CN101654515A - Method for suspending and polymerizing p-dioxane ketone in supercritical carbon dioxide - Google Patents
Method for suspending and polymerizing p-dioxane ketone in supercritical carbon dioxide Download PDFInfo
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- CN101654515A CN101654515A CN200810210098A CN200810210098A CN101654515A CN 101654515 A CN101654515 A CN 101654515A CN 200810210098 A CN200810210098 A CN 200810210098A CN 200810210098 A CN200810210098 A CN 200810210098A CN 101654515 A CN101654515 A CN 101654515A
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Abstract
The invention relates to a method for suspending and polymerizing p-dioxane ketone in supercritical carbon dioxide. The method comprises the following steps: serving metal salt, a metal alkyl compoundor an alkoxy metal compound as an initiator; serving the p-dioxane ketone as a reaction monomer; adopting an alternating copolymer, a block copolymer or a graft copolymer containing silicon, fluorineor hydrocarbon as a surface active agent to carry out a suspension polymerization reaction to prepare poly-p-dioxane ketone microspheres with excellent shapes and uniform sizes. The method is simpleand practical, has pure products, excellent microsphere shapes without subsequent processing, no toxicity and pollution of reaction media and green and environmental protection.
Description
Technical field
The present invention relates to suspension polymerization P-Dioxane ketone in supercritical co, obtain form poly-P-Dioxane ketone microballoon good, the size homogeneous.The invention belongs to macromolecular material and Biodegradable material field.
Background technology
As everyone knows, similar with polymer phases such as poly(lactic acid), polyglycolic acids, poly-P-Dioxane ketone (PPDO) also is a kind of biodegradable polymers that can be used clinically by drugs approved by FDA, and its homopolymer and multipolymer have obtained widespread use as the solid support material that can absorb suture for surgery or controlled drug delivery system.
But the synthetic method of conventional P PDO exists apparent in view defective, at first because poly-P-Dioxane ketone is insoluble to common organic solvent, the general mode of mass polymerization that adopts is synthesized, and it is block that resulting polymerisate is, and needs Special Equipment to carry out pulverization process when reality is used; Secondly,, contain a large amount of unreacted monomers in the polymerisate, before reality is used, need special program to remove unreacted monomer because the polyreaction of PPDO is a balanced reaction.Therefore, need a kind of polymerization process that dispersion state can directly be obtained and need not the PPDO of complicated last handling process of development.
Supercutical fluid is all fluids on critical temperature and emergent pressure of a kind of temperature and pressure.In the common supercutical fluid, supercritical co has stable, nonflammable explosive, the non-corrosiveness of nontoxic pollution-free, chemical property, criticality and easily realizes (31.1 ℃, 7.39MPa), low price, easy characteristic such as recovery, and with its medium as Polymer Synthesizing also have unreactiveness, the monomer dissolving power is adjustable, polymkeric substance is had advantages such as very strong swelling and diffusibility, the easy purifying of product, noresidue, speed of reaction be controlled, thereby has caused people's extensive concern.
According to monomer and polymkeric substance solubleness different in supercritical co, relevant polyreaction is mainly divided following a few class: polymerization in homogeneous phase (monomer, draw the method agent and polymkeric substance all is dissolved in supercritical co external phase); Precipitation polymerization and dispersion polymerization (monomer and initiator are dissolved in supercritical co external phase, and polymkeric substance is insoluble to supercritical co external phase); Suspension polymerization and letex polymerization (monomer, draw the method agent and polymkeric substance all is insoluble to supercritical co external phase or in supercritical co external phase solubleness very low).
Supercritical co has been applied to the building-up reactions of biodegradable superpolymer more and more widely at present.
1 polylactide (DLLA, LLA)
Polylactide is a kind of Biodegradable material of green, be widely used at biomedicine field at present, such as PLA tubular fibre, PLA Nano microsphere, be used for the porous PLA film of medicament slow release, as the PLA foam of organization bracket and the porous PLA film etc. that is used for culturing cell.The research of synthetic polylactide is more relatively in supercritical co at present.
Because the solubleness of rac-Lactide in supercritical co is very low, can consider generally speaking to prepare by letex polymerization.Sosnowski and co-worker thereof are PLLA microballoon (Sosnowski, the S. that stablizer has successfully obtained to have good form with poly-dodecyl acrylate-g-poly-epsilon-caprolactone; Gadzinowski, M.; Slomowski, S.Macromolecules1996; 29:4556-4564).Bratton etc. use triblock copolymer to synthesize L rac-Lactide by dispersion polymerization as tensio-active agent in supercritical co.When the content of stablizer reaches 5wt%, can obtain the good particulate of form (diameter is at 5-10 μ m), this is polymer particles (D.Bratton, the M.Brown and S.M.Howdle.Macromolecules 2003 that makes fine form for the first time in supercritical co by ring-opening polymerization; 36:5908-5911).
2 poly-(lactic acid-co-oxyacetic acid) (PLGA)
Poly-(lactic acid-co-oxyacetic acid) also is a kind of very important Biodegradable high-molecular (PLGA), is widely used in the medicine controlled releasing field, and its aspect such as biocompatibility, degradability, workability and physical strength has in vivo all obtained the authentication of FDA.Hile and co-worker thereof have reported poly-(lactic acid-co-oxyacetic acid) work (PLGA) of preparation in supercritical co the earliest.It is initiator that stannous octoate is adopted in experiment, and after reaction finished, the intact monomer of unreacted can adopt the supercutical fluid extracting to remove, and what obtain is the good porosu solid of form.Use
13The ratio that C NMR records rac-Lactide and glycollide is 70.7: 29.3, and the molecular-weight average of measuring product with gel permeation chromatography is 3500, and polydispersity index is 1.4.Owing to avoid having used organic solvent, this polymerization technique to be expected to produce highly purified PLGA (David D.Hile, the MichaelV.Pishko.Macromol.Rapid Commun.1999 that is used for biomedical sector; 20:511-514).
3 poly-epsilon-caprolactones (PCL)
Poly-epsilon-caprolactone is a kind of aliphatic polyester with good biocompatibility and degradation property, its homopolymer and be widely used in the carrier of artificial skin, bone repairing support and medicine controlling slow release system with the multipolymer of rac-Lactide and glycollide.FrankC.Loeker etc. adopt enzyme catalyst ring-opening polymerization 6-caprolactone in supercritical co, the polymerisate that obtains has narrower molecular weight distribution (PDI:1.4-1.6) and higher productive rate (95-98%), molecular weight reaches 35000-37000g/mol (Frank C.Loeker, Christopher J.Duxbury, Rajesh Kumar, Wei Gao, Richard A.Gross, Steven M.Howdle.Macromolecules 2004; 37:2450-2453).
In sum, it is reaction medium with the supercritical co that report is not arranged so far as yet, the acquisition form is good, the poly-P-Dioxane ketone microballoon of size homogeneous, and the PPDO microballoon that is obtained can be used for absorbable suture, fields such as sustained release medicine and tissue engineering bracket.
Summary of the invention
The object of the present invention is to provide a kind of preparation method of poly-P-Dioxane ketone microballoon.
Above-mentioned purpose of the present invention can be by being reaction medium with the supercritical co, metal-salt, alkyl metal cpd or alkoxide compound are initiator, P-Dioxane ketone is reaction monomers, adopt siliceous, fluorine or hydrocarbon polymer alternately, block or graft copolymer be that tensio-active agent carries out suspension polymerization, obtains form poly-P-Dioxane ketone microballoon good, the size homogeneous.
The concrete reaction conditions and the step of the polymerization process that the present invention proposes are: feed high pure nitrogen 30 minutes to drain air and moisture in reactor, under protection of nitrogen gas, add reaction monomers, initiator and tensio-active agent, initiator amount is the 0.01-1wt% of reaction monomers consumption, and the consumption of tensio-active agent is the 0.1-20wt% of reaction monomers consumption; Subsequently reaction system is evacuated, to remove initiator solvent and rare gas element, feeds carbon dioxide again, the control reacting kettle inner pressure is 10-50MPa, and temperature is 0-150 ℃, and polyreaction is carried out 0.5-72h under the constant temperature perseverance; Reaction is slowly opened purging valve after finishing, and the control deflation time falls unreacted monomer at 1-120min with extraction, opens reactor at last and obtains polymer microballoon.
Preferable described initiator in the above-mentioned synthetic method, metal-salt is tin protochloride, stannous octoate, tin acetate etc., alkyl metal cpd is zinc ethyl, triethyl aluminum, triisopropylaluminiuand, dibutyl magnesium etc., and alkoxide compound is diethylaluminum ethoxide, aluminum isopropylate etc.
Preferable described initiator amount is the 0.01-1wt% of described reaction monomers consumption.
Preferable described tensio-active agent is by the close carbonic acid gas segment of siliceous or fluorine and close polydioxanone segment, or by hydrocarbon parent's carbonic acid gas segment of not siliceous, fluorine and close polydioxanone segment formed alternately, block, graft copolymer.
Preferable described dosage of surfactant is the 0.1-20wt% of described reaction monomers consumption.
Preferable described reacting kettle inner pressure is 10-50MPa.
Preferable described temperature of reaction is 0-150 ℃.
The preferable described reaction times is 0.5-72h.
Preferable described purging valve deflation time is at 1-120min.
Characteristics of the present invention are, as reaction medium, obtain poly-P-Dioxane ketone microballoon by suspension polymerization with supercritical co, method is simple and practical, product is pure, the microballoon form well need not subsequent disposal, and reaction medium nontoxic pollution-free, environmental protection.
Embodiment
Embodiment 1
Under protection of nitrogen gas, in autoclave, add 10.2g P-Dioxane ketone; 0.01g stannous octoate and 0.1g gather poly-P-Dioxane ketone (PPDO-PPO-PPDO) triblock copolymer (molecular weight is 3500) of P-Dioxane ketone-b-polypropylene glycol-b-; closed reaction vessel then; vacuumize to remove initiator solvent and rare gas element; feed carbon dioxide; heating; when temperature reaches 50 ℃; postreaction still internal pressure; when temperature reaches 80 ℃; the control reacting kettle inner pressure is 25MPa, opens electromagnetic mixing apparatus, finishes reaction behind the 72h; slowly open purging valve; control deflation time be 60min to remove a small amount of unreacted monomer, open reactor then, obtain the good poly-P-Dioxane ketone microballoon of form.
Embodiment 2
Under protection of nitrogen gas, in autoclave, add 3.06g P-Dioxane ketone; 0.01g stannous octoate and 0.15g gather poly-P-Dioxane ketone (PPDO-PFPE-PPDO) triblock copolymer (molecular weight is 2300) of P-Dioxane ketone-b-PFPE-b-; closed reaction vessel then; vacuumize to remove initiator solvent and rare gas element; feed carbon dioxide; heating; when temperature reaches 60 ℃; postreaction still internal pressure; when temperature reaches 110 ℃; the control reacting kettle inner pressure is 25MPa, opens electromagnetic mixing apparatus, finishes reaction behind the 24h; slowly open purging valve; control deflation time be 60min to remove a small amount of unreacted monomer, open reactor then, obtain the good poly-P-Dioxane ketone microballoon of form.
Embodiment 3
Under protection of nitrogen gas, in autoclave, add 6.12g P-Dioxane ketone; 0.02g aluminum isopropylate and 0.06g polydimethylsiloxane-b-gather P-Dioxane ketone (PDMS-PPDO) Synthetic rubber, isoprene-styrene, hydrogenated, block, diblock (molecular weight is 12800); closed reaction vessel then; vacuumize to remove initiator solvent and rare gas element; feed carbon dioxide; heating; when temperature reaches 40 ℃; postreaction still internal pressure; the control reacting kettle inner pressure is 25MPa; open electromagnetic mixing apparatus; finish reaction behind the 24h, slowly open purging valve, the control deflation time is that 60min is to remove a small amount of unreacted monomer; open reactor then, obtain the good poly-P-Dioxane ketone microballoon of form.
Embodiment 4
Under protection of nitrogen gas, in autoclave, add 10.2g P-Dioxane ketone; 0.05g aluminum isopropylate and 0.02g PFPE-g-gather P-Dioxane ketone graft copolymer (molecular weight is 3950); closed reaction vessel then; vacuumize to remove initiator solvent and rare gas element; feed carbon dioxide; heating; when temperature reaches 40 ℃; postreaction still internal pressure; when temperature reaches 95 ℃; the control reacting kettle inner pressure is 30MPa, opens electromagnetic mixing apparatus, finishes reaction behind the 2h; slowly open purging valve; control deflation time be 60min to remove a small amount of unreacted monomer, open reactor then, obtain the good poly-P-Dioxane ketone microballoon of form.
Claims (6)
1. the preparation method of a poly-P-Dioxane ketone microballoon, it is characterized in that: be reaction medium with the supercritical co, metal-salt, alkyl metal cpd or alkoxide compound are initiator, P-Dioxane ketone is reaction monomers, adopt siliceous, fluorine or hydrocarbon polymer alternately, block or graft copolymer be that tensio-active agent carries out suspension polymerization, obtains form poly-P-Dioxane ketone microballoon good, the size homogeneous.
2. the preparation method of poly-P-Dioxane ketone microballoon according to claim 1, it is characterized in that polymeric reaction condition and step are: in reactor, feed high pure nitrogen 30 minutes to drain air and moisture, under protection of nitrogen gas, add reaction monomers, initiator and tensio-active agent, initiator is metal-salt, alkyl metal cpd or alkoxide compound, initiator amount is the 0.01-1wt% of reaction monomers consumption, and the consumption of tensio-active agent is the 0.1-20wt% of reaction monomers consumption; Subsequently reaction system is evacuated, to remove initiator solvent and rare gas element, feeds carbon dioxide again, the control reacting kettle inner pressure is 10-50MPa, and temperature is 0-150 ℃, and polyreaction is carried out 0.5-72h at constant temperature and pressure; Reaction is slowly opened purging valve after finishing, and the control deflation time, is opened reactor at last and obtained polymer microballoon to remove unreacted monomer at 1-120min.
3. the preparation method of poly-P-Dioxane ketone microballoon according to claim 1 and 2, it is characterized in that described metal-salt is tin protochloride, stannous octoate or tin acetate, alkyl metal cpd is zinc ethyl, triethyl aluminum, triisopropylaluminiuand or dibutyl magnesium, and alkoxide compound is diethylaluminum ethoxide or aluminum isopropylate.
4. the preparation method of poly-P-Dioxane ketone microballoon according to claim 1 and 2, it is characterized in that: described tensio-active agent is made up of the close carbonic acid gas segment and the close polydioxanone segment of siliceous or fluorine, or by hydrocarbon parent's carbonic acid gas segment of not siliceous, fluorine and close polydioxanone segment formed alternately, block or graft copolymer.
5. the preparation method of poly-P-Dioxane ketone microballoon according to claim 1 and 2 is characterized in that: described initiator amount is the 0.01-1wt% of reaction monomers consumption.
6. the preparation method of poly-P-Dioxane ketone microballoon according to claim 4 is characterized in that: described dosage of surfactant is the 0.1-20wt% of described reaction monomers consumption.
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| Application Number | Priority Date | Filing Date | Title |
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| CN200810210098A CN101654515A (en) | 2008-08-20 | 2008-08-20 | Method for suspending and polymerizing p-dioxane ketone in supercritical carbon dioxide |
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Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014075061A3 (en) * | 2012-11-12 | 2014-10-23 | Saudi Arabian Oil Company | Densifying carbon dioxide with a dispersion of carbon dioxide-philic water capsules |
| EP3872099A1 (en) * | 2020-02-26 | 2021-09-01 | Kraton Polymers Research B.V. | Purified polymer and methods for making |
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2008
- 2008-08-20 CN CN200810210098A patent/CN101654515A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2014075061A3 (en) * | 2012-11-12 | 2014-10-23 | Saudi Arabian Oil Company | Densifying carbon dioxide with a dispersion of carbon dioxide-philic water capsules |
| US9546316B2 (en) | 2012-11-12 | 2017-01-17 | Saudi Arabian Oil Company | Densifying carbon dioxide with a dispersion of carbon dioxide-philic water capsules |
| US11060014B2 (en) | 2012-11-12 | 2021-07-13 | Saudi Arabian Oil Company | Densifying carbon dioxide with a dispersion of carbon dioxide-philic water capsules |
| EP3872099A1 (en) * | 2020-02-26 | 2021-09-01 | Kraton Polymers Research B.V. | Purified polymer and methods for making |
| US11866541B2 (en) | 2020-02-26 | 2024-01-09 | Kraton Corporation | Purified polymer and methods for making |
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Open date: 20100224 |