CN102977294A - Degradable temperature-sensitive block copolymer and preparation method thereof - Google Patents
Degradable temperature-sensitive block copolymer and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a degradable temperature-sensitive block copolymer and a preparation method thereof and belongs to the technical field of biomedical materials and functional polymer materials. The degradable temperature-sensitive segmented block combines the temperature response characteristic of Poly (N-isopropylacrylamide) (PNIPAM) and the biocompatibility and biodegradability of poly lactic acid (PLA); and a living ring opening polymerization and atom transfer radical polymerization (ATRP) technology is carried out to prepare a straight-chain diblock or triblock copolymer PLA-PNIPAM or PNIPAM-PLA-PNIPAM containing temperature-sensitive chain section PNIPAM and degradable chain section PLA. The living ring opening polymerization and ATRP are high in controllability, so that the molecular weight of the obtained copolymer is controllable, the chain structure is regular, the components of the chain section can be adjusted, and the characteristics of temperature response, biodegradability and biocompatibility are brought. The copolymer can form stable temperature-sensitive micelle in the water because of amphipathy and temperature sensibility, and the temperature-sensitive micelle can be applied to controlled release of drug, which means that the temperature response of a carrier and the controlled release of a drug can be realized on the basis of the coordination of PLA block and PNIPAM chain section.
Description
Technical field
The invention belongs to the preparing technical field of bio-medical material and functional high molecule material, particularly a kind of degradable temperature sensitive type segmented copolymer and preparation method thereof.
Background technology
Poly(lactic acid) (PLA) and multipolymer thereof are all excellent macromolecular materials of a class biocompatibility and biological degradability, because its degraded product is carbonic acid gas and water, whole degradation process and degraded product are harmless to organism, therefore are widely used in the research of the aspects such as medicine controlled release carrier, operating sutures and tissue repair.Poly N-isopropyl acrylamide (PNIPAM) is a kind of water-soluble polymers that typically has temperature response characteristics, colloidal sol (Sol)-gel (Gel) occurs when lowest critical solution temperature (LCST=32 ℃) its aqueous solution changes, this temperature and human body temperature approach, and change response rapidly.Atom transfer radical polymerization (ATRP) is a kind of effective ways of preparation segmented copolymer.In atom transfer radical polymerization, number of free radical in the system is very low, double-basis termination reaction between the free radical has obtained effective inhibition, can successfully realize living polymerization, so method composite structure that can be by ATRP is regular, molecular weight and the controlled segmented copolymer of composition.Matyjaszewski
[1]With Brittain
[2]Reported that Deng the people monomer of amides carries out the ATRP polymerization, the cupric ion in chain end active centre easily and the amide group generation passivation in the monomer reduce even lose activity, the amino halogen atom that also can replace the living chain end causes monomer conversion very low simultaneously.Select three-(N, N-dimethyl aminoethyl) very strong amine (Me of complex ability
6TREN) part cooperates with catalyzer cuprous halide (CuX), can strengthen the controllability to the ATRP reaction.
Patent CN 102558464A
[3]Design has prepared a kind of star block copolymer POSS-PCL-PNIPAM, and the nano-micelle for preparing with this has been carried out medicine carrying research, has proved the possibility that this micella is used aspect drugrelease.But the POSS-OH as the polymerization initial substance is the poly-hydroxy cagelike structure, and the hydroxy radical content that causes point as the 6-caprolactone ring-opening polymerization is also uncontrollable, so the side chain number of star block copolymer is uncontrolled; Simultaneously, its reaction solvent is dimethyl formamide (DMF), and the amide group in the solvent causes the copper atom passivation in active centre easily, and then affects reactive behavior.Patent CN 101053681A
[4]Take MPC as initiator, after modifying, causes end group the ATRP polymerization of NIPAM, and prepared a kind of three arm biblock star type segmented copolymer MPC-PNIPAM and be applied to vascular suppository material, and gelation rate and the cytotoxicity of this material has been illustrated; But its catalyzer that adopts is Isosorbide-5-Nitrae, 8,11-tetramethyl--Isosorbide-5-Nitrae, 8,11-tetraazacyclododecane, four decane (Me
4Cyclam), although can obtain higher monomer conversion, also lack controllability.More than the two the preparation segmented copolymer before, all need to prepare to realize the polyfunctionality molecule of hub-and-spoke configuration, the former need to prepare POSS-OH, afterwards both then need to prepare three-functionality-degree initiator " three (2-bromo isobutyl acyloxy) ethamine " (TrisE).
Summary of the invention
The purpose of this invention is to provide a kind of double di-block copolymer (PLA-PNIPAM) or triblock copolymer (PNIPAM-PLA-PNIPAM) that contains degradable poly lactic acid (PLA) segment and temperature sensitive poly N-isopropyl acrylamide (PNIPAM) segment, it can be used for targeted drug controlled release and intelligent temperature sensitive switching material.
Technical scheme of the present invention is: the poly(lactic acid) (PLA-X, X-PLA-X) that the end by active ring-opening polymerization gained or both-end hydroxyl are changed into behind the alkylogen atom is macromole evocating agent, cause NIPA (NIPAM) monomer and carry out atom transfer radical polymerization (ATRP), preparation PLA-PNIPAM or PNIPAM-PLA-PNIPAM straight chain type two blocks or triblock copolymer.
Degradable temperature sensitive type segmented copolymer of the present invention is double straight chain type di-block copolymer or the triblock copolymer that contains polylactic acid chain segment and poly N-isopropyl acrylamide segment; Polylactic acid chain segment is the first segment in the described di-block copolymer, and the polymerization degree is 15-83, and the poly N-isopropyl acrylamide segment is the second segment, and the polymerization degree is 10-26; Polylactic acid chain segment is middle segment in the described triblock copolymer, and the polymerization degree is 32-69, and the poly N-isopropyl acrylamide segment is the both-end segment, and the polymerization degree is 11-24; Described polylactic acid chain segment has degradability, and the poly N-isopropyl acrylamide segment has Thermo-sensitive.
Above-mentioned degradable temperature sensitive type segmented copolymer 0.01g-0.05g is dissolved among the 1ml DMF, then adds the 10-20ml deionized water and form temperature sensitive type degradable micella, this micella is take poly(lactic acid) as kernel, and poly N-isopropyl acrylamide is shell; This micella is along with temperature raises, and particle diameter diminishes, and when the temperature reduction, particle diameter increases.
The preparation method of degradable temperature sensitive type segmented copolymer of the present invention is: obtain straight chain type di-block copolymer or triblock copolymer take PLA-X or X-PLA-X as macromole evocating agent initiation NIPA monomer carries out atom transfer radical polymerization; X is Br or Cl; PLA is poly(lactic acid), and the polymerization degree is 12-83.
Described poly(lactic acid) is poly-(D, Pfansteihl), poly-(D-ALPHA-Hydroxypropionic acid) or PLLA.
The concrete preparation process of degradable temperature sensitive type segmented copolymer of the present invention is:
(1) anhydrous and oxygen-free under the nitrogen protection condition, adds the PLA-X of 1-2g or the NIPA of X-PLA-X, 2-4g in the reaction flask, and adds solvent dimethyl sulfoxide (DMSO) 5-10ml, and magnetic agitation makes it to dissolve fully;
(2) for the first time use liquid nitrogen that system is frozen reality, vacuumize-Tong nitrogen circulation 3-4 time; 25-40 ℃ of thawing after system taken out, liquid nitrogen freezes and vacuumizes after real-Tong nitrogen circulation 3-4 time for the second time, and the CuX of adding and PLA-X or X-PLA-X equimolar amount under the nitrogen protection vacuumizes-Tong nitrogen circulation 3-4 time; System is taken out rear 25-40 ℃ of thawing, liquid nitrogen freezes and vacuumizes after real-Tong nitrogen circulation 3-4 time for the third time, the nitrogen protection hemostasis adds CuX molar weight 1-1.5 three-(N, N-dimethyl aminoethyl) amine doubly, vacuumizes-3-4 rear sealing system of Tong nitrogen circulation;
(3) with after the whole reaction system sealing, use the liquid nitrogen termination reaction behind 60-80 ℃ of reaction 5-12h under the magnetic agitation; Mixed solution is Precipitation in deionized water, removes unreacted NIPA monomer or NIPA homopolymer; Filter rear 25-40 ℃ of vacuum-drying 24-48h, obtain containing the thick product of remaining copper salt catalyst; Thick product is dissolved in the methylene dichloride, is transferred to HCl aqueous solution extraction 2-3 time of using successively 2-5wt% behind the separating funnel, deionized water extraction 2-3 time, collection organic phase; Behind the concentrating under reduced pressure in ethanol Precipitation, deionized water wash is to colourless neutrality; Product is at 25-40 ℃ of vacuum-drying 24-48h; PLA-PNIPAM straight chain type di-block copolymer or the PNIPAM-PLA-PNIPAM straight chain type triblock copolymer behind the purifying.
NIPAM is acrylamide monomers, carrying out the ATRP polymerization, the cupric ion in chain end active centre easily and the amide group generation passivation in the monomer reduce even lose activity, simultaneously, aminoly also can replace the active halogen atom that connects end and cause monomer conversion very low.Therefore for preventing that itself and ATRP polymerization activity center from complexing occuring, the present invention selects the very strong Me of complex ability
6The TREN part cooperates the catalyst system as the ATRP reaction with Catalysts Cu X, strengthened the controllability to reaction.
The present invention is at CuBr/Me
6TREN is under the condition of catalyst system, consider influencing each other of solvent, catalyzer, active centre, in tetrahydrofuran (THF), three kinds of solvent systems of DMF, DMSO, carry out the ATRP polyreaction, the result shows only in the DMSO solvent, X-PLA-X could cause NIPAM and carry out the ATRP polymerization, analyzing reason may be, take dimethyl sulfoxide (DMSO) as solvent, avoided the passivation in solvent and active centre, simultaneously, DMSO is a kind of polar aprotic solvent, can dissolve each other with water, can dissolve most of polymkeric substance again, therefore be fit to the preparation amphipathic nature block polymer.
The present invention combines the temperature response characteristics of poly N-isopropyl acrylamide (PNIPAM) and biocompatibility and the degradable characteristic of poly(lactic acid) (PLA), by active ring-opening polymerization and atom transfer radical polymerisation technique, prepared double straight chain type two blocks or triblock copolymer PLA-PNIPAM or the PNIPAM-PLA-PNIPAM that contains temperature sensitive segment PNIPAM and degradable segment PLA.Because active ring-opening polymerization and ATRP polymerization have good controllability, the gained molecular weight of copolymer is controlled, and chain structure is regular, and segment forms adjustable, and has temperature response, biodegradable and biocompatible characteristic.Owing to have amphipathic simultaneously and Thermo-sensitive, this multipolymer can form stable temperature sensitive micella in water, can be used for the targeted drug controlled release, i.e. coordination by PLA block and PNIPAM segment realizes that the temperature response of carrier and the control of medicine discharge.
Description of drawings:
Fig. 1 is PNIPAM-PLA-PNIPAM, the Br-PLA-Br of embodiment 1 preparation, the IR contrast spectrogram of HO-PLA-OH, NIPAM.
Fig. 2 is the Br-PLA-Br of embodiment 1 preparation
1The H-NMR spectrogram.
Fig. 3 is the PNIPAM-PLA-PNIPAM of embodiment 1 preparation
1The H-NMR spectrogram.
Fig. 4 is the IR contrast spectrogram of the HO-PLA-OH of embodiment 1 preparation and the PLA-OH that embodiment 2 prepares.
Embodiment
1) preparation of macromole HO-PLA-OH:
Adopt rac-lactide (D, L-Lactide) ring-opening polymerization polymer to prepare hydroxyl-terminated polylactic acid PLA-OH, take BDO (Isosorbide-5-Nitrae-BD) as chainextender, prepare both-end hydroxyl poly(lactic acid) HO-PLA-OH, wherein stannous octoate [Sn (Oct)
2] be catalyzer.D, L-rac-Lactide crude product recrystallization 3 times in ethyl acetate, 125 ± 1 ℃ of fusing point tests are to guarantee D, the purity of L-rac-Lactide.Toluene adds sodium (Na) silk, and to stir the rear distillation that dewaters refining.
In the polymerization process, get 35g through the D of recrystallization purifying, the L-rac-Lactide adds the reaction flask that dewaters through high-temperature flame treatment, vacuumize-Tong nitrogen (air-discharging) processes more than 3 times sealing system; Magnetic agitation, 140 ℃ of oil baths make D, and the L-rac-Lactide dissolves fully; Measure 2g catalyst S n (Oct) 2 and be mixed with the toluene solution of 0.05mol/L, and the Isosorbide-5-Nitrae of 0.6g-BD is dissolved wherein, mix, rear with in all adding systems of syringe; Finish reaction behind 140 ℃ of reactions of constant temperature 5h; 90 ℃ with acetone reflux, the solvent polymerization product, and in a large amount of deionized waters, separate out, get the thick HO-PLA-OH of oyster white; Dissolving, precipitating step repeat 3 times HO-PLA-OH are carried out purifying, to obtain the narrow distribution of products of design molecular weight; Get Off-white solid poly(lactic acid) 31.19g behind 40 ℃ of dry 48h of vacuum, productive rate is 89.0%.
2) preparation of macromole evocating agent Br-PLA-Br:
Utilize terminal hydroxy group and the 2 bromo propionyl bromide generation esterification of HO-PLA-OH to generate terminal polylactide macromolecular initiator Br-PLA-Br with bromine atoms.The 2 bromo propionyl bromide underpressure distillation is refining.
In this reaction, be n in molar ratio
Hydroxyl: n
Pyridine: n
Acylbromide in the 2-bromineThe ratio of=1:2:5 joins 31g both-end hydroxyl poly(lactic acid), 2g pyridine and 120ml dichloromethane solvent in the 250ml there-necked flask; Ice-water bath (4 ℃), logical nitrogen, magnetic agitation is dissolved poly(lactic acid) fully; The volume ratio of pressing 5:1 with methylene dichloride dilutes 2 bromo propionyl bromide, is added drop-wise to subsequently in the reaction system, and rate of addition is 1 drops/sec; 24h is carried out in reaction under nitrogen protection.After reaction finished, product was used respectively 1%(wt) NaOH, 1%(wt) HCl solution, and washed with de-ionized water, behind the separatory, product is poured Precipitation in the ethanol into, after precipitation is placed 40 ℃ of dry 24h of vacuum drying oven, finally obtaining Br-PLA-Br is 26.05g, and productive rate is 83.6%.
IR test spectrogram as shown in Figure 1; Adopt U.S. Nicolet Nexus FT-IR670 type Fourier transformation infrared spectrometer to measure.
1H-NMR tests as shown in Figure 2, and (Br) content is 1.639 to the end group bromine of end group analysis product, and namely every HO-PLA-OH on average contains 1.639 terminal hydroxy group, and theory is 2.0.The ARX-600 type NMR spectrometer with superconducting magnet that adopts Switzerland BRUKER (Brooker) company to produce is tested, and interior mark TMS (tetramethylsilane), solvent are CDCl
3
3) preparation of PNIPAM-PLA-PNIPAM:
Take Br-PLA-Br as macromole evocating agent, CuBr/Me
6TREN is as catalyst system, and initiation NIPAM carries out the ATRP polymerization and prepares PNIPAM-PLA-PNIPAM.The NIPAM crude product is made solvent through normal hexane, and toluene is done precipitation agent and carried out crystallization purifying 3-4 time, and vacuum-drying is to constant weight under the room temperature condition.Solvent dimethyl sulfoxide (DMSO) (DMSO) is refining.
In the polymerization process, the high-temperature flame treatment reaction flask dewaters, vacuumize-Tong nitrogen circulation 3 times is except oxygen; Quality is the Br-PLA-Br of 1g, the reaction flask that the NIPAM monomer adds 50ml under nitrogen protection, and adds 5ml solvent DMSO, magnetic agitation is dissolved Br-PLA-Br fully; For the first time use liquid nitrogen that system is frozen reality, vacuumize-Tong nitrogen circulation 3 times; System is taken out rear 40 ℃ of for the first time thawings, and liquid nitrogen freezes and vacuumizes-Tong nitrogen circulation 3 times N after real for the second time
2The lower CuBr that adds 46mg of protection vacuumizes-Tong nitrogen circulation 3 times; For the second time 40 ℃ of thawings after system taken out, liquid nitrogen freezes and vacuumizes after real-Tong nitrogen circulation 3 times for the third time, and the nitrogen protection hemostasis adds the Me with the CuBr equimolar amount
6TREN, vacuumize-Tong nitrogen circulation 3 times after sealing system; Use the liquid nitrogen termination reaction behind whole reaction system sealing, 80 ℃ of reactions of the magnetic agitation 12h.Product is Precipitation in deionized water, removes unreacted NIPAM monomer or PNIPAM homopolymer; Filter rear 40 ℃ of vacuum-drying 24h, the PNIPAM-PLA-PNIPAM that finally obtains is 1.73g, and productive rate is 86.5%.
The 1.73g product is dissolved in the 50ml methylene dichloride, is transferred to the HCl aqueous solution extraction 2 times of using successively 5wt% behind the separating funnel, organic phase is collected in deionized water extraction 2 times; Behind the concentrating under reduced pressure in 50ml ethanol Precipitation, and washing is to colourless neutrality; Product is at 40 ℃ of vacuum-drying 24h; The PNIPAM-PLA-PNIPAM straight chain type triblock copolymer behind the 1.23g purifying.Ultimate yield is 61.5%.
IR test spectrogram as shown in fig. 1; Adopt U.S. Nicolet Nexus FT-IR670 type Fourier transformation infrared spectrometer to measure.
1H-NMR tests as shown in Figure 3, and assay products consists of PNIPAM
9-PLA
17-PNIPAM
9The ARX-600 type NMR spectrometer with superconducting magnet that adopts Switzerland BRUKER (Brooker) company to produce is tested, and interior mark TMS (tetramethylsilane), solvent are CDCl
3
4) PNIPAM
9-PLA
17-PNIPAM
9The preparation of micella:
PNIPAM with 0.05g
9-PLA
17-PNIPAM
9Be dissolved among the 1ml solvent THF, add the 10ml deionized water under the agitation condition, form take PLA as kernel, PNIPAM is the temperature sensitive type micella of shell, and this micella is along with temperature raises, and particle diameter diminishes, and when the temperature reduction, particle diameter increases.It is 33.4 ℃ that DSC tests its sol-gel Sol-Gel transition temperature.
The heat effect of the temperature sensitive micellar solution of copolymer p NIPAM-PLA-PNIPAM adopts Q100DSC type differential scanning calorimeter to measure in the DSC test heat-processed.The concentration of aqueous copolymers solution is 10wt%, and testing sample 3mg is put into crucible, and under nitrogen protection, temperature is warming up to 40 ℃ from 25 ℃, and temperature rise rate is 1 ℃/min.
Embodiment 2
1) preparation of macromole PLA-OH:
In the preparation process of macromole PLA-OH, except the propyl alcohol of BDO being used instead into one-ended hydroxy, consumption is beyond the 1g, and other processes all preparation process with HO-PLA-OH are identical;
The IR spectrogram adopts U.S. Nicolet Nexus FT-IR670 type Fourier transformation infrared spectrometer to measure, and compares with the IR spectrogram of HO-PLA-OH, as shown in Figure 4.
2) the 2nd), 3), 4) step operation all with embodiment 2), 3), 4) step is identical.
Claims (5)
1. a degradable temperature sensitive type segmented copolymer is characterized in that, this segmented copolymer is double straight chain type di-block copolymer or the triblock copolymer that contains polylactic acid chain segment and poly N-isopropyl acrylamide segment; Polylactic acid chain segment is the first segment in the described di-block copolymer, and the polymerization degree is 15-83, and the poly N-isopropyl acrylamide segment is the second segment, and the polymerization degree is 10-26; Polylactic acid chain segment is middle segment in the described triblock copolymer, and the polymerization degree is 32-69, and the poly N-isopropyl acrylamide segment is the both-end segment, and the polymerization degree is 11-24; Described polylactic acid chain segment has degradability, and the poly N-isopropyl acrylamide segment has Thermo-sensitive.
2. degradable temperature sensitive type segmented copolymer according to claim 1, it is characterized in that, degradable temperature sensitive type segmented copolymer 0.01g-0.05g claimed in claim 1 is dissolved among the 1ml DMF, then add the 10-20ml deionized water and form temperature sensitive type degradable micella, this micella is take poly(lactic acid) as kernel, and poly N-isopropyl acrylamide is shell; This micella is along with temperature raises, and particle diameter diminishes, and when the temperature reduction, particle diameter increases.
3. the preparation method of degradable temperature sensitive type segmented copolymer according to claim 1, it is characterized in that, obtain straight chain type di-block copolymer or triblock copolymer take PLA-X or X-PLA-X as macromole evocating agent initiation NIPA monomer carries out atom transfer radical polymerization; X is Br or Cl; PLA is poly(lactic acid), and the polymerization degree is 12-83.
4. the preparation method of degradable temperature sensitive type segmented copolymer according to claim 3 is characterized in that, described poly(lactic acid) is poly-(D, Pfansteihl), poly-(D-ALPHA-Hydroxypropionic acid) or PLLA.
5. the preparation method of degradable temperature sensitive type segmented copolymer according to claim 3 is characterized in that, its concrete preparation process is:
(1) anhydrous and oxygen-free under the nitrogen protection condition, adds the PLA-X of 1-2g or the NIPA of X-PLA-X, 2-4g in the reaction flask, and adds solvent dimethyl sulfoxide (DMSO) 5-10ml, and magnetic agitation makes it to dissolve fully;
(2) for the first time use liquid nitrogen that system is frozen reality, vacuumize-Tong nitrogen circulation 3-4 time; 25-40 ℃ of thawing after system taken out, liquid nitrogen freezes and vacuumizes after real-Tong nitrogen circulation 3-4 time for the second time, and the CuX of adding and PLA-X or X-PLA-X equimolar amount under the nitrogen protection vacuumizes-Tong nitrogen circulation 3-4 time; System is taken out rear 25-40 ℃ of thawing, liquid nitrogen freezes and vacuumizes after real-Tong nitrogen circulation 3-4 time for the third time, the nitrogen protection hemostasis adds CuX molar weight 1-1.5 three-(N, N-dimethyl aminoethyl) amine doubly, vacuumizes-3-4 rear sealing system of Tong nitrogen circulation;
(3) with after the whole reaction system sealing, use the liquid nitrogen termination reaction behind 60-80 ℃ of reaction 5-12h under the magnetic agitation; Mixed solution is Precipitation in deionized water, removes unreacted NIPA monomer or NIPA homopolymer; Filter rear 25-40 ℃ of vacuum-drying 24-48h, obtain containing the thick product of remaining copper salt catalyst; Thick product is dissolved in the methylene dichloride, is transferred to HCl aqueous solution extraction 2-3 time of using successively 2-5wt% behind the separating funnel, deionized water extraction 2-3 time, collection organic phase; Behind the concentrating under reduced pressure in ethanol Precipitation, deionized water wash is to colourless neutrality; Product is at 25-40 ℃ of vacuum-drying 24-48h; PLA-PNIPAM straight chain type di-block copolymer or the PNIPAM-PLA-PNIPAM straight chain type triblock copolymer behind the purifying.
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Cited By (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104163924A (en) * | 2014-07-27 | 2014-11-26 | 北京化工大学 | Preparation method of amphiphilic nitrile rubber with fluorescence thermosensitivity |
| CN105030672A (en) * | 2015-07-27 | 2015-11-11 | 同济大学 | Method for preparing temperature-sensitive stereocomplex polylactic acid copolymer drug-loaded micell |
| CN106467605A (en) * | 2016-09-22 | 2017-03-01 | 北京化工大学 | One kind is containing temperature sensitive and degradable segment triblock copolymer, preparation method and nano thin-film |
| CN106589414A (en) * | 2016-12-30 | 2017-04-26 | 合众（佛山）化工有限公司 | Compound magnetic microsphere hydrogel prepared through waterborne ATRP polymerization method |
| CN109010840A (en) * | 2018-09-29 | 2018-12-18 | 清华大学 | A kind of preparation method of amphipathic biodegradable carrier micelle |
| US11696952B2 (en) * | 2017-08-17 | 2023-07-11 | Lutronic Vision Inc. | Nanocapsule-based ocular therapy |
Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102558464A (en) * | 2010-12-10 | 2012-07-11 | 江南大学 | Preparation method of star block copolymer temperature-sensitive nanomicelle |
-
2012
- 2012-11-29 CN CN201210500780.7A patent/CN102977294B/en active Active
Patent Citations (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN102558464A (en) * | 2010-12-10 | 2012-07-11 | 江南大学 | Preparation method of star block copolymer temperature-sensitive nanomicelle |
Non-Patent Citations (2)
| Title |
|---|
| 尉洁: "温敏性嵌段共聚物的制备及其在药物缓释方面的应用研究", 《中国优秀硕士学位论文全文数据库工程科技I辑》 * |
| 武承林等: "具有可调通道复合胶束在药物控制释放中的应用", 《2009年全国高分子学术论文报告会》 * |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104163924A (en) * | 2014-07-27 | 2014-11-26 | 北京化工大学 | Preparation method of amphiphilic nitrile rubber with fluorescence thermosensitivity |
| CN105030672A (en) * | 2015-07-27 | 2015-11-11 | 同济大学 | Method for preparing temperature-sensitive stereocomplex polylactic acid copolymer drug-loaded micell |
| CN105030672B (en) * | 2015-07-27 | 2018-02-09 | 同济大学 | A kind of preparation method of the stereocomplex PLA copolymer carrier micelle of temperature-responsive |
| CN106467605A (en) * | 2016-09-22 | 2017-03-01 | 北京化工大学 | One kind is containing temperature sensitive and degradable segment triblock copolymer, preparation method and nano thin-film |
| CN106467605B (en) * | 2016-09-22 | 2018-07-27 | 北京化工大学 | One kind containing temperature sensitive and degradable segment triblock copolymer, preparation method and nano thin-film |
| CN106589414A (en) * | 2016-12-30 | 2017-04-26 | 合众（佛山）化工有限公司 | Compound magnetic microsphere hydrogel prepared through waterborne ATRP polymerization method |
| US11696952B2 (en) * | 2017-08-17 | 2023-07-11 | Lutronic Vision Inc. | Nanocapsule-based ocular therapy |
| CN109010840A (en) * | 2018-09-29 | 2018-12-18 | 清华大学 | A kind of preparation method of amphipathic biodegradable carrier micelle |
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