Preparation method and application of a nano self-assembled composition of arbutin-berberine

Abstract

The application discloses a preparation method and application of a nano self-assembly composition of arbutin-berberine, and comprises the following steps: dissolving berberine in methanol at 38-42 DEG C, adding an arbutin super-pure water solution at 38-42 DEG C, and stirring and keeping warm for 0.8-1.2 h to obtain a self-assembly solution; then, the self-assembly solution is subjected to vacuum rotary evaporation and freeze drying in sequence, and the nano self-assembly composition of arbutin-berberine is obtained. The traditional Chinese medicine nano self-assembly system based on arbutin and berberine is successfully constructed, the nanoparticles are spontaneously formed under mild conditions through intermolecular non-covalent interaction, the preparation process is simple and convenient, the conditions are mild, the damage of high temperature and other harsh conditions to active ingredients is effectively avoided, and the process adaptability is high.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine nanomedicine formulation technology, specifically relating to a method for preparing an arbutin-berberine nano self-assembled composition and its application. Background Technology

[0002] Hyperuricemia is a common metabolic disease caused by purine metabolism disorders. Its main pathogenesis involves excessive uric acid production or reduced excretion, leading to abnormally high serum uric acid levels. Long-term hyperuricemia can directly induce gouty arthritis and further cause serious complications such as kidney damage and cardiovascular diseases, significantly threatening patients' quality of life and health. Currently, commonly used uric acid-lowering drugs in clinical practice are mainly divided into two categories: one is xanthine oxidase inhibitors, such as allopurinol and febuxostat, which specifically inhibit xanthine oxidase activity, blocking the uric acid synthesis pathway and effectively lowering serum uric acid levels; the other is uric acid excretion promoters, such as benzbromarone, which act on renal uric acid transport proteins, enhancing the inhibition of uric acid reabsorption and promoting excretion in the renal tubules. Although these drugs can control serum uric acid levels relatively quickly in short-term treatment, long-term use is often accompanied by a series of significant adverse reactions. For example, allopurinol may induce severe hypersensitivity syndrome, febuxostat poses a potential risk of cardiovascular events, and benzbromarone has been restricted in some countries due to significant hepatotoxicity. Furthermore, these drugs mostly have single-target mechanisms of action, making it difficult to comprehensively regulate the complex uric acid metabolism network, and patients need to take them continuously for a long time, leading to poor clinical adherence. Therefore, developing highly effective, safe, low-toxicity, and long-term suitable natural-source uric acid-lowering agents has become an important clinical need that urgently needs to be addressed in the prevention and treatment of hyperuricemia, and has significant clinical and social value.

[0003] Arbutin, a natural phenolic glycoside, is widely found in various plant resources such as bearberry and pear. Recent studies have shown that it exerts a significant uric acid-lowering effect through two pathways: inhibiting xanthine oxidase activity and promoting uric acid excretion. Berberine, an isoquinoline alkaloid extracted from traditional Chinese medicinal herbs such as Coptis chinensis and Phellodendron amurense, can effectively regulate the expression level of renal uric acid transporters, promoting uric acid excretion and inhibiting inflammatory responses. The two exhibit obvious complementary characteristics in their molecular mechanisms of uric acid lowering, providing a theoretical basis for their combined application. However, in practical applications, both arbutin and berberine share common drawbacks such as poor solubility, low oral bioavailability, and rapid in vivo metabolism, severely limiting their therapeutic efficacy. Specifically, while arbutin has some water solubility, its poor lipid solubility limits its transmembrane transport capacity; berberine, due to its inherent low solubility, poor oral absorption efficiency, and rapid metabolism, struggles to maintain sufficient pharmacological activity and concentration in vivo. Traditional physical mixed drug delivery methods not only fail to effectively overcome the aforementioned formulation challenges, but also struggle to achieve simultaneous delivery of the two active ingredients in vivo and synergistic effects at the molecular level, thus limiting their clinical translation potential.

[0004] In recent years, with the deepening of research on the modernization of traditional Chinese medicine (TCM), nanomedicine delivery systems based on molecular self-assembly technology have shown broad application prospects in this field. The molecular self-assembly process mainly relies on non-covalent interactions between active ingredient molecules, including hydrophobic interactions, hydrogen bonding, π-π stacking interactions, and electrostatic interactions, which can guide natural active ingredients such as arbutin and berberine to spontaneously form highly ordered nano-aggregates. This technology can be completed under mild aqueous or organic phase conditions, without the need for harsh process conditions such as high temperature and high pressure, thus effectively avoiding the destruction of heat-sensitive natural product active ingredients, making it particularly suitable for the formulation development of effective components of TCM. Nanoparticles formed through self-assembly can significantly improve the apparent solubility of poorly soluble components, regulate drug release behavior, enhance transmembrane transport capacity, and thus greatly improve the bioavailability of active ingredients. More importantly, this technology can precisely assemble multiple active ingredients into the same nanocarrier, achieving molecular-level synergistic effects between components at the nanoscale. This fundamentally overcomes the inherent defects of traditional TCM compound preparations—"macroscopic mixing and microscopic separation"—and provides a new technical path for constructing efficient and safe TCM nano-preparations. Summary of the Invention

[0005] The purpose of this invention is to overcome the defects of the prior art and provide a method for preparing an arbutin-berberine nano-self-assembled composition.

[0006] Another object of the present invention is to provide the application of the arbutin-berberine nano-self-assembled composition prepared by the above preparation method.

[0007] The technical solution of the present invention is as follows:

[0008] A method for preparing an arbutin-berberine nano-self-assembled composition includes the following steps: dissolving berberine in methanol at 38-42 °C, then adding an ultrapure arbutin aqueous solution at 38-42 °C, and stirring for 0.8-1.2 h to obtain a self-assembled solution; then subjecting the self-assembled solution to rotary evaporation under reduced pressure and freeze-drying in sequence to obtain the final product.

[0009] In a preferred embodiment of the present invention, the molar ratio of berberine to arbutin is 1-10:1-10.

[0010] More preferably, the molar ratio of berberine to arbutin is 1:1.

[0011] In a preferred embodiment of the present invention, the ratio of berberine to arbutin, methanol, and ultrapure water in the arbutin ultrapure aqueous solution is 0.2-0.4 mol: 4-6 mL: 7-9 mL.

[0012] More preferably, the ratio of berberine to arbutin, methanol, and ultrapure water in the arbutin ultrapure aqueous solution is 0.3 mol: 5 mL: 8 mL.

[0013] In a preferred embodiment of the present invention, the molar ratio of berberine and arbutin is 1:1, and the ratio of berberine to arbutin, methanol, and ultrapure water in the arbutin ultrapure aqueous solution is 0.3 mol: 5 mL: 8 mL.

[0014] The use of the arbutin-berberine nano-self-assembled composition prepared by the above method in the preparation of a composition to improve high uric acid.

[0015] A composition for improving high uric acid, the raw materials of which include arbutin-berberine nano-self-assembled composition prepared by the above preparation method.

[0016] The beneficial effects of this invention are:

[0017] 1. This invention successfully constructed a traditional Chinese medicine nano-self-assembly system based on arbutin and berberine. Nanoparticles are spontaneously formed under mild conditions through non-covalent intermolecular interactions. The preparation process is simple and the conditions are mild, effectively avoiding the damage to active ingredients caused by harsh conditions such as high temperature. The process adaptability is strong.

[0018] 2. This invention can optimize the particle size distribution, surface charge, and colloidal stability of self-assembled particles by adjusting the molar ratio of the feed. Particles with different ratios exhibit different characteristics and can be flexibly selected according to application requirements. Among them, the particles formed under the preferred ratio have a concentrated particle size distribution and good stability, providing a reliable foundation for subsequent research and development.

[0019] 3. In vivo pharmacodynamic experiments show that the nano-self-assembled composition prepared in this invention can significantly reduce serum uric acid levels in hyperuricemia model animals. Its uric acid-lowering effect is superior to that of arbutin monomer and its physical mixture, achieving molecular-level synergistic delivery of the two active ingredients.

[0020] 4. The nano-self-assembled composition prepared by the present invention can promote uric acid excretion and inhibit uric acid reabsorption by synergistically regulating the mRNA expression level of renal uric acid transporter protein, thereby exerting a uric acid-lowering effect at multiple target levels.

[0021] 5. The system of this invention overcomes the defects of traditional physical mixing methods of "macro-mixing and micro-separation", providing a new technical path for the precise co-delivery of active ingredients in traditional Chinese medicine compound preparations. It has both safety and efficacy, and provides an innovative traditional Chinese medicine nano-preparation strategy for the clinical intervention of hyperuricemia, with good industrialization prospects. Attached Figure Description

[0022] Figure 1 The image shows a comparison of the optical paths of arbutin-berberine self-assembled solutions with different molar ratios (1:1, 5:1, 10:1, 1:2) in Example 1 of this invention, illustrating the differences in the intensity of the Tyndall effect.

[0023] Figure 2 The results of serum uric acid level measurement in each group of mice in Example 3 of the present invention are shown, and the effects of different intervention measures on serum uric acid in hyperuricemia model mice are compared.

[0024] Figure 3 This shows the results of the relative expression level of OAT-3 mRNA in the kidneys of mice in each group in Example 4 of this invention.

[0025] Figure 4 This shows the results of the relative expression level of URAT-1 mRNA in the kidneys of mice in each group in Example 4 of the present invention.

[0026] Figure 5 This shows the results of the relative expression level of OAT-1 mRNA in the kidneys of mice in each group in Example 4 of this invention.

[0027] Figure 6 This shows the results of the relative expression level of Glut-9 mRNA in the kidneys of mice in each group in Example 4 of the present invention. Detailed Implementation

[0028] The technical solution of the present invention will be further explained and described below with reference to specific embodiments and accompanying drawings.

[0029] Example 1: Preparation and Characterization of Self-Assembled Particles

[0030] (1) Raw material preparation:

[0031] Accurately weigh berberine and arbutin raw materials according to different molar ratios (1:5, 1:10, 2:1, 5:1, 10:1, 1:1) shown in Table 1, keeping the total molar amount constant at 0.3 mmol. All weighing operations were performed on an analytical balance, accurate to 0.1 mg.

[0032] (2) Self-assembly preparation:

[0033] Berberine was weighed and placed in a suitable glass container. 5 mL of chromatographic grade methanol was added, and the mixture was magnetically stirred in a 40 °C water bath until completely dissolved, forming a clear yellow solution. Subsequently, an arbutin solution of the corresponding concentration, prepared from 8 mL of ultrapure water, was slowly added to the berberine methanol solution under stirring. The reaction was continued at 40 °C for 1 h. After the reaction was complete, the solution was placed in a 40 °C water bath and slowly evaporated under reduced pressure for 1 h to remove most of the methanol, obtaining a crude aqueous solution of nanoparticles. This crude aqueous solution of nanoparticles was pre-frozen at -80 °C for 12 h, and then immediately freeze-dried to constant weight in a freeze dryer pre-cooled to -40 °C to remove residual organic solvents and water, yielding nanoparticle powder. The obtained nanoparticle powder was analyzed by high performance liquid chromatography using a C18 reversed-phase column and an acetonitrile-water (containing 0.1% trifluoroacetic acid) gradient elution system. The peak purity of the self-assembled particles obtained under different molar ratios was higher than 96% by peak area normalization. The actual binding molar ratio of berberine to arbutin in the self-assembled particles was basically consistent with the initial feed ratio. This indicates that rotary evaporation and freeze drying can effectively remove free monomers and impurities under mild conditions, while maintaining the orderliness of the self-assembled structure and the stability of its chemical composition. Finally, arbutin-berberine self-assembled solutions with different molar ratios were obtained.

[0034] (3) Particle size and potential measurement:

[0035] The particle size distribution and zeta potential of the arbutin-berberine self-assembled solutions with different molar ratios were determined using dynamic light scattering (DLS). Before measurement, the samples were appropriately diluted to avoid multiple scattering effects. The measurement temperature was set at 25℃, and each sample was measured in triplicate, with the average value taken. The results are shown in Table 1.

[0036] When the molar ratio of berberine to arbutin was 1:1, two parallel measurements showed that the Z-mean particle sizes were 15158.99 nm and 15756.22 nm, respectively; the average particle sizes (intensity distribution) were 146.41 nm and 166.48 nm, respectively; the zeta potentials were -3.6413 mV and -3.6954 mV, respectively; and the polydispersity index (PDI) were 0.518 and 0.527, respectively. When the molar ratio was 1:5, the Z-mean particle sizes were 1423.03 nm and 1193.21 nm, respectively; the average particle sizes were 331.73 nm and 575.28 nm, respectively; the zeta potentials were -0.3343 mV and -0.4169 mV, respectively; and the PDI were 0.561 and 0.371, respectively. When the molar ratio is 1:10, the Z-average particle sizes are 791.30 nm and 834.09 nm, the average particle sizes are 518.65 nm and 451.85 nm, the zeta potentials are -4.9231 mV and -5.1604 mV, and the PDIs are 0.650 and 0.524, respectively.

[0037] A comprehensive comparison of particle size and potential data under different molar ratios reveals that the nanoparticles formed under a 1:1 ratio exhibit a relatively concentrated particle size distribution, a moderate PDI value, and a high absolute value of zeta potential. This indicates that the self-assembled particles formed under this ratio have better colloidal stability and are suitable as an optimal ratio for further research.

[0038] (4) Comparison and observation of optical paths:

[0039] Self-assembled solutions with different molar ratios (1:1, 5:1, 10:1, 1:2) were transferred to transparent glass sample vials. The vials were then illuminated from the side using a 650 nm red laser pointer in a dark room, and the optical path was observed and recorded. The results are as follows: Figure 1 As shown, samples of different proportions all exhibit a clear Tyndall effect, meaning that a clearly visible beam is formed when the laser passes through the sample, indicating the presence of particles with sizes ranging from nanometers to submicrometers in the system, confirming the formation of self-assembled structures. The differences in beam intensity among samples of different proportions may be related to particle concentration and particle size distribution.

[0040] Table 1. Results of particle size and potential determination of arbutin-berberine self-assembled particles with different molar ratios (1:1, 1:5, 1:10)

[0041] Ratio (berberine: arbutin) Z-average particle size (nm) Average particle size (d.nm) Potential (mV) PDI Electrophoretic mobility (µm·cm / Vs) Electrical conductivity (mS / cm) 1:1 15158.99 146.41 -3.6413 0.518 -0.2835 0.5176 15756.22 166.48 -3.6954 0.527 -0.2877 0.5176 1:5 1423.03 331.73 -0.3343 0.561 -0.026 0.1682 1193.21 575.28 -0.4169 0.371 -0.0325 0.1682 1:10 791.30 518.65 -4.9231 0.650 -0.3833 0.0835 834.09 451.85 -5.1604 0.524 -0.4018 0.0820

[0042] Example 2 Animal grouping and dosing regimen

[0043] Laboratory animals:

[0044] Fifty-six eight-week-old SPF-grade male ICR mice were purchased from Wu's Animal Experiment Center, with an initial weight of approximately 30g. All animals were housed in the SPF-grade animal facility of the Experimental Animal Center of Huaqiao University under strictly controlled conditions: the ambient temperature was maintained at 24℃ to 25℃, the relative humidity at 60% to 65%, and a 12-hour day-night cycle lighting system was used. Animals had free access to food and water, and bedding and water were changed regularly to maintain a clean environment. A 7-day acclimatization period was implemented before the formal experiments began. The animals were fasted for 12 hours prior to the start of the experiments, but water was allowed. All procedures in this embodiment complied with the ethical requirements for laboratory animals and were approved by the ethics review committee of the Experimental Animal Center.

[0045] Animal grouping and treatment:

[0046] Fifty-six mice after adaptive feeding were randomly divided into seven groups of eight each. Except for the control group, all mice underwent hyperuricemia modeling. The specific grouping and treatment are as follows:

[0047] Control group: The patient was given an equal volume of physiological saline by gavage and an equal volume of sodium carboxymethyl cellulose solution by intraperitoneal injection.

[0048] Model group (HUA): Administered an equal volume of physiological saline by gavage.

[0049] Positive control group (allopurinol): Allopurinol was administered orally at a dose of 10 mg / kg.

[0050] Arbutin monomer group (ARU): Arbutin monomer was administered by gavage at a dose of 100 mg / kg.

[0051] Arbutin + Berberine Mixture Group: Arbutin and berberine in a 1:1 molar ratio were administered by gavage at a dose of 100 mg / kg (based on total active ingredient).

[0052] AB-SPs low-dose group: Arbutin-berberine nano-self-assembled particles (arbutin to berberine molar ratio of 1:1) were administered by gavage at a dose of 100 mg / kg (based on total active ingredient).

[0053] AB-SPs high-dose group: Arbutin-berberine nano-self-assembled particles (arbutin to berberine molar ratio of 1:1) were administered by gavage at a dose of 200 mg / kg (based on total active ingredients).

[0054] Dosing and modeling protocols:

[0055] Starting from day 1 of the experiment, medication was administered via gavage at 11:00 AM daily. Each group received either the corresponding drug or saline (0.2 mL / animal) via gavage. Hyperuricemia modeling was initiated daily at 3:00 PM by intraperitoneal injection of potassium xanthine (150 mg / kg) and simultaneous gavage of hypoxanthine (300 mg / kg). Animals in the control group received an equal volume of sodium carboxymethyl cellulose solution intraperitoneally and an equal volume of saline via gavage. After 7 days of modeling (day 8 of the experiment), blood samples were taken from the control group to measure serum uric acid levels to verify successful modeling. Medication was then continued to maintain the model for a total of 20 days. On the last day of the experiment, all animals were fasted for 12 hours and then euthanized by cervical dislocation 1 hour after the last administration. Ocular venous blood was collected, allowed to stand for 30 minutes, and then centrifuged to separate the serum for subsequent uric acid level determination.

[0056] Example 3: Serum uric acid level measurement

[0057] In this embodiment, a commercially available uric acid assay kit (enzyme colorimetric method) was used to quantitatively detect the uric acid concentration in serum samples from each group of mice. The detection process strictly followed the operating steps in the kit instructions, and each sample was tested in duplicate. The results are expressed as mean ± standard deviation.

[0058] The results are as follows Figure 2 The corresponding data are as follows: The serum uric acid level in the control group (Control) mice was 55.80 μmol / L, while the serum uric acid level in the model group (HUA) mice significantly increased to 138.40 μmol / L, showing a statistically significant difference compared to the control group, indicating that the hyperuricemia model was successfully established. After intervention with the positive control group (allopurinol), the serum uric acid level decreased to 112.24 μmol / L. The serum uric acid level in the arbutin monomer group (ARU) was 84.82 μmol / L, the serum uric acid level in the arbutin + flavonoid mixed group was 83.92 μmol / L, the serum uric acid level in the low-dose AB-SPs group (100 mg / kg) was 60.79 μmol / L, and the serum uric acid level in the high-dose AB-SPs group (200 mg / kg) was 65.08 μmol / L.

[0059] Experimental results showed that, compared with the model group, arbutin monomers, physical mixtures, and nano-self-assembled particles all reduced serum uric acid levels in hyperuricemia model mice to varying degrees. Among them, the low-dose AB-SPs group (100 mg / kg) showed the most significant uric acid-lowering effect, with its serum uric acid level being closest to the blank group and significantly superior to the arbutin monomer group and the physical mixture group. This result suggests that the granular formulation formed by the nano-self-assembly of arbutin and berberine has a good synergistic uric acid-lowering effect, achieving a superior uric acid-lowering effect compared to monomers and physical mixtures at a lower dose.

[0060] Example 4: Determination of renal uric acid transporter mRNA expression level

[0061] To investigate the molecular mechanism by which arbutin-berberine nanoparticles exert their uric acid-lowering effect, this study used real-time quantitative PCR (qRT-PCR) to detect the relative mRNA expression levels of uric acid transport-related proteins OAT-3, URAT-1, OAT-1 and Glut-9 in the kidney tissues of mice in each group.

[0062] Total RNA extraction: Appropriate amounts of kidney tissue from each group of mice were placed in pre-cooled TRIzol reagent and homogenized thoroughly using a tissue homogenizer. Total RNA was extracted according to the TRIzol method. RNA concentration and purity were determined using a UV spectrophotometer to ensure the A260 / A280 ratio was between 1.8 and 2.0.

[0063] Reverse transcription and real-time quantitative PCR: Equal amounts of total RNA were reverse transcribed into complementary DNA (cDNA) using a reverse transcription kit. Subsequently, using the cDNA as a template, real-time quantitative PCR amplification was performed using the SYBR Green method. Primer sequences were synthesized by Sangon Biotech (Shanghai) Co., Ltd. GAPDH was used as an internal control gene, and the relative expression levels of each target gene were calculated using the 2^-ΔΔCt method. Each sample was tested in triplicate, and experimental results are expressed as mean ± standard deviation.

[0064] OAT-3 mRNA expression results are as follows: Figure 3 As shown, compared with the control group, the relative expression level of OAT-3 mRNA in the kidneys of mice in the model group was significantly decreased (P < 0.0001). After intervention with low-dose AB-SPs, the expression level of OAT-3 mRNA significantly rebounded, and the difference compared with the model group was highly statistically significant (P < 0.0001). These results indicate that arbutin-berberine nanoparticles can significantly upregulate the expression of the uric acid excretion-related transporter OAT-3, thereby promoting renal excretion of uric acid.

[0065] URAT-1 mRNA expression results are as follows Figure 4 As shown, compared with the control group, the relative expression level of URAT-1 mRNA in the kidneys of mice in the model group was significantly increased (P < 0.0001). After intervention with low-dose AB-SPs, the expression level of URAT-1 mRNA significantly decreased, and the difference compared with the model group was highly statistically significant (P < 0.0001). These results indicate that the nanoparticles can effectively inhibit the expression of URAT-1, a protein related to uric acid reabsorption, and reduce the reabsorption of uric acid in the renal tubules.

[0066] OAT-1 mRNA expression results are as follows: Figure 5As shown, compared with the control group, the relative expression level of OAT-1 mRNA in the kidneys of mice in the model group was significantly increased (P < 0.0001). After intervention with low-dose AB-SPs, the expression level of OAT-1 mRNA significantly decreased, and the difference compared with the model group was highly statistically significant (P < 0.0001). These results indicate that arbutin-berberine nanoparticles have a regulatory effect on the expression of the uric acid transporter OAT-1.

[0067] Glut-9 mRNA expression results are as follows Figure 6 As shown, compared with the control group, the relative expression level of Glut-9 mRNA in the kidneys of mice in the model group was significantly increased (P < 0.0001). After intervention with low-dose AB-SPs, the expression level of Glut-9 mRNA significantly decreased, and the difference compared with the model group was highly statistically significant (P < 0.0001). These results indicate that arbutin-berberine nanoparticles can inhibit the expression of Glut-9, a protein related to uric acid reabsorption.

[0068] Based on the above molecular mechanism research results, the arbutin-berberine nanoparticles prepared in Example 1 can synergistically regulate the expression network of renal uric acid transport proteins. On the one hand, it upregulates the expression of uric acid excretion-related protein OAT-3, and on the other hand, it downregulates the expression of uric acid reabsorption-related proteins URAT-1, OAT-1 and Glut-9. This promotes uric acid excretion and inhibits uric acid reabsorption at the molecular level, ultimately achieving the pharmacodynamic effect of reducing serum uric acid levels.

[0069] The above description is merely a preferred embodiment of the present invention, and therefore should not be construed as limiting the scope of the present invention. All equivalent changes and modifications made in accordance with the scope of the patent and the contents of the specification should still fall within the scope of the present invention.

Claims

1. A method for preparing an arbutin-berberine nano-self-assembled composition, characterized in that: The process includes the following steps: berberine is dissolved in methanol at 38-42 °C, and then an ultrapure aqueous solution of arbutin at 38-42 °C is added. The mixture is kept warm and stirred for 0.8-1.2 h to obtain a self-assembled solution. The self-assembled solution is then subjected to rotary evaporation under reduced pressure and freeze-drying in sequence to obtain the final product.

2. The preparation method according to claim 1, characterized in that: The molar ratio of berberine to arbutin is 1-10:1-10.

3. The preparation method according to claim 2, characterized in that: The molar ratio of berberine to arbutin is 1:

1.

4. The preparation method according to claim 1, characterized in that: The ratio of berberine to arbutin, methanol, and ultrapure water in the arbutin ultrapure aqueous solution is 0.2-0.4 mol: 4-6 mL: 7-9 mL.

5. The preparation method according to claim 4, characterized in that: The ratio of berberine to arbutin, methanol, and ultrapure water in the arbutin ultrapure aqueous solution is 0.3 mol: 5 mL: 8 mL.

6. The preparation method according to claim 1, characterized in that: The molar ratio of berberine to arbutin is 1:1, and the ratio of berberine to arbutin, methanol, and ultrapure water in the arbutin ultrapure aqueous solution is 0.3 mol: 5 mL: 8 mL.

7. Use of the arbutin-berberine nano-self-assembled composition prepared by the preparation method according to any one of claims 1 to 6 in the preparation of a high uric acid improvement composition.

8. A composition for improving high uric acid, characterized in that: The raw materials include arbutin-berberine nano-self-assembled compositions prepared by the preparation method described in any one of claims 1 to 6.

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