CN103169662A - Paclitaxel polymer nanoparticle and preparation method - Google Patents
Paclitaxel polymer nanoparticle and preparation method Download PDFInfo
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- CN103169662A CN103169662A CN2011104368818A CN201110436881A CN103169662A CN 103169662 A CN103169662 A CN 103169662A CN 2011104368818 A CN2011104368818 A CN 2011104368818A CN 201110436881 A CN201110436881 A CN 201110436881A CN 103169662 A CN103169662 A CN 103169662A
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Abstract
The invention discloses a paclitaxel polymer nanoparticle. The paclitaxel polymer nanoparticle can be used as a slow-release carrier of a paclitaxel medicament and is characterized in that the particle size of the nanoparticle is 50-800nm, a composition of the paclitaxel polymer nanoparticle contains the components of a biodegradable polymer material, the paclitaxel medicament and a stabilizing agent; the encapsulation rate of the paclitaxel medicament is within 2.0-6.0%; and the paclitaxel polymer nanoparticle has a paclitaxel slow-release effect. The invention also discloses a preparation method of the nanoparticle. The paclitaxel can be scattered in the nanoparticle prepared from the biodegradable polymer material under the condition of maintaining the original biological activity of the paclitaxel. Pure physical effects are played in the whole process, side effects brought by residue of other reagents in the chemical synthesis process can be effectively avoided, and the prepared nanoparticle can effectively play a role in medicament slow release. Compared with a conventional method, the preparation method does not need chemical reaction, and is simple in preparation process, relatively low in cost and relatively energy-saving.
Description
Technical field
The present invention relates to a kind of high molecular nanometer granule and preparation method, particularly relate to a kind of taxol polymer nano-particle and preparation method, apply to the clinical treatment of tumor.
Background technology
Paclitaxel is one of broad-spectrum anti-tumor medicine of tool curative effect clinically so far, yet the clinical side effects that when its water solublity extreme difference and vivo medicine-feeding, local excessive concentration causes has greatly limited it and used widely clinically.Avoid the side effect of disposable local high amount of drug toxicity in order to strengthen the problem that solves the paclitaxel indissoluble, it is the best way that paclitaxel is prepared into slow-releasing agent.
At present, the taxadol slow release medicament of open report has had liposome, and Emulsion, polymer microsphere and nano-particle etc. along with going deep into of research and clinical trial, are found existing taxadol slow release medicament separately pluses and minuses again:
(1) Paclitaxel liposome refers to adopt the lipoids bimolecular paclitaxel of oiliness to be encapsulated in the spherical preparation of superminiature of interior formation.Can stop combination between the paclitaxel granule in the interlayer of its hydrophobic group, increase taxol solubility.
Preparation technology generally adopts membrane process to prepare Paclitaxel liposome, paclitaxel in its formula, and cuorin, the mol ratio of lecithin and sodium deoxycholate is 1: 1: 5: 5, the solution clarification, without variable color and precipitation, but direct injection uses.But also find simultaneously, liposome has the class cellularity, and paclitaxel is mainly accumulated in the tissue of the parts such as liver, spleen, lung and bone marrow and organ.Although liposome self is nontoxic to human body, non-immunogenicity, biodegradable, easily break in the process of motion in vivo, in body, transportation is difficult to control, and the action effect of a large amount of reduction paclitaxels has strengthened the risk of paclitaxel side effect.
(2) paclitaxel emulsion, and liposome is similar is dissolved in the paclitaxel of oiliness in oil, is distributed to the stable oil in water emulsion of formation in water.
Kaufman etc. are dissolved in paclitaxel in safflower oil or soybean oil, then consist of stable oil in water emulsion with various surfactant-dispersed in water, also can add according to final use the additive such as glycerol to regulate the permeability of compositions, prepared yew alcohol micro-emulsion agent form rounding, mean diameter is 120-220nm.But equally with Paclitaxel liposome easily break in vivo and gather the situation that adds large volume, being difficult in vivo control.Simultaneously, some oily matter (as Oleum Ricini) as the oiliness solvent that uses in preparation can impel a large amount of histamine releasings, thereby causes serious anaphylaxis.Simultaneously, surfactant is essential in the preparation process of paclitaxel emulsion, and the accumulation of its consumption can strengthen security risk.
(3) polymer microsphere of paclitaxel or nano-particle, that degradable high polymer material (as polylactic acid etc.) with good biocompatibility mixes with the paclitaxel of oiliness and is dissolved in altogether in organic solvent, after the physics emulsifying, remove organic solvent, polymer microsphere or the nano-particle of paclitaxel that obtained load.Because dissolubility and the size of medicine is inversely proportional to, nano-particle can make medicine be embedded in nano-particle inside or be adsorbed in nano grain surface with enough little granule as the carrier that is insoluble in the paclitaxel of water, increase the specific surface area of insoluble medicine, thereby increase the dissolubility of medicine.
But the taxol nanoparticle that has is at present also met very large problem:
A) a kind of macromolecular material of one pack system can effectively be controlled the release of paclitaxel, as paclitaxel polylactic acid nano granule, a large amount of studies show that, load faster than perfect condition than theoretical releasing effect in the dispose procedure of lactic acid nano-particle of paclitaxel, simultaneously, owing to only having a kind of composition of polylactic acid, although can regulate the ratio of paclitaxel in polylactic acid, the situation that can not regulate the speed of polylactic acid rate of release.
B) the synthesis of polymer material cost of multi-component block altogether is very big, complicated process of preparation, there are simultaneously by-product and raw-material residue problem in chemosynthesis, as paclitaxel Poly(D,L-lactide-co-glycolide nano-particle, Poly(D,L-lactide-co-glycolide may have the remnants of lactic acid monomer in the material building-up process.
Contrast above-mentioned three kinds of medicaments, think at present the slow release effect of polymer microsphere and nano-particle generally acknowledges it is best.Can need the look for a kind of one pack system that can avoid (1) can be very big with the synthesis of polymer material cost of the release of controlling paclitaxel and (2) multi-component block altogether, the taxadol slow release medicament of complicated process of preparation and by-product residue problem.
Summary of the invention
The present invention discloses a kind of novel taxol polymer nano-particle, applies to the taxol drug slow-released carrier.
The invention provides a kind of taxol polymer nano-particle, can be used as the slow-released carrier of taxol drug, it is characterized in that, the particle diameter of nano-particle is 50nm-800nm; Its compositions comprises biodegradable macromolecular material, taxol drug and stabilizing agent; The envelop rate of taxol drug is at 2.0-6.0%; Has the taxadol slow release effect.
Described biodegradable macromolecular material is a kind of or its combination in polylactic acid, poly butyric ester, poly-(lactic acid-ethanol).
Described taxol drug is pure paclitaxel, or contains taxol drug mixture or compound recipe.
Described taxol polymer nano-particle is pulverous nano-particle that contains paclitaxel, or the suspension of above-mentioned granule.
The invention provides a kind of preparation method of taxol polymer nano-particle, it is characterized in that comprising the following steps:
(1) biodegradable macromolecular material is dissolved in organic solvent, magnetic agitation is dissolved to dissolving fully, then adds taxol drug, continues magnetic agitation to being uniformly dissolved, and forms organic facies;
(2) aqueous solution of stabilizing agent is water;
(3) with above-mentioned organic facies and stabilizing agent aqueous solution supersound process, form emulsion;
(4) emulsion is poured in Rotary Evaporators and to be processed to remove organic solvent;
(5) high speed centrifugation is also with the resuspended nano-particle of suspension;
(6) after the step of repeated multiple times " high speed centrifugation-resuspended ", can obtain the suspension of taxol polymer nano-particle.
(7) lyophilization is processed, and can obtain the taxol polymer nano-particle.
Described organic solvent is a kind of and combination in dichloromethane, chloroform.
Described stabilizing agent is a kind of or its combination in polyvinyl alcohol, Polyethylene Glycol, preferentially selects polyvinyl alcohol, and the concentration of stabilizing agent is 0.5-4.0g/100ml.
Organic facies before described emulsion is ultrasonic and the volume ratio of water are 1: 100～20: 100.
Described supersound process is that the time of supersound process is 5～20 minutes, works 3 seconds, has a rest 3 seconds.
The whole process of preparation is simple physical action, can effectively avoid the residual of other reagent in the chemosynthesis process or side effect that other surfactants bring, prepared nano-particle can effectively play the effect of medicament slow release, and safety can directly enter in body.
The taxol polymer nano-particle that the present invention relates to as the pharmaceutical carrier of paclitaxel, can apply to the slow-released system of the taxol drug in oncotherapy.It is advantageous that, compare with the paclitaxel loaded nano-particle of chemosynthesis, paclitaxel and macromolecular material are physical mixed, and the function Characteristics that does not change taxol drug has been avoided again the residual of by-product and catalyst simultaneously.Resulting taxol polymer nano particle diameter size homogeneous has the effect of significant medicament slow release, and preparation technology is more simple, and cost is lower.
Description of drawings:
Fig. 1 is that paclitaxel/polylactic acid nano granule prepares schematic diagram.
A is for to be placed in same beaker with organic facies and water; B is the supersound process process; C is emulsion; D removes the nano granule suspension after organic solvent; 1 for the stabilizing agent aqueous solution be water; 2 is organic facies; 3 are the Ultrasound Instrument probe; 4 is emulsion microemulsion pearl; 5 for wearing the nano-particle in load stabilizing agent aqueous solution.
Fig. 2 is the scanning electron microscope (SEM) photograph of paclitaxel/polylactic acid nano granule.
Fig. 3 is the paclitaxel release profiles of paclitaxel/polylactic acid nano granule.
The specific embodiment
Embodiment 1:
Investigate the macromolecular material kind to the impact of paclitaxel/polylactic acid nano granule.Glycolic=50: 50), poly butyric, (poly butyric: polylactic acid=50: 50) mixture is dissolved in respectively in the 100ml dichloromethane poly butyric/polylactic acid take respectively the polylactic acid of 3g, poly-(lactic acid-ethanol) (lactic acid:, room temperature magnetic force stirring and dissolving is to dissolving fully, the paclitaxel that adds 0.3g, the continuation magnetic agitation formed organic facies to being uniformly dissolved in 10 minutes.Take the 30g polyvinyl alcohol and be dissolved in 1000ml water, high-temperature digestion formed water to dissolving fully and cool to room temperature in 1 hour.Take out above-mentioned organic facies 2ml and water 200ml and be placed in dry beaker, the supersound process of 100W 10 minutes (worked 3 seconds, had a rest 3 seconds) forms emulsion.At once emulsion is poured into Rotary Evaporators and processed to remove dichloromethane.After 1 hour, high speed centrifugation can obtain paclitaxel/polylactic acid nano granule at resuspended nano-particle.Detect the prepared paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel.The computing formula of charging ratio is as follows:
Paclitaxel amount in charging ratio (%)=10mg nano-particle/10mg nano-particle * 100%
Data see Table 1.Wherein (poly butyric: polylactic acid=50: 50) the prepared paclitaxel of mixture/polylactic acid nano grain diameter size reasonable, the charging ratio of paclitaxel is maximum for poly butyric/polylactic acid.
The impact of table 1. macromolecular material kind on the paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel
Embodiment 2:
Investigate the organic solvent kind to the impact of paclitaxel/polylactic acid nano granule.(poly butyric: polylactic acid=50: 50) mixture is dissolved in respectively in 1: 1 mixed liquor of 100ml dichloromethane, chloroform, dichloromethane/chloroform to take respectively poly butyric/polylactic acid of 1g, room temperature magnetic force stirring and dissolving is to dissolving fully, the paclitaxel that adds 0.3g, the continuation magnetic agitation formed organic facies to being uniformly dissolved in 10 minutes.Take the 30g polyvinyl alcohol and be dissolved in 1000ml water, high-temperature digestion formed water to dissolving fully and cool to room temperature in 1 hour.Take out above-mentioned organic facies 40ml and water 200ml and be placed in dry beaker, the supersound process of 100W 10 minutes (worked 3 seconds, had a rest 3 seconds) forms emulsion.At once emulsion is poured into Rotary Evaporators and processed to remove organic solvent.After 1 hour, high speed centrifugation can obtain paclitaxel/polylactic acid nano granule at resuspended nano-particle.Detect the prepared paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel, the computing formula of charging ratio is as follows:
Paclitaxel amount in charging ratio (%)=10mg nano-particle/10mg nano-particle * 100%
Data see Table 2.Wherein 1: 1 mixed liquor of dichloromethane/chloroform is as the prepared paclitaxel of organic facies/polylactic acid nano grain diameter size reasonable, and the charging ratio of paclitaxel is maximum.
The impact of table 2. organic solvent kind on the paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel
Embodiment 3:
The impact of the concentration of investigation macromolecular material in organic facies on paclitaxel/polylactic acid nano granule.Take respectively 0.5g, 1g, 2g, 3g poly butyric polylactic acid (poly butyric: polylactic acid=50: 50) mixture is dissolved in respectively in 1: 1 mixed liquor of 100ml dichloromethane/chloroform, room temperature magnetic force stirring and dissolving is to dissolving fully, the paclitaxel that adds 0.3g, the continuation magnetic agitation formed organic facies to being uniformly dissolved in 10 minutes.Take the 30g polyvinyl alcohol and be dissolved in 1000ml water, high-temperature digestion formed water to dissolving fully and cool to room temperature in 1 hour.Take out above-mentioned organic facies 10ml and water 200ml and be placed in dry beaker, the supersound process of 100W 10 minutes (worked 3 seconds, had a rest 3 seconds) forms emulsion.At once emulsion is poured into Rotary Evaporators and processed to remove 1: 1 mixed liquor of dichloromethane/chloroform.After 1 hour, high speed centrifugation can obtain paclitaxel/polylactic acid nano granule at resuspended nano-particle.Detect the prepared paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel, the computing formula of charging ratio is as follows:
Paclitaxel amount in charging ratio (%)=10mg nano-particle/10mg nano-particle * 100%
Data see Table 3.Wherein, the 1g poly butyric polylactic acid (poly butyric: polylactic acid=50: 50) the prepared paclitaxel of mixture/polylactic acid nano grain diameter size reasonable, the charging ratio of paclitaxel is maximum.
The impact of the concentration of macromolecular material on the paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel in table 3. organic facies
Embodiment 4:
Investigate the impact of content of taxol on paclitaxel/polylactic acid nano granule in organic facies.(poly butyric: polylactic acid=50: 50) mixture is dissolved in respectively in 1: 1 mixed liquor of 100ml dichloromethane/chloroform to take respectively poly butyric/polylactic acid of 1g, room temperature magnetic force stirring and dissolving is to dissolving fully, the paclitaxel that adds 0.1g, 0.2g, 0.3g, 0.4g, the continuation magnetic agitation formed organic facies to being uniformly dissolved in 10 minutes.Take the 30g polyvinyl alcohol and be dissolved in 1000ml water, high-temperature digestion formed water to dissolving fully and cool to room temperature in 1 hour.Take out above-mentioned organic facies 10ml and water 200ml and be placed in dry beaker, the supersound process of 100W 10 minutes (worked 3 seconds, had a rest 3 seconds) forms emulsion.At once emulsion is poured into Rotary Evaporators and processed to remove organic solvent.After 1 hour, high speed centrifugation can obtain paclitaxel/polylactic acid nano granule at resuspended nano-particle.Detect the prepared paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel, the computing formula of charging ratio is as follows:
Paclitaxel amount in charging ratio (%)=10mg nano-particle/10mg nano-particle * 100%
Data see Table 4.Wherein, the size of the prepared paclitaxel of the paclitaxel of 0.3g and 0.4g/polylactic acid nano granule is all reasonable, and the charging ratio of paclitaxel is also basic identical, for avoiding the loss amount of paclitaxel in preparation excessive, selects the paclitaxel of 0.3g to produce.
The impact of content of taxol on the paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel in table 4. organic facies
Embodiment 5:
Investigate the aqueous phase polyvinyl alcohol content to the impact of paclitaxel/polylactic acid nano granule.(poly butyric: polylactic acid=50: 50) mixture is dissolved in respectively in 1: 1 mixed liquor of 100ml dichloromethane/chloroform to take respectively poly butyric/polylactic acid of 1g, room temperature magnetic force stirring and dissolving is to dissolving fully, add the 0.3g paclitaxel, the continuation magnetic agitation formed organic facies to being uniformly dissolved in 10 minutes.The polyvinyl alcohol that takes respectively 10g, 20g, 30g and 40g is dissolved in 1000ml water, and high-temperature digestion formed water to dissolving fully and cool to room temperature in 1 hour.Take out above-mentioned organic facies 10ml and water 200ml and be placed in dry beaker, the supersound process of 100W 10 minutes (worked 3 seconds, had a rest 3 seconds) forms emulsion.At once emulsion is poured into Rotary Evaporators and processed to remove organic solvent.After 1 hour, high speed centrifugation can obtain paclitaxel/polylactic acid nano granule at resuspended nano-particle.Detect the prepared paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel, the computing formula of charging ratio is as follows:
Paclitaxel amount in charging ratio (%)=10mg nano-particle/10mg nano-particle * 100%
Data see Table 5.Wherein, the prepared paclitaxel of the polyvinyl alcohol water solution of 20g/1000ml/polylactic acid nano grain diameter size reasonable, the charging ratio of paclitaxel is maximum.
The impact of table 5. aqueous phase polyvinyl alcohol content on the paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel
Embodiment 6:
The ratio of organic facies and water of investigating is on the impact of paclitaxel/polylactic acid nano granule.(poly butyric: polylactic acid=50: 50) mixture is dissolved in respectively in 1: 1 mixed liquor of 100ml dichloromethane/chloroform to take respectively poly butyric/polylactic acid of 1g, room temperature magnetic force stirring and dissolving is to dissolving fully, add the 0.3g paclitaxel, the continuation magnetic agitation formed organic facies to being uniformly dissolved in 10 minutes.The polyvinyl alcohol that takes respectively 20g is dissolved in 1000ml water, and high-temperature digestion formed water to dissolving fully and cool to room temperature in 1 hour.The above-mentioned organic facies and the water 200ml that take out respectively 5ml, 7.5ml, 10ml and 12.5ml are placed in dry beaker, and the supersound process of 100W 10 minutes (worked 3 seconds, had a rest 3 seconds) forms emulsion.At once emulsion is poured into Rotary Evaporators and processed to remove organic solvent.After 1 hour, high speed centrifugation can obtain paclitaxel/polylactic acid nano granule at resuspended nano-particle.Detect the prepared paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel, the computing formula of charging ratio is as follows:
Paclitaxel amount in charging ratio (%)=10mg nano-particle/10mg nano-particle * 100%
Data see Table 6.Wherein, the prepared paclitaxel of the ratio of the organic facies of 10ml and 150ml water/polylactic acid nano grain diameter size reasonable, the charging ratio of paclitaxel is maximum.
The impact of the ratio of table 6. organic facies and water on the paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel
Embodiment 7:
Investigate emulsifying manner to the impact of paclitaxel/polylactic acid nano granule.(poly butyric: polylactic acid=50: 50) mixture is dissolved in respectively in 1: 1 mixed liquor of 100ml dichloromethane/chloroform to take respectively poly butyric/polylactic acid of 1g, room temperature magnetic force stirring and dissolving is to dissolving fully, add the 0.3g paclitaxel, the continuation magnetic agitation formed organic facies to being uniformly dissolved in 10 minutes.The polyvinyl alcohol that takes respectively 20g is dissolved in 1000ml water, and high-temperature digestion formed water to dissolving fully and cool to room temperature in 1 hour.Take out respectively above-mentioned organic facies 10ml and water 200ml and be placed in dry beaker, the supersound process of 100W 5 minutes, 10 minutes, 15 minutes and 20 minutes (worked 3 seconds, had a rest 3 seconds) form emulsion.At once emulsion is poured into Rotary Evaporators and processed to remove organic solvent.After 1 hour, high speed centrifugation can obtain paclitaxel/polylactic acid nano granule at resuspended nano-particle.Detect the prepared paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel, the computing formula of charging ratio is as follows:
Paclitaxel amount in charging ratio (%)=10mg nano-particle/10mg nano-particle * 100%
Data see Table 7.Wherein, the supersound process of 100W 15 minutes and 20 minutes prepared paclitaxel/polylactic acid nano grain diameter sizes are all reasonable, and the supersound process of the 100W paclitaxel charging ratio of 15 minutes is maximum.
The impact of table 7. supersound process time on the paclitaxel/mean diameter of polylactic acid nano granule and the charging ratio of paclitaxel
Embodiment 8:
Precision takes the Erlenmeyer flask that sample 5mg in embodiment 7 is placed in the 50ml of sterilization, adds the 10ml phosphate buffered solution.Be placed on jolting release medicine in 37 ℃ of constant temperature air bath agitators, the jolting frequency is 100 rev/mins.After certain interval of time, sample is taken out centrifugal 10min under rear 12000 rev/mins, nano-particle is separated with releaser.Microsphere is carried out further drug release with new phosphate buffer Eddy diffusion, with 1ml acetonitrile/water solution (60/40) dissolving taxol drug, measure with the method for high performance liquid chromatography (HPLC) the taxol drug amount that discharges after the supernatant lyophilizing.And calculate burst size with following formula:
The taxol drug amount discharges the total taxol drug amount of taxol drug amount/sample * 100% in (%)=supernatant
Each sample of release experiment is parallel does three, and final result is got the meansigma methods of three Duplicate Samples.
Claims (9)
1. taxol polymer nano-particle can be used as the slow-released carrier of taxol drug, it is characterized in that, the particle diameter of nano-particle is 50nm-800nm; Its compositions comprises biodegradable macromolecular material, taxol drug and stabilizing agent; The envelop rate of taxol drug is at 2.0-6.0%; Has the taxadol slow release effect.
2. a kind of taxol polymer nano-particle according to claim 1, is characterized in that, described biodegradable macromolecular material is a kind of or its combination in polylactic acid, poly butyric ester, poly-(lactic acid-ethanol).
3. a kind of taxol polymer nano-particle according to claim 1, is characterized in that, described taxol drug is pure paclitaxel, or contains taxol drug mixture or compound recipe.
4. a kind of taxol polymer nano-particle according to claim 1, is characterized in that, described taxol polymer nano-particle is pulverous nano-particle that contains paclitaxel, or the suspension of above-mentioned granule.
5. according to claim 1, or 2, or 3, or the preparation method of 4 described a kind of taxol polymer nano-particle, it is characterized in that comprising the following steps:
(1) biodegradable macromolecular material is dissolved in organic solvent, magnetic agitation is dissolved to dissolving fully, then adds taxol drug, continues magnetic agitation to being uniformly dissolved, and forms organic facies;
(2) aqueous solution of stabilizing agent is water;
(3) with above-mentioned organic facies and stabilizing agent aqueous solution supersound process, form emulsion;
(4) emulsion is poured in Rotary Evaporators and to be processed to remove organic solvent;
(5) high speed centrifugation is also with the resuspended nano-particle of suspension;
(6) after the step of repeated multiple times " high speed centrifugation-resuspended ", can obtain the suspension of taxol polymer nano-particle.
(7) lyophilization is processed, and can obtain the taxol polymer nano-particle.
6. a kind of preparation method of taxol polymer nano-particle according to claim 5, is characterized in that, described organic solvent is a kind of and combination in dichloromethane, chloroform.
7. a kind of preparation method of taxol polymer nano-particle according to claim 5, it is characterized in that, described stabilizing agent is a kind of or its combination in polyvinyl alcohol, Polyethylene Glycol, preferentially selects polyvinyl alcohol, and the concentration of stabilizing agent is 0.5-4.0g/100ml.
8. a kind of preparation method of taxol polymer nano-particle according to claim 5, is characterized in that, the organic facies before described emulsion is ultrasonic and the volume ratio of water are 1: 100～20: 100.
9. a kind of preparation method of taxol polymer nano-particle according to claim 5, is characterized in that, described supersound process is that the time of supersound process is 5～20 minutes, works 3 seconds, has a rest 3 seconds.
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| CN103446060A (en) * | 2013-09-22 | 2013-12-18 | 上海市第八人民医院 | Docetaxel polydroxybutyrate nanoparticle, manufacturing method and pisum sativum agglutinin modification method and application |
| CN104826129A (en) * | 2015-05-14 | 2015-08-12 | 安徽农业大学 | Nanometer traditional Chinese medicine quercetin-PLGA (poly lactic acid-glycolic acid) and preparation method thereof |
| CN105055312A (en) * | 2015-09-07 | 2015-11-18 | 苏州纳诺康生物技术有限公司 | Method for preparing docetaxel drug-loaded nanoparticles with polylactic acid/hydroxyglycollic acid copolymer as material |
| CN106546706A (en) * | 2015-09-21 | 2017-03-29 | 上海复旦张江生物医药股份有限公司 | The release in vitro method of testing of liposome medicament prepared by pH gradient active loading method |
| CN106546705A (en) * | 2015-09-21 | 2017-03-29 | 上海复旦张江生物医药股份有限公司 | A kind of method of testing of liposome medicament release in vitro |
| CN107348507A (en) * | 2017-07-06 | 2017-11-17 | 天津工业大学 | Carry the preparation of bata-carotene PLA (PLA) nanoparticle |
| US10363219B2 (en) | 2016-10-28 | 2019-07-30 | Zhejiang Academy Of Forestry | Method of preparing albumin nanoparticle carrier wrapping taxane drug |
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- 2011-12-22 CN CN2011104368818A patent/CN103169662A/en active Pending
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| HYUN JUNG LIM ETAL: "A Novel Technique for Loading of Paclitaxel-PLGA Nanoparticles onto ePTFE Vascular Grafts", 《BIOTECHNOL. PROG》 * |
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| CN103446060A (en) * | 2013-09-22 | 2013-12-18 | 上海市第八人民医院 | Docetaxel polydroxybutyrate nanoparticle, manufacturing method and pisum sativum agglutinin modification method and application |
| CN103446060B (en) * | 2013-09-22 | 2015-09-02 | 上海市第八人民医院 | Carry Docetaxel sativum agglutinin and preparation method, pisum sativum agglutinin method of modifying and application |
| CN104826129A (en) * | 2015-05-14 | 2015-08-12 | 安徽农业大学 | Nanometer traditional Chinese medicine quercetin-PLGA (poly lactic acid-glycolic acid) and preparation method thereof |
| CN105055312A (en) * | 2015-09-07 | 2015-11-18 | 苏州纳诺康生物技术有限公司 | Method for preparing docetaxel drug-loaded nanoparticles with polylactic acid/hydroxyglycollic acid copolymer as material |
| CN106546706A (en) * | 2015-09-21 | 2017-03-29 | 上海复旦张江生物医药股份有限公司 | The release in vitro method of testing of liposome medicament prepared by pH gradient active loading method |
| CN106546705A (en) * | 2015-09-21 | 2017-03-29 | 上海复旦张江生物医药股份有限公司 | A kind of method of testing of liposome medicament release in vitro |
| CN106546705B (en) * | 2015-09-21 | 2020-03-17 | 上海复旦张江生物医药股份有限公司 | Test method for in-vitro release of liposome drug |
| US10363219B2 (en) | 2016-10-28 | 2019-07-30 | Zhejiang Academy Of Forestry | Method of preparing albumin nanoparticle carrier wrapping taxane drug |
| CN107348507A (en) * | 2017-07-06 | 2017-11-17 | 天津工业大学 | Carry the preparation of bata-carotene PLA (PLA) nanoparticle |
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Application publication date: 20130626 |