Method for preparing traditional chinese medicine nano-micelle formulation encapsulating hesperidin

WO2025162512A3PCT designated stage Publication Date: 2026-03-05CANCER CENT OF GUANGZHOU MEDICAL UNIV
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Patent Information

Authority / Receiving Office
WO · WO
Patent Type
Applications
Current Assignee / Owner
Filing Date
2025-04-21
Publication Date
2026-03-05

AI Technical Summary

Technical Problem

The preparation methods of existing nano micelle preparations are complex and costly, resulting in low solubility of hesperidin in vivo, affecting its bioavailability and clinical application effect.

Method used

A Chinese medicine nano micelle preparation containing hesperidin was prepared by stirring, dropping, rotary evaporation and ultrafiltration, which was prepared by forming a nano-scale micelle structure.

Benefits of technology

It significantly improves the solubility and stability of hesperidin in water, enhances the absorption and distribution of drugs in the body, and improves bioavailability and therapeutic effects.

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Abstract

The present invention belongs to the technical field of pharmaceutical formulations. Specifically, provided is a method for preparing a traditional Chinese medicine nano-micelle formulation encapsulating hesperidin. The specific steps and process of the method for preparing the traditional Chinese medicine nano-micelle formulation encapsulating hesperidin are as follows: a polyethylene glycol-polylactic acid block copolymer, hesperidin, dichloromethane and poloxamer 188 are selected for later use. According to the present application, the traditional Chinese medicine nano-micelle formulation encapsulating hesperidin is prepared by means of mixing the polyethylene glycol-polylactic acid block copolymer, hesperidin, dichloromethane and poloxamer 188. The preparation process is simple and involves single raw material selection, such that the production cost is effectively controlled. The preparation method is suitable for industrial large-scale production and can be widely used in clinical practice.
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Description

Preparation method of hesperidin-encapsulated traditional Chinese medicine nano-micelle preparation Technical Field

[0001] The present invention relates to the technical field of pharmaceutical preparations, in particular to a method for preparing a hesperidin-encapsulated traditional Chinese medicine nano-micelle preparation. Background Art

[0002] Nanomicelles are a nanoscale colloidal system formed by self-assembly of amphiphilic polymers in aqueous solution. Due to their unique core-shell structure, they exhibit good solubilization ability, stability, and potential targeting, making them an effective carrier for improving the bioavailability of poorly soluble drugs.

[0003] Hesperidin, a flavonoid extracted from the peel of citrus fruits such as dried tangerine peel (Chenpi), a traditional Chinese medicine, exhibits numerous significant pharmacological activities, including antioxidant, anti-inflammatory, antibacterial, lipid-lowering, and cardiovascular protective properties. However, hesperidin's poor water solubility significantly limits its dissolution, absorption, and distribution in the body, resulting in low bioavailability and severely impacting its clinical efficacy.

[0004] Encapsulating hesperidin in nanomicelles significantly improves its pharmacokinetic properties and enhances its therapeutic effect.

[0005] However, the current preparation methods of nanomicelle preparations have problems of complex processes and high costs, which have led to their inability to be widely used in clinical medicine in the future.

[0006] To this end, a method for preparing a hesperidin-loaded traditional Chinese medicine nano-micelle preparation is proposed to solve the above-mentioned problems. Summary of the Invention

[0007] The object of the present invention is to provide a method for preparing a hesperidin-encapsulated traditional Chinese medicine nano-micelle preparation to solve the problems raised in the above background technology.

[0008] To achieve the above-mentioned object, the present invention provides the following technical solution: a method for preparing a hesperidin-loaded traditional Chinese medicine nano-micelle preparation, wherein the specific steps of the method for preparing the hesperidin-loaded traditional Chinese medicine nano-micelle preparation are as follows:

[0009] Step 1: Prepare polyethylene glycol-polylactic acid block copolymer, hesperidin, dichloromethane and poloxamer 188 for later use;

[0010] Step 2: Using an electronic balance, weigh 180-220 mg of the polyethylene glycol-polylactic acid block copolymer and 45-55 mg of hesperidin, pour the mixture into a beaker, add 4-6 ml of dichloromethane to the beaker, place the beaker in a constant temperature water bath, set the temperature of the constant temperature water bath to 25° C., and continuously stir the mixture in the beaker using a stirring device at a stirring speed of 180-220 r / min for 20 minutes until the polyethylene glycol-polylactic acid block copolymer and hesperidin are completely dissolved in the dichloromethane to form a clear and transparent organic solution;

[0011] Weigh 90-110 mg of Poloxamer 188 again and pour it into a beaker. Add 45-55 ml of deionized water to the beaker and stir using a stirring device to obtain a surfactant solution. Place the solution in a constant temperature water bath and maintain the solution temperature at 30°C for later use.

[0012] Step 3: The organic solution containing the polyethylene glycol-polylactic acid block copolymer and hesperidin is slowly added dropwise to a container containing the poloxamer 188 aqueous solution through a dropping funnel. During the addition, a stirring device is used to continuously mix and stir at a speed of 500 rpm to ensure that the organic solution and the aqueous phase are fully mixed. After the addition is completed, stirring is continued for 50-60 minutes to promote the self-assembly of the amphiphilic polyethylene glycol-polylactic acid block copolymer in the aqueous solution, encapsulating the hesperidin therein to form a nanomicelle structure;

[0013] Step 4: Transfer the mixed solution containing the nanomicelles to a flask of a rotary evaporator, set the vacuum degree of the rotary evaporator to 0.05 MPa, the temperature to 35-40°C, turn on the rotation and heating functions, and gradually evaporate the dichloromethane under reduced pressure. Continue the evaporation process until no obvious bubbles are generated in the system, remove the organic solvent, and obtain a preliminary nanomicelle solution;

[0014] Step 5: Pour the preliminary nanomicelle solution into the feed tank of the ultrafiltration device, select an ultrafiltration membrane with a molecular weight cutoff of 10,000, turn on the circulation pump of the ultrafiltration device, control the flow rate at 30-50 mL / min, and allow the solution to circulate and filter on the surface of the ultrafiltration membrane. Unencapsulated hesperidin, excess polyethylene glycol-polylactic acid block copolymer, and poloxamer 188 small molecules are removed through the ultrafiltration membrane, while the nanomicelles encapsulating hesperidin are retained above the ultrafiltration membrane. The ultrafiltration cycle is repeated 3-5 times, and an appropriate amount of deionized water is added after each ultrafiltration to ensure that impurities are fully removed. Finally, a purified traditional Chinese medicine nanomicelle preparation encapsulating hesperidin is obtained.

[0015] Preferably, in the step 1, the polyethylene glycol-polylactic acid block copolymer selected has a molecular weight of PEG in the range of 4000-6000 and a molecular weight of PLA in the range of 8000-12000.

[0016] Preferably, in step 1, the purity of hesperidin needs to be greater than 98%.

[0017] Preferably, in the step 3, the organic solution is added dropwise into the container containing the poloxamer 188 aqueous solution through a dropping funnel at a rate of 1-3 drops per second.

[0018] Preferably, after obtaining the hesperidin-encapsulated traditional Chinese medicine nano-micelle preparation, its particle size and particle size distribution need to be measured, its encapsulation efficiency and drug loading amount need to be measured, and its morphology needs to be observed.

[0019] Compared with the prior art, the present invention has the following beneficial effects:

[0020] The present application prepares a traditional Chinese medicine nano-micelle preparation encapsulating hesperidin by mixing polyethylene glycol-polylactic acid block copolymer, hesperidin, dichloromethane and poloxamer 188. The preparation process is simple and the raw material selection is single, thereby effectively controlling the production cost. The preparation is suitable for industrial large-scale production and can be used on a large scale in clinical practice. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] FIG1 is a schematic structural diagram of the present invention; DETAILED DESCRIPTION

[0022] The following will clearly and completely describe the technical solutions in the embodiments of the present invention in conjunction with the accompanying drawings. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without making creative efforts are within the scope of protection of the present invention.

[0023] In the description of the present invention, it should be understood that the terms "upper", "lower", "front", "back", "left", "right", "top", "bottom", "inside", "outside", etc., indicating directions or positional relationships, are based on the directions or positional relationships shown in the accompanying drawings, and are only for the convenience of describing the present invention and simplifying the description, rather than indicating or implying that the device or element referred to must have a specific direction, be constructed and operated in a specific direction, and therefore should not be understood as limiting the present invention.

[0024] Please refer to Figure 1, the present invention provides a technical solution:

[0025] A method for preparing a hesperidin-loaded traditional Chinese medicine nano-micelle preparation is provided. The specific steps of the method for preparing the hesperidin-loaded traditional Chinese medicine nano-micelle preparation are as follows:

[0026] Step 1: Prepare polyethylene glycol-polylactic acid block copolymer, hesperidin, dichloromethane and poloxamer 188 for later use;

[0027] Step 2: Using an electronic balance, weigh 180-220 mg of the polyethylene glycol-polylactic acid block copolymer and 45-55 mg of hesperidin, pour the mixture into a beaker, add 4-6 ml of dichloromethane to the beaker, place the beaker in a constant temperature water bath, set the temperature of the constant temperature water bath to 25° C., and continuously stir the mixture in the beaker using a stirring device at a stirring speed of 180-220 r / min for 20 minutes until the polyethylene glycol-polylactic acid block copolymer and hesperidin are completely dissolved in the dichloromethane to form a clear and transparent organic solution;

[0028] Weigh 90-110 mg of Poloxamer 188 again and pour it into a beaker. Add 45-55 ml of deionized water to the beaker and stir using a stirring device to obtain a surfactant solution. Place the solution in a constant temperature water bath and maintain the solution temperature at 30°C for later use.

[0029] Step 3: The organic solution containing the polyethylene glycol-polylactic acid block copolymer and hesperidin is slowly added dropwise to a container containing the poloxamer 188 aqueous solution through a dropping funnel. During the addition, a stirring device is used to continuously mix and stir at a speed of 500 rpm to ensure that the organic solution and the aqueous phase are fully mixed. After the addition is completed, stirring is continued for 50-60 minutes to promote the self-assembly of the amphiphilic polyethylene glycol-polylactic acid block copolymer in the aqueous solution, encapsulating the hesperidin therein to form a nanomicelle structure;

[0030] Step 4: Transfer the mixed solution containing the nanomicelles to a flask of a rotary evaporator, set the vacuum degree of the rotary evaporator to 0.05 MPa, the temperature to 35-40°C, turn on the rotation and heating functions, and gradually evaporate the dichloromethane under reduced pressure. Continue the evaporation process until no obvious bubbles are generated in the system, remove the organic solvent, and obtain a preliminary nanomicelle solution;

[0031] Step 5: Pour the preliminary nanomicelle solution into the feed tank of the ultrafiltration device, select an ultrafiltration membrane with a molecular weight cutoff of 10,000, turn on the circulation pump of the ultrafiltration device, control the flow rate at 30-50 mL / min, and allow the solution to circulate and filter on the surface of the ultrafiltration membrane. Unencapsulated hesperidin, excess polyethylene glycol-polylactic acid block copolymer, and poloxamer 188 small molecules are removed through the ultrafiltration membrane, while the nanomicelles encapsulating hesperidin are retained above the ultrafiltration membrane. The ultrafiltration cycle is repeated 3-5 times, and an appropriate amount of deionized water is added after each ultrafiltration to ensure that impurities are fully removed. Finally, a purified traditional Chinese medicine nanomicelle preparation encapsulating hesperidin is obtained.

[0032] This hesperidin-encapsulated TCM nanomicelle formulation can improve solubility. The hydrophobic core of the nanomicelles can encapsulate hesperidin, significantly increasing its solubility in water. Experimental data show that compared with the hesperidin API, the solubility of the hesperidin-encapsulated nanomicelle formulation in water can be increased by several times or even dozens of times. This facilitates the dissolution and absorption of the drug in the body, thereby improving its bioavailability.

[0033] Enhanced stability: Nanomicelles can provide a relatively stable microenvironment for hesperidin, reducing its contact with the external environment and slowing down the degradation rate of the drug. Under the same storage conditions, the content of hesperidin in the nanomicelle preparation encapsulated with hesperidin decreased significantly less than that of the hesperidin API over a certain period of time, indicating that nanomicelles can effectively enhance the stability of hesperidin.

[0034] Improved in vivo distribution: Nanomicelles have a small particle size and good tissue permeability and targeting properties. They can reach the lesion more easily through passive or active targeting, increasing the concentration of the drug in the lesion tissue and thus enhancing the therapeutic effect. For example, in some tumor model experiments, nanomicelle preparations containing anticancer drugs can be enriched in tumor tissue, enhancing the killing effect on tumor cells while reducing toxic side effects on normal tissues.

[0035] In the step 1, the polyethylene glycol-polylactic acid block copolymer is selected, wherein the molecular weight of PEG is 4000-6000, and the molecular weight of PLA is 8000-12000.

[0036] In the step 1, the purity of hesperidin needs to be greater than 98%.

[0037] In the step 3, the organic solution is added dropwise into the container containing the poloxamer 188 aqueous solution through a dropping funnel at a rate of 1-3 drops per second.

[0038] After obtaining the traditional Chinese medicine nano-micelle preparation encapsulating hesperidin, its particle size and particle size distribution need to be measured. The specific steps of the measurement are: take an appropriate amount of nano-micelle preparation, detect it with a dynamic light scattering instrument, inject the sample into the sample pool, set the detection temperature to 20-25°C, measure 3 times and take the average value, record the average particle size and particle size distribution index of the nano-micelles, and ensure that the average particle size is 70-90nm and the PDI is less than 0.2.

[0039] After obtaining the hesperidin-encapsulated traditional Chinese medicine nanomicelle preparation, its encapsulation efficiency and drug loading need to be measured. The specific steps of the measurement are as follows: using high-performance liquid chromatography, first prepare a hesperidin standard solution and establish a standard curve. Take a certain amount of nanomicelle preparation, break the emulsion with an appropriate amount of organic solvent, filter through a microporous filter membrane, and analyze the sample. The total amount of hesperidin in the sample is calculated based on the standard curve. Then, the amount of hesperidin encapsulated in the nanomicelles is calculated by the difference method, and the encapsulation efficiency and drug loading are then obtained. The encapsulation efficiency is required to be no less than 80%, and the drug loading is required to be 15-25%.

[0040] After obtaining the hesperidin-encapsulated traditional Chinese medicine nanomicelle preparation, its encapsulation efficiency and drug loading need to be measured. The specific steps of the measurement are as follows: using high-performance liquid chromatography, first prepare a hesperidin standard solution and establish a standard curve. Take a certain amount of nanomicelle preparation, break the emulsion with an appropriate amount of organic solvent, filter through a microporous filter membrane, and analyze the sample. The total amount of hesperidin in the sample is calculated based on the standard curve. Then, the amount of hesperidin encapsulated in the nanomicelles is calculated by the difference method, and the encapsulation efficiency and drug loading are then obtained. The encapsulation efficiency is required to be no less than 80%, and the drug loading is required to be 15-25%.

[0041] In order to ensure the quality and effectiveness of hesperidin-encapsulated TCM nanomicelle preparations, a comprehensive quality evaluation is required;

[0042] The main evaluation indicators include:

[0043] Particle size and particle size distribution: Dynamic light scattering (DLS) technology is used to determine the particle size and particle size distribution of nanomicelles. The appropriate particle size range and narrow particle size distribution have a significant impact on the stability, in vivo distribution and efficacy of nanomicelle preparations;

[0044] Morphological observation: Observe the morphology of the nanomicelles using transmission electron microscopy (TEM) or scanning electron microscopy (SEM) to see whether they are regular spherical or other expected morphologies;

[0045] Drug encapsulation efficiency and drug loading: The high performance liquid chromatography (HPLC) method was used to determine the hesperidin content in the nanomicelles, and the drug encapsulation efficiency (the percentage of the amount of drug encapsulated in the nanomicelles to the total amount of drug input) and drug loading (the mass of the drug contained in the nanomicelles to the percentage of the total mass of the nanomicelles) were calculated. Higher encapsulation efficiency and drug loading are beneficial to improving the efficacy of the drug and reducing drug waste.

[0046] Example 1:

[0047] The specific steps of the preparation method of the hesperidin-loaded traditional Chinese medicine nano-micelle preparation are as follows:

[0048] Step 1: Prepare polyethylene glycol-polylactic acid block copolymer, hesperidin, dichloromethane and poloxamer 188 for later use;

[0049] Step 2: Using an electronic balance, weigh 180 mg of polyethylene glycol-polylactic acid block copolymer and 45 mg of hesperidin, pour them into a beaker, add 4 ml of dichloromethane to the beaker, place the beaker in a constant temperature water bath, set the temperature of the constant temperature water bath to 25° C., and use a stirring device to continuously stir the mixture in the beaker at a stirring speed of 180 r / min for 20 minutes until the polyethylene glycol-polylactic acid block copolymer and hesperidin are completely dissolved in the dichloromethane to form a clear and transparent organic solution;

[0050] Weigh 90 mg of Poloxamer 188 again and pour it into the beaker. Add 45 ml of deionized water to the beaker and stir using a stirring device to obtain a surfactant solution. Place the solution in a constant temperature water bath and maintain the solution temperature at 30°C for later use.

[0051] Step 3: The organic solution containing the polyethylene glycol-polylactic acid block copolymer and hesperidin is slowly added dropwise to a container containing the poloxamer 188 aqueous solution through a dropping funnel. During the addition, a stirring device is used to continuously mix and stir at a speed of 500 r / min to ensure that the organic solution and the aqueous phase are fully mixed. After the addition is completed, stirring is continued for 50 minutes to promote the self-assembly of the amphiphilic polyethylene glycol-polylactic acid block copolymer in the aqueous solution, encapsulating the hesperidin therein to form a nanomicelle structure;

[0052] Step 4: Transfer the mixed solution containing the nanomicelles to a flask of a rotary evaporator, set the vacuum degree of the rotary evaporator to 0.05 MPa and the temperature to 35°C, turn on the rotation and heating functions, and gradually evaporate the dichloromethane under reduced pressure. Continue the evaporation process until no obvious bubbles are generated in the system, remove the organic solvent, and obtain a preliminary nanomicelle solution;

[0053] Step 5: Pour the preliminary nanomicelle solution into the feed tank of the ultrafiltration device, select an ultrafiltration membrane with a molecular weight cutoff of 10,000, turn on the circulation pump of the ultrafiltration device, control the flow rate at 30 mL / min, and allow the solution to circulate and filter on the surface of the ultrafiltration membrane. Unencapsulated hesperidin, excess polyethylene glycol-polylactic acid block copolymer, and poloxamer 188 small molecules are removed through the ultrafiltration membrane, while the nanomicelles encapsulating hesperidin are retained above the ultrafiltration membrane. The ultrafiltration cycle is repeated three times, and an appropriate amount of deionized water is added after each ultrafiltration to ensure sufficient removal of impurities. Finally, a purified traditional Chinese medicine nanomicelle preparation encapsulating hesperidin is obtained.

[0054] Example 2:

[0055] The specific steps of the preparation method of the hesperidin-loaded traditional Chinese medicine nano-micelle preparation are as follows:

[0056] Step 1: Prepare polyethylene glycol-polylactic acid block copolymer, hesperidin, dichloromethane and poloxamer 188 for later use;

[0057] Step 2: Using an electronic balance, weigh 220 mg of polyethylene glycol-polylactic acid block copolymer and 45-55 mg of hesperidin, pour them into a beaker, add 6 ml of dichloromethane to the beaker, place the beaker in a constant temperature water bath, set the temperature of the constant temperature water bath to 25° C., and use a stirring device to continuously stir the mixture in the beaker at a stirring speed of 220 r / min for 20 minutes until the polyethylene glycol-polylactic acid block copolymer and hesperidin are completely dissolved in the dichloromethane to form a clear and transparent organic solution;

[0058] Weigh 110 mg of Poloxamer 188 again and pour it into the beaker. Add 55 ml of deionized water to the beaker and stir using a stirring device to obtain a surfactant solution. Place the solution in a constant temperature water bath and maintain the solution temperature at 30°C for later use.

[0059] Step 3: The organic solution containing the polyethylene glycol-polylactic acid block copolymer and hesperidin is slowly added dropwise to a container containing the poloxamer 188 aqueous solution through a dropping funnel. During the addition, a stirring device is used to continuously mix and stir at a speed of 500 r / min to ensure that the organic solution and the aqueous phase are fully mixed. After the addition is completed, stirring is continued for 60 minutes to promote the self-assembly of the amphiphilic polyethylene glycol-polylactic acid block copolymer in the aqueous solution, encapsulating the hesperidin therein to form a nanomicelle structure;

[0060] Step 4: Transfer the mixed solution containing the nanomicelles to a flask of a rotary evaporator, set the vacuum degree of the rotary evaporator to 0.05 MPa and the temperature to 40°C, turn on the rotation and heating functions, and gradually evaporate the dichloromethane under reduced pressure. Continue the evaporation process until no obvious bubbles are generated in the system, remove the organic solvent, and obtain a preliminary nanomicelle solution;

[0061] Step 5: Pour the preliminary nanomicelle solution into the feed tank of the ultrafiltration device, select an ultrafiltration membrane with a molecular weight cutoff of 10,000, turn on the circulation pump of the ultrafiltration device, control the flow rate at 50 mL / min, and allow the solution to circulate and filter on the surface of the ultrafiltration membrane. Unencapsulated hesperidin, excess polyethylene glycol-polylactic acid block copolymer, and poloxamer 188 small molecules are removed through the ultrafiltration membrane, while the nanomicelles encapsulating hesperidin are retained above the ultrafiltration membrane. The ultrafiltration cycle is repeated 5 times, and an appropriate amount of deionized water is added after each ultrafiltration to ensure that impurities are fully removed. Finally, a purified traditional Chinese medicine nanomicelle preparation encapsulating hesperidin is obtained.

[0062] The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention. For those skilled in the art, it is obvious that the present invention is not limited to the details of the above exemplary embodiments, and the present invention can be implemented in other specific forms without departing from the spirit or basic characteristics of the present invention; therefore, no matter from which point of view, the embodiments should be regarded as exemplary and non-restrictive. The scope of the present invention is limited by the appended claims rather than the above description. Therefore, it is intended that all changes that fall within the meaning and scope of the equivalent elements of the claims are included in the present invention, and any figure signs in the claims should not be regarded as limiting the claims involved.

[0063] While embodiments of the present invention have been shown and described, it will be appreciated by those skilled in the art that various changes, modifications, substitutions, and variations may be made to these embodiments without departing from the principles and spirit of the invention, and that the scope of the invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing a traditional Chinese medicine nano-micelle preparation containing hesperidin, characterized in that: The specific steps of the preparation method of the hesperidin-loaded traditional Chinese medicine nano-micelle preparation are as follows: Step 1: Prepare polyethylene glycol-polylactic acid block copolymer, hesperidin, dichloromethane and poloxamer 188 for later use; Step 2: Using an electronic balance, weigh 180-220 mg of the polyethylene glycol-polylactic acid block copolymer and 45-55 mg of hesperidin, pour the mixture into a beaker, add 4-6 ml of dichloromethane to the beaker, place the beaker in a constant temperature water bath, set the temperature of the constant temperature water bath to 25° C., and continuously stir the mixture in the beaker using a stirring device at a stirring speed of 180-220 r / min for 20 minutes until the polyethylene glycol-polylactic acid block copolymer and hesperidin are completely dissolved in the dichloromethane to form a clear and transparent organic solution; Weigh 90-110 mg of Poloxamer 188 again and pour it into a beaker. Add 45-55 ml of deionized water to the beaker and stir using a stirring device to obtain a surfactant solution. Place the solution in a constant temperature water bath and maintain the solution temperature at 30°C for later use. Step 3: The organic solution containing the polyethylene glycol-polylactic acid block copolymer and hesperidin is slowly added dropwise to a container containing the poloxamer 188 aqueous solution through a dropping funnel. During the addition, a stirring device is used to continuously mix and stir at a speed of 500 rpm to ensure that the organic solution and the aqueous phase are fully mixed. After the addition is completed, stirring is continued for 50-60 minutes to promote the self-assembly of the amphiphilic polyethylene glycol-polylactic acid block copolymer in the aqueous solution, encapsulating the hesperidin therein to form a nanomicelle structure; Step 4: Transfer the mixed solution containing the nanomicelles to a flask of a rotary evaporator, set the vacuum degree of the rotary evaporator to 0.05 MPa, the temperature to 35-40°C, turn on the rotation and heating functions, and gradually evaporate the dichloromethane under reduced pressure. Continue the evaporation process until no obvious bubbles are generated in the system, remove the organic solvent, and obtain a preliminary nanomicelle solution; Step 5: Pour the preliminary nanomicelle solution into the feed tank of the ultrafiltration device, select an ultrafiltration membrane with a molecular weight cutoff of 10,000, turn on the circulation pump of the ultrafiltration device, control the flow rate at 30-50 mL / min, and allow the solution to circulate and filter on the surface of the ultrafiltration membrane. Unencapsulated hesperidin, excess polyethylene glycol-polylactic acid block copolymer, and poloxamer 188 small molecules are removed through the ultrafiltration membrane, while the nanomicelles encapsulating hesperidin are retained above the ultrafiltration membrane. The ultrafiltration cycle is repeated 3-5 times, and an appropriate amount of deionized water is added after each ultrafiltration to ensure that impurities are fully removed. Finally, a purified traditional Chinese medicine nanomicelle preparation encapsulating hesperidin is obtained.

2. The method for preparing a hesperidin-loaded traditional Chinese medicine nano-micelle preparation according to claim 1, characterized in that: In the step 1, the polyethylene glycol-polylactic acid block copolymer is selected, wherein the molecular weight of PEG is 4000-6000, and the molecular weight of PLA is 8000-12000.

3. The method for preparing a hesperidin-loaded traditional Chinese medicine nano-micelle preparation according to claim 1, characterized in that: In the step 1, the purity of hesperidin needs to be greater than 98%.

4. The method for preparing a hesperidin-loaded traditional Chinese medicine nano-micelle preparation according to claim 1, characterized in that: In the step 3, the organic solution is added dropwise into the container containing the poloxamer 188 aqueous solution through a dropping funnel at a rate of 1-3 drops per second.

5. The method for preparing a hesperidin-loaded traditional Chinese medicine nano-micelle preparation according to claim 1, characterized in that: After obtaining the hesperidin-encapsulated traditional Chinese medicine nano-micelle preparation, its particle size and particle size distribution need to be measured, its encapsulation efficiency and drug loading amount need to be measured, and its morphology needs to be observed.

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