Summary of the invention
The objective of the invention is to overcome deficiency of the prior art, a kind of crystallinity that can reduce PCL is provided, accelerate the degradation rate and TPGS-b-(PCL-ran-PGA) multipolymer that improves its hydrophilicity of PCL.
Second purpose of the present invention provides the preparation method of a kind of TPGS-b-(PCL-ran-PGA) multipolymer.
The 3rd purpose of the present invention provides the purposes of a kind of TPGS-b-(PCL-ran-PGA) multipolymer.
Technical scheme of the present invention is summarized as follows:
TPGS-b-(PCL-ran-PGA) multipolymer has formula:
With
Wherein: n=20-140, caprolactone fragment (A+B+ ... )=2-490, NSC 403079 fragment (a+b+ ... )=2-900.
N=21-30 preferably, caprolactone fragment (A+B+ ... )=3-420, NSC 403079 fragment (a+b+ ... )=2-829.
The preparation method of TPGS-b-(PCL-ran-PGA) multipolymer; Comprise the steps: to get by mass percentage that the caprolactone monomer of 2%-95%, the glycolide monomer of 2%-95% and the polyethylene glycol 1000 vitamin E succinic acid ester of 3%-40% are that raw material is put into polymerization unit; Add the catalyzer of the 0.1%-1% of said raw materials quality, vacuumize, inflated with nitrogen; In airtight polymerization unit; 140-160 ℃ of reaction 12-20 hour, promptly obtain the TPGS-b-that molecular weight is 3600-51000 (PCL-ran-PGA) multipolymer bullion (I) and (II), wherein: n=20-90 caprolactone fragment (A+B+ ... )=2-490 NSC 403079 fragment (a+b+ ... )=2-900.
The preparation method of TPGS-b-(PCL-ran-PGA) multipolymer also comprises: TPGS-b-(PCL-ran-PGA) multipolymer bullion (I) and (II) are dissolved in methylene dichloride or the ETHYLE ACETATE; Add methyl alcohol or sherwood oil and make TPGS-b-(PCL-ran-PGA) multipolymer deposition; Filter; 30-50 ℃ of vacuum-drying be will be deposited in, the TPGS-b-that molecular weight is 3600-51000 (PCL-ran-PGA) multipolymer (I) and (II) promptly obtained.
The inferior tin of catalyzer preferably octanoic acid, organic guanidine, metallic zinc, tributyltin chloride, ferric acetyl acetonade, zinc lactate, nano zine oxide, taurine, ethanol iron, n-propyl alcohol iron, Virahol iron or propyl carbinol iron.
Vacuumize the number of times of inflated with nitrogen preferably 1-3 time.
Temperature of reaction is advisable with 145 ℃.
TPGS-b-(PCL-ran-PGA) multipolymer is as the application of pharmaceutical excipient.
Said medicine is antitumor drug preferably.
TPGS-b-of the present invention (PCL-ran-PGA) multipolymer has excellent biological compatibility, biodegradability.
Method preparation of the present invention is simple, pollution-free.
TPGS-b-of the present invention (PCL-ran-PGA) multipolymer is applied to pharmaceutical prepn (for example drug-carrying nanometer particle, gel and medicine carrying microballoons or the like) and field of tissue engineering technology (for example artificial organs, sutures and intravascular stent etc.).
TPGS-b-of the present invention (PCL-ran-PGA) multipolymer is applied to the pharmaceutical excipient of anti-tumor medicinal preparation especially.
Description of drawings
Fig. 1 is the chemical structural formula of TPGS.
Fig. 2 is the synthetic synoptic diagram of TPGS-b-(PCL-ran-PGA) multipolymer.
Fig. 3 is the Fourier transform infrared spectroscopy figure of TPGS-b-(PCL-ran-PGA) multipolymer and TPGS.
Fig. 4 is the nmr spectrum chart of TPGS-b-(PCL-ran-PGA) multipolymer and TPGS.
Fig. 5 is the gel chromatography figure of TPGS-b-(PCL-ran-PGA) multipolymer and TPGS.
Fig. 6 is the thermogravimetric analyzer characterization result of TPGS-b-(PCL-ran-PGA) multipolymer and Vitamin E TPGS.
Fig. 7 is the FESEM figure (A) and the TEM figure (B) of carrying docetaxel TPGS-b-(PCL-ran-PGA) nanoparticle.
Fig. 8 detects the particle diameter and the size distribution result of medicine carrying TPGS-b-(PCL-ran-PGA) nanoparticle for laser particle analyzer.
Fig. 9 measures the result of medicine carrying TPGS-b-(PCL-ran-PGA) nanoparticle for zeta potential instrument.
Figure 10 characterizes the result of Docetaxel crystal and carrying docetaxel PCL and TPGS-b-(PCL-ran-PGA) nanoparticle for DSC.
Figure 11 is for being that to prepare drug loading be 10% the carrying docetaxel PCL and the vitro drug release curve of TPGS-b-(PCL-ran-PGA) nanoparticle to emulsifying agent with 0.03%TPGS.
After Figure 12 .24 hour, carrying docetaxel TPGS-b-(PCL-ran-PGA) nanoparticle,
(identical Docetaxel dosage with drug-carrying nanometer particle) and blank TPGS-b-(PCL-ran-PGA) nanoparticle (the identical nanoparticle suspension concentration with drug-carrying nanometer particle) are to the cell viability experimental result of MCF-7 cell
After Figure 13 .48 hour, carrying docetaxel TPGS-b-(PCL-ran-PGA) nanoparticle,
(identical Docetaxel dosage with drug-carrying nanometer particle) and blank TPGS-b-(PCL-ran-PGA) nanoparticle (the identical nanoparticle suspension concentration with drug-carrying nanometer particle) are to the cell viability experimental result of MCF-7 cell
After Figure 14 .72 hour, carrying docetaxel TPGS-b-(PCL-ran-PGA) nanoparticle,
(identical Docetaxel dosage with drug-carrying nanometer particle) and blank TPGS-b-(PCL-ran-PGA) nanoparticle (the identical nanoparticle suspension concentration with drug-carrying nanometer particle) are to the cell viability experimental result of MCF-7 cell
Figure 15. the laser confocal scanning electron microscope observation is with the MCF-7 cell that tonka bean camphor-6 nanoparticle was hatched under 37 ℃ 4 hours that carries of TPGS-b-(PCL-ran-PGA) copolymer material preparation.Nucleus is dyed redness with PI, and it is green carrying tonka bean camphor-6 nano particle, and respectively through EGFP passage and PI passage observation of cell picked-up situation: figure A is the situation of observing through the EGFP passage; Figure B is the situation of observing through the white light passage; Figure C is the situation of observing through the PI passage; Figure D is through the EGFP passage with through the result after the doubling of the image of PI passage observation.
Figure 16. carry ESEM (SEM) figure of taxol TPGS-b-(PCL-ran-PGA) microballoon.
Embodiment
Below in conjunction with specific embodiment the present invention is further described.
Embodiment 1
The preparation method of TPGS-b-(PCL-ran-PGA) multipolymer comprises the steps:
By the quality percentage composition get 95% ε caprolactone monomer, 2% glycolide monomer and 3% polyethylene glycol 1000 vitamin E succinic acid ester is raw material; Put into polymerizing pipe; Add the acetic acid tetramethyl-dibutyl guanidine of raw materials quality 0.5%, vacuumize inflated with nitrogen; The polymerizing pipe tube sealing; 145 ℃ of heating, reacted 16 hours, promptly obtain molecular weight and be 46000 TPGS-b-(PCL-ran-PGA) multipolymer (I) and (II) wherein: n=21 caprolactone fragment (A+B+ ... )=379 NSC 403079 fragment (a+b+ ... )=23.Shown in Figure 2 is the building-up reactions formula of TPGS-b-(PCL-ran-PGA) multipolymer.TPGS is as initiator.
Fig. 3 is the Fourier transform infrared spectroscopy figure of TPGS-b-(PCL-ran-PGA) multipolymer and TPGS.The carbonyl peak of TPGS is at 1739cm
-1The place, and the carbonyl peak of TPGS moves to 1736cm in TPGS-b-(PCL-ran-PGA) multipolymer
-1About.The hydrocarbon stretching vibration peak of the methylene radical of TPGS, PCL and PGA overlaps and concentrates on 2867-2949cm
-1The place.3400-3650cm
-1The place is the peak of multipolymer terminal hydroxy group, 1045-1295cm
-1The place is carbon oxygen stretching vibration peak, wherein 1105-1242cm
-1The place is respectively among the TPGS-OCH
2CH
2The carbon oxygen stretching vibration peak of repeating unit and GA and CL.1295cm
-1The peak at place is commonly used to study the change of crystal property among the PCL.Fourier transform infrared analytical results explanation TPGS-b-(PCL-ran-PGA) multipolymer synthesizes successfully.
Embodiment 2
The preparation method of TPGS-b-(PCL-ran-PGA) multipolymer comprises the steps:
By the quality percentage composition get 58% ε caprolactone monomer, 2% glycolide monomer and 40% polyethylene glycol 1000 vitamin E succinic acid ester is that raw material is put into polymerizing pipe; Add 1% zinc powder of said raw materials quality, vacuumize inflated with nitrogen; The polymerizing pipe tube sealing; 145 ℃ of heating, reacted 12 hours, promptly obtain molecular weight and be 4200 TPGS-b-(PCL-ran-PGA) multipolymer (I) and (II).
TPGS-b-(PCL-ran-PGA) multipolymer bullion (I) and (II) are dissolved in the methylene dichloride; Add methyl alcohol and make TPGS-b-(PCL-ran-PGA) multipolymer deposition; Filter; To be deposited in 50 ℃ of vacuum-dryings, promptly obtain molecular weight and be 4200 TPGS-b-(PCL-ran-PGA) multipolymer (I) and (II), wherein: n=23 caprolactone fragment (A+B+ ... )=21 NSC 403079 fragment (a+b+ ... )=2.
Embodiment 3
The preparation method of TPGS-b-(PCL-ran-PGA) multipolymer comprises the steps:
By the quality percentage composition get 95% ε caprolactone monomer, 2% glycolide monomer and 3% polyethylene glycol 1000 vitamin E succinic acid ester is that raw material is put into polymerizing pipe; Add the ethanol iron of said raw materials quality 0.2%, vacuumize inflated with nitrogen; In airtight polymerization unit; 150 ℃ of heating, reacted 12 hours, promptly obtain molecular weight and be 51000 TPGS-b-(PCL-ran-PGA) multipolymer (I) and (II).
TPGS-b-(PCL-ran-PGA) multipolymer bullion (I) and (II) are dissolved in the ETHYLE ACETATE; Add sherwood oil and make TPGS-b-(PCL-ran-PGA) multipolymer deposition; Filter; To be deposited in 30 ℃ of vacuum-dryings, promptly obtain molecular weight and be 51000 TPGS-b-(PCL-ran-PGA) multipolymer (I) and (II), wherein: n=23 caprolactone fragment (A+B+ ... )=420 NSC 403079 fragment (a+b+ ... )=26.
Embodiment 4
The preparation method of TPGS-b-(PCL-ran-PGA) multipolymer comprises the steps:
(ε-Caprolactone), 1.5g glycolide monomer (Glycolide), 1g Vitamin ETPGS are raw material accurately to take by weighing the 7.5g caprolactone monomer; The inferior tin catalyst of octoate catalyst of getting raw materials quality 0.1% adds in the polymerizing pipe; Carry out vacuumize degassing and nitrogen replacement process; Triplicate seals polymerizing pipe, under 145 ℃ of oil bath heating, carries out ring-opening polymerization.After the polyreaction 16 hours, product is dissolved in the methylene dichloride through cooling, and the adding excessive methanol makes the multipolymer deposition.Remove by filter unreacted monomer of methyl alcohol and Vitamin E TPGS.Gained is deposited in 45 ℃ of vacuum-dryings promptly got polymerisate TPGS-b-(PCL-ran-PGA) multipolymer in 48 hours.Fourier transform infrared spectroscopy, proton nmr spectra, gel chromatography and thermogravimetric analysis result prove that TPGS-b-(PCL-ran-PGA) multipolymer synthesizes successfully.Can calculate each components contents and number-average molecular weight thereof in TPGS-b-(PCL-ran-PGA) multipolymer through proton nmr spectra.Fig. 4 is the nmr spectrum chart of TPGS-b-(PCL-ran-PGA) multipolymer and TPGS.3.65ppm (c peak) is in the TPGS polyoxyethylene glycol-CH
2The peak, this is the characteristic peak of TPGS.Chemical displacement value belongs to the proton under the different chemical environment in the vitamin E molecule respectively than the several little short peak of lower region.5.2ppm these two peaks of (a peak) and 1.69ppm (e peak) are respectively PLA-CH and-CH
3Proton peak.4.06ppm (c peak), 2.31-2.44ppm (f peak), 1.67ppm (g peak) and 1.39ppm (h peak) are in the polycaprolactone (PCL)-OCH
2,-COCH
2,-CH
2(4H) ,-CH
2(2H) characteristic peak of proton.4.06 (c) and the difference at 4.16ppm (b) peak show two kinds of multipolymers and synthesize successfully.4.62-4.82ppm (a peak) belongs among the PGA-CH
2The characteristic peak of proton.The proton nmr spectra analytical results also explains that TPGS-b-(PCL-ran-PGA) multipolymer synthesizes successfully.As shown in Figure 4; The peak area ratio of the characteristic peak 3.65ppm (c peak) of characteristic peak 4.62-4.82ppm (a peak) through PGA in TPGS-b-(PCL-ran-PGA) multipolymer, the characteristic peak 4.06ppm (b peak) of PCL and TPGS can calculate that contained each components in proportions is respectively 24.5% (PGA), 68.9% (PCL) and 6.6% (TPGS) in TPGS-b-(PCL-ran-PGA) multipolymer; Be 23,852 according to the molecular weight of TPGS 1513 and the number-average molecular weight that in TPGS-b-(PCL-ran-PGA) multipolymer, can calculate TPGS-b-(PCL-ran-PGA) multipolymer again with the molar ratio of glycolide monomer, caprolactone monomer.Fig. 5 is the gel chromatography figure of TPGS-b-(PCL-ran-PGA) multipolymer and TPGS.As can be seen from the figure, reaction product is not the physical mixture of glycolide monomer, caprolactone monomer and TPGS, but TPGS-b-(PCL-ran-PGA) multipolymer.Wherein, the appearance time of TPGS is 28.2min, and TPGS-b-(PCL-ran-PGA) multipolymer appearance time be 17.5min.Detect peak among the GPC result of TPGS-b-(PCL-ran-PGA) multipolymer less than TPGS, and only occur one narrow unimodal.The number-average molecular weight that calculates TPGS-b-(PCL-ran-PGA) multipolymer through gel permeation chromatography figure is 25811, matches with the result who is calculated by nmr spectrum (23852).Fig. 6 is the thermogravimetric analyzer characterization result of TPGS-b-(PCL-ran-PGA) multipolymer and TPGS.What thermogravimetric analyzer detected is with variation of temperature, and composition causes the situation of weight change in the sample because of evaporation cracking etc.As can be seen from the figure; TPGS only has a flex point at 380-450 ℃; And the figure of TPGS-b-(PCL-ran-PGA) has three flex points; A composition in each flex point representation polymer is weightless because of heating, and the 150-350 ℃ of weightless peak with 350-450 ℃ is respectively partly to be caused by PCL-PGA in the polymkeric substance and TPGS, and wherein the weightless temperature of PGA and PCL overlaps to some extent.The thermogravimetric analysis detected result proves that further TPGS-b-(PCL-ran-PGA) (I) and (II) multipolymer synthesize successfully.
Wherein: n=23 caprolactone fragment (A+B+ ... )=144 NSC 403079 fragment (a+b+ ... )=109)
Embodiment 5
The preparation method of TPGS-b-(PCL-ran-PGA) multipolymer comprises the steps:
Getting 2% ε caprolactone monomer, 58% glycolide monomer and 40% polyethylene glycol 1000 vitamin E succinic acid ester by the quality percentage composition is that raw material is put into polymerization unit; Add 0.5% catalyzer tributyltin chloride of said raw materials quality, vacuumize inflated with nitrogen; Vacuumize again; Inflated with nitrogen is in airtight polymerization unit, 140 ℃ of reactions 20 hours; Promptly obtain molecular weight and be 3600 TPGS-b-(PCL-ran-PGA) multipolymer bullion (I) and (II) wherein: n=23, caprolactone fragment (A+B+ ... )=3 NSC 403079 fragment (a+b+ ... )=36.
Embodiment 6
The preparation method of TPGS-b-(PCL-ran-PGA) multipolymer comprises the steps:
Getting 2% ε caprolactone monomer, 95% glycolide monomer and 3% polyethylene glycol 1000 vitamin E succinic acid ester by the quality percentage composition is that raw material is put into polymerization unit, adds 0.1% catalyzer ferric acetyl acetonade of said raw materials quality, vacuumizes; Inflated with nitrogen; Vacuumize, inflated with nitrogen is in airtight polymerization unit again; 160 ℃ of reactions 12 hours; Promptly obtain molecular weight and be 50600 TPGS-b-(PCL-ran-PGA) multipolymer bullion (I) and (II), wherein: n=30, caprolactone fragment (A+B+ ... )=8 NSC 403079 fragment (a+b+ ... )=829.
The catalyzer of present embodiment can also adopt zinc lactate, nano zine oxide, taurine, n-propyl alcohol iron, Virahol iron or propyl carbinol iron to carry out catalyzed reaction.
Embodiment 7
Molecular weight is TPGS-b-(PCL-ran-PGA) multipolymer (I) and (II) application in the preparation pharmaceutical excipient of 3600-51000.
Utilize ultrasonic emulsification/solvent evaporation method to prepare carrying docetaxel (Docetaxel) TPGS-b-(PCL-ran-PGA) nanoparticle.The preparation method is following: accurately take by weighing 100mg TPGS-b-(PCL-ran-PGA) multipolymer and a certain amount of Docetaxel medicine of embodiment 4 preparations, be dissolved in the 8ml methylene dichloride.Under agitation condition, this solution is joined in the 0.03%TPGS aqueous solution of 120ml.Under condition of ice bath, disperse 120s with the 25w power ultrasonic, form emulsion oil-in-water, organic solvent is removed in the decompression volatilization.The centrifugal 20min of 23000rpm is with deionized water wash three times, to remove de-emulsifier and free medicine.The gained deposition is resuspended in the 10m deionized water, and lyophilize gets carrying docetaxel TPGS-b-(PCL-ran-PGA) nanoparticle product.ESEM result and transmission electron microscope show (Fig. 7), and the nanoparticle size is than homogeneous, smooth in appearance, and spherical in shape, particle diameter is greatly about about 250nm.As shown in Figure 8, the nanoparticle narrower particle size distribution, particle diameter about about 200nm, has further confirmed the observations of ESEM greatly.As shown in Figure 9, the Zeta potential of nanoparticle is about-20mV, and the absolute value of surface charge is than higher, and repulsive interaction is stronger between the particle, thereby stable at the disperse phase camber.As shown in table 1, using 0.03%TPGS to prepare drug loading as emulsifying agent is 10% polyene-containing taxol nanoparticle, and encapsulation rate is reached more than 90%.Shown in figure 10; Docetaxel crystalline endotherm(ic)peak is at 173 ℃; And carrying docetaxel PCL and TPGS-b-(PCL-ran-PGA) nanoparticle is not all seen Docetaxel crystalline endotherm(ic)peak, explains that Docetaxel is wrapped in the nanoparticle, and its endotherm(ic)peak has disappeared.Shown in figure 11, carrying docetaxel PCL has similar release profiles with TPGS-b-(PCL-ran-PGA) nanoparticle, is two phase release characteristics and follows initial " burst effect ".Like Figure 12, shown in 13 and 14, blank TPGS-b-(PCL-ran-PGA) nanoparticle of medicine carrying does not have excellent biological compatibility, because its pair cell does not all have tangible toxicity under different nanoparticle suspension concentration; Behind 48h and 72h, carrying docetaxel TPGS-b-(PCL-ran-PGA) nanoparticle is more much bigger to the toxicity of MCF-7 cell under the drug level same case than commercial Docetaxel preparation
; Along with incubation time increases, the cell survival rate after drug-carrying nanometer particle is handled with
all obviously descends.For example; Under the drug level of 12.5mg/l; Using the cell survival rate of medicament-carried nano particle disposal behind the 24h is 71.22%; Cell survival rate under
the same terms is 78.34%, that is to say the cytotoxicity of medicament-carried nano particulate cytotoxicity than
low 32.92% behind the 24h.Under same medicine concentration, the cytotoxicity high 66.57% and 108.21% of cytotoxicity of handling with drug-carrying nanometer particle behind 48h and the 72h than
.MTT experimental result explanation carrying docetaxel TPGS-b-(PCL-ran-PGA) nanoparticle has time and concentration dependent to the toxicity of MCF-7 cell.
Table 1. prepares in the polyene-containing taxol nanoparticle process with TPGS-b-(PCL-ran-PGA) copolymer material, and drug loading and emulsifying agent are to the influence of nanoparticle encapsulation rate
Embodiment 8
Utilize ultrasonic emulsification/solvent evaporation method preparation to carry TPGS-b-(PCL-ran-PGA) nanoparticle of tonka bean camphor-6.The preparation method is following: accurately take by weighing TPGS-b-(PCL-ran-PGA) multipolymer of 100mg embodiment 4 preparations and the tonka bean camphor-6 of 12mg, be dissolved in the 8ml methylene dichloride.Under agitation condition, this solution is joined in the 0.03%TPGS aqueous solution of 120ml.Under condition of ice bath, disperse 120s with the 25w power ultrasonic, form emulsion oil-in-water, organic solvent is removed in the decompression volatilization.The centrifugal 20min of 23000rpm is with deionized water wash three times, to remove de-emulsifier and free tonka bean camphor-6.The gained deposition is resuspended in the 10m deionized water, and lyophilize must be carried TPGS-b-(PCL-ran-PGA) the nanoparticle product of tonka bean camphor-6.The nanoparticle particle diameter is about 250 nanometers.Utilize the nuclear staining of PI pair cell, can in the cellular uptake experiment, confirm to carry the position of tonka bean camphor-6 nanoparticle in cell through the location of pair cell nuclear.Figure 15 is to the picked-up result of carrying tonka bean camphor-6 nano particle by TPGS-b-(PCL-ran-PGA) preparation with laser confocal scanning electron microscope observation MCF-7 cell.As can be seen from the figure, only after hatching 2 hours with cell, nanoparticle is just absorbed by cell.Merge the figure D that obtains from figure A, figure B with figure C and can know to such an extent that see, greeny nanoparticle great majority are arranged in tenuigenin, tightly surround the nucleus that takes on a red color.
The experiment proof utilizes ultrasonic emulsification/solvent evaporation method to utilize TPGS-b-(PCL-ran-PGA) multipolymer of embodiment 1,2,3,5 or 6 preparations and tonka bean camphor-6 can prepare corresponding TPGS-b-(PCL-ran-PGA) nanoparticle that carries tonka bean camphor-6 for raw material.
Embodiment 8
Utilize the solvent evaporation method preparation to carry taxol (Paclitaxel) TPGS-b-(PCL-ran-PGA) microballoon.The preparation method is following: accurately take by weighing TPGS-b-(PCL-ran-PGA) multipolymer of 200mg embodiment 4 preparations and the taxol powder of 50mg, be dissolved in the 16ml methylene dichloride.Under agitation condition, this solution is joined in 1% polyvinyl alcohol water solution of 500ml.The 1000rpm rotating speed stirred two hours down, formed emulsion oil-in-water, and 800rpm rotating speed volatilization down spends the night.The centrifugal 15min of 2000rpm is with deionized water wash three times, to remove de-emulsifier and free medicine.The gained deposition is resuspended in the 10m deionized water, and lyophilize must be carried taxol TPGS-b-(PCL-ran-PGA) microball prepn.Shown in figure 16, carry taxol TPGS-b-(PCL-ran-PGA) microsphere features smooth surface, particle diameter is about 15 microns.The drug loading of taxol TPGS-b-(PCL-ran-PGA) microballoon is 20%, and encapsulation rate is more than 80%.
It is raw material with TPGS-b-(PCL-ran-PGA) multipolymer and the taxol of embodiment 1,2,3,5 or 6 preparations that the experiment proof is utilized solvent evaporation method, also can prepare corresponding taxol (Paclitaxel) TPGS-b-(PCL-ran-PGA) microballoon that carries.
The experiment proof can also be prepared by method of the present invention:
N=20, caprolactone fragment (A+B+ ... )=490, NSC 403079 fragment (a+b+ ... The TPGS-b-of)=23 (PCL-ran-PGA) multipolymer (I) and (II); And, prepare corresponding taxol (Paclitaxel) TPGS-b-(PCL-ran-PGA) microballoon that carries through experiment showed, that this multipolymer (I) and (II) can be raw material with taxol.The experiment proof can also be prepared by method of the present invention:
N=23, caprolactone fragment (A+B+ ... )=2, NSC 403079 fragment (a+b+ ... The TPGS-b-of)=900 (PCL-ran-PGA) multipolymer (I) and (II); And, prepare corresponding taxol (Paclitaxel) TPGS-b-(PCL-ran-PGA) microballoon that carries through experiment showed, that this multipolymer (I) and (II) can be raw material with taxol.
The experiment proof can also be prepared by method of the present invention:
Or n=140, caprolactone fragment (A+B+ ... )=50, NSC 403079 fragment (a+b+ ... The TPGS-b-of)=2 (PCL-ran-PGA) multipolymer (I) and (II).And, prepare corresponding taxol (Paclitaxel) TPGS-b-(PCL-ran-PGA) microballoon that carries through experiment showed, that this multipolymer (I) and (II) can be raw material with taxol.
It is raw material that the present invention adopts tonka bean camphor-6 and taxol, is to be used to explain the present invention, is not used for limiting the present invention.All can prepare corresponding medicine carrying TPGS-b-(PCL-ran-PGA) microballoon with the medicine of their similar performances.