CN103242536B - Method for preparing polypeptide-polylactic acid-polyethyleneglycol dual-graft copolymer - Google Patents
Method for preparing polypeptide-polylactic acid-polyethyleneglycol dual-graft copolymer Download PDFInfo
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Abstract
The invention discloses a method for preparing a polypeptide-polylactic acid-polyethyleneglycol dual-graft copolymer. The method is characterized in that the molecular weight of a polypeptide chain segment in the copolymer is 20000-50000; the molecular weight of a polylactic acid chain segment is 1000-2000; and the molecular weight of a polyethylene glycol chain segment is 500-700. The preparation method comprises the following steps of: 1) synthesizing a polypeptide-polylactic acid graft copolymer, namely, adding a polypeptide homopolymer, polylactic acid lauryl ether, a solvent and a catalyst to a dry reactor, stirring and reacting for 3-4 days under an inert atmosphere at 55-58 DEG C, so as to prepare the target in manners of filtering, dialyzing and drying; and 2) synthesizing the polypeptide-polylactic acid-polyethyleneglycol dual-graft copolymer, namely adding the polypeptide-polylactic acid copolymer, the catalyst, the solvent and the methoxy polyethylene glycol to the dry reactor, stirring and reacting for 2-3 days under the inert atmosphere at 55-59 DEG C, so as to obtain the target in manners of filtering, dialyzing and drying. The method is simple in process; and the obtained target is a novel biodegradable material.
Description
Technical field
The preparation method who the present invention relates to a kind of poly-peptide-polylactic acid-polyglycol dual graft multipolymer, belongs to biodegradated polymer materal preparing technical field.
Background technology
Poly-peptide have good biocompatibility, biological degradability, low genetic immunization and nontoxic, have no side effect, various functional groups can be introduced relatively easily forms poly-peptide derivant, it is the important carrier of preparing slow releasing pharmaceutical system, be widely used in pharmacy and biomedical aspect [Yin Jingbo etc., Chinese patent, application number 200610116386.8].Also affected its application but poly-fret peptide wetting ability is poor.
Poly(lactic acid) is a kind of polymeric biomaterial with good biocompatibility and biological degradability, is widely used at biomedical sector.But because the acidity of poly(lactic acid) degraded initial stage product lactic acid is stronger, its localized accumulated, can have certain hormesis to tissue, makes its application be subject to certain restrictions [Yao Kangde etc., Chinese patent, application number 02155475.7].
Polyoxyethylene glycol have good biocompatibility, biological degradability, wetting ability and nontoxic, have no side effect etc., therefore be widely used in biomedicine field, as: [woods is praised equality for solid support material, the tissue engineering bracket material etc. of medicament slow release, Chinese patent, application number 200410067960.6].
First polylactic acid chain segment is grafted to and on poly-peptide molecule chain, obtains poly-peptide-polylactic acid graft copolymer, and then polyoxyethylene glycol segment is grafted on the poly-peptide molecule chain in poly-peptide-polylactic acid graft copolymer, poly-peptide-polylactic acid-polyglycol dual graft multipolymer the set obtaining poly-peptide, poly(lactic acid) and polyoxyethylene glycol three's advantage, overcome shortcoming separately, have complementary advantages, certainly will there is good application potential in pharmacy and biomedical aspect.This dual graft multipolymer yet there are no bibliographical information at present.
Summary of the invention
The object of this invention is to provide a kind of preparation method of poly-peptide-polylactic acid-polyglycol dual graft multipolymer of having gathered poly-peptide, poly(lactic acid) and polyoxyethylene glycol three advantage.Its technical scheme is:
A kind of preparation method of poly-peptide-polylactic acid-polyglycol dual graft multipolymer, it is characterized in that: in multipolymer, the molecular weight of poly-peptide segment is 20000~50000, the molecular weight of polylactic acid chain segment is 1000~2000, the molecular weight of polyoxyethylene glycol segment is 500~700, and its preparation method adopts following steps:
1) poly-peptide-polylactic acid graft copolymer is synthetic: in dry reactor, add poly-peptide homopolymer, poly(lactic acid) monododecyl ether, solvent and catalyzer, under inert atmosphere, after 3 days~4 days, make target compound by filtering, dialyse, being dried in 55 DEG C~58 DEG C stirring reactions;
2) poly-peptide-polylactic acid-polyglycol dual graft multipolymer is synthetic: in dry reactor, add poly-peptide-polylactic acid graft copolymer, catalyzer, solvent and poly glycol monomethyl ether, under inert atmosphere, after 2 days~3 days, make target compound by filtering, dialyse, being dried in 55 DEG C~59 DEG C stirring reactions.
The preparation method of described poly-peptide-polylactic acid-polyglycol dual graft multipolymer, step 1) in, reactant solution concentration is 5~10g/100ml, wherein poly-peptide homopolymer adopts poly-(γ-phenmethyl-Pidolidone ester), poly-(γ-ethyl-Pidolidone ester) or poly-(γ-methyl-Pidolidone ester), poly(lactic acid) monododecyl ether adopts PLLA monododecyl ether, and the mol ratio of poly(lactic acid) monododecyl ether and poly-peptide homopolymer is 15~25:1; Solvent adopts vinyl trichloride or dimethyl sulfoxide (DMSO); Catalyzer adopts tosic acid, and the mol ratio of catalyzer and poly-peptide homopolymer is 25~45:1.
The preparation method of described poly-peptide-polylactic acid-polyglycol dual graft multipolymer, step 2) in, reactant solution concentration is 5~10g/100ml, wherein the mol ratio of poly glycol monomethyl ether and poly-peptide-polylactic acid graft copolymer is 20~30:1, solvent adopts 1,1,2-trichloroethane or dimethyl sulfoxide (DMSO); Catalyzer adopts tosic acid, and the mol ratio of catalyzer and poly-peptide-polylactic acid graft copolymer is 25~45:1.
Compared with prior art, its advantage is in the present invention:
1, described poly-peptide-polylactic acid-polyglycol dual graft multipolymer preparation method is simple;
2, described poly-peptide-polylactic acid-polyglycol dual graft multipolymer is a kind of novel biodegradable material and has wetting ability, has not yet to see bibliographical information.
Brief description of the drawings
Fig. 1 is the infrared spectrum of the poly-peptide-polylactic acid-polyglycol dual graft multipolymer embodiment of the present invention.
In figure: 3288cm
-1, 1652cm
-1, 1549cm
-1the absorption peak at place is the characteristic peak of poly-peptide segment; 2995cm
-1, 2927cm
-1the characteristic peak that the absorption peak at place is polylactic acid chain segment; 2870cm
-1, 1107cm
-1the absorption peak at place is the characteristic peak of polyoxyethylene glycol segment.
Embodiment
Embodiment mono-, adopts following steps:
1) poly-peptide-polylactic acid graft copolymer is synthetic
In dry reactor, adding 8 gram molecular weights is 20000 poly-(γ-phenmethyl-Pidolidone ester), PLLA monododecyl ether, the 1.75 grams of tosic acid that 6.1 gram molecular weights are 1000, add again 200 milliliter 1,1,2-trichloroethane solvent, under inert atmosphere, in 55 DEG C of stirring reactions 3 days, termination reaction, make target compound by filtering, dialyse, being dried again, target compound molecular weight is 25235.
2) poly-peptide-polylactic acid-polyglycol dual graft multipolymer is synthetic:
In dry reactor, add poly glycol monomethyl ether and 1.21 grams of tosic acid that 7 grams of poly-peptide-polylactic acid graft copolymers, 2.8 gram molecular weights are 500, add again 140 milliliter 1,1,2-trichloroethane solvent, under inert atmosphere, in 55 DEG C of stirring reactions 2 days, termination reaction, make target compound by filtering, dialyse, being dried again, its molecular weight is 29727.
Fig. 1 is the infrared spectrum of the poly-peptide-polylactic acid-polyglycol dual graft multipolymer of the present embodiment.
After tested: 24 hours water-intake rates of this target compound are 10.2%.
Embodiment bis-
1) poly-peptide-polylactic acid graft copolymer is synthetic
In dry reactor, adding 7 gram molecular weights is 30000 poly-(γ-ethyl-Pidolidone ester), PLLA monododecyl ether, 1.21 grams of tosic acid and the 180 milliliters of dimethyl sulfoxide solvents that 7 gram molecular weights are 1500, under inert atmosphere, in 56 DEG C of stirring reactions 4 days, termination reaction, make target compound by filtering, dialyse, being dried again, the molecular weight of target compound is 35644.
2) poly-peptide-polylactic acid-polyglycol dual graft multipolymer is synthetic:
In dry reactor, add poly glycol monomethyl ether and 0.91 gram of tosic acid that 6 grams of poly-peptide-polylactic acid graft copolymers, 2.6 gram molecular weights are 600, add again 130 milliliters of dimethyl sulfoxide solvents, under inert atmosphere, in 57 DEG C of stirring reactions 3 days, termination reaction, make target compound by filtering, dialyse, being dried again, its molecular weight is 43206.
After tested: 24 hours water-intake rates of this target compound are 12.5%.
Embodiment tri-
1) poly-peptide-polylactic acid graft copolymer is synthetic
In dry reactor, add 9 gram molecular weights are 50000 poly-(γ-methyl-Pidolidone ester), 8.8 gram molecular weights are 2000 PLLA monododecyl ether, 1.35 grams of tosic acid and 250 milliliter 1,1,2-trichloroethane solvent, under inert atmosphere, in 58 DEG C of stirring reactions 3 days, termination reaction, then make target compound by filtering, dialyse, being dried, the molecular weight of target compound is 56756.
2) poly-peptide-polylactic acid-polyglycol dual graft multipolymer is synthetic
In dry reactor, add poly glycol monomethyl ether and 1.05 grams of tosic acid that 8 grams of poly-peptide-polylactic acid graft copolymers, 2.8 gram molecular weights are 700, add again 150 milliliter 1,1,2-trichloroethane solvent, under inert atmosphere, in 59 DEG C of stirring reactions 3 days, termination reaction, make target compound by filtering, dialyse, being dried again, its molecular weight is 66298.
After tested: 24 hours water-intake rates of this target compound are 14.8%.
Claims (5)
1. the preparation method of poly-peptide-polylactic acid-polyglycol dual graft multipolymer, it is characterized in that: in multipolymer, the molecular weight of poly-peptide segment is 20000~50000, the molecular weight of polylactic acid chain segment is 1000~2000, the molecular weight of polyoxyethylene glycol segment is 500~700, and its preparation method adopts following steps:
1) poly-peptide-polylactic acid graft copolymer is synthetic: in dry reactor, add poly-peptide homopolymer, poly(lactic acid) monododecyl ether, solvent and catalyzer, under inert atmosphere in 55 DEG C~58 DEG C stirring reactions after 3 days~4 days, make target compound by filtering, dialyse, being dried, wherein solvent adopts 1,1,2-trichloroethane or dimethyl sulfoxide (DMSO), catalyzer adopts tosic acid, and the mol ratio of catalyzer and poly-peptide homopolymer is 25~45:1;
2) poly-peptide-polylactic acid-polyglycol dual graft multipolymer is synthetic: in dry reactor, add poly-peptide-polylactic acid graft copolymer, catalyzer, solvent and poly glycol monomethyl ether, under inert atmosphere in 55 DEG C~59 DEG C stirring reactions after 2 days~3 days, make target compound by filtering, dialyse, being dried, wherein solvent adopts 1,1,2-trichloroethane or dimethyl sulfoxide (DMSO), catalyzer adopts tosic acid, and the mol ratio of catalyzer and poly-peptide-polylactic acid graft copolymer is 25~45:1.
2. the preparation method of poly-peptide-polylactic acid-polyglycol dual graft multipolymer according to claim 1, it is characterized in that: step 1) in, poly-peptide homopolymer adopts poly-(γ-phenmethyl-Pidolidone ester), poly-(γ-ethyl-Pidolidone ester) or poly-(γ-methyl-Pidolidone ester), poly(lactic acid) monododecyl ether adopts PLLA monododecyl ether, and the mol ratio of poly(lactic acid) monododecyl ether and poly-peptide homopolymer is 15~25:1.
3. the preparation method of poly-peptide-polylactic acid-polyglycol dual graft multipolymer according to claim 1, is characterized in that: step 1) in, reactant solution concentration is 5~10g/100ml.
4. the preparation method of poly-peptide-polylactic acid-polyglycol dual graft multipolymer according to claim 1, is characterized in that: step 2) in, the mol ratio of poly glycol monomethyl ether and poly-peptide-polylactic acid graft copolymer is 20~30:1.
5. the preparation method of poly-peptide-polylactic acid-polyglycol dual graft multipolymer according to claim 1, is characterized in that: step 2) in, reactant solution concentration is 5~10g/100ml.
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CN104448842B (en) * | 2015-01-06 | 2016-08-31 | 山东理工大学 | A kind of method that polylactic acid improves poly-peptide film hydrophilic and compliance with polyacrylic acid |
CN104448843B (en) * | 2015-01-06 | 2016-10-05 | 山东理工大学 | A kind of method that polycaprolactone improves poly-peptide film hydrophily and compliance with polyacrylic acid |
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CN104479367B (en) * | 2015-01-12 | 2016-08-31 | 山东理工大学 | A kind of method that PLA improves poly-peptide film hydrophily and compliance with aqueous polyurethane |
CN104559224B (en) * | 2015-01-12 | 2017-02-22 | 山东理工大学 | Method for improving hydrophilicity and flexibility of polypeptide film by polypropylene glycol and waterborne polyurethane |
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