Method for co-producing baicalin, baicalein and wogonin from scutellaria baicalensis extraction waste residues

Abstract

The invention provides a method for co-producing baicalin, baicalein and wogonin from scutellaria baicalensis extraction waste residues, which comprises the following steps: firstly, extracting the waste residues by adopting an ethanol solution, heating an extracting solution, adjusting the pH value, crystallizing to obtain a crude baicalin product, and refluxing and purifying by using ethanol to obtain the baicalin; the method comprises the following steps: respectively adjusting the pH value of mother liquor, concentrating, combining, extracting by using a water-saturated ethyl acetate-n-butyl alcohol mixed solvent, concentrating an extract phase, diluting by using ethanol, heating, adjusting the pH value, and crystallizing to obtain baicalein; and further adjusting the pH value of the residual filtrate, dealcoholizing, concentrating, cooling and crystallizing, and refining the obtained solid to obtain wogonin. According to the method disclosed by the invention, extraction, fractional precipitation and solvent extraction are combined for use, and the process conditions of each stage are optimized, so that high-purity baicalin, baicalein and wogonin are prepared from the scutellaria baicalensis extraction waste residues, and the utilization value of the waste residues is improved.

Description

Technical Field

[0001] This invention relates to the field of plant extraction technology, specifically to a method for co-producing baicalin, baicalein and wogonin from the waste residue of Scutellaria baicalensis extraction. Background Technology

[0002] Scutellaria baicalensis, the dried root of plants in the genus Scutellaria of the Lamiaceae family, is a traditional and commonly used Chinese medicinal herb. It contains flavonoids such as baicalin, baicalein, and wogonin, which possess significant pharmacological activities. Baicalin, in particular, exhibits antibacterial, anti-inflammatory, and hepatoprotective effects, and is widely used in the treatment of respiratory infections and hepatitis. Baicalein and wogonin not only demonstrate stronger antioxidant, antitumor, and immunomodulatory activities but also possess the advantage of penetrating the blood-brain barrier, making them highly valuable in antitumor drugs and neuroprotective agents. With the continuous growth in demand for high-purity flavonoids in the pharmaceutical industry, the preparation of high-purity flavonoids has become a subject of extensive research.

[0003] Currently, the extraction and preparation of baicalin, baicalein, and wogonin mainly involve the direct extraction and separation of Scutellaria baicalensis raw material. However, Scutellaria baicalensis resources are limited and the cost is high. During the industrial production of baicalin or other Scutellaria baicalensis extracts, a large amount of extraction waste is generated. This waste usually still contains certain amounts of target components such as baicalin, baicalein, and wogonin. Directly discarding it not only wastes resources but may also create environmental pressure.

[0004] Existing technologies have methods for extracting and separating the aforementioned flavonoids from Scutellaria baicalensis waste, but most methods focus on the extraction and purification of single components, failing to co-produce other effective active ingredients; they have failed to systematically achieve the simultaneous and efficient co-production of multiple active ingredients such as baicalin, baicalein, and wogonin, and have failed to fully utilize the value of the waste residue. Moreover, for the waste residue system, conventional extraction solvents and processes cannot fully dissolve the residual target substances. In the separation and purification stage, especially the separation of baicalein and wogonin, due to their similar structures and polarities, conventional separation methods often result in insufficient separation, leading to low product purity, or a lengthy separation process, resulting in significant product loss and low yield. Summary of the Invention

[0005] The technical problem to be solved by this invention is to provide a method for co-producing baicalin, baicalein and wogonin from the waste residue of Scutellaria baicalensis extraction, which addresses the shortcomings of the existing technology. This invention adopts a combination of extraction, fractional precipitation and solvent extraction, and by optimizing the process conditions at each stage, high-purity baicalin, baicalein and wogonin are prepared from the waste residue of Scutellaria baicalensis extraction, thereby improving the utilization value of the waste residue.

[0006] To solve the above-mentioned technical problems, the technical solution of the present invention is as follows:

[0007] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0008] (1) Ethanol solution was used as the extraction solvent to extract the waste residue of Scutellaria baicalensis extraction. The obtained extract was then post-treated to obtain the first solution to be treated.

[0009] (2) The above-mentioned liquid to be treated is heated and the pH is adjusted, stirred and crystallized, and then filtered to obtain filter cake 1 and filtrate 1; filter cake 1 and ethanol solution are mixed and refluxed, and after reflux, they are filtered to obtain filter cake 2 and filtrate 2; filter cake 2 is dried to obtain baicalin; filtrate 1 is adjusted and concentrated and then mixed with filtrate 2 which has been successively treated by alcohol removal, pH adjustment and concentration to obtain liquid to be treated 2;

[0010] (3) Use water-saturated ethyl acetate-n-butanol as the extractant to extract the second solution of the treatment solution multiple times and collect the extract phase; concentrate the above extract phase to remove ethyl acetate-n-butanol and then add ethanol to dilute to obtain the third solution of the treatment solution;

[0011] (4) After heating the solution to be treated, adjust the pH and stir to crystallize. After crystallization, filter while hot to obtain filter cake three and filtrate three. Dry filter cake three to obtain baicalin.

[0012] (5) After adjusting the pH of filtrate three, remove alcohol, concentrate and cool to crystallize, filter after crystallization to obtain filter cake four and filtrate four; filter cake four is purified and dried to obtain baicalin.

[0013] Preferably, in step (1), when using an ethanol solution as the extraction solvent to extract the waste residue from the Scutellaria baicalensis extraction, at least one of the following characteristics is included:

[0014] The concentration of the ethanol solution is 50-55% v / v;

[0015] The amount of ethanol solution used is 5-8 times the weight of the waste residue from the Scutellaria baicalensis extraction.

[0016] The extraction temperature is 81-83℃, and the extraction time is 1-3 hours each time;

[0017] The extraction is performed 3-5 times.

[0018] Preferably, in step (1), the post-processing process includes: concentrating and de-alcoholizing the extracts from multiple extractions to obtain a liquid to be treated with a solid content of 3-5 wt%.

[0019] Preferably, in step (2), the heating temperature is 90-100℃, and the pH of the above-mentioned liquid to be treated is adjusted to 1.5-1.8 after heating.

[0020] Preferably, in step (2), the stirring crystallization process takes 0.5-1 hour.

[0021] Preferably, in step (2), the concentration of the ethanol solution is 50-55% v / v, the mass ratio of the filter cake to the ethanol solution is 1:(8-10), and the reflux temperature is 83-85℃ for 1-3h.

[0022] Preferably, in step (2), the pH of filtrate one and filtrate two are adjusted to 3.0-3.5 respectively.

[0023] Preferably, in step (2), the pH of filtrate one and filtrate two are adjusted and then the solid content is concentrated to 20-25 wt%.

[0024] Preferably, in step (3), the volume ratio of ethyl acetate to n-butanol in the water-saturated ethyl acetate-n-butanol mixture is (8.5-9.0):1; during extraction, the volume ratio of the solution to be treated to the extractant is 1:(1-3), and the number of extractions is 3-4.

[0025] Preferably, in step (3), the solid content of the liquid to be treated is 5-8 wt%, and the ethanol concentration is 25-35% v / v.

[0026] Preferably, in step (4), the heating temperature is 70-80℃, the pH is adjusted to 2.0-2.2, and the stirring crystallization time is 3-5h.

[0027] Preferably, in step (5), the pH of the filtrate is adjusted to 2.8-3.0; the solid content is concentrated to 25-35 wt%; the temperature for cooling and crystallization is 40-45℃ and the time is 1-3h.

[0028] Preferably, in step (5), the four filtrates are combined into one filtrate.

[0029] Preferably, in step (5), the process of refining filter cake four includes: mixing filter cake four with ethanol solution and refluxing to precipitate, then filtering while hot to obtain filter cake five and filtrate five, and drying filter cake five to obtain scutellaria baicalensis.

[0030] Preferably, in step (5), the filter cake undergoes a refining process that includes at least one of the following characteristics:

[0031] The concentration of the ethanol solution is 10-15% v / v, and the mass ratio of the filter cake to the ethanol solution is 1:(3-5); the reflux precipitation temperature is 91-96℃, and the time is 2-3h.

[0032] Preferably, in step (5), the filtrate is concentrated and de-alcoholized and then recycled to the liquid to be treated.

[0033] By adopting the above technical solution, the present invention has at least the following beneficial effects:

[0034] This invention provides a method for co-producing baicalin, baicalein and wogonin from the waste residue of Scutellaria baicalensis extraction. The method directly uses the waste residue after Scutellaria baicalensis extraction as raw material, and achieves the co-production of baicalin, baicalein and wogonin through re-extraction and purification, realizing the resource utilization of waste residue and significantly reducing production costs.

[0035] This invention purifies the extract from the waste residue of Scutellaria baicalensis extraction by controlling the solid content of the extract and preferentially crystallizing baicalin at specific temperatures and pH levels to achieve preliminary separation. Then, crude baicalin is mixed with a specific concentration of ethanol solution and heated at a certain temperature for purification to obtain high-purity baicalin. The waste liquid generated during the baicalin purification process is concentrated, pH adjusted, and then extracted with water-saturated ethyl acetate-n-butanol to enrich baicalein and wogonin. After desolventizing the extracted phase, ethanol is added to adjust the solid content and polarity of the solution. The mixture is then heated again and the pH is adjusted. Utilizing the differences in solubility of different flavonoid compounds at specific temperatures and pH levels, sequential crystallization separation of baicalein and wogonin is achieved.

[0036] This invention fully recovers and utilizes the waste liquid in the recovery of active ingredients, reducing product loss and increasing the overall yield.

[0037] The method of this invention mainly uses an ethanol-water system, which has low toxicity and high production safety, and solves the problem of waste residue treatment after the initial extraction of Scutellaria baicalensis. Moreover, this invention combines graded crystallization and extraction, which has lower cost and is more suitable for large-scale production. Detailed Implementation

[0038] To better understand the above-mentioned objectives, features, and advantages of the present invention, the solutions of the present invention will be further described below. It should be noted that, unless otherwise specified, the embodiments of the present invention and the features thereof can be combined with each other.

[0039] Many specific details are set forth in the following description in order to provide a full understanding of the invention, but the invention may also be practiced in other ways different from those described herein; obviously, the embodiments in the specification are only some embodiments of the invention, and not all embodiments.

[0040] This invention provides a method for co-producing baicalin, baicalein and wogonin from the waste residue of Scutellaria baicalensis extraction, comprising the following steps:

[0041] (1) Ethanol solution was used as the extraction solvent to extract the waste residue of Scutellaria baicalensis extraction. The obtained extract was then post-treated to obtain the first solution to be treated.

[0042] (2) The above-mentioned liquid to be treated is heated and the pH is adjusted, stirred and crystallized, and then filtered to obtain filter cake one and filtrate one; filter cake one and ethanol solution are mixed and refluxed, and after reflux, they are filtered to obtain filter cake two and filtrate two; filter cake two is dried to obtain baicalin; filtrate one is adjusted to pH and concentrated, and then mixed with filtrate that has been successively treated by alcohol removal, pH adjustment and concentration to obtain liquid to be treated two;

[0043] (3) Use water-saturated ethyl acetate-n-butanol as the extractant to extract the second solution of the treatment solution multiple times and collect the extract phase; concentrate the above extract phase to remove ethyl acetate-n-butanol and then add ethanol to dilute to obtain the third solution of the treatment solution;

[0044] (4) After heating the solution to be treated, adjust the pH and stir to crystallize. After crystallization, filter while hot to obtain filter cake three and filtrate three. Dry filter cake three to obtain baicalin.

[0045] (5) After adjusting the pH of filtrate three, remove alcohol, concentrate and cool to crystallize, filter after crystallization to obtain filter cake four and filtrate four; filter cake four is purified and dried to obtain baicalin.

[0046] Regarding step (1):

[0047] In some embodiments, when using an ethanol solution as the extraction solvent to extract the waste residue from Scutellaria baicalensis, the concentration of the ethanol solution is 50-55% v / v. This concentration of ethanol solution can sufficiently dissolve baicalin and free flavonoids. Excessive ethanol concentration not only increases costs but also leads to an increase in lipid-soluble impurities, affecting the subsequent purification of the active ingredients. Conversely, excessively low ethanol concentration results in a decrease in extraction efficiency.

[0048] In some embodiments, when using an ethanol solution as the extraction solvent to extract the waste residue from Scutellaria baicalensis, the amount of ethanol solution used is 5-8 times the weight of the waste residue; the extraction temperature is 81-83℃, the extraction time for each extraction is 1-3 hours, and the number of extractions is 3-5 times. Since the waste residue contains low levels of active ingredients, this invention, through multiple extractions and reasonable temperature control, ensures that the remaining active ingredients are fully dissolved.

[0049] In some embodiments, the post-processing includes: concentrating and de-alcoholizing the extracts from multiple extractions to obtain a pre-treatment solution with a solid content of 3-5 wt%. To facilitate the subsequent selective crystallization of baicalin, the present invention rationally adjusts the solid content of the extract. Excessive solid content can lead to premature precipitation of impurities, while excessively low concentration results in low subsequent crystallization efficiency.

[0050] Regarding step (2):

[0051] Baicalin accounts for a much higher proportion in the extract than baicalein and wogonin, and the three have similar physicochemical properties. Therefore, this invention utilizes the difference in the mass of the physicochemically bound compounds of baicalin to preferentially precipitate and separate them under certain conditions, avoiding subsequent interference with free flavonoids.

[0052] In some embodiments, the heating temperature is 90-100°C, and the pH of the solution to be treated is adjusted to 1.5-1.8 after heating. The high temperature of 90-100°C can dissolve some thermally stable impurities, preventing them from encapsulating baicalin crystals; while under the pH conditions of 1.5-1.8, the carboxyl groups in the baicalin structure are completely protonated, the molecular polarity drops sharply, and the solubility decreases drastically, thus selectively precipitating.

[0053] In some embodiments, the stirring crystallization time is 0.5-1 hour.

[0054] In some embodiments, the concentration of the ethanol solution is 50-55%, and the mass ratio of the filter cake one to the ethanol solution is 1:(8-10); the reflux temperature is 83-85℃, and the time is 1-3 hours. In the purification of crude baicalin, this invention mixes filter cake one with an ethanol solution of a certain concentration. By controlling the liquid-solid ratio and reflux conditions, the small amount of baicalin and wogonin entrained in filter cake one dissolves. The resulting filtrate two is combined with filtrate one, ensuring that all effective components proceed to the next step of processing and improving the overall yield.

[0055] In some implementations, the pH of filtrate one and filtrate two are adjusted to 3.0-3.5, respectively.

[0056] In some embodiments, filtrate one and filtrate two are adjusted to pH and then concentrated to a solid content of 20-25 wt%. This invention, by adjusting the pH and solid content of the second solution, can prevent premature precipitation of baicalin and wogonin, and also improve subsequent extraction efficiency. If the solid content is too low, a large amount of extraction solvent is required, resulting in high energy consumption; conversely, if the solid content is too high, impurities are more likely to enter the organic phase along with the target components.

[0057] Regarding step (3):

[0058] To achieve the enrichment of baicalin and wogonin, this invention utilizes their higher solubility in organic solvents to enrich baicalin and wogonin with a specific extractant, removing water-soluble impurities, thus facilitating the subsequent separation of baicalin and wogonin.

[0059] In some embodiments, the volume ratio of ethyl acetate to n-butanol in the water-saturated ethyl acetate-n-butanol mixture is (8.5-9.0):1; during extraction, the volume ratio of the solution to be treated to the extractant is 1:(1-3). Ethyl acetate has moderate polarity and good solubility for baicalin and wogonin. n-Butanol is partially miscible with water, serving to demulsify and increase the extraction capacity for slightly more polar components; this invention mixes the two in a specific ratio to form an extraction system that is immiscible with water but has suitable polarity, which can effectively extract baicalin and wogonin while leaving highly polar impurities in the aqueous phase.

[0060] In some embodiments, the solid content of the solution to be treated (Part 3) is 5-8 wt%, and the ethanol concentration is 25-35% v / v. To achieve effective separation of baicalin and wogonin, the solid content and ethanol concentration of the solution to be treated need to be appropriately adjusted. After removing the extractant, dilution with ethanol can prevent the free flavonoids from agglomerating and precipitating due to excessive concentration. Furthermore, a suitable ethanol concentration in the solution to be treated can balance the solubility of baicalin and wogonin, facilitating subsequent selective precipitation.

[0061] Regarding step (4):

[0062] Based on the acidity difference between baicalein and wogonin, this invention achieves the initial separation of baicalein and wogonin by rationally adjusting the pH of the solution to be treated to allow baicalein to crystallize out preferentially.

[0063] In some embodiments, the heating temperature is 70-80℃, the pH is adjusted to 2.0-2.2, and the stirring crystallization time is 3-5 hours. These temperature and pH conditions not only ensure the selective precipitation of baicalin but also prevent impurities from being trapped during crystallization, while ensuring uniform crystallization.

[0064] Regarding step (5):

[0065] To separate baicalein from the filtrate, this invention selects pH, crystallization temperature, and solid content to selectively precipitate baicalein under specific conditions, followed by purification to improve purity. At the same time, the mother liquor from the purification process is recycled to maximize resource utilization.

[0066] In some embodiments, the pH of the filtrate is adjusted to 2.8-3.0; the solution is concentrated to a solid content of 25-35 wt%; and the crystallization temperature is set at 40-45°C for 1-3 hours. Under the premise of a certain solid content, combined with specific pH and temperature, baicalin is selectively crystallized out.

[0067] In some embodiments, the process of refining the filter cake four includes: mixing the filter cake four with an ethanol solution and refluxing to precipitate, then filtering while hot to obtain filter cake five and filtrate five, and drying the filter cake five to obtain baicalin.

[0068] In some embodiments, the filter cake undergoes a fourth refining process that includes at least one of the following characteristics:

[0069] The concentration of the ethanol solution is 10-15% v / v, and the mass ratio of the filter cake to the ethanol solution is 1:(3-5). The reflux precipitation temperature is 91-96℃, and the time is 2-3 hours. During purification, the 10-15% v / v ethanol can dissolve the small amount of residual baicalein, and the high temperature can enhance the solubility of impurities, thereby improving the purity of baicalein.

[0070] In some embodiments, the filtrate is concentrated and de-alcoholized before being recycled to the treatment solution. Unprecipitated baicalin and wogonin in the filtrate are recovered for the next batch, thereby increasing the overall yield.

[0071] In summary, on the one hand, this invention achieves efficient separation of the effective components in the extract by sequentially precipitating baicalin, baicalein, and wogonin through gradient pH control at each stage. On the other hand, this invention achieves efficient separation and purification of the target substances by jointly adjusting the system's solid content, ethanol concentration, pH, and other conditions in the extraction, crystallization, extraction, and purification steps.

[0072] To further understand the present invention, preferred embodiments of the present invention are described below in conjunction with examples. However, it should be understood that these descriptions are only for further illustrating the features and advantages of the present invention, and not for limiting the scope of the claims of the present invention.

[0073] Example 1

[0074] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0075] (1) Take 5.0 kg of Scutellaria baicalensis extraction residue, add 35 L of 53% v / v ethanol solution, reflux at 82℃ for 4 times, 2 h each time, combine the extracts, concentrate under reduced pressure to remove alcohol, and obtain 12.1 L of untreated liquid one with a solid content of 4.0 wt%; the content of baicalin in untreated liquid one is 6.541 mg / ml, the content of baicalein is 1.740 mg / ml, and the content of wogonin is 1.314 mg / ml;

[0076] (2) Heat the liquid to be treated to 98°C, adjust the pH to 1.7 with dilute hydrochloric acid, stir and crystallize for 0.8 h, filter while hot after crystallization to obtain filter cake 1 and filtrate 1; mix filter cake 1 with 53% v / v ethanol solution (mass ratio of filter cake 1 to ethanol solution is 1:9), reflux at 84°C for 2 h, filter while hot after reflux, dry filter cake 2 to obtain 82.2 g baicalin with a purity of 87.4 wt% and a yield of 90.8%; adjust the pH of filtrate 1 to 3.2 and concentrate under reduced pressure to a solid content of 23 wt%, then mix with filtrate 2 which has been de-alcoholized, adjusted to pH 3.2 and concentrated under reduced pressure to a solid content of 23 wt% to obtain liquid to be treated 2;

[0077] (3) Using water-saturated ethyl acetate-n-butanol (the volume ratio of ethyl acetate to n-butanol is 8.8:1) as the extractant, the solution to be treated was extracted 3 times (the volume ratio of solution to be treated to the extractant was 1:2 each time). The extract phases were combined, and the solvent was recovered under reduced pressure. Ethanol was added to dilute the extract phase to obtain solution to be treated with a solid content of 6.5 wt%. The ethanol concentration in solution to be treated was 31% v / v.

[0078] (4) The solution to be treated was heated to 77°C, the pH was adjusted to 2.1, and the mixture was stirred and crystallized for 4 hours. After crystallization, the solution was filtered while hot, and the filter cake was dried to obtain 19.5 g of baicalin with a purity of 96.8 wt% and a yield of 89.7%.

[0079] (5) Adjust the pH of filtrate three to 2.9, de-alcoholize under reduced pressure and concentrate to a solid content of 29wt%, cool to 42℃, crystallize for 2h, filter to obtain filter cake four, reflux filter cake four with ethanol solution of 13% v / v at 93℃ for 2.5h, filter while hot after reflux, and dry filter cake five to obtain 14.3g of baicalein with a purity of 98.6wt% and a yield of 88.7%; filtrate four is combined with filtrate one in step (1), and filtrate five is concentrated and de-alcoholized and returned to the liquid to be treated three in step (3) for recycling.

[0080] Example 2

[0081] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0082] (1) Take 5.0 kg of Scutellaria baicalensis extraction residue, add 25 L of 50% v / v ethanol solution, reflux extract at 83℃ 5 times, 1 h each time, combine the extracts, concentrate under reduced pressure to remove alcohol, and obtain 15.6 L of untreated liquid one with a solid content of 3 wt%; the content of baicalin in untreated liquid one is 4.971 mg / ml, the content of baicalein is 1.340 mg / ml, and the content of wogonin is 1.000 mg / ml;

[0083] (2) Heat the liquid to be treated to 90°C, adjust the pH to 1.8 with dilute hydrochloric acid, stir and crystallize for 0.5 h, filter while hot after crystallization to obtain filter cake 1 and filtrate 1; mix filter cake 1 with 50% v / v ethanol solution (mass ratio of filter cake 1 to ethanol solution is 1:8), reflux at 85°C for 1 h, filter while hot after reflux, dry filter cake 2 to obtain 80.5 g baicalin with a purity of 87.3 wt% and a yield of 90.6%; adjust the pH of filtrate 1 to 3.0 and concentrate under reduced pressure to a solid content of 20 wt%, then mix with filtrate 2 which has been de-alcoholized, adjusted to pH 3.0 and concentrated under reduced pressure to a solid content of 20 wt% to obtain liquid to be treated 2;

[0084] Steps (3), (4), and (5): The operation is the same as in Example 1, yielding 19.3g of baicalein with a purity of 96.3wt% and a yield of 88.9%; and 14.0g of wogonin with a purity of 98.4wt% and a yield of 88.3%.

[0085] Example 3

[0086] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0087] (1) The operation is the same as in Example 1; the content of baicalin in the first solution to be treated is 6.541 mg / ml, the content of baicalein is 1.740 mg / ml, and the content of wogonin is 1.314 mg / ml;

[0088] (2) Heat the liquid to be treated to 100°C, adjust the pH to 1.5 with dilute hydrochloric acid, stir and crystallize for 1 hour. After crystallization, filter while hot to obtain filter cake 1 and filtrate 1. Mix filter cake 1 with 55% v / v ethanol solution (mass ratio of filter cake 1 to ethanol solution is 1:10), reflux at 83°C for 3 hours, filter while hot after reflux, and dry filter cake 2 to obtain 82.4g of baicalin with a purity of 87.1wt% and a yield of 90.7%. Adjust the pH of filtrate 1 to 3.5 and concentrate under reduced pressure to a solid content of 25wt%, then mix it with filtrate 2 which has been de-alcoholized, adjusted to pH 3.5 and concentrated under reduced pressure to a solid content of 25wt% to obtain liquid to be treated 2.

[0089] Steps (3), (4), and (5) are performed in the same manner as in Example 1, yielding 19.5g of baicalein with a purity of 96.4wt% and a yield of 89.3%; and 14.2g of wogonin with a purity of 98.6wt% and a yield of 88.1%.

[0090] Example 4

[0091] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0092] The operation of steps (1) and (2) is the same as in Example 1; the content of baicalin in the solution to be treated is 6.541 mg / ml, the content of baicalein is 1.740 mg / ml, and the content of wogonin is 1.314 mg / ml;

[0093] (3) Using water-saturated ethyl acetate-n-butanol (the volume ratio of ethyl acetate to n-butanol is 8.5:1) as the extractant, extract the second solution to be treated 4 times (the volume ratio of the second solution to the extractant is 1:1 each time). Combine the extract phases, and after the solvent is recovered under reduced pressure, dilute with ethanol to obtain the third solution to be treated with a solid content of 5wt%. The ethanol concentration in the third solution to be treated is 25%v / v.

[0094] Steps (4) and (5) are performed in the same manner as in Example 1;

[0095] 82.2g of baicalin with a purity of 87.3wt% and a yield of 90.7% were obtained; 19.7g of baicalein with a purity of 96.2wt% and a yield of 90.0% were obtained; and 14.4g of wogonin with a purity of 98.2wt% and a yield of 88.9% were obtained.

[0096] Example 5

[0097] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0098] (1) and (2) are the same as in Example 1; the content of baicalin in the solution to be treated is 6.541 mg / ml, the content of baicalein is 1.740 mg / ml, and the content of wogonin is 1.314 mg / ml;

[0099] (3) Using water-saturated ethyl acetate-n-butanol (the volume ratio of ethyl acetate to n-butanol is 9.0:1) as the extractant, extract the solution to be treated 3 times (the volume ratio of solution to be treated to the extractant is 1:3 each time). Combine the extract phases, and after the solvent is recovered under reduced pressure, dilute with ethanol to obtain solution to be treated 3 with a solid content of 8wt% and an ethanol concentration of 35%v / v.

[0100] (4) and (5) are operated in the same way as in Example 1;

[0101] 82.1g of baicalin with a purity of 87.5wt% and a yield of 90.8% were obtained; 19.5g of baicalein with a purity of 96.4wt% and a yield of 89.3% were obtained; and 14.1g of wogonin with a purity of 98.6wt% and a yield of 87.4% were obtained.

[0102] Example 6

[0103] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0104] (1), (2), and (3) are performed in the same manner as in Example 1; the baicalin content in the first solution to be treated is 6.541 mg / ml, the baicalein content is 1.740 mg / ml, and the wogonin content is 1.314 mg / ml; 81.9 g of baicalin was obtained, with a purity of 87.4 wt% and a yield of 90.4%;

[0105] (4) The solution to be treated was heated to 70°C, the pH was adjusted to 2.2, and the mixture was stirred and crystallized for 3 hours. After crystallization, the mixture was filtered while hot, and the filter cake was dried to obtain 19.2 g of baicalin with a purity of 96.9 wt% and a yield of 88.4%.

[0106] (5) The operation is the same as in Example 1;

[0107] 14.2g of baicalein was obtained with a purity of 98.4wt% and a yield of 87.9%.

[0108] Example 7

[0109] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0110] (1), (2), and (3) are performed in the same manner as in Example 1; the baicalin content in the first solution to be treated is 6.541 mg / ml, the baicalein content is 1.740 mg / ml, and the wogonin content is 1.314 mg / ml; 81.6 g of baicalin was obtained, with a purity of 87.6 wt% and a yield of 90.3%;

[0111] (4) The solution to be treated was heated to 80°C, the pH was adjusted to 2.0, and the mixture was stirred and crystallized for 5 hours. After crystallization, the mixture was filtered while hot, and the filter cake was dried to obtain 19.6 g of baicalin with a purity of 96.2 wt% and a yield of 89.6%.

[0112] (5) The operation was the same as in Example 1, and 14.1g of baicalein was obtained with a purity of 98.2wt% and a yield of 87.1%.

[0113] Example 8

[0114] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0115] (1), (2), (3), (4) are the same as in Example 1; the content of baicalin in the first solution to be treated is 6.541 mg / ml, the content of baicalein is 1.740 mg / ml, and the content of wogonin is 1.314 mg / ml;

[0116] (5) Adjust the pH of filtrate three to 2.8, de-alcoholize under reduced pressure and concentrate to a solid content of 25%, cool to 45°C, crystallize for 3 hours, filter to obtain filter cake four, reflux filter cake four with ethanol solution of 15% v / v at 91°C for 2 hours, filter while hot after reflux, and dry filter cake five to obtain baicalein; filtrate four is combined with filtrate one in step (1), and filtrate five is concentrated and de-alcoholized and returned to the liquid to be treated three in step (3) for recycling.

[0117] 82.1g of baicalin with a purity of 87.4wt% and a yield of 90.7% were obtained; 19.4g of baicalein with a purity of 96.5wt% and a yield of 88.9% were obtained; and 14.2g of wogonin with a purity of 98.3wt% and a yield of 87.8% were obtained.

[0118] Example 9

[0119] A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis includes the following steps:

[0120] (1), (2), (3), (4) are the same as in Example 1; the content of baicalin in the first solution to be treated is 6.541 mg / ml, the content of baicalein is 1.740 mg / ml, and the content of wogonin is 1.314 mg / ml;

[0121] (5) Adjust the pH of filtrate three to 3.0, de-alcoholize under reduced pressure and concentrate to a solid content of 35wt%, cool to 40℃, crystallize for 1h, filter to obtain filter cake four, reflux filter cake four with 10% v / v ethanol solution at 96℃ for 3h, filter while hot after reflux, and dry filter cake five to obtain baicalin; filtrate four is combined with filtrate one in step (1), and filtrate five is concentrated and de-alcoholized and returned to the liquid to be treated three in step (3) for recycling.

[0122] 82.4g of baicalin with a purity of 87.2wt% and a yield of 90.8% were obtained; 19.5g of baicalein with a purity of 96.4wt% and a yield of 89.3% were obtained; and 14.2g of wogonin with a purity of 98.5% and a yield of 88.0% were obtained.

[0123] Comparative Example 1

[0124] The difference between this example and Example 1 is that in step (2), the liquid to be treated is heated to 80°C, and the other operations are the same as in Example 1.

[0125] 86.1g of baicalin with a purity of 83.8wt% and a yield of 91.2% were obtained; 17.9g of baicalein with a purity of 96.2wt% and a yield of 81.8% were obtained; and 12.9g of wogonin with a purity of 98.1wt% and a yield of 79.6% were obtained.

[0126] Comparative Example 2

[0127] The difference between this example and Example 1 is that in step (2), the pH is adjusted to 1.3 with dilute hydrochloric acid, and the other operations are the same as in Example 1;

[0128] 87.5g of baicalin with a purity of 82.6wt% and a yield of 91.3% were obtained; 17.5g of baicalein with a purity of 95.9wt% and a yield of 79.7% were obtained; and 12.5g of wogonin with a purity of 97.8wt% and a yield of 76.9% were obtained.

[0129] Comparative Example 3

[0130] The difference between this example and Example 1 is that in step (2), the pH is adjusted to 2.0 with dilute hydrochloric acid, and the other operations are the same as in Example 1;

[0131] 73.4g of baicalin with a purity of 87.6wt% and a yield of 81.2% were obtained; 19.6g of baicalein with a purity of 95.1wt% and a yield of 88.5% were obtained; and 12.0g of wogonin with a purity of 97.5wt% and a yield of 73.6% were obtained.

[0132] Comparative Example 4

[0133] The difference between this example and Example 1 is that in step (2), the concentration of the ethanol solution is 45% v / v, and the other operations are the same as in Example 1.

[0134] 85.5g of baicalin with a purity of 84.7wt% and a yield of 91.5% were obtained; 18.3g of baicalein with a purity of 96.7wt% and a yield of 84.1% were obtained; and 12.8g of wogonin with a purity of 99.0wt% and a yield of 79.7% were obtained.

[0135] Comparative Example 5

[0136] The difference between this example and Example 1 is that in step (2), the concentration of the ethanol solution is 60% v / v, and the other operations are the same as in Example 1.

[0137] 72.2g of baicalin with a purity of 87.5wt% and a yield of 79.8% were obtained; 18.6g of baicalein with a purity of 93.2wt% and a yield of 82.3% were obtained; and 12.6g of wogonin with a purity of 97.3wt% and a yield of 77.1% were obtained.

[0138] Comparative Example 6

[0139] The difference between this example and Example 1 is that in step (2), the pH of the solution to be treated is 2.5, and the other operations are the same as in Example 1;

[0140] 82.5g of baicalin with a purity of 87.3wt% and a yield of 91.0% were obtained; 21.5g of baicalein with a purity of 88.9wt% and a yield of 90.8% were obtained; and 11.1g of wogonin with a purity of 96.3wt% and a yield of 67.2% were obtained.

[0141] Comparative Example 7

[0142] The difference between this example and Example 1 is that in step (2), the pH of the solution to be treated is 4.0, and the other operations are the same as in Example 1;

[0143] 82.3g of baicalin with a purity of 87.2wt% and a yield of 90.7% were obtained; 10.5g of baicalein with a purity of 96.3wt% and a yield of 48.0% were obtained; and 8.2g of wogonin with a purity of 98.0wt% and a yield of 50.5% were obtained.

[0144] Comparative Example 8

[0145] The difference between this example and Example 1 is that in step (2), the solid content of the liquid to be treated is 15wt%, and the other operations are the same as in Example 1.

[0146] 82.4g of baicalin with a purity of 87.4wt% and a yield of 91.0% were obtained; 16.8g of baicalein with a purity of 96.1wt% and a yield of 76.7% were obtained; and 12.9g of wogonin with a purity of 98.2wt% and a yield of 79.7% were obtained.

[0147] Comparative Example 9

[0148] The difference between this example and Example 1 is that in step (2), the solid content of the liquid to be treated is 30wt%, and the other operations are the same as in Example 1;

[0149] 82.0g of baicalin with a purity of 87.5wt% and a yield of 90.7% were obtained; 20.5g of baicalein with a purity of 94.4wt% and a yield of 91.9% were obtained; and 13.6g of wogonin with a purity of 97.9wt% and a yield of 83.7% were obtained.

[0150] Comparative Example 10

[0151] The difference between this example and Example 1 is that in step (3), the volume ratio of ethyl acetate to n-butanol in the water-saturated ethyl acetate-n-butanol is 8.0:1, and the other operations are the same as in Example 1;

[0152] 82.5g of baicalin with a purity of 87.2wt% and a yield of 90.9% were obtained; 20.6g of baicalein with a purity of 94.1wt% and a yield of 92.1% were obtained; and 13.4g of wogonin with a purity of 97.6wt% and a yield of 82.3% were obtained.

[0153] Comparative Example 11

[0154] The difference between this example and Example 1 is that in step (3), the volume ratio of ethyl acetate to n-butanol in the water-saturated ethyl acetate-n-butanol is 9.5:1, and the other operations are the same as in Example 1;

[0155] 82.4g of baicalin with a purity of 87.4wt% and a yield of 91.0% were obtained; 17.4g of baicalein with a purity of 96.5wt% and a yield of 79.8% were obtained; and 12.9g of wogonin with a purity of 98.2wt% and a yield of 79.7% were obtained.

[0156] Comparative Example 12

[0157] The difference between this example and Example 1 is that in step (3), the solid content of the liquid to be treated is 3wt%, and the other operations are the same as in Example 1.

[0158] 82.2g of baicalin with a purity of 87.3wt% and a yield of 90.7% were obtained; 17.2g of baicalein with a purity of 96.9wt% and a yield of 79.2% were obtained; and 13.2g of wogonin with a purity of 97.9wt% and a yield of 81.3% were obtained.

[0159] Comparative Example 13

[0160] The difference between this example and Example 1 is that in step (3), the solid content of the liquid to be treated is 10wt%, and the other operations are the same as in Example 1.

[0161] 82.1g of baicalin with a purity of 87.3wt% and a yield of 90.6% were obtained; 20.6g of baicalein with a purity of 93.1wt% and a yield of 91.1% were obtained; and 11.1g of wogonin with a purity of 97.7wt% and a yield of 68.2% were obtained.

[0162] Comparative Example 14

[0163] The difference between this example and Example 1 is that in step (3), the ethanol concentration in the solution to be treated is 15% v / v, and the other operations are the same as in Example 1.

[0164] 82.4g of baicalin with a purity of 87.4wt% and a yield of 91.0% were obtained; 20.3g of baicalein with a purity of 94.8wt% and a yield of 91.4% were obtained; and 12.6g of wogonin with a purity of 97.6wt% and a yield of 77.3% were obtained.

[0165] Comparative Example 15

[0166] The difference between this example and Example 1 is that in step (3), the ethanol concentration in the solution to be treated is 45% v / v, and the other operations are the same as in Example 1.

[0167] 82.0g of baicalin with a purity of 87.2wt% and a yield of 90.3% were obtained; 16.8g of baicalein with a purity of 96.8wt% and a yield of 77.2% were obtained; and 10.9g of wogonin with a purity of 97.3wt% and a yield of 66.7% were obtained.

[0168] Comparative Example 16

[0169] The difference between this example and Example 1 is that in step (4), the liquid to be treated is heated to 60°C, and the other operations are the same as in Example 1.

[0170] 82.4g of baicalin with a purity of 86.9wt% and a yield of 90.5% were obtained; 20.2g of baicalein with a purity of 94.9wt% and a yield of 91.1% were obtained; and 12.9g of wogonin with a purity of 98.2wt% and a yield of 79.7% were obtained.

[0171] Comparative Example 17

[0172] The difference between this example and Example 1 is that in step (4), the pH is adjusted to 1.5, and the other operations are the same as in Example 1;

[0173] 82.2g of baicalin with a purity of 87.6wt% and a yield of 91.0% were obtained; 21.8g of baicalein with a purity of 89.0wt% and a yield of 92.2% were obtained; and 11.6g of wogonin with a purity of 98.1wt% and a yield of 71.6% were obtained.

[0174] Comparative Example 18

[0175] The difference between this example and Example 1 is that in step (4), the pH is adjusted to 2.5, and the other operations are the same as in Example 1;

[0176] 82.3g of baicalin with a purity of 87.4wt% and a yield of 90.9% were obtained; 13.3g of baicalein with a purity of 96.7wt% and a yield of 61.1% were obtained; and 9.5g of wogonin with a purity of 97.1wt% and a yield of 58.0% were obtained.

[0177] Comparative Example 19

[0178] The difference between this example and Example 1 is that in step (5), the pH of the filtrate is adjusted to 2.5, and the other operations are the same as in Example 1;

[0179] 82.2g of baicalin with a purity of 87.2wt% and a yield of 90.6% were obtained; 19.5g of baicalein with a purity of 96.7wt% and a yield of 89.6% were obtained; and 11.4g of wogonin with a purity of 95.2wt% and a yield of 68.3% were obtained.

[0180] Comparative Example 20

[0181] The difference between this example and Example 1 is that in step (5), the pH of the filtrate is adjusted to 3.5, and the other operations are the same as in Example 1;

[0182] 82.5g of baicalin with a purity of 87.0wt% and a yield of 90.7% were obtained; 19.6g of baicalein with a purity of 96.5wt% and a yield of 89.8% were obtained; and 9.0g of wogonin with a purity of 98.3wt% and a yield of 55.6% were obtained.

[0183] Comparative Example 21

[0184] The difference between this example and Example 1 is that in step (5), the alcohol is removed under reduced pressure and concentrated to a solid content of 20 wt%, while the other operations are the same as in Example 1.

[0185] 82.4g of baicalin with a purity of 86.9wt% and a yield of 90.5% were obtained; 19.4g of baicalein with a purity of 96.6wt% and a yield of 89.0% were obtained; and 11.5g of wogonin with a purity of 98.4wt% and a yield of 71.2% were obtained.

[0186] Comparative Example 22

[0187] The difference between this example and Example 1 is that in step (5), the alcohol is removed under reduced pressure and concentrated to a solid content of 40 wt%, while the other operations are the same as in Example 1.

[0188] 82.5g of baicalin with a purity of 87.3wt% and a yield of 91.0% were obtained; 19.5g of baicalein with a purity of 96.8wt% and a yield of 89.7% were obtained; and 11.8g of wogonin with a purity of 97.1wt% and a yield of 72.1% were obtained.

[0189] Comparative Example 23

[0190] The difference between this example and Example 1 is that in step (5), the concentration of the ethanol solution is 5% v / v, and the other operations are the same as in Example 1.

[0191] 82.1g of baicalin with a purity of 87.4wt% and a yield of 90.7% were obtained; 19.4g of baicalein with a purity of 96.5wt% and a yield of 88.9% were obtained; and 14.8g of wogonin with a purity of 96.7wt% and a yield of 90.0% were obtained.

[0192] Comparative Example 24

[0193] The difference between this example and Example 1 is that in step (5), the concentration of the ethanol solution is 20% v / v, and the other operations are the same as in Example 1;

[0194] 82.7g of baicalin with a purity of 87.1wt% and a yield of 91.0% were obtained; 19.6g of baicalein with a purity of 96.3wt% and a yield of 89.6% were obtained; and 12.8g of wogonin with a purity of 98.7wt% and a yield of 79.5% were obtained.

[0195] This document uses specific examples to illustrate the principles and implementation methods of the present invention. The descriptions of these embodiments are merely to aid in understanding the method and core ideas of the present invention, including the best mode, and to enable any person skilled in the art to practice the present invention, including manufacturing and using any device or system, and implementing any combined method. It should be noted that those skilled in the art can make various improvements and modifications to the present invention without departing from its principles, and these improvements and modifications also fall within the scope of protection of the claims. The scope of protection of this patent is defined by the claims and may include other embodiments that can be conceived by those skilled in the art. If these other embodiments have structural elements similar to those expressed in the claims, or if they include equivalent structural elements that are not substantially different from those expressed in the claims, then these other embodiments should also be included within the scope of the claims.

Claims

1. A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis, characterized in that, Includes the following steps: (1) Ethanol solution was used as the extraction solvent to extract the waste residue of Scutellaria baicalensis extraction. The obtained extract was then post-treated to obtain the first solution to be treated. (2) The above-mentioned liquid to be treated is heated and the pH is adjusted, stirred and crystallized, and then filtered to obtain filter cake 1 and filtrate 1; filter cake 1 and ethanol solution are mixed and refluxed, and after reflux, they are filtered to obtain filter cake 2 and filtrate 2; filter cake 2 is dried to obtain baicalin; filtrate 1 is adjusted and concentrated and then mixed with filtrate 2 which has been successively treated by alcohol removal, pH adjustment and concentration to obtain liquid to be treated 2; (3) Use water-saturated ethyl acetate-n-butanol as the extractant to extract the second solution of the treatment solution multiple times and collect the extract phase; concentrate the above extract phase to remove ethyl acetate-n-butanol and then add ethanol to dilute to obtain the third solution of the treatment solution; (4) After heating the solution to be treated, adjust the pH and stir to crystallize. After crystallization, filter while hot to obtain filter cake three and filtrate three. Dry filter cake three to obtain baicalin. (5) After adjusting the pH of filtrate three, remove alcohol, concentrate and cool to crystallize, filter after crystallization to obtain filter cake four and filtrate four; filter cake four is purified and dried to obtain baicalin.

2. The method for co-producing baicalin, baicalein and wogonin from the waste residue of Scutellaria baicalensis extraction according to claim 1, characterized in that, In step (1), when using ethanol solution as the extraction solvent to extract the waste residue from Scutellaria baicalensis extraction, at least one of the following characteristics must be included: The concentration of the ethanol solution is 50-55% v / v; The amount of ethanol solution used is 5-8 times the weight of the waste residue from the Scutellaria baicalensis extraction. The extraction temperature is 81-83℃, and the extraction time is 1-3 hours each time; The extraction is performed 3-5 times.

3. The method for co-producing baicalin, baicalein and wogonin from the waste residue of Scutellaria baicalensis extraction according to claim 1, characterized in that, In step (1), the post-processing process includes: concentrating and de-alcoholizing the extracts from multiple extractions to obtain a liquid to be treated with a solid content of 3-5 wt%.

4. The method for co-producing baicalin, baicalein and wogonin from the waste residue of Scutellaria baicalensis extraction according to claim 1, characterized in that, In step (2), the preparation of baicalin shall include at least one of the following characteristics: The heating temperature is 90-100℃, and the pH of the above-mentioned liquid to be treated is adjusted to 1.5-1.8 after heating. The stirring crystallization process takes 0.5-1 hour. The concentration of the ethanol solution is 50-55% v / v; The mass ratio of the filter cake to the ethanol solution is 1:(8-10). The reflux temperature is 83-85℃, and the time is 1-3 hours.

5. A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis according to claim 1, characterized in that, When preparing the second solution to be treated, at least one of the following characteristics must be included: Adjust the pH of filtrate one and filtrate two to 3.0-3.5 respectively; After adjusting the pH of filtrate 1 and filtrate 2, the solid content of each filtrate was concentrated to 20-25 wt%.

6. The method for co-producing baicalin, baicalein and wogonin from the waste residue of Scutellaria baicalensis extraction according to claim 1, characterized in that, In step (3), the volume ratio of ethyl acetate to n-butanol in the water-saturated ethyl acetate-n-butanol solution is (8.5-9.0):1; and / or during extraction, the volume ratio of the solution to be treated to the extractant is 1:(1-3); and / or the number of extractions is 3-4; and / or the solid content of the solution to be treated is 5-8wt%, and the ethanol concentration is 25-35%v / v.

7. A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis according to claim 1, characterized in that, In step (4), the heating temperature is 70-80℃, the pH is adjusted to 2.0-2.2, and the stirring crystallization time is 3-5h.

8. A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis according to claim 1, characterized in that, In step (5), the pH of the filtrate is adjusted to 2.8-3.0; the solid content is concentrated to 25-35wt%; the temperature for cooling and crystallization is 40-45℃ and the time is 1-3h.

9. A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis according to claim 1, characterized in that, In step (5), the filtrate four is combined with filtrate one; and / or the process of refining the filter cake four includes: mixing filter cake four with ethanol solution and refluxing to precipitate, then filtering while hot to obtain filter cake five and filtrate five, and drying filter cake five to obtain baicalin.

10. A method for co-producing baicalin, baicalein and wogonin from waste residue extracted from Scutellaria baicalensis according to claim 1, characterized in that, In step (5), the filter cake undergoes a four-stage refining process that includes at least one of the following characteristics: The concentration of the ethanol solution is 10-15% v / v, and the mass ratio of the filter cake to the ethanol solution is 1:(3-5); the reflux precipitation temperature is 91-96℃, and the time is 2-3h. The filtrate is concentrated and de-alcoholized before being recycled to the third solution to be treated.