CN1035678C - Biodegradable polycaprolactone polyether block polymer and preparing process thereof - Google Patents
Biodegradable polycaprolactone polyether block polymer and preparing process thereof Download PDFInfo
- Publication number
- CN1035678C CN1035678C CN 92113100 CN92113100A CN1035678C CN 1035678 C CN1035678 C CN 1035678C CN 92113100 CN92113100 CN 92113100 CN 92113100 A CN92113100 A CN 92113100A CN 1035678 C CN1035678 C CN 1035678C
- Authority
- CN
- China
- Prior art keywords
- polycaprolactone
- polyethers
- polyether block
- block polymer
- poly
- 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
Images
Landscapes
- Polyesters Or Polycarbonates (AREA)
- Biological Depolymerization Polymers (AREA)
- Materials For Medical Uses (AREA)
Abstract
The present invention relates to a biodegradable block copolymer of polycaprolactone and polyether and a synthesis method of the copolymer. Epsilon-caprolactone or an alkyl derivative thereof and alkylene oxide polyether are used to obtain the copolymer in the presence of butyl titanate as a catalyst at the reaction temperature and the reaction time of respectively 130 to 190DEG C and 1 to 20 hours, the molecular weight of a polycaprolactone chain segment and the molecular weight of a polyether chain segment are respectively from 450 to 50000 and from 44 to 22000. The obtained block copolymer has the advantages of biodegradability superior to that of homopolymerized polycaprolactone, adjustable biodegradation rate of the copolymer, simple and convenient preparation method and easy production.
Description
The present invention relates to polycaprolactone polyether block polymer that has biological degradability and preparation method thereof.
Biodegradation high molecular be a kind of have under physiological condition can degrade voluntarily, collapse or metabolism, thereby can be absorbed or excrete the polymer of characteristics by life entity, when therefore suture material is repaired in conduct on operative surgery, can avoid the trouble that after operation, needs the underwent operative method to remove again; As pharmaceutical excipient the time, can become the pharmaceutical carrier or the additive of drug delivery system, be an important component that guarantees medicament slow release and controlled release.Therefore biodegradable polymer has very wide application prospect in the bio-medical field.
Aliphatic polyester is owing to the easy hydrolysis of its ester bond causes backbone breaking, therefore be class biodegradation high molecular likely, wherein polycaprolactone particularly has good drug permeability, has more good prospects for application as the drug release material aspect of drug delivery system.Yet pure equal polycaprolactone crystallinity is extremely strong, and degree of crystallinity is higher, and stability is better relatively, and biological degradability is unsatisfactory.For improving the biological degradability of polycaprolactone, (Macro-molecules such as Teyssie, 1986,19,1828 [U.S.s]) once synthesized 6-caprolactone, methyl substituted 6-caprolactone segmented copolymer and random copolymers with propiolactone with Al/Zn bimetal oxo bridge alkoxide catalyzer, attempt to prepare and both had good drug permeability, the multipolymer that has controllable biodegradable speed again, but the catalyst preparation process of this method is miscellaneous, the synthesis step of multipolymer is longer, and the multipolymer biodegradation rate that makes thus still is difficult to control.
The present invention is by the method for polycaprolactone with the polyethers copolymerization, reduce the crystallinity of polycaprolactone, improve the wetting ability of multipolymer, to reach the purpose of improving polycaprolactone multipolymer biological degradability, use a step open loop and direct copolycondensation synthetic copolymer, building-up process is simple, is convenient to scale operation.
The biodegradation rate of multipolymer of the present invention can be by the proportioning of polycaprolactone and polyethers composition, polycaprolactone block length, and the kind of polyethers and molecular weight, and the variation of the multiple factors such as wetting ability of multipolymer is regulated.
First technical characterictic of the present invention is to use the copolymer composition of polyethers as polycaprolactone.With the molecular weight of different polyethers and change polyethers, make polycaprolactone segmental crystallization generation obstruction in various degree, regulate multipolymer degree of crystallinity thereby reach, change the purpose of multipolymer biodegradation rate.
Second technical characterictic of the present invention is to use stronger polyester of wetting ability and polycaprolactone copolymerization, to improve the wetting ability of multipolymer, regulates the purpose of polycaprolactone owing to ester chain hydrolysis causing biological degradability thereby reach.
It is the copolycondensation catalyzer that the 3rd technical characterictic of the present invention is to use commercial butyl (tetra) titanate, and a step is directly synthesized polycaprolactone polyether block polymer, have inexpensive, easy, be convenient to scale operation.Also can adopt bimetal oxo bridge alkoxide in addition is catalyzer.
Polycaprolactone composition in the polycaprolactone polyether block polymer of the present invention is poly-epsilon-caprolactone and poly-ε-methyl caprolactone and poly-ε-alkyl caprolactone, and described alkyl is C
1-C
4Alkyl, they be in poly-ε-methyl caprolactone, ε-ethyl caprolactone and poly-ε-propyl group (or sec.-propyl) caprolactone, poly-ε-butyl (or isobutyl-) caprolactone any.Any that best is in poly-epsilon-caprolactone and the poly-ε-methyl caprolactone.Polyether components can be in the poly-alkylene oxygen polyethers such as poly-ethylene oxide,1,2-epoxyethane polyethers, poly-Sanya methylene oxygen polyethers, poly-four methylenes support oxygen polyethers any.In preferably poly-ethylene oxide,1,2-epoxyethane polyethers and the poly-four methylenes support oxygen polyethers any.
Polycaprolactone segmental molecular weight can be 450-50000 in the polycaprolactone polyether block polymer of the present invention, and the molecular weight of polyether segment can be 44-22000.
The preparation method of polycaprolactone polyether block polymer of the present invention is with after caprolactone monomer and the polyethers mixing, the directly synthetic preparation of copolycondensation under catalyzer existence and protection of inert gas and continuous stirring condition.Polymeric reaction temperature is 130-190 ℃, and the reaction times is 1-20 hour.Best polymerization temperature is 140-170 ℃, and the reaction times is 4-8 hour.
The representative chemical structural formula of Biodegradable polycaprolactone polyether block polymer of the present invention is as follows:
In the formula: R=H or C
1-C
4Alkyl
m＝2-10
n＝4-440
p＝1-500
The polymerized unit of polycaprolactone component and polyether component (alkylene oxygen unit) molar ratio is 100: 1 to 1: 100, preferable polycaprolactone chain segment molecular weight is 1000-40000, the polyether segment molecular weight is 44-15000, and the best polycaprolactone component and polymerized unit (the alkylene oxygen unit) molar ratio of polyether component are 100: 3-30: 100.
Polycaprolactone polyether block polymer of the present invention directly commodity in use butyl (tetra) titanate is a catalyzer, and catalyst levels is the 0.001-2% of caprolactone monomer and polyethers gross weight of feeding intake.Best catalyst levels is the 0.01-1% of caprolactone monomer and polyethers gross weight of feeding intake.
Polycaprolactone polyether block polymer of the present invention has than equal polycaprolactone excellent biodegradability and excellent drug permeability, and nontoxic and good biocompatibility is the bio-medical material that a class is new, have widespread use.The synthetic method of multipolymer, do not need special conversion unit, method is simple, because the performance of copolymer products can the variation on a large scale in along with the different of the molecular weight of the kind of the ratio of components of feed intake caprolactone and polyethers, polyethers, polyethers and caprolactone monomer alkyl substituent, therefore can be simply by the change feed components when that feeds intake, the performance of regulating copolymerization product easily.
Embodiment 1:
6-caprolactone 42.14 gram and molecular weight are that 6000 poly-ethylene oxide,1,2-epoxyethane polyethers 6.06 restrains and mixes; after adding butyl (tetra) titanate 0.20 gram; under inert atmosphere (nitrogen or argon gas) protection and stirring; 160 ℃ of reactions 6 hours; the reaction later stage drops to about 1 mmhg with pressure; continue reaction half an hour, behind the stopped reaction in the inert atmosphere protection bottom discharge.The molecular weight of gained multipolymer is 46000, and the unitary mol ratio of caprolactone units and ethylene oxide,1,2-epoxyethane is 69: 31, by the tensile strength of film that chloroform dissolving back casts be 83 kilograms/[centimetre]
2, extension at break is 24%.
Embodiment 2:
6-caprolactone 24.5 gram and molecular weight are that 1000 poly-ethylene oxide,1,2-epoxyethane glycol 0.5 gram is in the presence of catalyst Ti acid butyl ester 0.20 gram, under embodiment 1 same reaction unit and condition, carry out copolycondensation, the molecular weight that generates copolymerization product is 40500, and the unitary mol ratio of caprolactone units and ethylene oxide,1,2-epoxyethane is 94: 6.
Embodiment 3:
The polycaprolactone polyether block polymer that has different caprolactone units and ethylene oxide,1,2-epoxyethane unit mol ratio by embodiment 1 method synthetic is simulated the degraded test of biotic condition under pH6.5 and 37 ℃ of conditions.The degree ([η] that descends in time with copolymer intrinsic viscosity
t/ [η].* 100%) as the evaluation of biodegradation rate.The biodegradation rate of the together equal polycaprolactone of the biodegradation rate of multipolymer more as shown in Figure 1.
Embodiment 4:
The water ratio of the together equal polycaprolactone of polycaprolactone polyether block polymer, and under pH6.5 and 37 ℃ of conditions, handle the variation of mechanical strength later in 7 days, as shown in table 1.
Table 1 water ratio and mechanical property are relatively
Equal polycaprolactone polycaprolactone polyether block polymer percent crystallization in massecuite (%) 49.2 39.1 water ratio (%) 19.3 54.2 tensile strength, 4.9 6.8 rates of descent (%)
The caprolactone units of multipolymer/equal polycaprolactone of ethylene oxide,1,2-epoxyethane unit (mol ratio)=57/43 Fig. 1 is with comparison-zero-equal polycaprolactone-△-caprolactone units/ethylene oxide,1,2-epoxyethane unit (mol ratio)=69/31--caprolactone units/ethylene oxide,1,2-epoxyethane unit (mol ratio)=57/43 of polycaprolactone polyether block polymer biodegradation rate
Claims (12)
1, a kind of polycaprolactone polyether block polymer with biological degradability, its chemical structural formula is:
In the formula: R=H or C
1-C
4Alkyl
m＝2-10
n＝4-440
p＝1-500
Wherein the polycaprolactone chain segment molecular weight is 456-50000, and the polyether segment molecular weight is 44-22000.
2, polycaprolactone polyether block polymer as claimed in claim 1 is characterized in that polycaprolactone is a poly-epsilon-caprolactone.
3, polycaprolactone polyether block polymer as claimed in claim 1 is characterized in that polycaprolactone is poly-ε-alkyl caprolactone, and described alkyl is C
1-C
4Alkyl in any.
4, polycaprolactone polyether block polymer as claimed in claim 3 is characterized in that polylactone is any in poly-ε-methyl caprolactone and the poly-ε-ethyl caprolactone.
5, polycaprolactone polyether block polymer as claimed in claim 1 is characterized in that described polyethers is poly-ethylene oxide,1,2-epoxyethane polyethers, poly-Sanya methylene oxygen polyethers, any in the poly-four methylenes support oxygen polyethers.
6, polycaprolactone polyether block polymer as claimed in claim 5 is characterized in that in preferably poly-ethylene oxide,1,2-epoxyethane polyethers of described polyethers and the poly-four methylenes support oxygen polyethers any.
7, as claim 1,2,3,4,5,6 described polycaprolactone polyether block polymers, it is characterized in that the polycaprolactone chain segment molecular weight is 1000-40000 preferably, the polyether segment molecular weight is 44-15000.
8, a kind of method for preparing the polycaprolactone polyether block polymer of claim 1 art, polymerized unit (the alkylene oxygen unit) molar ratio that it is characterized in that caprolactone monomer and polyethers is 100: 1-1: 100, use catalyzer to be butyl (tetra) titanate, its consumption is the 0.001-2% of caprolactone monomer and polyethers gross weight of feeding intake, and temperature of reaction and time are respectively 130-190 ℃ and 1-20 hour.
9, preparation polycaprolactone polyether block polymer method as claimed in claim 8 is characterized in that the best caprolactone monomer and the molar ratio of polyethers polymerized unit are 100: 3-30: 100.
10,, it is characterized in that the catalyzer optimum amount is the 0.01-1% of caprolactone monomer and polyethers gross weight of feeding intake as preparation polycaprolactone polyether block polymer method as described in the claim 8.
11, preparation polycaprolactone polyether block polymer method as claimed in claim 9 is characterized in that the catalyzer optimum amount is the 0.01-1% of caprolactone monomer and polyethers gross weight of feeding intake.
12,, it is characterized in that optimal reaction temperature and time are 140-170 ℃ and 4-8 hour as claim 8,9,10,11 described preparation polycaprolactone polyether block polymer methods.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 92113100 CN1035678C (en) | 1992-11-19 | 1992-11-19 | Biodegradable polycaprolactone polyether block polymer and preparing process thereof |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN 92113100 CN1035678C (en) | 1992-11-19 | 1992-11-19 | Biodegradable polycaprolactone polyether block polymer and preparing process thereof |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1087098A CN1087098A (en) | 1994-05-25 |
| CN1035678C true CN1035678C (en) | 1997-08-20 |
Family
ID=4946234
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN 92113100 Expired - Fee Related CN1035678C (en) | 1992-11-19 | 1992-11-19 | Biodegradable polycaprolactone polyether block polymer and preparing process thereof |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN1035678C (en) |
Families Citing this family (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1060188C (en) * | 1996-07-03 | 2001-01-03 | 中国科学院化学研究所 | Bio-degradatable resin azeotropic mixture |
| CN1080744C (en) * | 1997-09-25 | 2002-03-13 | 中国科学院化学研究所 | Biodegradation high molecular composition and its preparing method and use |
| CN1098882C (en) * | 1998-06-03 | 2003-01-15 | 中国科学院化学研究所 | Biodegradable high polymer and its preparation method |
-
1992
- 1992-11-19 CN CN 92113100 patent/CN1035678C/en not_active Expired - Fee Related
Also Published As
| Publication number | Publication date |
|---|---|
| CN1087098A (en) | 1994-05-25 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| US6093792A (en) | Bioresorbable copolymers | |
| JP3140791B2 (en) | Bulk reactive extrusion polymerization process for producing aliphatic ester polymer compositions | |
| EP0260415A2 (en) | Synthesis and application of high molecular weight polyanhydrides | |
| EP1366104A2 (en) | Environmentally degradable polymeric compounds, their preparation and use as hot melt adhesive | |
| JP2001514279A (en) | Biodegradable lactone copolymer | |
| JPH09504565A (en) | High molecular weight polyester polycarbonates and their use for producing biodegradable matrices | |
| CN1035678C (en) | Biodegradable polycaprolactone polyether block polymer and preparing process thereof | |
| CA3116431A1 (en) | Controlled production of polyglycolic acid and glycolide | |
| Ganguly et al. | Synthesis and Production of Polylactic Acid (PLA) | |
| KR100354828B1 (en) | Method for preparing biodegradable polyester and itself prepared thereby | |
| CN1241970C (en) | Process of snthesizing medical biological degradative material by acetic acid organic guanidine as catalast | |
| JP3287425B2 (en) | Polylactic acid having hydroxyl-terminated ester ester and method for producing the same | |
| CN1271742A (en) | Biodegradable three-element copolymerized ester and its processing process | |
| CN1073582C (en) | Method of synthesis for biodegradable copolyester | |
| CN1098882C (en) | Biodegradable high polymer and its preparation method | |
| JP3517858B2 (en) | Polylactic acid production method | |
| JP3144231B2 (en) | Aliphatic polyester and / or copolymer thereof | |
| JP3374530B2 (en) | Method for producing aliphatic polyester copolymer | |
| CN101591349B (en) | Nitrogen-bridged bis(phenolate) yttrium dibenzyl oxygen compound and preparation and application thereof | |
| JP3144416B2 (en) | Aliphatic polyester and / or copolymer thereof | |
| EP1776405B1 (en) | Copolymerization of 1,4-dioxan-2-one and a cyclic ester monomer producing thermal stabilized stabilized 1,4-dioxan-2-one (co) polymers | |
| KR100288002B1 (en) | Star copolymer of polyelactide and polyethylene oxide | |
| KR100308535B1 (en) | Polyester resin composition and method for producing the same | |
| JPH0616792A (en) | Production of copolymer of epsilon-caproloctone with glycoside | |
| KR19980082076A (en) | Polyester resin composition and its manufacturing method |
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 | ||
| C15 | Extension of patent right duration from 15 to 20 years for appl. with date before 31.12.1992 and still valid on 11.12.2001 (patent law change 1993) | ||
| OR01 | Other related matters | ||
| 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 |