Diosmetin and phospholipid complex and preparation method and solubility testing method thereof

Abstract

The invention discloses a diosmetin-phospholipid complex and a preparation method and solubility testing method thereof, and the preparation method comprises the following steps: putting diosmetin and phospholipid into a flask according to a molar ratio of 1: (6-15), adding a proper amount of absolute ethyl alcohol, dissolving and uniformly mixing under an ultrasonic condition, sealing, putting into a magnetic stirring pot, stirring and reacting, filtering, washing, and drying to obtain the diosmetin-phospholipid complex. After the reaction is finished, transferring into a rotary evaporator, and evaporating to remove absolute ethyl alcohol to obtain diosmetin, phospholipid and a diosmetin and phospholipid compound; adding a proper amount of petroleum ether into the flask for ultrasonic dissolution, carrying out suction filtration with a filter membrane, washing the precipitate with petroleum ether, filtering out diosmetin which does not form a compound with phospholipid, transferring the filtrate into a rotary evaporator, and evaporating the petroleum ether to obtain the diosmetin-phospholipid compound, so that the water solubility and bioavailability of the diosmetin are improved through the phospholipid, and the bioavailability of the diosmetin is improved through the phospholipid. A diosmetin compound is prepared by adopting a solvent evaporation method, a stable diosmetin phospholipid compound is formed, and the drug effect of diosmetin is improved.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical preparations, and in particular relates to a diosmetin phospholipid complex and a preparation method thereof. Background Art

[0002] Dioscorea is a flavonoid compound widely found in citrus fruits, with multiple pharmacological effects such as antibacterial, antioxidant, and anti-inflammatory. Recent studies have shown that dioscorea has an inhibitory effect on various tumor cells such as breast cancer, liver cancer, lung cancer, and prostate cancer. However, flavonoids have the disadvantages of poor water solubility, high first-pass effect, and low oral bioavailability, which seriously limit the clinical application of this type of compound.

[0003] Phospholipids are substances naturally present in the cell membranes of various animals and plants. They play an important role in the field of pharmaceutical science. They have significant pharmacological effects and can affect the functions of cells and tissues. Phospholipids have good biocompatibility. Phospholipid complexes prepared from phospholipids are widely considered to be a promising drug delivery system because of their good compatibility with organisms. Preparing parent drugs as phospholipid complexes can effectively improve the physical and chemical properties of parent drugs and increase their bioavailability. The preparation method of phospholipid complexes is simple, low-cost and economically efficient. The application of phospholipid complexes, a special drug delivery system, in pharmaceutical preparations is becoming more and more widespread and increasingly prominent, especially in the field of traditional Chinese medicine. Its research has made significant progress and is considered to be one of the important directions for the modernization of traditional Chinese medicine.

[0004] Although phospholipids have broad application prospects in drug delivery systems, there are no reports on the complex of diosmetin and phospholipids. The poor water solubility and low bioavailability of diosmetin need to be solved urgently, and the potential of phospholipids as carriers of drug delivery systems in improving drug solubility and bioavailability has not been fully explored in the study of diosmetin. Therefore, combining diosmetin with phospholipids to prepare diosmetin phospholipid complexes provides a new way to solve the problems of poor solubility of diosmetin in water and low oral bioavailability. Summary of the invention

[0005] The purpose of the present invention is to overcome the deficiencies of the prior art and to provide a diosmetin phospholipid complex and a preparation method and a solubility test method thereof.

[0006] One of the technical solutions adopted by the present invention to solve the technical problem is:

[0007] Provided is a method for preparing a lignin-phospholipid complex. The method comprises: placing lignin and phospholipid in a molar ratio of 1:6-15 in a flask, adding an appropriate amount of anhydrous ethanol, dissolving and mixing under ultrasonic conditions, sealing the flask and placing the flask in a magnetic stirring pot for stirring and reaction, transferring the flask into a rotary evaporator after the reaction is completed, evaporating the anhydrous ethanol to obtain lignin, phospholipid and lignin-phospholipid complex; then adding an appropriate amount of petroleum ether into the flask for ultrasonic dissolution, filtering with a filter membrane, washing and precipitating with petroleum ether, filtering out lignin that has not formed a complex with phospholipid, transferring the filtrate into a rotary evaporator, evaporating the petroleum ether, and drying to obtain the lignin-phospholipid complex.

[0008] Furthermore, the stirring reaction temperature is 30°C to 50°C.

[0009] Furthermore, the stirring reaction time is 1 to 3 hours.

[0010] Furthermore, the mixture is placed in a magnetic stirring pot and stirred for reaction, and the surface tension of the aqueous phase is reduced by the phospholipid, so that the dispersion of diosmetin is promoted, and the hydrophobic tail of the phospholipid and the benzene ring of diosmetin are formed with van der Waals force, and the hydrophilic head of the phospholipid and the functional groups such as hydroxyl and keto groups in diosmetin are formed with hydrogen bonds, so that the binding force between the phospholipid and diosmetin is strengthened, the formation of the complex is promoted, the diosmetin is wrapped by the phospholipid, and the solubility of the diosmetin is improved.

[0011] Furthermore, the pore size of the filter membrane is 0.45 μm.

[0012] Furthermore, the filter membrane is an organic filter membrane.

[0013] The second technical solution adopted by the present invention to solve its technical problem is:

[0014] Provided is a lignin phospholipid complex, which is prepared by the above-mentioned lignin phospholipid complex preparation method.

[0015] The third technical solution adopted by the present invention to solve its technical problem is:

[0016] Provided is a method for testing the solubility of diosmetin in diosmetin phospholipid complex, the method comprising: taking an excess of diosmetin phospholipid complex and adding it to 5 ml of deionized water, vortex mixing for 10 minutes, placing it in a constant temperature oscillator at 37°C, and rotating at 100 r·min -1 After continuous oscillation for 48 hours, a supersaturated solution was obtained with insoluble matter visible at the bottom. -1 The mixture was centrifuged for 10 min under the same conditions, the supernatant was filtered through a 0.22 μm microporous membrane, and diluted with ethanol to an appropriate multiple, and the solubility of the lignin phospholipid complex in water was determined and calculated.

[0017] Compared with the background technology, the technical scheme of the present invention has the following advantages: the present invention improves the water solubility and bioavailability of diosmetin through phospholipids, adopts the solvent volatilization method to prepare, forms a stable diosmetin phospholipid complex, improves the stability and purity of the complex, and effectively separates the diosmetin that has not formed a complex through membrane filtration and petroleum ether washing, thereby ensuring the high purity of the complex finally obtained. The results show that the complex rate of the diosmetin phospholipid complex is 93.06%, and the solubility in water is 16.56 μg / ml (calculated according to the diosmetin content), thereby improving the efficacy of diosmetin and promoting its practical application in cancer treatment and other fields. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] The present invention will be further described below in conjunction with the accompanying drawings and embodiments.

[0019] Figure 1 The spectrum of petroleum ether solution of diosmetin, phospholipid and diosmetin phospholipid complex;

[0020] Figure 2 is the standard curve of dioscorea lignin;

[0021] Figure 3 This is the effect of feed ratio on recombination rate (n=3);

[0022] Figure 4 is the effect of reaction time on recombination rate (n=3);

[0023] Figure 5 is the effect of reaction temperature on recombination rate (n=3);

[0024] Figure 6 is the effect of drug concentration on recombination rate (n=3);

[0025] Figure 7 The contour map and three-dimensional response surface map of the factors affecting the complexation rate of dioscorea phospholipid complex;

[0026] Figure 8 Optimal prescription prediction plot for the model built for response surface methodology;

[0027] Fig. 9 The UV spectra of diosmetin, phospholipids, physical mixtures, and diosmetin-phospholipid complexes;

[0028] Fig.10 The infrared spectra of diosmetin, phospholipids, physical mixtures, and diosmetin phospholipid complexes are shown;

[0029] Fig.11 These are the DSC graphs of lignin, phospholipids, physical mixtures, and lignin-phospholipid complexes. DETAILED DESCRIPTION

[0030] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0031] Example 1: Preparation method of lignin phospholipid complex

[0032] Accurately weigh 2 mg of appropriate amount of lignin and 13 mg of phospholipids and place them in a beaker, add 20 ml of appropriate amount of anhydrous ethanol, dissolve by ultrasonication, mix well, seal with sealing film, put into a magnetic stirring pot and stir at a certain temperature for a period of time. The surface tension of the aqueous phase is reduced by phospholipids, which promotes the dispersion of lignin, forms van der Waals force between the hydrophobic tail of phospholipids and the benzene ring of lignin, and forms hydrogen bonds between the hydrophilic head of phospholipids and functional groups such as hydroxyl and keto groups in lignin, strengthens the binding force between phospholipids and lignin, and promotes the formation of complexes. Under the influence of the amphiphilic properties of phospholipids, phospholipid molecules form micelles or membrane structures in water to wrap the hydrophobic part of lignin. The hydrophilic head of the phospholipid faces the water phase, while the hydrophobic tail faces the encapsulated lignin, effectively isolating the lignin in the water phase, so that the hydrophobic part of the lignin is inside the hydrophobic tail of the phospholipid. This closed structure reduces the direct contact between lignin and water and improves the effective solubility of lignin in water. At the same time, the hydrophilic head of the phospholipid improves the stability of the complex in the water phase. After the reaction is completed, it is transferred to a rotary evaporator to evaporate the anhydrous ethanol. After evaporation, the flask contains lignin, phospholipids, and lignin phospholipid complexes. Add 25 ml of appropriate petroleum ether (60-90 ° C) to the flask, ultrasonically dissolve, filter with a 0.45 μm organic filter membrane, wash the precipitate with 5 ml of petroleum ether, repeat 3 times, and remove the lignin that has not formed a complex with the phospholipid. The filtrate is rotary evaporated to remove the petroleum ether, and transferred to a 37 ° C constant temperature drying oven for further drying to obtain the lignin phospholipid complex.

[0033] Experimental Example 1: Determination of separation solvent

[0034] With petroleum ether solution as the background, the petroleum ether solution of diosmetin, phospholipids and diosmetin phospholipid complex was scanned at a wavelength of 200-400nm. The results show that the petroleum ether solution of diosmetin is a straight line with an absorbance close to 0, indicating that diosmetin is almost insoluble in petroleum ether; the petroleum ether solution of phospholipids has a significant absorption peak at 207nm and no absorption at 343nm, indicating that phospholipids are soluble in petroleum ether; the petroleum ether solution of diosmetin phospholipid complex has significant absorption peaks at both 207nm and 343nm, indicating that diosmetin wrapped by phospholipids, that is, diosmetin phospholipid complex, is soluble in petroleum ether, so petroleum ether is suitable for separating diosmetin that has not formed a complex with phospholipids.

[0035] Test Example 2: Drawing of the standard curve of dioscorea lignin

[0036] Accurately weigh an appropriate amount of lignin standard and place it in a volumetric flask, dilute it with anhydrous ethanol to prepare a lignin standard solution, dilute it with anhydrous ethanol to 1, 2, 4, 8, 16 μg / ml, 5 different concentrations of lignin solution, measure the absorbance A value at 343nm, and draw a standard curve based on the mass concentration (C) and absorbance value (A) of the lignin standard solution. Get the equation: Y = 0.07163X-0.01771 (R 2 =0.99968, n=3). Dioscorea lignans had a good linear relationship in the range of 1-16 μg / mL.

[0037] Example 3: Optimization of the preparation process of dioscorea phospholipid complex

[0038] Calculation of compounding rate

[0039] Add 25 ml of anhydrous ethanol to the evaporating flask and dissolve it by ultrasonic. Pour the obtained lignin phospholipid complex solution into a 50 ml volumetric flask to make up the volume. After diluting it a certain number of times, measure the absorbance at a wavelength of 343 nm using a UV-visible spectrophotometer. Substitute the obtained data into the standard curve to calculate the recombination rate.

[0040]

[0041] Wherein, W1 is the mass of composite lignin, and W2 is the total mass of lignin input.

[0042] 1. Single factor investigation

[0043] (1) Feed ratio of lignin and phospholipids

[0044] According to the preliminary experimental results, the experiment was carried out with a reaction time of 2h, a reaction temperature of 40℃, and a drug concentration of 0.1%. The results are as follows Figure 3As shown in the figure, with the increase of the molar feed ratio, the compounding rate of the dioscorea phospholipid complex first increased and then decreased. When the molar feed ratio was 12, the compounding rate was the highest, reaching 92.56%.

[0045] The results of variance analysis are shown in Table 1. When the significance level α=0.05, p=0.000<0.05, indicating that the molar feed ratio has a significant effect on the complexation rate of the dioscorea phospholipid complex.

[0046] Table 1 Variance analysis table of the effect of molar feed ratio on recombination rate (n=3)

[0047]

[0048] (2) Stirring reaction time in a magnetic stirring pot

[0049] According to the preliminary experiment and the results of the molar feed ratio investigation, the experiment was carried out with a molar feed ratio of 12, a reaction temperature of 40°C, and a drug concentration of 0.1%. Figure 4 As shown, with the increase of reaction time, the recombination rate of dioscorea phospholipid complex first increased and then decreased. When the reaction time was 2h, the recombination rate was the highest, reaching 92.56%.

[0050] The results of variance analysis are shown in Table 2. When the significance level α=0.05, p=0.000<0.05, indicating that the reaction time has a significant effect on the complexation rate of the dioscorea phospholipid complex.

[0051] Table 2 Analysis of variance of the effect of reaction time on recombination rate (n=3)

[0052]

[0053] (3) Stirring reaction temperature in a magnetic stirring pot

[0054] According to the results of the preliminary experiment and the above single factor experiment, the experiment was carried out with a molar feed ratio of 12, a reaction time of 2h, and a drug concentration of 0.1%. Figure 5 As shown, with the increase of reaction temperature, the recombination rate of dioscorea phospholipid complex first increased and then decreased. When the reaction temperature was 40°C, the recombination rate was the highest, reaching 92.56%.

[0055] The results of variance analysis are shown in Table 3. When the significance level α=0.05, p=0.001<0.05, indicating that the reaction temperature has a significant effect on the complexation rate of the dioscorea phospholipid complex.

[0056] Table 3 Analysis of variance of the effect of reaction temperature on recombination rate (n=3)

[0057]

[0058] (4) Drug concentration

[0059] According to the preliminary experiment, the experiment was carried out with a molar feed ratio of 12, a reaction time of 2h, and a reaction temperature of 40°C. Figure 6 As shown, with the increase of drug concentration, the complexation of dioscorea phospholipid complex first increased and then decreased. When the drug concentration was 0.1, the complexation rate was the highest, reaching 92.56%.

[0060] The results of variance analysis are shown in Table 4. When the significance level α=0.05, p=0.518>0.05, indicating that the drug concentration has no significant effect on the complexation rate of dioscorea phospholipid complex.

[0061] Table 4 Analysis of variance table of the effect of drug concentration on recombination rate (n=3)

[0062]

[0063] 2. Box-Behnken design-response surface method optimization

[0064] (1) Optimize coding and level

[0065] Based on the single factor experiment, the molar feed ratio (X1), reaction time (X2) and reaction temperature (X3) were selected as the three factors that had a significant impact on the lignin phospholipid complex as the investigation factors, and the composite rate (Y) was used as the evaluation index. The Box-Behnken design-response surface method was used to optimize the preparation process of the lignin phospholipid complex. The factor levels are shown in Table 5, and Table 6 is the experimental design and results.

[0066] Table 5 Factors and levels of Box-Behnken design

[0067]

[0068] Table 6 Experimental design and results (n=3)

[0069]

[0070] (2) Establishment of multivariate quadratic regression equation

[0071] Design Expert 12.0 software was used to fit the test results with a multivariate quadratic regression equation. The resulting equation model was Y = 92.92 + 0.9275X1-1.62X2-2.62X3 + 0.11X1X2 + 0.555X1X3 + 0.2875X2X3-3.78X1 2 -3.69X2 2 -5.54X32 .

[0072] The determination coefficient R of the binary multiple regression equation model obtained by the above fitting is 2 is 0.9929, the correction coefficient Adj R 2 The value of the coefficient of X2 and X3 in the equation model is relatively large, and the influence is significantly higher than that of X1. The results of variance analysis are shown in Table 7. X1 (P = 0.0054) and X2 (P = 0.0003) have significant differences (P < 0.0500), while X3 and X1 have significant differences (P < 0.0500). 2 , X2 2 and X3 2 The difference was extremely significant (P<0.0001), while the other items were not significant.

[0073] Table 7 Analysis of variance

[0074]

[0075] (3) Response surface optimization, prediction and verification

[0076] Draw a contour map and a three-dimensional response surface map of the factors affecting the complex rate of lignin phospholipid complex. In the figure, A and B: the influence of independent variables X1 and X2, C and D: the influence of independent variables X1 and X3, E and F: the influence of independent variables X2 and X3, Figure 7 It can be seen that when the reaction temperature is fixed, as the molar feed ratio or reaction time increases, the recombination rate first increases and then decreases; when the reaction time is fixed, as the molar feed ratio or reaction temperature increases, the recombination rate first increases and then decreases; when the molar feed ratio is fixed, as the reaction time or reaction temperature increases, the recombination rate increases and then decreases. The influence of reaction temperature > the influence of reaction time > the influence of molar feed ratio.

[0077] The model predicts that the optimal recipe is molar feed ratio X1 = 12.1021, reaction time X2 = 1.88682h, reaction temperature X3 = 38.8165℃, and the predicted recombination rate is 93.4608%. For ease of operation, the optimal recipe of the lignin phospholipid complex is adjusted to X1 = 12.1, X2 = 1.9h, and X3 = 39℃.

[0078] According to the predicted optimal prescription process, three batches of lignin phospholipid complex were prepared in parallel, and the measured complex rates were 92.71%, 93.13% and 93.34%, respectively. The average complex rate was 93.06%, which was slightly different from the theoretical value. This proves that the model established by the response surface methodology is stable and feasible for the optimization of the preparation of lignin phospholipid complex.

[0079] Test Example 4: UV spectroscopy analysis

[0080] Accurately weigh appropriate amounts of lignin, phospholipids, physical mixtures and lignin phospholipid complexes, where the physical mixture is a mixture of lignin and soybean phospholipids, dilute with an appropriate amount of anhydrous ethanol, and perform UV scanning in the wavelength range of 200-400nm with anhydrous ethanol as the background. The scanning results are detailed in Fig. 9 The results show that phospholipids have almost no absorption in the range of 250-400nm; diosmetin, physical mixture and diosmetin phospholipid complexes all have absorption peaks at 253, 270 and 343nm, and their spectra are similar, indicating that diosmetin and phospholipids do not form new absorption groups during the compounding process, that is, the chemical structure of the drug has not changed.

[0081] Test Example 5: Infrared spectroscopy analysis

[0082] Take appropriate amounts of lignin (A), phospholipids (B), physical mixture (C), and lignin phospholipid complex (D) and place them at the probe. After fully pressing each sample, use total reflection infrared spectroscopy to scan, and adjust the scanning range to 4000-400 cm -1 , resolution 0.5cm -1 , scan times 32. The scan results are as follows Fig.10 As shown in the infrared spectrum, geraniol is present in the range of 1650-1500 cm -1 There is an obvious infrared absorption peak in the region, which is caused by the benzene ring structure. The infrared spectra of phospholipids and diosmetin are significantly different, while the infrared characteristic peaks of diosmetin phospholipid complexes are almost consistent with phospholipids, indicating that diosmetin is almost completely wrapped in phospholipids. In the spectrum of diosmetin phospholipid complexes, the characteristic absorption peak of diosmetin is 1650cm -1 The characteristic absorption peak of phospholipids is 1735cm -1 Both can be found, but the peak intensity of the characteristic absorption peak of diosmetin is significantly smaller. The main difference is that some characteristic peaks of diosmetin in the fingerprint region are 1335, 1298, 1254 cm -1 The above shows that no new chemical bonds are formed between diosmetin and phospholipids, and no new compounds are formed but complexes are formed. From the changes in the characteristic peaks in the fingerprint region, it can be inferred that hydrogen bonds or van der Waals forces may be formed between diosmetin and phospholipids.

[0083] Test Example 6: Differential Scanning Calorimetry (DSC) Analysis

[0084] Take appropriate amount of lignin, soybean lecithin, physical mixture, and lignin lecithin complex and place them in crucibles respectively. Take blank crucible as reference, use N2 as carrier gas, flow rate of 20.0mL / min, heating rate of 5℃ / min, scanning range of 35~300℃, and perform DSC analysis. The results are shown in Fig.11 As can be seen from the figure, the lignin curve begins to drop sharply at 256°C, which corresponds to the melting point of lignin, and there is a significant endothermic peak at 263°C; the curve of the physical mixture of lignin and soybean lecithin is basically a simple superposition of the lignin curve and the soybean lecithin curve, indicating that there is no close connection between the two substances when simply mixed; the characteristic endothermic peaks of lignin and soybean lecithin disappear in the curve of the lignin-phospholipid complex, and the curve is different from the curve of the physical mixture, so it is believed that the complex is a new phase different from lignin, soybean lecithin or the physical mixture.

[0085] Test Example 7: Solubility Determination

[0086] Take excess lignin phospholipid complex and add it to 5 ml of deionized water, vortex mix for 10 min, place it in a constant temperature oscillator at 37 ° C, 100 r·min -1 After continuous oscillation for 48 hours, a supersaturated solution was obtained with insoluble matter visible at the bottom. -1 Centrifuge for 10 minutes under the same conditions, take the supernatant and filter it with a 0.22μm microporous filter membrane, add ethanol to dilute it by an appropriate multiple, and measure and calculate that the solubility of the lignin phospholipid complex in water is 16.56μg / ml (based on the lignin content). The solubility of lignin in deionized water is 0.39μg / ml. This shows that the lignin phospholipid complex greatly improves the solubility of lignin.

[0087] The present invention adopts solvent volatilization method to prepare diosmetin phospholipid complex, takes the composite rate of diosmetin and phospholipid as evaluation index, and optimizes the preparation process by Box-Behnken design-response surface method. The results show that: anhydrous ethanol is the reaction solvent, the molar feed ratio of phospholipid to diosmetin is 12:1, the reaction temperature is 39°C, the reaction time is 1.9h, and the composite rate of phospholipid complex is 93.06%. Differential scanning calorimetry (DSC) analysis showed that no new absorption group was formed between dioscorea and soybean lecithin during the compounding process, that is, the chemical structure of the drug did not change, and a complex rather than a compound was formed. The water solubility and bioavailability of dioscorea were improved by phospholipids, and the dioscorea complex was prepared by solvent volatilization method to form a stable dioscorea phospholipid complex, thereby improving the stability and purity of the complex. The dioscorea that did not form a complex was effectively separated by membrane filtration and petroleum ether washing to ensure the high purity of the final complex. The results showed that the compounding rate of the dioscorea phospholipid complex was 93.06%, and the solubility in water was 16.56 μg / ml (based on the dioscorea content), which improved the efficacy of dioscorea and promoted its practical application in cancer treatment and other fields.

[0088] The above description is only a preferred embodiment of the present invention, and therefore cannot be used to limit the scope of the present invention. That is, equivalent changes and modifications made according to the patent scope of the present invention and the contents of the specification should still fall within the scope of the present invention.

Claims

1. A method for preparing a dioscorea phospholipid complex, characterized in that: The method comprises: putting lignin and phospholipid in a molar ratio of 1:6-15 into a flask, adding an appropriate amount of anhydrous ethanol, dissolving and mixing under ultrasonic conditions, sealing the flask and putting the flask into a magnetic stirring pot for stirring and reacting, transferring the flask into a rotary evaporator after the reaction is completed, evaporating the anhydrous ethanol to obtain lignin, phospholipid and lignin phospholipid complex; then adding an appropriate amount of petroleum ether into the flask for ultrasonic dissolution, filtering with a filter membrane, washing the precipitate with petroleum ether, filtering out lignin that has not formed a complex with the phospholipid, transferring the filtrate into a rotary evaporator, evaporating the petroleum ether, and drying to obtain the lignin phospholipid complex.

2. The method for preparing the dioscorea phospholipid complex according to claim 1, characterized in that: The temperature of the stirring reaction is 30°C to 50°C.

3. The method for preparing the dioscorea phospholipid complex according to claim 1, characterized in that: The stirring reaction time is 1 to 3 hours.

4. The method for preparing the diosmetin phospholipid complex according to any one of claims 1 to 3, characterized in that: The mixture is placed in a magnetic stirring pot and stirred for reaction, and the surface tension of the water phase is reduced by the phospholipid, so that the dispersion of diosmetin is promoted, and the hydrophobic tail of the phospholipid and the benzene ring of diosmetin are formed with van der Waals force, and the hydrophilic head of the phospholipid and the functional groups such as hydroxyl group and keto group in diosmetin are formed with hydrogen bonds, so that the binding force between the phospholipid and diosmetin is strengthened, the formation of the complex is promoted, the diosmetin is wrapped by the phospholipid, and the solubility of the diosmetin is improved.

5. The method for preparing the diosmetin phospholipid complex according to claim 1, characterized in that: The pore size of the filter membrane is 0.45 μm.

6. The method for preparing the diosmetin phospholipid complex according to claim 1 or 5, characterized in that: The filter membrane is an organic filter membrane.

7. A dioscorea phospholipid complex, characterized in that: The diosmetin phospholipid complex is prepared by the preparation method of the diosmetin phospholipid complex according to any one of claims 1 to 6.

8. A method for testing the solubility of diosmetin in diosmetin phospholipid complex, characterized in that: The method comprises: taking an excess of the diosmetin phospholipid complex prepared by the preparation method of the diosmetin phospholipid complex according to any one of claims 1 to 6, adding it to 5 ml of deionized water, vortex mixing for 10 minutes, placing it in a constant temperature oscillator at 37°C, and rotating at 100 r·min -1 After continuous oscillation for 48 hours, a supersaturated solution was obtained with insoluble matter visible at the bottom. -1 The mixture was centrifuged for 10 min under the same conditions, the supernatant was filtered through a 0.22 μm microporous membrane, and diluted with ethanol to an appropriate multiple, and the solubility of the lignin phospholipid complex in water was determined and calculated.

Images