Echinacoside self-microemulsifying drug delivery system and preparation method thereof

Abstract

The invention discloses an echinacoside self-microemulsifying drug delivery system and a preparation method thereof, and belongs to the technical field of pharmaceutical preparations, the echinacoside self-microemulsifying drug delivery system comprises the following components by weight: 0.5%-5% of echinacoside, 10%-50% of an oil phase, 30%-70% of a compound emulsifier and 10%-40% of a co-emulsifier. According to the echinacoside self-microemulsifying drug delivery system and the preparation method thereof, the defects of incomplete in-vivo absorption and low bioavailability of echinacoside caused by the problems of unstable chemical structure, poor water solubility, low passive diffusion absorption efficiency in intestinal tracts and the like of the echinacoside are overcome, the preparation process is simple, and the preparation method is suitable for industrial production. The oral intestinal absorption characteristic of echinacoside is obviously improved.

Description

Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, and in particular to an echinacoside self-microemulsifying drug delivery system and a preparation method thereof. Background Art

[0002] Cistanche deserticola (Cistanche deserticola) is the dried fleshy stem of Cistanche deserticola or Cistanche tubulosa, both members of the Orobanchaceae family. Echinacoside (ECH), the primary active ingredient in Cistanche deserticola, belongs to the phenylethanoid glycoside family. Its unique caffeoyl-β-D-glucopyranoside domain confers significant pharmacological activity. Numerous basic research studies have demonstrated that ECH exhibits multiple pharmacological effects, including neuroprotection, hepatoprotection, cardioprotection, anti-tumor, and anti-aging, demonstrating promising development and application prospects. However, ECH faces numerous challenges in drug development and application. The compound suffers from structural instability, poor water solubility, and low passive diffusion absorption efficiency in the intestine, resulting in incomplete absorption and a bioavailability of only 0.83±0.15%. These limitations severely restrict the clinical application and industrial development of ECH, posing a critical scientific challenge that needs to be addressed. To address these challenges, researchers need to develop novel drug delivery systems to enhance the bioavailability of ECH.

[0003] A self-microemulsifying drug delivery system (SMEDDS) consists of a drug, an oil phase, an emulsifier, and a co-emulsifier. It can spontaneously form O / W emulsion droplets with a particle size of less than 100 nm in the gastrointestinal tract. This drug delivery system has multiple advantages: first, its nanoparticle size significantly increases the contact area between the drug and the intestinal mucosa; second, it effectively reduces surface tension, promoting drug penetration through the hydration layer of the gastrointestinal wall and improving its absorption efficiency; in addition, the system has high biocompatibility, good controlled-release properties, and can improve drug stability and reduce toxicity. Compared with traditional emulsions, SMEDDS has better physical and chemical stability and exhibits significant advantages in improving the oral bioavailability of poorly soluble drugs.

[0004] In view of this, the present invention is proposed. Summary of the Invention

[0005] In response to the problems of unstable chemical structure, poor water solubility and low passive diffusion absorption efficiency of echinacoside in the intestine, which lead to incomplete absorption and low bioavailability in the body, the present application provides an echinacoside self-microemulsifying drug delivery system and a preparation method thereof. The preparation process is simple and significantly improves the oral intestinal absorption characteristics of echinacoside.

[0006] The present invention is achieved in that: The present invention provides an echinacoside self-microemulsifying drug delivery system, comprising the following components in weight percentage: 0.5%-5% echinacoside, 10%-50% oil phase, 30%-70% composite emulsifier, and 10%-40% co-emulsifier; the composite emulsifier is selected from at least two of Tween 80, polyoxyethylene hydrogenated castor oil 40, poloxamer 188, and Span 80.

[0007] In some preferred embodiments, the oil phase is selected from one of castor oil, glyceryl trilaurate, polylactic acid-co-glycolic acid and isopropyl myristate, preferably glyceryl trilaurate.

[0008] In some preferred embodiments, the composite emulsifier is preferably Tween 80 and polyoxyethylene hydrogenated castor oil.

[0009] In some preferred embodiments, the weight ratio of Tween 80 to polyoxyethylene hydrogenated castor oil in the composite emulsifier is 1:1-2.5.

[0010] In some preferred embodiments, the co-emulsifier is selected from one of polyethylene glycol 200, polyethylene glycol 400 and diethylene glycol monoethyl ether, preferably polyethylene glycol 200.

[0011] In some preferred embodiments, the weight ratio of the oil phase to the composite emulsifier is 1:2-9.

[0012] In some preferred embodiments, the weight ratio of the co-emulsifier to the composite emulsifier is 1:1-2.5.

[0013] The present invention also provides a method for preparing an echinacoside self-microemulsifying drug delivery system, comprising the following steps: dissolving an appropriate amount of echinacoside in an emulsifier to form a first solution, mixing an oil phase and a composite emulsifier to form a second solution, uniformly mixing the first solution and the second solution to obtain a mixed solution, and finally stirring and dissolving the mixed solution in water to obtain an echinacoside self-microemulsification solution.

[0014] In some preferred embodiments, the stirring condition is to drop the mixed solution into water at 30-45° C. and stir evenly with magnetic stirring.

[0015] In some preferred embodiments, the echinacoside self-microemulsion has a microemulsion particle size of 24.5-25.48 nm.

[0016] The present invention has the following beneficial effects: The echinacoside self-microemulsifying drug delivery system of the present invention has the advantages of small particle size, large drug loading capacity, and good stability. It significantly improves the solubility and bioavailability of echinacoside, significantly enhancing the clinical efficacy of the drug, and provides broad prospects and application potential for the development of echinacoside. In addition, the preparation process of the echinacoside self-microemulsifying drug delivery system is simple and easy to industrialize. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the following briefly introduces the drawings required for use in the embodiments. It should be understood that the following drawings only illustrate certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other relevant drawings can be obtained based on these drawings without paying any creative work.

[0018] Figure 1 Particle size distribution (A) and zeta potential distribution (B) of ECH-SMEDDS; Figure 2 Ultrastructural images of ECH-SMEDDS (A: TEM, ×20000; B: TEM, ×60000). DETAILED DESCRIPTION

[0019] To make the purpose, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention are described clearly and completely below. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are used. Where the manufacturer of the reagents or instruments is not specified, all are conventional products that can be purchased commercially.

[0020] The following is a detailed description of the echinacoside self-microemulsifying drug delivery system and its preparation method proposed in the present invention.

[0021] The present invention provides an echinacoside self-microemulsifying drug delivery system, comprising the following components in weight percentage: 0.5%-5% echinacoside, 10%-50% oil phase, 30%-70% composite emulsifier, and 10%-40% co-emulsifier; the composite emulsifier is selected from at least two of Tween 80, polyoxyethylene hydrogenated castor oil 40, poloxamer 188, and Span 80.

[0022] A self-microemulsifying drug delivery system (SMEDDS) is a homogeneously mixed system consisting of an oil phase, an emulsifier, and a co-emulsifier. Compared to other delivery systems, SMEDDS offers the following advantages: First, they exhibit excellent thermodynamic and kinetic stability; second, their small droplet size allows for a larger contact area between the drug and the gastrointestinal wall, promoting rapid release of bioactive substances; and finally, their manufacturing requires simple equipment, resulting in a facile process, low cost, and ease of large-scale production. The application of SMEDDS offers unique advantages for traditional Chinese medicine (TCM) active ingredients that are poorly water-soluble, highly toxic, and unstable. For example, the natural product paclitaxel, an important drug for treating malignancies such as breast cancer, non-small cell lung cancer, and gastric cancer, has significantly improved its bioavailability through the SMEDDS delivery system, while reducing the toxicity and adverse reactions associated with injectable paclitaxel. This suggests that SMEDDSs promote the utilization of bioactive substances and hold great potential for development in pharmaceutical applications. Furthermore, the inventors have discovered that the use of a composite emulsifier can enhance the physical stability of SMEDDSs.

[0023] Among them, the commonly used oil phases of SMEDDS are vegetable oils and fatty acid esters. Fatty acid esters are superior to vegetable oils in safety, fluidity, solubility and self-emulsification properties. Medium-chain fatty acid esters are generally selected as the oil phase; the oil phase is preferably selected from one of castor oil, glyceryl trilaurate, polylactic acid-glycolic acid copolymer and isopropyl myristate. In the present invention, glyceryl trilaurate (GLT) is preferably used as the oil phase.

[0024] In some preferred embodiments, the emulsifier is primarily a non-toxic, high HLB value (11-15) nonionic surfactant, which can loosen cell junctions, increase the fluidity of small intestinal epithelial cells, and promote drug penetration and absorption. The composite emulsifier is preferably Tween 80 and polyoxyethylene hydrogenated castor oil. Furthermore, the weight ratio of Tween 80 to polyoxyethylene hydrogenated castor oil (RH40) in the composite emulsifier is 1:1-2.5, with the optimal ratio of Tween 80 to polyoxyethylene hydrogenated castor oil (RH40) being 2:3.

[0025] In some preferred embodiments, the co-emulsifier is selected from polyethylene glycol 200, polyethylene glycol 400, and diethylene glycol monoethyl ether, preferably polyethylene glycol 200 (PEG200). Co-emulsifiers can assist in dissolving the drug, forming a complex hydration layer. They also help the active ingredient form a uniform, transparent solution and maintain solution stability. The addition of a co-emulsifier not only reduces interfacial tension and reduces the amount of co-emulsifier used, but also increases the solubility of the drug in the formulation.

[0026] In some preferred embodiments, the weight ratio of the oil phase to the composite emulsifier is 1:2-9. Optimizing the ratio of the oil phase to the composite emulsifier can significantly enhance self-emulsification efficiency, enabling the system to rapidly form a nanoemulsion under mild conditions, thereby improving the solubility and bioavailability of poorly soluble drugs. Furthermore, a suitable oil phase to emulsifier ratio helps maintain the long-term stability of the system, preventing phase separation or drug precipitation during storage, while also reducing potential toxicity risks associated with excessive emulsifier use.

[0027] In some preferred embodiments, the weight ratio of the co-emulsifier to the composite emulsifier is 1:1-2.5. The ratio of the composite emulsifier to the co-emulsifier directly affects the self-emulsification efficiency, reducing interfacial tension and promoting the rapid formation of a nanoemulsion (typically with a particle size <100 nm) from the oil phase in the aqueous phase, thereby improving drug solubility and release rate. Furthermore, the co-emulsifier can adjust the HLB value of the emulsifier, optimizing its hydrophilic-lipophilic balance, further enhancing the stability of the microemulsion and preventing phase separation or Ostwald ripening during storage. Furthermore, it helps reduce system viscosity and improve fluidity, making it easier to disperse in the gastrointestinal environment. It also avoids potential irritation or toxicity issues caused by excessive use of co-emulsifiers. It can also reduce the amount of excipients and lower production costs.

[0028] The present invention also provides a method for preparing an echinacoside self-microemulsifying drug delivery system, comprising the following steps: dissolving an appropriate amount of echinacoside in an emulsifier to form a first solution, mixing an oil phase and a composite emulsifier to form a second solution, uniformly mixing the first solution and the second solution to obtain a mixed solution, and finally stirring and dissolving the mixed solution in water to obtain an echinacoside self-microemulsification solution.

[0029] The stirring condition is to drop the mixed solution into water at 30-45° C. and stir evenly with magnetic force.

[0030] During the SMEDDS preparation process, the self-microemulsification process and the order of excipient addition are adjusted based on the drug's solubility characteristics and physicochemical properties to increase drug loading. The inventors discovered that echinacoside has excellent solubility in aqueous co-emulsifiers. Therefore, they first dissolved ECH in the aqueous co-emulsifier, then mixed the oil phase and the composite emulsifier. Finally, the two solutions were evenly mixed to produce a clear, light yellow self-microemulsion, significantly improving the low drug loading of ECH-SMEDDS.

[0031] In addition, the microemulsion particle size of the finally prepared echinacoside self-microemulsion is 24.5-25.48 nm.

[0032] The features and performance of the present invention are further described in detail below with reference to the embodiments.

[0033] Example 1 This embodiment provides an echinacoside self-microemulsifying drug delivery system, comprising the following components in weight percentage: 5% echinacoside, 15.47% GLT, 35.35% Tween 80, 23.57% RH40, and 25.61% PEG200.

[0034] The preparation method comprises the following steps: Weigh the formulated amount of ECH and dissolve it in PEG200 to prepare a first solution; Weigh GLT, Tween 80, and RH40, mix, and heat to dissolve to prepare a second solution; The first solution and the second solution were mixed evenly to prepare a mixed solution, and then 50 uL of the solution was slowly dripped into 50 mL of 37° C. ultrapure water on a magnetic stirrer to completely emulsify the solution to obtain an echinacoside self-microemulsion.

[0035] Physicochemical properties of echinacoside self-microemulsifying drug delivery system: The particle size, zeta potential and polydispersity index (PDI) of echinacoside self-microemulsion were determined by laser particle size analyzer. The results are shown in Table 1 and Figure 1 .

[0036] Table 1. In vitro characterization of echinacoside self-microemulsifying drug delivery system

[0037] Ultrastructural characterization of echinacoside self-microemulsifying drug delivery system: An appropriate amount of echinacoside microemulsion was added to the copper grid, and after spreading evenly, 2.0% phosphotungstic acid solution was added. The negative staining was carried out for 10 minutes, and the excess microemulsion was removed from the edge. The grid was naturally dried at room temperature, and the morphology of the microemulsion was observed using a transmission electron microscope (TEM). The results are shown in FIG. Figure 2 As shown in the figure, the microemulsion formed after self-microemulsification is evenly dispersed, non-adhesive, and has spherical droplets of uniform size.

[0038] Determination of drug loading and encapsulation efficiency of echinacoside self-microemulsification drug delivery system: Accurately weigh 50 mg of ECH-SMEDDS (W) and place it in a 5 mL brown volumetric flask. Add an appropriate amount of methanol and sonicate until completely dissolved. Dilute to the mark with methanol and pass through a microporous filter. Chromatographic conditions were used for determination of ECH content (W1) using a Sham-pack GIST® C18 column (250 mm × 4.6 mm, 5 μm). The mobile phase consisted of acetonitrile and 0.1% formic acid in water (85:15). The detection wavelength was 330 nm, the injection volume was 10 μL, and the flow rate was 1.0 mL / min. Accurately weigh 50 mg of ECH-SMEDDS and dilute 100-fold with ultrapure water to prepare a microemulsion. A 5 mL sample was placed in a centrifuge tube and centrifuged at 10,000 rpm for 20 min. Accurately measure 1 mL of the supernatant and place it in a 5 mL brown volumetric flask. Add an appropriate amount of methanol and sonicate for 20 min. Dilute to the mark with methanol and shake well. Pass through a microporous filter and determine the ECH content (W2). The drug loading and encapsulation efficiency were calculated according to the following formula.

[0039]

[0040]

[0041] The results showed that the drug loading capacity of ECH-SMEDDS was (26.28±0.49) mg / g and the encapsulation efficiency was (97.63±0.17)%, indicating that the self-microemulsification formulation and preparation process met the requirements.

[0042] Stability of echinacoside self-microemulsifying drug delivery system: Three portions of the prepared self-microemulsification dispersion were taken and the particle size, PDI and Zeta potential of ECH-SMEDDS were measured within 0, 2, 4, 6, 8 and 10 days respectively.

[0043] Table 2. Particle size, PDI and Zeta potential of self-microemulsion at different storage times

[0044] The results are shown in Table 2. After the microemulsion was uniformly emulsified, the particle size, PDI and Zeta potential remained almost unchanged during the measurement time, indicating that the microemulsion had good stability.

[0045] Study on drug absorption of echinacoside self-microemulsifying drug delivery system: Twenty-four healthy Sprague-Dawley rats were fasted for 12 hours before the experiment and randomly divided into two groups: the ECH-SMEDDS group and the ECH aqueous solution group. Each group was further divided into four subgroups (duodenal, jejunal, ileal, and colonic) with three rats in each group. After intraperitoneal injection of 3% sodium pentobarbital (0.2 mL / 100 g), the abdominal cavity was opened along the midline of the abdomen, and the intestinal segments to be investigated were selected. Silicone tubing was inserted and secured at both ends of each intestinal segment. The inlet was connected to a peristaltic pump, and the outlet was connected to a centrifuge tube of known mass. The segments were then covered with saline-soaked gauze to maintain moisture. The intestine was first flushed with saline preheated to 37°C until the washout was clear. Then, the intestinal segment was perfused with 37°C KR solution at 1 mL / min for 15 min to balance. After further balancing for 30 min using ECH intestinal perfusion, the volume flow rate was adjusted to 0.2 mL / min for constant rate perfusion. The centrifuge tube was replaced at 0, 15, 30, 45, 60, 75, 90, 105, and 120 min, the effluent was collected, and the mass of the centrifuge tube was recorded.

[0046] 0.5 mL of the collected perfusion fluid was aspirated, 0.5 mL of methanol was added, vortexed and centrifuged at 5000 r / min for 10 min. The supernatant was aspirated and filtered through a 0.22 μm microporous filter membrane. The chromatographic column was selected: Sham-pack GIST® C18 (250 mm×4.6 mm, 5 μm); mobile phase: acetonitrile-0.1% formic acid aqueous solution (85:15); detection wavelength: 330 nm; injection volume: 10 μL; volume flow rate: 1.0 mL / min. The echinacoside content in the perfusion fluid was determined according to the above chromatographic conditions. After the perfusion was completed, the perfusion intestinal segment was cut and the diameter and length were recorded. The absorption rate constant (Ka) and apparent absorption coefficient (Papp) were calculated according to formula (1) (2). The data were expressed as follows: Graphpad 9.5 software was used for statistical analysis. One-way ANOVA was performed after normal distribution and homogeneity of variance tests were performed on the data. Tukey test was used for comparison between groups. The difference was considered statistically significant when P < 0.05.

[0047] K a = (1-C out V out / C in V in )Q / 2πrl(1) P app = Q ln (C in V in / C out V out ) / 2πrl(2) Cin 、C out are the drug concentrations in the inlet and outlet perfusates of the intestine, V in 、V out are the volumes of perfusate at the inlet and outlet of intestinal perfusion, r is the cross-sectional radius of the perfused intestinal segment, l is the length of the perfused intestinal segment, and Q is the perfusion volume flow rate (0.2 mL / min).

[0048] Table 3. Absorption parameters of ECH and ECH-SMEDDS in different intestinal segments

[0049] Note: Compared with the ECH perfusate group, *P<0.05 The absorption parameters of echinacoside (ECH) and echinacoside self-microemulsification preparation (ECH-SMEDDS) in various intestinal segments of rats are shown in Table 3. The results show that the absorption performance of echinacoside self-microemulsification preparation in all intestinal segments is significantly better than that of ordinary echinacoside. In the duodenal segment, the K a The value (3.38±0.18×10⁻² min⁻¹) was 1.48 times higher than that of ECH (2.29±0.83×10⁻² min⁻¹). app The value (21.33±0.57×10⁻³ cm·min⁻¹) is 5.05 times that of ECH (4.22±1.34×10⁻³ cm·min⁻¹), indicating that the self-microemulsification technology has greatly improved the problem of low drug absorption in the duodenum. a The value (11.51±0.91×10⁻² min⁻¹) was 2.24 times that of ECH (5.14±1.07×10⁻² min⁻¹), P app The value (24.95±1.40×10⁻³ cm·min⁻¹) also increased by 3.11 times, further verifying its absorption advantage. The absorption enhancement in the ileum and colon was also significant: the K a and P app The values ​​increased by 2.16 times and 1.85 times, respectively, while the K a and P app The values ​​increased by 1.86 times and 3.48 times, respectively. These data consistently indicate that ECH-SMEDDS significantly improves the intestinal permeability and absorption rate of echinacoside through self-microemulsification technology, and this enhancement effect is prominent throughout the entire intestinal segment, providing a reliable basis for efficient absorption in the jejunum and ileum, while also solving the problem of limited colonic absorption. Therefore, ECH-SMEDDS is a highly promising delivery system that can comprehensively optimize the bioavailability of echinacoside.

[0050] Example 2 This embodiment provides an echinacoside self-microemulsifying drug delivery system, comprising the following components in weight percentage: 5% echinacoside, 20% GLT, 21.67% Tween 80, 43.33% RH40, and 15% PEG200.

[0051] The preparation method comprises the following steps: Weigh the formulated amount of ECH and dissolve it in PEG200 to prepare a first solution; Weigh GLT, Tween 80, and RH40, mix, and heat to dissolve to prepare a second solution; The first solution and the second solution were mixed evenly to prepare a mixed solution, and then 50 uL of the solution was slowly dripped into 50 mL of 37° C. ultrapure water on a magnetic stirrer to completely emulsify the solution to obtain an echinacoside self-microemulsion.

[0052] Example 3 This embodiment provides an echinacoside self-microemulsifying drug delivery system comprising the following components by weight: 5% echinacoside, 30% GLT, 16% Tween 80, 24% RH40, and 30% PEG200. The preparation method comprises the following steps: Weigh the formulated amount of ECH and dissolve it in PEG200 to prepare a first solution; Weigh GLT, Tween 80, and RH40, mix, and heat to dissolve to prepare a second solution; The first solution and the second solution were mixed evenly to prepare a mixed solution, and then 50 uL of the solution was slowly dripped into 50 mL of 37° C. ultrapure water on a magnetic stirrer to completely emulsify the solution to obtain an echinacoside self-microemulsion.

[0053] Comparative Example 1 This comparative example provides an echinacoside self-microemulsifying drug delivery system, which differs from Example 1 only in that: echinacoside 5%, GLT 15.47%, RH40 58.93% and PEG200 25.6%, and Tween 80 is not added.

[0054] The prepared echinacoside self-microemulsifying drug delivery system may show stratification, precipitation, uneven viscosity or flocculent suspension after dilution after storage, and has poor stability.

[0055] Comparative Example 2 This comparative example provides an echinacoside self-microemulsifying drug delivery system, which is prepared in the same manner as in Example 1, with the following differences: echinacoside 5%, GLT 30%, Tween 80 35.3%, RH40 23.6%, and PEG200 11.1%.

[0056] The prepared echinacoside self-microemulsifying drug delivery system is dark grayish white, slightly oily droplets, because the ratio of Tween 80 and RH40 in the complex emulsifier is 1:0.67, the proportion of Tween 80 is high, and the ratio of oil phase and complex emulsifier is 1:1.9.

[0057] Comparative Example 3 The present comparative example provides an echinacoside self-microemulsifying drug delivery system, which comprises the following components in parts by weight: echinacoside 5%, GLT 15.47%, Tween 35.3%, RH40 0% and PEG200 49.23%.

[0058] The preparation method of the present comparative example is as follows: The prescribed amount of echinacoside is weighed, and the prescribed amount of GLT, Tween 80, RH40 and PEG200 are added, and then they are uniformly dissolved in a 37°C water bath with magnetic stirring. Then, they are slowly dropped into 50 mL of 37°C ultrapure water on a magnetic stirrer to completely emulsify, and an echinacoside self-microemulsion is obtained.

[0059] The prepared echinacoside self-microemulsifying drug delivery system has poor compatibility, and the drug is suspended in the system in the form of a lump, i.e. the drug is not loaded in the system, which reduces the drug loading capacity and drug loading rate of the final echinacoside self-microemulsion.

[0060] The above only describes the preferred embodiments of the present application and is not used to limit the present application. For those skilled in the art, the present application can have various modifications and changes. Any modification, equivalent replacement, improvement, etc. made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. An echinacoside self-microemulsifying drug delivery system, characterized in that: The invention comprises the following components in weight percentage: 0.5%-5% echinacoside, 10%-50% oil phase, 30%-70% compound emulsifier and 10%-40% co-emulsifier; the compound emulsifier is selected from at least two of Tween 80, polyoxyethylene hydrogenated castor oil 40, poloxamer 188 and Span 80.

2. The echinacoside self-microemulsifying drug delivery system according to claim 1, characterized in that: The oil phase is selected from one of castor oil, glyceryl trilaurate, polylactic acid-glycolic acid copolymer and isopropyl myristate, preferably glyceryl trilaurate.

3. The echinacoside self-microemulsifying drug delivery system according to claim 1, characterized in that: The composite emulsifier is preferably Tween 80 and polyoxyethylene hydrogenated castor oil.

4. The echinacoside self-microemulsifying drug delivery system according to claim 3, characterized in that: The weight ratio of Tween 80 to polyoxyethylene hydrogenated castor oil in the composite emulsifier is 1:1-2.

5.

5. The echinacoside self-microemulsifying drug delivery system according to claim 1, characterized in that: The co-emulsifier is selected from one of polyethylene glycol 200, polyethylene glycol 400 and diethylene glycol monoethyl ether, preferably polyethylene glycol 200.

6. The echinacoside self-microemulsifying drug delivery system according to claim 1, characterized in that: The weight ratio of the oil phase to the composite emulsifier is 1:2-9.

7. The echinacoside self-microemulsifying drug delivery system according to claim 1, characterized in that: The weight ratio of the auxiliary emulsifier to the composite emulsifier is 1:1-2.

5.

8. A method for preparing the echinacoside self-microemulsifying drug delivery system according to any one of claims 1 to 7, characterized in that: The following steps are involved: Take an appropriate amount of echinacoside and dissolve it in an emulsifier to form a first solution, mix the oil phase and the composite emulsifier to form a second solution, mix the first solution and the second solution evenly to obtain a mixed solution, and finally stir and dissolve the mixed solution in water to obtain an echinacoside self-microemulsion.

9. The method for preparing an echinacoside self-microemulsifying drug delivery system according to claim 8, characterized in that: The stirring condition is to drop the mixed solution into water at 30-45° C. and stir evenly with magnetic force.

10. The method for preparing an echinacoside self-microemulsifying drug delivery system according to claim 8, characterized in that: The microemulsion particle size of the echinacoside self-microemulsion is 24.5-25.48 nm.

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