a phenmethyl carboxide removing action. The process method has characteristics that: the acetic bicyclo-guanidine serving as a catalyst is bionic organic guanidinium which is effective, nontoxic and free from metals; the monomer transformation ratio is high (more than or equal to 95 percent); the yield is over 93 percent; a product does not contain any metal or other toxic residue, and has high biological safety; the number average molecular weight is adjustable in the range of 1.5-2.8*10<4>, and the molecular weight distribution is narrow (PDI (Protein Disulfide Isomerase) is less than or equal to 1.30); the molar content of lysine in the copolymer is adjustable in the range of 1-5 percent; and the synthesized lactic acid-lysine copolymer isan amphiphilic functional group biodegradable polymer, is suitable for serving as targeted and controlled release medicament carriers, and can be applied on other aspects in the field of biological medical tissue engineering.

Description

technical field [0001] The invention belongs to the technical field of biodegradable materials for medicine, and relates to a biomimetic organic guanidine salt—bicyclic guanidine acetate as a catalyst, lactide and lysine morpholine dione lactate as monomers, through catalyzed ring-opening copolymerization reaction, Synthesize polylactide-lysine morpholine dione, and obtain biodegradable polymer lactic acid-lysine copolymer with high biosafety after catalytic removal of benzyloxycarbonyl group (lysine molar content in the copolymer is 1~ 5%). The synthesized lactic acid-lysine copolymer is an amphiphilic functional-based biodegradable material, which is suitable as a carrier for targeted and controlled release drugs (especially water-soluble anticancer drugs), and can be used in many fields in the field of biomedical tissue engineering. aspect. Background technique [0002] In recent years, with the rapid development of medicine and pharmaceutical science, polylactic acid b...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C08G63/91C08G63/685C08G63/87A61K47/34A61P35/00
Inventor 李弘宗绪鹏孔丽君
Owner NANKAI UNIV
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