CN103271874A - Paclitaxel-encapsulated PEG-PLGA-PEG (Polyethylene Glycol-Polylactic-Co-Glycolic Acid-Polyethylene Glycol) nanoparticle and preparation method thereof - Google Patents
Paclitaxel-encapsulated PEG-PLGA-PEG (Polyethylene Glycol-Polylactic-Co-Glycolic Acid-Polyethylene Glycol) nanoparticle and preparation method thereof Download PDFInfo
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Abstract
The invention discloses a paclitaxel-encapsulated PEG-PLGA-PEG (Polyethylene Glycol- Polylactic-Co-Glycolic Acid-Polyethylene Glycol, PELGE for short) nanoparticle and a preparation method thereof. The nanoparticle preparation comprises paclitaxel, a PEG-PLGA-PEG triblock copolymerization compound, a surface active agent and water for injection. The preparation method of the paclitaxel-encapsulated PEG-PLGA-PEG nanoparticle comprises the following steps of: mixing an oil phase and a water phase in proportion, wherein the paclitaxel and the copolymerization compound carrier material are dissolved in the oil phase, and the surface active agent is dissolved in the water phase, obtaining a milk-white emulsion under the action of high pressure or high shear force, and then removing an organic solvent to obtain the nanoparticle preparation. The nanoparticle preparation is subjected to freeze drying to obtain freeze-dried powder injection. According to the preparation method, few preparation steps are needed, the operation is simple, the requirements on instruments and equipment are low, and the prepared nanoparticle preparation has uniform particle size, high encapsulation efficiency and good stability as well as the advantages of long circularity, low toxic and side effects and the like.
Description
Technical field
The present invention relates to the PELGE nano particle preparations that a kind of bag carries paclitaxel, the invention still further relates to the preparation method of this nanoparticle simultaneously, belong to medical technical field.
(Paclitaxel is a kind of tetracyclic diterpene compounds that extracts from Chinese yew genus plants PTX) to paclitaxel, and it has good anti-cancer activity, and is especially obvious to breast carcinoma and ovarian cancer therapeutical effect, as one of present clinical line cancer therapy drug.But, paclitaxel is insoluble in water, so often use surfactant polyoxyethylene Oleum Ricini (Cremophor EL) and ethanol solubilising clinically, wherein polyoxy ethyl Oleum Ricini can produce untoward reaction such as allergy, nephrotoxicity, cardiac toxicity, neurotoxicity.These toxic and side effects have seriously limited the curative effect of paclitaxel and application clinically.
For these reasons, research worker constantly kit carry the new formulation of paclitaxel.For example: patent documentation CN102302786A discloses the preparation method of beta cyclo dextrin polymer-included taxol.Wherein used beta-schardinger dextrin-as the enclose material, the beta-schardinger dextrin-low price, easy to prepare, preparation becomes the clathrate rear stability and dissolubility has very big raising, but beta-schardinger dextrin-itself has nephrotoxicity and hemolytic, can not be used for intravenous injection, greatly restrict the clinical practice of its preparation.
Patent documentation CN102125521A discloses a kind of paclitaxel emulsion, Preparation Method And The Use.But Emulsion belongs to the heterogeneous disperse system of thermodynamic instability, and oxidation takes place easily, become sour, layering, flocculation, phase inversion, merging and destruction, has greatly limited the performance of paclitaxel drug effect.
Patent documentation CN101011357A discloses a kind of preparation method of Paclitaxel liposome preparation.But liposome encapsulation is low, stability is low, leaks out the medicine of parcel under the situation of transportation and long term store easily, is unfavorable for injection.
Patent documentation CN101167716A discloses a kind of taxol nanometer particle and its preparation method and application.Wherein used chitosan as carrier material, chitosan is poly-excellent biological compatibility and biological activity, be easy to advantage such as chemical improvement.But as a kind of natural macromolecular material, chitosan has the shortcoming that self is difficult to overcome always: the chitosan molecule amount distributed pole that difficult quality is accurately controlled, produced is wide, poor repeatability, has increased the difficulty that large-scale industrialization is produced.
This shows that along with the continuous development and progress of new formulation and drug-supplying system, the problem that part exists is solved, such as poorly soluble, poor stability, erious adverse reaction etc.But their defectives have separately also limited its application clinically, cause these preparations can only rest on the experimental stage, can't drop into commercial production.So, be badly in need of a kind of more suitably paclitaxel carrier material and preparation and break these technical bottlenecks, prepare that stability is high, toxic and side effects is little, the tangible preparation of curative effect is for clinical use.
In recent years, research worker finds that the polymeric material of novel degradable has good biocompatibility, non-immunogenicity, copolymer ratio and molecular weight and can accurately control, be easy to outstanding advantages such as preparation.Therefore the nanoparticle that is prepared from these polymeric materials also becomes the research focus of anti-cancer medicament carrier in recent years.The common carrier material is polyacrylic resin (Polyacrylic acid resin), polyglycolic acid (Polyglycolic acid, PGA), polylactic acid (Polylactice acid, PLA), polylactic acid-glycolic guanidine-acetic acid copolymer (Poly (lactic-co-glycolic acid, PLGA), pla-pcl (Poly-caprolactone, PCL) etc.Wherein, PLGA has excellent biological compatibility, and non-immunogenicity can decompose and advantage such as absorption in vivo, is applied in the human body (intramuscular injection) by food and drug administration (FDA) approval.
Simultaneously, (polyethylene glycol PEG) grafts on the attention that PLGA has caused research worker with Polyethylene Glycol.PEG has stronger hydrophilic and excellent biological compatibility, does not have immunogenicity in vivo and can be biodegradable into nontoxic natural metabolism product.Be used for human body by the FDA approval as pharmaceutical carrier.Therefore, be called for short PELGE with PLGA and the synthetic novel high polymer degradation material PEG-PLGA-PEG(of PEG) or PEG-PLGA(abbreviation PELGA) be good drug carrier material.Experiment shows: compare with simple PLGA nanoparticle, can escape the phagocytosis of macrophage through the PLGA nanoparticle of PEG modification effectively.So behind the quiet notes PELGE nanoparticle, the holdup time of the medicine in the nanoparticle in blood circulation obviously prolongs.
Preparation has above advantage in view of the polymeric material of novel degradable, many pharmaceutical researchers with PLGA,, PELGA, PELGE material bag medicine carrying thing.Present acquired preparation and technology of preparing were compared to being greatly improved in the past, but they also have various shortcomings.
Patent documentation CN 102949347A discloses PLGA nanoparticle of bag carrying docetaxel and preparation method thereof, but PLGA nanoparticle surface has certain hydrophobicity, easily identified, engulf by the macrophage in the body behind the quiet notes of its nanoparticle that is prepared from, make this nanoparticle time decreased in blood circulation, curative effect reduces.
Patent documentation CN 101884618A discloses a kind of long-circulating paclitaxel nanoparticles and preparation method thereof.This preparation method is carried paclitaxel with the PEG-PLGA bag, and PEG-PLGA is the termination branch PEG with PLGA, though more simple PLGA circulation time has had raising, its stability and circulation time can not show a candle to the PELGE at PLGA two ends grafting PEG.And its preparation process is many, complex operation.Be chosen in the preparation method under the condition of stirring at low speed and remove organic agent, need more than 3-5 hour, preparation time is long.
At Paclitaxel-loaded PEGylated PLGA-based nanoparticles:In vitro and invivo evaluation (Journal of Controlled Release 133 (2009) 11 – 17), Surface modification of paclitaxel-loaded polymeric nanoparticles:Evaluation of in vitro cellular behavior and in vivo pharmacokinetic(Polymer 53 (2012) 5078-5086) etc. in the document, adopt the method for nanometer precipitation, during with PEG-PLGA bag medicine carrying thing, it need prepare colostrum, and colostrum is added dropwise to water with certain speed, rate of addition has played crucial effect to the formation of nanoparticle, cause this method and technology instability, separated out medicine easily.And on commercial production, when liquor capacity is big, be difficult to accurately control its dropping and diffusion velocity.Use the nanoparticle sedimentation method to prepare standard compliant nanoparticle in the chamber by experiment.
In sum, the novel bag that also do not have good stability, envelop rate height, good effect now, preparation method is simple, preparation time is short, is easy to accurately control carries formulation for paclitaxel, at above-mentioned defective, the present invention is intended to develop the novel formulation that a kind of bag carries paclitaxel.Novel formulation will provide selection for the clinical treatment of tumor, produce good social influence and economic benefit.
Summary of the invention
At the deficiency of existing preparation, one of the object of the invention, provide a kind of particle diameter evenly, good stability, have long cyclicity, be suitable for the intravenous injection use, nano particle preparations that toxic and side effects is little bag carries paclitaxel.
At the deficiency of existing technology of preparing, one of the object of the invention provides the nanoparticle preparation method that a kind of preparation process is few, simple to operate, the instrument requirement is low, be easy to industrialized great production, can prepare standard compliant nanoparticle quickly and easily.
One of purpose of the present invention, the solution that the PELGE nano particle preparations and the lyophilized injectable powder thereof that provide a kind of bag to carry paclitaxel, its lyophilized injectable powder can be diluted to variable concentrations carries out intravenous injection.
Bag provided by the invention carries the PELGE nanoparticle particle diameter of paclitaxel: 20-500nm, and envelop rate is: 70%-99%, drug loading is: 0.5%-20%.This nanometer formulation also can add freeze drying protectant and other adjuvant, and lyophilization is prepared into powder.
The present invention relates to the PELGE nanoparticle that a kind of bag carries paclitaxel, comprise each component that contains in weight portion: paclitaxel: 1-20 part; Carrier material: 10-100 part; Surfactant: 1-10 part.
Used carrier material: be PELGE(PEG-PLGA-PEG), its molecular weight is: 5 * 10
3-1 * 10
5The content of PLGA is 50%-95%, and molecular weight is: 3 * 10
3-5 * 10
4, LA:GA is 100:0-50:50; The content of PEG is 5-50%, and molecular weight is 5 * 10
2-5 * 10
3
Described surfactant Ovum Gallus domesticus Flavus lecithin, soybean lecithin, GLYCEROL,DIMYRISTOYL PHOSPHATIDYL, two palmityl phosphatidyl glycerols, distearoyl phosphatidylcholine, dimyristoyl phosphatidyl choline, phosphatidylcholine, the distearyl phosphatidyl glycerol, PHOSPHATIDYL ETHANOLAMINE, lauric acid, sodium lauryl sulphate, Palmic acid, stearic acid, ceryl alcohol sodium sulfate, stearyl alcohol sodium sulfate, the fatty acid azochlorosulfonate acid compound, the alkyl aryl sulphonic acid thing, benzalkonium chloride, benzalkonium bromide, tween, span, Myrij, Brij, pluronic, nonyl phenol, octyl phenol, in the paregal O one or several are pressed the combination of recipe quantity; Concentration is: 0.1%-5%
(g/ml)。
Preparation method is as follows:
1 is dissolved in paclitaxel and triblock copolymer chemical compound in the organic facies jointly, as the oil phase of preparation; Surfactant is dissolved in organic facies or the water for injection, as the water of preparation;
2 with oil phase and water mix homogeneously by a certain percentage, obtains milky emulsion under high pressure or high-shear conditions;
3 remove organic solvent, obtain the paclitaxel nano grain.
Wherein, described organic facies be in ethanol, acetonitrile, ether, ethyl acetate, petroleum ether, dichloromethane, chloroform, the acetone one or more organic solvents by the recipe quantity mixed.
The concentration of paclitaxel is in the described oil phase: 0.1mg/ml-20mg/ml, carrier concn is: 1mg/ml-50mg/ml.
Described surfactant is: Ovum Gallus domesticus Flavus lecithin, soybean lecithin, dimyristoyl phosphatidyl choline, GLYCEROL,DIMYRISTOYL PHOSPHATIDYL, dipalmitoyl phosphatidyl choline, two palmityl phosphatidyl glycerols, distearoyl phosphatidylcholine, the distearyl phosphatidyl glycerol, phosphatidylcholine, PHOSPHATIDYL ETHANOLAMINE, sodium lauryl sulphate, lauric acid, Palmic acid, stearic acid, oleic acid, spermol sodium sulfate, stearyl alcohol sodium sulfate, the fatty acid azochlorosulfonate acid compound, the alkyl aryl sulphonic acid thing, benzalkonium chloride, benzalkonium bromide, span, tween, Myrij, Brij, pluronic, nonyl phenol, octyl phenol, octyl cresol, paregal O, in the benzalkonium chloride one or several are pressed the combination of recipe quantity; Concentration is: 0.1%-5% (g/ml);
Volume ratio when described oil phase and water mix is: 1:(3-30).
Described high pressure and high-shear conditions are: at ultrasonic cell pulverization instrument, high-shear mixer, high-shear mixer, high pressure dispersing emulsification machine with carry out the even effect of breast under the analogous instrument with it.
The described organic solvent condition of removing is: use falling film evaporator, Rotary Evaporators or with it similarly the instrument evaporation remove, or organic solvent is removed in directly lyophilization, spray drying.
The described nano particle preparations that is prepared into can add freeze drying protectant and other adjuvant, and lyophilization becomes injectable powder.Its freeze drying protectant is: one or several in sucrose, lactose, mannose, glucose, mannose, maltose, glycine, Polyethylene Glycol, glucosan, sodium glutamate, glycine, phosphate, acetate, the citrate are pressed the combination of recipe quantity, and concentration is 0.1%-10% (g/ml).
The invention has the beneficial effects as follows:
1. bag of the present invention carries the PELGE nano particle preparations of paclitaxel, has greatly put forward dissolubility and the stability of paclitaxel, is conducive to store and transportation;
2. carrier material good biocompatibility of the present invention, non-immunogenicity, biodegradable have greatly reduced toxic and side effects;
3. carrier material of the present invention prepares simple, with low cost, polymer and can accurately control to satisfy different administration needs with molecular weight;
4. long-circulating nanoparticles preparation of the present invention can slow releasing pharmaceutical, to reach the prolong drug purpose of action time, can significantly increase patient's compliance;
5. nano particle preparations particle diameter of the present invention evenly, also the control particle diameter exists easily: between the 20-500nm, can realize the targeting of drug delivery.
7. nanometer formulation preparation method of the present invention is simple, operating procedure is few, good reproducibility, instrument require low, be suitable for industrialized great production.
8. lyophilized injectable powder of the present invention is fit to be diluted to variable concentrations and carries out intravenously administrable, satisfies different patients' needs, is very easy to clinical administration.
Description of drawings
Fig. 1 carries paclitaxel nano grain transmission electron microscope photo among the embodiment 1 with the bag for preparing in the method for the present invention;
Fig. 2 carries paclitaxel nano grain particle size distribution figure among the embodiment 1 with the bag for preparing in the method for the present invention;
Fig. 3 carries paclitaxel nano grain transmission electron microscope photo for the bag for preparing with the nanometer sedimentation method among the embodiment 2;
Fig. 4 carries paclitaxel nano grain particle size distribution figure among the embodiment 2 with the bag for preparing in the nanometer sedimentation method;
Fig. 5 is transmission electron microscope photo behind the embodiment 1 nanoparticle placement 24h;
Fig. 6 is transmission electron microscope photo behind the embodiment 2 nanoparticles placement 24h;
The specific embodiment:
Further specify the present invention with embodiment below, but the present invention its be not limited.
The preparation that embodiment 1 bag carries the PELGE nanoparticle of paclitaxel
The paclitaxel of PELGE, the 1mg of 20mg is dissolved in the dichloromethane of 3ml as oil phase, the 30mg sodium cholate is dissolved in the distilled water of 15ml as water, oil phase is evenly mixed with water, under 300 W power probes ultrasonic 2 minutes, obtain milky emulsion, 40 ℃ of following distilling under reduced pressure 30min of bath temperature remove organic solvent, make the PELGE nano particle preparations that bag carries paclitaxel, record mean diameter: 160.9nm, PDI:0.168, envelop rate: 93.2%, according to transmission electron microscope.Transmission electron microscope photo as shown in Figure 1, particle size distribution is as shown in Figure 2.
PELGE with 20mg, the paclitaxel of 1mg is dissolved in the dichloromethane of 3ml as oil phase, the 30mg sodium cholate is dissolved in the distilled water of 15ml as water, the organic facies of 3ml is evenly mixed with the water of 5ml, under the power probe of 300W ultrasonic 2 minutes, the first emulsion droplet that forms is added dropwise among the 10ml sodium cholate solution with the speed of 1ml/min, after stirring 10 minutes with the rotating speed of 500r/min, obtain milky emulsion, 40 ℃ of following distilling under reduced pressure 30min of bath temperature, remove organic solvent, make the PELGE nano particle preparations that bag carries paclitaxel, record mean diameter: 142.9nm, PDI:0.243, envelop rate: 82.4%.Transmission electron microscope photo as shown in Figure 3, its particle size distribution is as shown in Figure 4.
Embodiment 3 is relatively with the nano particle preparations of the inventive method preparation and the nanometer formulation stability for preparing with the nanometer sedimentation method
By the nano particle preparations that embodiment 1 and embodiment 2 prepare, room temperature was placed after 24h hour, according to transmission electron microscope, found the nanoparticle good stability among the embodiment 1, and particle diameter is even.Have paclitaxel crystal to separate out in the nanoparticle of discovery embodiment 2 preparations, size is inhomogeneous, has the situation of focusing to produce.Place 24h embodiment 1 nanoparticle transmission electron microscope photo as shown in Figure 5, place 24h, embodiment 2 nanoparticle transmission electron microscope photos as shown in Figure 6.
The preparation that embodiment 4 bags carry the PELGE nanoparticle of paclitaxel
The paclitaxel of PELGE, the 1mg of 20mg is dissolved in the dichloromethane of 3ml as oil phase, the F-68 of 30mg is dissolved in the distilled water of 15ml as water, oil phase is evenly mixed with water, under the power probe of 300 W ultrasonic 2 minutes, obtain milky emulsion, 40 ℃ of following distilling under reduced pressure 30min of bath temperature, remove organic solvent, obtain wrapping the nanoparticle that carries paclitaxel, record nanoparticle mean diameter: 164.9nm, PDI:0.135, envelop rate: 95.3%.
The preparation that embodiment 5 bags carry the PELGE nanoparticle of paclitaxel
The paclitaxel of PELGE, the 1mg of 20mg is dissolved in the mixing organic facies of the dichloromethane of 1.5ml and 1.5ml ethyl acetate as oil phase, the 30mg sodium cholate is dissolved in the distilled water of 15ml as water, oil phase is evenly mixed with water, under the power probe of 300 W ultrasonic 3 minutes, obtain milky emulsion, 40 ℃ of following distilling under reduced pressure 30min of bath temperature, remove organic solvent, obtain wrapping the nanoparticle that carries paclitaxel, record nanoparticle mean diameter: 159.6nm, PDI:0.152, envelop rate: 91.8%.
The preparation that embodiment 6 bags carry the PELGE nanoparticle of paclitaxel
With in the mixing organic facies of the paclitaxel of PELGE, the 1mg of 20mg, dichloromethane that the 0.5mg soybean lecithin is dissolved in 1.5ml and 1.5ml ethyl acetate as oil phase, in the distilled water of 15ml as water, oil phase is evenly mixed with water, under the power probe of 300 W ultrasonic 2 minutes, obtain milky emulsion, 40 ℃ of following distilling under reduced pressure 30min of bath temperature, remove organic solvent, obtain wrapping the nanoparticle that carries paclitaxel, record nanoparticle mean diameter: 167.1nm, PDI:0.189, envelop rate: 89.3%.
The preparation that embodiment 7 bags carry the PELGE nanoparticle of paclitaxel
The paclitaxel of the PELGE of 20mg and 1mg is dissolved in the mixing organic facies of the dichloromethane of 1.5ml and 1.5ml ethyl acetate as oil phase, the 30mg sodium cholate is dissolved in the distilled water of 15ml as water, oil phase is evenly mixed with water, under the power probe of 500 W ultrasonic 5 minutes, obtain milky emulsion, 40 ℃ of following distilling under reduced pressure 30min of bath temperature, remove organic solvent, obtain wrapping the nanoparticle that carries paclitaxel, record nanoparticle mean diameter: 82.6nm, PDI:0.152, envelop rate: 92.1%.
The mensuration that embodiment 8 bags carry the PELGE nanoparticle envelop rate of paclitaxel
Adopt LC-MS (LC-MS) to measure the content of paclitaxel, the paclitaxel nano grain for preparing is crossed the G-50 sephadex column, obtain wrapping the PELGE nanoparticle solution that is loaded with paclitaxel, get untreated with volume nanoparticle original solution simultaneously, add the methanol identical with volume and carry out breakdown of emulsion, cross feed liquor matter behind 0.2 micron organic filter membrane, the ratio of both peak areas is envelop rate:
The amount of envelop rate (%)=nanoparticle Chinese medicine/medicine total amount * 100%
The lyophilizing that embodiment 9 bags carry the PELGE nanoparticle of paclitaxel
The nanoparticle solution for preparing is added volume fraction 5% maltose, at-40 ℃ of following pre-freeze 4h.Be under the 150mBar condition at condenser temperature for-40 ℃, vacuum then, lyophilization 24h namely gets paclitaxel nano grain lyophilized powder.The lyophilized powder appearance is smooth, and exquisite quality can be multiple soluble in water fast, records particle diameter and keep good, do not have the phenomenon of precipitation and focusing to take place.Record again water-soluble nanoparticle particle diameter 180.3nm, PDI:0.152.
The lyophilizing that embodiment 10 bags carry the PELGE nanoparticle of paclitaxel
The nanoparticle solution for preparing is added volume fraction 5% sucrose, at-40 ℃ of following pre-freeze 4h, is under-40 ℃ of conditions at condenser temperature then, and true width is under the 150mBar condition, and lyophilization 24h namely gets paclitaxel nano grain lyophilized powder.The lyophilized powder appearance is smooth, and exquisite quality can be multiple soluble in water fast, records particle diameter and keep good, do not have the phenomenon of precipitation and focusing to take place, and records again water-soluble nanoparticle particle diameter 178.9nm, PDI:0.189.
Claims (8)
1. the nano particle preparations of a bag year paclitaxel is characterized in that: comprise paclitaxel, PEG-PLGA-PEG triblock copolymer chemical compound, surfactant and water for injection in the described preparation.
2. carry the nano particle preparations of paclitaxel according to the described bag of claim 1, it is characterized in that, comprise each component in weight portion: paclitaxel 1-20 part, PEG-PLGA-PEG triblock copolymer chemical compound 10-100 part, surfactant 1-10 part.
3. bag according to claim 1 carries the nanometer formulation of paclitaxel, it is characterized in that, described triblock copolymer chemical compound is: poly glycol monomethyl ether (PEG) is modified synthetic PEG-PLGA-PEG (being called for short PELGE) to lactic acid/co-glycolic acid (PLGA), and its molecular weight is: 5 * 10
3-1 * 10
5Wherein, the content of PLGA is 50%-95%, and molecular weight is: 3 * 10
3-5 * 10
4, LA:GA is 100:0-50:50; The content of PEG is 5-50%, and molecular weight is 5 * 10
2-5 * 10
3, described surfactant Ovum Gallus domesticus Flavus lecithin, soybean lecithin, GLYCEROL,DIMYRISTOYL PHOSPHATIDYL, two palmityl phosphatidyl glycerols, distearoyl phosphatidylcholine, dimyristoyl phosphatidyl choline, phosphatidylcholine, the distearyl phosphatidyl glycerol, PHOSPHATIDYL ETHANOLAMINE, lauric acid, sodium lauryl sulphate, Palmic acid, stearic acid, ceryl alcohol sodium sulfate, stearyl alcohol sodium sulfate, the fatty acid azochlorosulfonate acid compound, the alkyl aryl sulphonic acid thing, benzalkonium chloride, benzalkonium bromide, tween, span, Myrij, Brij, pluronic, nonyl phenol, octyl phenol, in the paregal O one or several are pressed the combination of recipe quantity; Concentration is: 0.1%-5% (g/ml).
4. bag according to claim 1 carries the paclitaxel nano preparation, it is characterized in that, described nanoparticle particle diameter is: 20-500nm, envelop rate is: 70%-99%, drug loading is: 0.5%-20%.
5. according to the paclitaxel nano grain preparation described in the claim 1-4, the step of its preparation is as follows:
I. paclitaxel and triblock copolymer chemical compound are dissolved in the organic facies jointly, as the oil phase of preparation; Surfactant is dissolved in organic facies or the water for injection, as the water of preparation;
II. with oil phase and water mix homogeneously by a certain percentage, obtain milky emulsion under high pressure or high shear, III is removed organic solvent, obtains bag and carries a paclitaxel nano grain.
6. preparation method according to claim 5 is characterized in that, organic facies is described in the step I: one or more organic solvents are pressed the recipe quantity mixed in ethanol, acetonitrile, ether, ethyl acetate, petroleum ether, dichloromethane, chloroform, the acetone.
7. preparation method according to claim 5 is characterized in that, the concentration of paclitaxel is in the described oil phase of step I: 0.1mg/ml-20mg/ml, and the triblock copolymer compound concentrations is: 1mg/ml-50mg/ml; Volume ratio when the described oil phase of step II and water mix is: 1:(3-30); The described high pressure of step II and high speed shear power condition are: at ultrasonic cell pulverization instrument, high-shear mixer, high-shear mixer, high pressure dispersing emulsification machine with carry out the even effect of breast under the analogous instrument with it.
8. preparation method according to claim 5; it is characterized in that; the resulting nano particle preparations of step III; can add freeze drying protectant and other adjuvant; lyophilization becomes injectable powder; its freeze drying protectant is: one or several in sucrose, lactose, mannose, glucose, mannose, maltose, glycine, Polyethylene Glycol, glucosan, sodium glutamate, glycine, phosphate, acetate, the citrate are pressed the combination of recipe quantity, and concentration is 0.1%-10% (g/ml).
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| CN103585634A (en) * | 2013-10-22 | 2014-02-19 | 汤民 | Docetaxel polymer nano-medicament preparation and preparation method thereof |
| CN106474049A (en) * | 2016-11-01 | 2017-03-08 | 华东师范大学 | A kind of photopolymerized hydrogel topical drug delivery systems and preparation method and application |
| CN104292468B (en) * | 2014-09-28 | 2017-05-10 | 哈尔滨理工大学 | Amphiprotic compound containing betulinic acid and preparation method and application thereof |
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| CN101283976A (en) * | 2008-05-30 | 2008-10-15 | 济南基福医药科技有限公司 | Anticancer sustained-release gel injection containing taxone medicine |
| CN101884618A (en) * | 2010-06-28 | 2010-11-17 | 山东大学 | Long-circulating paclitaxel nanoparticles and preparation method thereof |
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| CN101283976A (en) * | 2008-05-30 | 2008-10-15 | 济南基福医药科技有限公司 | Anticancer sustained-release gel injection containing taxone medicine |
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103585634A (en) * | 2013-10-22 | 2014-02-19 | 汤民 | Docetaxel polymer nano-medicament preparation and preparation method thereof |
| CN104292468B (en) * | 2014-09-28 | 2017-05-10 | 哈尔滨理工大学 | Amphiprotic compound containing betulinic acid and preparation method and application thereof |
| CN106474049A (en) * | 2016-11-01 | 2017-03-08 | 华东师范大学 | A kind of photopolymerized hydrogel topical drug delivery systems and preparation method and application |
| CN106474049B (en) * | 2016-11-01 | 2019-08-23 | 华东师范大学 | A kind of photopolymerized hydrogel topical drug delivery systems and preparation method and application |
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