Method for improving water solubility of silybum marianum

Abstract

The method for improving the water solubility of silybum marianum comprises the following steps: S1, grinding silybum marianum fruits into powder, and dissolving and extracting through a degreasing solvent to obtain silybum marianum powder; s2, selecting a dissolving solvent, dissolving the silybum marianum powder in the dissolving solvent, and stirring and mixing to obtain a silybum marianum solution; s3, the silybum marianum solution is subjected to nanocrystallization treatment, and silybin is degraded into nanoparticles; and S4, adding a hydrophilic material into the nano-crystallized silybum marianum solution to obtain the water-solubility-improved silybum marianum solution. By improving the water solubility of the silybum marianum, the absorption and bioavailability of a subsequent preparation are facilitated, and the health-care effect of the silybum marianum is enhanced.

Description

Technical Field

[0001] This invention belongs to the pharmaceutical field, and in particular relates to a method for improving the water solubility of milk thistle. Background Technology

[0002] Milk thistle is an annual or biennial herbaceous plant belonging to the genus *Silybum* in the family Asteraceae. Native to southern Europe and North Africa, it is now widely distributed throughout many parts of my country. Its fruit is rich in various active ingredients and has important applications in the pharmaceutical field.

[0003] In recent years, scientific research has shown that the active ingredients in milk thistle are beneficial to various health conditions, especially for the treatment of liver diseases. It is believed to possess antioxidant, anti-inflammatory, and protective properties against toxins in liver cell membranes. Furthermore, milk thistle has been studied as an adjunct treatment for various liver-related diseases, including chronic liver disease, alcoholic liver disease, cirrhosis, and non-alcoholic fatty liver disease. In addition to its liver-protective effects, milk thistle has also shown potential against certain cancer cell lines, primarily due to its antioxidant properties and ability to regulate cell growth.

[0004] Silymarin is the main active ingredient of silymarin and a key substance for its hepatoprotective effects. However, silymarin is a poorly soluble compound with extremely low solubility in water. This characteristic severely affects its bioavailability, resulting in slow and incomplete absorption in the body. During formulation development, low water solubility makes it difficult to achieve effective blood concentrations, which not only reduces the therapeutic effect but also limits the application of silymarin in more dosage forms and routes of administration, significantly hindering the further development and clinical application of silymarin-based drugs. Summary of the Invention

[0005] The purpose of this invention is to provide a method for improving the water solubility of milk thistle, so as to solve the technical problem of low water solubility of silybin.

[0006] To achieve the above objectives, the specific technical solution of the method for improving the water solubility of milk thistle according to the present invention is as follows:

[0007] A method for improving the water solubility of milk thistle includes the following steps:

[0008] S1. Grind milk thistle fruit into powder, and then extract it by dissolving it with a defatting solvent to obtain milk thistle powder;

[0009] S2. Select a solvent, dissolve milk thistle powder in the solvent, stir and mix to obtain milk thistle solution;

[0010] S3. Nanoparticle processing is performed on the milk thistle solution to degrade silybin into nanoparticles;

[0011] S4. Add a hydrophilic material to the milk thistle solution after nano-processing to obtain a milk thistle solution with improved water solubility.

[0012] As a further improvement of the present invention, in S1, milk thistle fruit is ground into powder, added to an extractor, and petroleum ether is used as a defatting solvent. The powder is then refluxed at 70-75°C for 4-6 hours to defatt it. After recovering the solvent, the residue is dried to obtain defatted milk thistle powder.

[0013] As a further improvement of the present invention, the solvent in S2 is ethanol, and milk thistle powder and ethanol are mixed at a mass-volume ratio of 1:(5-20)g / mL, and stirred at 50-60℃ and 300-600r / min for 3-4 hours.

[0014] As a further improvement of the present invention, the solvent in S2 is propylene glycol, and milk thistle powder and propylene glycol are mixed at a mass-volume ratio of 1:(5-20)g / mL, and stirred at 60-70℃ and 300-600r / min for 3-4 hours.

[0015] As a further improvement of the present invention, the nano-sizing treatment in S3 is a high-pressure homogenization treatment, in which a high-pressure homogenizer is used to pass the milk thistle solution through the gap of the homogenization valve at a pressure of 150-250 MPa for 40-60 minutes.

[0016] As a further improvement of the present invention, the nano-sizing process in S3 is ultrasonic processing, which is performed at an ultrasonic frequency of 30-40 kHz for 60-90 minutes, with a working time of 3-5 seconds and an interval of 2-3 seconds.

[0017] As a further improvement of the present invention, the hydrophilic material in S4 is a cyclodextrin solution with a mass concentration of 15-20%. The cyclodextrin solution and the silymarin solution are mixed at a mass ratio of (2-4):1 and stirred at a speed of 150-200 r / min for 10-15 minutes. Then the temperature is raised to 30-35°C and stirred at a speed of 250-350 r / min for 20-30 minutes. Finally, the stirring speed is reduced to 120-150 rpm and stirred for 10-15 minutes.

[0018] As a further improvement of the present invention, the cyclodextrin is one or more of α-cyclodextrin, β-cyclodextrin or γ-cyclodextrin.

[0019] As a further improvement of the present invention, the hydrophilic material in S4 is one or more of cyclodextrin, polyethylene glycol, polyvinylpyrrolidone, and hydroxypropyl methylcellulose.

[0020] Beneficial effects:

[0021] In step S1, the method for improving the water solubility of milk thistle in this invention involves grinding milk thistle fruit into powder and defatting it to effectively remove impurities such as oil from the fruit, avoiding interference from impurities in subsequent silybin extraction and water solubility improvement, thereby increasing the purity of silybin and laying a good foundation for subsequent processes. In step S2, a suitable solvent is selected to fully dissolve the milk thistle powder, and stirring and mixing are carried out to promote the full dissolution of silybin, ensuring the full release of the active ingredient and providing sufficient raw materials for subsequent water solubility improvement. In step S3, the nano-sizing treatment degrades silybin into nanoparticles, significantly increasing its specific surface area. According to the principle of material dissolution, the increase in specific surface area significantly improves the dispersibility and dissolution rate of silybin in water. In step S4, a hydrophilic material is added to form a stable complex with silybin, further improving the solubility and stability of silybin in water, allowing silybin to be better dispersed in the aqueous solution, thereby significantly improving the water solubility of milk thistle. Through the synergistic effect of the above series of steps, not only is the bioavailability of silymarin improved, but it also provides the possibility for the development of more efficient silymarin-related drug formulations, which has important application value and broad market prospects in the pharmaceutical field. Detailed Implementation

[0022] To better understand the purpose, structure, and function of this invention, a method for improving the water solubility of milk thistle is described in further detail.

[0023] Implementation example:

[0024] A method for improving the water solubility of milk thistle involves grinding milk thistle fruit into powder, dissolving and extracting it with a defatting solvent to obtain milk thistle powder; dissolving the milk thistle powder in a solvent and stirring to mix; then, through nano-processing, degrading silybin into nanoparticles; finally, adding a hydrophilic material, thereby obtaining a milk thistle solution with significantly improved water solubility. The specific steps are as follows:

[0025] Select mature, plump, and mold-free milk thistle fruits. Rinse the fruits with clean water to remove surface dust, mud, and other impurities. Place the washed fruits in a well-ventilated and dry place or in an oven, and dry them at 50℃ until the moisture content is below 5%, increasing the fruit's firmness for easier grinding. After drying, break the outer shell of the fruits to release the kernels. Grind the kernels in a grinder and sieve them to collect 50-mesh milk thistle powder. Unsieved particles are ground again. The resulting powder is placed in a filter paper tube and then placed in a Soxhlet extractor. Petroleum ether is added to the flask of the extractor as a solvent, with the solid-liquid ratio controlled at 1:8 to 1:10 g / mL. Reflux extraction is performed in a 70℃ constant temperature water bath. This temperature ensures good solubility of petroleum ether while avoiding the loss of active ingredients such as silybin due to excessive temperature. The extraction process lasts for 4 hours, during which petroleum ether continuously circulates in the extractor to fully dissolve and extract the oil components from the milk thistle powder until the extract becomes colorless and transparent, indicating that the oil extraction is essentially complete. After extraction, petroleum ether is recovered using a heating device for recycling, thus reducing production costs. The defatted milk thistle powder is placed in a vacuum drying oven and dried at 40°C to constant weight to remove residual petroleum ether and moisture, yielding defatted milk thistle powder.

[0026] According to the mass-volume ratio of milk thistle powder to 70% (v / v) ethanol solution (1:5 g / mL), slowly add the weighed milk thistle powder to the measured ethanol solution. During the addition process, turn on the stirrer and stir at a low speed of 100 rpm to initially disperse the powder and prevent clumping. Place the reaction vessel in a constant temperature water bath, controlling the temperature at 50–60°C to avoid excessively high temperatures that could cause rapid ethanol evaporation and decomposition of silybin. Gradually increase the stirring speed to 300 rpm and continue stirring for 3 hours to enhance the contact between the solvent and the milk thistle powder and accelerate the dissolution rate.

[0027] The amplitude transformer of the ultrasonic processor is vertically immersed in the milk thistle solution, with the immersion depth controlled at half the solution height. This depth range allows for a relatively uniform distribution of ultrasonic energy within the solution. The device is then turned on, and parameters such as ultrasonic power, time, and pulse mode are set. Initially, the ultrasonic power can be set to 400W, the ultrasonic frequency to 30kHz, the ultrasonic time to 60 minutes, and the pulse mode to a 3-second on-time followed by a 2-second pause. This pulse mode ensures the effectiveness of the ultrasonic action while also preventing the solution from overheating due to prolonged continuous ultrasonication. During operation, the device utilizes the cavitation effect and mechanical vibration generated by the ultrasonic waves to break down the milk thistle particles, gradually reducing their size to the nanometer level. During the treatment process, the solution is stirred every 10 minutes at a speed of 100 rpm. This helps the particles in the solution receive uniform ultrasonic treatment, preventing over- or under-treatment in certain areas. After processing, a 0.22μm filter membrane can be used for filtration. This pore size of the filter membrane can effectively intercept large particles, while allowing nano-sized silymarin particles to pass through smoothly, thus obtaining a relatively pure nano-sized solution.

[0028] Slowly pour a 20% (w / w) cyclodextrin solution into the nano-sized milk thistle solution, adding it slowly along the container wall to avoid excessive foaming. Maintain a cyclodextrin to silybin mass ratio of 4:1. After adding the cyclodextrin solution, stir at 200 rpm for 15 minutes to ensure initial homogeneity. Then, slightly increase the temperature to 30°C and increase the stirring speed to 300 rpm, continuing stirring for 30-60 minutes to promote thorough inclusion of cyclodextrin and silybin. Temperature control helps prevent turbidity or flocculent formation. After the inclusion reaction is complete, reduce the stirring speed to 120 rpm and continue stirring for 10 minutes to stabilize the solution and prevent aggregation and precipitation of the inclusion complex. After mixing, allow the solution to stand for 20-30 minutes to allow any bubbles generated during stirring to escape naturally.

[0029] The water-soluble milk thistle solution, improved by the method of this invention, can be used in the pharmaceutical field to formulate oral preparations such as oral liquids, capsules, and tablets. Its high water solubility accelerates the dissolution and absorption of drugs in the body, significantly improving bioavailability and thus enhancing the therapeutic effect on liver diseases such as acute and chronic hepatitis and cirrhosis. When developed into injectable formulations, its excellent water solubility ensures that the drug can directly enter the bloodstream, quickly reach the lesion, effectively shorten the onset time, and buy precious treatment opportunities for patients with critical conditions. In the health supplement field, when added to functional beverages, it not only endows the product with liver-protecting and health-promoting functions, but also ensures uniform dispersion of ingredients due to its high water solubility, preventing precipitation, stratification, and other phenomena that affect product quality. When formulated into gummy candies, jellies, and other nutritional supplements, it improves taste and appearance, and its water solubility makes the active ingredients easier for the body to absorb, meeting consumers' daily needs for convenient health maintenance. In the cosmetics industry, when added to skincare products, silymarin's high water solubility allows it to penetrate deeper into all layers of the skin, fully exerting its antioxidant and other effects. This effectively combats skin aging, repairs damaged cells, and enhances skincare results, providing consumers with a superior skincare experience and offering cosmetic brands a unique competitive advantage.

[0030] The method of this invention uses petroleum ether to extract and defatt the fruit of milk thistle through heating and reflux during the raw material processing stage. This process can accurately remove impurities such as oils, effectively avoiding their interference with subsequent silybin extraction and dissolution, significantly improving the purity of silybin and laying a solid foundation for improving water solubility. By using specific mass-volume ratios of the dissolving solvent, mixing temperatures, and stirring conditions, silybin can be fully dissolved, ensuring high-concentration extraction of the active ingredient and providing a high-quality solution system for subsequent processes. The nano-processing stage degrades silybin into nanoparticles, greatly increasing its specific surface area and significantly improving its dispersibility and dissolution rate in water, effectively improving the solubility of silybin. By adding hydrophilic materials to form stable complexes with silybin, its solubility and stability in water are further improved. In particular, the unique inclusion effect of cyclodextrin can significantly improve the water solubility of silybin.

[0031] It is understood that the present invention has been described through some embodiments, and those skilled in the art will recognize that various changes or equivalent substitutions can be made to these features and embodiments without departing from the spirit and scope of the invention. Furthermore, under the teachings of the present invention, these features and embodiments can be modified to adapt to specific situations and materials without departing from the spirit and scope of the invention. Therefore, the present invention is not limited to the specific embodiments disclosed herein, and all embodiments falling within the scope of the claims of this application are within the protection scope of the present invention.

Claims

1. A method for improving the water solubility of milk thistle, characterized in that, Includes the following steps: S1. Grind milk thistle fruit into powder, and then extract it by dissolving and extracting it with a defatting solvent to obtain milk thistle powder; S2. Select a solvent, dissolve milk thistle powder in the solvent, stir and mix to obtain milk thistle solution; S3. Nanoparticle processing is performed on the milk thistle solution to degrade silybin into nanoparticles; S4. Add a hydrophilic material to the milk thistle solution after nano-processing to obtain a milk thistle solution with improved water solubility.

2. The method for improving the water solubility of milk thistle according to claim 1, characterized in that, S1 milk thistle fruit was ground into powder, added to an extractor, and extracted by reflux at 70-75℃ for 4-6 hours using petroleum ether as the defatting solvent. After solvent recovery, the residue was dried to obtain defatted milk thistle powder.

3. The method for improving the water solubility of milk thistle according to claim 1, characterized in that, In S2, the solvent is ethanol. Milk thistle powder and ethanol are mixed at a mass-volume ratio of 1:(5~20)g / mL and stirred at 50~60℃ and 300~600r / min for 3~4 hours.

4. The method for improving the water solubility of milk thistle according to claim 1, characterized in that, In S2, the solvent is propylene glycol. Milk thistle powder and propylene glycol are mixed at a mass-to-volume ratio of 1:(5-20) g / mL and stirred at 60-70℃ and 300-600 r / min for 3-4 hours.

5. The method for improving the water solubility of milk thistle according to claim 1, characterized in that, The nano-sizing process in S3 is a high-pressure homogenization process, in which a high-pressure homogenizer is used to pass the milk thistle solution through the gap of the homogenization valve at a pressure of 150-250 MPa for 40-60 minutes.

6. The method for improving the water solubility of milk thistle according to claim 1, characterized in that, The nano-sizing process in S3 is ultrasonic processing, which is performed at an ultrasonic frequency of 30-40kHz for 60-90 minutes, with a working time of 3-5 seconds and an interval of 2-3 seconds.

7. The method for improving the water solubility of milk thistle according to claim 1, characterized in that, The hydrophilic material in S4 is a cyclodextrin solution with a mass concentration of 15-20%. The cyclodextrin solution and silymarin solution are mixed at a mass ratio of (2-4):1 and stirred at a speed of 150-200 r / min for 10-15 minutes. Then heat to 30-35℃ and stir at 250-350 rpm for 20-30 minutes; finally reduce the stirring speed to 120-150 rpm and stir for 10-15 minutes.

8. The method for improving the water solubility of milk thistle according to claim 7, characterized in that, Cyclodextrin is one or more of α-cyclodextrin, β-cyclodextrin, or γ-cyclodextrin.

9. The method for improving the water solubility of milk thistle according to claim 1, characterized in that, The hydrophilic material in S4 is one or more of cyclodextrin, polyethylene glycol, polyvinylpyrrolidone, and hydroxypropyl methylcellulose.