CN100434120C - Amphipathic fluorescence target nano micelle and its preparation method - Google Patents
Amphipathic fluorescence target nano micelle and its preparation method Download PDFInfo
- Publication number
- CN100434120C CN100434120C CNB2006101160450A CN200610116045A CN100434120C CN 100434120 C CN100434120 C CN 100434120C CN B2006101160450 A CNB2006101160450 A CN B2006101160450A CN 200610116045 A CN200610116045 A CN 200610116045A CN 100434120 C CN100434120 C CN 100434120C
- Authority
- CN
- China
- Prior art keywords
- amphipathic
- micelle
- preparation
- drug
- nano
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Images
Landscapes
- Medicinal Preparation (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Abstract
The invention discloses an amphipathic fluorescent targeting nanometer micelle and preparing method, which comprises the following steps: polymerizing decomposable polyester and multi-ammino polymer to synthesize amphipathic drug carrier, adopting solvent evaporating method to prepare carrier micelle, packing the drug into hydrophobic or little water-soluble tumour prevention drug, grafting targeting molecular folacin on the micelle with ammino, grafting isothiocyanic acid fluorescein on the residual ammino.
Description
Technical field
The invention belongs to the chemicals technical field, be specifically related to a kind of amphipathic fluorescence target nano micelle and preparation method thereof.
Technical background
In recent years, studies show that polymeric micelle can be used as the potential carrier that is difficult to water-soluble medicine, M.Jones etc. have carried out the trial of preparation, sign evaluation and the medicinal application of polymeric micelle.Polymeric micelle provides the attraction characteristic aspect main at two: (1) can be in hydrophobic inner core solubilizing hydrophobic medicine or water soluble drug slightly; (2) can avoid medicine to be absorbed by RES (reticuloendothelial system) or MPS (phagocyte system) external.
Transport carrier a kind of of the medicine that is insoluble in water although micelle volume is seemingly best, they still exist the problem that makes of the stability in infusion or body fluid.X.Zhang etc. have reported that the diblock copolymer of polylactide and mono methoxy polyethylene glycol (mPEG) has the purposes of paclitaxel carrier.Because the material that uses in said preparation is nontoxic, and their hydrolyzate is got rid of from health at an easy rate.
EP03970307A2 discloses a kind of polymer micelle of AB type amphiphilic diblock copolymer, this copolymer comprises as the polyoxyethylene of hydrophilic component with as poly-(aminoacid) of hydrophobic components, wherein is connected on the hydrophobic components of this polymer the therapeutic activity pharmaceutical chemistry.Yet though this polymer micelle can be used as a kind of means of administration hydrophobic drug, it also has disadvantage: promptly need introduce functional group in block copolymer.EP0583955A2 discloses the method for coated by hydrophobic medicine in a kind of diblock copolymer micelle of describing in EP03970307A2.This method has solved the above-mentioned disadvantage that needs to introduce functional group.EP0520888A1 discloses a kind of nano-scale particle of being made by polylactic acid and poly-(alkylene oxide) block copolymer, and this nano-scale particle demonstrates reduction by the absorption of reticuloendothelial system.
The micellar amphipathic carrier of traditional preparation, except that hydrophobic components is degradable high polymer, hydrophilic component mostly is Polyethylene Glycol (PEG), polyoxyethylene (PEO) etc., but the process of synthetic vectors is complicated, and can't effectively introduce more active end group with convenient further functionalization.
In recent years, the targeted drug delivery system becomes the emphasis that scholars study as one of important means for the treatment of tumor and cancer, it both can solve existing drug selectivity does not cause drug distribution in each organ problem of whole body by force, can improve pharmaceutically active again, reduces poisonous side effect of medicine.Improve the tumor treatment effect, need to improve the tumor-selective of medicine, reduce its gathering at non-target site.The targeting of medicine is not subjected to the influence at medication and position under the perfect condition, can avoid that some patient's compliances are poor, the administering mode of inconvenient operation, can also reduce drug dose and reduce the treatment cost, drug targeting makes at the partial drug level of target site and increases in addition.
Along with the continuous progress of tumor molecular level research, initiatively the targeted drug delivery system becomes a big focus in recent years.A series of receptors have been found at tumor cell surface or the relevant blood vessel surface of tumor, they and tumor growth propagation is closely related and in the tumor tissues overexpression, the receptor of these tumour-specifics provides target spot for oncotherapy, will overexpression such as: folacin receptor at some tumor tissues place, then be low expression level at the normal structure place or do not express.
(folic acid FA) has another name called vitamin B to folic acid
11Structural formula is seen last figure, is the micromolecule vitamin that contains the petrin ring in a kind of molecular structure, by eukaryotic cell list carbon metabolism nucleoside synthetic essential, its structure one end contains two carboxyls, and it is the passive less likely that is diffused into cell membrane under physiological temp and pH condition.The approach that matrix initiatively absorbs folic acid has two kinds: first kind of mechanism is the folic acid-binding protein by low-affinity, directly folic acid is imported endochylema; Second kind of mechanism is the specificity folic acid-binding protein by high-affinity, and promptly (Folate Receptor, FR) the mediated cell internalization is taken in endochylema with folic acid to folacin receptor.Preparation is the medicine of " target missile head " with folic acid, has the characteristics of transfer efficiency height and targeting delivery.
Fluorescein isothiocyanate Fluorescein isothiocyanate (FITC) is a kind of of fluorescein derivative, and 5-FITC is than the more frequent use of 6-FITC.The isothiocyanic acid base of FITC can react with amino, can be used for the amido modified DNA of labelling, in case form, product is very stable.Be applicable to the 488nm spectral line of Argon-ion Laser, Abs/Em=492/519nm (pH=9.0).FITC can be used as tracer molecule, and in cell experiment or zoopery, by fluorescence microscope, the position of show tags thing directly perceived becomes the direct approach that characterizes targeting.
Summary of the invention
The objective of the invention is to propose a kind of have biocompatibility and degradability can the long-term safety release amphipathic fluorescence target nano micelle and preparation method thereof.
The preparation method of the amphipathic fluorescence target nano micelle that the present invention proposes, with hydrophobic components biodegradable polymer and hydrophilic component polymine (PEI) copolymer is the micelle carrier, adopt solvent evaporation method that hydrophobicity or summary water solublity antitumor drug are wrapped in the micelle, by micellar surface amino, targeted molecular folic acid and spike fluorescent material are grafted to micellar surface, obtain amphipathic fluorescence target nano micelle, concrete steps are as follows:
(1) preparation amphipathic nature polyalcohol carrier
Activatory hydrophobicity biodegradable polymer (as polylactic acid (PLA)) and polymine (PEI) are dissolved in the organic solvent, and aminolysis 1～12hr obtains amphipathic nature polyalcohol biodegradable polymer-polymine.When polymer was PLA, reaction equation was as follows:
Here n is the degree of polymerization of polymer in [], and n is 50-10000.
(2) preparation amphiphilic nano carrier micelle
The amphipathic nature polyalcohol of step (1) gained is dissolved in the organic solvent, the weight concentration of polymer in organic solvent is 1%～10%, with hydrophobicity or slightly water soluble drug be dissolved in or be suspended in the above-mentioned organic solvent and form oil phase, the weight concentration of medicine in organic solvent is 0.01%～1%; Above-mentioned oil phase is added drop-wise in stirring or ultransonic certain water-bearing media, and emulsifying 6～48hr obtains the nano drug-carrying micelle.
(3) the amphipathic targeted nano micelle of preparation
Get the nano drug-carrying micelle of step (2) gained, be suspended in and form system A among the PBS that pH value is 4.0-4.5.Get folic acid (folate), 1-ethyl-1-3-(3-dimethylamino-propyl group)-carbodiimides (EDAC) is dissolved in formation system B in the dimethyl sulfoxine (DMSO).System A being added drop-wise among the system B going, stir and keep 1～10hr down, is the PBS solution adjusting of 4.0-4.5 with pH value, and the pH value that remains system is prepared into amphipathic targeted nano micelle less than 5.0.
(4) preparation amphipathic fluorescence target nano micelle
Get the amphipathic targeted nano micelle of step (3) preparation, with pH value is the micellar solution that 9.5 carbonate buffer solution (PBS) is configured to 1%～10%g/ml, adopt paddling process to connect fluorescein: with pH value is that 9.5 carbonate buffer solution dissolves fluorescent material, be added drop-wise in the micellar solution, stir 1～10hr, dialysis is removed free fluorescent material.Suspension process in the bag filter is centrifugal, tri-distilled water rinse three times, and centrifugal, cold doing obtains Powdered micelle.
The hydrophobic components of the amphipathic nature polyalcohol carrier described in the present invention is selected from a kind of of following biodegradable polymers: polylactide (PLA), poly-Acetic acid, hydroxy-, bimol. cyclic ester (PGA), lactide and glycolide copolymer (PLGA), polycaprolactone (PCL), poly-former ester acid, lactide and 1, the copolymer of 4-diox-2-ketone, caprolactone and 1, the copolymer of 4-diox-2-ketone.
Amphipathic nature polyalcohol carrier described in the present invention, the molecular weight of its hydrophobic components and hydrophilic component is respectively 5000～50000g/mol and 423～25000g/mol, and the ratio of both amounts is 1: 0.1～1: 5.0.
Organic solvent described in the present invention can be dichloromethane, chloroform, ethyl acetate or acetone etc.
The hydrophobicity of the amphiphilic nano carrier micelle described in the present invention or water slightly soluble drug are selected from 10-deacetyltaxol, vinca alkaloids, anthracene nucleus class, table podophyllin class, camptothecine, amycin, cisplatin or 5-fluorouracil etc.
In the amphiphilic nano carrier micelle preparation described in the present invention, its water-bearing media can adopt 0.9% sodium-chloride water solution (normal saline solution), 5% D/W, the water for injection that contains 5% glucose and 0.9% sodium chloride, the ringer's inj that contains 5% glucose perhaps contains the aqueous solution of Tween-80 (tween 80) or polyvinyl alcohol surfactants such as (PVA).
Amphiphilic nano carrier micelle described in the present invention, thus medicine caught with physical means and be coated in the micelle, but not be covalently bonded in hydrophobic core; This hydrophobic core is formed by the hydrophobic PLA component of amphipathic nature polyalcohol.
The micellar preparation method of amphipathic targeted nano described in the present invention, utilize micellar surface active amino and targeted molecular coupling connection.
The micellar preparation method of amphipathic targeted nano described in the present invention, targeted molecular enters the material of cell for following folacin receptor approach on the cell membrane, and this targeted molecular can deaminize for folic acid, folinic acid, dihydrofoilic acid, tetrahydrofolic acid, tetrahydrobiopterin, the many glutamic acid of the acyl of talking endlessly, 2--hydroxyl folic acid, 1-denitrification folic acid, 3-denitrification folic acid and 8-denitrification folic acid.
The preparation method of the amphipathic fluorescence target nano micelle described in the present invention, the fluorescent material of employing can be Fluorescein isothiocyanate (FITC), RB 200 (RB200) or Tetramethylrhodamine isothiocyanate (TRITC) or 5-(4,6-Dichlorotriazinyl)aminofluorescein etc.
The preparation method of the amphipathic fluorescence target nano micelle described in the present invention, the rate of charge of described folic acid and surface amino groups, fluorescent material and surface amino groups are 0.1/1～1/1.
The synthesizing amphipathic polymer P LA-PEI of the present invention elder generation obtains the polymer of different hydrophilic and hydrophobics, different molecular weight by different rate of charges; Prepare nano level carrier micelle then, the antitumor drug physical package is overlayed on micelle inside; Be exposed to the active amino of micellar surface again by amphipathic carrier, grafting targeted molecular folic acid and tracer molecule fluorescent material, thus obtain functional drug-loading system.The amphipathic fluorescence target nano micelle that the present invention obtains, particle diameter is less, is evenly distributed, and has excellent biological compatibility and degradability, can effectively arrive diseased region and concentrate drug effect, realizes the long-term safety release; Simultaneously, can be by the spike effect of fluorescent material, in experiment and testing process, targeting and drug effect situation are investigated in intuitive and convenient ground.
Description of drawings
Fig. 1 is different proportion PLA in the embodiment of the invention 1: the gel permeation chromatography of PEI synthetic product.
Fig. 2 is the particle diameter and the particle size distribution of the carrier micelle of the amphipathic nature polyalcohol preparation that different proportioning PLA/PEI prepare in the embodiment of the invention 2.
Fig. 3 is the transmission electron microscope photo of the embodiment of the invention 2 carrier micelles.
Fig. 4 is the targeting colour developing picture of the embodiment of the invention 1 (2) in test cell line.
The specific embodiment
Further describe the present invention by the following examples, but be not limited to these embodiment.
Embodiment 1: the amphipathic carrier of preparation PLA-PEI
(1)PLA∶PEI＝1∶0.4
Get PLA, N, N-dicyclohexyl carbimide (DCC), N-maloyl imines (NHS) are dissolved in the dichloromethane (DCM), stirring at room 24hr, preparation activation PLA; Get activatory PLA1g, be dissolved in 10mlDCM (A), 0.0121g PEI is dissolved in the acetone of 5ml (B); After mixing evenly separately, the B system is slowly added in the A system of high-speed stirred aminolysis 6hr; The solution that obtains is added in the ice-cold ether of high-speed stirred and precipitate; Buchner funnel filters, and vacuum drying obtains white PLA-PEI powder.
Resulting PLA-PEI, Mn=6447g/mol, Mw=16076g/mol.(seeing accompanying drawing 1)
(2)PLA∶PEI＝1∶0.8
Get PLA, DCC, NHS are dissolved among the DCM, stirring at room 24hr, preparation activation PLA; Get activatory PLA1g, be dissolved in (A) among the 10mlDCM, 0.0242g PEI is dissolved in the acetone of 5ml (B); After mixing evenly separately, the B system is slowly added in the A system of high-speed stirred aminolysis 6hr; The solution that obtains is added in the ice-cold ether of high-speed stirred and precipitate; Buchner funnel filters, and vacuum drying obtains white PLA-PEI powder.
Resulting PLA-PEI, Mn=6259g/mol, Mw=15648g/mol.(seeing accompanying drawing 1)
(3)PLA∶PEI＝1∶1.2
Get PLA, DCC, NHS are dissolved among the DCM, stirring at room 24hr, preparation activation PLA; Get activatory PLA1g, be dissolved in (A) among the 10mlDCM, 0.0363g PEI is dissolved in the acetone of 5ml (B); After mixing evenly separately, the B system is slowly added in the A system of high-speed stirred aminolysis 6hr; The solution that obtains is added in the ice-cold ether of high-speed stirred and precipitate; Buchner funnel filters, and vacuum drying obtains white PLA-PEI powder.
Resulting PLA-PEI, Mn=6047g/mol, Mw=14959g/mol.(seeing accompanying drawing 1)
Embodiment 2: preparation PLA-PEI is the carrier micelle of carrier
0.5gPLA-PEI be dissolved among the 20mlDCM, become oil phase after the dissolving evenly, and with 5-Fu powder ultrasound suspending in oil phase; 1g Tweeen-80 is dissolved in the 100ml water becomes water; Under the condition of high-speed stirred, oil phase is added drop-wise to aqueous phase, continues to stir 48hr and volatilize, be put into the freezing 24hr of refrigerator, micelle is further solidified until organic solvent; Centrifugal, tri-distilled water rinse three times, lyophilization obtains nano drug-carrying micelle powder.
Gained nano drug-carrying micelle, particle diameter are about 100nm (sees accompanying drawing 2), becomes the rounding sphere, and size evenly.(seeing accompanying drawing 3)
5-Fu standard curve equation at 265nm place in the 0.1M dilute hydrochloric acid is:
A=0.0567563C+0.000651 (r=0.9999) C is 5-Fu concentration (μ g/ml), and A is an absorbance.
Getting an amount of carrier micelle dissolves with DCM, then with dilute hydrochloric acid extraction three times, the 5-Fu solution of collecting the upper strata dilute hydrochloric acid is settled to 50ml then, measure the absorbance A at 265nm place with U-1800 type ultraviolet spectrophotometer, bring the standard curve equation of 5-Fu in the 0.1M dilute hydrochloric acid into, calculate envelop rate for seeing the following form with drug loading:
The amphipathic targeted nano micelle of embodiment 3 preparations
Get the carrier micelle that PLA-PEI is a carrier, be suspended in a certain amount of pH value and be in 4.0 the phosphatic buffer solution (PBS) (C); Get 0.026g folate, 0.0226g EDAC is dissolved in (D) among the 5ml DMSO, 3hr under magnetic agitation; The C system slowly being added drop-wise in the D system, keeping 10hr under the magnetic agitation, is that 4.0 PBS solution is regulated with pH value, remains the pH value 5.0 of system; Centrifugal micelle suspension, tri-distilled water rinse three times, lyophilization 24hr obtains Powdered targeted nano micelle.
Take by weighing a certain amount of targeted nano micelle, it is dissolved among the DMSO, measure the absorbance at 362nm place, and substitution standard curve equation:
C (μ g/ml)=0.83037+65.63382*A, C is the concentration of folic acid, and A is an absorbance, and r=0.99953 calculates the grafting amount and sees the following form:
Embodiment 4 preparation amphipathic fluorescence target nano micelles
Take by weighing 1.5417g NaHCO
3With 0.25g Na
2CO
3Use the 250ml dissolved in distilled water, the pH value that is configured to 0.05M is 9.5 carbonate buffer solution, gets the nano target carrier micelle of above-mentioned preparation, adopts paddling process to connect fluorescein: getting a certain amount of carrier micelle, to be suspended in pH value be 9.5 carbonate buffer solution; With the 80mlpH value is 9.5 carbonate buffer solution dissolving FITC, is added drop-wise in the micellar solution of magnetic agitation the pH value of the hierarchy of control 〉=9.0 during dropping; After dropwising, under the room temperature, magnetic agitation 10hr; Dialysis is removed free fluorescein: above-mentioned system is injected in the bag filter, and the outside is 0.9% normal saline, constantly changes outside normal saline, is zero until outer aqueous phase fluorescein concentration; Suspension process in the bag filter is centrifugal, tri-distilled water rinse three times, and centrifugal, cold doing obtains Powdered fluorescent target to nano-micelle.
Claims (5)
1, a kind of preparation method of amphipathic fluorescence target nano micelle, it is characterized in that: with hydrophobic components biodegradable polymer and hydrophilic component polyethylene imine copolymer is the micelle carrier, adopt solvent evaporation method that hydrophobic anticancer drug is wrapped in the micelle, by micellar surface amino, targeted molecular folic acid and spike fluorescence molecule are grafted to micellar surface, obtain amphipathic fluorescence target nano micelle, concrete steps are as follows:
(1) synthesizing amphipathic polymer support
Hydrophobic components biodegradable polymer and hydrophilic component polymine are dissolved in the organic solvent, and aminolysis 1～12hr obtains amphipathic nature polyalcohol hydrophobic polymer-polymine; Here, the molecular weight of described hydrophobic components and hydrophilic component is respectively 5000～50000g/mol and 423～25000g/mol, and the ratio of both amounts is 1: 0.1～1: 5.0;
(2) preparation amphiphilic nano carrier micelle
The amphipathic nature polyalcohol of step (1) gained is dissolved in the organic solvent, the mass concentration of polymer in organic solvent is 1%～10%, hydrophobic drug is dissolved in or is suspended in the above-mentioned organic solvent that dissolves amphipathic nature polyalcohol, form oil phase, the weight concentration of medicine in organic solvent is 0.01%～1%; Above-mentioned oil phase is added drop-wise in stirring or the ultransonic water-bearing media, and emulsifying 6～48hr obtains the nano drug-carrying micelle;
(3) the amphipathic targeted nano micelle of preparation
Get the nano drug-carrying micelle of step (2) gained, be suspended in and form system A in the carbonate buffer solution that pH value is 4-4.5, get folic acid, 1-ethyl-1-3-(3-dimethylamino-propyl group)-carbodiimides is dissolved in the dimethyl sulfoxine, formation system B, system A being added drop-wise among the system B going, stir and keep 1～10hr down, is the carbonate buffer solution adjusting of 4-4.5 with pH value, the pH value that remains system is prepared into amphipathic targeted nano micelle less than 5.0;
(4) preparation amphipathic fluorescence target nano micelle
Get the amphipathic targeted nano micelle of step (3) preparation, with pH value is the micellar solution that 9.5 carbonate buffer solution is configured to 1%～10%g/ml, adopt paddling process to connect fluorescent material: with pH value is that 9.5 carbonate buffer solution dissolves fluorescent material, be added drop-wise in the above-mentioned micellar solution, stir 1～10hr, dialysis is removed free fluorescent material, suspension in the bag filter is through centrifugal, tri-distilled water rinse three times, centrifugal, cold doing obtains Powdered micelle; Here, described fluorescent material is Fluorescein isothiocyanate, RB 200, Tetramethylrhodamine isothiocyanate or 5-(4,6-Dichlorotriazinyl)aminofluorescein.
2, the preparation method of amphipathic fluorescence target nano micelle according to claim 1, it is characterized in that described hydrophobic components is selected from a kind of of following biodegradable polymers: polylactide, poly-Acetic acid, hydroxy-, bimol. cyclic ester, lactide and glycolide copolymer, polycaprolactone, poly-former ester acid, lactide and 1, the copolymer of 4-diox-2-ketone, caprolactone and 1, the copolymer of 4-diox-2-ketone.
3, the preparation method of amphipathic fluorescence target nano micelle according to claim 1 and 2 is characterized in that described hydrophobic drug is selected from a kind of of paclitaxel, vinca alkaloids, anthracene nucleus, table podophyllin, camptothecine, amycin, cisplatin or 5-fluorouracil.
4, the preparation method of amphipathic fluorescence target nano micelle according to claim 1 and 2, the sodium-chloride water solution that it is characterized in that described water-bearing media selection 0.9%, 5% D/W, the water for injection that contains 5% glucose and 0.9% sodium chloride, the ringer's inj that contains 5% glucose perhaps contains the aqueous solution of tween 80 or polyvinyl alcohol surfactant.
5, as the amphipathic fluorescence target nano micelle of method preparation as described in one of claim 1-4.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101160450A CN100434120C (en) | 2006-09-14 | 2006-09-14 | Amphipathic fluorescence target nano micelle and its preparation method |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB2006101160450A CN100434120C (en) | 2006-09-14 | 2006-09-14 | Amphipathic fluorescence target nano micelle and its preparation method |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1919181A CN1919181A (en) | 2007-02-28 |
| CN100434120C true CN100434120C (en) | 2008-11-19 |
Family
ID=37777123
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB2006101160450A Expired - Fee Related CN100434120C (en) | 2006-09-14 | 2006-09-14 | Amphipathic fluorescence target nano micelle and its preparation method |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100434120C (en) |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103172845B (en) * | 2011-12-23 | 2015-09-02 | 国家纳米科学中心 | Polyethylenimine-aliphatic polyester graft polymer and preparation method thereof and nanoparticle |
| CN103251955B (en) * | 2012-02-17 | 2016-03-23 | 中国科学院化学研究所 | A kind of macromolecule target medicine carrier for tumor of bladder perfusion therapy and preparation method thereof |
| CN103122379A (en) * | 2012-12-24 | 2013-05-29 | 深圳先进技术研究院 | Method for real-time monitoring on gene transfection |
| CN105860101B (en) * | 2016-04-28 | 2018-03-27 | 中国科学院化学研究所 | A kind of hybridized hydrogel based on the crosslinking of polyester nano chemistry of particles and preparation method and application |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1307866A (en) * | 2000-02-09 | 2001-08-15 | 那野伽利阿株式会社 | Production process of polymerized micelle with injected medicine and polymerized micelle composite |
| CN1447683A (en) * | 2000-06-29 | 2003-10-08 | 制药实验室有限公司 | Polymeric micelle compsns. |
| CN1772782A (en) * | 2005-11-14 | 2006-05-17 | 武汉大学 | Amphipatic fluorescent polymer and its prepn and use |
-
2006
- 2006-09-14 CN CNB2006101160450A patent/CN100434120C/en not_active Expired - Fee Related
Patent Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1307866A (en) * | 2000-02-09 | 2001-08-15 | 那野伽利阿株式会社 | Production process of polymerized micelle with injected medicine and polymerized micelle composite |
| CN1447683A (en) * | 2000-06-29 | 2003-10-08 | 制药实验室有限公司 | Polymeric micelle compsns. |
| CN1772782A (en) * | 2005-11-14 | 2006-05-17 | 武汉大学 | Amphipatic fluorescent polymer and its prepn and use |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1919181A (en) | 2007-02-28 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Prabaharan et al. | Folate-conjugated amphiphilic hyperbranched block copolymers based on Boltorn® H40, poly (l-lactide) and poly (ethylene glycol) for tumor-targeted drug delivery | |
| Kang et al. | Tailoring the stealth properties of biocompatible polysaccharide nanocontainers | |
| CN102740895B (en) | Nanoconjugate and nanoconjugate preparation | |
| CN101910274B (en) | Amphiphilic block copolymer micelle composition containing taxane and manufacturing process of the same | |
| CN104056275B (en) | Multi-functional active targeting hyaluronic acid PLA carrier synthesis and its antineoplastic micella preparation method | |
| CN101787119A (en) | Polymer with tumor organization pH responsiveness and micelle thereof | |
| CN104530256B (en) | Hyaluronic acid-vitamin E succinate polymer as well as preparation and application thereof | |
| CN102641246B (en) | Anti-tumor double-drug nano drug carrying microsphere and preparation method thereof | |
| JP2014518862A (en) | Polymer nanoparticles for drug delivery | |
| CN103435718B (en) | The hyaluronic acid cholesteryl ester that PEG modifies | |
| Han et al. | Redox-sensitive micelles for targeted intracellular delivery and combination chemotherapy of paclitaxel and all-trans-retinoid acid | |
| CN103242517A (en) | Preparation of multifunctional linear-dendritic segmented copolymer and application in pharmaceutics thereof | |
| CN103251596A (en) | 7-ethyl-10-hydroxycamptothecin amphiphilic polymer prodrug as well as preparation method and nano-particles thereof | |
| CN105518031A (en) | Process for preparing stealth nanoparticles | |
| AU2016374669A1 (en) | Biodegradable amphiphilic polymer, polymer vesicle prepared therefrom and use in preparing target therapeutic medicine for lung cancer | |
| CN104116709A (en) | Tumor-targeting pH-sensitive polymeric micelle composition resisting tumor drug resistance | |
| CN103656653A (en) | Polyelectrolyte compound based on hyaluronic acid drug-loading nano particles, preparation method and application thereof | |
| CN105476975A (en) | Active targeting brain-tumor-resisting drug and preparation method thereof | |
| Chen et al. | Thermal responsive micelles for dual tumor-targeting imaging and therapy | |
| Suo et al. | Galactosylated poly (ethylene glycol)-b-poly (L-lactide-co-β-malic acid) block copolymer micelles for targeted drug delivery: preparation and in vitro characterization | |
| CN103720675B (en) | A kind of have the curcumin prodrug micelle of isotope of redox-sensitive, micelle monomer and preparation method thereof | |
| CN101007174A (en) | Biodegradable polymer docetaxel bonded drug and preparation method thereof | |
| CN100434120C (en) | Amphipathic fluorescence target nano micelle and its preparation method | |
| CN106137962B (en) | A kind of glioma target polymer micella and preparation method thereof loading Carmustine | |
| CN104116711A (en) | pH-sensitive polymeric micelle composition resisting tumor drug resistance |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| C17 | Cessation of patent right | ||
| CF01 | Termination of patent right due to non-payment of annual fee |
Granted publication date: 20081119 Termination date: 20130914 |