CN101555316A - Synthetic method of amino-terminated polyethylene glycol-polylactide block copolymer - Google Patents
Synthetic method of amino-terminated polyethylene glycol-polylactide block copolymer Download PDFInfo
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- CN101555316A CN101555316A CNA2009100148898A CN200910014889A CN101555316A CN 101555316 A CN101555316 A CN 101555316A CN A2009100148898 A CNA2009100148898 A CN A2009100148898A CN 200910014889 A CN200910014889 A CN 200910014889A CN 101555316 A CN101555316 A CN 101555316A
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- 238000010189 synthetic method Methods 0.000 title claims abstract description 19
- 239000004698 Polyethylene Substances 0.000 title claims abstract description 15
- -1 polyethylene Polymers 0.000 title claims abstract description 15
- 229920000573 polyethylene Polymers 0.000 title claims abstract description 15
- 229920001400 block copolymer Polymers 0.000 title abstract 2
- 229920000747 poly(lactic acid) Polymers 0.000 title abstract 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims abstract description 56
- 238000006243 chemical reaction Methods 0.000 claims abstract description 46
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims abstract description 28
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims abstract description 22
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 22
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims abstract description 14
- IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 claims abstract description 14
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical compound CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 claims abstract description 13
- 229960000583 acetic acid Drugs 0.000 claims abstract description 11
- 239000012362 glacial acetic acid Substances 0.000 claims abstract description 11
- 235000017557 sodium bicarbonate Nutrition 0.000 claims abstract description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims abstract description 7
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 25
- 238000000710 polymer precipitation Methods 0.000 claims description 22
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 claims description 20
- 229920001577 copolymer Polymers 0.000 claims description 14
- 239000004310 lactic acid Substances 0.000 claims description 14
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 12
- 229910052786 argon Inorganic materials 0.000 claims description 10
- 238000005119 centrifugation Methods 0.000 claims description 10
- 239000007789 gas Substances 0.000 claims description 10
- 238000003756 stirring Methods 0.000 claims description 10
- 238000001291 vacuum drying Methods 0.000 claims description 10
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 8
- 238000000967 suction filtration Methods 0.000 claims description 8
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 6
- 229960000935 dehydrated alcohol Drugs 0.000 claims description 6
- 229920000642 polymer Polymers 0.000 abstract description 7
- 238000009776 industrial production Methods 0.000 abstract description 3
- 239000003999 initiator Substances 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 3
- 238000005580 one pot reaction Methods 0.000 abstract description 2
- 230000002349 favourable effect Effects 0.000 abstract 2
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 abstract 1
- 239000012300 argon atmosphere Substances 0.000 abstract 1
- 230000015572 biosynthetic process Effects 0.000 abstract 1
- 229920002521 macromolecule Polymers 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- 239000002574 poison Substances 0.000 abstract 1
- 231100000614 poison Toxicity 0.000 abstract 1
- XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 abstract 1
- 239000012264 purified product Substances 0.000 abstract 1
- 238000003786 synthesis reaction Methods 0.000 abstract 1
- 229920001553 poly(ethylene glycol)-block-polylactide methyl ether Polymers 0.000 description 12
- 238000005160 1H NMR spectroscopy Methods 0.000 description 6
- 230000005311 nuclear magnetism Effects 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000005033 Fourier transform infrared spectroscopy Methods 0.000 description 5
- 238000006116 polymerization reaction Methods 0.000 description 4
- KSBAEPSJVUENNK-UHFFFAOYSA-L tin(ii) 2-ethylhexanoate Chemical compound [Sn+2].CCCCC(CC)C([O-])=O.CCCCC(CC)C([O-])=O KSBAEPSJVUENNK-UHFFFAOYSA-L 0.000 description 4
- 125000000524 functional group Chemical group 0.000 description 3
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- 125000003368 amide group Chemical group 0.000 description 2
- 230000000903 blocking effect Effects 0.000 description 2
- 238000006555 catalytic reaction Methods 0.000 description 2
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 2
- 238000002156 mixing Methods 0.000 description 2
- 235000011164 potassium chloride Nutrition 0.000 description 2
- 239000001103 potassium chloride Substances 0.000 description 2
- YBJHBAHKTGYVGT-ZKWXMUAHSA-N (+)-Biotin Chemical compound N1C(=O)N[C@@H]2[C@H](CCCCC(=O)O)SC[C@@H]21 YBJHBAHKTGYVGT-ZKWXMUAHSA-N 0.000 description 1
- YQGIMYRUMRCSTB-SFHVURJKSA-N (2S)-2-[bis(phenylmethoxycarbonyl)amino]-4-methylsulfanylbutanoic acid Chemical compound C=1C=CC=CC=1COC(=O)N([C@@H](CCSC)C(O)=O)C(=O)OCC1=CC=CC=C1 YQGIMYRUMRCSTB-SFHVURJKSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229930003756 Vitamin B7 Natural products 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 125000003172 aldehyde group Chemical group 0.000 description 1
- 238000005576 amination reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
- 230000007812 deficiency Effects 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 235000014655 lactic acid Nutrition 0.000 description 1
- 239000000693 micelle Substances 0.000 description 1
- 239000002105 nanoparticle Substances 0.000 description 1
- 238000007344 nucleophilic reaction Methods 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 125000006239 protecting group Chemical group 0.000 description 1
- 238000007151 ring opening polymerisation reaction Methods 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000002110 toxicologic effect Effects 0.000 description 1
- 231100000027 toxicology Toxicity 0.000 description 1
- 239000011735 vitamin B7 Substances 0.000 description 1
- 235000011912 vitamin B7 Nutrition 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
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- Polyesters Or Polycarbonates (AREA)
Abstract
The invention discloses a synthetic method of an amino-terminated polyethylene glycol-polylactide block copolymer, which belongs to the technical field of the high molecular material. The synthetic method comprises the following steps: firstly, the 10-15 parts of tetrahydrofuran by weight, the 1-6 parts of hexamethyldisilazane potassium salt by weight and the 2-15 parts of ethylene oxide by weight are added to a reaction bottle in sequence in the argon atmosphere and react for 4-5 days under ice bath to form yellow viscous solution; secondly, the 5-50 parts of lactide by weight is added to the reaction bottle to react for 8-18 h at the temperature of 35-40 DEG C; thirdly, the reaction bottle is dripped with 1-5 parts of hydrochloric acid solution or acetone solution of glacial acetic acid by weight, stirred for 20-45 min at the room temperature and then is dripped with sodium bicarbonate solution or absolute ether until the polymer is fully deposited; and fourthly, the polymer is deposited, centrifugally separated and purified, and the purified product is dried under vacuum to constant weight. The synthetic method is simple in steps, can finish the synthesis with one pot by a one-step method and is favorable for the industrial production, the yield is high and up to 90 percent above, and the used KHMDS potassium salt initiator has no poison and harm to the human body, therefore, the synthetic method is favorable for the application of the medical macromolecule.
Description
Technical field
The present invention relates to a kind of synthetic method of segmented copolymer, particularly the synthetic method of the amino polyethylene glycol-lactic acid segmented copolymer of end.
Background technology
Polyethylene glycol-lactic acid segmented copolymer (PEG-b-PLA) has excellent biocompatibility, biological degradability, and can form the nano-micelle particle of nucleocapsid structure in water.The PEG-b-PLA that the synthetic end of the chain of design contains functional group can utilize terminated functional group to connect targeted molecular, thereby preparation has the nanoparticle of target function.Common has: contain the HOOC-PEG-b-PLA that holds carboxyl, the OHC-PEG-b-PLA of terminal aldehyde group, the amino H of end
2N-PEG-b-PLA etc.Wherein, amino is active high, and it is of a great variety to carry out the targeted molecular of ligation with it, therefore, and to the amino H of synthetic end
2The demand of N-PEG-b-PLA is more and more higher, and wishes that synthetic route is simple, so that industrial production.
The amino H of synthetic at present end
2The N-PEG-b-PLA method mainly contains: (1) earlier synthetic end contains the amino PEG of useful vitamin H protection, and polymerization lactic acid LA under stannous octoate catalysis then removes to generate behind the blocking group and contains the amino H of end
2N-PEG-b-PLA; (2) with contain the amino PEG of end under the catalysis of stannous octoate with the LA polymerization, obtained an end and contained amino H
2The N-PEG-b-PLA block polymer; (3) utilize Maleimide-PEG-NH
2Carry out linked reaction with PLA-SH, synthesized H
2N-PEG-b-PLA; (4) with H
2The amino acid of N-PEG and amido protecting generates multipolymer by nucleophilic reaction, causes the rac-Lactide ring-opening polymerization with stannous octoate as catalyzer, can obtain amination H after removing blocking group
2The N-PEG-b-PLA multipolymer.
Yet, above synthetic method, the promptly synthetic earlier PEG that contains amino, then with stannous octoate as catalyzer, the repolymerization rac-Lactide, perhaps PEG by containing functional group and the linked reaction of PLA obtain corresponding block polymer, synthetic route is loaded down with trivial details, and productive rate is lower.
Summary of the invention
The objective of the invention is to overcome above-mentioned deficiency, the synthetic method of the amino polyethylene glycol-lactic acid of a kind of end segmented copolymer is provided, synthetic route is simple, and the sylvite initiator of usefulness does not have toxicity to human body.
The present invention's technical scheme of taking of dealing with problems is: the synthetic method of holding amino polyethylene glycol-lactic acid segmented copolymer, it is characterized in that may further comprise the steps: 1) under argon gas atmosphere, successively the tetrahydrofuran (THF) (THF) of 10～50 weight parts, the potassium hexamethyldisilazide (KHMDS) of 1～6 weight part, the oxyethane (EO) of 2～15 weight parts are added in the reaction flask, ice bath reacted 4～5 days down, formed yellow viscous solution; 2) rac-Lactide with 5～50 weight parts joins in the reaction flask, reacts 8h～18h down at 35～40 ℃; 3) in reaction flask, splash into the hydrochloric acid soln of 1-5 weight part or the acetone soln of Glacial acetic acid, stirring at room 20～45min, it is complete to polymer precipitation to splash into sodium hydrogen carbonate solution or anhydrous diethyl ether then; 4) with polymer precipitation centrifugation and purifying, with the product vacuum-drying behind the purifying to constant weight.
The synthetic method of the amino polyethylene glycol-lactic acid of described end segmented copolymer, preferred following steps: 1) under argon gas atmosphere, successively the tetrahydrofuran (THF) (THF) of 15 weight parts, the potassium hexamethyldisilazide (KHMDS) of 2 weight parts, the oxyethane (EO) of 2.5 weight parts are added in the reaction flask, ice bath reacted 4 days down, formed yellow viscous solution; 2) rac-Lactide with 5 weight parts joins in the reaction flask, and 40 ℃ are reacted 8h down; 3) in reaction flask, splash into the hydrochloric acid soln of 1 weight part or the acetone soln of Glacial acetic acid, stirring at room 20min, it is complete to polymer precipitation to splash into sodium hydrogen carbonate solution or anhydrous diethyl ether then; 4) with polymer precipitation centrifugation and purifying, with the product vacuum-drying behind the purifying to constant weight.
The acetone soln of the Glacial acetic acid described in the step 3) in the synthetic method of the amino polyethylene glycol-lactic acid of described end segmented copolymer, the volume ratio of Glacial acetic acid and acetone is 1: 6～1: 9; Described concentration of hydrochloric acid solution is 0.1N; The mass concentration of described sodium hydrogen carbonate solution is 0.5%.
The purifying of the polymer precipitation described in the step 4) is first with methylene dichloride or acetone or tetrahydrofuran (THF) dissolving in the synthetic method of the amino polyethylene glycol-lactic acid of described end segmented copolymer, adds excessive dehydrated alcohol or methyl alcohol suction filtration then.
The amino polyethylene glycol-lactic acid of the end segmented copolymer that utilizes the present invention to obtain; its end amino is initiated polymerization carbobenzoxy-(Cbz) Methionin acid anhydrides Lys (z)-NCA further, can obtain containing the block polymer PLL-b-PEG-b-PLA of a plurality of ammonia side groups behind the removal amido protecting group.
Advantage of the present invention is:
1. the synthetic method step is simple, can one pot, finish syntheticly to single stage method, be beneficial to industrial production, and the productive rate height is more than 90%.
2. used KHMDS sylvite initiator to the human body toxicological harmless, utilizes the application of medical polymer.
3. utilize terminated amino, can further cause Lys (z)-NCA polymerization easily, the synthetic block polymer that contains a plurality of side amino.
Embodiment
Further specify the present invention below in conjunction with embodiment.
Embodiment 1
Under argon gas atmosphere, THF, 2g KHMDS, the 2.5g EO with 15g adds in the reaction flask successively, and ice bath reacted 4 days down, formed yellow viscous solution; Rac-Lactide with 5g joins in the reaction flask then, and 40 ℃ of reactions are after 8 hours, and splashing into the 1g volume ratio in reaction flask is 1: 6 the Glacial acetic acid and the mixing solutions of acetone, stirring at room 20min; It is complete to polymer precipitation to splash into anhydrous diethyl ether in reaction flask, with the polymer precipitation centrifugation, earlier with the methylene dichloride dissolving, adds the excessive methanol suction filtration more then, and the product vacuum-drying behind the purifying to constant weight, is got white solid, and productive rate is 93.6%.
GPC(THF)：Mn＝9500，PDI＝1.14。Infrared (FTIR): 3480cm
-1(
vO-H), 3010.3cm
-1, 2960.7cm
-1(
vC-H), 2878cm
-1(
v-CH
2-), 1759cm
-1(
vC=O), 1090cm
-1(
vC-O-C), 1525cm
-1(
vC-N).Nuclear-magnetism (
1HNMR) (CDCl
3) data: PLA (δ CH
3=1.57ppm and δ CH=5.15ppm), PEG (δ CH
2=3.61ppm), (δ-NH
2=2.80) link to each other with amino-CH
2-in hydrogen because H
2The influence of N-is split it to be divided into triplet, can to prove that an end is connected with amino about δ=2.80.
Embodiment 2
Under argon gas atmosphere, THF, 3.5g KHMDS, the 4g EO with 30g adds in the reaction flask successively, and ice bath reacted 4 days down, formed yellow viscous solution; Rac-Lactide with 7.5g joins in the reaction flask then, and 40 ℃ of reactions are after 9 hours, and splashing into the 2.5g volume ratio in reaction flask is 1: 9 the Glacial acetic acid and the mixing solutions of acetone, stirring at room 25min; It is complete to polymer precipitation to splash into anhydrous diethyl ether in reaction flask, with the polymer precipitation centrifugation, uses acetone solution earlier then, adds excessive dehydrated alcohol suction filtration again, and the product vacuum-drying behind the purifying to constant weight, is got white solid, and productive rate is 94.7%.
GPC(THF)：Mn＝12800，PDI＝1.13。Infrared (FTIR) and nuclear-magnetism (
1HNMR) spectrogram is with example 1.
Embodiment 3
Under argon gas atmosphere, THF, 4.5g KHMDS, the 5.5g EO with 45g adds in the reaction flask successively, and ice bath reacted 4 days down, formed yellow viscous solution; Rac-Lactide with 9g joins in the reaction flask then, behind 40 ℃ of reaction 10h, splashes into the hydrochloric acid of 1g 0.1N in reaction flask, stirring at room 20min; It is complete to polymer precipitation to splash into anhydrous diethyl ether in reaction flask, with the polymer precipitation centrifugation, uses acetone solution earlier then, adds excessive dehydrated alcohol suction filtration again, and the product vacuum-drying behind the purifying to constant weight, is got white solid, and productive rate is 92.5%.
GPC(THF)：Mn＝14000，PDI＝1.17。Infrared (FTIR) and nuclear-magnetism (
1HNMR) spectrogram is with example 1.
Embodiment 4
Under argon gas atmosphere, THF, 5.2g MDS, the 6.8g EO with 60g adds in the reaction flask successively, and ice bath reacted 4 days down, formed yellow viscous solution; Rac-Lactide with 14.5g joins in the reaction flask then, behind 40 ℃ of reaction 12h, splashes into the hydrochloric acid of 3.5g 0.1N in reaction flask, stirring at room 20min; In reaction flask, splash into 0.5% NaHCO
3Solution is complete to polymer precipitation, with the polymer precipitation centrifugation, with the methylene dichloride dissolving, adds the excessive methanol suction filtration more then, and the product vacuum-drying behind the purifying to constant weight, is got white solid, and productive rate is 92.8%.
GPC(THF)：Mn＝16200，PDI＝1.15。Infrared (FTIR) and nuclear-magnetism (
1H NMR) spectrogram is with example 1.
Embodiment 4
Under argon gas atmosphere, THF, 7.2g KHMDS, the 10.5g EO with 80g adds in the reaction flask successively, and ice bath reacted 5 days down, formed yellow viscous solution; Rac-Lactide with 18.5g joins in the reaction flask then, behind 40 ℃ of reaction 16h, splashes into the hydrochloric acid of 4.5g 0.1N in reaction flask, stirring at room 25min; In solution, splash into 0.5% NaHCO
3Solution is complete to polymer precipitation, with the polymer precipitation centrifugation, uses acetone solution then, adds excessive dehydrated alcohol suction filtration again, and the product vacuum-drying behind the purifying to constant weight, is got white solid, and productive rate is 94.8%.
GPC(THF)：Mn＝19000，PDI＝1.18。Infrared (FTIR) and nuclear-magnetism (
1H NMR) spectrogram is with example 1.
Embodiment 5
Under argon gas atmosphere, THF, 8.5g KHMDS, the 14.5g EO with 100g adds in the reaction flask successively, and ice bath reacted 5 days down, formed yellow viscous solution; Rac-Lactide with 26.5g joins in the reaction flask then, behind 40 ℃ of reaction 18h, splashes into the hydrochloric acid of 6.5g 0.1N in reaction flask, stirring at room 45min; Splash into 0.5% NaHCO in the reaction flask
3Solution is complete to polymer precipitation, with the polymer precipitation centrifugation, with the THF dissolving, adds excessive dehydrated alcohol suction filtration more then, and the product vacuum-drying behind the purifying to constant weight, is got white solid, and productive rate is 93.6%.
GPC(THF)：Mn＝24000，PDI＝1.19。Infrared (FTLR) and nuclear-magnetism (
1H NMR) spectrogram is with example 1.
Claims (4)
1, the synthetic method of the amino polyethylene glycol-lactic acid segmented copolymer of end, it is characterized in that may further comprise the steps: 1) under argon gas atmosphere, successively the tetrahydrofuran (THF) of 10～50 weight parts, the potassium hexamethyldisilazide of 1～6 weight part, the oxyethane of 2～15 weight parts are added in the reaction flask, ice bath reacted 4～5 days down, formed yellow viscous solution; 2) rac-Lactide with 5～50 weight parts joins in the reaction flask, and 35～40 ℃ are reacted 8h～18h down; 3) in reaction flask, splash into the hydrochloric acid soln of 1-5 weight part or the acetone soln of Glacial acetic acid, stirring at room 20～45min, it is complete to polymer precipitation to splash into sodium hydrogen carbonate solution or anhydrous diethyl ether then; 4) with polymer precipitation centrifugation and purifying, with the product vacuum-drying behind the purifying to constant weight.
2, according to the synthetic method of the amino polyethylene glycol-lactic acid of the described end of claim 1 segmented copolymer, it is characterized in that may further comprise the steps: 1) under argon gas atmosphere, successively the tetrahydrofuran (THF) of 15 weight parts, the potassium hexamethyldisilazide of 2 weight parts, the oxyethane of 2.5 weight parts are added in the reaction flask, ice bath reacted 4 days down, formed yellow viscous solution; 2) rac-Lactide with 5 weight parts joins in the reaction flask, and 40 ℃ are reacted 8h down; 3) in reaction flask, splash into the hydrochloric acid soln of 1 weight part or the acetone soln of Glacial acetic acid, stirring at room 20min, it is complete to polymer precipitation to splash into sodium hydrogen carbonate solution or anhydrous diethyl ether then; 4) with polymer precipitation centrifugation and purifying, with the product vacuum-drying behind the purifying to constant weight.
3, according to the synthetic method of claim 1 or the amino polyethylene glycol-lactic acid of 2 described ends segmented copolymer, it is characterized in that, the acetone soln of the Glacial acetic acid described in the step 3), the volume ratio of Glacial acetic acid and acetone is 1: 6～1: 9; Described concentration of hydrochloric acid solution is 0.1N; The mass concentration of described sodium hydrogen carbonate solution is 0.5%.
4, according to the synthetic method of claim 1 or the amino polyethylene glycol-lactic acid of 2 described ends segmented copolymers, it is characterized in that, the purifying of the polymer precipitation described in the step 4) is first with methylene dichloride or acetone or tetrahydrofuran (THF) dissolving, adds dehydrated alcohol or methyl alcohol suction filtration then.
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Cited By (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101974152A (en) * | 2010-09-28 | 2011-02-16 | 山东大学 | Lipoid-cation polymer and preparation method thereof |
| CN102964582A (en) * | 2012-12-04 | 2013-03-13 | 中国科学院长春应用化学研究所 | Segmented copolymer, preparation method thereof and hydrogel |
| CN104559215A (en) * | 2015-01-06 | 2015-04-29 | 山东理工大学 | Method for improving hydrophily and flexibility of polypeptide membrane by polylactic acid and polyethylene glycol |
| US11066430B2 (en) * | 2014-12-04 | 2021-07-20 | Shin-Etsu Chemical Co., Ltd. | Method for producing polyalkylene glycol derivative having amino group at end |
| CN113150375A (en) * | 2021-03-29 | 2021-07-23 | 中国科学院青岛生物能源与过程研究所 | Method for recycling polylactic acid material under catalysis of zinc catalyst |
| US11236200B2 (en) | 2015-08-10 | 2022-02-01 | Gelest, Inc. | Bifunctional poly(alkyleneoxides) with aminoalkyl and unsaturated termini and derivatives thereof |
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| CN115449062B (en) * | 2022-09-29 | 2023-04-28 | 山东宝斯泰医用材料有限公司 | Polyethylene glycol-polyester block copolymer containing sulfobetaine end group and preparation method thereof |
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- 2009-05-11 CN CN2009100148898A patent/CN101555316B/en not_active Expired - Fee Related
Cited By (10)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101974152A (en) * | 2010-09-28 | 2011-02-16 | 山东大学 | Lipoid-cation polymer and preparation method thereof |
| CN101974152B (en) * | 2010-09-28 | 2012-07-11 | 山东大学 | Lipoid-cation polymer and preparation method thereof |
| CN102964582A (en) * | 2012-12-04 | 2013-03-13 | 中国科学院长春应用化学研究所 | Segmented copolymer, preparation method thereof and hydrogel |
| CN102964582B (en) * | 2012-12-04 | 2014-10-22 | 中国科学院长春应用化学研究所 | Segmented copolymer, preparation method thereof and hydrogel |
| US11066430B2 (en) * | 2014-12-04 | 2021-07-20 | Shin-Etsu Chemical Co., Ltd. | Method for producing polyalkylene glycol derivative having amino group at end |
| CN104559215A (en) * | 2015-01-06 | 2015-04-29 | 山东理工大学 | Method for improving hydrophily and flexibility of polypeptide membrane by polylactic acid and polyethylene glycol |
| CN104559215B (en) * | 2015-01-06 | 2017-06-30 | 山东理工大学 | A kind of method that PLA improves poly- peptide film hydrophily and compliance with polyethylene glycol |
| US11236200B2 (en) | 2015-08-10 | 2022-02-01 | Gelest, Inc. | Bifunctional poly(alkyleneoxides) with aminoalkyl and unsaturated termini and derivatives thereof |
| CN113150375A (en) * | 2021-03-29 | 2021-07-23 | 中国科学院青岛生物能源与过程研究所 | Method for recycling polylactic acid material under catalysis of zinc catalyst |
| CN115025290A (en) * | 2022-06-15 | 2022-09-09 | 浙江天妍生物科技有限公司 | Degradable microsphere and production process thereof |
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