Berberine and galangin self-assembled nano-drug, preparation method and application

Abstract

The application discloses a self-assembled nano drug of berberine and galangin, which comprises berberine and galangin, and the molar ratio of the berberine and the galangin is 1:1-2. The berberine and the galangin can be self-assembled through a pi-pi bond, electrostatic force and a hydrogen bond to form the self-assembled nano drug, so that the problem of poor water solubility of single berberine and single galangin is improved. Meanwhile, when the self-assembled nano drug is applied to a mouse model of ulcerative colitis, compared with single berberine or single galangin, the self-assembled nano drug significantly relieves the colon shortening, the increase of disease activity index and the intestinal pathological damage phenomenon of the mouse with ulcerative colitis caused by sodium sulfate.

Description

Technical Field

[0001] This invention relates to the field of biomedical technology, specifically to a self-assembled nanomedicine of berberine and galangin, its preparation method, and its application. Background Technology

[0002] Ulcerative colitis (UC) is a chronic, relapsing, nonspecific inflammatory bowel disease that primarily affects the rectum and colon, and its incidence is on the rise globally. Pathological manifestations of UC include intestinal mucosal inflammation, impaired intestinal epithelial barrier, and intestinal flora imbalance. Currently, commonly used clinical treatments for UC include 5-aminosalicylic acid, glucocorticoids, immunosuppressants, and biologics. However, some drugs have limited efficacy, can cause immune non-response, and long-term use may lead to drug resistance or dose-dependent gastrointestinal adverse reactions and allergic reactions related to individual constitution. Therefore, there is an urgent need to discover novel drugs to advance the treatment of ulcerative colitis.

[0003] Natural active ingredients have shown excellent therapeutic potential in drug applications, thus attracting widespread attention. Berberine and galangin have both been reported to have therapeutic effects on ulcerative colitis, but their poor water solubility, limited bioavailability, and low stability limit their application in the treatment of ulcerative colitis (Deng Jianping, et al. Berberine-Loaded Nanostructured Lipid Carriers Enhance the Treatment of Ulcerative Colitis. Int J Nanomedicine. 2020, 3;15:3937-3951.; Lin Yang, et al. Galangin Targets HSP90β to Alleviate Ulcerative Colitis by Controlling Fatty Acid Synthesis and Subsequent NLRP3 Inflammasome Activation. Mol Nutr Food Res. 2023, 67(11):e2200755.).

[0004] Natural drugs can self-assemble through non-covalent interactions such as hydrogen bonds, π-π stacking, and coordination bonds between molecules to form stable nanosystems. These systems offer advantages such as high drug loading capacity, good biocompatibility, controllable degradation, and synergistic pharmacological activity. Berberine, due to its quaternary ammonium base structure, is a compound with good self-assembly properties. It can assemble with polyphenolic compounds such as tannic acid, magnolol, gallic acid, and epigallocatechin gallate through intermolecular forces to form nanoparticles with good therapeutic effects and high safety.

[0005] Therefore, there is an urgent need to find a self-assembled drug that can improve the water solubility of berberine and galangin and enhance their efficacy in treating UC. Summary of the Invention

[0006] To address the aforementioned technical problems, this invention provides a self-assembled nanomedicine of berberine and galangin, which improves upon the poor water solubility of both berberine and galangin alone, and is particularly suitable for the treatment of ulcerative colitis.

[0007] A self-assembled nanomedicine of berberine and galangin, comprising berberine and galangin, wherein the molar ratio of berberine to galangin is 1:1 to 2.

[0008] In this invention, berberine and galangin can self-assemble through π-π bonds, electrostatic interactions, and hydrogen bonds to form self-assembled nanomedicines, thus improving the poor water solubility of both berberine and galangin alone. Furthermore, when applied to a mouse model of ulcerative colitis, the self-assembled nanomedicines significantly alleviated colonic shortening, increased disease activity index, and intestinal pathological damage induced by sodium dextran sulfate in mice, compared to berberine or galangin alone.

[0009] Preferably, the particle size of the self-assembled nanomedicine of berberine and galangin is 150~4200 nm.

[0010] More preferably, the particle size of the self-assembled nanomedicine of berberine and galangin is 150~200nm.

[0011] This invention also provides a method for preparing the self-assembled nanomedicine of berberine and galangin, comprising the following steps: (1) Berberine and galangin were dissolved in methanol to prepare berberine-methanol solution and galangin-methanol solution, respectively, and the two were mixed evenly to obtain berberine-galangin-methanol solution; (2) Place the pre-cooled deionized water in a dark environment and stir. Add the berberine-galangin-methanol solution obtained in step (1) to the deionized water to obtain a mixed solution. (3) After heating and evaporating the mixed solution to remove methanol, berberine-galangin-water solution was obtained. After dialysis and freeze-drying, self-assembled nanomedicine of berberine and galangin was obtained.

[0012] In this invention, the preparation method of self-assembled nanomedicine is simple, possesses the advantages of nanoscale drugs, and simultaneously achieves the self-delivery of pure drugs without excipients, thus improving delivery efficiency.

[0013] Preferably, in step (1), the concentration of berberine in the berberine-methanol solution is 10~30 mM and the concentration of galangin in the galangin-methanol solution is 10~30 mM.

[0014] Preferably, in step (1), the volume ratio of berberine-methanol solution and galangin-methanol solution is 1:1.

[0015] Preferably, in step (2), the volume ratio of berberine-galangin-methanol solution to deionized water is 1:25~50.

[0016] More preferably, the molar ratio of berberine to galangin in the berberine-galangin-methanol solution is 1:1, and the volume ratio of the berberine-galangin-methanol solution to deionized water is 1:50.

[0017] In this invention, when the molar ratio of berberine to galangin is 1:1 and the volume ratio of berberine-galangin-methanol solution to deionized water is 1:50, the self-assembled nanomedicine obtained has a smaller particle size and more uniform dispersion.

[0018] Preferably, in step (2), the stirring speed is 500~600 rpm.

[0019] Preferably, in step (2), the dripping step uses a single-channel syringe pump, and the dripping speed is 90~110 μL / min.

[0020] Preferably, in step (3), the heating and evaporation temperature is 60~80 ℃ and the time is 30~40 min.

[0021] Preferably, in step (3), the dialysis bag used for dialysis has a molecular weight of 2000~3000 Da and the dialysis time is 20~28 h.

[0022] Preferably, in step (3), the freeze-drying includes pre-freezing and vacuum freeze-drying. The pre-freezing temperature is -80℃ and the time is 24 h. The vacuum freeze-drying temperature is -66℃ and the time is 48 h. The vacuum degree is 0.001 Pa.

[0023] The present invention also provides the application of the above-mentioned self-assembled nanomedicine of berberine and galangin in the preparation of drugs for treating ulcerative colitis.

[0024] In this invention, compared with berberine or galangin alone, the self-assembled nanomedicine of berberine and galangin significantly alleviated the colonic shortening, increased disease activity index, and intestinal pathological damage in mice with ulcerative colitis induced by sodium dextran sulfate.

[0025] Compared with the prior art, the beneficial effects of the present invention are as follows: In this invention, berberine and galangin can self-assemble through π-π bonds, electrostatic interactions, and hydrogen bonds to form self-assembled nanomedicines, thus improving the poor water solubility of both berberine and galangin alone. Furthermore, when applied to a mouse model of ulcerative colitis, the self-assembled nanomedicine significantly alleviated the colonic shortening, increased disease activity index, and intestinal pathological damage induced by sodium dextran sulfate in mice, compared to berberine or galangin alone. Attached Figure Description

[0026] Figure 1 The plots show the particle size, polydispersity index, and zeta potential of the self-assembled nanomedicine of berberine and galangin prepared in Example 2, where A and B are the particle size and polydispersity index plots and the zeta potential plot, respectively.

[0027] Figure 2 Transmission electron microscopy (TEM) image of the self-assembled nanomedicine of berberine and galangin prepared in Example 2.

[0028] Figure 3 The images show the ultraviolet and infrared spectra of the self-assembled nanomedicines of berberine and galangin (BGNP), berberine (BBR), and galangin (GAL) prepared in Example 2, where A and B are the ultraviolet and infrared spectra, respectively.

[0029] Figure 4 The figure shows the in vitro release results of the self-assembled nanomedicines of berberine and galangin prepared in Example 2 in simulated gastric and colonic fluids, where A and B are released in simulated gastric and colonic fluids, respectively.

[0030] Figure 5 The image shows the simulation results of the self-assembly of berberine and galangin, where green represents berberine and purple represents galangin.

[0031] Figure 6 The figures show the weight change curves and disease activity index change curves of the self-assembled nanomedicine of berberine and galangin prepared in Example 2 in a mouse model of ulcerative colitis, where A and B are the weight change curve and disease activity index change curve, respectively.

[0032] Figure 7 The images show the colonic images and length statistics of the self-assembled nanomedicines of berberine and galangin prepared in Example 2 in a mouse model of ulcerative colitis, where A and B are the colonic images and length statistics, respectively.

[0033] Figure 8 This is a hematoxylin-eosin staining image of colon tissue in a mouse model of ulcerative colitis, showing the self-assembled nanomedicine of berberine and galangin prepared in Example 2. Detailed Implementation

[0034] The present invention will be further described in detail below with reference to the embodiments, but the implementation of the present invention is not limited to the following embodiments.

[0035] All raw materials used in this invention are commercially available.

[0036] Example 1 Self-assembled nanomedicines of berberine and galangin were prepared using a nanoprecipitation method, specifically: (1) Prepare 1 mL of berberine (BBR) solution (20 mM) and 1 mL of galangin (GAL) solution (20 mM) with methanol respectively, and mix them at a volume ratio of 1:1 to obtain berberine-galangin-methanol solution; (2) In a light-proof environment, set the magnetic heating stirrer to 600 rpm. During the stirring process, use a single-channel syringe pump with a dropping rate of 100 μL / min to add 100 μL of berberine-galangin-methanol solution to 2.5 mL of pre-cooled deionized water to obtain a mixed solution. (3) The mixed solution was heated to 70 °C in the dark and stirred for 30 min to evaporate methanol to obtain berberine-galangin-water solution. The solution was dialyzed in water in the dark for 24 h to remove free BBR and GAL. The molecular weight of the dialysis bag was 2000 Da. After dialysis, it was freeze-dried at -80 °C for 24 h and then freeze-dried in a freeze dryer (temperature -66 °C, vacuum degree 0.001 Pa) for 48 h to obtain yellow self-assembled nanomedicine of berberine and galangin. It was stored in the dark at 4 °C.

[0037] Examples 2-4 The preparation method is the same as in Example 1, with the differences shown in the table below.

[0038] Table 1: Differences in preparation methods of Examples 1-4

[0039] Sample Analysis I. Particle size, polydispersity index (PDI), and zeta potential analysis The particle size of Examples 1-4 was measured using a Malvern particle size analyzer, and the polydispersity index (PDI) and zeta potential of Examples 2 and 3 were measured. The results are shown in Table 2.

[0040] Table 2: Particle size, polydispersity index (PDI), and zeta potential results for Examples 1-4

[0041] Note: " / " indicates that no test was performed.

[0042] Figure 1 The figures show the particle size, polydispersity index, and zeta potential of the self-assembled nanomedicine of berberine and galangin prepared in Example 2. Figures A and B show the particle size and polydispersity index, and the zeta potential, respectively. As shown, when the molar ratio of berberine to galangin is 1:1, and the volume ratio of berberine-galangin-methanol solution to deionized water is 1:50, the self-assembled nanomedicine has the smallest particle size (194.9 ± 1.81 nm), a polydispersity index of 0.2 ± 0.02, indicating that the prepared self-assembled nanomedicine forms a relatively uniform dispersion system in water, and a zeta potential of -15 ± 0.88 mV.

[0043] II. Transmission Electron Microscopy Analysis The dispersion of the self-assembled nanomedicine of berberine and galangin prepared in Example 2 was dropped onto a 300-mesh copper grid. After the filter paper absorbed the excess liquid, tungsten phosphate negative staining solution was added. After complete adsorption, the mixture was ventilated and dried for 15 min. The morphology of the self-assembled nanomedicine of berberine and galangin was detected by TEM.

[0044] Figure 2 The image shows a transmission electron microscope (TEM) image of the self-assembled nanomedicine of berberine and galangin prepared in Example 2. As shown in the figure, the self-assembled nanomedicine consists of spherical nanoparticles with a particle size of approximately 200 nm.

[0045] III. Ultraviolet and Infrared Spectra of Self-Assembled Nanomedicines Preparation of berberine solution (10 μg / mL) and galangin solution (10 μg / mL): Weigh 10 mg of BBR or GAL standard into a beaker, add 100 mL of methanol to fully dissolve and prepare BBR or GAL stock solution (100 μg / mL), take 1 mL of BBR or GAL stock solution into a 10 mL volumetric flask, and dilute to 10 mL to obtain a 10 μg / mL BBR or GAL solution.

[0046] 1 mg of the self-assembled nanomedicine (BGNP) of berberine and galangin prepared in Example 2 was weighed and dissolved in methanol. The methanol solution was used as a blank control and the sample was scanned in the range of 200-800 nm using a UV spectrophotometer.

[0047] Weigh 2 mg each of BBR, GAL, and lyophilized BGNP, add 200 mg of infrared-dried potassium bromide powder, mix well, and compress into potassium bromide tablets. Detect using a Fourier transform infrared (FT-IR) spectrophotometer. From 4000 cm⁻¹ -1 up to 500 cm -1 Data collection was performed 200 times with a step size of 4 cm. -1 .

[0048] Figure 3 The images show the UV and IR spectra of the self-assembled nanomedicines of berberine and galangin (BGNP), berberine (BBR), and galangin (GAL) prepared in Example 2, where A and B are the UV and IR spectra, respectively. Figure 3 As shown in Figure A, BBR exhibits characteristic absorption peaks at 228, 265, 348, and 430 nm, while GAL shows characteristic absorption peaks at 265 and 340 nm. The self-assembled nanomedicine, however, exhibits peaks at 228, 265, and 340 nm, encompassing the characteristic peaks of both. The Fourier transform infrared spectroscopy characterization results are as follows: Figure 3 As shown in Figure B, the self-assembled nanomedicine contains characteristic infrared peaks of BBR and GAL, and BBR also exhibits a peak at 1558 cm⁻¹. -1 The C=C double bond peak shifted to 1560 cm⁻¹. -1 GAL is 1564 cm -1 The C=C double bond peak shifted to 1567 cm⁻¹. -1 This confirms the occurrence of π-π conjugation.

[0049] IV. In vitro simulated gastrointestinal drug release Preparation of simulated gastric juice (SGF): Adjust the pH of 1×PBS to 1.8 with hydrochloric acid; Preparation of simulated colonic fluid (SCF): Adjust the pH of 1×PBS to 7.4 with sodium hydroxide.

[0050] Two mL of the self-assembled nanomedicine of berberine and galangin (BGNP, 200 μg / mL) prepared in Example 2 was placed in a dialysis bag (MWCO 2000 Da) and immersed in 15 mL of PBS. The mixture was continuously stirred on a magnetic stirrer at a temperature of 37 °C. At set time points (0.5, 1, 2, 4, 6, 8, 12, 24, 48), 3 mL of the release medium was extracted, and the berberine content was detected by UV light. The mixture was then replenished with an equal volume of fresh release medium.

[0051] Figure 4 The figure shows the in vitro release results of the self-assembled nanomedicines of berberine and galangin prepared in Example 2 in simulated gastric and colonic fluids. Release media A and B are simulated gastric and colonic fluids, respectively. As shown in the figure, in simulated gastric fluid at pH 1.8, the release rate and cumulative release amount of berberine in the self-assembled nanomedicine were lower than those of free berberine. In simulated colonic fluid at pH 7.4, free berberine reached release equilibrium after 4 hours, while the self-assembled nanomedicine could continue to release for up to 48 hours, indicating that the self-assembled nanomedicine has intestinal sustained-release capability.

[0052] V. Molecular Dynamics Simulation of the Self-Assembly Process of Berberine-Galangin Initial structural models of BBR and GAL were constructed using Chem3D software. Subsequently, the initial structures of BBR and GAL were optimized in Gaussian16 using the DFT-based B3LYP functional under the 6-311g(d) basis set. After structural optimization, the RESP charges of BBR and GAL were calculated using the Multiwfn 3.8 program. Force field parameter files for BBR and GAL were generated using the Sobtop program; GAFF force fields were used to describe BBR and GAL, and the TIP3P model was used for water. The simulation system was constructed using Gromacs 2023.3 software with a size of 9×9×9 nm. 3 A box was constructed, and appropriate amounts of BBR and GAL molecules were added in a 1:1 molar ratio, totaling 30 BBR molecules and 30 GAL molecules, initially randomly distributed within the box. Water molecules were then added to solubilize the system, and Cl ions were added to neutralize the net charge. Kinetic simulations were performed using Gromacs 2023, with 100 ns of kinetic simulations conducted after energy minimization and pre-equilibrium of the NVT and NPT systems. Simulation parameter settings: Steep method was used for energy minimization (1000 kJ / mol / nm), followed by 100 ps of NVT and NPT pre-equilibrium simulations. The temperature was 298.15 K (25 °C), with temperature coupling using a V-rescale temperature controller and pressure-temperature coupling using a C-rescale pressure controller, with the pressure set to 1 bar. Long-range van der Waals interactions were truncated at 12 Å. Electrostatic interactions were handled using particle-mesh Ewald. The production simulations were performed at 2 fs intervals, with the trajectory saved every 10 ps. Trajectory snapshots were obtained using VMD, and interaction details were plotted using PyMOL software. Periodic boundary conditions were applied to all simulations, including those in the x, y, and z directions.

[0053] Figure 5The figure shows the simulated self-assembly trajectory of berberine and galangin, where green represents berberine and purple represents galangin. As shown, initially, BBR and GAL are in a disordered state in the system. With the increase of simulation time, BBR and GAL gradually self-assemble together to form nanoparticles. At the end of the 100 ns kinetic simulation, all BBR and GAL molecules have assembled into stable nanoparticles.

[0054] VI. Application in ulcerative colitis Forty-two 6-8 week old male C57BL / 6J mice were randomly divided into groups of six according to body weight and housed separately. The groups included a control (CON) group, an ulcerative colitis model (DSS) group, a 5-aminosalicylic acid (5-ASA) group, a berberine (BBR) group, a galangin (GAL) group, a physical mixture group (BGMIX), and a self-assembled nanomedicine (BGNP) group prepared in Example 2.

[0055] After 7 days of acclimatization feeding, mice were given 3% DSS aqueous solution for nine consecutive days to induce ulcerative colitis. 5-ASA (100 mg / kg), BBR (20 mg / kg), GAL (16 mg / kg), BGMIX (BBR 20 mg / kg + GAL 16 mg / kg), and BGNP (containing BBR 20 mg / kg) were administered by gavage daily starting on the third day. The control group and the ulcerative colitis group were administered an equal volume of physiological saline by gavage. The body weight, loose stools, and occult blood of each mouse were recorded daily. The Disease Activity Index (DAI) was equal to the sum of the body weight, loose stool, and occult blood scores. The scoring criteria are shown in Table 3.

[0056] Table 3: Scoring Criteria for Disease Activity Index

[0057] Figure 6 Figure 1 shows the weight change curves and disease activity index change curves of the self-assembled nanomedicine of berberine and galangin prepared in Example 2 in a mouse model of ulcerative colitis. Figures A and B represent the weight change curve and disease activity index change curve, respectively. As shown in the figure, there was a significant difference in body weight between the control group (CON) and the model group (DSS) on day 9. The DSS group showed a significant decrease in body weight, and the disease activity index gradually increased with the increase in the number of days of administration. After administration of berberine or galangin alone or in combination, the body weight and disease activity index were not significantly different from those of the model group. However, after administration of the self-assembled nanomedicine of berberine and galangin, there were significant differences in body weight and disease activity index compared to the model group, significantly reducing the proportion of weight loss and the disease activity index. This indicates that BGNP significantly slowed down the weight loss and disease activity index increase induced by DSS in ulcerative colitis.

[0058] Mice were euthanized and dissected on day nine. Colon tissue was collected from each group after dissection. After washing the surface contents with 1×PBS, residual liquid was gently absorbed with filter paper. The colons were neatly arranged on white paper, and their length was measured with a ruler. One-way ANOVA was performed using GraphPad Prism 10.0, and the data are presented as mean ± SD.

[0059] Figure 7 The figures show actual colonic images and length statistics of the self-assembled nanomedicines of berberine and galangin prepared in Example 2 in a mouse model of ulcerative colitis, where A and B are the actual colonic image and length statistics, respectively. As shown in the figures, compared with the control group, the colonic length of the model group was significantly shortened. The self-assembled nanomedicine group of berberine and galangin was able to alleviate the colonic length shortening caused by DSS compared with single BBR, GAL and mixed BBR and GAL (BGMX group).

[0060] After dissecting the mice, colon tissue was collected from each group and fixed with 4% paraformaldehyde solution. Specifically: I) The tissue was removed from the paraformaldehyde solution, placed in an embedding cassette, dehydrated with ethanol of different concentrations, embedded in paraffin, and serially sectioned into 5mm thick sections. II) Paraffin section dehydration: Place the paraffin sections sequentially in xylene I for 10 minutes, then in xylene II for 10 minutes; then sequentially in anhydrous ethanol, 95%, 90%, 80%, and 70% ethanol for 10 minutes each, and then wash with distilled water; III) Hematoxylin staining: Place the sections in hematoxylin staining solution for 3-5 minutes, rinse with deionized water for 10 minutes, differentiate with differentiation solution, and rinse again with deionized water for 10 minutes; IV) Eosin staining: Dehydrate the sections sequentially in ethanol solutions with alcohol concentration gradients of 70%, 80%, 90%, and 95%, 2 minutes each, then stain with eosin staining solution for 5 minutes; finally, clear with xylene; V) After removing the sections, quickly add an appropriate amount of neutral resin before the xylene dries, and finally seal with a coverslip and observe under an upright microscope.

[0061] Figure 8 Figure 2 shows the colon tissue staining of the self-assembled nanomedicine of berberine and galangin prepared in Example 2 in a mouse model of ulcerative colitis. As shown in the figure, compared with the control group, the DSS group showed destruction of colonic crypt structure, epithelial cell shedding and inflammatory cell infiltration. BGNP was able to alleviate the destruction of crypt structure, epithelial cell shedding and inflammatory cell infiltration in ulcerative colitis more than BBR, GAL and their physical blend group (BGMX).

[0062] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Although the present invention has been described in detail with reference to the foregoing embodiments, those skilled in the art can still modify the technical solutions described in the foregoing embodiments or make equivalent substitutions for some of the technical features. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the protection scope of the present invention.

Claims

1. A self-assembled nanomedicine of berberine and galangin, characterized in that, It includes berberine and galangin, wherein the molar ratio of berberine to galangin is 1:1~2.

2. The self-assembled nanomedicine of berberine and galangin according to claim 1, characterized in that, The particle size of the self-assembled nanomedicine of berberine and galangin is 150~4200 nm.

3. The method for preparing self-assembled nanomedicine of berberine and galangin according to claim 1 or 2, characterized in that, Includes the following steps: (1) Berberine and galangin were dissolved in methanol to prepare berberine-methanol solution and galangin-methanol solution, respectively, and the two were mixed evenly to obtain berberine-galangin-methanol solution; (2) Place the pre-cooled deionized water in a dark environment and stir. Add the berberine-galangin-methanol solution obtained in step (1) to the deionized water to obtain a mixed solution. (3) After heating and evaporating the mixed solution to remove methanol, berberine-galangin-water solution was obtained. After dialysis and freeze-drying, self-assembled nanomedicine of berberine and galangin was obtained.

4. The method for preparing self-assembled nanomedicine of berberine and galangin according to claim 3, characterized in that, In step (1), the concentration of berberine in the berberine-methanol solution is 10~30 mM and the concentration of galangin in the galangin-methanol solution is 10~30 mM.

5. The method for preparing self-assembled nanomedicine of berberine and galangin according to claim 3, characterized in that, In step (2), the volume ratio of berberine-galangin-methanol solution to deionized water is 1:25~50.

6. The method for preparing self-assembled nanomedicine of berberine and galangin according to claim 3, characterized in that, In step (2), the stirring speed is 500~600 rpm.

7. The method for preparing self-assembled nanomedicine of berberine and galangin according to claim 3, characterized in that, In step (2), the dripping step uses a single-channel syringe pump, and the dripping speed is 90~110 μL / min.

8. The method for preparing self-assembled nanomedicine of berberine and galangin according to claim 3, characterized in that, In step (3), the heating and evaporation temperature is 60~80 ℃ and the time is 30~40 min.

9. The method for preparing self-assembled nanomedicine of berberine and galangin according to claim 3, characterized in that, In step (3), the dialysis bag used for dialysis has a molecular weight of 2000~3000 Da, and the dialysis time is 20~28h.

10. The use of the self-assembled nanomedicine of berberine and galangin according to claim 1 or 2 in the preparation of a drug for treating ulcerative colitis.

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