Method for improving bioavailability of puerarin
By preparing a complex of puerarin and berberine, the problem of low bioavailability of puerarin was solved, resulting in a significant improvement in bioavailability and efficacy, especially in metabolic diseases caused by a high-fat diet.
Patent Information
- Application Number
- CN202511301195.8
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2023-04-19
- Publication Date
- 2025-11-07
AI Technical Summary
Puerarin has low bioavailability, and its salts are unstable, which cannot significantly improve bioavailability and affect efficacy.
The preparation of a complex of puerarin and berberine is specifically achieved by dissolving puerarin and berberine in an alkaline solution and then mixing them to form a puerarin-berberine salt with a molar ratio of 1:0.1-10, preferably 1:0.5-2.
It significantly improves the bioavailability of puerarin and enhances its efficacy, especially in a metabolic disease model induced by a high-fat diet.
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Abstract
Description
[0001] The present application is a divisional application of the invention patent application "A method for improving the bioavailability of puerarin" with the application number 202310420449.2 and the filing date of April 19, 2023. TECHNICAL FIELD
[0002] The present application provides a method for improving the bioavailability of puerarin, belonging to the technical field of biological material preparation. BACKGROUND
[0003] Puerarin is also known as puerarin flavone. It is an isoflavone derivative with coronary expansion effect isolated from traditional Chinese medicine pueraria. It exists in the roots of Pueraria lobata (Willd) Ohwi and Pueraria thunbergiana Benth. of the Leguminosae family. It has the effects of reducing fever, sedation and increasing coronary artery blood flow, and has a protective effect on acute myocardial bleeding caused by pituitary posterior lobe. It is clinically used for coronary heart disease angina pectoris and hypertension. Appearance: white to slightly yellow crystalline powder. Solubility: soluble in methanol, slightly soluble in ethanol, slightly soluble in water, insoluble in chloroform or diethyl ether. Puerarin is a stable compound, but clinical use shows that its bioavailability is not high, and the substance is not easy to make into a salt, and there is the disadvantage that the salt is not stable. Even if it is made into a salt, it cannot significantly improve its bioavailability. This problem has not been solved in the research field, and whether improving bioavailability can significantly improve the efficacy of related drugs is also unknown in the art. SUMMARY
[0004] To solve the above technical problems, the applicant provides a method for improving the bioavailability of puerarin, which involves preparing a puerarin-berberine complex from puerarin and berberine.
[0005] Further, in the above method, the berberine is hydrochloric acid berberine.
[0006] Further, in the above method, the molar ratio of puerarin to berberine in the puerarin-berberine complex is 1:0.1-10.
[0007] Further, in the above method, the preparation method of the puerarin-berberine complex is: dissolving puerarin in an alkaline solution, dissolving the berberine in an aqueous solution, or dissolving puerarin and berberine in an aqueous solution respectively, adding an alkali, mixing and stirring to precipitate, and filtering to obtain the puerarin-berberine complex. Further, in the above method, the weight ratio of puerarin to berberine is 1:0.1-10.
[0008] Further, in the above method, the molar ratio of puerarin to berberine is 1:0.5-2.
[0009] Further, in the above method, the molar ratio of puerarin: berberine is 1:0.8-1.5.
[0010] Further, in the above method, the alkali solution is selected from KOH or NaOH solution.
[0011] Further, the present application provides a puerarin-berberine complex obtained by the above method.
[0012] Further, the present application provides an application of the puerarin-berberine complex in the preparation of a drug for treating metabolic diseases caused by high-fat diet.
[0013] In the present application, the puerarin-berberine complex is mainly a puerarin berberine salt, so it can be generally considered as the same name.
[0014] The present application provides a method for improving the bioavailability of puerarin, wherein the method is creatively combined with the synthesis of berberine compound, and it is found that the two components can interact to obtain a new complex, which has good bioavailability of puerarin and is different from the previous teaching that berberine is beneficial to the bioavailability of puerarin. Because the previous bioavailability improvement cannot achieve such a tens of times leap, the preparation method of the present application is simple, only by dissolving puerarin and berberine into solutions respectively, adding an alkali solution to promote the reaction, and then precipitating a new complex, which belongs to a new preparation method. From various high-fat diet model evaluation indexes, the method significantly improves the bioavailability of puerarin, and the dissolution and bioavailability of berberine do not change, thereby proving that the significant improvement of the related salt is from the improvement of the bioavailability of puerarin, and the effect of berberine almost does not change, which belongs to the significance of the improved bioavailability of puerarin by the present method. BRIEF DESCRIPTION OF DRAWINGS
[0015] Figure 1 is the nuclear magnetic resonance spectrum of berberine puerarin salt;
[0016] Figure 2 is the nuclear magnetic resonance spectrum of the physical mixture of berberine and puerarin;
[0017] Figure 3 is the infrared spectrum of berberine puerarin salt;
[0018] Figure 4 is the infrared spectrum of the physical mixture of berberine and puerarin;
[0019] Figure 5 is the DSC graph of berberine puerarin salt;
[0020] Figure 6 DSC pattern of the physical mixture of berberine and puerarin;
[0021] Figure 7 Single crystal diffraction pattern of the berberine puerarin salt;
[0022] Figure 8 Cell packing pattern of the berberine puerarin salt;
[0023] Figure 9 Cumulative dissolution curve of puerarin in water in the sample;
[0024] Figure 10 Cumulative dissolution curve of berberine in water;
[0025] Figure 11 Blood concentration-time curve of puerarin in the plasma of C57 mice administered with each sample by gavage;
[0026] Figure 12 Blood concentration-time curve of berberine in the plasma of C57 mice administered with each sample by gavage;
[0027] Figure 13 Comparison of the liver triglyceride content of experimental animals in different administration groups in a C57 mouse metabolic disease model induced by a high-fat diet;
[0028] Figure 14 Comparison of the plasma cholesterol content of experimental animals in different administration groups in a C57 mouse metabolic disease model induced by a high-fat diet;
[0029] Figure 15 Comparison of the plasma low-density lipoprotein-cholesterol content of experimental animals in different administration groups in a C57 mouse metabolic disease model induced by a high-fat diet;
[0030] Figure 16 Comparison of the plasma triglyceride content of experimental animals in different administration groups in a C57 mouse metabolic disease model induced by a high-fat diet;
[0031] Figure 17 Comparison of the blood glucose content of experimental animals in different administration groups in a C57 mouse metabolic disease model induced by a high-fat diet;
[0032] Figure 18 Comparison of the plasma alanine aminotransferase (ALT) content of experimental animals in different administration groups in a C57 mouse metabolic disease model induced by a high-fat diet;
[0033] Figure 19 Comparison of the plasma aspartate aminotransferase (AST) content of experimental animals in different administration groups in a C57 mouse metabolic disease model induced by a high-fat diet;
[0034] Figure 20 Figure 3 is the result of oil red staining of liver tissue sections of experimental animals in different administration groups in a high-fat diet-induced C57 mouse metabolic disease model. DETAILED DESCRIPTION
[0035] The following examples are used to further illustrate the present application but are not limiting of the present application. Any technique based on the above description of the present application falls within the scope of the present application. The following rats and mice are provided by Beijing Vital River Laboratory Animal Technology Co., Ltd.
[0036] The beneficial effects of the traditional Chinese medicine composition of the present application are further illustrated by the following experiments.
[0037] Example 1 Determination of cumulative dissolution curve of puerarin and berberine in water
[0038] Preparation of berberine-puerarin salt 5 g of berberine chloride (molecular weight: 371.86) was added to 300 mL of water and dissolved by heating at 80°C. Separately, 5.6 g of puerarin (molecular weight: 416.36) was added to 100 mL of water, and 0.49 g of potassium hydroxide was added to the system until it became colorless and clear. The above-mentioned berberine aqueous solution was slowly added dropwise under stirring at room temperature. After the dropwise addition was completed, stirring was continued at room temperature, and solids were precipitated. The solids were filtered and dried at 50°C for 5 h to obtain 9.5 g of berberine-puerarin salt.
[0039] (molar ratio about 1:1)
[0040] Preparation of berberine-puerarin mixture 7.5 g of berberine chloride and 8.4 g of puerarin were placed in a mortar and ground repeatedly to obtain a mixture of 15.8 g of berberine-puerarin (molar ratio 1:1).
[0041] NMR of berberine-baiyunoside salt 1 H NMR determination
[0042] The prepared berberine-puerarin salt and berberine-puerarin mixture were subjected to hydrogen nuclear magnetic resonance analysis.
[0043] Preparation of berberine-puerarin salt 2 10 g of berberine chloride was added to 300 mL of water and dissolved by heating at 80°C. Separately, 5.6 g of puerarin was added to 100 mL of water, and 0.98 g of potassium hydroxide was added to the system until it became colorless and clear. The above-mentioned berberine aqueous solution was slowly added dropwise under stirring at room temperature. After the dropwise addition was completed, stirring was continued at room temperature, and solids were precipitated. The solids were filtered and dried at 50°C for 5 h to obtain 9.5 g of berberine-puerarin salt (molar ratio of puerarin to berberine: 1:2).
[0044] Preparation of Berberine-Puerarin Salt 3 5 g of berberine chloride was added to 300 mL of water and dissolved by heating at 80 °C. Separately, 11.2 g of puerarin was added to 100 mL of water, to which 0.49 g of potassium hydroxide was added until the system became colorless and clear. The above berberine aqueous solution was slowly added dropwise while stirring at room temperature. After the dropwise addition was completed, stirring was continued at room temperature, and solids were precipitated. The solids were filtered and dried at 50 °C for 5 h to obtain 9.5 g of berberine-puerarin salt (molar ratio of puerarin:berberine: 1:0.5).
[0045] In the above preparation method, the applicant tried to mix berberine and puerarin in an aqueous solution, or to mix them after being dissolved in water separately, and then to add an alkaline solid. It was found that it was almost impossible to obtain the relevant complex solid, which proves the contingency and specificity of the preparation method.
[0046] Figure 1 NMR spectrum of berberine-puerarin salt.
[0047] 1H NMR (500 MHz, DMSO-d6) δ 9.88 (s, 1H), 8.92 (s, 1H), 8.19 (d, J = 9.1 Hz, 1H), 7.98 (d, J = 9.0 Hz, 1H), 7.94 (s, 1H), 7.79 (s, 1H), 7.53 (d, J = 9.0 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.08 (s, 1H), 6.75 (d, J = 8.3 Hz, 2H), 6.32 (d, J = 9.0 Hz, 1H), 6.17 (s, 2H), 4.92 (d, J = 7.9 Hz, 2H), 4.83 (s, 2H), 4.59 (d, J = 9.9 Hz, 1H), 4.09 (s, 3H), 4.06 (s, 3H), 4.03 (t, J = 9.3 Hz, 1H), 3.66 (d, J = 11.5 Hz, 1H), 3.42 (d, J = 5.1 Hz, 3H), 3.23 (t, J = 8.4 Hz, 2H), 3.20 - 3.13 (m, 4H).
[0048] Figure 2 NMR spectrum of berberine-puerarin physical mixture.
[0049] 1H NMR (600 MHz, DMSO-d6) δ 9.89 (s, 1H), 9.60 (s, 1H), 8.93 (s, 1H), 8.32 (s, 1H), 8.18 (d, J = 9.1 Hz, 1H), 7.99 (d, J = 9.0 Hz, 1H), 7.90 (d, J = 8.8 Hz, 1H), 7.78 (s, 1H), 7.44 - 7.32 (m, 2H), 7.07 (s, 1H), 7.04 (d, J = 8.8 Hz, 1H), 6.85 - 6.75 (m, 2H), 6.17 (s, 2H), 5.04 (d, J = 16.1 Hz, 2H), 4.93 (t, J = 6.4 Hz, 2H), 4.89 - 4.76 (m, 2H), 4.56 (s, 1H), 4.10 (s, 3H), 4.06 (s, 3H), 4.03 (d, J = 10.2 Hz, 1H), 3.78 - 3.68 (m, 1H), 3.46 (s, 1H), 3.29 (t, J = 8.6 Hz, 1H), 3.27 - 3.22 (m, 2H), 3.20 (t, J = 6.4 Hz, 2H).
[0050] From the above results, it can be concluded that the berberine-puerarin salt is a new substance, not a mixture. Figure 1 、 2 The comparison found that the berberine-puerarin salt belongs to a new substance, not a mixture.
[0051] Figure 3 、 Figure 4 The infrared spectra of berberine-puerarin salt and physical mixture of berberine and puerarin. The samples were mixed with KBr and pressed into tablets. The scanning range was 400-4000 cm -1 . As can be seen from the figure, the characteristic absorption peak of berberine at 3549 cm -1 disappears, the characteristic absorption peak of puerarin at 2901 cm -1 disappears, and new characteristic absorption peaks appear at 441.5 cm -1 , 503.3 cm -1 , and 536.1 cm -1 .
[0052] Figure 5 、 Figure 6DSC pattern of berberine-puerarin salt, berberine and puerarin physical mixture. Each sample was accurately weighed 2-5 mg in an aluminum crucible, while the same type of empty crucible was used as a reference. The protective atmosphere was 99% pure nitrogen with a flow rate of 60 mL / min, and the sample scanning rate was 10°C / min with a scanning range of 25-280°C. As can be seen from the figure, the berberine-puerarin salt has an endothermic peak at 97.3 cel, and the berberine-puerarin physical mixture has endothermic peaks at 96.7 cel, 150.4 cel, and 197.2 cel.
[0053] Further, the prepared berberine-puerarin salt crystal was subjected to structure analysis, and the crystal analysis parameters are shown below, the crystal structure diagram (ignoring the solvent part) is shown in Figure 7 , and the cell packing diagram is shown in Figure 8 .
[0054] Berberine-puerarin salt crystal data and structure:
[0055]
[0056]
[0057] Chromatographic conditions for puerarin determination Chromatographic column: Agilent ZORBAX SB-C 18 18 (4.6 x 250 mm, 5 μm); mobile phase: methanol-water (25:75); column temperature: 30°C; detection wavelength: 250 nm; flow rate: 1 mL·min -1 ; injection volume: 10 μL.
[0058] Chromatographic conditions for berberine determination Chromatographic column: Kromasil C 18 18 4.6 x 150 mm, 5 μm); mobile phase: acetonitrile-0.05 mol / L sodium dihydrogen phosphate (pH adjusted to 3 with phosphoric acid) (28:72); column temperature: room temperature; detection wavelength: 345 nm; flow rate: 1 mL·min -1 ; injection volume: 10 μL.
[0059] Each sample was taken and subjected to paddle method according to the relevant paddle method in Chinese Pharmacopoeia 2015 edition, with a rotation speed of 100 ± 1 r / min, a water bath temperature of 37°C, a dissolution medium of water, a drug amount equivalent to 16 mg of berberine and 18 mg of puerarin, and 2 mL of sample was taken at 0.25, 0.5, 1, 2, 3, 4, 6, 8, 10, 12, and 24 h, and 0.45 μm filter membrane was used for filtration while supplementing 2 mL of dissolution medium at the same temperature. 1 mL of filtrate was taken, diluted with mobile phase, and the cumulative dissolution amount was determined by the above HPLC method. Figures 9-10 Cumulative dissolution curves of berberine and puerarin in each sample. From Figures 9-10It is evident that only 2.9% of puerarin dissolves from the physical mixture after 24 hours. After the berberine-puerarin salt is formed, the solubility of puerarin significantly increases, with a cumulative dissolution of 30% over 4 hours.
[0060] Berberine aqueous puerarin salts slowed down the dissolution rate of berberine.
[0061] Example 2: Bioavailability of puerarin in mice
[0062] Chromatographic conditions for puerarin: Column: Agilent ZORBAX SB-C 18 Column (4.6 × 250 mm, 5 μm); Mobile phase: methanol - 10 mmol / L -1 Ammonium acetate buffer-acetonitrile (70:20:10); column temperature: 30℃; detection wavelength: 250nm; flow rate: 0.2mL·min -1 Injection volume: 5 μL; Internal standard (IS): hesperidin.
[0063] Mass spectrometry conditions: Ion source: electrospray ionization (ESI); voltage: 5500V; temperature: 350℃; multiple reaction ion detection (MRM) mode for positive ion detection; monitored ion pairs: puerarin m / z 417.2 / 267.2, 15 m / z 611.2 / 303.2.
[0064] Chromatographic conditions for berberine determination: Column: Shim-pack XR-ODSⅡ column (3mm×75mm, 2.3μm); Internal standard (IS): berberine hydrochloride; Column temperature: 30℃; Injection volume: 10μL; Mobile phase: A is 0.5% formic acid aqueous solution, B is acetonitrile, gradient elution (0-4min, 85% A + 15% B; 5-6min, 20% A + 80% B); Flow rate: 0.5mL / min.
[0065] Mass spectrometry conditions: Ion source: electrospray ionization (ESI); IS: 5500V; Temperature: 550℃; CUR: 20V; CE: 35V; DP: 50V; CAD: mediam; Detection mode: positive ion mode; Monitored ion pairs: BBR m / z 398.2 / 308.2, IS m / z 392.1 / 312.1.
[0066] 165 C57 mice were randomly divided into 3 groups, respectively, and were given puerarin, berberine and puerarin physical mixture, berberine-puerarin salt by gavage. Respectively, 0.25, 0.5, 1, 2, 4, 6, 8, 12, 16, 20, 24h after administration, 5 mice in each group were sacrificed, 500ul of blood was taken and placed in EP tube containing 1% sodium heparin, 3000rpm 4℃ centrifugal 10min, 300ul of plasma was taken in 1.5ml EP tube, 300ul of 10mmol / L ammonium acetate buffer and 20ul of internal standard solution were added, mixed and then loaded on a solid phase extraction column, washed with 1.0ml of double distilled water, eluted with 0.5ml of methanol, and the eluate was collected in a nitrogen blowing instrument at 45℃, 150ul of mobile phase was redissolved, 5ul was injected for analysis. Figures 11-12 The drug-time curves of puerarin and berberine in each sample were obtained. Figures 11-12 It can be seen that the bioavailability of puerarin in the berberine-puerarin physical mixture is the same as that of puerarin single drug, and the bioavailability of puerarin in the berberine-puerarin salt is significantly higher than that of puerarin single drug and the berberine-puerarin physical mixture. The bioavailability of berberine in the berberine-puerarin salt is the same as that of berberine single drug and the berberine-puerarin physical mixture.
[0067] Table 1
[0068]
[0069] Table 2
[0070]
[0071]
[0072] Example 3
[0073] Application of berberine-puerarin salt
[0074] The application is characterized by being used for preparing drugs for treating metabolic related diseases. The application feeds C57 mice with high-sugar and high-fat feed to establish a hyperlipidemia, high-sugar, obesity, hypercoagulopathy and fatty liver disease model. The experimental design
[0075] C57 mice (8 weeks old) were randomly divided into 5 groups, the control group (normal diet), the model group (high-sugar and high-fat diet), the puerarin group (high-fat diet + puerarin single drug), the berberine and puerarin physical mixture group (high-fat diet + berberine and puerarin physical mixture), and the berberine-puerarin salt group (high-fat diet + berberine-puerarin salt), 6 mice in each group.
[0076] The above groups of animals were respectively given intragastrically, the control group and the model group mice were given 10 mL / kg / d distilled water. In the puerarin, berberine-puerarin physical mixture group and the berberine-puerarin salt group, the dose of berberine was 100 kg / d, and the dose of puerarin was 120 mg / kg / d, once a day, and the administration was continuous for 8 weeks.
[0077] The body weight was measured every week, after the administration, the animals were anesthetized by intraperitoneal injection of 1 mL of 20% chloral hydrate, and were sacrificed by enucleation of the eyeball to collect blood and liver. The blood biochemical indexes were determined by using an automatic biochemical analyzer. The experimental results showed that the berberine-puerarin salt had the effects of reducing the triglyceride in the liver, reducing blood lipids, reducing blood sugar and reducing body weight increase, and the effects were better than those of the berberine and puerarin physical mixture, and were better than those of the puerarin single drug. Therefore, the berberine and puerarin salt can effectively prevent and treat metabolic diseases such as hyperlipidemia, hyperglycemia, obesity, platelet aggregation and fatty liver disease.
[0078] 1. Effect of berberine-puerarin salt on liver triglyceride content of experimental animals
[0079] The results of liver triglyceride content determination are shown in Figure 13 and Table 3.
[0080] Table 3 Results of liver triglyceride content determination
[0081]
[0082] The triglyceride in the liver of the high-fat diet model animals was significantly increased compared with the blank group. The berberine-puerarin salt effectively reduced the increase of liver triglyceride content caused by high-fat diet, and the degree of reduction was more significant than that of the berberine-puerarin physical mixture, and the puerarin had no significant effect on reducing liver triglyceride.
[0083] 2. Effect of berberine-puerarin salt on blood lipids and blood sugar of experimental animals
[0084] The detection of blood lipids mainly aimed at the content of cholesterol, low-density lipoprotein and triglyceride in plasma.
[0085] The results of plasma cholesterol content are shown in Figure 14 and Table 4.
[0086] Table 4 Plasma total cholesterol content
[0087]
[0088] The results of plasma low-density lipoprotein content are shown in Figure 15 and Table 5.
[0089] Table 5 Plasma low-density lipoprotein-cholesterol content
[0090]
[0091] The results of the plasma triglyceride content are shown in Figure 16 and Table 6.
[0092] Table 6 Plasma triglyceride content
[0093]
[0094] The results of the glucose content are shown in Figure 17 and Table 7
[0095] Table 7 Glucose content
[0096]
[0097]
[0098] After the high-fat diet modeling, the glucose, cholesterol, low-density lipoprotein and triglyceride in the plasma of the animals increased significantly. The physical mixture of berberine and puerarin had the effect of reducing blood glucose and blood lipids. The berberine-puerarin salt could effectively reduce the increase of blood lipids caused by the high-fat diet, and the degree of reduction was more significant than that of the physical mixture of berberine and puerarin. Puerarin single drug did not have a significant effect of reducing blood glucose and blood lipids.
[0099] 3. Changes of liver function of experimental animals by berberine-puerarin salt
[0100] Figure 18 Table 8 is a comparison of the alanine aminotransferase (ALT) levels of mice in each group after the intervention ends.
[0101] Table 8 Alanine aminotransferase (ALT) level
[0102]
[0103] As can be seen from the figure, compared with the blank control group, the ALT level of the model group increased significantly. Compared with the model group, the berberine-puerarin salt significantly reduced the ALT level caused by the high-fat diet, and the degree of reduction was more significant than that of the physical mixture of berberine and puerarin. Puerarin single drug did not have a significant effect of reducing ALT.
[0104] Figure 19 Table 9 is a comparison of the aspartate aminotransferase (AST) levels of mice in each group after the intervention ends.
[0105] Table 9 Aspartate aminotransferase (AST) level
[0106]
[0107] As can be seen from the figure, compared with the blank control group, the AST level of the model group animals had no significant difference. Compared with the model group, puerarin, berberine-puerarin salt and berberine-puerarin physical mixture had no significant difference.
[0108] Figure 20 The oil red staining results of the liver tissue sections of the experimental animals.
[0109] As shown in the figure, compared with the blank control group, the lipid deposition in the liver tissue of the high-fat diet group increased significantly; the liver oil red staining of the berberine-puerarin salt group of mice was significantly reduced, and the liver lipid deposition was reduced. The results show that after drug intervention, it can inhibit the deposition of triglyceride and other neutral fats in the liver, improve liver steatosis, and the degree of improvement of liver tissue degeneration is significantly stronger than that of the berberine-puerarin physical mixture group. Puerarin has no significant inhibitory effect on the deposition of triglyceride and other neutral fats in the liver, therefore, increasing the bioavailability of puerarin while inhibiting the effect of liver fat deposition, which is also a new function brought by the compound after improving the bioavailability of puerarin by relevant methods.
Claims
1. A berberine puerarin salt, characterized in that, It has a nuclear magnetic hydrogen spectrum shown in Figure 1, and the nuclear magnetic hydrogen spectrum data is as follows: 1H NMR (500 MHz, DMSO-d6) δ 9.88 (s, 1H), 8.92 (s, 1H), 8.19 (d, J = 9.1 Hz, 1H), 7.98 (d, J = 9.0 Hz, 1H), 7.94 (s, 1H), 7.79 (s, 1H), 7.53 (d, J = 9.0 Hz, 1H), 7.34 (d, J = 8.4 Hz, 2H), 7.08 (s, 1H), 6.75 (d, J = 8.3 Hz, 2H), 6.32 (d, J = 9.0 Hz, 1H), 6.17 (s, 2H), 4.92 (d, J = 7.9 Hz, 2H), 4.83 (s, 2H), 4.59 (d, J = 9.9 Hz, 1H), 4.09 (s, 3H), 4.06 (s, 3H), 4.03 (t, J = 9.3 Hz, 1H), 3.66 (d, J = 11.5 Hz, 1H), 3.42 (d, J = 5.1 Hz, 3H), 3.23 (t, J = 8.4 Hz, 2H), 3.20-3.13 (m, 4H).
2. The berberine puerarin salt of claim 1, wherein which has an infrared spectrum as shown in Figure 3; in the infrared spectrum, the scanning range is 400-4000 cm -1 -1, the characteristic absorption peak of berberine at 3549 cm -1 -1 disappears, the characteristic absorption peak of puerarin at 2901 cm -1 -1 disappears, and new characteristic absorption peaks appear at 441.5 cm -1 , 503.3 cm -1 , 536.1 cm -1 .
3. The berberine puerarin salt of claim 1, wherein, It has a DSC graph shown in Figure 5, and the differential scanning calorimetry protective atmosphere is 99% pure nitrogen, the flow rate is 60 mL / min, the sample scanning rate is 10 ℃ / min, and the scanning range is 25-280 ℃, and there is an endothermic peak at 97.3 cel.
4. The berberine puerarin salt of claim 1, wherein, It has a single crystal diffraction graph shown in Figure 7 and / or a cell packing graph shown in Figure 8.
5. The berberine puerarin salt according to any one of claims 1 to 4, wherein The molar ratio of berberine to puerarin is 1:
1.
6. A method for preparing berberine puerarin salt according to claim 1, characterized in that, 5g of berberine chloride was added to 300mL of water and dissolved at 80℃, and 5.6g of puerarin was added to 100mL of water, and 0.49g of potassium hydroxide was added to it until the system became colorless and clear, and the above-mentioned berberine aqueous solution was slowly added dropwise under stirring at room temperature, and after the addition was completed, stirring was carried out at room temperature, and solid was precipitated after standing, and the solid was filtered and dried at 50℃ for 5h to obtain 9.5g of berberine puerarin salt.
7. The use of the berberine puerarin salt of claim 1 in the preparation of a drug for improving the bioavailability of puerarin.
8. The use of the berberine puerarin salt of claim 1 in the preparation of a drug for treating metabolic diseases caused by high-fat diet.
9. The use of the berberine puerarin salt of claim 1 in the preparation of a drug for reducing plasma total cholesterol and / or low-density lipoprotein cholesterol.
10. The use of the berberine puerarin salt of claim 1 in the preparation of a drug for reducing plasma glutathione and / or reducing liver tissue lipid deposition.