Baicalin for injection and preparation method thereof

Abstract

The invention provides baicalin for an injection and a preparation method thereof, and belongs to the technical field of traditional Chinese medicine preparations, the preparation method comprises the following steps: taking a radix scutellariae medicinal material, extracting, adding low-carbon alcohol into the obtained solution, carrying out ultrafiltration, heating the obtained liquid medicine, carrying out heat preservation and acid adjustment, and sequentially carrying out heat preservation, filtering while hot, washing with hot low-carbon alcohol and drying to obtain the baicalin for the injection. And filtering to obtain the baicalin for the injection. The preparation method disclosed by the invention is few in steps, high in yield, low in cost and convenient for large-scale production; the baicalin produced by the method is high in purity, good in solubility, few in insoluble impurities and low in bacterial endotoxin, can meet the use requirements of injections, and can be used by the injections.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine preparation, and in particular to a baicalin for injection and its preparation method. Background Technology

[0002] Baicalin is the main medicinal component of Scutellaria baicalensis, possessing antioxidant, anti-inflammatory, antibacterial, antiviral, antitumor, and blood pressure and lipid-lowering activities. Clinically, it is often used to treat diseases such as pneumonia, hepatitis, and infections. High-purity baicalin can be used in traditional Chinese medicine injections, such as Qingkailing injection and Yinzhihuang injection.

[0003] The invention patent CN115785178A discloses a method for purifying baicalin based on subcritical extraction. Baicalin is obtained from scutellaria through subcritical extraction, acid precipitation, filtration, and washing, with a yield of up to 14.45%. However, it requires high-quality equipment and the purity of baicalin can only reach 85%.

[0004] The invention patent CN115785178A discloses a method for preparing high-purity baicalin for injection and its application. The method involves grinding, pulverizing, flash extraction, concentration, resin adsorption and elution, acid adjustment and crystallization, filtration, and drying of Scutellaria baicalensis to obtain baicalin. The purity of baicalin can reach over 98%, but the highest yield is only 9.1%. The purification steps are relatively cumbersome, resulting in high production costs and hindering large-scale production.

[0005] The invention patent CN105566416A discloses a method for preparing high-purity baicalin for injection. The method involves adding crude baicalin with a purity below 85% to dimethyl sulfoxide and a low-carbon alcohol, heating to dissolve, filtering, continuing to add low-carbon alcohol, stirring and maintaining the temperature, cooling, filtering, and washing to obtain baicalin with a purity of over 97%. However, the purification process results in significant baicalin loss, exceeding 25%, and the dimethyl sulfoxide used in the purification has a certain degree of toxicity, which significantly impacts large-scale production and the application range of baicalin.

[0006] The invention patent CN105566416A discloses a method for preparing high-purity baicalin from Scutellaria baicalensis. The method involves pulverizing Scutellaria baicalensis and extracting it using ethanol under reflux, followed by concentration and drying to obtain a crude extract. The crude extract is then dissolved in water and purified using a porous adsorption resin and high-speed countercurrent chromatography to obtain baicalin with a purity of over 92%. However, this process results in low baicalin purity and is difficult to scale up for production.

[0007] The invention patent CN101475618A discloses a purification method for baicalin for injection, which involves processes such as heating and alkali dissolution, filtration, acidification, filtration, and washing to obtain baicalin with a purity of over 92%. However, this method results in low purity and yield of baicalin, and high production costs.

[0008] None of the aforementioned invention patents have been able to effectively remove the insoluble impurities and bacterial endotoxins in baicalin. Since baicalin contains insoluble impurities and bacterial endotoxins, it is difficult to meet the requirements for use in injections.

[0009] In summary, existing high-purity baicalin production processes are numerous and cumbersome, resulting in generally low purity or yield. Industrial production requires sophisticated equipment, leading to high production costs or difficulty in scaling up production. Furthermore, the produced baicalin exhibits poor solubility, contains many insoluble impurities, and has high levels of bacterial endotoxins, making it difficult to meet the requirements for injectable formulations. Summary of the Invention

[0010] To address the above problems, this invention provides baicalin for injection and its preparation method.

[0011] To achieve the above objectives, the technical solution adopted by the present invention is as follows: A method for preparing baicalin for injection, wherein the preparation method involves taking Scutellaria baicalensis, extracting it, adding low-carbon alcohol to the resulting solution, ultrafiltration, heating the resulting solution, adjusting the acidity by heat preservation, and then sequentially continuing to heat preservation, filtering while hot, washing with hot low-carbon alcohol, and drying to obtain the baicalin for injection. The solution can be the extract directly, or the extract after concentration.

[0012] Furthermore, the lower alcohol is at least one of methanol, ethanol, propylene glycol, and glycerol.

[0013] Furthermore, the added low-carbon alcohol is 0.1 to 2 times the weight of the solution.

[0014] Furthermore, the temperature of the liquid after heating, the temperature for maintaining the temperature and adjusting the acidity, the temperature for continuing to maintain the temperature, and the temperature for filtering while hot are all 70~100℃.

[0015] Furthermore, the pH value of the system after heat preservation and acidification is 1.0~4.0.

[0016] Furthermore, the pore size of the ultrafiltration membrane is 10~100kD.

[0017] Furthermore, the continued heat preservation time is 30 minutes or more.

[0018] Furthermore, the extraction involves adding 4 to 20 times the weight of water to the Scutellaria baicalensis herb for extraction.

[0019] Furthermore, the extraction is performed 1 to 5 times at a temperature of 90 to 100°C.

[0020] A baicalin for injection prepared by the above preparation method, wherein the baicalin for injection has a purity ≥90%, bacterial endotoxin <0.1 EU / g, and yield ≥9.8%.

[0021] The beneficial effects of the baicalin for injection and its preparation method of the present invention are as follows: The preparation method of the present invention has fewer steps, higher yield, and lower cost, making it easy to scale up production. The baicalin produced by the present invention has high purity, good solubility, fewer insoluble impurities, and lower bacterial endotoxins, which can meet the requirements for use in injections. This invention allows for the one-step production of high-purity baicalin by adding low-carbon alcohols to the extract (or concentrate) and then filtering it while hot after heating, acid adjustment, and heat preservation. This invention improves the purity of baicalin and reduces insoluble impurities and bacterial endotoxins by adding specific types and amounts of low-carbon alcohols to the extract (or concentrate) and then performing ultrafiltration. This invention obtains baicalin with high purity by controlling the type and amount of low-carbon alcohols and the temperature during acid adjustment. Changing these parameters will lead to a decrease in the purity of baicalin. Detailed Implementation

[0022] The technical solutions in the embodiments of the present invention will be clearly and completely described below. Many specific details are set forth in the following description to provide a thorough understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art can make similar extensions without departing from the spirit of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0023] Examples 1-15: A method for preparing baicalin for injection. Examples 1-15 are all methods for preparing baicalin for injection. Specific process parameters are shown in Tables 1-2, and the specific preparation steps are as follows: S1. Take Scutellaria baicalensis and crush it to 1-2 cm. Add 10 times its weight of water and decoct it 3 times. Concentrate the resulting extract under reduced pressure to a volume of 5 times the weight of the herb to obtain a concentrated solution.

[0024] S2. Add a certain amount of low-carbon alcohol to the concentrate, and filter it using an ultrafiltration membrane to obtain the filtered drug solution.

[0025] S3. Heat the drug solution and maintain the temperature after heating. Add hydrochloric acid to adjust the pH value. After adding the hydrochloric acid, continue to keep it warm for 30 minutes. Then filter it while it is hot. Wash the precipitate with hot low-carbon alcohol and dry it under reduced pressure to obtain baicalin for injection.

[0026] S4. Further detection of bacterial endotoxins in the obtained baicalin was performed. The specific detection method (refer to Chinese Pharmacopoeia 2020, Part III, General Chapter 1143, Bacterial Endotoxin Test Method) is as follows: Preparation of test sample: Accurately weigh about 10 mg of baicalin, add 0.45 mL of 0.05 mol / L sodium hydroxide aqueous solution and 1.55 mL of water for injection in sequence, mix and dissolve on a vortex mixer, and then dilute with water for testing 100 to 200 times according to the method to obtain the test sample solution. Standard curve: Take one vial of bacterial endotoxin working standard, dissolve it in test water, and dilute it according to the method to prepare bacterial endotoxin standard solutions of 1 EU / mL, 0.1 EU / mL, and 0.01 EU / mL; take two vials of horseshoe crab reagent, tap them lightly, disinfect them with 75% ethanol, break them open, add the corresponding volume of test water to dissolve them, mix well, and then prepare the standard curve. Detection method: Take 8 test tubes and add 0.1 mL of horseshoe crab reagent to each. Add 0.2 mL of positive control solution to 2 of the tubes as positive control tubes; add 0.2 mL of test water to 2 of the tubes as negative control tubes; make 2 test sample tubes and 2 test sample positive control tubes, add 0.2 mL of solution to each tube, mix well, and place them in a bacterial endotoxin detector for detection under the specified conditions.

[0027] The specific process parameters and test results of Examples 1 to 12 are shown in Table 1.

[0028] Table 1. Summary of Process Parameters

[0029] As can be seen from Examples 1-12, the present invention, by using specific types and amounts of low-carbon alcohols and controlling the temperature and pH value after acidification, can effectively improve the yield and purity of baicalin and reduce bacterial mycotoxins.

[0030] The steps in Examples 13-15 are basically the same as those in Example 1, except that some process parameters are different. The specific process parameters and test results are shown in Table 2.

[0031] Table 2 Summary of Process Parameters

[0032] Comparative Examples 1-16: A method for preparing baicalin for injection Comparative Examples 1-16 are comparative experiments on the preparation method of baicalin for injection in Example 1, using the same batch of Scutellaria baicalensis as in Example 1 as the raw material. The steps are basically the same as in Example 1, with the only difference being some process parameters. The specific process parameters and test results are as follows: Table 3. Summary of process parameters and results for Comparative Examples 1-16

[0033] A comparison of Tables 1 and 2 shows that reducing the amount of low-carbon alcohol added, lowering the temperature after the drug solution is heated, or changing the type of low-carbon alcohol will all lead to a decrease in the purity of baicalin (all purity is below 90%). Increasing the proportion of low-carbon alcohol added and adjusting the pH value after acidification will significantly reduce the yield of baicalin. Increasing the pore size of the ultrafiltration membrane will increase the bacterial endotoxin of baicalin.

[0034] Furthermore, at room temperature, baicalin (content 88.7%) prepared in Comparative Example 1 was dispersed in 4 times its weight of water, the pH was adjusted to 6.5 with sodium hydroxide solution, and then an equal volume of anhydrous ethanol was added. The mixture was filtered, and the pH of the filtrate was adjusted to 2.0 with hydrochloric acid. After filtration, the precipitate was dried under reduced pressure to obtain baicalin, with a content of 96.7%. The experimental results show that reducing the amount of low-carbon alcohol added or lowering the temperature of the drug solution after heating results in baicalin with a purity below 90%. Further purification using low-carbon alcohol can effectively improve the purity of baicalin.

[0035] Obviously, the described embodiments are only some, not all, of the embodiments of the present invention. All other embodiments obtained by those skilled in the art based on the embodiments of the present invention without inventive effort are within the scope of protection of the present invention.

Claims

1. A method for preparing baicalin for injection, characterized in that, The preparation method is to take Scutellaria baicalensis, extract it, add low-carbon alcohol to the resulting solution, ultrafilter it, heat the resulting solution, keep it warm and adjust the acidity, and then continue to keep it warm, filter it while it is hot, wash it with hot low-carbon alcohol, and dry it to obtain the baicalin for injection.

2. The method for preparing baicalin for injection according to claim 1, characterized in that, The lower alcohol is at least one of methanol, ethanol, propylene glycol and glycerol.

3. The method for preparing baicalin for injection according to claim 1 or 2, characterized in that, The added low-carbon alcohol is 0.1 to 2 times the weight of the solution.

4. The method for preparing baicalin for injection according to claim 1 or 2, characterized in that, The temperature for heat preservation and acid conditioning, as well as the temperature for hot filtration, are both 70~100℃.

5. The method for preparing baicalin for injection according to claim 1 or 2, characterized in that, The pH value of the system after heat preservation and acidification is 1.0~4.

0.

6. The method for preparing baicalin for injection according to claim 1 or 2, characterized in that, The ultrafiltration membrane has a pore size of 10~100kD.

7. The method for preparing baicalin for injection according to claim 1 or 2, characterized in that, The heat preservation time is at least 30 minutes.

8. The method for preparing baicalin for injection according to claim 1 or 2, characterized in that, The extraction process involves adding 4 to 20 times the weight of water to the Scutellaria baicalensis herb for extraction.

9. The method for preparing baicalin for injection according to claim 1 or 2, characterized in that, The extraction is performed 1 to 5 times at a temperature of 90 to 100°C.

10. A baicalin for injection prepared by the method according to any one of claims 1-9, characterized in that, The baicalin used in the injection has a purity of ≥90%, bacterial endotoxin <0.1 EU / g, and a yield of ≥9.8%.

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