CN103784421B - Carry solid lipid nanoparticle of curcumin and piperine and preparation method thereof - Google Patents
Carry solid lipid nanoparticle of curcumin and piperine and preparation method thereof Download PDFInfo
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Abstract
The present invention relates to the solid lipid nanoparticle of a kind of year curcumin and piperine, be made up of the component of following percentage by weight: curcumin 0.1% ~ 5%, piperine 0.1% ~ 5%, solid lipid material 10% ~ 70%, liquid oil phase 5% ~ 30%, emulsifying agent 10% ~ 60%, surplus is water.Preparation method can adopt film dispersion method, microemulsion method or Emulsion evaporation-solidification at low temperature.Compared with existing dosage form, the present invention adopts the advantage of solid lipid nanoparticle to be improve the dissolubility of curcumin and piperine medicine, the stability adding nanoparticle Chinese medicine and vitro release, improves antitumor and the reverse multidrug drug resistance effect of curcumin.
Description
Technical field
The present invention relates to a kind of solid lipid nanoparticle, particularly a kind of containing antitumor and the curcumin of reverse multidrug drug resistance activity and the solid lipid nanoparticle of piperine and preparation method, belong to field of pharmaceutical technology.
Background technology
The high expressed of P-glycoprotein (P-glycoprotein, P-gp) is the topmost mechanism of tumor multi-medicine drug-resistant (MultidrugResistance, MDR).The study hotspot of current pharmaceutics carrys out reversion MDR by nano-medicament carrier.In recent years, solid lipid nanoparticle (SolidLipidNanoparticles, SLN), due to the advantage of its uniqueness, becomes a kind of extremely promising Novel medicine feeding carrier.SLN be a kind of using in vivo degradable, natural or synthesis solid lipid material as carrier, the submicron drug-supplying system of absorption or packaging medicine, particle diameter is within the scope of 50-1000nm, and preparation method has high-pressure stripping, microemulsion method, solvent emulsion evaporation and Emulsion evaporation-solidification at low temperature etc.
Curcumin (Curcumin, Cur) is the main active extracted from the rhizome of Zingiberaceae curcuma Rhizoma Curcumae Longae.In recent years, about the research of curcumin antitumor action more and more comes into one's own.The patent that current curcumin is relevant has: solid dispersion (CN100340238C, 2007), nanoparticle (CN101711740A, 2010), self-emulsifiable preparation (CN101627969A, 2010), nano suspension (CN102961368A, 2013), solid lipid nanoparticle (CN102949344A, 2013) etc., in increase drug bioavailability, raising therapeutic effect, there is remarkable result, but curcumin is in vivo as the substrate of P-gp, easily be discharged cell, therefore suppress P-gp to be still to strengthen its curative effect the problem needing to solve further.Conduct extensive research for P-gp inhibitor both at home and abroad, as verapamil, ciclosporin A etc., but limit its clinical practice because toxic and side effects is large.
Piperine (Piperine, Pip) is proved to be the reinforcing agent of many drug bioavailabilities, and research shows that piperine can suppress the function of P-gp.Therefore this patent is by piperine and curcumin conbined usage, is intended to suppress P-gp to reduce the outer row of curcumin by piperine, thus improves interior curative effect.
Some nonionic surfactant of discovered in recent years has inhibitory action to P-gp, can the multidrug resistance of reversing tumor cell effectively, is thus widely used in the transmission system of antitumor drug.The present invention selects to have the inhibiting nonionic surfactant of P-gp, if TPGS and Brij78 is as the adjuvant preparing solid lipid nanoparticle, not only increase curcumin and piperine solid lipid nanoparticle to the reverse effect of drug resistance of tumor cell phenomenon, improve the stability of nanoparticle simultaneously.
Summary of the invention
The technical problem to be solved in the present invention is to provide a kind of curcumin and piperine solid lipid nanoparticle and preparation method thereof of reverse multidrug drug resistance, and the method technique is simple, easy and simple to handle; Preparation has the features such as dissolubility is high, good stability, bioavailability are high, collaborative performance curative effect of medication.
For reaching above-mentioned purpose, inventing the solid lipid nanoparticle of a kind of year curcumin and piperine, being made up of the component of following percentage by weight: curcumin 0.1% ~ 5%, piperine 0.1% ~ 5%, solid lipid material 10% ~ 70%, liquid oil phase 5% ~ 30%, emulsifying agent 10% ~ 60%, surplus is water.
Matrix material is the key factor determining drug loading, the good matrix material of crystallinity can form tight perfectly lattice, and the space holding medicine is less, and the matrix material of complexity can form the lattice of a large amount of defect, thus can more drug be held, envelop rate is increased.Solid lipid nanoparticle of the present invention, wherein preferred described solid lipid material is the mixture of one or more arbitrary proportions in glyceride, phospholipid, steroid, wax fat.
Further preferably, described glyceride is selected from one or more the mixture in glyceryl monostearate, glycerol distearate, glyceryl tristearate, Glyceryl Behenate (Compritol888), monopalmitin, two tripalmitin, tripalmitin, glycerol trioleate, glyceryl laurate ester, myristin; Described phospholipid is soybean lecithin or Ovum Gallus domesticus Flavus lecithin; Steroid is cholesterol; Described wax fat is one or more the mixture in microcrystalline wax, spermol cetylate, cetyl palmitate.
Solid lipid nanoparticle of the present invention, more preferably described solid lipid material is glyceryl monostearate and soybean lecithin, and preferably its mass ratio is 1:(1 ~ 3).
Liquid fatty substance has stronger solvability to medicine, and can insert in lattice and replace Solid lipid molecule, destroys its lattice arrangement, reduces degree of crystallinity, thus improves envelop rate and the drug loading of medicine.Solid lipid nanoparticle of the present invention, wherein preferred described liquid oil phase is selected from the one in injection soybean oil, oleic acid sorbitol ester, Polyethylene Glycol glyceryl laurate ester, tricaprylin, olein, glyceryl linoleate, oleic acid, ethyl oleate, more preferably oleic acid.
The consumption of emulsifying agent and ratio are also the key factors determining solid lipid nanoparticle performance, and emulsifying agent can make system more stable, and the particle diameter of usual nanoparticle reduces with the increase of consumption.Solid lipid nanoparticle of the present invention, wherein preferably described emulsifying agent is selected from the mixture of one or more arbitrary proportions in polyethylene glycol 1000 vitamin E succinic acid ester (TPGS), cholate, dexycholate, poloxamer, polysorbate, polyoxyethylene aliphatic alcohol ether, polyoxyethylene fatty acid ester class, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini; Preferred described cholate be selected from sodium cholate, sodium glycocholate, Bile Salts one or both; The preferred tween 80 of described polysorbate, Tween-60, Tween-40 or tween 20; Polyoxyethylene aliphatic alcohol ether preferred Brij78, Brij58, Brij35 or Brij30; Poloxamer preferred poloxamer188, poloxamer182 or poloxamer108; Preferred Myrj53 or Myrj59 of polyoxyethylene fatty acid ester.
Further preferably, described emulsifying agent is TPGS and Brij78, and preferably its mass ratio is 1:(0.5 ~ 1.5).
Solid lipid nanoparticle of the present invention, nanoparticle particle diameter is less than 200nm, epigranular, and more stable.
The preparation method of solid lipid nanoparticle of the present invention, any one that can adopt in following distinct methods prepares:
(1) film dispersion method: the curcumin of accurately weighed above-mentioned weight proportion and piperine, solid lipid material and liquid oil phase, add in organic solvent, heats and ultrasonicly makes it dissolve formation organic facies; Organic facies is transferred in round-bottomed flask, controls water-bath, reduction vaporization removing organic solvent film forming; Getting emulsifying agent is dissolved in distilled water, forms aqueous phase; Added in round-bottomed flask by aqueous phase and rotate eluting, the suspension after eluting is transferred in beaker, ultrasonic rear cooling curing and get final product;
(2) microemulsion method: the solid lipid material of above-mentioned weight proportion, liquid oil phase and emulsifying agent are placed in vial, heating makes oil phase melt, and ultrasonicly makes it emulsifying; Be dissolved in organic solvent by curcumin and piperine, transfer in the vial containing oil phase and emulsifying agent, heated and stirred removing organic solvent, adds the distilled water of preheating; Continue heated and stirred and form oil-in-water microemulsion, by the drug-carrying nanometer particle cooling curing formed, to obtain final product;
(3) Emulsion evaporation-solidification at low temperature: the curcumin of accurately weighed above-mentioned weight proportion and piperine, solid lipid material and liquid oil phase, add in organic solvent, heats and ultrasonicly makes it dissolve formation organic facies; Getting emulsifying agent is dissolved in distilled water, and heated and stirred forms aqueous phase; Under heated and stirred, organic facies is slowly noted in people's aqueous phase, treat the complete follow-up continuous stirring of organic solvent volatilization; The colostrum of gained is placed in psychrolusia and stirs solidification cooling (or the refrigerator and cooled of 2-5 DEG C is but solidified), the solid lipid nanoparticle of curcumin and piperine must be carried.
The preparation method of solid lipid nanoparticle of the present invention, wherein said organic solvent is selected from one or more the mixed solution in methanol, dehydrated alcohol, ether, acetone, ethyl acetate, chloroform, be preferably the mixed solution of dehydrated alcohol and ethyl acetate, mass ratio is 1:(0.5 ~ 3).
The invention still further relates to the application of above-mentioned solid lipid nanoparticle, use it for and prepare appts for medical injection or oral formulations, described injection or oral formulations separately or with other antitumor drug conbined usage, to strengthen the curative effect of antitumor drug, and the multi-drug resistance phenomenon of reversing tumor cell simultaneously.
Compared with existing dosage form, the present invention adopts the advantage of solid lipid nanoparticle to be improve the dissolubility of curcumin and piperine medicine, the stability adding solid lipid nanoparticle Chinese medicine and vitro release, improves antitumor and the reverse multidrug drug resistance effect of curcumin.Owing to containing double bond in curcumin molecular structure, multiple active group such as phenolic hydroxyl group, piperine is extremely unstable also, responsive to photo-thermal, therefore preferably adopts Emulsion evaporation-solidification at low temperature, preparation process mild condition, does not affect the stability of medicine.Meanwhile, through great many of experiments, adopt above-mentioned film dispersion method and microemulsion method can obtain all satisfactory preparation of envelop rate, particle diameter and nanoparticle stability equally.Compared with other existing technology, the present invention adopts these three kinds of methods to prepare curcumin and piperine solid lipid nanoparticle, and preparation method is simple, nanoparticle particle diameter is less than 200nm, and stability better and have certain slow-releasing and controlled-releasing action, convenient storage, can intravenous injection or oral administration, taking convenience.The solid lipid nanoparticle of provided by the invention year curcumin and piperine can separately or with other antitumor drug conbined usage, the multi-drug resistance phenomenon of the curative effect strengthening antitumor drug reversing tumor cell simultaneously.
Below in conjunction with accompanying drawing, solid lipid nanoparticle of of the present invention year curcumin and piperine and preparation method thereof is described further.
Accompanying drawing explanation
Fig. 1 (Cur+Pip)-SLN transmission electron microscope picture;
Fig. 2 A and Fig. 2 B is respectively curcumin and piperine solid lipid nano potential diagram and grain-size graph;
Fig. 3 A and Fig. 3 B curcumin and piperine solid lipid nanoparticle drug release determination result (A curcumin, B piperine; Mean ± SD, n=3; PH=5.5(▲), pH=7.4(■)).
Detailed description of the invention
Be below embodiment and test data etc. thereof, but content of the present invention is not limited to the scope of these embodiments.
Embodiment 1:
According to Emulsion evaporation-solidification at low temperature, accurately weighed curcumin 5mg and piperine 5mg respectively, glyceryl monostearate 100mg and soybean lecithin 150mg, oleic acid 90mg, add in 5mL organic solvent (dehydrated alcohol: ethyl acetate=3:2), heat and ultrasonicly make it dissolve, ultrasonic rear heating in water bath stirs and forms organic facies.Getting TPGS100mg and Brij78150mg is dissolved in distilled water, and heated and stirred forms aqueous phase.Respectively by organic facies and heated aqueous extremely about 60 DEG C, under heated and stirred, organic facies is slowly noted in people's aqueous phase, treat the complete follow-up continuous stirring of organic solvent volatilization.The colostrum of gained is placed in 4 DEG C of refrigerators to cool rapidly, obtains the suspension of solid lipid nanoparticle.
The curcumin obtain embodiment 1 and the physicochemical property of piperine solid lipid nanoparticle are studied, and comprise Zeta potential, particle diameter, envelop rate and release in vitro.
(1) morphologic observation
Get (Cur+Pip)-SLN solution 1 to be placed in and to be covered with on the copper mesh of support membrane, after fixing dyeing, under being placed in transmission electron microscope, observe its form.The results are shown in Figure 1, result shows, obtained (Cur+Pip)-SLN form is that class is spherical, and size is even, substantially without being adhered between nanoparticle.
(2) Zeta potential and particle size distribution
Get (Cur+Pip)-SLN solution of fresh preparation, after appropriate distilled water diluting, measure its current potential and particle diameter with ZetasizerNanoZS90 particle diameter potentiometric analyzer.The results are shown in Figure 2A to Fig. 2 B.
The Zeta potential of nanoparticle is shown in Fig. 2 A, and Zeta potential is-23.5mV, and result shows, the nanoparticle of preparation is more stable.Particle size distribution is shown in Fig. 2 B, and mean diameter is 130.8nm.Polydispersity coefficient is 0.152, shows that the nanoparticle particle diameter prepared is less, even particle size distribution.
(3) envelop rate
Measure the envelop rate of curcumin and piperine, in (Cur+Pip)-SLN, curcumin envelop rate is 87.4%, and piperine envelop rate is 14.7%.
(4) extracorporeal releasing experiment
(Cur+Pip) release in vitro of-SLN the results are shown in Figure 3A and Fig. 3 B.As seen from the figure, curcumin and piperine discharge more complete in the environment of pH5.5, show that two kinds of medicines discharge faster in tumor environment.During 96h, curcumin cumulative percent in the environment of pH5.5 is 83.7%, and in pH7.4, cumulative percent is 71.5%.Piperine than curcumin discharge faster, discharge cumulative percent during 24h and be all greater than 90%.Result shows that the nanoparticle prepared can discharge medicine slowly, and release is comparatively complete, has good sustained release performance.
The present invention selects to have inhibiting TPGS and Brij78 of P-gp as the adjuvant preparing solid lipid nanoparticle, significantly improve the dissolution in vitro of curcumin and piperine, not only increase curcumin and piperine solid lipid nanoparticle to the reverse effect of drug resistance of tumor cell phenomenon, improve the stability of nanoparticle simultaneously.
Embodiment 2:
According to microemulsion method, get glyceryl monostearate 100mg, Ovum Gallus domesticus Flavus lecithin 100mg and oleic acid 90mg as oil phase, TPGS100mg and Brij7850mg is placed in vial as emulsifying agent, and heating makes oil phase melt, and ultrasonic agitation makes it emulsifying.Weigh curcumin 10mg and piperine 5mg to be dissolved in 2mL dehydrated alcohol, transfer in the vial containing oil phase and emulsifying agent, heated and stirred removing dehydrated alcohol, adds the distilled water of preheating.Continue heated and stirred and form oil-in-water microemulsion, by the direct cool to room temperature of drug-carrying nanometer particle formed, obtain curcumin and piperine solid lipid nanoparticle.
The physicochemical property of the curcumin obtained and piperine solid lipid nanoparticle studied, result shows that its mean diameter is 168.5nm; Zeta potential is-20.1mV; Curcumin envelop rate is 88.2%, and piperine envelop rate is 14.1%; Extracorporeal releasing experiment shows that nanoparticle can discharge medicine slowly, and release is comparatively complete, has good sustained release performance.
Embodiment 3:
According to film dispersion method, weigh curcumin 10mg and piperine 5mg, glyceryl monostearate 100mg and soybean lecithin 200mg respectively, oleic acid 110mg, add in 5mL organic solvent (dehydrated alcohol: ethyl acetate=2:1), heating in water bath is ultrasonic makes it dissolve formation organic facies.Organic facies be transferred in round-bottomed flask, control bath temperature about 60 DEG C, round-bottomed flask and horizontal plane keep suitable angle.Open air in vacuum pump extraction system, organic solvent is shot completely, rotary evaporation film forming.Getting emulsifying agent TPGS90mg and Brij78120mg is dissolved in distilled water, forms aqueous phase.Aqueous phase is added in round-bottomed flask and rotates eluting.Suspension is transferred in beaker, after water bath sonicator, places 4 DEG C of refrigerator and cooled and but solidify and obtain curcumin and piperine solid lipid nanoparticle.
The physicochemical property of the curcumin obtained and piperine solid lipid nanoparticle studied, result shows that its mean diameter is 152.4nm; Zeta potential is-22.3mV; Curcumin envelop rate is 84.5%, and piperine envelop rate is 12.7%; Extracorporeal releasing experiment shows that nanoparticle can discharge medicine slowly, and release is comparatively complete, has good sustained release performance.
Embodiment 4:
Preparation method: with embodiment 1 Emulsion evaporation-solidification at low temperature
The physicochemical property of the curcumin obtained and piperine solid lipid nanoparticle studied, result shows that its mean diameter is 142.4nm; Zeta potential is-23.2mV; Curcumin envelop rate is 86.3%, and piperine envelop rate is 13.8%; Extracorporeal releasing experiment shows that nanoparticle can discharge medicine slowly, and release is comparatively complete, has good sustained release performance.
Embodiment 5:
Preparation method: with embodiment 2 microemulsion method
The physicochemical property of the curcumin obtained and piperine solid lipid nanoparticle studied, result shows that its mean diameter is 127.6nm; Zeta potential is-22.8mV; Curcumin envelop rate is 82.7%, and piperine envelop rate is 11.3%; Extracorporeal releasing experiment shows that nanoparticle can discharge medicine slowly, and release is comparatively complete, has good sustained release performance.
Embodiment 6:
Preparation method: with embodiment 3 film dispersion method
The physicochemical property of the curcumin obtained and piperine solid lipid nanoparticle studied, result shows that its mean diameter is 147.2nm; Zeta potential is-24.5mV; Curcumin envelop rate is 84.8%, and piperine envelop rate is 13.7%; Extracorporeal releasing experiment shows that nanoparticle can discharge medicine slowly, and release is comparatively complete, has good sustained release performance.
Prove through lot of experiments, curcumin content is 0.1% ~ 5%, and piperine 0.1% ~ 5%, solid lipid material 10% ~ 70%, liquid oil phase 5% ~ 30%, emulsifying agent is in 10% ~ 60% scope, and the solid lipid nanoparticle obtained all has good physicochemical property.As having less mean diameter, epigranular and add its stability; The envelop rate of curcumin and piperine is better, significantly improves the dissolution in vitro of curcumin and piperine, has good sustained release performance.Therefore the content of each component is not limited to enumerating of above-described embodiment, if curcumin content can also be 1%, 1.5%, 2%, 3%, 4%, 5%, the content of piperine can also be 0.5%, 1%, 1.5%, 2%, 3%, 4%, 5%, the content of solid lipid material can also be 10%, 15%, 20%, 30%, 50%, 70%, the content of liquid oil phase can also be 5%, 10%, 15%, 20%, 30%, and the content of emulsifying agent can also be 10%, 15%, 20%, 30%, 50%, 60%.
Prove through lot of experiments, the kind of above-mentioned each component is also not limited to enumerating of above-described embodiment.As the mixture that above-mentioned solid lipid material can be one or more arbitrary proportions in glyceride, phospholipid, steroid, wax fat, the nanoparticle physical property obtained is better, mass ratio when selecting glyceryl monostearate and soybean lecithin is 1:(1 ~ 3) time, the physical property of nanoparticle can be better.Therefore in the present invention, the mass ratio of solid lipid bill of materials tristerin and soybean lecithin can also be 1:(1 ~ 3 such as 1:1,1:1.5,1:2,1:3) between arbitrary numerical value.
Liquid oil phase can also be oleic acid sorbitol ester, Polyethylene Glycol glyceryl laurate ester, tricaprylin, olein, glyceryl linoleate, ethyl oleate etc., more preferably oleic acid.
Emulsifying agent can also select the mixture of one or more arbitrary proportions in cholate, dexycholate, polyoxyethylene fatty acid ester class, polyoxyethylene castor oil, polyoxyethylene hydrogenated Oleum Ricini, when emulsifying agent be TPGS and Brij78, mass ratio is 1:(0.5 ~ 1.5) time, the nanoparticle physical property obtained is better.Therefore, in emulsifying agent, the mass ratio of TPGS and Brij78 can also be 1:(0.5 ~ 1.5 such as 1:0.5,1:1,1:1.2,1:1.5) between arbitrary numerical value.
Solid lipid nanoparticle of the present invention can adopt above-mentioned film dispersion method, microemulsion method and Emulsion evaporation-solidification at low temperature either method to prepare, preferred Emulsion evaporation-solidification at low temperature.The organic solvent used in preparation technology can be selected from one or more the mixed solution in methanol, dehydrated alcohol, ether, acetone, ethyl acetate, chloroform, and preferred mass is than for 1:(0.5 ~ 3) dehydrated alcohol and ethyl acetate mixture.The solid lipid nanoparticle particle diameter obtained is less than 200nm, epigranular and stable performance.Therefore, in organic solvent, the mass ratio of dehydrated alcohol and ethyl acetate can also be 1:(0.5 ~ 3 such as 1:1,1:1.5,1:2,1:3) between arbitrary numerical value.
There is no the open report of curcumin and piperine solid lipid nanoparticle at present, the present invention adopts solid lipid nanoparticle to significantly improve the dissolution in vitro of curcumin and piperine, add its stability, the present invention simultaneously selects to have inhibiting Brij78 and TPGS of P-gp as adjuvant, strengthens the reverse effect to drug resistance of tumor cell phenomenon.The curcumin that patent system of the present invention is standby and piperine solid lipid nanoparticle provide good basis for the research of later stage reverse both multidrug resistance.
Above-described embodiment is only be described the preferred embodiment of the present invention; not scope of the present invention is limited; under not departing from the present invention and designing the prerequisite of spirit; the various distortion that those of ordinary skill in the art make technical scheme of the present invention and improvement, all should fall in protection domain that claims of the present invention determines.
Claims (10)
1. one kind carries the solid lipid nanoparticle of curcumin and piperine, it is characterized in that: be made up of the component of following percentage by weight: curcumin 0.1% ~ 5%, piperine 0.1% ~ 5%, solid lipid material 10% ~ 70%, liquid oil phase 5% ~ 30%, emulsifying agent 10% ~ 60%, surplus is water; Described solid lipid material is glyceryl monostearate and soybean lecithin; Described emulsifying agent is TPGS and Brij78.
2. solid lipid nanoparticle according to claim 1, is characterized in that: described glyceryl monostearate and soybean lecithin mass ratio are 1:1 ~ 3.
3. solid lipid nanoparticle according to claim 1, is characterized in that: described liquid oil phase is selected from the one in injection soybean oil, oleic acid sorbitol ester, Polyethylene Glycol glyceryl laurate ester, tricaprylin, olein, glyceryl linoleate, oleic acid, ethyl oleate.
4. solid lipid nanoparticle according to claim 3, is characterized in that: described liquid oil phase is oleic acid.
5. solid lipid nanoparticle according to claim 1, is characterized in that: described TPGS and Brij78 mass ratio is 1:0.5 ~ 1.5.
6. solid lipid nanoparticle according to claim 1, is characterized in that: particle diameter is less than 200nm.
7. the preparation method of solid lipid nanoparticle described in any one of claim 1-6, is characterized in that: adopt in following distinct methods any one:
(1) film dispersion method: the curcumin of weight proportion described in accurately weighed claim 1 and piperine, solid lipid material and liquid oil phase, add in organic solvent, heats and ultrasonicly makes it dissolve formation organic facies; Organic facies is transferred in round-bottomed flask, controls water-bath, reduction vaporization removing organic solvent film forming; Getting emulsifying agent is dissolved in distilled water, forms aqueous phase; Added in round-bottomed flask by aqueous phase and rotate eluting, the suspension after eluting is transferred in beaker, ultrasonic rear cooling curing and get final product;
(2) microemulsion method: the solid lipid material of weight proportion described in claim 1, liquid oil phase and emulsifying agent are placed in vial, heating makes oil phase melt, and ultrasonicly makes it emulsifying; Be dissolved in organic solvent by curcumin and piperine, transfer in the vial containing oil phase and emulsifying agent, heated and stirred removing organic solvent, adds the distilled water of preheating; Continue heated and stirred and form oil-in-water microemulsion, by the drug-carrying nanometer particle cooling curing formed, to obtain final product;
(3) Emulsion evaporation-solidification at low temperature: the curcumin of weight proportion described in accurately weighed claim 1 and piperine, solid lipid material and liquid oil phase, add in organic solvent, heats and ultrasonicly makes it dissolve formation organic facies; Getting emulsifying agent is dissolved in distilled water, and heated and stirred forms aqueous phase; Under heated and stirred, organic facies is slowly noted in people's aqueous phase, treat the complete follow-up continuous stirring of organic solvent volatilization; The colostrum of gained is placed in psychrolusia and stirs solidification cooling, the solid lipid nanoparticle of curcumin and piperine must be carried.
8. preparation method as claimed in claim 7, is characterized in that: described organic solvent is selected from one or more the mixed solution in methanol, dehydrated alcohol, ether, acetone, ethyl acetate, chloroform.
9. preparation method as claimed in claim 8, it is characterized in that: described organic solvent is the mixed solution of dehydrated alcohol and ethyl acetate, mass ratio is 1:0.5 ~ 3.
10. the application of solid lipid nanoparticle described in any one of claim 1-6, it is characterized in that: use it for and prepare appts for medical injection or oral formulations, described injection or oral formulations separately or with other antitumor drug conbined usage, to strengthen the curative effect of antitumor drug, and the multi-drug resistance phenomenon of simultaneously reversing tumor cell.
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