CN1283692C - Preparation method of polyethylene-b-polylactic acid amphiphilic diblock copolymer - Google Patents
Preparation method of polyethylene-b-polylactic acid amphiphilic diblock copolymer Download PDFInfo
- Publication number
- CN1283692C CN1283692C CN 02124114 CN02124114A CN1283692C CN 1283692 C CN1283692 C CN 1283692C CN 02124114 CN02124114 CN 02124114 CN 02124114 A CN02124114 A CN 02124114A CN 1283692 C CN1283692 C CN 1283692C
- Authority
- CN
- China
- Prior art keywords
- polyethylene glycol
- lactic acid
- diblock copolymer
- amphiphilic diblock
- capped
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
- 229920000359 diblock copolymer Polymers 0.000 title claims abstract description 18
- 238000002360 preparation method Methods 0.000 title claims abstract description 17
- 239000004626 polylactic acid Substances 0.000 title claims abstract description 12
- 229920000747 poly(lactic acid) Polymers 0.000 title claims abstract description 11
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims abstract description 28
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims abstract description 26
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims abstract description 16
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims abstract description 16
- -1 polyethylene Polymers 0.000 claims abstract description 16
- 235000014655 lactic acid Nutrition 0.000 claims abstract description 14
- 239000004310 lactic acid Substances 0.000 claims abstract description 14
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 13
- 238000000034 method Methods 0.000 claims abstract description 12
- 229920001223 polyethylene glycol Polymers 0.000 claims abstract description 12
- 229920001577 copolymer Polymers 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 10
- 239000002202 Polyethylene glycol Substances 0.000 claims abstract description 9
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 8
- IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 claims abstract description 5
- 238000001556 precipitation Methods 0.000 claims abstract description 4
- 239000007864 aqueous solution Substances 0.000 claims abstract description 3
- 239000012043 crude product Substances 0.000 claims abstract description 3
- 238000006116 polymerization reaction Methods 0.000 claims abstract description 3
- 239000004698 Polyethylene Substances 0.000 claims abstract 5
- 229920000573 polyethylene Polymers 0.000 claims abstract 5
- 239000011259 mixed solution Substances 0.000 claims abstract 2
- JVTAAEKCZFNVCJ-REOHCLBHSA-N L-lactic acid Chemical compound C[C@H](O)C(O)=O JVTAAEKCZFNVCJ-REOHCLBHSA-N 0.000 claims description 18
- 229920001553 poly(ethylene glycol)-block-polylactide methyl ether Polymers 0.000 claims description 18
- 239000000047 product Substances 0.000 claims description 18
- 238000006068 polycondensation reaction Methods 0.000 claims description 7
- 238000007789 sealing Methods 0.000 claims description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 7
- 239000002994 raw material Substances 0.000 claims description 5
- 229930182843 D-Lactic acid Natural products 0.000 claims description 2
- JVTAAEKCZFNVCJ-UWTATZPHSA-N D-lactic acid Chemical compound C[C@@H](O)C(O)=O JVTAAEKCZFNVCJ-UWTATZPHSA-N 0.000 claims description 2
- 229910021626 Tin(II) chloride Inorganic materials 0.000 claims description 2
- 125000005907 alkyl ester group Chemical group 0.000 claims description 2
- 238000007334 copolymerization reaction Methods 0.000 claims description 2
- 229940022769 d- lactic acid Drugs 0.000 claims description 2
- 150000002148 esters Chemical class 0.000 claims description 2
- 238000001914 filtration Methods 0.000 claims description 2
- 238000000926 separation method Methods 0.000 claims description 2
- 235000011150 stannous chloride Nutrition 0.000 claims description 2
- GOOHAUXETOMSMM-UHFFFAOYSA-N Propylene oxide Chemical compound CC1CO1 GOOHAUXETOMSMM-UHFFFAOYSA-N 0.000 claims 2
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 claims 1
- 150000005215 alkyl ethers Chemical class 0.000 claims 1
- 150000002334 glycols Chemical class 0.000 claims 1
- 239000000155 melt Substances 0.000 claims 1
- 239000001119 stannous chloride Substances 0.000 claims 1
- 238000003828 vacuum filtration Methods 0.000 claims 1
- NWONKYPBYAMBJT-UHFFFAOYSA-L zinc sulfate Chemical compound [Zn+2].[O-]S([O-])(=O)=O NWONKYPBYAMBJT-UHFFFAOYSA-L 0.000 claims 1
- 239000003814 drug Substances 0.000 abstract description 5
- 229940079593 drug Drugs 0.000 abstract description 3
- 238000013270 controlled release Methods 0.000 abstract 1
- 238000001514 detection method Methods 0.000 abstract 1
- 239000002077 nanosphere Substances 0.000 abstract 1
- 239000000243 solution Substances 0.000 description 14
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 238000006243 chemical reaction Methods 0.000 description 11
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 8
- 229920003171 Poly (ethylene oxide) Polymers 0.000 description 8
- 229920000151 polyglycol Polymers 0.000 description 8
- 239000010695 polyglycol Substances 0.000 description 8
- 230000001376 precipitating effect Effects 0.000 description 8
- 230000006837 decompression Effects 0.000 description 7
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
- 238000005119 centrifugation Methods 0.000 description 6
- WGCNASOHLSPBMP-UHFFFAOYSA-N hydroxyacetaldehyde Natural products OCC=O WGCNASOHLSPBMP-UHFFFAOYSA-N 0.000 description 6
- JJTUDXZGHPGLLC-UHFFFAOYSA-N lactide Chemical group CC1OC(=O)C(C)OC1=O JJTUDXZGHPGLLC-UHFFFAOYSA-N 0.000 description 6
- 238000002156 mixing Methods 0.000 description 6
- 238000001291 vacuum drying Methods 0.000 description 6
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 5
- 125000005474 octanoate group Chemical group 0.000 description 5
- 238000005516 engineering process Methods 0.000 description 4
- 230000002209 hydrophobic effect Effects 0.000 description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
- ROGIWVXWXZRRMZ-UHFFFAOYSA-N 2-methylbuta-1,3-diene;styrene Chemical compound CC(=C)C=C.C=CC1=CC=CC=C1 ROGIWVXWXZRRMZ-UHFFFAOYSA-N 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
- 238000012653 anionic ring-opening polymerization Methods 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000003937 drug carrier Substances 0.000 description 2
- 238000001035 drying Methods 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000002105 nanoparticle Substances 0.000 description 2
- 229920001515 polyalkylene glycol Polymers 0.000 description 2
- 229910052700 potassium Inorganic materials 0.000 description 2
- 239000011591 potassium Substances 0.000 description 2
- 229920003051 synthetic elastomer Polymers 0.000 description 2
- 239000005061 synthetic rubber Substances 0.000 description 2
- 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 2
- 125000003545 alkoxy group Chemical group 0.000 description 1
- 150000001346 alkyl aryl ethers Chemical class 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000000129 anionic group Chemical group 0.000 description 1
- 238000000149 argon plasma sintering Methods 0.000 description 1
- 230000015556 catabolic process Effects 0.000 description 1
- 239000007795 chemical reaction product Substances 0.000 description 1
- 238000006731 degradation reaction Methods 0.000 description 1
- 239000006185 dispersion Substances 0.000 description 1
- 238000009826 distribution Methods 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 230000008713 feedback mechanism Effects 0.000 description 1
- 238000009472 formulation Methods 0.000 description 1
- 125000003827 glycol group Chemical group 0.000 description 1
- 238000001727 in vivo Methods 0.000 description 1
- 229920001427 mPEG Polymers 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 230000007246 mechanism Effects 0.000 description 1
- 239000004005 microsphere Substances 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- IJJSYKQZFFGIEE-UHFFFAOYSA-N naphthalene;potassium Chemical compound [K].C1=CC=CC2=CC=CC=C21 IJJSYKQZFFGIEE-UHFFFAOYSA-N 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 239000003921 oil Substances 0.000 description 1
- 239000002245 particle Substances 0.000 description 1
- 229920000642 polymer Polymers 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000000376 reactant Substances 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 230000001105 regulatory effect Effects 0.000 description 1
- 238000007151 ring opening polymerisation reaction Methods 0.000 description 1
- 238000001338 self-assembly Methods 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 239000002904 solvent Substances 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
Landscapes
- Polyesters Or Polycarbonates (AREA)
- Polyethers (AREA)
- Medicinal Preparation (AREA)
Abstract
本发明公开了一种聚乙二醇-b-聚乳酸两亲性二嵌段共聚物(PEG-b-PLA)的制备方法。其过程是乳酸水溶液和单封端的聚乙二醇或单封端的环氧乙烷与环氧丙烷共聚物按一定比例加入聚合釜中，在氮气保护下，120℃～160℃减压除水，加入适量的催化剂，在低于20mmHg，160～200℃下继续反应得粗产物，室温下用氯仿溶解，在10℃以下加入丙酮/乙醚的混合溶液进行沉析，离心分离或减压抽滤得到PEG-b-PLA两亲性二嵌段共聚物。本发明所制备的聚乙二醇-b-聚乳酸两亲性二嵌段共聚物特点是能够自组装成纳米球，可作为药物控释的纳米载体，也可用于医学和生物检测。The invention discloses a preparation method of polyethylene glycol-b-polylactic acid amphiphilic diblock copolymer (PEG-b-PLA). The process is that lactic acid aqueous solution and mono-capped polyethylene glycol or mono-capped ethylene oxide and propylene oxide copolymer are added to the polymerization kettle in a certain proportion, and under the protection of nitrogen, the water is removed under reduced pressure at 120 ° C to 160 ° C. Add an appropriate amount of catalyst, continue to react at 160-200°C below 20mmHg to obtain a crude product, dissolve it in chloroform at room temperature, add acetone/ether mixed solution below 10°C for precipitation, centrifuge or vacuum filter to obtain PEG-b-PLA amphiphilic diblock copolymer. The polyethylene glycol-b-polylactic acid amphiphilic diblock copolymer prepared by the invention is characterized in that it can be self-assembled into nanospheres, can be used as a nanometer carrier for drug controlled release, and can also be used in medicine and biological detection.
Description
Technical field
The present invention relates to the preparation method of a kind of polyethylene-b-polylactic acid amphiphilic diblock copolymer (PEG-b-PLA).The technology of preparing that belongs to amphiphilic diblock copolymer.
Background technology
The structural formula of polyethylene-b-polylactic acid Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock (PEG-b-PLA) is:
HO[COCH (CH
3) O]
m[CH
2CH
2O]
nR '=CH in R ' (1) formula
3, CH
2CH
3Deng group.
This amphiphilic diblock copolymer is biodegradable, and can be self-assembled into the stabilized nano particle in water, is a kind of very potential nano-medicament carrier.
The preparation method of the PEG-b-PLA Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock of document and patent report mainly contains two kinds.First method is to adopt the pink salt compounds to make catalyzer, by poly glycol monomethyl ether (mPEG) and rac-Lactide ring-opening polymerization preparation.General reaction mechanism is as follows:
The preparation method's of this PEG-b-PLA technological process mainly comprises drying, reaction, purification.Detailed process is that highly purified rac-Lactide and polyoxyethylene glycol add in the exsiccant reactor by a certain percentage, add appropriate amount of catalysts (mainly being stannous octoate), 70 ℃ of drying under reduced pressure 2 hours, vacuum lower seal reactor, copolyreaction was carried out 5 hours at 170 ℃, and product is dissolved in methylene dichloride, made precipitation agent with excessive sherwood oil, at 40-60 ℃ PEG-b-PLA is precipitated out, vacuum-drying.Or reactant is dissolved in toluene, and remove minor amount of water by evaporation section toluene, add the toluene solution of catalyzer then, reaction was purified to product after 8 hours under reflux temperature.In this method be that solvent can produce product and environment and pollutes with toluene.
Second method is to adopt the anionic ring-opening polymerization reaction, and anionic catalyzer commonly used has sodium alkoxide, potassium alcoholate, butyllithium etc.The preparation feedback mechanism of a kind of α-acetal-PEG-PLA segmented copolymer is shown below:
This method is to adopt terminal PEG and the rac-Lactide copolymerization that has reactive group, and the PEG that end has reactive group causes ethylene oxide polymerization by the alkoxyl group potassium that has the defencive function group to prepare, and entire reaction can be finished in same reactor.Detailed process is, equimolar naphthalene potassium and alkoxyl alcohol are dissolved in tetrahydrofuran (THF), logical supercooled syringe adds spissated oxyethane after the stirred for several minute, room temperature reaction 2 days, generate viscous solution, add the tetrahydrofuran solution of rac-Lactide then, polyreaction is proceeded 4 hours, reaction product obtains the PEG-b-PLA amphiphilic diblock copolymer with 30 times cold isopropanol precipitating.This anionic ring-opening polymerization technology is complicated, is difficult to realize suitability for industrialized production.
The preparation method of above-mentioned two kinds of PEG-b-PLA all uses poly glycol monomethyl ether and rac-Lactide to be raw material, wherein rac-Lactide costs an arm and a leg, with it is raw material synthetic PEG-b-PLA production cost height, and valuable product can increase the preparation cost greatly as pharmaceutical carrier.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of polyethylene-b-polylactic acid amphiphilic diblock copolymer, this method technology is simple, preparation process is reliable and stable, and can regulate the molecular weight of PEG-b-PLA according to service requirements, the abundant raw material of employing, be easy to get.Prepared multipolymer can be self-assembled into the stabilized nano particle in water, hydrophobic drug is had good parcel performance.
For achieving the above object; the present invention is realized by following technical proposals: adopting lactic acid and single end capped polyoxyethylene glycol or single end capped oxyethane and epoxy propane copolymer is raw material; dewater through decompression; under catalyst action, directly carry out melt polycondensation reaction; product obtains polyoxyethylene glycol-polylactic acid amphiphilic diblock copolymer after precipitating and filtering separation; it is characterized in that: with lactic acid and molecular weight is 500～20000 the end capped polyoxyethylene glycol of list or single end capped oxyethane and the feed ratio adding polymeric kettle of epoxy propane copolymer by mass ratio 0.5～5; after the sealing; under nitrogen protection; 120～160 ℃ of decompressions dewatered 2～4 hours; the stannous octoate that adds 0.01～0.1 part; or tin protochloride; or Catalyzed by p-Toluenesulfonic Acid agent; be lower than the pressure of 20mmHg, 160 ℃～200 ℃ were reacted 8～30 hours down.Crude product with the chloroform dissolving, carries out precipitating at the mixing solutions that adds 4～10 parts 1: 4 acetone of volume ratio below 10 ℃ then under 20 ℃～30 ℃, centrifugation or decompress filter obtain the PEG-b-PLA amphiphilic diblock copolymer.
It is 75%～90% lactic acid aqueous solution that above-mentioned lactic acid can directly use purity, and the lactic acid kind is L-lactic acid, D-lactic acid, D, L-lactic acid.
The end capped polyoxyethylene glycol of above-mentioned list comprises single end capped polyethyleneglycol derivative such as polyalkylene glycol monoalkyl ether, polyalkylene glycol monoalkyl ester, and single end capped oxyethane and epoxy propane copolymer comprise alkyl oxide or end capped oxyethane of alkyl ester list and epoxy propane copolymer.
The consumption of lactic acid and polyoxyethylene glycol unit is bigger to the performance impact of multipolymer, and along with the increase of lactic acid consumption, multipolymer hydrophobic segment relative molecular weight increases, and the dispersive ability of multipolymer in water weakened.The feed ratio of lactic acid and polyoxyethylene glycol is preferably in 0.5～5 scope.
The PEG-b-PLA amphiphilic diblock copolymer macromole of the inventive method preparation can spontaneously be assembled into nanometer ball in water.The determination of light scattering result shows the size of PEG-b-PLA self-assembly microspheres in water between 40～200nm, and has narrower size distribution (dispersion index＜0.2).The particle diameter of PEG-b-PLA self-assembled nanometer ball is relevant with the ratio and the molecular weight of two blocks, and generally the increase with hydrophilic section PEG ratio reduces, and increases with the increase of molecular weight.By ratio and the molecular weight of regulating two blocks, can obtain the PEG-b-PLA nanometer ball of different-grain diameter.
PEG-b-PLA is biological degradation in vivo, and degraded product is nontoxic, and therefore, the PEG-b-PLA amphipathic nature block polymer of the inventive method preparation can be used as a kind of good pharmaceutical carrier, is the good auxiliary material of exploitation hydrophobic drug nanometer formulation.
Embodiment
With embodiment the present invention further is illustrated again below.
Embodiment 1:
The L-lactic acid solution 17g of adding 88% in a round-bottomed flask, molecular weight is 2000 poly glycol monomethyl ether 15g, after the sealing, under nitrogen protection, 140 ℃ of decompressions dewatered 2 hours.Add the inferior tin 0.06g of octoate catalyst then under the normal pressure, 200 ℃, be lower than under the condition of 20mmHg pressure, logical nitrogen and carried out melt polycondensation reaction 8 hours.Reaction is dissolved in chloroform to product after finishing, and carries out precipitating at the mixing solutions that adds 4～10 parts 1: 4 acetone of volume ratio below 10 ℃ then, centrifugation, and 30 ℃～50 ℃ vacuum-dryings get product.
Embodiment 2:
Device and operation add 88% L-lactic acid solution 27g with embodiment 1 in flask, molecular weight is 2000 poly glycol monomethyl ether 6g, and after the sealing, under nitrogen protection, 140 ℃ of decompressions dewatered 2 hours.Add the inferior tin 0.06g of octoate catalyst then under the normal pressure,, be lower than under the 20mmHg pressure, carried out melt polycondensation reaction 8 hours under the condition of logical nitrogen at 200 ℃.Reaction is dissolved in chloroform to product after finishing, and carries out precipitating at the mixing solutions that adds 4～10 parts 1: 4 acetone of volume ratio below 10 ℃ then, centrifugation, and 30～50 ℃ of vacuum-dryings get product.
Embodiment 3:
Device and operation add 88% L-lactic acid solution 17g with embodiment 1 in flask, molecular weight is 2000 poly glycol monomethyl ether 15g, and after the sealing, under nitrogen protection, 140 ℃ of decompressions dewatered 2 hours.Add the inferior tin 0.06g of octoate catalyst then under the normal pressure, equimolar tosic acid 0.028g at 200 ℃, is being lower than under the 20mmHg pressure, carries out melt polycondensation reaction 8 hours under the condition of logical nitrogen.Reaction is dissolved in chloroform to product after finishing, and carries out precipitating at the mixing solutions that adds 4～10 parts 1: 4 acetone of volume ratio below 10 ℃ then, centrifugation, and 30 ℃～50 ℃ vacuum-dryings get product.
Embodiment 4:
Device and operation add 85%D with embodiment 1 in flask, L-lactic acid solution 17.6g, molecular weight are 2000 poly glycol monomethyl ether 15g, and after the sealing, under nitrogen protection, 140 ℃ of decompressions dewatered 2 hours.Add the inferior tin 0.06g of octoate catalyst then under the normal pressure, equimolar tosic acid 0.028g at 200 ℃, is being lower than under the 20mmHg pressure, carries out melt polycondensation reaction 8 hours under the condition of logical nitrogen.Reaction is dissolved in chloroform to product after finishing, and carries out precipitating at the mixing solutions that adds 4～10 parts 1: 4 acetone of volume ratio below 10 ℃ then, centrifugation, and 30 ℃～50 ℃ vacuum-dryings get product.
Embodiment 5:
Device and operation add 85% D with embodiment 4 in flask, L-lactic acid solution 17.6g, molecular weight are 5000 poly glycol monomethyl ether 15g, and after the sealing, under nitrogen protection, 140 ℃ of decompressions dewatered 2 hours.Add the inferior tin 0.06g of octoate catalyst then under the normal pressure, equimolar tosic acid 0.028g at 200 ℃, is being lower than under the 20mmHg pressure, carries out melt polycondensation reaction 8 hours under the condition of logical nitrogen.Reaction is dissolved in chloroform to product after finishing, and carries out precipitating at the mixing solutions that adds 4～10 parts 1: 4 acetone of volume ratio below 10 ℃ then, centrifugation, and 30 ℃～50 ℃ vacuum-dryings get product.
Embodiment 6:
Device and operation are with embodiment 1～5, and poly glycol monomethyl ether wherein changes polyethyleneglycol ether or other single end capped polyoxyethylene glycol or single end capped oxyethane and epoxy propane copolymer into.
Claims (3)
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02124114 CN1283692C (en) | 2002-07-12 | 2002-07-12 | Preparation method of polyethylene-b-polylactic acid amphiphilic diblock copolymer |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 02124114 CN1283692C (en) | 2002-07-12 | 2002-07-12 | Preparation method of polyethylene-b-polylactic acid amphiphilic diblock copolymer |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1412220A CN1412220A (en) | 2003-04-23 |
| CN1283692C true CN1283692C (en) | 2006-11-08 |
Family
ID=4745332
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 02124114 Expired - Fee Related CN1283692C (en) | 2002-07-12 | 2002-07-12 | Preparation method of polyethylene-b-polylactic acid amphiphilic diblock copolymer |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1283692C (en) |
Families Citing this family (13)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AU2003272127A1 (en) * | 2003-10-24 | 2005-05-11 | Samyang Corporation | Polymeric composition for drug delivery |
| CN101007868B (en) * | 2007-01-25 | 2010-06-16 | 复旦大学 | A kind of preparation method of biodegradable nano-micelle controlled-release preparation |
| CN100535033C (en) * | 2007-02-13 | 2009-09-02 | 四川大学 | Polylactic-acid block copolymer and preparation method thereof |
| CN101265312B (en) * | 2008-05-07 | 2010-07-21 | 天津大学 | Amphiphilic tri-block copolymer and its preparation method and application |
| EP2417975A4 (en) | 2009-08-31 | 2012-11-14 | Xi An Libang Medical Technology Co Ltd | Fulvestrant nanosphere/microsphere and preparative method and use thereof |
| CN102627756A (en) * | 2012-03-28 | 2012-08-08 | 南京工业大学 | Synthetic method of polylactic acid-polyethylene glycol |
| CN102924695A (en) * | 2012-09-19 | 2013-02-13 | 上海科院生物材料有限公司 | Method for preparing three-dimensional block polylactic acid at high efficiency |
| FR3008413B1 (en) * | 2013-07-11 | 2015-08-07 | Arkema France | PROCESS FOR PERPENDICULAR ORIENTATION OF NANODOMAINES OF BLOCK COPOLYMERS USING STATISTICAL OR GRADIENT COPOLYMERS WHERE THE MONOMERS ARE AT LEAST DIFFERENT FROM THOSE PRESENT SPECIFICALLY IN EACH BLOCK OF BLOCK COPOLYMER |
| CN103980466B (en) * | 2014-04-28 | 2016-05-11 | 苏州岸谷纳米材料科技有限公司 | A kind of preparation method of biodegradable polylactic acid-polyethyleneglycol block copolymer |
| CN104558504B (en) * | 2015-01-12 | 2017-10-20 | 杨凌瑞丰环保科技有限公司 | A kind of preparation method of polylactic acid poly glycol copolymer |
| CN107964110A (en) * | 2017-12-23 | 2018-04-27 | 上海理仁博振环保科技有限公司 | It is a kind of by block copolymer-modified amphipathic polymeric lactic acid compound film and preparation method |
| BR112022020991A2 (en) * | 2020-08-31 | 2023-03-07 | Vaim Co Ltd | BIODEGRADABLE POLYMER DISPERSION, COMPOSITION COMPRISING THE SAME AND SKIN ENHANCEMENT SYSTEM |
| CN116041673B (en) * | 2022-12-30 | 2026-03-13 | 北京诺康达医药科技股份有限公司 | A polycaprolactone and its synthesis method |
-
2002
- 2002-07-12 CN CN 02124114 patent/CN1283692C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1412220A (en) | 2003-04-23 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1283692C (en) | Preparation method of polyethylene-b-polylactic acid amphiphilic diblock copolymer | |
| Zhou et al. | Biodegradable poly (ε-caprolactone)-poly (ethylene glycol) block copolymers: characterization and their use as drug carriers for a controlled delivery system | |
| CN102838734B (en) | Polylactic acid block polymer and preparation method thereof | |
| Peng et al. | Controlled enzymatic degradation of poly (ɛ-caprolactone)-based copolymers in the presence of porcine pancreatic lipase | |
| CN101812227B (en) | Micelle based on non-linear polyethylene glycol-polylactic acid block copolymer and preparation method thereof | |
| EP3583144B1 (en) | Triblock copolymers | |
| Abdolmaleki et al. | Acidic ionic liquids catalyst in homo and graft polymerization of ε-caprolactone | |
| CN101434699B (en) | A kind of polyglutamate microsphere with active surface and preparation method thereof | |
| JP2000505831A (en) | Copolymer having a polyester polycarbonate block containing poly (caprolactone) segments and its use for producing a biodegradable matrix | |
| Hua et al. | Synthesis, characterization, effect of architecture on crystallization of biodegradable poly (ε‐caprolactone)‐b‐poly (ethylene oxide) copolymers with different arms and nanoparticles thereof | |
| Su et al. | Effects of chemical composition on the in vitro degradation of micelles prepared from poly (D, L-lactide-co-glycolide)-poly (ethylene glycol) block copolymers | |
| CN111320747B (en) | A kind of functionalized high molecular polymer and preparation method thereof | |
| KR20010044625A (en) | Method for preparing biodegradable polyester and itself prepared thereby | |
| CN100523002C (en) | Chitin/polydioxide cyclohexanone graft copolymer and its production | |
| CN100389140C (en) | Method for preparing nano- and micro-scale self-assembled bodies from polypeptide-b-polytetrahydrofuran-b-polypeptide triblock copolymer | |
| US20230143164A1 (en) | One pot process for the preparation of poly (1, 3-alkenes)-block-poly (alkylene oxides) copolymers | |
| CN118420886A (en) | Grafted graphene oxide polybutylene succinate composite material and preparation method thereof | |
| CN1626082A (en) | Nano particles of polyglycol-poly(lactide-caprolactone) of carrying camptothecin and preparation method | |
| CN102676603B (en) | Method for preparing polycaprolactone | |
| WO2013008156A1 (en) | Branched lactic acid polymers with high viscosity in the molten state and high shear sensitivity, and nanocomposites thereof | |
| Studer et al. | Amino end-functionalized poly (ethylene oxide)-block-poly (methylidene malonate 2.1. 2) block copolymers: synthesis, characterization, and chemical modification for targeting purposes | |
| FR2995901A1 (en) | NOVEL BIOSOURCES PRE-POLYMERS AND THEIR USES FOR THE PREPARATION OF USEFUL POLYMERS AS ADDITIVES IN A POLY (LACTIC ACID) MATRIX | |
| CN113024850A (en) | Method for preparing polylactic acid microspheres by free radical polymerization without solvent | |
| WO2007148471A1 (en) | Pdc-lactic acid copolyester and molded article thereof | |
| CN102532501A (en) | Refining method for poly(L-lactic acid) and poly(L-lactic acid-glycolic acid) |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C19 | Lapse of patent right due to non-payment of the annual fee | ||
| CF01 | Termination of patent right due to non-payment of annual fee |