Large-particle diosmin prepared based on crystallization regulating agent as well as preparation method and application of large-particle diosmin

Abstract

The invention discloses large-particle diosmin prepared based on a crystallization regulating agent and a method and application thereof, and relates to the technical field of diosmin synthesis, the method comprises the following steps: S1, dissolving diosmin in a sodium hydroxide aqueous solution, and adding hydrochloric acid to adjust the pH value of the solution to 10-11; s2, adding a crystallization regulator, namely polyvinylpyrrolidone, with the use amount of the crystallization regulator being 0.01%-0.1% of the weight of diosmin, stirring, and uniformly mixing; s3, hydrochloric acid is added, the pH value of a solution system is adjusted to be 6-7, stirring is conducted, diosmin is separated out, centrifugation and washing crystallization are conducted, crystals separated out after washing are dried, a large-particle diosmin finished product is obtained, the particle size of the obtained large-particle diosmin is increased by 2-4 times, the repose angle is optimized to be 30-35 degrees, and the large-particle diosmin is obviously superior to 40-45 degrees of a traditional technology, and the large-particle diosmin is obtained. The technical bottlenecks of small diosmin particle size and poor powder fluidity in the traditional process are effectively broken through.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of dioxadromine synthesis, in particular to a large-particle dioxadromine prepared based on a crystallization regulator and a method and application thereof. BACKGROUND

[0002] Dioxadromine, as a natural flavonoid compound, is an active ingredient with clear pharmacological effects and health functions. Its core mechanism of action is multiple vascular protection: it enhances venous tension by prolonging the contraction time of adrenaline on the venous wall, reduces body fluid leakage by reducing capillary permeability and improving structural stability, and improves lymphatic return and reduces tissue edema by accelerating lymphatic drainage and enhancing lymphatic contraction. Based on the above pharmacological activities, dioxadromine has become a key drug ingredient for treating chronic venous insufficiency, acute hemorrhoids and other diseases in the medical field. At the same time, its unique advantages of improving microcirculation and enhancing vascular elasticity have also been widely recognized in the health product field, and the market demand continues to grow.

[0003] However, the special physicochemical properties of dioxadromine, especially its extremely narrow solubility window, have brought significant technical bottlenecks to its industrial-scale production. Experimental verification shows that dioxadromine only has solubility in dimethyl sulfoxide, is completely insoluble in water, methanol, ethanol and other commonly used solvents, is slightly soluble in 0.1 mol / L sodium hydroxide solution, and is almost insoluble in 0.1 mol / L hydrochloric acid solution. This solubility characteristic determines that the existing industrial preparation process generally relies on alkaline dissolution and acid precipitation crystallization method, but this method has a core defect - the particle size of the obtained dioxadromine product is generally too fine, which in turn causes a series of production and application problems. In the prior art, for example, the patent application with publication number "CN117069778A" and title "Dioxadromine preparation process" published on November 17, 2023, mentions dissolving the raw material with sodium hydroxide solution, adjusting the pH of the system to 8-9 with hydrochloric acid to precipitate the solid, and obtaining dioxadromine crude product by pressure filtration. The dioxadromine crystals obtained by this process are very small in size, and the filtration process is slow and the filter cloth is easily clogged, significantly reducing production efficiency.

[0004] In summary, the technical problems caused by fine particle size in the production process of dioxadromine mainly include the following three aspects: First, the filtration efficiency is low, and the fine crystals are easily attached and clog the pores of the filter material, resulting in a significant extension of the filtration period, which not only increases the labor intensity of operation, but also significantly increases the energy consumption of production; Second, the drying cost is high, the specific surface area of fine particle crystals is large, the residual moisture of the filter cake is usually more than 50%, more energy is consumed and the drying time is prolonged, and the related energy consumption accounts for 35-40% of the total production cost, which seriously affects the economic efficiency of production; Thirdly, the application of health care products is limited, and the production of health care products has strict requirements for the flowability, filling uniformity and storage stability of raw materials. Large particle size raw materials need to be used to ensure the quality of subsequent preparations. However, the existing process products cannot directly meet the requirements, and additional subsequent treatment processes such as granulation or coating are required, which not only increases the production cost, but also may affect the stability of active ingredients.

[0005] In summary, the current preparation method of dioxybenzone cannot effectively solve the problems of filtering difficulty caused by small particle size, high energy consumption, limited application range and the like, especially cannot meet the special requirements of large particle size and high flowability of raw materials in the field of health care products and pharmaceuticals. Therefore, developing a preparation method capable of precisely controlling the particle size of dioxybenzone crystals while considering production efficiency and product quality has important technical value and broad market prospects for breaking through the bottleneck of existing technology and improving industrial competitiveness. SUMMARY

[0006] The purpose of the present application is to solve the problems of slow filtering, easy clogging of filter cloth and low production efficiency in the filtering process of the dioxybenzone crystals obtained by the existing preparation method of dioxybenzone, and to provide a large particle dioxybenzone and a preparation method and application thereof based on a crystallization regulator.

[0007] The present application is realized by the following technical solutions: A method for preparing large particle dioxybenzone based on a crystallization regulator, comprising the following steps: S1. Dissolving dioxybenzone in a sodium hydroxide aqueous solution, and adding hydrochloric acid to adjust the pH value of the solution to 10-11; S2. Adding a crystallization regulator, polyvinylpyrrolidone, the amount of which is 0.01%-0.1% of the weight of dioxybenzone, and stirring and mixing uniformly; S3. Adding hydrochloric acid to adjust the pH value of the solution system to 6-7, stirring, precipitating dioxybenzone, centrifuging and washing the crystals, and then drying the separated crystals after washing to obtain large particle dioxybenzone finished product.

[0008] In the present application, the crystallization regulator is preferably added at a pH value of 10-11. If the pH value is too high, the polyvinylpyrrolidone polymer may be degraded, which may affect its regulating effect. If the pH value is too low, it may promote the rapid precipitation of dioxybenzone, and the regulating effect of the crystallization regulator may be significantly weakened or even not play a regulating role.

[0009] Further, in step S2, the polyvinylpyrrolidone includes K30 and K25. In the present application, the most commonly used and versatile type (K30 and K25) of pharmaceutical PVP is used as the crystallization regulator, which is easy to obtain and safe.

[0010] In the present application, the amount of polyvinylpyrrolidone used is only 0.01% to 0.1% by weight of dioxadromine, and the residual amount is very small.

[0011] Further, in step S2, the stirring rate is 50 to 80 rpm, and the stirring time is 5 to 10 min.

[0012] Further, in step S3, the stirring rate is 50 to 80 rpm, and the stirring time is 30 to 60 min; the drying temperature is 110±10℃, and the moisture content in the filter cake is not higher than 6%.

[0013] A large particle dioxadromine prepared based on a crystallization regulator, which is prepared by the method as described above.

[0014] Further, the rest angle of the large particle dioxadromine is 30 to 35°.

[0015] The application of the large particle dioxadromine in the preparation of tablets, capsules, granules, powders and pills, wherein the large particle dioxadromine is the large particle dioxadromine with a rest angle of 30 to 35° as described above, or the large particle dioxadromine prepared by the method as described above, and no extra granulation is needed.

[0016] Compared with the prior art, the present application has the following advantages and beneficial effects: I. In the present application, a method for preparing large particle dioxadromine based on a crystallization regulator is proposed. In the preparation of dioxadromine powder product, by adding a specific high molecular polymer as a crystallization regulator, the relative ratio of crystal growth rate and nucleation rate is controlled, the nucleation rate is inhibited, and the crystal growth process is dominant, so that the particle size of dioxadromine is increased by 2 to 4 times, and the rest angle is optimized to 30 to 35°, which is significantly better than the 40 to 45° of the traditional process, effectively breaking through the technical bottleneck of small particle size and poor powder flowability of dioxadromine in the traditional process.

[0017] II. In the present application, a method for preparing large particle dioxadromine based on a crystallization regulator is proposed, which shortens the filtration time by 60% or more and reduces the drying energy consumption by 50% or more, significantly improves the centrifugal and filtration efficiency, optimizes the production process, and greatly reduces the industrial production cost.

[0018] Thirdly, this invention proposes a method for preparing large-particle diosmin based on a crystallization regulator. This method provides a preparation scheme for large-particle diosmin with controllable particle size, good flowability, and stable processing. The large-particle diosmin with controllable particle size, good flowability, and stable processing can be directly used in the production of diosmin-related dosage forms such as tablets, capsules, granules, powders, and pills without the need for additional granulation, showing broad application prospects. In Europe, the United States, and other regions, diosmin is also used as a dietary supplement. The large-particle diosmin prepared in this method is also beneficial for the application of diosmin in other fields such as dietary supplements and health products. Attached Figure Description

[0019] Figure 1 This is a particle size distribution diagram of diosmin in Example 1.

[0020] Figure 2 This is a particle size distribution diagram of diosmin in Comparative Example 1.

[0021] Figure 3 This is a picture of an angle of repose tester. Detailed Implementation

[0022] The present invention will be further described in detail below with reference to embodiments, but the implementation of the present invention is not limited thereto.

[0023] The present invention aims to provide a method for preparing large-particle diosmin based on a crystallization regulator. This process can significantly improve the particle size and powder flowability of diosmin products, while significantly improving the centrifugation efficiency in the production of diosmin and greatly reducing drying energy consumption.

[0024] In the following examples, PVP-K30 is used as an example of a crystallization regulator.

[0025] The detection methods and reference standards involved in the following embodiments are as follows: The angle of repose of diosmin powder was tested according to the 2025 edition of the Chinese Pharmacopoeia, 9604 Guidelines for Powder Flowability.

[0026] The method for detecting the angle of repose is as follows: The static angle of repose of diosmin powder is measured by the injection method. The powder is slowly added from above the funnel, allowing it to leak out from the bottom of the funnel under gravity, forming a conical accumulation on a horizontal surface. The angle of inclination is then read, which is the angle of repose of the powder. The detection device used in this invention is described below. Figure 3 .

[0027] The particle size of diosmin powder was determined using a laser particle size distribution analyzer (JL-177, manufacturer: Chengdu Jingxin Powder Testing Equipment Co., Ltd.). The testing method was as follows: The particle size analyzer was powered on and preheated for half an hour. An appropriate amount of water was added to the sample cell. A small amount of the sample was placed in a sample spoon, and a small amount of surfactant solution was added to wet it. The sample was then measured according to the particle size distribution testing operating procedure. (Dispersion medium: water; refractive index: 1.33)

[0028] Example 1 This embodiment proposes a method for preparing large-particle diosmin based on a crystallization regulator, including the following steps: S1. Dissolve 50 kg of diosmin in 250 L of a 4% sodium hydroxide aqueous solution and stir until completely dissolved. Then, add hydrochloric acid to adjust the pH of the solution to 11. S2. Add 5g of crystallization regulator—polyvinylpyrrolidone (which is 0.01% of the mass of diosmin), stir at 80 rpm for 10 minutes, and mix well. S3. Continue adding dilute hydrochloric acid of the aforementioned concentration to adjust the pH of the solution to 6-7. Stir at 80 rpm for 30 minutes to allow diosmin to fully crystallize. After the reaction is complete, centrifuge the mixture, rinse the filter cake with 100 L of water, and then dry it with hot air at 110 ± 10 °C for 5 hours until the moisture content is below 6%, thus obtaining the large-particle diosmin product.

[0029] The particle size of the large-particle diosmin product was then determined using a laser particle size distribution analyzer. The particle size distribution diagram is shown below. Figure 1 The cumulative volumetric size distribution (D90) of this particle is 103.348 μm.

[0030] The angle of repose of the large-particle diosmin product was tested to be 32°, indicating that its powder flow properties are excellent.

[0031] Example 2 This embodiment proposes a method for preparing large-particle diosmin based on a crystallization regulator, including the following steps: S1. Dissolve 50 kg of diosmin in 250 L of a 4% sodium hydroxide aqueous solution and stir until completely dissolved. Then, add hydrochloric acid to adjust the pH of the solution to 10.5. S2. Add 5g of crystallization regulator—polyvinylpyrrolidone (which is 0.01% of the mass of diosmin), stir at 80 rpm for 10 minutes, and mix well. S3. Continue adding dilute hydrochloric acid of the aforementioned concentration to adjust the pH of the solution to 6-7. Stir at 80 rpm for 60 minutes to allow diosmin to fully crystallize. After the reaction is complete, centrifuge the mixture, rinse the filter cake with 100 L of water, and then dry it with hot air at 110 ± 10 °C for 6 hours until the moisture content is below 6%, thus obtaining the large-particle diosmin product.

[0032] The cumulative volumetric particle size distribution (D90) of the large-particle diosmin product was then measured using a laser particle size distribution analyzer and found to be 103.378 μm.

[0033] The angle of repose of the large-particle diosmin product was tested to be 35°, indicating that its powder flow properties are excellent.

[0034] Example 3 This embodiment proposes a method for preparing large-particle diosmin based on a crystallization regulator, including the following steps: S1. Dissolve 50 kg of diosmin in 250 L of a 4% sodium hydroxide aqueous solution and stir until completely dissolved. Then, add hydrochloric acid to adjust the pH of the solution to 10. S2. Add 5g of crystallization regulator—polyvinylpyrrolidone (which is 0.01% of the mass of diosmin), stir at 80 rpm for 10 minutes, and mix well. S3. Continue adding dilute hydrochloric acid of the aforementioned concentration to adjust the pH of the solution to 6-7. Stir at 80 rpm for 30 minutes to allow diosmin to fully crystallize. After the reaction is complete, centrifuge the mixture, rinse the filter cake with 100 L of water, and then dry it with hot air at 110 ± 10 °C for 5 hours until the moisture content is below 6%, thus obtaining the large-particle diosmin product.

[0035] The cumulative volumetric particle size distribution (D90) of the large-particle diosmin product was then measured using a laser particle size distribution analyzer and found to be 104.153 μm.

[0036] The angle of repose of the large-particle diosmin product was tested to be 31°, indicating that its powder flow properties are excellent.

[0037] Example 4 This embodiment proposes a method for preparing large-particle diosmin based on a crystallization regulator, including the following steps: S1. Dissolve 50 kg of diosmin in 250 L of a 4% sodium hydroxide aqueous solution and stir until completely dissolved. Then, add hydrochloric acid to adjust the pH of the solution to 11. S2. Add 10g of crystallization regulator—polyvinylpyrrolidone (which is 0.02% of the mass of diosmin), stir at 80 rpm for 10 min, and mix well. S3. Continue adding dilute hydrochloric acid of the aforementioned concentration to adjust the pH of the solution to 6-7. Stir at 80 rpm for 45 minutes to allow diosmin to fully crystallize. After the reaction is complete, centrifuge the mixture, rinse the filter cake with 100 L of water, and then dry it with hot air at 110 ± 10 °C for 5 hours until the moisture content is below 6%, thus obtaining the large-particle diosmin product.

[0038] The cumulative volumetric particle size distribution (D90) of the large-particle diosmin product was then measured using a laser particle size distribution analyzer and found to be 104.792 μm.

[0039] The angle of repose of the large-particle diosmin product was tested to be 33°, indicating that its powder flow properties are excellent.

[0040] Example 5 This embodiment proposes a method for preparing large-particle diosmin based on a crystallization regulator, including the following steps: S1. Dissolve 50 kg of diosmin in 250 L of a 4% sodium hydroxide aqueous solution and stir until completely dissolved. Then, add hydrochloric acid to adjust the pH of the solution to 11. S2. Add 15g of crystallization regulator—polyvinylpyrrolidone (which is 0.03% of the mass of diosmin), stir at 80 rpm for 10 minutes, and mix well. S3. Continue adding dilute hydrochloric acid of the aforementioned concentration to adjust the pH of the solution to 6-7. Stir at 80 rpm for 60 minutes to allow diosmin to fully crystallize. After the reaction is complete, centrifuge the mixture, rinse the filter cake with 100 L of water, and then dry it with hot air at 110 ± 10 °C for 5 hours until the moisture content is below 6%, thus obtaining the large-particle diosmin product.

[0041] The cumulative volumetric particle size distribution (D90) of the large-particle diosmin product was then measured using a laser particle size distribution analyzer and found to be 103.698 μm.

[0042] The angle of repose of the large-particle diosmin product was tested to be 32°, indicating that its powder flow properties are excellent.

[0043] Example 6 This embodiment proposes a method for preparing large-particle diosmin based on a crystallization regulator, including the following steps: S1. Dissolve 50 kg of diosmin in 250 L of a 4% sodium hydroxide aqueous solution and stir until completely dissolved. Then, add hydrochloric acid to adjust the pH of the solution to 11. S2. Add 50g of crystallization regulator—polyvinylpyrrolidone (which is 0.1% of the mass of diosmin), stir at 80 rpm for 10 min, and mix well. S3. Continue adding dilute hydrochloric acid of the aforementioned concentration to adjust the pH of the solution to 6-7. Stir at 80 rpm for 30 minutes to allow diosmin to fully crystallize. After the reaction is complete, centrifuge the mixture, rinse the filter cake with 100 L of water, and then dry it with hot air at 110 ± 10 °C for 6 hours until the moisture content is below 6%, thus obtaining the large-particle diosmin product.

[0044] The cumulative volumetric particle size distribution (D90) of the large-particle diosmin product was then measured using a laser particle size distribution analyzer and found to be 105.361 μm.

[0045] The angle of repose of the large-particle diosmin product was tested to be 31°, indicating that its powder flow properties are excellent.

[0046] Comparative Example 1 Diosmin was prepared using the existing alkaline dissolution and acid precipitation crystallization method. S1. Weigh 50 kg of diosmin, add 250 L of 4% sodium hydroxide aqueous solution, and stir until completely dissolved; S2. Subsequently, adjust the pH of the solution to 3-5 with dilute hydrochloric acid and stir for 30 to 60 minutes to allow diosmin to crystallize fully. S3. After the reaction is complete, centrifuge the filter cake and rinse it with 100L of water. Then dry it with hot air at 110±10℃ for 12 hours until the moisture content is less than 6%, and the diosmin product is obtained.

[0047] The particle size of the diosmin product in this comparative example was measured using the same test method and instruments as in Example 1. The particle size distribution diagram is shown below. Figure 2 The cumulative particle size distribution (D90) of the Osmin finished powder is 21.140 μm.

[0048] The angle of repose of the diosmin product in the comparative test was 45°, indicating that its powder flowability was poor.

[0049] Comparative Example 2 The difference between this comparative example and Example 1 is that a high molecular weight polymer—polyacrylic acid—is used as a crystallization regulator, and the amount of polyacrylic acid added is 0.05% (25g) of the mass of diosmin.

[0050] In this comparative example, after diosmin was fully crystallized, it was centrifuged and the resulting filter cake was rinsed with 100L of water. Then, the temperature was controlled at 110±10℃ and hot air was used to dry it for 12 hours until the moisture content was less than 6%, thus obtaining the finished diosmin product.

[0051] The particle size of the diosmin product in this comparative example was tested using the same test method and instrument as in Example 1. The cumulative particle size distribution D90 of the diosmin product powder was 39.218 μm.

[0052] The angle of repose of the diosmin product in the comparative test was 45°, indicating that its powder flowability was poor.

[0053] Comparative Example 3 The difference between this comparative example and Example 1 is that anionic polyacrylamide, a high molecular weight polymer, was used as a crystallization regulator, and the amount of anionic polyacrylamide added was 0.05% (25g) of the mass of diosmin.

[0054] In this comparative example, after diosmin was fully crystallized, it was centrifuged and the resulting filter cake was rinsed with 100L of water. Then, the temperature was controlled at 110±10℃ and hot air was used to dry it for 13 hours until the moisture content was less than 6%, thus obtaining the finished diosmin product.

[0055] The particle size of the diosmin product in this comparative example was tested using the same test method and instrument as in Example 1. The cumulative particle size distribution D90 of the diosmin product powder was 51.139 μm.

[0056] The angle of repose of the diosmin product in the comparative test was 44°, indicating that its powder flowability was poor.

[0057] Comparative Example 4 The difference between this comparative example and Example 1 is that a high molecular weight polymer—cationic polyacrylamide—is used as a crystallization regulator, and the amount of cationic polyacrylamide added is 0.02% (10g) of the mass of diosmin.

[0058] In this comparative example, after diosmin was fully crystallized, it was centrifuged and the resulting filter cake was rinsed with 100L of water. Then, the temperature was controlled at 110±10℃ and hot air was used to dry it for 13 hours until the moisture content was less than 6%, thus obtaining the finished diosmin product.

[0059] The particle size of the diosmin product in this comparative example was tested using the same test method and instrument as in Example 1. The cumulative particle size distribution D90 of the diosmin product powder was 32.147 μm.

[0060] The angle of repose of the diosmin product in the comparative test was 45°, indicating that its powder flowability was poor.

[0061] Comparative Example 5 The only difference between this comparative example and Example 1 is that in step S3, after the pH is adjusted to 6-7, the stirring operation is canceled and the crystals are allowed to stand still for crystallization.

[0062] The particle size of the diosmin product in this comparative example was tested using the same test method and instrument as in Example 1. The cumulative particle size distribution D90 of the diosmin product powder was 30.679 μm.

[0063] The angle of repose of the diosmin product in the comparative test was 45°, indicating that its powder flowability was poor.

[0064] The particle size and flowability of the diosmin powder obtained in Example 1 and Comparative Examples 1-5 are shown in Table 1 below (unit: μm).

[0065] Table 1

[0066] As shown in Table 1, compared with Comparative Example 1 (the traditional preparation method of diosmin), Example 1 shows that: (1) According to the D10 index analysis, the proportion of fine particles in the large-particle diosmin product prepared in Example 1 is significantly reduced; in the product of Comparative Example 1 (original process), the proportion of particles with a diameter less than 2.85 μm is 10%, while in the product of Example 1 (process of the present invention), the proportion of particles with a diameter less than 12.42 μm is 10%. This indicates that the content of fine particles in the diosmin product prepared by the process of the present invention is significantly reduced.

[0067] (2) According to the D50 index analysis, in the large-particle diosmin product prepared in Example 1, the neutral position (D50) of the particle group shifted significantly to the right, indicating that the overall particle size of the product particles has been increased by orders of magnitude.

[0068] (3) The D90 index reflects that the coarse particle segment in the large-particle diosmin product prepared in Example 1 shows a significant increase: compared with the maximum particle size of about 21 μm in the original process product, a large number of particles with a particle size exceeding 100 μm have appeared in the diosmin product of Example 1. This result shows that the crystallization regulator used in this invention has a clear promoting effect on the aggregation and growth process of particles.

[0069] (4) The D(4,3) index reflects that the increase in volume average particle size even exceeds the increase in D50, which means that from the perspective of volume (or mass, density uniformity), the effect of increasing particle size is more significant.

[0070] (5) The angle of repose of the powder indicates that the angle of repose of the diosmin powder prepared by the existing process (Comparative Example 1) is 45°, while the angle of repose of the diosmin powder prepared in Example 1 of this invention is 32°. Based on the powder flowability guidelines in the Chinese Pharmacopoeia (see Table 2), the flowability of the diosmin powder prepared by the existing process is acceptable (but may have defects), only meeting basic requirements and insufficient for industrial production. The diosmin powder prepared using the process of this invention has good flowability, significantly improving the flowability of the diosmin powder.

[0071] Table 2: Powder flowability and corresponding angle of repose (Source: Chinese Pharmacopoeia Powder Flowability Guidelines).

[0072]

[0073] Referring to Table 1, a comparison between Example 1 and Comparative Examples 1-4 shows that after adding polyvinylpyrrolidone (Example 1), polyacrylic acid (Comparative Example 2), anionic polyacrylamide (Comparative Example 3), and cationic polyacrylamide (Comparative Example 4), respectively, it was found that compared with the traditional process for preparing diosmin (Comparative Example 1), adding only polyvinylpyrrolidone as a crystallization regulator can significantly increase the particle size of diosmin and greatly improve its powder flowability. While the other three polymers showed some improvement in related properties (particle size) compared to the existing alkali-dissolution and acid-precipitation crystallization process (Comparative Example 1), the flowability of the resulting diosmin powder was still at a "good" level and failed to meet practical application requirements. When using these diosmin powders to prepare pharmaceuticals containing diosmin in dosage forms such as tablets, capsules, granules, powders, and pills, or in the fields of dietary fiber supplements and health products, a granulation process is still required.

[0074] As can be seen from the comparison between Example 1 and Comparative Example 5, the static crystallization method does not significantly adjust the particle size of diosmin, and the powder prepared by the traditional method (Comparative Example 1) is basically the same.

[0075] The centrifugation efficiency and drying time of osmin produced by Example 1 and Comparative Example 1 (conventional preparation process) are compared in Table 3 below.

[0076] Table 3

[0077] As shown in Table 3, when polyvinylpyrrolidone is added as a crystallization regulator, the filtration time in the preparation of diosmin is shortened by 60% compared with the traditional process, and the drying energy consumption is reduced by 50% compared with the traditional process. Compared with the traditional process, the filtration efficiency of the present invention is significantly improved and the energy consumption is significantly reduced, with outstanding comprehensive performance advantages.

[0078] The above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention in any way. Any simple modifications or equivalent changes made to the above embodiments based on the technical essence of the present invention shall fall within the protection scope of the present invention.

Claims

1. A method for preparing large-particle diosmin based on a crystallization regulator, characterized in that, Includes the following steps: S1. Dissolve diosmin in an aqueous sodium hydroxide solution, and add hydrochloric acid to adjust the pH of the solution to 10-11; S2. Add crystallization regulator—polyvinylpyrrolidone. The amount of crystallization regulator is 0.01%~0.1% of the weight of diosmin. Stir and mix well. S3. Add hydrochloric acid to adjust the pH of the solution to 6-7, stir, and diosmin will precipitate. Centrifuge, wash and crystallize, and then dry the crystals separated after washing to obtain large-particle diosmin product.

2. A method for preparing large-particle diosmin based on a crystallization regulator according to claim 1, characterized in that: In step S2, polyvinylpyrrolidone includes PVP-K30 and PVP-K25.

3. A method for preparing large-particle diosmin based on a crystallization regulator according to claim 1, characterized in that: In step S2, the stirring speed is 50~80 rpm and the stirring time is 5~10 min.

4. A method for preparing large-particle diosmin based on a crystallization regulator according to claim 1, characterized in that: In step S3, the stirring rate is 50~80 rpm and the stirring time is 30~60 min; the drying temperature is 110±10℃, and the drying is carried out until the moisture content in the filter cake is not higher than 6%.

5. A large-particle diosmin prepared based on a crystallization regulator, characterized in that: The large-particle diosmin was prepared using any one of the methods described in claims 1 to 4.

6. The large-particle diosmin prepared based on a crystallization regulator according to claim 5, characterized in that: The angle of repose for large-particle diosmin is 30-35°.

7. The application of large-particle diosmin in the preparation of tablets, capsules, granules, powders, and pills, characterized in that: The large-particle diosmin is the large-particle diosmin of claim 5 or 6, or the large-particle diosmin is prepared by any one of the methods of claims 1 to 4 without additional granulation.

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