CN111568882A - Compound curcumin nanoparticle and preparation method and application thereof - Google Patents
Compound curcumin nanoparticle and preparation method and application thereof Download PDFInfo
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- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
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- A61K9/513—Organic macromolecular compounds; Dendrimers
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4525—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a five-membered ring with oxygen as a ring hetero atom
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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
- A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
- A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
- A61K9/51—Nanocapsules; Nanoparticles
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- A—HUMAN NECESSITIES
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- A61P35/00—Antineoplastic agents
Abstract
The invention relates to a compound curcumin nanoparticle which is prepared by adopting an encapsulation rate optimized membrane dispersion-low temperature curing method, and is prepared from the following components in parts by weight: curcumin: piperine: the organic phase comprises (10), (1-30), (120-440) and (120-400) of water phase. The invention also provides a preparation method and application of the compound curcumin nanoparticles. The compound curcumin nanoparticles prepared by the invention have low toxicity to tumor drug resistance, and the uptake rate of tumor drug-resistant cells to the preparation is high. The compound curcumin nanoparticles have good anti-tumor and multi-drug resistance reversing effects.
Description
Technical Field
The invention relates to a compound nanoparticle, in particular to an application of a compound curcumin nanoparticle. Belongs to the application field of new Chinese medicine preparation.
Background
Cancer is one of the important diseases that present day seriously threaten human health. Chemotherapy (abbreviated as chemotherapy) is an important means for the clinical treatment of cancer. Data show that more than 90% of tumor patients have causes of death associated with multidrug resistance. Reversing the drug resistance of the tumor cells, improving the sensitivity of the tumor cells to chemotherapy and having great significance for tumor treatment.
The appearance of multidrug resistance is associated with decreased drug accumulation in tumor cells, and studies indicate that increased drug efflux may be the primary cause of drug resistance. The membrane glycoprotein involved in the drug efflux mechanism mainly comprises P-glycoprotein (P-glycoprotein, P-gp), lung drug resistance related protein, multidrug resistance related protein and the like. The nano drug delivery system can avoid the efflux function of P-gp on the surface of the cell membrane to a certain extent. Another method for overcoming multidrug resistance is to combine antitumor drugs with efflux transporter inhibitors, which can make MDR cells regain sensitivity. P-gp is an energy-dependent drug efflux pump, and after being combined with an anti-tumor drug, the P-gp can provide energy through ATP hydrolysis and pump the anti-tumor drug out of cells, so that the concentration of the drug in the cells is reduced, the cytotoxicity is weakened or completely disappears, and the drug resistance is generated. P-gp can be combined with a wide range of drugs, including paclitaxel, doxorubicin and vinblastine, and many other commonly used antineoplastic drugs.
Curcumin (Curcumin, Cur), a herbaceous polyphenol compound extracted from turmeric rhizome, is widely used as a spice, a food preservative and a colorant. In recent years, studies on the antitumor effect of curcumin have been receiving more and more attention. Various animal and human body researches prove that the curcumin is safe and tolerant under high dosage and has higher safety. But curcumin is less absorbed in intestinal tract, rapidly metabolized and rapidly cleared in the whole body, so that the oral bioavailability of curcumin is low, and the clinical application is limited. Aiming at the characteristics of poor oral absorption rate and low bioavailability of curcumin, various drug delivery systems are provided to solve the problem, including polymer nanoparticles, liposomes, micelles, self-microemulsions, solid dispersions, nanoparticles, phospholipid complexes and the like. Combination adjuvants, which improve curcumin bioavailability by inhibiting curcumin inactivation or slowing its elimination, have been the subject of research in recent years. Some in vitro studies, naringenin, genistein, epigallocatechin gallate and eugenol, all may affect curcumin bioavailability. Piperine (Pip) inhibits P-gp and has been shown to be an enhancer of the bioavailability of many drugs. Therefore, the patent combines curcumin and piperine which is a metabolic enzyme inhibitor of the curcumin, and reduces the discharge of the curcumin by inhibiting metabolic enzymes through the piperine.
In addition, curcumin and other antitumor drugs are used as P-gp substrates in vivo and are easy to be discharged out of cells, so that the current research focus is on further inhibiting P-gp to enhance the antitumor curative effect of the curcumin. P-gp inhibitors such as verapamil, cyclosporin A, etc. have limited clinical use due to their high toxic and side effects. In recent years, some nonionic surfactants have an inhibiting effect on P-gp and can effectively reverse the multidrug resistance of tumor cells, so that the nonionic surfactants are widely used in a delivery system of antitumor drugs. The invention selects non-ionic surface active agents with P-gp inhibition effect, such as polyethylene glycol vitamin E succinate (D-alpha-tocopherol succinate 1000, TPGS) and Pluronic P85 as auxiliary materials for preparing nanoparticles. TPGS is a water-soluble vitamin E derivative, and is a nonionic surfactant with excellent performance. TPGS has been reported in a number of documents to have a P-gp inhibitory effect. Pluronic or Poloxamer is an amphiphilic triblock copolymer, is a nonionic surfactant, is composed of hydrophilic polyethylene oxide (PEO) and hydrophobic polypropylene oxide (PPO), and has a structure of PEO-PPO-PEO. The physicochemical properties of pluronic, such as HLB, CMC, etc., vary with the number of EO and PO chains. Pluronic is an excellent pharmaceutical adjuvant, and is included in United states pharmacopoeia and the 2000 th edition of Chinese pharmacopoeia. In the aspect of preparation, the compound is mainly used as an emulsifier, a stabilizer, a cream matrix and the like, and also used as a solid dispersion carrier, a micelle drug delivery system carrier material and the like in the preparation of a new dosage form. In the research process, the pluronic is found to have the effect of inhibiting the P-gp drug pump. P85 is polyoxyethylene alkyl ether nonionic surfactant, and multiple studies prove that pluronic P85 has the effect of inhibiting P-gp.
The compound curcumin nanoparticle prepared by the patent inhibits the activity of curcumin metabolic enzyme through piperine, increases the concentration of curcumin in cells, and uses TPGS and Pluronic P85 with P-gp inhibition as auxiliary materials. TPGS and Pluronic P85 are used as carriers and P-gp inhibitors, and can increase the intracellular concentration of the medicine, enhance the anti-tumor curative effect of curcumin and reverse the multi-drug resistance of tumor cells by inhibiting the over-expressed P-gp on the surface of the tumor cells.
The inventor applies for an invention patent, patent application No.: CN201410068689.1, the difference between the present invention patent and the patent (application No. CN201410068689.1) is that:
the auxiliary materials used in the invention screen triblock copolymers such as pluronic F68, F88, F108, F127, P85, P81, P61, P123, P188, L35, L44 and P407, preferably pluronic P85 with P-gp inhibition effect; the auxiliary materials used in CN201410068689.1 are: TPGS and polyoxyethylene fatty alcohol ether Brij 78.
The invention comprises the following components in parts by weight: curcumin: piperine: the organic phase comprises (10), (1-30), (120-440) and (120-400) of water phase.
The curcumin and the piperine used in the invention have the following preferred weight part ratios: curcumin: the piperine is 10 (1-30); not described in CN 201410068689.1.
According to the nanoparticle preparation method, a film dispersion-low temperature curing method is preferably selected according to the encapsulation efficiency; the preparation method of the nano-particles in CN201410068689.1 is preferably an emulsion evaporation-low temperature solidification method.
The nanoparticle of the invention has definite inhibition rate and uptake rate data on tumor cells.
The nanoparticles prepared by the invention are applied to local mucosa preparations, injections or oral preparations; the application of the nano-particles in CN201410068689.1 is injection or oral preparation.
The inventor of the invention published a graduation paper research on curcumin-loaded and piperine solid lipid nanoparticle delivery system in 2014, which is distinguished as follows:
the auxiliary materials used in the invention screen triblock copolymers such as pluronic F68, F88, F108, F127, P85, P81, P61, P123, P188, L35, L44 and P407, preferably pluronic P85 with P-gp inhibition effect; the adjuvants used in the thesis were: TPGS and polyoxyethylene fatty alcohol ether Brij 78.
The invention comprises the following components in parts by weight: curcumin: piperine: the organic phase comprises (10), (1-30), (120-440) and (120-400) of water phase.
The curcumin and the piperine used in the invention have the following preferred weight part ratios: curcumin: the piperine is 10 (1-30); not described in the paper.
According to the nanoparticle preparation method, a film dispersion-low temperature curing method is preferably selected according to the encapsulation efficiency; the preparation method of the nanoparticles in the paper is preferably an emulsion evaporation-low temperature solidification method.
The nanoparticles prepared by the invention are applied to local mucosa preparations, injections or oral preparations; the application of the nanoparticles in the paper is injection or oral preparation.
Disclosure of Invention
The first purpose of the invention is to provide a compound curcumin nanoparticle aiming at the defects in the prior art.
The second purpose of the invention is to provide a preparation method of the compound curcumin nanoparticles.
The third purpose of the invention is to provide the application of the compound curcumin nanoparticles.
In order to achieve the first purpose, the invention adopts the technical scheme that:
the compound curcumin nanoparticles are prepared by adopting an encapsulation rate optimized membrane dispersion-low temperature curing method, and are prepared from the following components in parts by weight: curcumin: piperine: the organic phase comprises (10), (1-30), (120-440) and (120-400) of water phase.
The organic phase comprises a solid lipid material and an organic solvent capable of dissolving the solid lipid material; the aqueous phase includes an emulsifier and water.
The solid lipid material comprises one or more of glyceride, soybean lecithin, egg yolk lecithin and cholesterol, and the organic solvent is one or more of methanol, anhydrous ethanol, diethyl ether, acetone, ethyl acetate and chloroform.
The solid lipid material is preferably glyceryl monostearate and soybean lecithin, the mass ratio of the glyceryl monostearate to the soybean lecithin is 1 (1-3), and the organic solvent is preferably a mixed solution of absolute ethyl alcohol and ethyl acetate, and the mass ratio of the absolute ethyl alcohol to the ethyl acetate is 1 (0.5-3).
The emulsifier is selected from auxiliary materials with P-gp inhibition effect: triblock copolymers such as pluronic F68, F88, F108, F127, P85, P81, P61, P123, P188, L35, L44, and P407; brij 58, Brij 35, Brij 78 or Brij 30 polyoxyethylene fatty alcohol ether; one or more of vitamin E succinate and polyethylene glycol 1000 vitamin E succinate (TPGS).
The emulsifier is TPGS and pluronic P85, and the mass ratio of the emulsifier to the emulsifier is 1 (0.5-1.5).
In order to achieve the second object, the invention adopts the technical scheme that:
the preparation method of the compound curcumin nano-particle adopts a film dispersion-low temperature curing method to prepare: precisely weighing curcumin, piperine, lecithin and glyceryl monostearate, adding a mixed solution of anhydrous ethanol and ethyl acetate, heating and ultrasonically dissolving to form an organic phase, transferring the organic phase into a round-bottom flask, and controlling the temperature of a water bath. Opening a vacuum pump to extract air in the system, completely volatilizing the organic solvent, and performing rotary evaporation to form a light yellow transparent film on the flask; dissolving emulsifier TPGS and Pluronic P85 in distilled water to form water phase; adding the water phase into a round-bottom flask, and performing rotary elution; transferring the suspension into a beaker, and performing ultrasonic curing in water bath to obtain the compound curcumin nanoparticles
In order to achieve the third object, the invention adopts the technical scheme that:
application of compound curcumin nanoparticles in preparing medicine for treating tumor is provided.
The tumor cell is selected from ovarian tumor, breast tumor, liver tumor, lung tumor, prostate tumor, stomach tumor, pancreatic tumor, nasopharyngeal carcinoma, intestinal cancer, gallbladder cancer, bile duct cancer, gallbladder cancer, cervical cancer, thyroid cancer, colon cancer, bladder cancer, pancreatic cancer or bronchial cancer.
The invention has the advantages that: the compound nanoparticles adopted by the invention have the advantages of improving the solubility and stability of the medicine, realizing slow in-vitro release and improving the anti-tumor and multi-drug resistance reversing effects of the curcumin. Curcumin and piperine are sensitive to light and heat and unstable in vitro, so a film dispersion-low temperature curing method is preferred, the preparation method is simple, the particle size of the nanoparticles is uniform, the stability is good, the drug can be slowly released, and the curcumin and the piperine can be administrated locally through mucosa, intravenously or orally, and are convenient to administer. The compound curcumin nanoparticles provided by the invention can be used independently or in combination with other antitumor drugs, so that the curative effect of the antitumor drugs is enhanced, and the multi-drug resistance phenomenon of tumor cells is reversed. The compound curcumin nanoparticles have a certain inhibition rate on the growth of tumor drug-resistant cells, and the tumor drug-resistant cells have a higher uptake rate on the compound curcumin nanoparticles.
Drawings
Fig. 1 is an appearance diagram of the preparation (the left penicillin bottle is a compound curcumin nanoparticle solution, the middle penicillin bottle is a piperine aqueous solution, and the right penicillin bottle is a curcumin aqueous solution).
Fig. 2 is a transmission electron microscope image of compound curcumin nanoparticles.
Figure 3 shows the particle size of the compound curcumin nanoparticles.
Fig. 4 cytotoxicity assay (n-6,
)
FIG. 5 results of drug-resistant cell uptake (. times.20). (A: negative control; B: free piperine solution; C: free curcumin solution; D: TPGS; E: P85; F: blank nanoparticle; G: curcumin nanoparticle; H: compound curcumin nanoparticle).
Detailed Description
The following examples are provided to illustrate specific embodiments of the present invention.
Example 1:
a thin film dispersion-low temperature solidification method is adopted, 10mg of curcumin and 1mg of piperine, 100mg of lecithin and 150mg of glyceryl monostearate are precisely weighed, 5mL of mixed solution (absolute ethyl alcohol: ethyl acetate: 3:2) is added, heating and ultrasonic treatment are carried out to dissolve the materials to form an organic phase, the organic phase is transferred into a round bottom flask, and the water bath temperature is controlled. And opening a vacuum pump to extract air in the system, completely volatilizing the organic solvent, and performing rotary evaporation to form a light yellow transparent film on the flask. Dissolving emulsifier TPGS100mg and P85150 mg in distilled water, and heating and stirring to obtain water phase. The aqueous phase was added to a round bottom flask and the flask was spun to elute. And transferring the suspension into a beaker, and carrying out ultrasonic curing in a water bath to obtain the compound curcumin nanoparticles.
The physicochemical properties of the compound curcumin nanoparticles obtained in example 1 were studied, including Zeta potential, particle size, encapsulation efficiency, and in vitro release.
(1) Appearance of the formulation
The prepared compound curcumin nanoparticle solution is shown in figure 1, (the left penicillin bottle is compound curcumin nanoparticle solution, the middle penicillin bottle is piperine aqueous solution, and the right penicillin bottle is curcumin aqueous solution)
(2) Morphological observation
And (3) dripping 1 drop of the compound curcumin nanoparticle solution on a copper net covered with a support film, fixing and dyeing, and observing the form of the compound curcumin nanoparticle solution under a transmission electron microscope. The results are shown in figure 2, and the results show that the prepared compound curcumin nanoparticles are spherical-like in shape and uniform in size, and the nanoparticles are basically free of adhesion.
(2) Particle size distribution
The freshly prepared compound curcumin nanoparticle solution is diluted by a proper amount of distilled water, and the particle size of the solution is measured by a Zetasizer NanoZS90 particle size potential analyzer. The particle size distribution is shown in FIG. 3, and the average particle size is 146.9 nm. The polydispersity is 0.186, which shows that the prepared compound curcumin nanoparticles have smaller particle size and uniform particle size distribution.
(3) Encapsulation efficiency
The encapsulation rate of curcumin and piperine is determined, and the encapsulation rate of curcumin and piperine in the compound curcumin nanoparticles is 84.3% and 15.9%.
(4) Cytotoxicity test
The cytotoxicity test result of the compound curcumin nanoparticles is shown in figure 4. As can be seen from the figure, the inhibition effect of curcumin and piperine on cells is very small, and both are less than 10%. The nonionic surfactants P85 and TPGS as P-gp inhibitors have small inhibition effect on cells, and the auxiliary materials TPGS and Brij8 in the preparation have no cytotoxic effect. The compound curcumin nanoparticles have the strongest inhibition effect on cells (P <0.01), and the inhibition rate of the cells is (66.24 +/-6.35)%. The nanoparticles can carry the medicine into cells, and the medicine concentration in the cells is enhanced. The results show that the compound curcumin nanoparticles have stronger inhibition effect on cells as a new preparation formulation and a medicine composition, and can better play the anti-tumor and multi-drug resistance reversing effects of curcumin.
(5) Cell uptake assay
In the experiment, the P-gp uptake and discharge of the compound curcumin nanoparticles are inspected by adopting laser confocal observation, and the result is shown in figure 5. The cell is treated by the nonionic surfactants TPGS and P85, the intracellular fluorescence intensity can be increased, and the intracellular fluorescence intensity after the TPGS treatment is higher, so that the inhibition effect of the TPGS on P-gp is greater than that of P85, and the cytotoxicity of the TPGS is lower as seen from the in vitro cytotoxicity result, and the result indicates that the TPGS is a good carrier material for reversing the multi-drug resistance phenomenon of tumor cells. Blank SLNs prepared by using TPGS and P85 with P-gp inhibition as emulsifiers can also increase the uptake of Rh123 by cells. In all the uptake results, the fluorescence intensity of Rh123 in the cells after the compound curcumin nanoparticles are treated is the largest, which indicates that the concentration of Rh123 in the cells is the highest. The nanoparticles are used as a novel carrier, can carry a medicament to enter cells, and improve the concentration of the medicament in the cells, thereby playing a role. Therefore, the compound curcumin nanoparticle drug delivery system has a certain effect on reversing multidrug resistance.
Example 2:
a thin film dispersion-low temperature solidification method is adopted, 10mg of curcumin and 5mg of piperine, 60mg of soybean lecithin and 60mg of glyceryl monostearate are precisely weighed, 6mL of mixed solution (absolute ethyl alcohol: ethyl acetate: 3) is added, heating and ultrasonic treatment are carried out to dissolve the materials to form an organic phase, the organic phase is transferred to a round bottom flask, and the water bath temperature is controlled. And opening a vacuum pump to extract air in the system, completely volatilizing the organic solvent, and performing rotary evaporation to form a light yellow transparent film on the flask. Dissolving emulsifiers TPGS100mg and P85150 mg in distilled water, and heating and stirring to obtain water phase. The aqueous phase was added to a round bottom flask and the flask was spun to elute. And transferring the suspension into a beaker, and carrying out ultrasonic curing in a water bath to obtain the compound curcumin nanoparticles.
The physical and chemical properties of the obtained compound curcumin nanoparticles are researched, and the result shows that the average particle size of the compound curcumin nanoparticles is 186.5 nm; the Zeta potential is-16.5 mV; the encapsulation rate of curcumin is 72.6 percent, and the encapsulation rate of piperine is 13.6 percent; in vitro release experiments show that the nanoparticles can slowly release the medicine, release the medicine completely and have good slow release performance.
Example 3:
according to the thin film dispersion-low temperature solidification method, 10mg of curcumin, 5mg of piperine, 200mg of glyceryl monostearate, 150mg of egg yolk lecithin and 90mg of oleic acid are respectively weighed, added into 5mL of organic solvent (absolute ethyl alcohol: ethyl acetate ═ 2:3), and heated in a water bath and ultrasonically dissolved to form an organic phase. The organic phase was transferred to a round bottom flask and the water bath temperature was controlled at about 60 c, the round bottom flask was kept at a suitable angle to the horizontal. Opening a vacuum pump to extract air in the system, completely volatilizing the organic solvent, and performing rotary evaporation to form a film. The emulsifiers TPGS 80mg and pluronic P85100 mg were dissolved in distilled water to form an aqueous phase. The aqueous phase was added to a round bottom flask and the flask was spun to elute. And transferring the suspension into a beaker, carrying out water bath ultrasonic treatment, and then placing the beaker in a refrigerator at 4 ℃ for cooling and solidification to obtain the curcumin and piperine nanoparticles.
The physicochemical properties of the obtained compound curcumin nanoparticles are researched, and the result shows that the average particle size of the compound curcumin nanoparticles is 178.4 nm; the Zeta potential is-23.6 mV; the encapsulation rate of curcumin is 81.6 percent, and the encapsulation rate of piperine is 12.8 percent; in vitro release experiments show that the nanoparticles can slowly release the medicine, release the medicine completely and have good slow release performance.
Example 4:
the preparation method comprises the following steps: film Dispersion-Low temperature curing method as in example 1
The physicochemical properties of the obtained compound curcumin nanoparticles are researched, and the result shows that the average particle size of the compound curcumin nanoparticles is 192.6 nm; the Zeta potential is-21.6 mV; the encapsulation rate of curcumin is 79.5 percent, and the encapsulation rate of piperine is 15.6 percent; in vitro release experiments show that the nanoparticles can slowly release the medicine, release the medicine completely and have good slow release performance.
Example 5:
the preparation method comprises the following steps: film Dispersion-Low temperature curing method as in example 1
The physical and chemical properties of the obtained compound curcumin nanoparticles are researched, and the result shows that the average particle size of the compound curcumin nanoparticles is 186.7 nm; the Zeta potential is-23.5 mV; the encapsulation rate of curcumin is 71.7 percent, and the encapsulation rate of piperine is 18.6 percent; in vitro release experiments show that the nanoparticles can slowly release the medicine, release the medicine completely and have good slow release performance.
A large number of tests prove that the composition comprises the following components in parts by weight: curcumin: piperine: the organic phase comprises (10), (1-30), (120-440) and (120-400), and the obtained nanoparticles have good physicochemical properties. Such as having a smaller average particle size, a uniform particle size, and increased stability; the encapsulation rate of the curcumin and the bioavailability enhancer is better, the in-vitro dissolution rate of the medicine is obviously improved, and the curcumin and the bioavailability enhancer have good slow release performance. Therefore, the content of each component is not limited to the list of the above examples, and the emulsifier is selected from the auxiliary materials with P-gp inhibition effect, and also can be three-block copolymers such as pluronic F68, F88, F108, F127, P81, P61, P123, P188, L35, L44, P407 and the like; polyoxyethylene fatty alcohol ethers such as Brij 58, Brij 35, Brij 78, and Brij 30; one or more of vitamin E succinate and polyethylene glycol 1000 vitamin E succinate (TPGS).
It is also evident from a number of experiments that the types of the above-mentioned components are not limited to the examples given above.
The nano-particles of the invention can adopt a film dispersion-low temperature curing method. The obtained nanoparticles have particle size less than 200nm, uniform particle size and stable performance.
The invention adopts nanoparticles to remarkably improve the in-vitro dissolution rate of the medicament and increase the stability of the medicament, and simultaneously selects pluronic P85 and TPGS with P-gp inhibition as auxiliary materials to enhance the reversal effect of the medicament resistance phenomenon of tumor cells. The compound curcumin nanoparticles prepared by the invention provide a better basis for the research of late reversal of multi-drug resistance of cells.
The above description is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, several modifications and additions can be made without departing from the method of the present invention, and these modifications and additions should also be regarded as the protection scope of the present invention.
Claims (9)
1. The compound curcumin nanoparticles are characterized by being prepared by adopting an encapsulation rate optimized membrane dispersion-low temperature curing method, and are prepared from the following components in parts by weight: curcumin: piperine: organic phase-aqueous phase-10 (1)～30):(120～440):(120～400)。
2. The compound curcumin nanoparticle according to claim 1, wherein: the organic phase comprises a solid lipid material and an organic solvent capable of dissolving the solid lipid material; the aqueous phase includes an emulsifier and water.
3. The compound curcumin nanoparticle according to claim 2, wherein: the solid lipid material comprises one or more of glyceride, soybean lecithin, egg yolk lecithin and cholesterol, and the organic solvent is one or more of methanol, anhydrous ethanol, diethyl ether, acetone, ethyl acetate and chloroform.
4. The compound curcumin nanoparticle according to claim 3, wherein: the solid lipid material is preferably glyceryl monostearate and soybean lecithin, and the mass ratio of the glyceryl monostearate to the soybean lecithin is 1 (1)～3) The organic solvent is preferably a mixed solution of absolute ethyl alcohol and ethyl acetate, and the mass ratio of the absolute ethyl alcohol to the ethyl acetate is 1 (0.5)～3)。
5. The compound curcumin nanoparticle according to claim 1, wherein: the emulsifier is selected from auxiliary materials with P-gp inhibition effect: triblock copolymers such as pluronic F68, F88, F108, F127, P85, P81, P61, P123, P188, L35, L44, and P407; brij 58, Brij 35, Brij 78 or Brij 30 polyoxyethylene fatty alcohol ether; one or more of vitamin E succinate and polyethylene glycol 1000 vitamin E succinate.
6. The compound curcumin nanoparticle according to claim 5, wherein: the emulsifier is TPGS and pluronic P85, and the mass ratio of the emulsifier to the emulsifier is 1 (0.5)～1.5)。
7. The preparation method of the compound curcumin nanoparticles as claimed in any one of claims 1 to 6, is characterized in that: the preparation method is characterized by adopting a film dispersion-low temperature curing method: precisely weighing curcumin, piperine, lecithin and glyceryl monostearate in the weight ratio of the raw materials in the claim 1, adding a mixed solution of absolute ethyl alcohol and ethyl acetate, heating and ultrasonically dissolving to form an organic phase, transferring the organic phase into a round-bottom flask, and controlling the water bath temperature. Opening a vacuum pump to extract air in the system, completely volatilizing the organic solvent, and performing rotary evaporation to form a light yellow transparent film on the flask; dissolving emulsifier TPGS and Pluronic P85 in distilled water to form water phase; adding the water phase into a round-bottom flask, and performing rotary elution; and transferring the suspension into a beaker, and carrying out ultrasonic curing in a water bath to obtain the compound curcumin nanoparticles.
8. The use of the compound curcumin nanoparticles of any one of claims 1-6 in the preparation of a medicament for treating tumors.
9. Use according to claim 8, characterized in that: the tumor cell is selected from ovarian tumor, breast tumor, liver tumor, lung tumor, prostate tumor, stomach tumor, pancreatic tumor, nasopharyngeal carcinoma, intestinal cancer, gallbladder cancer, bile duct cancer, gallbladder cancer, cervical cancer, thyroid cancer, colon cancer, bladder cancer, pancreatic cancer or bronchial cancer.
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| CN113171462A (en) * | 2021-04-02 | 2021-07-27 | 江西建昌帮食疗科技有限公司 | Pharmaceutical composition and preparation method and application thereof |
| CN114404390A (en) * | 2022-02-07 | 2022-04-29 | 复旦大学附属中山医院青浦分院(上海市青浦区中心医院) | Preparation method and application of compound paclitaxel solid lipid nanoparticles |
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