CN105878187A - Delivery system of self-assembly polymer nanoparticles of paclitaxel and preparation method of self-assembly polymer nanoparticles - Google Patents
Delivery system of self-assembly polymer nanoparticles of paclitaxel and preparation method of self-assembly polymer nanoparticles Download PDFInfo
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- CN105878187A CN105878187A CN201610247223.7A CN201610247223A CN105878187A CN 105878187 A CN105878187 A CN 105878187A CN 201610247223 A CN201610247223 A CN 201610247223A CN 105878187 A CN105878187 A CN 105878187A
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- Prior art keywords
- paclitaxel
- self
- soluplus
- supplying system
- assembling polymers
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Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/141—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers
- A61K9/146—Intimate drug-carrier mixtures characterised by the carrier, e.g. ordered mixtures, adsorbates, solid solutions, eutectica, co-dried, co-solubilised, co-kneaded, co-milled, co-ground products, co-precipitates, co-evaporates, co-extrudates, co-melts; Drug nanoparticles with adsorbed surface modifiers with organic macromolecular compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/337—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having four-membered rings, e.g. taxol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K9/00—Medicinal preparations characterised by special physical form
- A61K9/14—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles
- A61K9/19—Particulate form, e.g. powders, Processes for size reducing of pure drugs or the resulting products, Pure drug nanoparticles lyophilised, i.e. freeze-dried, solutions or dispersions
Abstract
The invention provides a delivery system of self-assembly polymer nanoparticles of paclitaxel and a preparation method of the self-assembly polymer nanoparticles. The delivery system of the self-assembly polymer nanoparticles of paclitaxel mainly comprises paclitaxel and Soluplus and is in a form of a liquid dispersed preparation or freeze-dried preparation. According to the delivery system, the self-assembly polymer nanoparticles of paclitaxel are prepared with an amphiphilic polymer material Soluplus as the carrier with an injection method, and the cell uptake rate is increased and toxic and side effects are reduced compared with a solution.
Description
(1) technical field
The present invention relates to a kind of novel paclitaxel self-assembling polymers nanoparticle drug-supplying system and preparation method thereof.
(2) background technology
Paclitaxel is to extract a kind of broad-spectrum high efficacy cancer therapy drug obtained in bark of Ramulus et folium taxi cuspidatae, be mainly used in ovarian cancer, breast carcinoma,
The treatment of small cell lung cancer, carcinoma of prostate, head and neck cancer, the esophageal carcinoma, spermocytoma, recurrence Fei Hejin lymphomas etc..Purple
Dissolubility in China fir alcohol water is extremely low (about 0.3 μ g/mL)；And serious toxic and side effects limits its clinical practice.For improving its water
Dissolubility, main measure has: paclitaxel surface hydrophilicity chemical modification (Gund M, Khanna A, Dubash N, Damre A,
Singh KS,Satyam A.Water-soluble prodrugs of paclitaxel containing self-immolative disulfide
Linkers.Bioorg Med Chem Lett.2015,25 (1): 122-127)；Make suitable drug-supplying system: as commercial preparation is purple
China fir alcohol injection (, taxol, 6mg/ml), Injectable liposomal (), injection paclitaxel (albumin
Conjunction type,) and injection paclitaxel micelle ().Wherein paclitaxel injection is polyoxyethylene
The solubilizing systems that Oleum Ricini and ethanol (50:50, v/v) are prepared, concentration 5mg/ml, but polyoxyethylene castor oil toxicity is big, easily
Cause allergy, haemolysis, nephrotoxicity and neurotoxicity etc..Injectable liposomal () it is first generation liposome, by greatly
Fabaceous lecithin, cholesterol and Tween 80 form, and have the side effect such as allergy equally.Paclitaxel polymeric micelles for injection
() with PEG-PLA as carrier, the polymer micelle of particle diameter 20～50nm, relatively paclitaxel injection carries
The high medicine distribution at tumor locus.Injection paclitaxel (albumin bound type) () it is that albumin is stable
Paclitaxel nano suspending system, mean diameter about 130nm, every 100mg, prepared before use becomes 5mg/ml suspensoid iv
Instiling, relatively paclitaxel injection reduces toxic and side effects, improves dosage, strengthens anticancer therapeutic.Additionally, still there is PEG to modify
The research report such as paclitaxel, paclitaxel long circulating, cation, active targeting liposome, cyclodextrin clathrate, microsphere.
Polyvinylcaprolactame-polyvinyl acetate-polyethyleneglycol-graft copolymer (trade name Soluplus) be N-vinyl-ε-
Caprolactam-vinyl acetate-Polyethylene Glycol (57:30:13) copolymerization forms, and molecular weight is 90,000～140,000g/mol,
It it is a kind of novel high polymer material of BASF AG's research and development listing in 2009.Use the oral ring spore of hot-melt extruded method preparation
Element over-saturation polymer micelle (Yu H, Xia D, Zhu Q, Zhu C, Chen D, Gan Y.Supersaturated polymeric
Micelles for oral cyclosporine A delivery.Eur J Pharm Biopharm, 2013,85 (3 Pt B): 1325-36), thin
Film dispersion-F127 aquation method oral the Quercetin of preparation and rheum emodin polymer micelle (Dian L, Yu E, Chen X, Wen X,
Zhang Z,Qin L,Wang Q,Li G,Wu C.Enhancing oral bioavailability of quercetin using novel
soluplus polymeric micelles.Nanoscale Res Lett,2014,9(1):2406.；Allusion quotation spirit brightness, Yu Enjiang, Cheng Jilun,
Guo Xianghua, Huang Zirong, Zhang Zhensheng. the preparation of rheum emodin Soluplus polymer micelle and quality evaluation. the Chinese experimental pharmacology of Chinese medical formulae
Magazine, 2014,20 (16): 15-18.), the solution that insoluble drug Sapacitabine Yu Soluplus is configured to solubilising can
Improve the anticancer therapeutic of this medicine, but the drug level that this medicine is in Soluplus is extremely low, maximum only 49.6 μ g/ml (Obata T,
Suzuki Y,Ogawa N,Kurimoto I,Yamamoto H,Furuno T,Sasaki T,Tanaka M.Improvement of
the antitumor activity of poorly soluble sapacitabine(CS-682)by usingas a surfactant.
Biol Pharm Bull.2014；37(5):802-7.).
(3) summary of the invention
It is contemplated that with Soluplus as carrier, it is provided that a kind of injection method, prepare novel paclitaxel self-assembling polymers nanometer
Grain drug-supplying system, for the treatment of cancer.Compared with commercially available injection, drug-supplying system of the present invention does not contains polyoxyethylene caster
Oil.Unlike existing research, present invention discover that the carrier that Soluplus is formed is self-assembling polymers nanoparticle, and system
Preparation Method is injection method, different from the Soluplus polymer micelle method of existing report.
Novel paclitaxel self-assembling polymers nanoparticle drug-supplying system provided by the present invention, bag load has good stability, can directly with
Liquid dispersed preparation or freeze-dried powder form, promote the cell picked-up to paclitaxel, and reduce paclitaxel toxic and side effects.
The present invention adopts the following technical scheme that
A kind of paclitaxel self-assembling polymers nanoparticle drug-supplying system, mainly includes paclitaxel and Soluplus；Based on described purple
China fir alcohol and Soluplus, the percetage by weight of described paclitaxel is 0.1%～15%, and the percetage by weight of described Soluplus is
99.9%～85%；
Preferably, based on described paclitaxel and Soluplus, the percetage by weight of described paclitaxel is 1%～12.5%, described
The percetage by weight of Soluplus is 99%～82.5%；
More preferably, based on described paclitaxel and Soluplus, the percetage by weight of described paclitaxel is 5%～10%, institute
The percetage by weight stating Soluplus is 95%～90%；
Paclitaxel self-assembling polymers nanoparticle drug-supplying system of the present invention is liquid dispersed dosage form or is lyophilized formulations
Form.
Concrete, when described paclitaxel self-assembling polymers nanoparticle drug-supplying system is liquid dispersed dosage form, by paclitaxel,
Soluplus, aqueous phase form；Based on described paclitaxel and Soluplus, the percetage by weight of described paclitaxel is 0.1%～15%,
The percetage by weight of described Soluplus is 99.9%～85%, and the volume of described aqueous phase is 5～200mL/g Soluplus；
Preferably, based on described paclitaxel and Soluplus, the percetage by weight of described paclitaxel is 1%～12.5%, described
The percetage by weight of Soluplus is 99%～82.5%；
More preferably, based on described paclitaxel and Soluplus, the percetage by weight of described paclitaxel is 5%～10%, institute
The percetage by weight stating Soluplus is 95%～90%；
The volume of the most described aqueous phase is 10～100mL/g Soluplus；The volume of the most described aqueous phase is
15～50mL/g Soluplus.
Described aqueous phase is soluble in water formulated by pH adjusting agent, or without pH adjusting agent, is directly water；Described
Water is pure water, water for injection or sterilized water for injection, preferably sterilized water for injection；The pH value of described aqueous phase is 3.0～9.0, excellent
Select 4.0～7.6；
Described pH adjusting agent be sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, sodium hydroxide,
At least one in hydrochloric acid, citric acid, tartaric acid, preferably phosphoric acid sodium dihydrogen, sodium hydroxide or hydrochloric acid.
Present invention also offers the preparation method of the paclitaxel self-assembling polymers nanoparticle drug-supplying system of liquid dispersed dosage form,
Described preparation method is:
Paclitaxel and Soluplus are dissolved in organic solvent, obtain mixed liquor, under stirring, gained mixed liquor is injected in aqueous phase,
Removing organic solvent, aseptic filtration afterwards, the paclitaxel self-assembling polymers nanoparticle obtaining liquid dispersed dosage form is administered system
System；
The volumetric usage of described aqueous phase with the quality of Soluplus be calculated as 5～200mL/g (preferably 10～100mL/g, more preferably
15～50mL/g), the volumetric usage of described organic solvent is calculated as 0.014～1mL/mg (preferably with the quality of paclitaxel
0.02～0.1mL/mg, more preferably 0.03～0.05mL/mg).
Described preparation method generally operates at 0～30 DEG C, and described organic solvent is: ethanol, methanol, acetone, second
One in acetoacetic ester, dimethylformamide, dimethyl acetylamide, dimethyl sulfoxide, dichloromethane, butanol, amylalcohol or two
Plant the mixed solvent of any of the above ratio, preferred alcohol or acetone.
The method of described removing organic solvent can be the decompression vacuum pumping method of this area routine, ultrafiltration, dialysis etc..Generally,
If organic solvent is dichloromethane or ethyl acetate, it is recommended that decompression vacuum pumping method, vacuum 0～0.05MPa；If organic solvent is
Organic solvent miscible with water (such as: acetone, ethanol, methanol, dimethylformamide, dimethyl acetylamide, dimethyl sulfoxide,
Butanol or amylalcohol), it is recommended that ultrafiltration, ultrafilter membrane aperture 10～50kD.
Described aseptic filtration, lyophilization are conventional practices commonly used in the art.
Freeze drying protectant is added also in the paclitaxel self-assembling polymers nanoparticle drug-supplying system of gained liquid dispersed dosage form
Lyophilization, obtains the paclitaxel self-assembling polymers nanoparticle drug-supplying system of lyophilized formulations form；
The quality consumption of described freeze drying protectant is given with the paclitaxel self-assembling polymers nanoparticle of described liquid dispersed dosage form
The volume of medicine system is calculated as 5～250mg/ml, preferably 10～150mg/ml, more preferably 50～100mg/ml；
Described freeze drying protectant be the one in glucose, fructose, lactose, sucrose, chitosan, trehalose, mannitol or
The mixture of two or more arbitrary proportions, preferably mannitol.
Compared with prior art, the beneficial effects of the present invention is: the present invention with amphiphilic macromolecular material Soluplus as carrier,
Using injection method preparation to carry the self-assembling polymers nanoparticle of paclitaxel, relatively solution improves the uptake ratio of cell and reduces poison
Side effect.
(4) accompanying drawing explanation
Fig. 1 is pyrene emission spectrum in Soluplus dispersion liquid in embodiment 1；
Fig. 2 is paclitaxel-Soluplus self-assembled nanometer grain TEM figure in embodiment 2；
Fig. 3 is that in embodiment 4, paclitaxel-Soluplus self-assembled nanometer grain compares with the cell toxicant of solution (with cytosis
72h)；
Fig. 4 is that in embodiment 5, paclitaxel-Soluplus self-assembled nanometer grain compares with the cellular uptake of solution.
(5) detailed description of the invention
Below by specific embodiment, technical scheme is described further, but protection scope of the present invention is not limited to
This.
The structural identification of embodiment 1:Soluplus self-assembled nanometer grain
Pyrene is a kind of micropolar fluorescent probe of medium, belongs to condensed-nuclei aromatics class, under room temperature, when the concentration of pyrene is less than 10-5mol/L
Time, after pyrene solution excites at 335nm, 373,379,384,394 and 480nm, 5 fluorescent emission occur respectively
Electronic vibration peak.The ratio I of the fluorescence intensity of first electronic vibration peak 373nm and the 3rd electronic vibration peak 384nm1/I3With
The polarity of pyrene molecule local environment is in the strongest dependency.I1/I3The least, the polarity of corresponding environment is the least, i.e. hydrophobicity is the strongest.
Generally, it is considered that I1/I3The turning point of ratio is critical micelle concentration.
Precision weighs pyrene 19.62mg, adds anhydrous alcohol solution, and is diluted to 10ml measuring bottle, is configured to containing pyrene 1.962mg/ml
Solution.Precision measures this liquid 0.25ml, adds ethanol dilution to 50ml measuring bottle, is configured to containing pyrene 9.81 μ g/ml solution.Accurate
Measure this liquid 100 μ l, be placed in the clean test tube being dried, volatilize.Be separately added into containing Soluplus 0,10,50,100,150,
200, the dispersion liquid of 300,500,1000,5000,10000 μ g/ml, 37 DEG C of lucifuge constant temperature oscillation 12h.Glimmering in F-4600
Light spectrophotometer, fixing excitation wavelength 335nm, excite slit 5nm, launch slit 2.5nm, sweep speed 240nm/min,
350～500nm scannings, record emission spectrum figure, and calculate I373/I384。
It can be seen from figure 1 that along with the fluorescence intensity increasing pyrene of Soluplus concentration is gradually increased, illustrate that Soluplus has increasing to pyrene
Molten effect, but I373/I384Ratio do not occur reduce phenomenon.
Can there is macroscopic light blue opalescence when concentration is 5mg/ml, record Soluplus by laser granulometry
The scope of concentration 0.01～80mg/ml, mean diameter 56nm ± 5nm.
Embodiment 2: the preparation of paclitaxel-Soluplus self-assembled nanometer grain
| Prescription forms | Consumption |
| Paclitaxel | 200mg |
| Soluplus | 2000mg |
| Dehydrated alcohol | 10ml |
| Water for injection adds to | 100ml |
Paclitaxel and Soluplus are dissolved in dehydrated alcohol, under magnetic agitation, inject in water for injection, stir.
Measure the particle diameter of self-assembled nanometer grain, envelop rate and dilution stability respectively.Result display self-assembled nanometer grain mean diameter
Being about 95nm, more blank nanoparticle slightly increases；Envelop rate is all more than 99%；When Soluplus concentration is from 20mg/ml
When being diluted to 0.4mg/ml, almost without drug leakage；But continue dilution, gradually have drug leakage, during to 0.04mg/ml
Slip about 35%.
Embodiment 3: the preparation of paclitaxel-Soluplus self-assembled nanometer grain lyophilized preparation
Preparation: paclitaxel and Soluplus are dissolved in dehydrated alcohol, under magnetic agitation, injects in water for injection, stirs；
Again through ultrafilter membrane Biomax 30kD ultrafiltration, in nano suspension: fresh water for injection (1:50) ratio ultrafiltration removes anhydrous
Ethanol；Adding freeze drying protectant mannitol, sucrose or lactose, the quality consumption of freeze drying protectant is respectively water for injection quality
5%, 10% and 15%；Lyophilization, obtains paclitaxel-Soluplus self-assembled nanometer grain lyophilized preparation.
Result: with mannitol as freeze drying protectant, complete appearance, without subsiding.Other freeze drying protectant outward appearances exist in various degree
Defect；But redispersion and envelop rate are all had little to no effect.Mannitol consumption increases, and the particle diameter after lyophilized powder redispersion is slightly
There is increase.Therefore freeze drying protectant is excellent with 5% mannitol.
Embodiment 4: paclitaxel-Soluplus self-assembled nanometer grain compares with the cell in vitro poison of solution
MCF-7 breast cancer cell or A549 lung carcinoma cell, concentration 1 × 105Individual/mL is inoculated into 96 orifice plates, every hole 100 μ L,
Overnight incubation in 37 DEG C of incubators, to cell attachment, absorbs culture fluid.Every hole adds 100 μ L with diluting containing serum free culture system liquid
Paclitaxel solution and paclitaxel self-assembled nanometer grain and the empty vectors of respective concentration, paclitaxel concentration is respectively 0.1,1.2,5.9,
11.8 and 23.50 μMs, every concentration sets 3, multiple hole, sets blank well (containing culture medium and MTT but without cell), comparison simultaneously
Hole (containing culture medium, MTT and cell but not pastille).In incubator, cultivate 72h, in every hole, add 0.5% respectively
MTT solution 20 μ L, continues in 37 DEG C of incubators to cultivate 4h, carefully absorbs culture fluid, add DMSO 200 μ L, water in every hole
Flat shaking 10min, microplate reader 570nm and 630nm measure absorbance, calculate cell survival rate.
It can be seen from figure 3 that compared with solvent C remophoreEL of paclitaxel solution group, blank Soluplus self-assembled nanometer grain
Without any surfactant, it is 0.1～23.5 μM of scope at paclitaxel concentration, and MCF-7 or A549 co-culture of cells 72h,
Cell survival rate, all more than 90%, illustrates that it is almost without toxic and side effects.Compared with paclitaxel solution, paclitaxel-Soluplus
Self-assembled nanometer grain reduces the toxic and side effects of free drug, improves the safety of use.
Embodiment 4: paclitaxel-Soluplus self-assembled nanometer grain absorbs with the cell in vitro of solution and compares
MCF-7 breast cancer cell or A549 lung carcinoma cell, concentration 2 × 105Individual cell is inoculated in 12 orifice plates, every hole 1mL,
Being placed in 37 DEG C of incubators cultivation 24h, treat that cell attachment grows, sucking-off culture fluid, every hole adds the paclitaxel of concentration 58 μMs
-Soluplus self-assembled nanometer grain or solution 1mL, cultivate 1 respectively, 2,4,6h, remove culture fluid, with the PBS of 4 DEG C
Solution flushes three times, and removes cell surface absorption medicine and nanoparticle.Collect cell, add the SDS solution 100 μ L of 2%,
Concussion 5min, is sufficiently destroyed cell, adds 0.5mL ethanol extraction paclitaxel, and 10000rpm is centrifuged 5min, takes supernatant,
HPLC method measures, operation repetitive 3 parts, calculates cellular uptake amount.
As seen from Figure 4, each time point records MCF-7 cell and A549 cell is above solution group to the intake of nanoparticle.
A549 cellular uptake paclitaxel-Soluplus self-assembled nanometer grain in 1h to 4h scope, prolongation over time, intake by
Cumulative but 6h declines greatly, may the paclitaxel of picked-up cause caused by partial-length apoptosis because of cytotoxicity.MCF-7 cell
Picked-up paclitaxel-Soluplus self-assembled nanometer grain is then in 1h to 6h scope, prolongation in time, and intake is gradually increased.
Illustrate that Soluplus nanoparticle self-assembled nanometer promotes the cell picked-up to paclitaxel.
Claims (9)
1. a paclitaxel self-assembling polymers nanoparticle drug-supplying system, it is characterised in that described paclitaxel self assembly polymerization
Thing nanoparticle drug-supplying system mainly includes paclitaxel and Soluplus；Based on described paclitaxel and Soluplus, described paclitaxel
Percetage by weight be 0.1%～15%, the percetage by weight of described Soluplus is 99.9%～85%.
2. paclitaxel self-assembling polymers nanoparticle drug-supplying system as claimed in claim 1, it is characterised in that described purple
China fir alcohol self-assembling polymers nanoparticle drug-supplying system is liquid dispersed dosage form or is lyophilized formulations form.
3. the paclitaxel self-assembling polymers nanoparticle drug-supplying system of a liquid dispersed dosage form, it is characterised in that by purple
China fir alcohol, Soluplus, aqueous phase form；Based on described paclitaxel and Soluplus, the percetage by weight of described paclitaxel is
0.1%～15%, the percetage by weight of described Soluplus is 99.9%～85%, and the volume of described aqueous phase is 5～200mL/g
Soluplus；Described aqueous phase is soluble in water formulated by pH adjusting agent, or without pH adjusting agent, is directly water；Institute
The water stated is pure water, water for injection or sterilized water for injection；The pH value of described aqueous phase is 3.0～9.0.
4. the paclitaxel self-assembling polymers nanoparticle drug-supplying system of liquid dispersed dosage form as claimed in claim 3, its
Being characterised by, described pH adjusting agent is sodium dihydrogen phosphate, potassium dihydrogen phosphate, disodium hydrogen phosphate, dipotassium hydrogen phosphate, hydrogen-oxygen
Change at least one in sodium, hydrochloric acid, citric acid, tartaric acid.
5. the system of the paclitaxel self-assembling polymers nanoparticle drug-supplying system of liquid dispersed dosage form as claimed in claim 3
Preparation Method, it is characterised in that described preparation method is:
Paclitaxel and Soluplus are dissolved in organic solvent, obtain mixed liquor, under stirring, gained mixed liquor is injected in aqueous phase,
Removing organic solvent, aseptic filtration afterwards, the paclitaxel self-assembling polymers nanoparticle obtaining liquid dispersed dosage form is administered system
System；
The volumetric usage of described aqueous phase is calculated as 5～200mL/g with the quality of Soluplus, and the volumetric usage of described organic solvent is with purple
The quality of China fir alcohol is calculated as 0.014～1mL/mg.
6. preparation method as claimed in claim 5, it is characterised in that described organic solvent is: ethanol, methanol, third
In ketone, ethyl acetate, dimethylformamide, dimethyl acetylamide, dimethyl sulfoxide, dichloromethane, butanol, amylalcohol one
Plant or the mixed solvent of two or more arbitrary proportion.
7. the paclitaxel self-assembling polymers nanoparticle drug-supplying system of a lyophilized formulations form, it is characterised in that described lyophilizing
The paclitaxel self-assembling polymers nanoparticle drug-supplying system of dosage form is by the purple of liquid dispersed dosage form described in claim 3
China fir alcohol self-assembling polymers nanoparticle drug-supplying system adds freeze drying protectant postlyophilization and prepares.
8. the paclitaxel self-assembling polymers nanoparticle drug-supplying system of lyophilized formulations form as claimed in claim 7, its feature
Being, the quality consumption of described freeze drying protectant is given with the paclitaxel self-assembling polymers nanoparticle of described liquid dispersed dosage form
The volume of medicine system is calculated as 5～250mg/ml.
9. the paclitaxel self-assembling polymers nanoparticle drug-supplying system of lyophilized formulations form as claimed in claim 7, its feature
Being, described freeze drying protectant is the one in glucose, fructose, lactose, sucrose, chitosan, trehalose, mannitol
Or the mixture of two or more arbitrary proportion.
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113058027A (en) * | 2021-03-10 | 2021-07-02 | 浙江工业大学 | Preparation method of paclitaxel microparticles surface-modified by soybean agglutinin and tannic acid |
Citations (2)
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| CN1417242A (en) * | 2002-11-14 | 2003-05-14 | 天津大学 | Polyglycol grafted and modified cyanoacrylate copolymer and its prepn |
| CN101791411A (en) * | 2010-01-25 | 2010-08-04 | 中国药科大学 | Preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof |
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2016
- 2016-04-19 CN CN201610247223.7A patent/CN105878187A/en active Pending
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1417242A (en) * | 2002-11-14 | 2003-05-14 | 天津大学 | Polyglycol grafted and modified cyanoacrylate copolymer and its prepn |
| CN101791411A (en) * | 2010-01-25 | 2010-08-04 | 中国药科大学 | Preparation and application of amphiphilic polysaccharide conjugate and medicinal compositions thereof |
Non-Patent Citations (2)
| Title |
|---|
| EZEQUIEL BERNABEU ET AL.: ""Novel Soluplus®—TPGS mixed micelles for encapsulation of paclitaxel with enhanced in vitro cytotoxicity on breast and ovarian cancer cell lines"", 《COLLOIDS AND SURFACES B: BIOINTERFACES》 * |
| 孟胜男等: "《药剂学》", 31 January 2016, 中国医药科技出版社 * |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113058027A (en) * | 2021-03-10 | 2021-07-02 | 浙江工业大学 | Preparation method of paclitaxel microparticles surface-modified by soybean agglutinin and tannic acid |
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Application publication date: 20160824 |