CN102512369A - Glycyrrhetinic acid solid lipid nanoparticles and preparation method for same - Google Patents

Abstract

The invention relates to glycyrrhetinic acid solid lipid nanoparticles and a preparation method thereof, belonging to the field of pharmaceutical preparations. The main components of the glycyrrhetinic acid solid lipid nanoparticle include active raw material glycyrrhetinic acid, pharmaceutically acceptable phospholipids, lipid materials and surfactants. The glycyrrhetinic acid solid lipid nanoparticle solution and its freeze-dried powder injection prepared by the invention have small particle size, high encapsulation efficiency and good stability, and can be used in various administration routes such as oral administration and injection administration. The glycyrrhetinic acid solid lipid nanoparticles of the present invention can not only reduce the dosage of drugs, enhance the curative effect, but also reduce the toxic and side effects of drugs, and are suitable for treating hepatitis, liver cancer, lung cancer, ovarian cancer, gastritis, gastric cancer, leukemia and AIDS, etc. disease.

Description

Glycyrrhetinic acid solid Lipid nanoparticle and preparation method thereof

technical field

The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to glycyrrhetinic acid solid lipid nanoparticles and a preparation method thereof.

Background technique

Glycyrrhetinic acid (Glycyrrhetinic acid, GA) is derived from the hydrolysis of glycyrrhizic acid, the main component of licorice, and is also an active metabolite of glycyrrhizic acid in the body. It is a pentacyclic triterpenoid compound. GA is also called glycyrrhetinic acid, its molecular formula is C ₃₀ H ₄₆ O ₄ , it is white needle crystal, and its melting point is 289~291℃. The structure is as follows:

Modern studies have shown that glycyrrhetinic acid has anti-inflammatory, anti-ulcer, anti-allergic, anti-viral, blood lipid-lowering, cough-relieving, asthma-relieving, and pain-relieving effects, as well as anti-tumor hyperplasia [Liu Bin, Qi Yun. Advances in pharmacological research of glycyrrhizic acid and glycyrrhetinic acid. Foreign Medicine · Herbal Drugs Volume, 2006, 21 (3): 100-104.]. Studies have found that glycyrrhetinic acid has a significant inhibitory effect on rat hepatocellular carcinoma, human liver cancer cells, Ehrlich ascites carcinoma, skin cancer, malignant melanoma, human breast cancer cells, human leukemia cells, and AIDS. [1, Huang Wei et al. 18β-glycyrrhetinic acid and glycyrrhetinic acid inhibit the proliferation and induce differentiation of human liver cancer cells. Chinese Medicine Science and Technology. 2009,9(2):92-95; 2, René Csuk, Stefan Schwarz , Ralph Kluge, Dieter Ströhl. Synthesis and biological activity of some antitumor active derivatives from glycyrrhetinic acid, European Journal of Medicinal Chemistry, 2010, 45: 5718-5723.].

Glycyrrhetinic acid has aroused extensive interest of medical workers at home and abroad. Japan is studying the use of glycyrrhetinic acid to treat cancer, and anti-liver cancer preparations have been clinically available. The National Cancer Research Center of the United States is also studying the effect of "triterpenoids" in licorice on inhibiting the growth of cancer cells and preventing tooth decay. Western countries import a large amount of licorice, from which glycyrrhetinic acid is extracted to treat AIDS. In recent years, my country has also begun to attach importance to and strengthen the research and development of glycyrrhetinic acid. Since glycyrrhetinic acid is a water-insoluble compound, it has poor absorption in the body after oral administration, low bioavailability, and large individual differences. As an anti-cancer agent, prolonging the residence time of the drug in the body and allowing it to concentrate at the treatment site is of great significance for enhancing the efficacy of the drug and improving the bioavailability of the drug.

Solid lipid nanoparticles (SLN) are a new type of drug delivery system developed in the early 1990s. It is a particle size between 50-1000nm formed by encapsulating drugs in lipid cores. Colloid drug delivery system. SLN has the advantages of good stability, high drug loading capacity, low toxicity of liposomes, large-scale production, targeting, and sustained release [Muller RH, et al. Solid lipid nanoparticles (SLN) for controlled drug delivery a review of the state of the art. Eur J Pharm Biopharm, 2000, 50(1): 161-177].

Ordinary solid lipid nanoparticles enter the systemic circulation and are easily recognized and phagocytized by macrophages, and release drugs through lysosomes in macrophages, making them passively targeted and easily aggregated into the liver, spleen, and lymph nodes. In order to prolong the action time of nanoparticles in vivo, nanoparticles can usually be modified with PEG to increase their surface hydrophilicity and form steric hindrance, so that nanoparticles can avoid the recognition of mononuclear macrophage cell line (MPS), prolong the nanoparticle The residence time of particles in the blood circulation allows them to reach the target site with more sufficient time, so as to achieve the purpose of active targeting [Gref R, et al. “Stealth” corona-core nanoparticles surface modified by polyethylene glycol ( PEG) : influences of the corona(PEG chain length and surface density) and of the core composition on phagocyt ic uptake and plasma protein absorption [J]. Colloid Surf B, 2000, 18(3 - 4): 301- 313].

Contents of the invention

The technical problem to be solved by the present invention is to provide a glycyrrhetinic acid solid lipid nanoparticle with stable properties and suitable for industrial production and a preparation method thereof. The glycyrrhetinic acid solid lipid nanoparticle of the present invention encapsulates glycyrrhetinic acid in a lipid core, has good stability, high encapsulation rate, and can achieve effects such as targeting and sustained release. Glycyrrhetinic acid solid lipid nanoparticles of the present invention can be prepared by a variety of methods, including emulsification evaporation-high pressure homogenization or ultrasonic, film dispersion-high pressure homogenization or ultrasonic and melting-high pressure homogenization method to prepare the solid lipid of glycyrrhetinic acid The plasma nanoparticle solution is further obtained by adding a scaffolding agent and freeze-drying to obtain the freeze-dried powder of the glycyrrhetinic acid solid lipid nanoparticle which is convenient for storage and transportation.

The glycyrrhetinic acid solid lipid nanoparticle of the invention consists of a therapeutically effective dose of active ingredients encapsulated in a lipid core. Specifically, wherein the mass percentages of each component are as follows:

Glycyrrhetinic acid 1-10%

Phospholipids 10-80%

lipid 5-50%

Surfactant 10-50%

When the surfactant used in the prescription is a polyethylene glycol (PEG) modified material, it is glycyrrhetinic acid long-circulation solid lipid nanoparticles. Commonly used polyethylene glycol modification materials are lipid derivatives of PEG, such as polyethylene glycol-phosphatidylethanolamine (mPEG-PE), methoxypolyethylene glycol-distearoylphosphatidylethanolamine (mPEG-DSPE), One of polyethylene glycol monomethyl ether cholesterol succinate (PEGCHS), etc.

The phospholipids can be egg yolk lecithin, soybean lecithin, hydrogenated soybean lecithin, hydrogenated egg yolk lecithin, phosphatidylinositol, phosphatidylserine, diphosphatidylethanolamine, dipalmitoylphosphatidylcholine, dipalmitoylphosphatidylethanolamine, Distearoylphosphatidylcholine, distearoylphosphatidylethanolamine, etc.

The lipids include glycerol lipids, including glyceryl monostearate, glyceryl distearate, glyceryl tristearate, glyceryl trimyristate, glyceryl monopalmitate, glyceryl dipalmitate Esters, tripalmitin, trilaurate, triolein, behenate, and mixtures thereof; fatty acids, including stearic, palmitic, oleic, behenic, capric and their mixtures; sterols, including cholesterol, etc.; waxes, including cetyl palmitate, cetyl palmitate and microcrystalline paraffin.

The surfactant can be polyethylene glycol derivatives, including polyethylene glycol-phosphatidylethanolamine (mPEG-PE), methoxypolyethylene glycol-distearoylphosphatidylethanolamine (mPEG-DSPE) , polyethylene glycol monomethyl ether cholesterol succinate (PEGCHS), etc.; bile salts, including sodium cholate, sodium glycocholate, sodium taurocholate; deoxycholate, including sodium deoxycholate, Sodium taurodeoxycholate; Poloxamers, including Poloxamers 108, 188, 407, 908; Polysorbates, including Tween 80, 85, 65, 60, 40.

The particle size of the solid lipid nanoparticles prepared by the method of the invention is controllable, and nanoparticles with different particle sizes from 50 nm to 800 nm and uniform particle sizes can be prepared according to requirements.

The above-mentioned glycyrrhetinic acid solid lipid nanoparticles can be prepared by the following method:

Method 1: Weigh glycyrrhetinic acid, phospholipids, lipids and surfactants in proportion, dissolve them in an organic solvent; evaporate under reduced pressure, remove the organic solvent, form a thin film on the container wall, inject an aqueous solution with a pH of 6-8, and make the membrane material Dissolve and hydrate for 1-2 hours; the formed emulsion is further reduced in nanoparticle size by high-pressure emulsification or ultrasound, and then passed through a microporous filter to obtain a solid lipid nanoparticle solution with uniform particle size and controllable size.

Method 2: Weigh glycyrrhetinic acid, phospholipids, lipids and surfactants in proportion, and dissolve them in an organic solvent; inject the organic solution directly into an aqueous solution with a pH of 6-8 under stirring to form an emulsion, and then evaporate under reduced pressure to remove the organic solvent. Solvent; the formed emulsion is further reduced in nanometer particle size by high-pressure emulsification or ultrasound, and then passed through a microporous filter to obtain a solid lipid nanoparticle solution with uniform particle size and controllable size.

Method 3: weighing glycyrrhetinic acid, phospholipids, lipids and surfactants in proportion, directly heating and melting;

Inject the aqueous solution of pH 6-8 into the molten mixture under stirring; the formed emulsion is further reduced in nanometer particle size by high-pressure emulsification or ultrasound, and then passed through a microporous filter to obtain uniform particle size and controllable size solid lipid nanoparticle solution.

To facilitate storage and transportation, the glycyrrhetinic acid solid lipid nanoparticle solution can be spray-dried or freeze-dried into solid powder, wherein excipients need to be added. Excipients used include mannitol, glucose, cyclodextrin, lactose, sucrose, trehalose, dextran, glycine, sodium chloride, etc.

The inventive method, used organic solvent can use common organic solvent, as one or its mixture in methanol, ethanol, ether, acetone, chloroform, ethyl acetate, dichloromethane etc.

The aqueous solution with a pH of 6-8 can be distilled water, water for injection, phosphate buffer, and an aqueous solution or phosphate buffer containing β-cyclodextrin, hydroxypropyl β-cyclodextrin or methyl β-cyclodextrin.

The glycyrrhetinic acid solid lipid nanoparticle preparation of the invention can be used for treating diseases such as hepatitis, liver cancer, breast cancer, lung cancer, gastritis, stomach cancer, ovarian cancer, leukemia and AIDS.

The method of the invention is simple and easy to perform, easy to disinfect and suitable for large-scale production. The prepared glycyrrhetinic acid solid lipid nanoparticles have uniform particle size, high encapsulation efficiency and good stability, and are suitable for various administration routes such as oral or injection. The selected carrier materials are safe, non-toxic and have good physiological compatibility , can target inflammation or cancerous sites, and can slowly release drugs to achieve long-term effects.

Description of drawings

Fig. 1 Transmission electron micrograph of glycyrrhetinic acid solid lipid nanoparticles in Example 1.

Fig. 2 is the particle size distribution diagram of glycyrrhetinic acid solid lipid nanoparticles in Example 1.

Fig. 3 The elution curve of glycyrrhetinic acid solid lipid nanoparticles prepared in Example 1 through CL-4B gel column.

Fig. 4 The in vitro dissolution profile of glycyrrhetinic acid solid lipid nanoparticles.

Detailed ways

Example 1

formula Mass percentage (%)

Glycyrrhetinic acid 5

egg yolk lecithin 40

stearic acid 30

mPEG-DSPE 25

Weigh glycyrrhetinic acid, egg yolk lecithin, stearic acid and mPEG-DSPE, dissolve them in 2ml of ethanol, and ultrasonically dissolve them to form a transparent solution, pour them into 50ml of distilled water at 50°C, keep stirring for 30 minutes, and place in a rotating Evaporate under reduced pressure on the evaporator to further volatilize the organic solvent, then circulate and homogenize for 3-5 times through a high-pressure homogenizer, let it cool at room temperature, and pass through a 0.45µm filter membrane to obtain a colloidal solution of glycyrrhetinic acid solid lipid nanoparticles , the colloidal solution is translucent, blue opalescent. The drug content in the drug was determined by a reversed-phase high-performance liquid chromatography column. The chromatographic column was ODS C ₁₈ column (4.6*250mm, 5µm), the mobile phase was methanol-water-glacial acetic acid (volume ratio 89:10:1), the flow rate was 1.0ml/min, the detection wavelength was 250nm, and the injection volume was 10µL. The standard curve of glycyrrhetinic acid was established, and the results showed that the linear relationship of glycyrrhetinic acid in the range of 1µg/mL-80µg/mL was good. Get 0.2ml of the obtained liposome solution to pass through the agarose CL-4B gel column, use the phosphate buffer solution of pH 7.4 as the eluent, collect the effluent in the amount of 1ml per test tube, and calculate the encapsulation according to the elution curve. The rate reached 94.6%. The elution curve of glycyrrhetinic acid liposomes through CL-4B gel column is shown in Figure 3. Measure its particle size 130.1nm with Zeta potential particle size analyzer, Zeta potential is-36.2mv.

Example 2

formula Mass percentage (%)

Glycyrrhetinic acid 1

egg yolk lecithin 80

Oleic acid 9

PEGCHS 10

Weigh glycyrrhetinic acid, egg yolk lecithin, oleic acid and mPEG-DSPE into a 50ml round-bottomed flask, add 2ml chloroform to dissolve them, place a 40°C water bath on a rotary evaporator to recover the organic solvent under reduced pressure, and form A layer of film was further placed in a desiccator under reduced pressure to completely remove the organic solvent. Inject pH 8 phosphate buffer solution for hydration for 1 hour, place it in a probe ultrasonic breaker and sonicate for 10-30 minutes, pass through a 0.45 µm filter membrane, dilute the obtained liposome solution to volume, add 10% (g/ml) sucrose, and pass through Freeze-dry to obtain glycyrrhetinic acid solid lipid nanoparticle freeze-dried powder. After reconstitution, take 0.2ml to pass through the agarose CL-4B gel column, use pH 7.4 phosphate buffer as the eluent, collect the effluent according to the amount of 1ml per test tube, and calculate the encapsulation efficiency up to 90% according to the elution curve. %. Also as in Example 1, the content of glycyrrhetinic acid in the solid lipid nanoparticles was determined by high performance liquid chromatography. The particle size of the nanoparticles was measured to be 178.2nm, and the Zeta potential was -30.6mv.

Example 3

formula Mass percentage (%)

Glycyrrhetinic acid 4

Soy lecithin 46

glyceryl palmitate 5

Poloxamer 50

Weigh glycyrrhetinic acid, egg yolk lecithin, glyceryl palmitate, and poloxamer, melt and mix at 60°C, inject water at 60°C into the melt under stirring, continue stirring for 30 minutes, and circulate through a high-pressure homogenizer After massaging for 3-5 times, let cool at room temperature, pass through a 0.45µm filter membrane, stabilize the volume of solid lipid nanoparticles obtained by ultrasound, add 5% (g/ml) mannitol, and freeze-dry to obtain glycyrrhetinic acid solid lipid nanoparticles. granules of freeze-dried powder. After adding distilled water to redissolve, take 0.2ml to pass through the agarose CL-4B gel column, use pH 7.4 phosphate buffer as the eluent, collect the effluent in an amount of 1ml per test tube, and calculate the encapsulation according to the elution curve The rate reached 98%. The particle size of the nanoparticles was determined to be 231.7nm, and the Zeta potential was -33.15mv.

Example 4

formula Mass percentage (%)

Glycyrrhetinic acid 10

Hydrogenated Soy Lecithin 40

Glyceryl monostearate 40

Tween 80 10

Weigh glycyrrhetinic acid, egg yolk lecithin, and glyceryl monostearate and add 5ml of ethyl acetate to dissolve them, slowly inject the aqueous solution containing Tween 80 at 60°C under magnetic stirring with a syringe, continue to stir for 30 minutes, and then transfer to In a rotary evaporator, volatilize the organic solvent until it is completely removed. After being homogenized by a high-pressure homogenizer for 3-5 times, let it cool at room temperature, and pass through a 0.8µm filter membrane to obtain a colloidal solution of glycyrrhetinic acid solid lipid nanoparticles. Take 0.2ml to pass through the agarose CL-4B gel column, use pH 7.4 phosphate buffer as the eluent, collect the effluent in an amount of 1ml per test tube, and calculate the encapsulation efficiency up to 87.3% according to the elution curve. The measured particle size is 384.1nm, Zeta potential -25.12mv. 10% (g/ml) lactose is added, and the glycyrrhetinic acid solid lipid nanoparticle solid powder is obtained by spray drying, and the solid powder can be further prepared into capsules or tablets.

Example 5

formula Mass percentage (%)

Glycyrrhetinic acid 5

Hydrogenated egg yolk lecithin 10

stearic acid 50

Sodium deoxycholate 35

Weigh glycyrrhetinic acid, hydrogenated egg yolk lecithin, stearic acid and mPEG-DSPE into a 50ml round bottom flask, add 2ml of dichloroethane to dissolve it, put it in a 40°C water bath on a rotary evaporator to recover the organic solvent under reduced pressure , forming a layer of film on the wall of the bottle, and further placed in a decompression desiccator to completely remove the organic solvent. Inject into an aqueous solution containing sodium deoxycholate for hydration for 1 hour, sonicate for 10-30 minutes, pass through a 0.45 µm filter membrane, and dilute the resulting solid lipid nanoparticle solution to volume. Calculate the encapsulation efficiency to 92.4% according to the elution curve. The measured particle size is 155.3nm, Zeta potential -26.57mv. Add 10% (g/ml) trehalose, and freeze-dry to obtain glycyrrhetinic acid solid lipid nanoparticle freeze-dried powder. The freeze-dried powder can be further prepared into capsules or tablets.

Example 6

formula Mass percentage (%)

Glycyrrhetinic acid 3

Hydrogenated egg yolk lecithin 47

capric acid 15

mPEG-DSPE 35

Weigh glycyrrhetinic acid, hydrogenated egg yolk lecithin, cholesterol and mPEG-DSPE into a 50ml round-bottomed flask, add 2ml of chloroform to dissolve them, place a 40°C water bath on a rotary evaporator to recover the organic solvent under reduced pressure, and form A layer of film was further placed in a desiccator under reduced pressure to completely remove the organic solvent. Inject into an aqueous solution of pH 8 containing 0.1M β-cyclodextrin for hydration for 1 hour, freeze and thaw repeatedly 3 times, and pass through a high-pressure extruder to dilute the obtained solid lipid nanoparticle solution to volume, and calculate the encapsulation efficiency according to the elution curve Up to 95.7%. The measured particle size is 152.6nm, Zeta potential -23.15mv.

Example 7 Determination of release rate of glycyrrhetinic acid solid lipid nanoparticles in vitro. With 200mL of PBS solution containing 0.5% (g/ml) sodium lauryl sulfate and 30% (g/ml) ethanol at pH 7.4 as the medium, accurately pipette 2mL of glycyrrhetinic acid solid lipid nanoparticle solution, Placed in a dialysis bag (molecular weight cut off 3000), magnetically stirred. At 0.5, 1, 2, 3, 4, 6, 8, 10, 12, 24, and 48 hours, take 0.5 mL of the release solution, pass through a 0.45 µm microporous membrane for HPLC analysis, and supplement the dissolution medium at the same temperature 1mL. The concentration of GA was measured, and the cumulative release percentage was calculated. Calculate the release amount according to the formula Q(%)=C _t /C ₀ ×100%. Wherein C _t is the amount of drug released, and C ₀ is the initial amount of drug in the liposome. Taking time as the abscissa and the cumulative release percentage as the ordinate, draw the drug release curve in vitro, see Figure 4 for details. The obtained data were fitted according to the first-order, Higuchi and Weibull equations, and the relevant equations and fitting degrees are shown in Table 1. The results showed that the release rule was more in line with the first-order rate process, indicating that glycyrrhetinic acid was mainly released into the dissolution medium in the form of passive diffusion in solid lipid nanoparticles.

Table 1 In vitro drug release curve fitting of glycyrrhetinic acid solid lipid nanoparticles

Model regression equation Goodness of fit ( γ ² ) Formula 1 Y=0.0467X+4.4998 0.9952 Higuchi equation Q=13.556t ^1/2 +0.5998 0.9923 Weibull equation Y=0.6824X-2.0195 0.9846

Example 8 Cytotoxicity of glycyrrhetinic acid liposomes to liver cancer cells SK-HEP-1

SK-Hep-1 liver cancer cells with logarithmic growth were planted in 96-well plates at 0.5×10 ⁴ , and the free drug dexamethasone was used as a positive control. Dexamethasone, glycyrrhetinic acid and glycyrrhetinic acid liposomes were Diluted into a series of concentrations at a multiple of 1:4, added to a 96-well plate planted with liver cancer cells, made 3 wells in parallel under various conditions, cultured in an incubator at 37°C and 5% CO ₂ saturated humidity for 48 hours, and added 20µL of 5mg per well .mL ^-1 of MTT solution, continue to culture for 4 hours, absorb the culture medium, add 200 µL of dimethyl sulfoxide to each well, oscillate to fully dissolve, place on a microplate reader to measure the absorbance of each well at a wavelength of 570 nm, and compare the concentration logarithm The cell viability was plotted, and the calculated IC ₅₀ values of each sample against liver cancer cell SK-HEP-1 were 199±10 μM for free drug dexamethasone, 32±7 μM for glycyrrhetinic acid and 141±5 μM for liposome glycyrrhetinic acid.

Example 9 Cytotoxicity of glycyrrhetinic acid liposomes to leukemia cells MV4-11

Acute myeloid leukemia cells MV4-11 with logarithmic growth were planted in a 96-well plate at 1× ¹⁰⁵ , free drug doxorubicin hydrochloride (doxorubicin) and dexamethasone were used as positive controls, and doxorubicin , dexamethasone, glycyrrhetinic acid, and glycyrrhetinic acid liposomes were diluted into a series of concentrations by a multiple of 1:4, added to a 96-well plate planted with leukemia cells, and 3 wells were made in parallel under various conditions, at 37 ° C, 5% Cultivate in an incubator with saturated humidity of CO ₂ for 48 hours, add 20 µL of 5 mg.mL ^-1 MTT solution to each well, continue to incubate for 4 hours, absorb the culture solution, add 200 µL of dimethyl sulfoxide to each well, shake to fully dissolve, and place on the enzyme label The absorbance of each well was measured at a wavelength of 570nm on the instrument, and the logarithm value of the concentration was plotted against the cell survival rate, and the IC ₅₀ values of each sample against leukemia cells MV4-11 were calculated as free drug doxorubicin 0.16±0.1µM, dexamethasone 25±3µM, glycyrrhetinic acid 20±5µM and glycyrrhetinic acid liposome 63±4µM.

Claims (8)

1. A glycyrrhetinic acid solid lipid nanoparticle is formed by encapsulating the active ingredient of a therapeutically effective dose in a lipid core, wherein the mass percentage of each component is as follows: Glycyrrhetinic acid 1-10% Phospholipids 10-80% lipid 5-80% Surfactant 10-50%. 2. The glycyrrhetinic acid solid lipid nanoparticles according to claim 1, characterized in that, the phospholipids are natural phospholipids or synthetic phospholipids. 3. The glycyrrhetinic acid solid lipid nanoparticle according to claim 1, wherein said lipid comprises glycerides, fatty acids, sterols or waxes. 4. Glycyrrhetinic acid solid lipid nanoparticles according to claim 1, is characterized in that, described tensio-active agent is polyethylene glycol derivatives, bile salts, deoxycholic acid salts, poloxane Muscles or polysorbates. 5. The glycyrrhetinic acid solid lipid nanoparticle according to claim 1, characterized in that its particle diameter is between 50-1000nm. 6. the preparation method of the described glycyrrhetinic acid solid lipid nanoparticle of claim 1 is characterized in that, take glycyrrhetinic acid and phospholipid, lipid and tensio-active agent in proportion, be dissolved in organic solvent; Evaporate under reduced pressure, remove Organic solvent forms a film on the container wall, injects an aqueous solution of pH 6-8 to dissolve the film material, and hydrates for 1-2 hours; the formed emulsion is further reduced in nanometer particle size by high-pressure emulsification or ultrasound, and then passed through micropores filter to obtain a solid lipid nanoparticle solution with uniform particle size and controllable size. 7. the preparation method of the described glycyrrhetinic acid solid lipid nanoparticle of claim 1 is characterized in that, take glycyrrhetinic acid and phospholipid, lipid and tensio-active agent in proportion, be dissolved in organic solvent; Under stirring, organic The solution is directly injected into an aqueous solution with a pH of 6-8 to form an emulsion, and then evaporated under reduced pressure to remove the organic solvent; the formed emulsion is further reduced in nanometer particle size by high-pressure emulsification or ultrasound, and then passed through a microporous filter to obtain A solid lipid nanoparticle solution with uniform particle size and controllable size. 8. the preparation method of the described glycyrrhetinic acid solid lipid nanoparticle of claim 1 is characterized in that, take glycyrrhetinic acid and phospholipid, lipid and tensio-active agent in proportion, direct heating and melting; Under stirring state, pH6 The aqueous solution of -8 is injected into the molten mixture; the formed emulsion is further reduced by high-pressure emulsification or ultrasound to reduce the nanoparticle size, and then passed through a microporous filter to obtain solid lipid nanoparticles with uniform particle size and controllable size solution.

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