CN106800641A - A kind of mPEG-b-PCL diblock polymers polymer and its application and preparation - Google Patents
A kind of mPEG-b-PCL diblock polymers polymer and its application and preparation Download PDFInfo
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Abstract
The invention discloses a kind of diblock polymer of polyethylene glycol crosslinked polycaprolactone, its structural formula is mPEG b PCL, and wherein mPEG and PCL molar ratios are 1:0.1~1:10.The diblock polymer of polyethylene glycol crosslinked polycaprolactone of the invention has good load medicine potentiality, can carrying medicament steady running, to the target spot of target, realizes the dispersion application of insoluble drug in vivo.And, the diblock polymer produces Adhesion inhibiyive effect for human body tumour cell or cancer cell so that tumor patient, the chemotherapeutic treatment effect of cancer patient are obviously improved.
Description
Technical field
The present invention relates to a kind of diblock polymer of polyethylene glycol crosslinked polycaprolactone, more particularly to polyethylene glycol crosslinked gathers in oneself
The preparation and its application of the diblock polymer of ester.
Background technology
Because of it, the small clinical practice for causing medicine of the solubility in water is restricted poorly water soluble drugs.Poorly water soluble drugs are passed through
Some carriers are wrapped up, and are a kind of effective methods that poorly water soluble drugs are carried out with solubilising.
The size of amphiphatic molecule copolymer, stability, versatility and biocompatibility are all very outstanding, this cause they
Drug delivery carrier and field of environment protection have very huge potentiality.In numerous amphiphilic polymers, especially with life
The copolymer of thing compatibility and biological degradability, such as PLA-PEG, PCL-PEG, PCL-PLA-PEG, performance is the most prominent and robs
Eye.
It is well known that the copolymer of amphiphatic molecule can be self-assembly of a hydrophobic core and hydrophilic shell in the solvent of selectivity
Micelle, such micelle size is typically smaller than 200nm, the characteristic with part nano material.Amphiphilic diblock polyphosphazene polymer
The characteristics of compound, makes micelle under the conditions of no additional stabilization agent hydrophilic when outside hydrophilic shell reaches maximum biological solubility
Property solvent in keep dissolving when, hydrophobic nuclear interaction, so as to load some medicines for being insoluble in water.
Used as the carrier of dewatering medicament, the colloid of diblock polymer is widely studied.At present, micelle paper and data master are studied
Focus on the release feature of the preparation of polymer, the effect between sign, medicine and carrier and medicine.In fact, so far
Untill it is still very limited for the research of the degraded of copolymerization micelle.
There are some researches show PCL-PEG films can show extremely different hydrolytic degradation characteristics, and table with vitro in vivo
Bright PCL-PEG films hydrolyze degradation process, may be influenceed by PEG molecule contents, environment temperature, acidity and basicity.
Research finds that the degraded mode of PCL-PEG micelles and the degraded mode of discrete material are different, may have many potential
Value.
The content of the invention
It is an object of the invention to be directed to not abundant enough, the existing diblock of the research on diblock polymer in the prior art
The potential value exploitation of polymer is incomplete, there is provided a kind of new mPEG-b-PCL diblock polymer polymer.Meanwhile,
The present invention provides the method for preparing this diblock polymer compound, and property to this diblock polymer compound is carried out
Research is characterized, the potential medical value of this macromolecular compound is disclosed.
In order to realize foregoing invention purpose, the invention provides following technical scheme:
A kind of diblock polymer of polyethylene glycol crosslinked polycaprolactone, its composition structure is mPEG-b-PCL, wherein mPEG
It is 1 with PCL molar ratios:0.1~1:10.
The diblock polymer of polyethylene glycol crosslinked polycaprolactone of the invention has good load medicine potentiality, can carrying medicament exist
Steady running realizes the dispersion application of insoluble drug to the target spot of target in organism.And, the diblock polymer for
Human body tumour cell or cancer cell produce Adhesion inhibiyive effect so that tumor patient, the chemotherapeutic treatment effect of cancer patient are shown
The lifting of work.
There is the ester bond in polycaprolactone in PEG-b-PCL diblock copolymers hydrolysis of the present invention so that the molecular weight distribution of compound,
Crystallinity etc. there occurs larger change.In the degradation process of PEG-b-PCL diblock copolymers, the molecule segment of polymer
Hydrolytic cleavage mechanism be totally different from general polyethylene glycol compound so that the stability of compound, Drug loading capacity have pole
Big lifting.
Further, preferably mPEG and PCL mass ratios are 1:1~1:6.When both ratios meet range above, two
Block polymer can show more suitable stability, degradation property so that the stability and rate of release of medicine more preferably,
Preferably promote the curative effect of medicine.When both ratios are 1:When 1, diblock polymer has good for the state of aggregation of cell
Facilitation, there is certain inhibitory action simultaneously for the coherent condition of tumour cell, cancer cell, it is possible to increase chemotherapy
Effect.
The present invention also provides a kind of method for preparing described diblock polymer simultaneously, comprises the following steps:
(1) taking polyethylene glycol, is dissolved in toluene, is dehydrated at 120-150 DEG C 1-3 hours, is preferably dehydrated 1.5-3 at 125-145 DEG C
Hour.
(2) ε-hexamethylene lactone and stannous octoate, nitrogen is added to protect, 130-160 DEG C is reacted 8-16 hours.Preferably, exist
135-155 DEG C is reacted 8-15 hours.
(3) after reaction terminates, room temperature is cooled to, adds methyl tertiary butyl ether(MTBE), it is ultrasonic 5-30 minutes, under ice bath, cooling weight
Crystallization 10-30 minutes, suction filtration collects filter residue, and vacuum drying both obtains target product.
The diblock polymer for obtaining is synthesized by above method and is target product of the invention, with good stability and knot
Brilliant performance, can be effectively applied to the load medicine of insoluble drug.And, method made above is simple and easy to apply, and reaction efficiency is high,
Substantially free of impurities is generated, the easily separated easy purification of product.
Application of the diblock polymer of above-mentioned polyethylene glycol crosslinked polycaprolactone in treating cancer or tumour medicine is prepared.This
The diblock polymer of the polyethylene glycol crosslinked polycaprolactone of invention can effectively suppress the adhesion of cancer cell, tumour cell, make
It keeps building up state, prevents the diffusion of cancer cell or tumour cell, improves therapeutic effect of the medicine for relevant disease.
Further, application of the diblock polymer of described polyethylene glycol crosslinked polycaprolactone in treatment breast cancer medicines are prepared.
Research display diblock polymer of the invention can play good suppression aggtegation for breast cancer cell line MCF-7.
Further, the diblock polymer of described polyethylene glycol crosslinked polycaprolactone is as medicine carrying material in treating cancer or tumour
Medicine in application.
Further, the nitrogen gas purity that described nitrogen protection is used is more than 99.99% High Purity Nitrogen.
Compared with prior art, beneficial effects of the present invention:
1. the diblock polymer of polyethylene glycol crosslinked polycaprolactone of the invention can be realized effectively for insoluble drug
Load, transhipment, and ensure the dispersion of insoluble drug.
2. diblock polymer of the invention produces Adhesion inhibiyive effect for human body tumour cell or cancer cell so that tumour is suffered from
Person, the chemotherapeutic treatment effect of cancer patient are obviously improved.
3. the preparation method that the present invention is provided is simple and easy to apply, and reaction efficiency is high, substantially free of impurities generation, the easily separated easy purification of product,
Can be with popularization and application and various pharmaceutical preparations.
Brief description of the drawings:
Fig. 1 is mPEG-b-PCL diblock copolymers1H NMR spectras.
Fig. 2 is mPEG-b-PCL (MmPEG:MPCL=1:1) diblock copolymer1H NMR spectras.
Fig. 3 is mPEG-b-PCL (MmPEG:MPCL=1:4) diblock copolymer1H NMR spectras.
Fig. 4 is mPEG-b-PCL (MMPEG:MPCL=1:6) diblock copolymer1H NMR spectras.
Fig. 5 is the mPEG-b-PCL (M that concentration is 10mg/mLmPEG:MPCL=1:1) diblock copolymer is in human breast carcinoma
Microphoto record on cell line mcf-7 culture medium in continuous culture a period of time.
Fig. 6 is the mPEG-b-PCL (M that concentration is 1mg/mLmPEG:MPCL=1:1) diblock copolymer is thin in human breast carcinoma
Microphoto record on born of the same parents system MCF-7 culture mediums in continuous culture a period of time.
Fig. 7 is the mPEG-b-PCL (M that concentration is 0.1mg/mLmPEG:MPCL=1:1) diblock copolymer is in human breast carcinoma
Microphoto record on cell line mcf-7 culture medium in continuous culture a period of time.
Specific embodiment
Reagent:Polyethylene glycol (mPEG, Mn=2000, Aldrich, USA), ε-hexamethylene lactone (ε-CL, density 1.07g/cm3
Alfa Aesar, USA), stannous octoate (Sn (Oct) 2, Sigma, USA), toluene, methyl tertiary butyl ether(MTBE), human breast carcinoma is thin
Born of the same parents MCF-7 (ATCC), DMEM cell culture mediums (HyClone), 0.25% trypsase (HyClone), hyclone
(Chinese holly), Pen .- Strep dual anti-(HyClone), physiological saline, PBS (phosphate buffer).
Instrument:Toluene azeotropic water removing device, oil bath pan, three-neck flask, condenser pipe, glass stopper, vacuum extractor, nitrogen gas
Ball, syringe, Vltrasonic device, reagent rifle, cooling device, Suction filtration device, Reagent Tube, vacuum desiccator, label, mark
Pen, assay balance, nuclear magnetic resonance, 96 orifice plates, Tissue Culture Dish, 15mL centrifuge tubes, EVOSFLAuto imaging systems.
With reference to test example and specific embodiment, the present invention is described in further detail.But this should not be interpreted as this hair
The scope of bright above-mentioned theme is only limitted to following embodiment, and all technologies realized based on present invention belong to model of the invention
Enclose.For the percentage of special instruction is usually percentage by weight in the present invention.
Embodiment 1
Synthesis mPEG-b-PCL (MmPEG:MPCL=1:1)
Test the form that feeds intake:
Polyethylene glycol 1.000g is accurately weighed using assay balance, is added in three-neck flask, 10mL toluene is added, in oil bath pan
Azeotropic water removing 2 hours under the conditions of 138 DEG C.0.94mL ε-hexamethylene lactone after cooling, adds appropriate stannous octoate catalyst, plus
Enter a magnetic stir bar, add 10mL toluene, three mouths of three-neck flask are used into glass stopper, condenser pipe (condensation respectively
Pipe upper end covers a tiny balloons full of nitrogen), vacuumizing joint is sealed, and connects vacuum extractor, opens condenser pipe upper end piston,
Vacuumizing joint piston is opened, opening vacuum extractor vacuumize 5 minutes, closes vacuumizing joint piston, closes condensation
Pipe upper end piston, closes vacuum extractor, disconnects three-necked bottle and is connected with vacuum extractor, is replaced with a balloon full of nitrogen
That balloon, opens condenser pipe upper end piston before.
This three-necked bottle is fixed on iron stand, is placed in oil bath pan, to 138 DEG C, magnetic agitation rotational speed regulation is into for temperature adjustment
Speed, reacts 12 hours, if solvent is reduced can be suitably added toluene in course of reaction.After reaction terminates, room temperature is cooled to,
Then add 10mL methyl tertiary butyl ether(MTBE)s, ultrasound 10 minutes, ice bath cooling recrystallization 20 minutes carries out suction filtration, collects filter
Slag, is put into vacuum desiccator, dries 1 hour, and product is loaded into plastic tube, is weighed, and sticks respective labels.
Fig. 1 is the PEG-PCL diblock copolymer of standard1H NMR spectras.Chemical shift is 3.65 × 10-6
Peak belong to the proton peak of polyethylene glycol segment methylene a, 2.3 × 10-6Triplet belong to proton at c, 4.1 × 10-6
Triplet belong to proton at f, 1.6 × 10-6Multiplet belong to proton at d, and be located at most High-Field 1.4 × 10-6's
Multiplet belongs to the proton peak at e.
By the mPEG-b-PCL (M of gainedmPEG:MPCL=1:1) sample is fitted into general 3 microns in nuclear magnetic tube, with syringe plus
Enter appropriate deuterochloroform, nuclear magnetic tube is clogged with stopper.MPEG-b-PCL (M are marked with marking penmPEG:MPCL=1:1).
Carry out nuclear magnetic resonance.Fig. 2 is mPEG-b-PCL (MmPEG:MPCL=1:1) diblock copolymer1H NMR spectras.
1H NMR (400MHz, DMSO-d6) δ 3.98 (t, J=6.5Hz, 7H), 3.46-3.30 (m, 2H), 3.32 (s,
5H), 3.24 (s,1H), 2.27 (t, J=7.4Hz, 7H), 1.61-1.45 (m, 15H), 1.29 (qd, J=9.6,9.0,
6.0Hz, 9H), 0.89-0.77 (m, 2H)
Nmr analysis result shows that synthetic product is the mPEG-b-PCL (M of targetmPEG:MPCL=1:1) diblock polymer.
Embodiment 1 | 1:1 | 1.000 | 0.94 |
Embodiment 2 | 1:4 | 1.000 | 3.74 |
Embodiment 3 | 1:6 | 1.000 | 5.61 |
Embodiment 2
Synthesis mPEG-b-PCL (MmPEG:MPCL=1:4)
Polyethylene glycol 1.000g is accurately weighed using assay balance, is added in three-neck flask, 10mL toluene is added, in oil bath pan
Azeotropic water removing 2 hours under the conditions of 140 DEG C.3.74mL ε-hexamethylene lactone after cooling, adds appropriate stannous octoate catalyst, plus
Enter magnetic stir bar, add 10mL toluene, three mouths of three-neck flask are used into glass stopper respectively, condenser pipe is (on condenser pipe
One tiny balloons full of nitrogen of end set), vacuumizing joint is sealed, and connects vacuum extractor, opens condenser pipe upper end piston, is beaten
Vacuumizing joint piston is opened, opening vacuum extractor vacuumize 5 minutes, closes vacuumizing joint piston, closes condenser pipe
Upper end piston, closes vacuum extractor, disconnects three-necked bottle and is connected with vacuum extractor, is replaced it with a balloon full of nitrogen
Preceding that balloon, opens condenser pipe upper end piston.This three-necked bottle is fixed on iron stand, is placed in oil bath pan, temperature adjustment
To 140 DEG C.Magnetic agitation rotational speed regulation is reacted 12 hours to middling speed, can be suitably added if solvent is reduced in course of reaction
Toluene.Reaction is cooled to room temperature after terminating, add 10mL methyl tertiary butyl ether(MTBE)s, and ultrasound 10 minutes is cooled down under ice bath and tied again
Brilliant 20 minutes, suction filtration is then carried out, filter residue is loaded into vessel, be put into vacuum desiccator and dry 1 hour, product loaded and is moulded
Expects pipe, weighs, and sticks respective labels.
By the mPEG-b-PCL (M of gainedmPEG:MPCL=1:4) sample is fitted into general 3 microns in nuclear magnetic tube, with syringe plus
Enter appropriate deuterochloroform, nuclear magnetic tube is clogged with stopper.MPEG-b-PCL (M are marked with marking penmPEG:MPCL=1:4).
Carry out nuclear magnetic resonance.Fig. 3 is mPEG-b-PCL (MmPEG:MPCL=1:4) diblock copolymer1H NMR spectras.
mPEG-b-PCL(1:4)
1H NMR (400MHz, DMSO-d6) δ 3.98 (t, J=6.5Hz, 4H), 3.51 (s, 20H), 2.27 (t, J=7.3
Hz, 4H), 1.54 (h, J=7.5Hz, 8H), 1.36-1.23 (m,1H), 1.29 (s, 4H)
Nmr analysis result shows that synthetic product is target mPEG-b-PCL (MmPEG:MPCL=1:4) diblock polymer.
Embodiment 3
Synthesis mPEG-b-PCL (MmPEG:MPCL=1:6)
Polyethylene glycol 1.000g is accurately weighed using assay balance, is added in three-neck flask, 10mL toluene is added, in oil bath pan
Azeotropic water removing 2 hours under the conditions of 140 DEG C.5.61mL ε-hexamethylene lactone after cooling, adds appropriate stannous octoate catalyst, plus
Enter magnetic stir bar, add 10mL toluene, three mouths of three-neck flask are used into glass stopper respectively, condenser pipe is (on condenser pipe
One tiny balloons full of nitrogen of end set), vacuumizing joint is sealed, and connects vacuum extractor, opens condenser pipe upper end piston, is beaten
Vacuumizing joint piston is opened, opening vacuum extractor vacuumize 5 minutes, closes vacuumizing joint piston, closes condenser pipe
Upper end piston, closes vacuum extractor, disconnects three-necked bottle and is connected with vacuum extractor, is replaced it with a balloon full of nitrogen
Preceding that balloon, opens condenser pipe upper end piston.This three-necked bottle is fixed on iron stand, is placed in oil bath pan, temperature adjustment
To 140 DEG C, magnetic agitation rotational speed regulation to middling speed is reacted 12 hours, can be suitably added if solvent is reduced in course of reaction
Toluene reactions are cooled to room temperature after terminating, and add 10mL methyl tertiary butyl ether(MTBE)s, and ultrasound 10 minutes cools down recrystallization under ice bath
20 minutes, suction filtration is then carried out, filter residue is loaded into vessel, be put into vacuum desiccator and dry 1 hour, product is loaded into plastics
Pipe, weighs, and sticks respective labels.
By the mPEG-b-PCL (M of gainedmPEG:MPCL=1:6) sample is fitted into general 3 microns in nuclear magnetic tube, with syringe plus
Enter appropriate deuterochloroform, nuclear magnetic tube is clogged with stopper.MPEG-b-PCL (M are marked with marking penmPEG:MPCL=1:6).
Carry out nuclear magnetic resonance.Fig. 4 is mPEG-b-PCL (MmPEG:MPCL=1:6) diblock copolymer1H NMR spectras.
mPEG-b-PCL(1:6)
1H NMR(400MHz,DMSO-d6) δ 3.98 (t, J=6.5Hz, 2H), 3.51 (s, 10H), 2.33-2.23 (m, 3H),
(m, the 1H) of 1.52 (dh, J=14.0,7.2Hz, 5H), 1.28 (dq, J=13.4,7.5,6.8Hz, 2H), 0.89-0.79
Nmr analysis result shows that synthetic product is the mPEG-b-PCL (M of targetmPEG:MPCL=1:6) diblock polymer.
Fig. 2-4 is contrasted with Fig. 1 respectively, peak position is gone out in nuclear magnetic spectrum and magnetic integration is all consistent with Fig. 1, illustrates embodiment
Three kinds of different polycaprolactone content ratio (M of 1-3 synthesisMPEG:MPCL=1:1, MMPEG:MPCL=1:4, MMPEG:
MPCL=1:6) PEG-PCL di-block copolymer is all the set goal product, and product is pure very high,
It is consistent with expected synthesis purpose.
Test example 1
The cell experiment of mPEG-b-PCL diblock copolymers
The human breast carcinoma cell lines MCF-7 of 1.ATCC purchases is washed once after being melted with 37 DEG C of water-baths rapidly with DMEM culture mediums,
1200rpm is centrifuged 3min, abandons supernatant, adds fresh culture medium, and cell is dispelled into cell suspension, is transferred to added with new
In 37 DEG C, 5%CO in the culture dish of fresh culture medium2Cultivated in condition incubator.
2. by the 1 of Preparatory work of experiment:The mPEG-b-PCL materials of 1 ratio are with being configured to 0.1mg/mL, 1mg/mL and 10mg/mL
Three solution of concentration, (compound method:MPEG-b-PCL (M are accurately weighed using assay balancemPEG:MPCL=1:1) sample
Product 10mg, adds the sample cell of 1.5mL, and deionized water is drawn using imbibition rifle, instills sample cell, is settled to 1mL scales
Line, ultrasound is carried out about 20 minutes by this sample cell, is then heated under 40 DEG C of water bath conditions about 5 minutes, and sample is complete
Dissolving, that is, obtain C1=10mg/mL mPEG-b-PCL (MmPEG:MPCL=1:1) sample solution;C is drawn using imbibition rifle1=10
mg/mL mPEG-b-PCL(MmPEG:MPCL=1:1) sample solution 0.1mL, adds another an equal amount of sample cell,
Imbibition rifle draws deionized water, is settled to 1mL graduation marks, that is, obtain C2=1mg/mL mPEG-b-PCL (MmPEG:MPCL=
1:1) sample solution;C is drawn using imbibition rifle2=1mg/mL mPEG-b-PCL (MmPEG:MPCL=1:1) sample solution
0.1mL, adds another an equal amount of sample cell, imbibition rifle to draw deionized water, be settled to 1mL graduation marks, that is, obtain
C3=0.1mg/mL mPEG-b-PCL (MmPEG:MPCL=1:1) sample solution.Then the solution of 3 concentration is pressed respectively
50 μ L/ holes are added in 96 orifice plates, and each concentration sets 3 multiple holes.Physiological saline is used respectively per hole after solution volatilizees naturally
100 μ L are washed 3 times, are dried naturally again standby.
3. cell is long sucks old culture medium when ware bottom is paved with, and with 2mL PBS drip wash once, adds the pancreas eggs of 2mL 0.25%
White enzyme is digested, and treats that cell loses original form and becomes bowlder addition complete medium termination digestion, collects cell, 1200rpm
Centrifugation 3min, abandons supernatant, and cell into single cell suspension is blown and beaten with new culture medium, and adjustment cell is counted by blood cell counting plate
Concentration is 105Individual/mL, is inoculated on 96 orifice plates by 100 μ L/ hole densities, and continuation is cultivated in incubator, every 24h aobvious
Micro- Microscopic observation is simultaneously taken pictures.
Propagation coefficient S=W of the cell on culture mediumcs-Wcc(Wcs:Represent the surface energy between cell and culture medium, Wcc:Represent
Surface energy between cell and cell).Work as Wcs<Wcc(S<0) when, cell tends to coherent condition;Work as Wcs>Wcc(S>0)
When, cell tends to coherent condition.The surface between cell and cell can be reduced in vivo, will depart from cancer cell original
Tumour, which results in transfer and the diffusion of cancer cell.Although the surface between cancer cell and cancer cell can be very big, cancer is thin
The cytoactive of born of the same parents' aggregate surface is very strong, and cause allows them to depart from original tumour, so as to cause the transfer of cancer cell and expand
Dissipate.Three kinds of copolymer solutions of concentration are tested with human breast carcinoma cell lines MCF-7, are clapped once every 24 hours, and 4 are clapped altogether
It is secondary, take pictures result as illustrated in figs. 5-7.Wherein, it is 10mg/mL (Fig. 5), 1mg/mL (figures that Fig. 5-7 corresponds respectively to concentration
6), the mPEG-b-PCL (M of 0.1mg/mL (Fig. 7)mPEG:MPCL=1:1) block copolymer is in MCF-7
Microphoto record on MCF-7 culture mediums in continuous culture a period of time.
From Fig. 5-7, the influence approximate trend of three kinds of various concentrations sample solutions to human breast carcinoma cell lines MCF-7 is:The
One day, there is not aggregation in cell, and cell is gradually assembled within second day, and cell aggregation in the 3rd day reaches maximum, the 4th day cell
Start apoptosis.Show three kinds of block polymers of various concentrations, cell can be effectively suppressed within initial a period of time
Adhesion.But, various concentration have certain difference, C again2The effect of=1mg/mL sample solutions is most preferable, C1=10mg/mL,
C3The effect of the sample solution of=0.1mg/mL is not ideal.The corresponding cell of sample solution of three kinds of concentration all occurred at the 4th day
Apoptosis, reason is exactly that the nutritional ingredient of culture dish was consumed at the 4th day and is over, and cell then starts without nutrition continued growth
Apoptosis.
Result shows that self assembly mPEG-b-PCL prepared by the present invention can effectively suppress the adhesion of cancer cell, accordingly
MPEG-b-PCL micellas are novel, reliable, safety, can be as the carrier for being insoluble in water medicine, and in cancer
Good carrier function and auxiliary therapeutic action is played in target medicine carrier, with huge clinical value.
Claims (6)
1. a kind of diblock polymer of polyethylene glycol crosslinked polycaprolactone, its composition structure is mPEG-b-PCL, and wherein mPEG and PCL molar ratios are 1:0.1~1:10.
2. the diblock polymer of polyethylene glycol crosslinked polycaprolactone as claimed in claim 1, it is characterised in that mPEG and PCL mass ratios are 1:1~1:6.
3. a kind of method for preparing described diblock polymer, comprises the following steps:
(1)Taking polyethylene glycol, is dissolved in toluene, is dehydrated 1-3 hours at 120-150 DEG C;
(2)ε-hexamethylene lactone and stannous octoate, nitrogen is added to protect, 130-160 DEG C is reacted 8-16 hours;
(3)After reaction terminates, room temperature is cooled to, addition methyl tertiary butyl ether(MTBE) is ultrasonic 5-30 minutes, under ice bath, cooling recrystallization 10-30 minutes, suction filtration collects filter residue, and vacuum drying both obtains target product.
4. application of the diblock polymer of above-mentioned polyethylene glycol crosslinked polycaprolactone in treating cancer or tumour medicine is prepared.
5. application process as claimed in claim 5, it is characterised in that application of the diblock polymer of polyethylene glycol crosslinked polycaprolactone in treatment breast cancer medicines are prepared.
6. application process as claimed in claim 5, it is characterised in that application of the diblock polymer of described polyethylene glycol crosslinked polycaprolactone as medicine carrying material in the medicine for the treatment of cancer or tumour.
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CN113135983A (en) * | 2021-04-12 | 2021-07-20 | 四川大学华西医院 | Antitumor compound and preparation method thereof |
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CN102670525A (en) * | 2012-05-07 | 2012-09-19 | 李晓林 | Application of ursolic-acid nano medicine-carrying microspheres for treating tumors and preparation |
CN104784712A (en) * | 2014-12-29 | 2015-07-22 | 王巧英 | A preparing method of a nanometer polymer micelle carrier integrating diagnosis and treatment |
CN104857502A (en) * | 2015-04-15 | 2015-08-26 | 南昌大学第二附属医院 | Vascular endothelial growth factor loaded nano controlled-release compound and a 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 |
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CN102198083A (en) * | 2010-05-27 | 2011-09-28 | 四川大学 | Micelles and freeze-dried preparations of diblock polymer-supported taxane medicines and preparation and use thereof |
CN102670525A (en) * | 2012-05-07 | 2012-09-19 | 李晓林 | Application of ursolic-acid nano medicine-carrying microspheres for treating tumors and preparation |
CN104784712A (en) * | 2014-12-29 | 2015-07-22 | 王巧英 | A preparing method of a nanometer polymer micelle carrier integrating diagnosis and treatment |
CN104857502A (en) * | 2015-04-15 | 2015-08-26 | 南昌大学第二附属医院 | Vascular endothelial growth factor loaded nano controlled-release compound and a 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 |
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CN113135983A (en) * | 2021-04-12 | 2021-07-20 | 四川大学华西医院 | Antitumor compound and preparation method thereof |
CN113135983B (en) * | 2021-04-12 | 2022-06-24 | 四川大学华西医院 | Antitumor compound and preparation method thereof |
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