Pinocembrin polymer micelle for resisting hyperuricemia and method for preparing same

By packaging Qiaosongsu in polymer micelles of Pluronic F-127 and vitamin E polyethylene glycol succinate, Qiaosongsu's poor water solubility and low bioavailability were solved, and its efficient absorption and release in the body was achieved.

WO2025111835A1PCT designated stage expired Publication Date: 2025-06-05JIANGSU UNIV
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Patent Information

Application Number
PCT/CN2023/134908
Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Filing Date
2023-11-29
Publication Date
2025-06-05

AI Technical Summary

Technical Problem

The poor water solubility, low in vitro release and low bioavailability of Qiaosongsu limit its use in clinical applications.

Method used

Pluronic F-127 and vitamin E polyethylene glycol succinate as carriers were used to prepare chosongin polymer micelles, which were completely dissolved in organic solvents by ultrasonic-assisted methods, and polymer micelles with nanoparticle sizes were formed by microfluidic technology.

Benefits of technology

It significantly improves the solubility and in vitro release of Qiaosongin, improves its oral bioavailability, and has a simple preparation method, low cost and good stability.

✦ Generated by Eureka AI based on patent content.

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Patent Text Reader

Abstract

Provided are a pinocembrin polymer micelle for resisting hyperuricemia and a method for preparing same. The pinocembrin polymer micelle comprises 4%-18% of pinocembrin, 33%-53% of Pluronic F-127, and 31%-56% of vitamin E polyethylene glycol succinate. The flow rate ratio of the continuous phase to the dispersed phase for the microfluidic preparation of the pinocembrin polymer micelle is 1: 11-1: 10. The continuous phase is a solution of Pluronic F-127 and vitamin E polyethylene glycol succinate in methanol, and the dispersed phase is double-distilled water.
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Description

A kind of anti-hyperuricemia pyrocatechol polymer micelle and preparation method thereof Technical Field

[0001] The present invention relates to a pharmaceutical preparation, in particular to a method for preparing chondrostenone polymer micelles for resisting hyperuricemia. Background Art

[0002] Pinocembrin, also known as pinocembrin, is a natural flavonoid compound of the 5,7-dihydroxyflavonoid class. It is found in licorice, propolis, etc. Its molecular formula is C 15 H 12 O4, with a relative molecular mass of 256.25, occurs as colorless crystals. It is a highly important active substance in licorice, exhibiting pharmacological activities such as antibacterial, anti-inflammatory, antioxidant, antitumor, cardioprotective, neuroprotective, and xanthine oxidase inhibition. Notably, both liquiritin and chondrostenone belong to the dihydroflavonoid class. Compared to liquiritin, chondrostenone has an additional 5-OH group on ring A that forms a p-π conjugation with the benzene ring, increasing the electron cloud density on ring A and activating both ring A and the 7-OH group, resulting in enhanced pharmacological activity. As a flavonoid, it is readily soluble in organic solvents such as methanol, ethanol, and dimethyl sulfoxide. However, its low water solubility makes it difficult to absorb and has low bioavailability, which significantly hinders its clinical application. In recent years, researchers at home and abroad have developed dosage forms such as cyclodextrin inclusion complexes and liposomes to address these issues.

[0003] Polymer micelles are nano-drug delivery systems formed by the self-assembly of various biocompatible amphiphilic block copolymers, such as Pluronic copolymers and methoxypolyethylene glycol polylactic acid (MPEG-PLA), in aqueous solution. When the block polymer concentration in water is low, it disperses or adsorbs on the solution surface as a single molecule, reducing surface tension. Upon reaching a certain concentration, the polymers tend to arrange themselves into an ordered structure, forming a shell-core structure with the hydrophobic groups on the inside and the hydrophilic groups on the outside. This concentration is known as the critical micelle concentration (CMC). The lower the polymer's CMC, the more stable the micelles. Amphiphilic polymers self-assemble in water through various driving forces, such as hydrophobic and electrostatic interactions, encapsulating poorly soluble drugs within the hydrophobic core and enhancing drug solubility. The resulting micelles have a small particle size (typically 1-100 nm) and a uniform distribution, which facilitates blood circulation, tissue penetration, and cellular uptake. Furthermore, polymer micelles form through simple self-assembly in solution, making them easier to mass-produce than other nanocarriers, such as polymer nanoparticles and liposomes.

[0004] Hyperuricemia (HUA) is a common metabolic disease caused by a disorder of purine metabolism and characterized by elevated uric acid levels. Generally speaking, under normal physiological conditions, uric acid levels exceeding 416 mmol / L in men and postmenopausal women, and exceeding 357 mmol / L in premenopausal women, are considered hyperuricemia. However, this is not absolute. Studies have shown that uric acid levels are also associated with age, race, and comorbidities. Because numerous factors influence purine metabolism, abnormal uric acid levels are multifactorial and exhibit significant inter-individual variability. Uric acid production is 67% endogenous, and 33% comes from dietary purine intake. To maintain normal daily uric acid levels, approximately 75% is excreted through the kidneys, and the remaining 25% is excreted through the gastrointestinal tract. Excessive uric acid production and kidney disease can lead to oversaturation of sodium urate crystals, which deposit in joints, increase inflammation, and contribute to gout. Gout is a type of arthritis accompanied by severe pain. In addition, there are cases of HUA without concurrent gout symptoms, known as asymptomatic hyperuricemia. Hyperuricemia and gout are considered the second most common disease in younger people after type 2 diabetes.

[0005] Summary of the Invention

[0006] The purpose of the present invention is to provide a pyralidin polymer micelle for treating hyperuricemia and a preparation method thereof, in order to address the problems of poor water solubility, low in vitro release and low bioavailability of pyralidin. The present invention prepares pyralidin with poor water solubility into polymer micelles, which can significantly improve the solubility and in vitro release of pyralidin, and the preparation method thereof should be simple.

[0007] To achieve the above objectives, the present invention adopts the following technical solution: a pyralidin polymer micelle for anti-hyperuricemia, wherein the polymer micelle is a carrier of Pluronic F-127 (a copolymer of propylene oxide and ethylene oxide) and vitamin E polyethylene glycol succinate to encapsulate pyralidin, and the mass fractions of each component are: pyralidin 4% to 18%, Pluronic F-127 33% to 53%, and vitamin E polyethylene glycol succinate 31% to 56%.

[0008] Furthermore, the mass fractions of the components are: 11.11% of pyrocatechol, 55.56% of Pluronic F-127, and 33.33% of vitamin E polyethylene glycol succinate.

[0009] Furthermore, the particle size of the polymer micelles is 25 to 40 nm, the polydispersity coefficient is 0.105 to 0.184, and the encapsulation efficiency is above 90%.

[0010] A method for preparing the above-mentioned anti-hyperuricemia pyrocatechol polymer micelles comprises the following steps:

[0011] (1) According to the ratio of the components, pyrocatechol, Pluronic F-127 and vitamin E polyethylene glycol succinate were weighed and completely dissolved in an organic solvent under ultrasound-assisted conditions to serve as the continuous phase for preparing pyrocatechol polymer micelles; double-distilled water was used as the dispersed phase;

[0012] (2) The prepared continuous phase and dispersed phase were placed in syringes respectively, and the syringes were placed on two calibrated constant flow pumps respectively, connected to the microfluidic chip through catheters, and the flow rates of the two phases were controlled to prepare chondrostenone polymer micelles.

[0013] Furthermore, the flow rate ratio of the continuous phase to the dispersed phase is 1:1 to 10, preferably 1:2.

[0014] Furthermore, the dispersed phase in the conduit is injected from the middle channel, and the continuous phase is injected from the channels on both sides, and the symmetrical continuous phase shears the dispersed phase to form droplets.

[0015] Beneficial effects of the present invention:

[0016] (1) The preparation method of the pineapple polymer micelle preparation of the present invention is simple, easy to operate, low in cost, and the preparation process is easy to control; the prepared pineapple polymer micelles spontaneously form polymer micelles with a particle size of less than 50 nm when in contact with water, and have a high encapsulation efficiency and drug loading capacity; the prepared pineapple polymer micelles are stored for one month at a temperature of 25±2°C and a relative humidity of 75±5%, and the particle size does not change significantly, and the EE decreases by no more than 10%, which is still above 90%. During this period, the pineapple polymer micelle solution is clear and transparent, without precipitation, and has good stability; the in vitro release of the prepared pineapple polymer micelles in four media within 24 hours is significantly higher than that of pineapple, and the in vitro cumulative release reaches more than 75%, which significantly improves the solubility and in vitro release of pineapple.

[0017] (2) The chondrostenone polymer micelles prepared by the present invention can be directly orally administered in actual application. Pharmacokinetic studies have shown that the solubility of chondrostenone is poor and its bioavailability is low. Encapsulating the drug in polymer micelles can increase the speed and extent of drug absorption in the body, greatly improving oral bioavailability. Based on the physical and chemical properties of hydrophobic drugs and the polymer chains that form the micelle structure, the core of the micelle can dissolve a large number of chondrostenone molecules. The increase in oral bioavailability may be due to: polymer micelles, as a nano-drug delivery system less than 100 nm, can be absorbed through adsorption and endocytosis; after most of the chondrostenone is encapsulated by micelles, the effect of gastrointestinal enzymes on the drug is reduced, thereby increasing the drug concentration in the body. The prepared chondrostenone polymer micelles improve the pharmacokinetic parameters of chondrostenone and improve the oral bioavailability of chondrostenone. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] FIG1 is a photograph of the appearance of the pyrocatechol polymer micelles prepared in Example 1.

[0019] FIG2 is a particle size distribution diagram of the diatomaceous earth polymer micelles prepared in Example.

[0020] FIG3 is a transmission electron micrograph of the pyrocatechol polymer micelles prepared in Example.

[0021] FIG4 is an in vitro release curve of the chondrostenone polymer micelles and the chondrostenone drug substance prepared in the examples in different pH media (A: pH 1.2 HCl solution, B: pH 6.8 PBS solution, C: pH 7.4 PBS solution, D: DDW).

[0022] Figure 5 is a graph showing the drug-drug curves of chondrostenone raw material and chondrostenone polymer micelles after oral administration to rats (n=5) (A: drug-drug curve 36 hours after oral administration, B: drug-drug curve 6 hours after oral administration).

[0023] Figure 6 shows the UA concentrations in each group three hours after modeling (### compared with NC, p<0.001; * compared with MC, p<0.05; ** compared with MC, p<0.01; *** compared with MC, p<0.001; ++ compared with the corresponding dose of chondrostenone raw material group, p<0.01).

[0024] Figure 7 shows the XOD activities in the serum and liver of rats in each group (compared with the XOD activities in the serum and liver of the NC group, ###p<0.001; compared with the XOD activity in the serum of the MC group, **p<0.01, ***p<0.001; compared with the XOD activity in the liver of the MC group, ▲ ▲ p<0.01, ▲▲▲ p<0.001).

[0025] Figure 8 shows the IL-1β levels in the serum and liver of rats in each group (compared with the IL-1β levels in the serum and liver of the NC group, ###p<0.001; compared with the IL-1β levels in the serum of the MC group, **p<0.01, ***p<0.001; compared with the IL-1β levels in the liver of the MC group, ▲▲ p<0.01, ▲▲▲ p<0.001).

[0026] Figure 9 shows the TNF-α levels in the serum and liver of rats in each group (compared with the TNF-α levels in the serum and liver of the NC group, ###p<0.001; compared with the TNF-α levels in the serum of the MC group, **p<0.01, ***p<0.001; compared with the TNF-α levels in the liver of the MC group, ▲▲ p<0.01, ▲▲▲ p<0.001). DETAILED DESCRIPTION

[0027] In order to enable those skilled in the art to better understand the present invention, the following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the drawings 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 in the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts should fall within the scope of protection of this application.

[0028] It should be noted that the terms "including" and "having" and any variations thereof in the specification and claims of this application and the above-mentioned drawings are intended to cover non-exclusive inclusions. For example, a process, method, system, product or apparatus that includes a series of steps or units is not necessarily limited to those steps or units clearly listed, but may include other steps or units that are not clearly listed or are inherent to these processes, methods, products or apparatuses.

[0029] Example 1

[0030] Screening of formulation and process for microfluidic preparation of chondrostenone polymer micelles:

[0031] (1) Screening of chondrostenone polymer micelle formulations

[0032] Orthogonal experiment was used to screen the prescription. F127 (A), TPGS (B) and PCB (C) were selected as the factors to be investigated. The particle size was taken as the target of investigation. The particle size was detected by laser particle size analyzer. Three levels were selected for each factor. SPSS software was used for design. L9 (3 4 )Orthogonal analysis table (Mean, n=3), the results are shown in Table 1.

[0033] Table 1

[0034] Using the range analysis method, according to the range R analysis, it can be found that the influence of each factor on the micelle particle size is: TPGS>F127>PCB, and the best prescription is: A3B1C2.

[0035] (2) Screening of flow rate for preparation of chondrostenone polymer micelles

[0036] After the continuous phase and dispersed phase were prepared according to the optimal formula, the two-phase flow rate was screened using particle size, polydispersity coefficient and encapsulation efficiency as indicators. The results are shown in Table 2.

[0037] Table 2

[0038] At different flow rate ratios between the continuous phase and the dispersed phase, the particle size tends to decrease with the increase of the dispersed phase flow rate, but the change is not significant and is all within the range of 50 nm; the PDI also does not change significantly and is all less than 0.2; however, as the aqueous phase flow rate continues to increase, the concentration of the prepared pyrocatechol polymer micelles will become too dilute, so a two-phase flow rate ratio of 1:2 is selected as the optimal flow rate condition for preparing pyrocatechol polymer micelles.

[0039] In summary, the optimal formula for preparing chondrostenone polymer micelles is A3B1C2, and the optimal flow rate condition is a continuous phase to dispersed phase flow rate ratio of 1:2.

[0040] Example 2

[0041] In vitro characterization of chondrostenone polymer micelles:

[0042] Observation of the appearance of the pyrocatechol polymer micelles: The polymer micelles prepared in Example 1 were observed to be a clear, transparent, colorless liquid at room temperature without precipitation, and exhibited an obvious Tyndall effect, as shown in FIG1 .

[0043] Polymer micelle size determination: The polymer micelle solution prepared in Example 1 was used to measure the polymer micelle droplet size (DS) and polydispersity index (PDI) using dynamic light scattering (DLS) and phase analysis light scattering (PALS) techniques using a Nano Brook 90 PALS instrument. The sample cell was maintained at a temperature of 25°C and a scattering angle of 90°. Three replicate measurements were performed. The results showed that the polymer micelle particle size ranged from 25 to 40 nm and was uniformly distributed. The particle size distribution is shown in Figure 2.

[0044] Observation of polymer micelle morphology: The polymer micelle solution prepared in Example 1 was added dropwise onto a copper mesh covered with a support film, allowed to dry, and then stained with a 2% phosphotungstic acid solution. The mesh was evaporated naturally and observed under a transmission electron microscope. The pyrocatechol polymer micelle solution appeared spherical and evenly distributed under a transmission electron microscope, without agglomeration, as shown in Figure 3.

[0045] Determination of in vitro release from polymer micelles: The pyralidin polymer micelles and pyralidin from Example 1 were placed in dialysis bags, and their in vitro release in water, pH 1.2 hydrochloric acid solution, pH 6.8 phosphate buffer, and pH 7.4 phosphate buffer was examined. The results showed that compared with pyralidin, the pyralidin polymer micelles dissolve more rapidly and completely, effectively improving the in vitro release rate of pyralidin, as shown in Figure 4.

[0046] Example 3

[0047] Evaluation of oral bioavailability of chondrostenone polymer micelles

[0048] 1. Blood sample processing method

[0049] Blood was collected from the preorbital venous plexus of rats into a 1.5 mL EP tube. After standing in a 37°C constant temperature water bath for 30 minutes, the sample was centrifuged at 3700 rpm for 10 minutes to obtain the upper serum layer. The serum was then aspirated into a 1.5 mL EP tube, and the internal standard solution was added. The sample was vortexed to thoroughly mix the internal standard with the serum. 400 μL of ethyl acetate was added, vortexed for 1 minute, and centrifuged at 10,000 rpm for 10 minutes. The upper ethyl acetate extract was collected and an additional 400 μL of ethyl acetate was added to the EP tube containing the remaining serum. This process was repeated to fully extract the pyrocatechol and internal standard from the serum. The two extracts were combined and dried with nitrogen in a 37°C water bath. The dried sample was then reconstituted in chromatographic methanol and vortexed. The sample was then centrifuged at 12,000 rpm for 10 minutes. The supernatant was collected and analyzed for pyrocatechol content by HPLC.

[0050] 2. In vivo pharmacokinetic experimental methods in SD rats

[0051] Male Sprague-Dawley rats of standard weight were selected and, after three days of self-acclimatization under laboratory standards, randomly divided into two groups: the sedative pine raw material drug group and the sedative pine polymer micelle group. Food was withheld for 12 hours prior to the experiment, but water was freely available. The rats in both groups were gavage-administered the same dose of the sedative pine raw material drug suspension and the sedative pine polymer micelles. Following administration, blood was collected from the rats' orbital venous plexus at various time points. Blood samples were allowed to rest in a 37°C water bath for 30 minutes, then centrifuged at 3700 rpm for 10 minutes. Serum was collected in 1.5 mL EP tubes. After the blood samples were processed as described above, they were injected and analyzed by HPLC, and the drug concentration in the rats' blood at the corresponding time was calculated. The blood concentration-time curve is plotted with the sampling time as the X-axis and the sedative pine plasma concentration as the Y-axis. Figure 5 shows the blood concentration-time curve.

[0052] Example 4

[0053] Improving hyperuricemia in rats by chondrostenone polymer micelles

[0054] 1. Establishment of a Rat Hyperuricemia Model

[0055] Ten male SD rats of standard weight were randomly divided into two groups, 5 rats in each group, namely the normal control group (NC) and the model group (MC), and raised in a standard laboratory environment for 3 days. In addition to the normal control group, the model group was given a hyperuricemia rat model by gavage of hypoxanthine suspension and intraperitoneal injection of potassium oxonate emulsion. Blood was first collected from the orbital venous plexus of the rats before modeling, and then blood was collected at 1h, 2h, 3h, 4h, 5h, 6h, 8h, and 10h after modeling. After processing, the blood samples were analyzed by HPLC and the uric acid concentration was calculated to determine whether the rat hyperuricemia model has been successfully established and to determine the time for uric acid level detection. 2. Animal grouping and drug administration

[0056] Fifty male SD rats of standard weight were randomly divided into 10 groups, with 5 rats in each group:

[0057] Normal control group (NC): gavage with 0.9% saline;

[0058] Model group (MC): gavage with 0.9% saline

[0059] Positive control group (PC): oral administration of allopurinol;

[0060] Low-dose group (PCB-L): oral administration of bromocriptine suspension (50 mg / kg);

[0061] Medium dose group (PCB-M): oral administration of bromocriptine suspension (100 mg / kg);

[0062] High-dose group (PCB-H): oral administration of borax suspension (200 mg / kg);

[0063] Low-dose polymer micelle group (PCB-ML): oral administration of bromocriptine polymer micelles (50 mg / kg);

[0064] Polymer micelle medium dose group (PCB-MM): oral administration of bromocriptine polymer micelles (100 mg / kg);

[0065] High-dose polymer micelle group (PCB-MH): oral administration of borax polymer micelle (200 mg / kg);

[0066] Blank polymer micelle group (BM): blank polymer micelles were administered orally.

[0067] 3. Detection indicators and methods

[0068] 3.1 Determination of serum uric acid

[0069] Drugs were administered 1 hour after modeling, and serum uric acid levels were measured 3 hours after modeling. Blood was collected from the orbital venous plexus of the rats 3 hours after modeling, and the blood samples from each group were processed and uric acid levels were measured by HPLC.

[0070] 3.2 Determination of xanthine oxidase (XOD) activity in serum and liver

[0071] Xanthine oxidase (XOD) can indirectly convert hypoxanthine or directly convert xanthine to uric acid. When XOD is abnormally active, it leads to uric acid metabolism disorders, thereby causing hyperuricemia. As can be seen from this, XOD is the key to uric acid secretion, and inhibiting the catalytic activity of XOD is crucial for the treatment of hyperuricemia. The serum of each group of rats was thawed at room temperature. Separately, rat liver was placed in a centrifuge tube, and low-temperature normal saline was added according to a ratio of 1:10 (g:mL). The liver was homogenized using a high-speed homogenizer in an ice-water bath, and the homogenate was centrifuged at 10,000 rpm for 10 minutes to separate the supernatant. The supernatant and serum were measured for xanthine oxidase (XOD) activity in the sample according to the operating instructions of the ELISA kit.

[0072] 3.3 Detection of inflammatory factors

[0073] TNF-α is a pro-inflammatory cytokine that plays an important role in the entire inflammatory response process. It is an initiator of the cytokine regulatory network in the patient's body, has a local pro-inflammatory effect, stimulates neutrophils, and then initiates the inflammatory response. IL-1β plays a special role in the inflammatory response and is the most representative inflammatory regulatory factor. Therefore, it is necessary to examine the levels of IL-1β and TNF-α. The serum of each group of rats was thawed at room temperature. Separately, the rat liver was collected in a centrifuge tube, and cold physiological saline was added at a ratio of 1:10 (g:mL). The liver was homogenized using a high-speed homogenizer in an ice-water bath. The homogenate was centrifuged at 10,000 rpm for 10 minutes, and the supernatant was separated. The serum and liver homogenate supernatant obtained from each group were operated according to the ELISA kit instructions to measure the levels of IL-1β and TNF-α.

[0074] 3.4 Data processing and statistical methods

[0075] All data were expressed as mean ± SD, and the t test was used to examine the significance between groups, with P < 0.05 or P < 0.01 as the significance index.

[0076] 4. Experimental Results

[0077] 4.1 Determination of serum uric acid

[0078] Figure 6 shows the serum uric acid levels of each group. Compared with the MC group, the BM and MC groups had similar uric acid levels, indicating that the excipients used in the polymer micelles had little effect on uric acid levels. Serum uric acid levels in PCB-L, PCB-M, PCBLH, PCB-ML, PCB-MM, PCB-MH, and PC groups were significantly reduced (P < 0.01). The chlorpyrifos polymer micelle group had a more significant effect on reducing uric acid levels than the chlorpyrifos API group. This indicates that chlorpyrifos and its polymer micelle preparation can reduce uric acid levels and have a certain improvement effect on hyperuricemia.

[0079] 4.2 Determination of XOD activity in serum and liver

[0080] Figure 7 shows the XOD activity in the serum and liver of each group. The XOD activity in the serum and liver of rats in the MC group was significantly higher than that in the NC group (P < 0.001), indicating that the hyperuricemia model was successfully established. Measurement of XOD activity in the plasma and liver of rats in the different dosing groups revealed a significant decrease compared to the MC group, with statistically significant results. This suggests that chondrostenone and chondrostenone polymer micelles can inhibit XOD activity, reduce uric acid production, and improve hyperuricemia.

[0081] 4.3 Detection of inflammatory factors

[0082] The levels of inflammatory factors in the serum and liver of each group are shown in Figure 8. The levels of inflammatory factors (IL-1β, TNF-α) in the serum and liver of rats in the MC group were significantly higher than those in the NC group (P<0.001), indicating that the HUA rat model was successfully established. The levels of inflammatory factors in the serum and liver of rats in the BM group were similar to those in the MC group, indicating that the excipients used in the micelles had no effect on improving the levels of inflammatory factors in the HUA model caused by the combination of HX and PO. The PC group was able to reduce the levels of IL-1β and TNF-α to levels similar to those in the NC group, improving inflammation. Compared with the MC group, the levels of inflammatory factors in the serum and liver of rats in the groups administered with the chondrostenone raw material and chondrostenone polymer micelles were reduced to varying degrees, and were dose-dependent. According to the low, medium and high doses, the chloranthracene raw material group reduced the serum IL-1β level by 16.93%, 29.20% and 37.76%, and reduced the IL-1β level in the liver by 18.48%, 21.52% and 31.32%; reduced the serum TNF-α level by 6.91%, 19.73% and 25.32%, and reduced the TNF-α level in the liver by 7.31%, 15.54% and 17.73%. At the same dose, the pyralidin polymer micelle group reduced the serum IL-1β level by 35.99%, 41.77%, and 48.96%, and reduced the IL-1β level in the liver by 27.81%, 34.29%, and 38.91%; reduced the serum TNF-α level by 17.43%, 24.99%, and 35.84%, and reduced the TNF-α level in the liver by 18.83%, 26.32%, and 35.28%, indicating that the pyralidin polymer micelles can improve the anti-inflammatory effect of pyralidin to a certain extent.

[0083] The above research results show that the chondrostenone polymer micelles of the present invention have a significant effect of improving hyperuricemia and can significantly improve the efficacy of the chondrostenone raw material drug.

[0084] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the technical principles of the present invention. These improvements and modifications should also be regarded as within the scope of protection of the present invention.

Claims

1. A pinocembrin polymer micelle for treating hyperuricemia, characterized in that: The polymer micelle uses Pluronic F-127 and vitamin E polyethylene glycol succinate as carriers to encapsulate pinocembrin, and the mass fractions of each component are: pinocembrin 4% - 18%, Pluronic F-127 33% - 53%, vitamin E polyethylene glycol succinate 31% - 56%.

2. The pinocembrin polymer micelle for treating hyperuricemia according to claim 1, characterized in that: The mass fractions of each component are: pinocembrin 11.11%, Pluronic F-127 55.56%, vitamin E polyethylene glycol succinate 33.33%.

3. The pinocembrin polymer micelle for treating hyperuricemia according to claim 1, characterized in that: The particle size of the polymer micelle is 25 - 40 nm, the polydispersity index is between 0.105 - 0.184, and the encapsulation efficiency is above 90%.

4. A method for preparing the pinocembrin polymer micelle for treating hyperuricemia according to any one of claims 1 to 3, characterized in that it includes the following steps: (1) Weigh pinocembrin, Pluronic F-127 and vitamin E polyethylene glycol succinate according to the proportion of the components, and completely dissolve them in an organic solvent under ultrasonic assistance to serve as the continuous phase for preparing the pinocembrin polymer micelle; double-distilled water is the dispersed phase; (2) Place the prepared continuous phase and dispersed phase in syringes respectively, place the syringes on two calibrated constant flow pumps respectively, connect them to a microfluidic chip through a catheter, and control the flow rates of the two phases to prepare the pinocembrin polymer micelle.

5. The preparation method according to claim 4, characterized in that: The flow rate ratio of the continuous phase to the dispersed phase is 1:1 - 10.

6. The preparation method according to claim 4, characterized in that: In the catheter, the dispersed phase is injected from the middle channel, and the continuous phase is injected from the two side channels. The symmetric continuous phases shear the dispersed phase to form droplets.

Citation Information

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