CN106800641B - A kind of mPEG-b-PCL diblock polymer polymer and its application and preparation - Google Patents
A kind of mPEG-b-PCL diblock polymer polymer and its application and preparation Download PDFInfo
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- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
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- A—HUMAN NECESSITIES
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- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/74—Synthetic polymeric materials
- A61K31/765—Polymers containing oxygen
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
- A61K47/30—Macromolecular organic or inorganic compounds, e.g. inorganic polyphosphates
- A61K47/34—Macromolecular compounds obtained otherwise than by reactions only involving carbon-to-carbon unsaturated bonds, e.g. polyesters, polyamino acids, polysiloxanes, polyphosphazines, copolymers of polyalkylene glycol or poloxamers
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- C—CHEMISTRY; METALLURGY
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- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/02—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from cyclic ethers by opening of the heterocyclic ring
- C08G65/32—Polymers modified by chemical after-treatment
- C08G65/329—Polymers modified by chemical after-treatment with organic compounds
- C08G65/331—Polymers modified by chemical after-treatment with organic compounds containing oxygen
- C08G65/332—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof
- C08G65/3322—Polymers modified by chemical after-treatment with organic compounds containing oxygen containing carboxyl groups, or halides, or esters thereof acyclic
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- C—CHEMISTRY; METALLURGY
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- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G65/00—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule
- C08G65/34—Macromolecular compounds obtained by reactions forming an ether link in the main chain of the macromolecule from hydroxy compounds or their metallic derivatives
- C08G65/48—Polymers modified by chemical after-treatment
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 ratio is 1:0.1 ~ 1:10.The diblock polymer of polyethylene glycol crosslinked polycaprolactone of the invention have good load medicine potentiality, can carrying medicament steady running realizes the dispersion application of insoluble drug to the target spot of target in vivo.Moreover, the diblock polymer generates Adhesion inhibiyive effect for human body tumour cell or cancer cell, so that the chemotherapeutic treatment effect of tumor patient, cancer patient is obviously improved.
Description
Technical field
The present invention relates to a kind of diblock polymers of polyethylene glycol crosslinked polycaprolactone, in particular to polyethylene glycol crosslinked
The preparation and its application of the diblock polymer of polycaprolactone.
Background technique
Poorly water soluble drugs are because the small clinical application for making drug of solubility is restricted in water for it.By slightly water-soluble medicine
Object is wrapped up by certain carriers, is a kind of effective method that poorly water soluble drugs are carried out with solubilising.
Size, stability, versatility and the biocompatibility of amphiphatic molecule copolymer are all very outstanding, this makes it
There are very huge potentiality in drug delivery carrier and field of environment protection.In numerous amphoteric polymers, especially with
Copolymer with biocompatibility and biological degradability, such as PLA-PEG, PCL-PEG, PCL-PLA-PEG, performance is the most prominent
With it is noticeable.
It is well known that the copolymer of amphiphatic molecule can be self-assembly of a hydrophobic core and parent in the solvent of selectivity
The micelle of water hull, such micelle size are usually less than 200nm, the characteristic with part nano material.Amphiphilic diblock is high
The characteristics of Molecularly Imprinted Polymer, makes micelle not have additional stabilization agent condition when outside hydrophilic shell reaches maximum biological solubility
Under in hydrophilic solvent keep dissolution when, hydrophobic nuclear interaction, to load some drugs for being insoluble in water.
As the carrier of dewatering medicament, the colloid of diblock polymer is widely studied.Currently, research micelle paper and money
Material focuses mainly on the effect between preparation, characterization, drug and the carrier of polymer and the release feature of drug.In fact,
It is still very limited for being copolymerized the research of the degradation of micelle so far.
Some researches show that the hydrolytic degradation extremely different with that can show under vitro is special in vivo for PCL-PEG film
Property, and show PCL-PEG film hydrolytic degradation process, it may be by PEG molecule content, environment temperature, acidity and basicity
It influences.Research finds that the degradation mode of PCL-PEG micelle and the degradation mode of discrete material are different, and may have various aspects
Potential value.
Summary of the invention
It is existing it is an object of the invention to be directed to be not enough about the research of diblock polymer in the prior art
The potential value exploitation of diblock polymer not exclusively, provides a kind of novel mPEG-b-PCL diblock polymer polymer.
Meanwhile the present invention provides the method for preparing this diblock polymer compound, and to this diblock polymer compound
Property has carried out characterization research, discloses the potential medical value of this high-molecular compound.
In order to achieve the above-mentioned object of the invention, the present invention provides following technical schemes:
The diblock polymer of polyethylene glycol crosslinked polycaprolactone inhibits the coherent condition of tumour cell in preparation, promotes to swell
Oncocyte keeps building up state, the application in anti-tumor drug for preventing tumour cell from spreading, which is characterized in that
MPEG and PCL mass ratio is 1:1~1:6 in the diblock polymer of the polyethylene glycol crosslinked polycaprolactone.
The diblock polymer of polyethylene glycol crosslinked polycaprolactone of the invention has good load medicine potentiality, can load
Steady running realizes the dispersion application of insoluble drug to the target spot of target to drug in vivo.Moreover, the diblock polymerize
Object generates coherent condition inhibiting effect for human body tumour cell or cancer cell, so that the chemotherapy of tumor patient, cancer patient is controlled
Therapeutic effect is obviously improved.
Ester bond in polycaprolactone occurs for PEG-b-PCL diblock copolymer hydrolysis of the present invention, so that the molecule of compound
Biggish variation has occurred in amount distribution, crystallinity etc..In the degradation process of PEG-b-PCL diblock copolymer, polymer
The hydrolytic cleavage mechanism of molecule segment is totally different from general polyethylene glycol compound, so that the stability of compound, load medicine
Ability has great promotion.
Further, preferably mPEG and PCL mass ratio is 1:1~1:6.When the ratio of the two meets range above, two
Block polymer can show the stability for being more suitable for, degradation property, so that the stability of drug and rate of release are more preferably,
Preferably promote the curative effect of drug.When the ratio of the two is 1:1, diblock polymer has the state of aggregation of cell good
Facilitation, simultaneously for tumour cell, cancer cell coherent condition have certain inhibiting effect, can be improved chemotherapy
Effect.
Further, the diblock polymer of the polyethylene glycol crosslinked polycaprolactone is in preparation treatment breast cancer medicines
Application.Gather researches show that diblock polymer of the invention can play good promotion for breast cancer cell line MCF-7
Collection effect.
Further, the diblock polymer of the polyethylene glycol crosslinked polycaprolactone is as medicine carrying material in treatment tumour
Drug in application.
The present invention also provides a kind of method for preparing the diblock polymer simultaneously, comprising the following steps:
(1) taking polyethylene glycol is dissolved in toluene, is dehydrated at 120-150 DEG C 1-3 hours, is preferably dehydrated at 125-145 DEG C
1.5-3 hour.
(2) be added ε-hexamethylene lactone and stannous octoate, nitrogen protection, 130-160 DEG C reaction 8-16 hours.Preferably, exist
135-155 DEG C reaction 8-15 hours.
(3) after reaction, it is cooled to room temperature, methyl tertiary butyl ether(MTBE) is added, it is 5-30 minutes ultrasonic, under ice bath, cooling weight
Crystallization 10-30 minutes filters, and collects filter residue, and vacuum drying both obtains target product.
It is target product of the invention by the diblock polymer that above method synthesizes, there is good stabilization
Property and crystal property, can be effectively applied to the load medicine of insoluble drug.Moreover, method made above is simple and easy, reaction
High-efficient, substantially free of impurities generates, the easily separated easy purification of product.
The diblock polymer of above-mentioned polyethylene glycol crosslinked polycaprolactone is in preparation treating cancer or tumour medicine
Using.The diblock polymer of polyethylene glycol crosslinked polycaprolactone of the invention can effectively inhibit cancer cell, tumour cell
Coherent condition, so that it is kept building up state, prevent the diffusion of cancer cell or tumour cell, improve therapeutic agent for related disease
The therapeutic effect of disease.
Further, the High Purity Nitrogen that the nitrogen gas purity that the nitrogen protection uses is 99.99% or more.
Compared with prior art, beneficial effects of the present invention:
1. the diblock polymer of polyethylene glycol crosslinked polycaprolactone of the invention can effectively be realized for slightly solubility
Load, the transhipment of drug, and ensure the dispersion of insoluble drug.
2. diblock polymer of the invention generates coherent condition inhibiting effect for human body tumour cell or cancer cell, make
Obtain tumor patient, the chemotherapeutic treatment effect of cancer patient is obviously improved.
3. provided by the invention, preparation method is simple, and reaction efficiency is high, and substantially free of impurities generates, and product is easily separated easily
Purifying, can promote and apply and various pharmaceutical preparations.
Detailed description of the invention:
Fig. 1 is the 1HNMR spectrogram of mPEG-b-PCL diblock copolymer.
Fig. 2 is the 1H NMR spectra of mPEG-b-PCL (MmPEG:MPCL=1:1) diblock copolymer.
Fig. 3 is the 1H NMR spectra of mPEG-b-PCL (MmPEG:MPCL=1:4) diblock copolymer.
Fig. 4 is the 1H NMR spectra of mPEG-b-PCL (MMPEG:MPCL=1:6) diblock copolymer.
Fig. 5 be concentration be 10mg/mL mPEG-b-PCL (MmPEG:MPCL=1:1) diblock copolymer in human breast carcinoma
The microphoto record in a period of time is continuously cultivated on cell line mcf-7 culture medium.
Fig. 6 be concentration be 1mg/mL mPEG-b-PCL (MmPEG:MPCL=1:1) diblock copolymer in human breast carcinoma
The microphoto record in a period of time is continuously cultivated on cell line mcf-7 culture medium.
Fig. 7 be concentration be 0.1mg/mL mPEG-b-PCL (MmPEG:MPCL=1:1) diblock copolymer in human milk gland
The microphoto record in a period of time is continuously cultivated on cancerous cell line MCF-7 culture medium.
Specific embodiment
Reagent: polyethylene glycol (mPEG, Mn=2000, Aldrich, USA), ε-hexamethylene lactone (ε-CL, density 1.07g/
Cm3Alfa 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 medium (HyClone), 0.25% trypsase (HyClone), the fetal calf serum (four seasons
It is green), 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 evacuation device, nitrogen gas
Ball, syringe, Vltrasonic device, reagent rifle, cooling device, Suction filtration device, Reagent Tube, vacuum desiccator, label, marking pen, point
Analyse balance, nuclear magnetic resonance, 96 orifice plates, Tissue Culture Dish, 15mL centrifuge tube, EVOSFLAuto imaging system.
Below with reference to test example and specific embodiment, the present invention is described in further detail.But this should not be understood
It is all that this is belonged to based on the technology that the content of present invention is realized for the scope of the above subject matter of the present invention is limited to the following embodiments
The range of invention.Percentage in the present invention for special instruction is usually weight percent.
Embodiment 1
It synthesizes mPEG-b-PCL (MmPEG:MPCL=1:1)
Test the table 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
Azeotropic water removing 2 hours under the conditions of 138 DEG C of bath.0.94mL ε-hexamethylene lactone, is added appropriate stannous octoate catalyst, adds after cooling
Enter a magnetic stir bar, add 10mL toluene, three mouths of three-neck flask are used into glass stopper, condenser pipe (condenser pipe respectively
Upper end cap one is full of the tiny balloons of nitrogen), vacuumizing joint seals, and connects vacuum evacuation device, condenser pipe upper end piston is opened,
Vacuumizing joint piston is opened, vacuum evacuation device is opened and vacuumize 5 minutes, close vacuumizing joint piston, close condensation
Pipe upper end piston closes vacuum evacuation device, disconnects three-necked bottle and connect with vacuum evacuation device, is replaced with a balloon full of nitrogen
That balloon before opens condenser pipe upper end piston.
This three-necked bottle is fixed on iron stand, is placed in oil bath pan, temperature is adjusted to 138 DEG C, magnetic agitation rotating speed tune
Section reacts 12 hours, to middling speed if solvent reduction can be suitably added toluene in reaction process.After reaction, it is cooled to
Room temperature, is added 10mL methyl tertiary butyl ether(MTBE), ultrasound 10 minutes, then the cooling recrystallization of ice bath 20 minutes is filtered, collects filter
Slag is put into vacuum desiccator, 1 hour dry, and product is packed into plastic tube, is weighed, is sticked respective labels.
Fig. 1 is the 1H NMR spectra of the polyethylene glycol-polycaprolactone diblock copolymer of standard.Chemical shift be 3.65 ×
The peak of 10-6 belongs to the proton peak of polyethylene glycol segment methylene a, and the triplet of 2.3 × 10-6 belongs to the proton at c,
The triplet of 4.1 × 10-6 belongs to the proton at f, and the multiplet of 1.6 × 10-6 belongs to the proton at d, and is located at highest
The multiplet of 1.4 × 10-6 of field belongs to the proton peak at e.
Resulting mPEG-b-PCL (MmPEG:MPCL=1:1) sample is fitted into nuclear magnetic tube general 3 microns, uses syringe
Suitable deuterated chloroform is added, clogs nuclear magnetic tube with plug.MPEG-b-PCL (MmPEG:MPCL=1:1) is marked with marking pen.
Carry out nuclear magnetic resonance.Fig. 2 is the 1H NMR spectra of mPEG-b-PCL (MmPEG:MPCL=1:1) diblock copolymer.
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 is the result shows that synthetic product is mPEG-b-PCL (MmPEG:MPCL=1:1) the diblock polymerization of target
Object.
Embodiment 2
It synthesizes 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
Azeotropic water removing 2 hours under the conditions of 140 DEG C of bath.3.74mL ε-hexamethylene lactone, is added appropriate stannous octoate catalyst, adds after cooling
Enter magnetic stir bar, add 10mL toluene, three mouths of three-neck flask are used into glass stopper, condenser pipe (condenser pipe upper end respectively
One, set is full of the tiny balloons of nitrogen), vacuumizing joint seals, and connects vacuum evacuation device, opens condenser pipe upper end piston, opens
Vacuumizing joint piston is opened vacuum evacuation device and vacuumize 5 minutes, close vacuumizing joint piston, closes on condenser pipe
Piston is held, vacuum evacuation device is closed, three-necked bottle is disconnected and is connect with vacuum evacuation device, before a balloon replacement full of nitrogen
That balloon opens condenser pipe upper end piston.This three-necked bottle is fixed on iron stand, is placed in oil bath pan, temperature is adjusted to
140℃.Magnetic agitation rotating speed is adjusted to middling speed, reacts 12 hours, if solvent reduction can be suitably added first in reaction process
Benzene.It is cooled to room temperature after reaction, 10mL methyl tertiary butyl ether(MTBE), ultrasound 10 minutes, the cooling recrystallization 20 under ice bath is added
Minute, it is then filtered, filter residue is packed into vessel, be put into drying 1 hour in vacuum desiccator, product is packed into plastic tube,
Weighing, sticks respective labels.
Resulting mPEG-b-PCL (MmPEG:MPCL=1:4) sample is fitted into nuclear magnetic tube general 3 microns, uses syringe
Suitable deuterated chloroform is added, clogs nuclear magnetic tube with plug.MPEG-b-PCL (MmPEG:MPCL=1:4) is marked with marking pen.
Carry out nuclear magnetic resonance.Fig. 3 is the 1H NMR spectra of mPEG-b-PCL (MmPEG:MPCL=1:4) diblock copolymer.
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=
7.3Hz, 4H), 1.54 (h, J=7.5Hz, 8H), 1.36-1.23 (m, 1H), 1.29 (s, 4H)
Nmr analysis is the result shows that synthetic product is the polymerization of target mPEG-b-PCL (MmPEG:MPCL=1:4) diblock
Object.
Embodiment 3
It synthesizes 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
Azeotropic water removing 2 hours under the conditions of 140 DEG C of bath.5.61mL ε-hexamethylene lactone, is added appropriate stannous octoate catalyst, adds after cooling
Enter magnetic stir bar, add 10mL toluene, three mouths of three-neck flask are used into glass stopper, condenser pipe (condenser pipe upper end respectively
One, set is full of the tiny balloons of nitrogen), vacuumizing joint seals, and connects vacuum evacuation device, opens condenser pipe upper end piston, opens
Vacuumizing joint piston is opened vacuum evacuation device and vacuumize 5 minutes, close vacuumizing joint piston, closes on condenser pipe
Piston is held, vacuum evacuation device is closed, three-necked bottle is disconnected and is connect with vacuum evacuation device, before a balloon replacement full of nitrogen
That balloon opens condenser pipe upper end piston.This three-necked bottle is fixed on iron stand, is placed in oil bath pan, temperature is adjusted to
140 DEG C, magnetic agitation rotating speed is adjusted to middling speed, reacts 12 hours, if solvent reduction can be suitably added first in reaction process
Benzene is cooled to room temperature after reaction, and 10mL methyl tertiary butyl ether(MTBE), ultrasound 10 minutes, the cooling recrystallization 20 under ice bath is added
Minute, it is then filtered, filter residue is packed into vessel, be put into drying 1 hour in vacuum desiccator, product is packed into plastic tube,
Weighing, sticks respective labels.
Resulting mPEG-b-PCL (MmPEG:MPCL=1:6) sample is fitted into nuclear magnetic tube general 3 microns, uses syringe
Suitable deuterated chloroform is added, clogs nuclear magnetic tube with plug.MPEG-b-PCL (MmPEG:MPCL=1:6) is marked with marking pen.
Carry out nuclear magnetic resonance.Fig. 4 is the 1H NMR spectra of mPEG-b-PCL (MmPEG:MPCL=1:6) diblock copolymer.
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), 1.52 (dh, J=14.0,7.2Hz, 5H), 1.28 (dq, J=13.4,7.5,6.8Hz, 2H), 0.89-0.79 (m, 1H)
Nmr analysis is the result shows that synthetic product is mPEG-b-PCL (MmPEG:MPCL=1:6) the diblock polymerization of target
Object.
Fig. 2-4 is compared with Fig. 1 respectively, and peak position is gone out in nuclear magnetic spectrum and magnetic integral is all consistent with Fig. 1, illustrates to implement
The different polycaprolactone content ratios of three kinds of example 1-3 synthesis (MMPEG:MPCL=1:1, MMPEG:MPCL=1:4, MMPEG:
MPCL=1:6 polyethylene glycol-polycaprolactone di-block copolymer) is all the set goal product, and product it is pure very
Height, it is consistent with expected synthesis purpose.
Test example 1
The cell experiment of mPEG-b-PCL diblock copolymer
The human breast carcinoma cell lines MCF-7 of 1.ATCC purchase washes one with DMEM culture medium with after 37 DEG C of water-baths thawings rapidly
It is secondary, 1200rpm be centrifuged 3min, abandon supernatant, fresh culture medium is added, cell is dispelled into cell suspension, be transferred to added with
It is cultivated in 37 DEG C, 5%CO2 condition incubator in the culture dish of fresh culture.
2. by the mPEG-b-PCL material of the 1:1 ratio of Preparatory work of experiment with being configured to 0.1mg/mL, 1mg/mL and 10mg/mL
The solution of three concentration (preparation method: accurately weighs mPEG-b-PCL (MmPEG:MPCL=1:1) sample using assay balance
The sample cell of 1.5mL is added in 10mg, draws deionized water using imbibition rifle, instills sample cell, 1mL graduation mark is settled to, by this
Sample cell carry out ultrasound about 20 minutes, then heated under 40 DEG C of water bath conditions about 5 minutes, sample be completely dissolved to get
To C1=10mg/mL mPEG-b-PCL (MmPEG:MPCL=1:1) sample solution；C1=10mg/mL is drawn using imbibition rifle
MPEG-b-PCL (MmPEG:MPCL=1:1) sample solution 0.1mL, is added another an equal amount of sample cell, and imbibition rifle is drawn
Deionized water is settled to 1mL graduation mark to get molten to C2=1mg/mL mPEG-b-PCL (MmPEG:MPCL=1:1) sample
Liquid；C2=1mg/mL mPEG-b-PCL (MmPEG:MPCL=1:1) sample solution 0.1mL is drawn using imbibition rifle, is added another
An equal amount of sample cell, imbibition rifle draw deionized water, are settled to 1mL graduation mark to get C3=0.1mg/mL mPEG- is arrived
B-PCL (MmPEG:MPCL=1:1) sample solution.Then the solution of 3 concentration is added to 96 orifice plates by 50 holes μ L/ respectively
In, 3 multiple holes are arranged in each concentration.Every hole is washed 3 times with 100 μ L of physiological saline respectively after solution volatilizees naturally, natural again
It dries spare.
3. cell is long to sucking old culture medium when being paved with ware bottom, primary with 2mL PBS drip wash, 2mL0.25% is added
Trypsase is digested, and loses when cell and complete medium termination digestion is added when original form is rounded, collect cell,
1200rpm is centrifuged 3min, abandons supernatant, with new culture medium piping and druming cell at single cell suspension, is counted by blood cell counting plate
Adjustment cell concentration is 105/mL, is inoculated on 96 orifice plates by 100 μ L/ hole densities, and continuation is cultivated in incubator, every
It observes and takes pictures under the microscope for 24 hours.
Cell on culture medium propagation coefficient S=Wcs-Wcc (Wcs: indicate surface between cell and culture medium can,
Wcc: the surface energy between cell and cell is indicated).When Wcs < Wcc (S < 0), cell tends to coherent condition；Work as Wcs > Wcc
When (S > 0), cell tends to coherent condition.The surface between cell and cell can be reduced in vivo, cancer cell will be made to be detached from
Tumour originally, which results in the transfer of cancer cell and diffusions.Although the surface between cancer cell and cancer cell can be very big,
Be cancer cell aggregate surface cell activity it is very strong, cause allow them to be detached from original tumour, so as to cause cancer cell
Transfer and diffusion.The copolymer solution and human breast carcinoma cell lines MCF-7 of three kinds of concentration are tested, and are clapped every 24 hours once, one
It claps 4 times altogether, takes pictures result as illustrated in figs. 5-7.Wherein, Fig. 5-7 corresponds respectively to concentration as 10mg/mL (Fig. 5), 1mg/mL (figure
6), mPEG-b-PCL (MmPEG:MPCL=1:1) block copolymer of 0.1mg/mL (Fig. 7) is in human breast carcinoma cell lines MCF-7
The microphoto record in a period of time is continuously cultivated on culture medium.
From Fig. 5-7 as it can be seen that influence approximate trend of three kinds of various concentration sample solutions to human breast carcinoma cell lines MCF-7
Be: first day, cell was not assembled, and cell is gradually assembled within second day, and the cell aggregation of third day reaches maximum value, and the 4th day
Cell starts apoptosis.The block polymer for showing three kinds of various concentrations can effectively inhibit within initial a period of time
The coherent condition of cell.But various concentration have certain difference again, the effect of C2=1mg/mL sample solution is most ideal, C1
The effect of the sample solution of=10mg/mL, C3=0.1mg/mL is not satisfactory.The corresponding cell of the sample solution of three kinds of concentration exists
All there is within 4th day apoptosis, reason is exactly that the nutritional ingredient of culture dish was consumed at the 4th day and is over, and cell continues to give birth to without nutrition
It is long, then start apoptosis.
The result shows that self assembly mPEG-b-PCL prepared by the present invention can effectively inhibit the coherent condition of cancer cell, phase
The mPEG-b-PCL micella answered be it is novel, reliable, safe, can be as the carrier for being insoluble in water drug, and in cancer
Target medicine carrier in play good carrier function and auxiliary therapeutic action, have huge clinical value.
Claims (3)
1. the diblock polymer of polyethylene glycol crosslinked polycaprolactone inhibits the coherent condition of tumour cell in preparation, promote tumour
Cell keeps building up state, the application in anti-tumor drug for preventing tumour cell from spreading, which is characterized in that
MPEG and PCL mass ratio is 1:1~1:6 in the diblock polymer of the polyethylene glycol crosslinked polycaprolactone.
2. application as described in claim 1, which is characterized in that the diblock of the polyethylene glycol crosslinked polycaprolactone polymerize
Application of the object in preparation treatment breast cancer medicines.
3. application as described in claim 1, which is characterized in that the diblock of the polyethylene glycol crosslinked polycaprolactone polymerize
Application of the object as medicine carrying material in the drug for the treatment of tumour.
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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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2016
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Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| 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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