CN1440995A - Ternary polyglycol-aliphatic polyester-polyamino acid block copolymer and its prepn - Google Patents
Ternary polyglycol-aliphatic polyester-polyamino acid block copolymer and its prepn Download PDFInfo
- Publication number
- CN1440995A CN1440995A CN 03121397 CN03121397A CN1440995A CN 1440995 A CN1440995 A CN 1440995A CN 03121397 CN03121397 CN 03121397 CN 03121397 A CN03121397 A CN 03121397A CN 1440995 A CN1440995 A CN 1440995A
- Authority
- CN
- China
- Prior art keywords
- lactide
- molecular weight
- rac
- aliphatic polyester
- average molecular
- 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.)
- Granted
Links
Landscapes
- Medicinal Preparation (AREA)
- Polyamides (AREA)
- Polyesters Or Polycarbonates (AREA)
Abstract
The present invention relates to biologically degradable ternary polyglycol-aliphatic polyester-polyamino acid block copolymer and its synthesis. Inside benzene or toluene solvent, in the presence of stannous octoate as catalyst and under the conditions of no water, no oxygen, heating and stirring, MPEG and aliphatic cyclic monomer are ring-opening polymerized to obtain binary block MPEG-aliphatic polyester copolymer. After the end hydroxyl radical in polyester segment is converted into phenprobamate, the ring-opening polymerization of alpha-amino acid-N-carboxylic anhydride is initiated with introduced macromolecular initiator to obtain the ternary polyglycol-aliphatic polyester-polyamino acid block copolymer.
Description
Technical field
The present invention relates to the biodegradable polyoxyethylene glycol-aliphatic polyester of a class-polyamino acid triblock copolymer and synthetic method thereof.
Technical background
Aliphatic polyester, for example poly-glycollide (PGA), polylactide (PLA), poly-epsilon-caprolactone (PCL) is a present widely used class biodegradable material.Aliphatic polyester has hypoimmunity, favorable biological degradability and biocompatibility, thus be widely used in biomedicine and field of medicaments, as: fracture fixation material, operating sutures, tissue engineering bracket material, the solid support material of medicament slow release etc.
Polyoxyethylene glycol has significant biocompatibility, anticoagulant property, and therefore nontoxic and hypoimmunity is widely used in biomedicine field.Polyoxyethylene glycol is used to improve the wetting ability and the biocompatibility of aliphatic polyester.The block polymer of polyoxyethylene glycol and aliphatic polyester has hydrophilic amphipathic with oleophylic, the aliphatic polyester section has favorable biological degradability and biocompatibility simultaneously, is one of biological degradation medical macromolecular materials that are considered to have at present the prospect of being extensive use of.
Synthetic polyamino acid has the character similar to natural polypeptides, can be degraded by enzyme in vivo, have good biological degradability and biocompatibility, the homopolymerization of polyamino acid and aliphatic polyester and multipolymer are one of ideal medical materials in organizational project and the drug delivery system solid support material.Simultaneously some polyamino acid with function side group can be introduced functional group in transgenosis and drug delivery system, has great application value.At present synthetic polyamino acid causes a-amino acid-N-carboxylic acid anhydride (NCA) ring-opening polymerization by primary amine usually and obtains.
Institute of the present invention synthetic polyoxyethylene glycol-aliphatic polyester-the polyamino acid triblock copolymer is integrated polyoxyethylene glycol, aliphatic polyester, the character of polyamino acid.Ratio by regulating three block each several parts can telomerized polymer performance such as hydrophilic, biocompatibility, biological degradability, polymkeric substance mechanical strength.Polyamino acid that the present invention adopts can obtain having the polymkeric substance that functional group is a carboxyl on the side chain after removing Side chain protective group simultaneously.In gene slowly-releasing, gene recognition and medicament slow release system, has great application prospect.Biodegradable polymer has excellent biological compatibility, can degrade voluntarily under physiological condition, collapse and metabolism, and then be absorbed by organism or excrete, and human body is had no side effect.Therefore when it is used as tissue engineering bracket material, the adhesive capacity of strongthener pair cell, hydrophilic polymer helps somatomedin and cell and adsorbs from the teeth outwards and grow, along with the breeding of cell, the growth of tissue and the formation gradually of organ, timbering material is degraded thereupon and is absorbed, excrete, thereby can reach the purpose of depleted organ of repairing effect and defective tissue; When being used as pharmaceutical carrier, can regulate drug release rate by control degradation speed.Has the unrivaled excellent specific property of many other materials just because of biodegradable polymer, in medical field, be subjected to increasing attention, therefore, institute of the present invention synthetic macromolecular material is with a wide range of applications in that very high use value is medically arranged.
Summary of the invention
One of content of the present invention is that at first synthetic end group is the polyoxyethylene glycol-aliphatic polyester macromole evocating agent of phenylalanine, and preparation process is as follows:
(1) with poly glycol monomethyl ether (MPEG) and aliphatic monomer glycollide (GA), rac-Lactide (LA, comprise the L-rac-Lactide, D, the mixture of L-rac-Lactide and L-rac-Lactide and D-rac-Lactide arbitrary proportion), one of in the 6-caprolactone (CL) or two or three monomeric mixture, under the anhydrous and oxygen-free condition, add solvent benzol (or toluene), adding lactide monomers weight is 0.5～0.02% stannous octoate catalyst, generates polyoxyethylene glycol-aliphatic polyester Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock under heating (80～140 ℃) and stirring condition.The MPEG molecular weight is 500～10000; The aliphatic polyester molecular weight is less than 100000.Polymerization time is 12～72 hours.Product precipitates with precipitation agent, filters, and washing, vacuum-drying obtains polyoxyethylene glycol-aliphatic polyester Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock;
(2) polyoxyethylene glycol-aliphatic polyester Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock and excessive tertiary butyl oxygen carbonyl-protection phenylalanine are dissolved in the dichloromethane solvent, are cooled to below 0 ℃.Added the dicyclohexylcarbodiimide stirring reaction 48 hours, the elimination insolubles is behind saturated sodium bicarbonate and solution washing, use methanol extraction, filter, washing, vacuum-drying, obtaining the end of the chain is the polyoxyethylene glycol-aliphatic polyester Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock of tertiary butyl oxygen carbonyl-protection phenylalanine ester;
(3) be that the polyoxyethylene glycol-aliphatic polyester Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock of tertiary butyl oxygen carbonyl-protection phenylpropyl alcohol amino acid ester is dissolved in methylene dichloride with the end of the chain, be cooled to 0 ℃.Add trifluoroacetic acid, stirred 1-2 hour, behind saturated sodium bicarbonate and solution washing, use methanol extraction, filter, washing, vacuum-drying, obtaining the polyester segments end group is the polyoxyethylene glycol-aliphatic polyester diblock polymer of phenylpropyl alcohol amino acid ester;
It is that the polyoxyethylene glycol-aliphatic polyester diblock polymer of phenylalanine ester is that macromole evocating agent causes the NCA ring-opening polymerization that another content of the present invention is with institute's synthetic end of the chain, generates biodegradable polyoxyethylene glycol-aliphatic polyester-polyamino acid triblock copolymer.Concrete steps are as follows:
Under the anhydrous and oxygen-free condition, macromole evocating agent and NCA monomer are dissolved in the solvent, the mol ratio of monomer and macromole evocating agent is 0～100: 1, and polymerization temperature is 25～60 ℃, and polymerization time is 24～72 hours; The product dissolution with solvents is settled out polymkeric substance with precipitation agent, after filtration, washing, vacuum-drying, weighing obtains polyoxyethylene glycol-aliphatic polyester-polyamino acid triblock copolymer.
In synthesizing polyethylene glycol-aliphatic polyester-polyamino acid triblock copolymer experiment that the present invention carried out, molecular weight polyethylene glycol is less than 10000, the aliphatic polyester molecular weight is less than 100000, the mol ratio of NCA monomer and macromole evocating agent is 0～100: 1 these processing parameters of adjusting, can obtain the polyoxyethylene glycol-aliphatic polyester-polyamino acid triblock copolymer of each several part adjustable ratio.
Embodiment
Embodiment provided by the invention is as follows:
Embodiment 1: end group is the preparation of the polyethylene glycol-rac-Lactide segmented copolymer of phenylpropyl alcohol amino acid ester.
(1) under the condition of anhydrous and oxygen-free, with 0.005 mole of poly glycol monomethyl ether (MPEG) respectively with 0.15,0.3,0.5, the 2mol rac-Lactide adds in the reaction flask, adding weight and lactide monomers weight ratio was 1: 1 the toluene solvant and the stannous octoate catalyst of lactide monomers weight 0.1%, 110 ℃ of following stirring reactions 48 hours.The product isopropanol precipitating filters, washing, and 35 ℃ of following vacuum-drying 24 hours is weighed, and obtaining end group is the polyethylene glycol-rac-Lactide of hydroxyl.The gained polymerization result sees Table one.
(2) 10g polyethylene glycol-rac-Lactide Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock and 5g tertiary butyl oxygen carbonyl-protection phenylalanine are dissolved in the 50ml dichloromethane solvent, are cooled to below 0 ℃.Add 4.2g dicyclohexylcarbodiimide water-removal agent; stirring reaction 48 hours; the elimination insolubles behind 50ml saturated sodium bicarbonate and 50ml solution washing, is used the methyl alcohol sedimentation; filter; washing, 35 ℃ of following vacuum-drying 24 hours, obtaining the end of the chain is the polyoxyethylene glycol-aliphatic polyester Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock of tertiary butyl oxygen carbonyl-protection phenylalanine; 8.5～the 9.5g that weighs, productive rate: 83～93%.
(3) be that the polyethylene glycol-rac-Lactide Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock of tertiary butyl oxygen carbonyl-protection phenylalanine is dissolved in the 30ml methylene dichloride with the 5g end of the chain, be cooled to 0 ℃.Add the 15ml trifluoroacetic acid, stirred 1～2 hour, behind 50ml saturated sodium bicarbonate and 50ml solution washing, use methanol extraction, filter, washing, vacuum-drying, obtaining the polyester segments end group is the polyoxyethylene glycol-aliphatic polyester diblock polymer of phenylalanine, the 4.3～4.7g that weighs, productive rate: 82～95%.Table one:
| Numbering | M n(MPEG) | ??A/I | ??Yield ????(％) | ??DP(PLA ????) | ???Mn a | ????Mn b |
| ????1 | ??750 | ??30 | ??93.1 | ????56 | ??4800 | ???4900 |
| ????2 | ??750 | ??60 | ??95.2 | ????113 | ??8900 | ???8800 |
| ????3 | ??750 | ??100 | ??97.5 | ????190 | ??14400 | ???14500 |
| ????4 | ??2000 | ??30 | ??93.5 | ????54 | ??5900 | ???5800 |
| ????5 | ??2000 | ??60 | ??96.4 | ????112 | ??10000 | ???9800 |
| ????6 | ??2000 | ??100 | ??97.6 | ????188 | ??15500 | ???16200 |
| ????7 | ??7000 | ??60 | ??97.3 | ????112 | ??15100 | ???15600 |
| ????8 | ??10000 | ??400 | ??97.5 | ????768 | ??65300 | ???66000 |
M in the last table
n(MPEG) refer to the number-average molecular weight of MPEG; A/I refers to the mol ratio of monomer L-rac-Lactide and MPEG; Productive rate is a polymer weight and the ratio of PEG and lactide monomer gross weight; DP (PLA) by
1HNMR obtains; M
n aBe the number-average molecular weight of polyethylene glycol-rac-Lactide, by
1HNMR obtains; M
n bNumber-average molecular weight for the polyethylene glycol-rac-Lactide is obtained by GPC.
Embodiment 2: end group is the preparation of the polyethylene glycol-rac-Lactide segmented copolymer of phenylpropyl alcohol amino acid ester under the differing temps.
Respectively at 90 ℃, 110 ℃, under 130 ℃. with 3.75g poly glycol monomethyl ether (M
n=750) and the 43.2g rac-Lactide add in the reaction flask, add 40ml toluene and 0.05g stannous octoate catalyst, other steps are identical with embodiment 1, various polymerization results see Table two.Table two:
| Numbering | ?M n(MPEG) | ????A/I | ??Yield ????(％) | ??DP(PLA ????) | ????Mn a | ????Mn b |
| ????1 | ????750 | ????90 | ???87.4 | ????116 | ????9100 | ????9200 |
| ????2 | ????750 | ????110 | ???95.2 | ????113 | ????8900 | ????8800 |
| ????3 | ????750 | ????130 | ???83.2 | ????103 | ????8200 | ????8300 |
M in the last table
n(MPEG) refer to the number-average molecular weight of MPEG; T (℃) refer to polymerization temperature; Productive rate is a polymer weight and the ratio of PEG and lactide monomer gross weight; DP (PLA) by
1HNMR obtains; M
n aBe the number-average molecular weight of polyethylene glycol-rac-Lactide, by
1HNMR obtains; M
n bNumber-average molecular weight for the polyethylene glycol-rac-Lactide is obtained by GPC.
Embodiment 3: end group is the preparation of the polyethylene glycol-6-caprolactone segmented copolymer of phenylpropyl alcohol amino acid ester.
Respectively with 0.15,0.3,0.5, the 2mol 6-caprolactone adds in the reaction flask with 0.005mol poly glycol monomethyl ether (MPEG), and other steps are identical with embodiment 1, and various polymerization results see Table three.
Table three:
| Numbering | ?M n(MPEG) | ?A/I | ?Yield ???(％) | ??DP(PLA ????) | ????Mn a | ???Mn b |
| ????1 | ????750 | ???30 | ???93.2 | ????28 | ??3900 | ??4100 |
| ????2 | ????750 | ??60 | ???96.1 | ????57 | ??7200 | ??7100 |
| ????3 | ????750 | ??100 | ???97.6 | ????95 | ??11600 | ??12800 |
| ????4 | ????2000 | ??30 | ???94.1 | ????27 | ??3800 | ??3700 |
| ????5 | ????2000 | ??60 | ???97.2 | ????56 | ??7100 | ??7400 |
| ????6 | ????2000 | ??100 | ???97.7 | ????93 | ??11500 | ??13100 |
| ????7 | ????7000 | ??60 | ???97.3 | ????56 | ??13400 | ??14000 |
| ????8 | ????10000 | ??400 | ???97.8 | ????382 | ??53500 | ??55000 |
M in the last table
n(MPEG) refer to the number-average molecular weight of MPEG; A/I refers to the mol ratio of monomer 6-caprolactone and MPEG; Productive rate is a polymer weight and the ratio of PEG and 6-caprolactone total monomer weight; DP (PCL) by
1HNMR obtains; M
n aBe the number-average molecular weight of polyethylene glycol-6-caprolactone, by
1HNMR obtains; M
n bNumber-average molecular weight for the polyethylene glycol-6-caprolactone is obtained by GPC.
Embodiment 4: end group is the preparation of the polyethylene glycol-glycollide segmented copolymer of phenylpropyl alcohol amino acid ester.
With 20g poly glycol monomethyl ether (M
n=2000) and the 11.6g glycollide add in the reaction flask, add 30ml toluene and 0.01g stannous octoate catalyst, other operation stepss are identical with embodiment 1.Obtain polyethylene glycol-glycollide bi-block copolymer: productive rate: 29.1g (92.1%), DP (PEG)=45 (number-average molecular weight 2000), DP (PGA)=17 (number-average molecular weight 1000), polyethylene glycol-glycollide bi-block copolymer number-average molecular weight is 3000.DP (PEG) and DP (PGA) by
1HNMR measures and obtains.
Embodiment 5: end group is the preparation of block polymer of the polyoxyethylene glycol-random copolymerization lactide/glycolides of phenylpropyl alcohol amino acid ester.
With 20g poly glycol monomethyl ether (M
n=2000), 28.8g rac-Lactide and 11.6g glycollide add in the reaction flask, add 60ml toluene and 0.04g stannous octoate catalyst, and other steps are identical with embodiment 1.Obtain the block polymer of polyoxyethylene glycol-random copolymerization lactide/glycolides: productive rate: 56.5g (93.5%), DP (PEG)=45 (number-average molecular weight 2000), DP (PLA)=36 (number-average molecular weight 2600), DP (PGA)=18 (number-average molecular weight 1000), the block polymer number-average molecular weight of polyoxyethylene glycol-random copolymerization lactide/glycolides is 5600.DP (PEG), DP (PLA) and DP (PLA) by
1HNMR measures and obtains.
Embodiment 6: end group is the preparation of block polymer of the polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone of phenylpropyl alcohol amino acid ester.
With 10g poly glycol monomethyl ether (M
n=2000), 14.4g rac-Lactide and 22.8g 6-caprolactone add in the reaction flask, add 40ml toluene and 0.04g stannous octoate catalyst, and other steps are identical with embodiment 1.Obtain the block polymer of polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone: productive rate: 45.9g (97.2%), DP (PEG)=45 (number-average molecular weight 2000), DP (PLA)=38 (number-average molecular weight 2700), DP (PCL)=37 (number-average molecular weight 4200), the block polymer number-average molecular weight of polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone is 8900.DP (PEG), DP (PLA) and DP (PCL) by
1HNMR measures and obtains.
Embodiment 7: end group is the preparation of block polymer of the polyoxyethylene glycol-random copolymerization glycollide/6-caprolactone of phenylpropyl alcohol amino acid ester.
With 10g poly glycol monomethyl ether (M
n=2000), 5.8g glycollide and 11.4g 6-caprolactone add in the reaction flask, add 30ml toluene and 0.02g stannous octoate catalyst, and other steps are identical with embodiment 1.Obtain the segmented copolymer of polyoxyethylene glycol-random copolymerization glycollide/6-caprolactone: productive rate: 25.6g (94.1%), DP (PEG)=45 (number-average molecular weight 2000), DP (PCL)=18 (number-average molecular weight 2100), DP (PGA)=18 (number-average molecular weight 1000), the block polymer number-average molecular weight of polyoxyethylene glycol-random copolymerization glycollide-6-caprolactone is 5100.DP (PEG), DP (PCL) and DP (PGA) by
1HNMR measures and obtains.
Embodiment 8: end group is the preparation of block polymer of the polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone of phenylpropyl alcohol amino acid ester.
With 10g poly glycol monomethyl ether (M
n=2000), the 5.8g glycollide, 14.4g rac-Lactide, 17.1g 6-caprolactone add in the reaction flask, add 50ml toluene and 0.04g stannous octoate catalyst, and other steps are identical with embodiment 1.Obtain the block polymer of polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone: productive rate: 46.1g (97.4%), DP (PEG)=45 (number-average molecular weight 2000), DP (PLA)=38 (number-average molecular weight 2700), DP (PCL)=28 (number-average molecular weight 3200), DP (PGA)=18 (number-average molecular weight 1000), the block polymer number-average molecular weight of polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone is 8900, wherein, DP (PEG), DP (PLA), DP (PCL) and DP (PGA) by
1HNMR measures and obtains.
Embodiment 9: the preparation of polyethylene glycol-rac-Lactide-poly-γ-benzyl-L-L-glutamic acid segmented copolymer.
Under the anhydrous and oxygen-free condition, with the 0.0025mol end group respectively polyoxyethylene glycol (the Mn=750)-polylactide (MPEG-PLA) and the 0.005mol of phenylpropyl alcohol amino acid ester, 0.01mol it is in 15: 1 the chloroformic solution that 0.015mol γ-benzyl-L-L-glutamic acid-N-carboxylic acid anhydride (BLG-NCA) is dissolved in volume and NCA monomer weight ratio.25 ℃ of following stirring reactions 72 hours; Product comes out with ether sedimentation, filters, and washing, 35 ℃ of following vacuum-drying 24 hours is weighed, and obtains polyethylene glycol-rac-Lactide-poly-γ-benzyl-L-L-glutamic acid triblock polymer, and the gained polymerization result sees Table four.Table four:
| Numbering | ??M n(I) | ??A/I | ?Yield(％ ????) | DP(PBLG ????) | ????M n |
| ????1 | ??4800 | ??20 | ??92.0 | ??17 | ??8500 |
| ????2 | ??4800 | ??40 | ??93.5 | ??36 | ??12700 |
| ????3 | ??4800 | ??60 | ??93.6 | ??55 | ??16800 |
| ????4 | ??8900 | ??20 | ??91.1 | ??16 | ??12400 |
| ????5 | ??8900 | ??40 | ??92.0 | ??35 | ??16600 |
| ????6 | ??8900 | ??60 | ??92.4 | ??53 | ??20500 |
M in the last table
n(I) refer to the number-average molecular weight of MPEG (Mn=750)-PLA; A/I refers to the mol ratio of monomers B LG-NCA and MPEG-PLA; Productive rate is a polymer weight and the ratio of MPEG-PLA and BLG-NCA total monomer weight; DP (PBLG) by
1HNMR measures and obtains; M
nBe the number-average molecular weight of polyethylene glycol-rac-Lactide-poly-γ-benzyl-L-L-glutamic acid, by
1HNMR measures and obtains.
Embodiment 10: the preparation of polyethylene glycol-rac-Lactide-poly-β-benzyl-L-aspartic acid segmented copolymer.
With the 1.2g end group is that polyoxyethylene glycol (the Mn=750)-polylactide (MPEG-PLA) and the 3.8g β-benzyl-L-aspartic acid-N-carboxylic acid anhydride (BLA-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 9.Obtain polyethylene glycol-rac-Lactide-poly-β-benzyl-L-aspartic acid; Productive rate: 4.7g (93.6%), DP (PEG)=17 (number-average molecular weight 750), DP (PLA)=56 (number-average molecular weight 4000), DP (PBLA)=56 (number-average molecular weight 11500), the polyethylene glycol-rac-Lactide-poly-β-benzyl-L-aspartic acid number-average molecular weight is 16300.DP (PEG), DP (PLA) and DP (PBLA) by
1HNMR measures and obtains.
Embodiment 11: the preparation of polyethylene glycol-6-caprolactone-poly-γ-benzyl-L-L-glutamic acid segmented copolymer.
With the 0.0025mol end group respectively polyoxyethylene glycol (the Mn=750)-poly-epsilon-caprolactone (MPEG-PCL) and the 0.005mol of phenylpropyl alcohol amino acid ester, 0.01mol, 0.015mol it is in 15: 1 the chloroformic solution that γ-benzyl-L-L-glutamic acid-N-carboxylic acid anhydride (BLG-NCA) is dissolved in volume and NCA monomer weight ratio, other steps are identical with embodiment 9, and various polymerization results see Table five.
Table five
| Numbering | ??M n(I) | ??A/I | ??Yield( ????％) | DP(PBLG ????) | ????M n |
| ????1 | ??3900 | ??20 | ??92.4 | ????18 | ??7900 |
| ????2 | ??3900 | ??40 | ??93.8 | ????38 | ??12300 |
| ????3 | ??3900 | ??60 | ??93.9 | ????56 | ??16200 |
| ????4 | ??7200 | ??20 | ??91.5 | ????17 | ??10900 |
| ????5 | ??7200 | ??40 | ??92.4 | ????35 | ??14900 |
| ????6 | ??7200 | ??60 | ??93.0 | ????54 | ??19000 |
M in the last table
n(I) refer to the number-average molecular weight of MPEG (Mn=750)-PCL; A/I refers to the mol ratio of monomers B LG-NCA and MPEG-PCL; Productive rate is a polymer weight and the ratio of MPEG-PCL and BLG-NCA total monomer weight; DP (PBLG) by
1HNMR obtains; M
nBe the number-average molecular weight of polyethylene glycol-rac-Lactide-poly-γ-benzyl-L-L-glutamic acid acid, by
1HNMR measures and obtains.
Embodiment 12: the preparation of polyethylene glycol-6-caprolactone-poly-β-benzyl-L-aspartic acid.
With the 1.0g end group is that the polyethylene glycol-6-caprolactone (MPEG-PCL) and the 3.8g β-benzyl-L-aspartic acid-N-carboxylic acid anhydride (BLA-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 11.Obtain polyethylene glycol-6-caprolactone-poly-β-benzyl-L-aspartic acid: productive rate: 4.5g (93.7%), DP (PEG)=17 (number-average molecular weight 750), DP (PCL)=28 (number-average molecular weight 3200), DP (PBLA)=56 (number-average molecular weight 11500), the polyethylene glycol-6-caprolactone-poly-β-benzyl-L-aspartic acid number-average molecular weight is 15500.DP (PEG), DP (PCL) and DP (PBLA) by
1HNMR measures and obtains.
Embodiment 13: the preparation of polyethylene glycol-glycollide-poly-γ-benzyl-L-L-glutamic acid.
With the 0.75g end group is that the polyethylene glycol-glycollide (MPEG-PGA) and the 4.0g γ-benzyl-L-L-glutamic acid-N-carboxylic acid anhydride (BLG-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 9.Obtain polyethylene glycol-glycollide-poly-γ-benzyl-L-L-glutamic acid; Productive rate: 4.5g (93.7%), DP (PEG)=45 (number-average molecular weight 2000), DP (PGA)=17 (number-average molecular weight 1000), DP (PBLG)=56 (number-average molecular weight 12300), the polyethylene glycol-glycollide-poly-γ-benzyl-L-L-glutamic acid number-average molecular weight is 15300.DP (PEG), DP (PGA) and DP (PBLG) by
1HNMR measures and obtains.
Embodiment 14: the preparation of polyethylene glycol-glycollide-poly-β-benzyl-L-aspartic acid.
With the 0.75g end group is that the polyoxyethylene glycol-poly-glycollide (MPEG-PGA) and the 3.8g β-benzyl-L-aspartic acid-N-carboxylic acid anhydride (BLA-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 13.Obtain polyethylene glycol-glycollide-poly-β-benzyl-L-aspartic acid: productive rate: 4.3g (93.8%), DP (PEG)=45 (number-average molecular weight 2000), DP (PGA)=17 (number-average molecular weight 1000), DP (PBLA)=57 (number-average molecular weight 11700), polyoxyethylene glycol-poly-glycollide-poly-β-benzyl-L-aspartic acid number-average molecular weight is 14700.DP (PEG), DP (PGA) and DP (PBLA) by
1HNMR measures and obtains.
Embodiment 15: the preparation of polyoxyethylene glycol-random copolymerization lactide/glycolides-poly-γ-benzyl-L-L-glutamic acid
With the 1.4g end group is that the polyoxyethylene glycol-random copolymerization lactide/glycolides and the 4.0g γ-benzyl-L-L-glutamic acid-N-carboxylic acid anhydride (BLG-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 9.Obtain polyoxyethylene glycol-random copolymerization lactide/glycolides-poly-γ-benzyl-L-L-glutamic acid: productive rate: 5.1g (93.6%), DP (PEG)=45 (number-average molecular weight 2000), DP (PLA)=36 (number-average molecular weight 2600), DP (PGA)=18 (number-average molecular weight 1000), DP (PBLG)=55 (number-average molecular weight 12000), polyoxyethylene glycol-random copolymerization lactide/glycolides-poly-γ-benzyl-L-L-glutamic acid number-average molecular weight is 17600.DP (PEG), DP (PLA), DP (PGA) and DP (PBLG) by
1HNMR measures and obtains.
Embodiment 16: the preparation of polyoxyethylene glycol-random copolymerization lactide/glycolides-poly-β-benzyl-L-aspartic acid.
With the 1.4g end group is that the polyoxyethylene glycol-random copolymerization lactide/glycolides and the 3.8g β-benzyl-L-aspartic acid-N-carboxylic acid anhydride (BLA-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 16.Obtain polyoxyethylene glycol-random copolymerization lactide/glycolides-poly-β-benzyl-L-aspartic acid: productive rate: 4.9 g (93.7%), DP (PEG)=45 (number-average molecular weight 2000), DP (PLA)=36 (number-average molecular weight 2600), DP (PGA)=18 (number-average molecular weight 1000), DP (PBLA)=56 (number-average molecular weight 11500), polyoxyethylene glycol-random copolymerization lactide/glycolides-poly-β-benzyl-L-aspartic acid number-average molecular weight is 17100.DP (PEG), DP (PLA), DP (PGA) and DP (PBLA) by
1HNMR measures and obtains.
Embodiment 17: the preparation of polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone-poly-γ-benzyl-L-L-glutamic acid.
With the 2.2g end group is that the polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone and the 4.0g γ-benzyl-L-L-glutamic acid-N-carboxylic acid anhydride (BLG-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 9.Obtain polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone-poly-γ-benzyl-L-L-glutamic acid: productive rate: 5.1g (92.8%), DP (PEG)=45 (number-average molecular weight 2000), DP (PLA)=38 (number-average molecular weight 2700), DP (PCL)=37 (number-average molecular weight 4200), DP (PBLG)=54 (number-average molecular weight 11800), polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone-poly-γ-benzyl-L-L-glutamic acid number-average molecular weight is 20700.DP (PEG), DP (PLA), DP (PCL) and DP (PBLG) by
1HNMR measures and obtains.
Embodiment 18: the preparation of polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone-poly-β-benzyl-L-aspartic acid.
With the 2.2g end group is that the polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone and the 3.8g β-benzyl-L-aspartic acid-N-carboxylic acid anhydride (BLA-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 17.Obtain polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone-poly-β-benzyl-L-aspartic acid: productive rate: 5.1g (93.0%), DP (PEG)=45 (number-average molecular weight 2000), DP (PLA)=38 (number-average molecular weight 2700), DP (PCL)=37 (number-average molecular weight 4200), DP (PBLA)=55 (number-average molecular weight 11300), polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone-poly-β-benzyl-L-aspartic acid number-average molecular weight is 20200.DP (PEG), DP (PLA), DP (PCL) and DP (PBLA) by
1HNMR measures and obtains.
Embodiment 19: the preparation of polyoxyethylene glycol-random copolymerization glycollide/6-caprolactone-poly-γ-benzyl-L-L-glutamic acid.
With the 1.3g end group is that the polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone and the 4.0g γ-benzyl-L-L-glutamic acid-N-carboxylic acid anhydride (BLG-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 9.Obtain polyoxyethylene glycol-random copolymerization glycollide/6-caprolactone-poly-γ-benzyl-L-L-glutamic acid: productive rate: 5.0g (93.8%), DP (PEG)=45 (number-average molecular weight 2000), DP (PCL)=18 (number-average molecular weight 2100), DP (PGA)=18 (number-average molecular weight 1000), DP (PBLG)=56 (number-average molecular weight 12300), polyoxyethylene glycol-random copolymerization glycollide/6-caprolactone-poly-γ-benzyl-L-L-glutamic acid number-average molecular weight is 17400.DP (PEG), DP (PCL), DP (PGA) and DP (PBLG) by
1HNMR measures and obtains.
Embodiment 20: the preparation of polyoxyethylene glycol-random copolymerization glycollide/6-caprolactone-poly-β-benzyl-L-aspartic acid.
With the 1.3g end group is that the polyoxyethylene glycol-random copolymerization rac-Lactide/6-caprolactone and the 3.8g β-benzyl-L-aspartic acid-N-carboxylic acid anhydride (BLA-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 19.Obtain polyoxyethylene glycol-random copolymerization glycollide/6-caprolactone-poly-β-benzyl-L-aspartic acid: productive rate: 4.8g (94.1%), DP (PEG)=45 (number-average molecular weight 2000), DP (PCL)=18 (number-average molecular weight 2100), DP (PGA)=18 (number-average molecular weight 1000), DP (PBLA)=57 (number-average molecular weight 11700), polyoxyethylene glycol-random copolymerization glycollide/6-caprolactone-poly-β-benzyl-L-aspartic acid number-average molecular weight is 16800.DP (PEG), DP (PCL), DP (PGA) and DP (PBLG) by
1HNMR measures and obtains.
Embodiment 21: the preparation of polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone-poly-γ-benzyl-L-L-glutamic acid.
With the 2.2g end group is that the polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone and the 4.0g γ-benzyl-L-L-glutamic acid-N-carboxylic acid anhydride (BLG-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 9.Obtain polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone-poly-γ-benzyl-L-L-glutamic acid: productive rate: 5.7g (92.8%), DP (PEG)=45 (number-average molecular weight 2000), DP (PLA)=38 (number-average molecular weight 2700), DP (PCL)=28 (number-average molecular weight 3200), DP (PGA)=18 (number-average molecular weight 1000), DP (PBLG)=55 (number-average molecular weight 12000), polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone-poly-γ-benzyl-L-L-glutamic acid number-average molecular weight is 20900.DP (PEG), DP (PLA), DP (PCL), DP (PGA) and DP (PBLG) by
1HNMR measures and obtains.
Embodiment 22: the preparation of polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone-poly-β-benzyl-L-aspartic acid.
With the 2.2g end group is that the polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone and the 3.8g γ-benzyl-L-L-glutamic acid-N-carboxylic acid anhydride (BLG-NCA) of phenylpropyl alcohol amino acid ester is dissolved in the 60ml chloroformic solution, and other steps are identical with embodiment 9.Obtain polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone-poly-β-benzyl-L-aspartic acid: productive rate: 5.6g (92.6%), DP (PEG)=45 (number-average molecular weight 2000), DP (PLA)=38 (number-average molecular weight 2700), DP (PCL)=28 (number-average molecular weight 3200), DP (PGA)=18 (number-average molecular weight 1000), DP (PBLA)=54 (number-average molecular weight 11100), polyoxyethylene glycol-random copolymerization glycollide/rac-Lactide/6-caprolactone-poly-β-benzyl-L-aspartic acid number-average molecular weight is 20000.DP (PEG), DP (PLA), DP (PCL), DP (PGA) and DP (PBLA) by
1HNMR measures and obtains.
Claims (7)
1, a kind of polyoxyethylene glycol-aliphatic polyester-polyamino acid triblock copolymer, wherein molecular weight polyethylene glycol is below 10000; Aliphatic polyester is the homopolymer of glycollide, rac-Lactide, 6-caprolactone and two kinds or three kinds of monomeric random copolymerss between them, and the polyester segments molecular weight is 1000～100000; Polyamino acid is poly-γ-benzyl-L-L-glutamic acid and/or poly-β-benzyl-L-aspartic acid, and molecular weight is 100～30000.
2, triblock copolymer as claimed in claim 1 is characterized in that, described rac-Lactide is L-rac-Lactide, D, the mixture of L-rac-Lactide and L-rac-Lactide and D-rac-Lactide arbitrary proportion
3, the described polyoxyethylene glycol-aliphatic polyester of a kind of preparation claim 1-polyamino acid triblock copolymer, main preparation process is:
A) with poly glycol monomethyl ether and aliphatics cyclic ester monomer through after dewatering with benzene or methylbenzene azeotropic, in benzene or toluene solvant, add the inferior tin of octoate catalyst, the add-on of catalyzer is 1%～0.01% of an aliphatics cyclic ester monomer monomer weight ratio, under stirring condition, heat 80～140 ℃, polymerization time is 12-72 hour, and product precipitation agent sedimentation is filtered, washing, vacuum-drying; Obtain polyoxyethylene glycol-aliphatic polyester Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock;
B) Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock that step a is obtained and excessive tertiary butyl oxygen carbonyl-protection phenylalanine are dissolved in the dichloromethane solvent, are cooled to below 0 ℃; Added the dicyclohexylcarbodiimide stirring reaction 24～72 hours, the elimination insolubles behind saturated sodium bicarbonate and solution washing, is used the methyl alcohol sedimentation, filters washing, vacuum-drying; Obtaining the end of the chain is the polyoxyethylene glycol-aliphatic polyester Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock of tertiary butyl oxygen carbonyl-protection phenylalanine;
C) product that step b is obtained is dissolved in methylene dichloride, be cooled to 0 ℃, add trifluoroacetic acid, stirred 1-2 hour, and behind saturated sodium bicarbonate and solution washing, used the methyl alcohol sedimentation, filter, washing, vacuum-drying, obtaining end group is the polyoxyethylene glycol-aliphatic polyester diblock polymer of phenylpropyl alcohol amino acid ester;
D) polymkeric substance that step c is obtained and amino acid monomer are dissolved in the organic solvent, and polymkeric substance and monomeric mol ratio are 1: 20～100, and polymerization temperature is 25～60 ℃, and polymerization time is 24-72 hour; The product dissolution with solvents is settled out polymkeric substance with precipitation agent, after filtration, and washing, vacuum-drying.
4, preparation method as claimed in claim 3 is characterized in that, the monomer of aliphatic polyester described in the step a is one or more mix monomers in glycollide, rac-Lactide and the 6-caprolactone.
5, preparation method as claimed in claim 3 is characterized in that, solvent described in the steps d is 1,4-dioxane or chloroform.
6, preparation method as claimed in claim 3 is characterized in that, amino acid monomer described in the steps d is γ-benzyl-L-L-glutamic acid-N-carboxylic acid anhydride.
7, preparation method as claimed in claim 3 is characterized in that, the monomer of amino ester described in the steps d is β-benzyl-L-aspartic acid-N-carboxylic acid anhydride.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031213979A CN1185277C (en) | 2003-03-28 | 2003-03-28 | Ternary polyglycol-aliphatic polyester-polyamino acid block copolymer and its prepn |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031213979A CN1185277C (en) | 2003-03-28 | 2003-03-28 | Ternary polyglycol-aliphatic polyester-polyamino acid block copolymer and its prepn |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1440995A true CN1440995A (en) | 2003-09-10 |
| CN1185277C CN1185277C (en) | 2005-01-19 |
Family
ID=27770479
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031213979A Expired - Lifetime CN1185277C (en) | 2003-03-28 | 2003-03-28 | Ternary polyglycol-aliphatic polyester-polyamino acid block copolymer and its prepn |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1185277C (en) |
Cited By (24)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1833958A2 (en) * | 2005-01-04 | 2007-09-19 | Intezyne Technologies Incorporated | Synthesis of hybrid block copolymers and uses thereof |
| CN100415801C (en) * | 2003-10-28 | 2008-09-03 | 北京键凯科技有限公司 | Polyethylene glycol amino acid N-internal ring carbonyl anhydride active derivatives, and medicinal bonding compound and gel thereof |
| CN100428964C (en) * | 2006-06-29 | 2008-10-29 | 武汉理工大学 | Composite material of RGD polypeptide grafted poly (hydroxyacetic acid-L- lysine-L- lactic acid) / beta tricalcium phosphate, and preparation method |
| CN100443547C (en) * | 2007-03-15 | 2008-12-17 | 上海交通大学 | Prepn process of nanometer particle of poly (amide-amine)-poly (L-benzyl-glutamate) |
| CN100592439C (en) * | 2005-08-08 | 2010-02-24 | 中国人民解放军军事医学科学院毒物药物研究所 | Bio-compatibility magnetic fluid |
| CN101280047B (en) * | 2008-05-06 | 2010-06-23 | 华南理工大学 | Poly benzyl glutamate-containing degradable composite material and preparation thereof |
| CN101265312B (en) * | 2008-05-07 | 2010-07-21 | 天津大学 | Amphipathic three block copolymer and its preparation method and application |
| CN102020765A (en) * | 2010-11-05 | 2011-04-20 | 北京工业大学 | Preparation methods of poly (aspartic acid-co-lactic acid) graft polymer and nanoparticles of poly (aspartic acid-co-lactic acid) graft polymer |
| CN102532531A (en) * | 2011-11-03 | 2012-07-04 | 中国科学院长春应用化学研究所 | Polyamino acid block copolymer and preparation method thereof |
| CN102526744A (en) * | 2010-12-16 | 2012-07-04 | 国家纳米科学中心 | Medicinal composition and preparation method and application thereof |
| CN102552922A (en) * | 2010-12-16 | 2012-07-11 | 国家纳米科学中心 | Drug combination and preparation method and application thereof |
| CN102603362A (en) * | 2012-01-20 | 2012-07-25 | 中国科学院长春应用化学研究所 | Preparation method of block polymer brush |
| CN103467729A (en) * | 2013-08-09 | 2013-12-25 | 四川大学 | Polyethylene glycol-poly amino acid-polyester triblock polymer, preparation method and use thereof |
| CN103865088A (en) * | 2014-03-10 | 2014-06-18 | 山东理工大学 | Method for improving hydrophilia of polypeptide membrane by polycaprolactone and polyethylene glycol |
| CN104207965A (en) * | 2013-05-30 | 2014-12-17 | 上海珀理玫化学科技有限公司 | Surfactant used for bath lotion and preparation method thereof |
| CN104524639A (en) * | 2014-12-19 | 2015-04-22 | 上海大学 | Polyamino acid-based meniscus tissue engineering scaffold and preparation method thereof |
| CN104524641A (en) * | 2014-12-19 | 2015-04-22 | 上海大学 | Polyamino acidic elastic vascular tissue engineering stent and preparation method thereof |
| CN105362223A (en) * | 2015-06-03 | 2016-03-02 | 郭玉岩 | Method for preparing triblock copolymer micelle of medicine capable of being targeted |
| CN106317416A (en) * | 2016-09-07 | 2017-01-11 | 国家纳米科学中心 | Double-pH-response amphiphilic copolymer and preparation method and application thereof |
| CN107556497A (en) * | 2017-10-10 | 2018-01-09 | 淮阴师范学院 | A kind of preparation method and application of hybridized hydrogel material |
| CN109897179A (en) * | 2019-04-02 | 2019-06-18 | 中国科学院长春应用化学研究所 | A kind of poly- (Pidolidone ester) block copolymer of multi-arm polyethylene glycol-and its preparation method and application |
| CN112442179A (en) * | 2019-09-04 | 2021-03-05 | 深圳市第二人民医院 | Amphiphilic polymer for surface biological functionalization and preparation method and application thereof |
| CN112807486A (en) * | 2021-02-09 | 2021-05-18 | 长春圣博玛生物材料有限公司 | Amphiphilic polyamino acid copolymer-based injectable filler and injection |
| CN113061248A (en) * | 2021-03-25 | 2021-07-02 | 电子科技大学 | Flexible biodegradable high-molecular polymer material and preparation method thereof |
-
2003
- 2003-03-28 CN CNB031213979A patent/CN1185277C/en not_active Expired - Lifetime
Cited By (39)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN100415801C (en) * | 2003-10-28 | 2008-09-03 | 北京键凯科技有限公司 | Polyethylene glycol amino acid N-internal ring carbonyl anhydride active derivatives, and medicinal bonding compound and gel thereof |
| EP2348096A3 (en) * | 2005-01-04 | 2011-11-09 | Intezyne Technologies Inc. | Synthesis of hybrid block copolymers and uses thereof |
| EP1833958A4 (en) * | 2005-01-04 | 2009-01-14 | Intezyne Technologies Inc | Synthesis of hybrid block copolymers and uses thereof |
| EP2067801A1 (en) * | 2005-01-04 | 2009-06-10 | Intezyne Technologies Incorporated | Synthesis of Hybrid Block Copolymers |
| EP1833958A2 (en) * | 2005-01-04 | 2007-09-19 | Intezyne Technologies Incorporated | Synthesis of hybrid block copolymers and uses thereof |
| CN100592439C (en) * | 2005-08-08 | 2010-02-24 | 中国人民解放军军事医学科学院毒物药物研究所 | Bio-compatibility magnetic fluid |
| CN100428964C (en) * | 2006-06-29 | 2008-10-29 | 武汉理工大学 | Composite material of RGD polypeptide grafted poly (hydroxyacetic acid-L- lysine-L- lactic acid) / beta tricalcium phosphate, and preparation method |
| CN100443547C (en) * | 2007-03-15 | 2008-12-17 | 上海交通大学 | Prepn process of nanometer particle of poly (amide-amine)-poly (L-benzyl-glutamate) |
| CN101280047B (en) * | 2008-05-06 | 2010-06-23 | 华南理工大学 | Poly benzyl glutamate-containing degradable composite material and preparation thereof |
| CN101265312B (en) * | 2008-05-07 | 2010-07-21 | 天津大学 | Amphipathic three block copolymer and its preparation method and application |
| CN102020765B (en) * | 2010-11-05 | 2012-06-06 | 北京工业大学 | Preparation methods of poly (aspartic acid-co-lactic acid) graft polymer and nanoparticles of poly (aspartic acid-co-lactic acid) graft polymer |
| CN102020765A (en) * | 2010-11-05 | 2011-04-20 | 北京工业大学 | Preparation methods of poly (aspartic acid-co-lactic acid) graft polymer and nanoparticles of poly (aspartic acid-co-lactic acid) graft polymer |
| CN102552922A (en) * | 2010-12-16 | 2012-07-11 | 国家纳米科学中心 | Drug combination and preparation method and application thereof |
| CN102526744A (en) * | 2010-12-16 | 2012-07-04 | 国家纳米科学中心 | Medicinal composition and preparation method and application thereof |
| CN102526744B (en) * | 2010-12-16 | 2013-05-15 | 国家纳米科学中心 | Medicinal composition and preparation method and application thereof |
| CN102532531A (en) * | 2011-11-03 | 2012-07-04 | 中国科学院长春应用化学研究所 | Polyamino acid block copolymer and preparation method thereof |
| CN102532531B (en) * | 2011-11-03 | 2014-03-26 | 中国科学院长春应用化学研究所 | Polyamino acid block copolymer and preparation method thereof |
| CN102603362A (en) * | 2012-01-20 | 2012-07-25 | 中国科学院长春应用化学研究所 | Preparation method of block polymer brush |
| CN102603362B (en) * | 2012-01-20 | 2013-12-11 | 中国科学院长春应用化学研究所 | Preparation method of block polymer brush |
| CN104207965A (en) * | 2013-05-30 | 2014-12-17 | 上海珀理玫化学科技有限公司 | Surfactant used for bath lotion and preparation method thereof |
| CN103467729A (en) * | 2013-08-09 | 2013-12-25 | 四川大学 | Polyethylene glycol-poly amino acid-polyester triblock polymer, preparation method and use thereof |
| CN103467729B (en) * | 2013-08-09 | 2015-11-04 | 四川大学 | Polyethylene glycol-amino acid-polyester three-block polymkeric substance and its production and use |
| CN103865088A (en) * | 2014-03-10 | 2014-06-18 | 山东理工大学 | Method for improving hydrophilia of polypeptide membrane by polycaprolactone and polyethylene glycol |
| CN103865088B (en) * | 2014-03-10 | 2016-06-22 | 山东理工大学 | A kind of polycaprolactone and Polyethylene Glycol improve the poly-hydrophilic method of peptide film |
| CN104524639A (en) * | 2014-12-19 | 2015-04-22 | 上海大学 | Polyamino acid-based meniscus tissue engineering scaffold and preparation method thereof |
| CN104524641A (en) * | 2014-12-19 | 2015-04-22 | 上海大学 | Polyamino acidic elastic vascular tissue engineering stent and preparation method thereof |
| CN105362223A (en) * | 2015-06-03 | 2016-03-02 | 郭玉岩 | Method for preparing triblock copolymer micelle of medicine capable of being targeted |
| CN106317416A (en) * | 2016-09-07 | 2017-01-11 | 国家纳米科学中心 | Double-pH-response amphiphilic copolymer and preparation method and application thereof |
| CN106317416B (en) * | 2016-09-07 | 2019-06-07 | 国家纳米科学中心 | A kind of amphipathic copolymer and its preparation method and application of double pH responses |
| CN107556497B (en) * | 2017-10-10 | 2019-03-19 | 淮阴师范学院 | A kind of preparation method and application of hybridized hydrogel material |
| WO2019071945A1 (en) * | 2017-10-10 | 2019-04-18 | 淮阴师范学院 | Preparation method for and use of hybrid hydrogel material |
| CN107556497A (en) * | 2017-10-10 | 2018-01-09 | 淮阴师范学院 | A kind of preparation method and application of hybridized hydrogel material |
| CN109897179A (en) * | 2019-04-02 | 2019-06-18 | 中国科学院长春应用化学研究所 | A kind of poly- (Pidolidone ester) block copolymer of multi-arm polyethylene glycol-and its preparation method and application |
| CN109897179B (en) * | 2019-04-02 | 2021-08-17 | 中国科学院长春应用化学研究所 | Multi-arm polyethylene glycol-poly (L-glutamate) block copolymer, and preparation method and application thereof |
| CN112442179A (en) * | 2019-09-04 | 2021-03-05 | 深圳市第二人民医院 | Amphiphilic polymer for surface biological functionalization and preparation method and application thereof |
| CN112442179B (en) * | 2019-09-04 | 2021-07-23 | 深圳市第二人民医院 | Amphiphilic polymer for surface biological functionalization and preparation method and application thereof |
| CN112807486A (en) * | 2021-02-09 | 2021-05-18 | 长春圣博玛生物材料有限公司 | Amphiphilic polyamino acid copolymer-based injectable filler and injection |
| CN112807486B (en) * | 2021-02-09 | 2024-03-26 | 长春圣博玛生物材料有限公司 | Amphiphilic polyamino acid copolymer-based injectable filler and injection |
| CN113061248A (en) * | 2021-03-25 | 2021-07-02 | 电子科技大学 | Flexible biodegradable high-molecular polymer material and preparation method thereof |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1185277C (en) | 2005-01-19 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN1185277C (en) | Ternary polyglycol-aliphatic polyester-polyamino acid block copolymer and its prepn | |
| CN1205248C (en) | Biodegradable poly (alkylene oxide)-poly cp-dioxanone) block copolymer soluble in organic solvents, and drug delivery composition comprising same | |
| US6800663B2 (en) | Crosslinked hydrogel copolymers | |
| CN102181060B (en) | Polyvinyl alcohol-polypeptide-polyethylene glycol graft copolymer and preparation method thereof | |
| JP2986509B2 (en) | Modified polyester resin composition, method for producing the same, and use thereof | |
| CN1800238A (en) | Aliphatic polyester-polyamino acids copolymer with biological function and its synthesis method | |
| CN1197396A (en) | Copolymeric micelle drug compsn. and method for the prepn. thereof | |
| CN1164675C (en) | Polymeric compsn. for solubilizing poorly water soluble drugs and process for prepn. thereof | |
| US8524254B2 (en) | Bioresorbable polymers | |
| US6805876B2 (en) | Phosphate based biodegradable polymers | |
| JPH0859811A (en) | Biocompatible block copolymer | |
| CN101215377A (en) | Aliphatic polyester-polyamino acid Y-type three-arm block copolymers and synthetic method thereof | |
| CN101058641A (en) | Poly L-glutamic acid-poly N-isopropylacrylamide graft copolymer and preparation method thereof | |
| CN1823726A (en) | Degradable temperature sensitive physical aquagel and its preparation method | |
| CN1531566A (en) | Positively charged amphiphilic block copolymer as drug carrier and complex thereof with negatively charged drug | |
| CN101054441A (en) | Terpolymer for controllable degradation of carbon dioxide/epoxide/lactone and preparation method thereof | |
| CN1746207A (en) | Aliphatic carbonic acid ester polymer and the synthetic method and the purposes of band side carboxyl | |
| US20130331526A1 (en) | Temperature-sensitive polyethylene glycol / polyester block copolymer in which bioactive functional group is introduced into side chain thereof | |
| CN1194704C (en) | Polyester with its main train having amino acid and contg. active drug, and its prepn. method | |
| EP1641471B1 (en) | Biocompatible polymer networks | |
| CN100365043C (en) | Synthesis of ABA polypeptide -b- polytetrahydrofuran-b-polypeptide triblock copolymer | |
| KR20090059880A (en) | Preparation of copolymer containing polyesters segment via ring-opening polymerization of cyclic ester monomer in the presence of activated agent | |
| CN1803884A (en) | Cyclic aliphatic acid ester carbonate, its polymer, synthesis method and uses thereof | |
| Theiler et al. | Synthesis, characterization and in vitro degradation of 3D-microstructured poly (ε-caprolactone) resins | |
| CN1254495C (en) | Biological degradable PES graft polyphosphonitrile copolymer and its preparation |
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 | ||
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20090306 Address after: Room 124, building 5625, Renmin Street, Changchun, Jilin Patentee after: Chen Xuesi Address before: No. 159 Renmin Street, Jilin, Changchun Patentee before: CHANGCHUN INSTITUTE OF APPLIED CHEMISTRY CHINESE ACADEMY OF SCIENCES |
|
| ASS | Succession or assignment of patent right |
Owner name: CHEN XUESI Free format text: FORMER OWNER: CHANGCHUN INST. OF APPLIED CHEMISTRY, CHINESE ACADEMY OF SCIENCES Effective date: 20090306 |
|
| ASS | Succession or assignment of patent right |
Owner name: CHANGCHUN SHENGBOMA BIOLOGICAL MATERIALS CO., LTD. Free format text: FORMER OWNER: CHEN XUESI Effective date: 20090515 |
|
| C41 | Transfer of patent application or patent right or utility model | ||
| TR01 | Transfer of patent right |
Effective date of registration: 20090515 Address after: Room 124, building 5625, Renmin Street, Changchun, Jilin Patentee after: CHANGCHUN SINOBIOMATERIALS Co.,Ltd. Address before: Room 124, building 5625, Renmin Street, Changchun, Jilin Patentee before: Chen Xuesi |
|
| CX01 | Expiry of patent term |
Granted publication date: 20050119 |
|
| CX01 | Expiry of patent term |