Carbenoxolone and a method of preparation thereof

Abstract

The application discloses a Zizyphus jujuba Mill. and valeriana compound subcritical extract and a preparation method thereof, and belongs to the technical field of Chinese medicine extract preparation. In view of the defects of the traditional decoction and alcohol extraction process, the subcritical fluid selective extraction process is adopted, liquid butane and ethanol are used as the mixed solvent, and specific extraction pressure, temperature and time are controlled, so that the fat-soluble and heat-sensitive active ingredients, such as Zizyphus jujuba Mill. saponin A, valerenic acid and total flavonoids of Albizia julibrissin, in the compound raw material can be effectively extracted, the active ingredient thermal degradation loss caused by high temperature is avoided, the extraction rate and enrichment degree of the active ingredient are significantly improved, the content of Zizyphus jujuba Mill. saponin in the obtained extract is not less than 5%, and the content of valerenic acid is not less than 2%.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine extract preparation technology, and more specifically, relates to a subcritical extract of jujube seed and spider lily and its preparation method. Background Technology

[0002] Traditional Chinese medicine products for calming the mind and aiding sleep are widely used in daily health care and clinical adjunctive treatment due to their mildness and few side effects. Spider incense, jujube seed, valerian, albizia bark, polygala, and polygonum multiflorum are all traditional herbal medicines for calming the mind and aiding sleep. Spider incense regulates qi, relieves pain, aids digestion, stops diarrhea, and calms the mind; jujube seed nourishes the heart and liver, and calms the mind; valerian calms the mind, regulates qi, and relieves pain; albizia bark relieves depression, calms the mind, promotes blood circulation, and reduces swelling; polygala calms the mind, improves intelligence, eliminates phlegm, and opens the orifices; and polygonum multiflorum nourishes blood, calms the mind, dispels wind, and unblocks the meridians. Combining these herbs can achieve a synergistic effect in calming the mind and aiding sleep.

[0003] Currently, the preparation of extracts from traditional Chinese medicine compound formulas mostly adopts the traditional water decoction and alcohol extraction process. Although this process is simple to operate and low in cost, it has significant drawbacks: First, the water decoction and alcohol extraction process requires a high-temperature step, and the core sedative components in herbs such as spider lily and jujube seed are mostly fat-soluble and heat-sensitive substances (such as jujube seed saponin A, valeric acid, and total flavonoids from albizia bark). High temperatures easily lead to the thermal degradation of these active ingredients, resulting in serious loss of effective components and reducing the sedative efficacy of the extract. Second, the traditional process has poor selectivity. While extracting active ingredients, it is easy to co-extract water-soluble impurities, tannins, and other useless components from the herbs, resulting in high impurity content, low purity, and insufficient enrichment of active ingredients in the extract. Third, excessive impurities will affect the stability and product quality of subsequent formulation processing, which is not conducive to the standardized production of Chinese medicine raw materials and makes it difficult to meet the needs of large-scale, high-quality production of sedative and sleep-aiding Chinese medicine products.

[0004] Subcritical fluid extraction is a novel natural product extraction technology with advantages such as low temperature, high efficiency, and strong selectivity. It can effectively retain heat-sensitive active ingredients while reducing impurities during co-extraction. It has been initially applied in the preparation of single Chinese herbal extracts. However, there are no reports on applying this technology to the compound extraction of multiple medicinal materials such as spider lily and jujube seed, optimizing the extraction process parameters according to the characteristics of the compound medicinal materials, and achieving efficient enrichment of active ingredients.

[0005] Therefore, a method for preparing a compound extract of spider lily and jujube seed based on subcritical fluid extraction was developed to overcome the shortcomings of traditional processes and achieve standardized and high-quality production of the compound extract. Summary of the Invention

[0006] To address the aforementioned problems in the existing technology, the technical problem to be solved by this invention is to provide a subcritical extract of jujube seed compound containing *Ziziphus jujuba* var. *spora*, wherein the content of jujube seed saponins is not less than 5%, the content of valeric acid is not less than 2%, and the solvent residue is lower than the limit requirements of the National Pharmacopoeia. Another technical problem to be solved by this invention is to provide a method for preparing the above-mentioned subcritical extract of jujube seed compound containing *Ziziphus jujuba* var. *spora*, which, compared with the traditional water decoction and alcohol extraction process, has higher extraction efficiency and more stable product quality.

[0007] To solve the above-mentioned technical problems, the technical solution adopted by the present invention is as follows:

[0008] A method for preparing a subcritical extract of jujube seed compound containing spider lily, comprising the following steps:

[0009] 1) Weigh out the following ingredients according to the weight ratio: spider lily, jujube seed, valerian, albizia bark, polygala root, and polygonum multiflorum stem. After drying, pulverize and mix evenly to obtain compound raw material powder.

[0010] 2) Place the compound raw material powder obtained in step 1) into a subcritical extraction tank, add extraction solvent to extract, and obtain the extract;

[0011] 3) The extract obtained in step 2) was concentrated by vacuum distillation to obtain the subcritical extract of spider lily jujube seed compound.

[0012] Preferably, in step 1), the weight ratio of spider lily, jujube seed, valerian, albizia bark, polygala root, and polygonum multiflorum is 10~30:20~30:20~30:10~15:15:15~20.

[0013] Preferably, in step 1), the low-temperature drying temperature is 50~60℃ and the drying time is 4~6h.

[0014] Preferably, in step 1), the powder is passed through an 80-100 mesh sieve.

[0015] Preferably, in step 2), the extraction solvent is a mixture of liquid butane and ethanol.

[0016] Preferably, in step 2), the ratio of the compound raw material powder to the extraction solvent is 5:7~11.

[0017] Preferably, in step 2), the extraction pressure is 0.5 MPa, the extraction temperature is 5°C, and the extraction time is 8 h.

[0018] Preferably, in step 3), the conditions for vacuum distillation are: vacuum degree 0.08~0.09MPa and temperature 5℃.

[0019] Preferably, the volume ratio of the liquid butane to ethanol is 5~10:0.5~2.

[0020] The method described above describes the preparation of the spider-scented jujube seed compound subcritical extract.

[0021] Beneficial effects: Compared with the prior art, the present invention has the following advantages:

[0022] 1) This invention addresses the shortcomings of traditional water-decoction and alcohol extraction processes by innovatively employing a subcritical fluid selective extraction process. Using liquid butane and ethanol as a mixed solvent, and controlling specific extraction pressure, temperature, and time, it can effectively extract fat-soluble and heat-sensitive active ingredients such as jujube seed saponin A, valeric acid, and total flavonoids from Albizia bark from compound raw materials. This avoids the thermal degradation loss of active ingredients caused by high temperatures, significantly improving the extraction rate and enrichment of active ingredients. The resulting extract contains no less than 5% jujube seed saponin and no less than 2% valeric acid, exhibiting significant calming and sleep-aiding effects.

[0023] 2) This invention optimizes the extraction solvent ratio and process parameters, and the extraction process has strong selectivity, which can effectively avoid the co-extraction of water-soluble impurities and tannins, reduce the impurity content in the extract, improve the purity of the extract, and at the same time, the solvent residue is lower than the national pharmacopoeia limit, ensuring the quality, safety and stability of the extract, and providing high-quality raw materials for subsequent formulation processing.

[0024] 3) The preparation method of the present invention is simple to operate, with clear process parameters, and the extraction solvent can be recycled, which reduces production costs. Moreover, the entire process is mild and has no pollutant emissions, meeting the requirements of green production. The obtained extract can be directly used in the subsequent preparation processing of external patches, ointments or essential oils, and is suitable for the standardized and large-scale production of raw materials for calming and sleep-aiding traditional Chinese medicine products, with broad application prospects.

[0025] 4) Compared with the traditional water decoction and alcohol extraction process, the preparation method of the present invention has higher extraction efficiency and more stable product quality. Compared with the subcritical extraction of a single medicinal material, it realizes the synergistic extraction of multiple medicinal materials and fills the gap in the subcritical extraction technology of spider lily and jujube seed compound. Detailed Implementation

[0026] To make the objectives, technical solutions, and advantages of this invention clearer, the invention is further described below with reference to specific embodiments. Unless otherwise specified, the technical means used in the following embodiments are all conventional means well known to those skilled in the art. Where specific conditions are not specified in the embodiments, conventional conditions or conditions recommended by the manufacturer are followed. Where the manufacturers of reagents or instruments are not specified, they are all conventional products that can be purchased commercially.

[0027] Example 1

[0028] A method for preparing a subcritical extract of jujube seed compound containing spider lily, comprising the following steps:

[0029] 1) Weigh 300g of spider lily, 200g of jujube seed, 200g of valerian, 150g of albizia bark, 150g of polygala root, and 150g of polygonum multiflorum stem. Remove impurities from each ingredient, wash them with distilled water, and dry them in an oven at 55℃ for 5 hours until constant weight. Then, pulverize them with a pulverizer, pass them through a 5-mesh sieve, and mix them evenly to obtain compound raw material powder.

[0030] 2) Place the compound raw material powder obtained in step 1) into a subcritical extraction vessel, add the extraction solvent, wherein the ratio of compound raw material to butane and ethanol is 5:10:0.5 g / mL / mL. Close the extraction vessel, purge the air from the vessel with nitrogen, control the extraction pressure at 0.5 MPa, the extraction temperature at 5℃, and perform static extraction for 8 hours. After extraction, collect the extract.

[0031] 3) The extract is fed into a vacuum distillation column, and the vacuum degree is controlled at 0.085 MPa and the temperature at 5℃. Vacuum distillation is carried out to recover liquid butane and ethanol solvent. The recovered solvent can be recycled for the next extraction after purification. Continue to concentrate under reduced pressure to a thick paste state to obtain the spider lily jujube seed compound subcritical extract.

[0032] Example 2

[0033] A method for preparing a subcritical extract of jujube seed compound containing spider lily, comprising the following steps:

[0034] 1) Weigh 200g of spider lily, 200g of jujube seed, 250g of valerian, 100g of albizia bark, 150g of polygala root, and 200g of polygonum multiflorum stem. Remove impurities and wash them with distilled water. Place them in an oven at 55℃ and dry for 5 hours until constant weight. Then, pulverize them with a pulverizer, pass them through a 5-mesh sieve, and mix them evenly to obtain compound raw material powder.

[0035] 2) Place the compound raw material powder obtained in step 1) into a subcritical extraction vessel, add the extraction solvent, wherein the ratio of compound raw material to butane and ethanol is 5:10:0.5 g / mL / mL. Close the extraction vessel, purge the air from the vessel with nitrogen, control the extraction pressure at 0.5 MPa, the extraction temperature at 5℃, and perform static extraction for 8 hours. After extraction, collect the extract.

[0036] 3) The extract is fed into a vacuum distillation column, and the vacuum degree is controlled at 0.085 MPa and the temperature at 5℃. Vacuum distillation is carried out to recover liquid butane and ethanol solvent. The recovered solvent can be recycled for the next extraction after purification. Continue to concentrate under reduced pressure to a thick paste state to obtain the spider lily jujube seed compound subcritical extract.

[0037] Example 3

[0038] A method for preparing a subcritical extract of jujube seed compound containing spider lily, comprising the following steps:

[0039] 1) Weigh 300g of spider lily, 200g of jujube seed, 200g of valerian, 150g of albizia bark, 150g of polygala root, and 150g of polygonum multiflorum stem. Remove impurities from each ingredient, wash them with distilled water, and dry them in an oven at 55℃ for 5 hours until constant weight. Then, pulverize them with a pulverizer, pass them through a 5-mesh sieve, and mix them evenly to obtain compound raw material powder.

[0040] 2) Place the compound raw material powder obtained in step 1) into a subcritical extraction vessel, add the extraction solvent, wherein the ratio of compound raw material to butane and ethanol is 5:9:1 (g / mL / mL), close the extraction vessel, purge the air from the vessel with nitrogen, control the extraction pressure at 0.5 MPa, the extraction temperature at 5℃, and perform static extraction for 8 hours. After extraction, collect the extract.

[0041] 3) The extract is fed into a vacuum distillation column, and the vacuum degree is controlled at 0.085 MPa and the temperature at 5℃. Vacuum distillation is carried out to recover liquid butane and ethanol solvent. The recovered solvent can be recycled for the next extraction after purification. Continue to concentrate under reduced pressure to a thick paste state to obtain the spider lily jujube seed compound subcritical extract.

[0042] Example 4

[0043] A method for preparing a subcritical extract of jujube seed compound containing spider lily, comprising the following steps:

[0044] 1) Weigh 300g of spider lily, 200g of jujube seed, 200g of valerian, 150g of albizia bark, 150g of polygala root, and 150g of polygonum multiflorum stem. Remove impurities from each ingredient, wash them with distilled water, and dry them in an oven at 55℃ for 5 hours until constant weight. Then, pulverize them with a pulverizer, pass them through a 5-mesh sieve, and mix them evenly to obtain compound raw material powder.

[0045] 2) Place the compound raw material powder obtained in step 1) into a subcritical extraction vessel, add the extraction solvent, wherein the ratio of compound raw material to butane and ethanol is 5:8:1 (g / mL / mL), close the extraction vessel, purge the air from the vessel with nitrogen, control the extraction pressure at 0.5 MPa, the extraction temperature at 5℃, and perform static extraction for 8 hours. After extraction, collect the extract.

[0046] 3) The extract is fed into a vacuum distillation column, and the vacuum degree is controlled at 0.085 MPa and the temperature at 5℃. Vacuum distillation is carried out to recover liquid butane and ethanol solvent. The recovered solvent can be recycled for the next extraction after purification. Continue to concentrate under reduced pressure to a thick paste state to obtain the spider lily jujube seed compound subcritical extract.

[0047] Example 5

[0048] A method for preparing a subcritical extract of jujube seed compound containing spider lily, comprising the following steps:

[0049] 1) Weigh 300g of spider lily, 200g of jujube seed, 200g of valerian, 150g of albizia bark, 150g of polygala root, and 150g of polygonum multiflorum stem. Remove impurities from each ingredient, wash them with distilled water, and dry them in an oven at 55℃ for 5 hours until constant weight. Then, pulverize them with a pulverizer, pass them through a 5-mesh sieve, and mix them evenly to obtain compound raw material powder.

[0050] 2) Place the compound raw material powder obtained in step 1) into a subcritical extraction vessel, add the extraction solvent, wherein the ratio of compound raw material to butane and ethanol is 5:7:1 (g / mL / mL), close the extraction vessel, purge the air from the vessel with nitrogen, control the extraction pressure at 0.5 MPa, the extraction temperature at 5℃, and perform static extraction for 8 hours. After extraction, collect the extract.

[0051] 3) The extract is fed into a vacuum distillation column, and the vacuum degree is controlled at 0.085 MPa and the temperature at 5℃. Vacuum distillation is carried out to recover liquid butane and ethanol solvent. The recovered solvent can be recycled for the next extraction after purification. Continue to concentrate under reduced pressure to a thick paste state to obtain the spider lily jujube seed compound subcritical extract.

[0052] Example 6

[0053] A method for preparing a subcritical extract of jujube seed compound containing spider lily, comprising the following steps:

[0054] 1) Weigh 300g of spider lily, 200g of jujube seed, 200g of valerian, 150g of albizia bark, 150g of polygala root, and 150g of polygonum multiflorum stem. Remove impurities from each ingredient, wash them with distilled water, and dry them in an oven at 55℃ for 5 hours until constant weight. Then, pulverize them with a pulverizer, pass them through a 5-mesh sieve, and mix them evenly to obtain compound raw material powder.

[0055] 2) Place the compound raw material powder obtained in step 1) into a subcritical extraction vessel, add the extraction solvent, wherein the ratio of compound raw material to butane and ethanol is 5:6:2 g / mL / mL, close the extraction vessel, purge the air in the vessel with nitrogen, control the extraction pressure to 0.5 MPa, the extraction temperature to 5℃, and perform static extraction for 8 hours. After extraction, collect the extract.

[0056] 3) The extract is fed into a vacuum distillation column, and the vacuum degree is controlled at 0.085 MPa and the temperature at 5℃. Vacuum distillation is carried out to recover liquid butane and ethanol solvent. The recovered solvent can be recycled for the next extraction after purification. Continue to concentrate under reduced pressure to a thick paste state to obtain the spider lily jujube seed compound subcritical extract.

[0057] Example 7

[0058] A method for preparing a subcritical extract of jujube seed compound containing spider lily, comprising the following steps:

[0059] 1) Weigh 300g of spider lily, 200g of jujube seed, 200g of valerian, 150g of albizia bark, 150g of polygala root, and 150g of polygonum multiflorum stem. Remove impurities from each ingredient, wash them with distilled water, and dry them in an oven at 55℃ for 5 hours until constant weight. Then, pulverize them with a pulverizer, pass them through a 5-mesh sieve, and mix them evenly to obtain compound raw material powder.

[0060] 2) Place the compound raw material powder obtained in step 1) into a subcritical extraction vessel, add the extraction solvent, wherein the ratio of compound raw material to butane and ethanol is 5:5:2 g / mL / mL, close the extraction vessel, purge the air in the vessel with nitrogen, control the extraction pressure to 0.5 MPa, the extraction temperature to 5℃, and perform static extraction for 8 hours. After extraction, collect the extract.

[0061] 3) The extract is fed into a vacuum distillation column, and the vacuum degree is controlled at 0.085 MPa and the temperature at 5℃. Vacuum distillation is carried out to recover liquid butane and ethanol solvent. The recovered solvent can be recycled for the next extraction after purification. Continue to concentrate under reduced pressure to a thick paste state to obtain the spider lily jujube seed compound subcritical extract.

[0062] Comparative Example 1

[0063] The preparation of the spider-scented jujube seed compound extract using the traditional water decoction and alcohol extraction process includes the following steps:

[0064] 1) Pretreatment: Weigh out 300g of spider incense, 200g of jujube seed, 200g of valerian, 150g of albizia bark, 150g of polygala root, and 150g of polygonum multiflorum stem. Remove impurities, wash with distilled water, clean the medicinal materials, dry them, and grind them into coarse powder of 15 mesh.

[0065] 2) Extraction: Use ethanol of appropriate concentration (95%) and extract by methods such as maceration, percolation, and reflux.

[0066] 3) Separation: Filter the extract, discard the residue, and obtain an ethanol extract containing the active ingredients;

[0067] 4) Concentration: Ethanol is recovered by vacuum distillation and concentrated to obtain an extract.

[0068] Example 8

[0069] The compound extracts prepared in Examples 1-7 and Comparative Example 1 were subjected to quality testing. The results are shown in Table 1.

[0070] Table 1. Quality test results of the compound extracts from Examples 1-7 and Comparative Example 1

[0071] Jujube seed saponin A content (%) Valerenoic acid content (%) Total flavonoid content (%) of Albizia bark Solvent residue (%) Example 1 5 2 1.5 0.5 Example 2 5 2.2 1.6 0.5 Example 3 5.5 2.3 1.7 0.5 Example 4 5.6 2.4 1.8 0.5 Example 5 5.5 2.4 1.8 0.5 Example 6 5.7 2.4 1.9 0.5 Example 7 5.8 2.5 1.9 0.5 Comparative Example 1 3.2 1.3 1 0.7

[0072] As shown in Table 1, the extract obtained by the subcritical extraction process of this invention has significantly higher contents of jujube seed saponin A, valeric acid, and total flavonoids from Albizia bark than the traditional water decoction and alcohol extraction process (Comparative Example 1), and the solvent residue is also lower. This effectively solves the defects of traditional processes, such as severe thermal degradation loss of active ingredients, high impurity content, and high solvent residue, and has obvious advantages.

[0073] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A method for preparing a subcritical extract of jujube seed and spider lily extract, characterized in that, Includes the following steps: 1) Weigh out the following ingredients according to the weight ratio: spider lily, jujube seed, valerian, albizia bark, polygala root, and polygonum multiflorum stem. After drying, pulverize and mix evenly to obtain compound raw material powder. 2) Place the compound raw material powder obtained in step 1) into a subcritical extraction tank, add extraction solvent to extract, and obtain the extract; 3) The extract obtained in step 2) was concentrated by vacuum distillation to obtain the subcritical extract of spider lily jujube seed compound.

2. The preparation method of the spider-scented jujube seed compound subcritical extract according to claim 1, characterized in that, In step 1), the weight ratio of spider lily, jujube seed, valerian, albizia bark, polygala root, and polygonum multiflorum is 10~30:20~30:20~30:10~15:15:15~20.

3. The preparation method of the spider-scented jujube seed compound subcritical extract according to claim 1, characterized in that, In step 1), the low-temperature drying temperature is 50~60℃ and the drying time is 4~6h.

4. The preparation method of the spider-scented jujube seed compound subcritical extract according to claim 1, characterized in that, In step 1), the powder is pulverized and then passed through a 5-mesh sieve.

5. The preparation method of the spider-scented jujube seed compound subcritical extract according to claim 1, characterized in that, In step 2), the extraction solvent is a mixture of liquid butane and ethanol.

6. The preparation method of the spider-scented jujube seed compound subcritical extract according to claim 1, characterized in that, In step 2), the ratio of the compound raw material powder to the extraction solvent is 5:7~11.

7. The preparation method of the spider-scented jujube seed compound subcritical extract according to claim 1, characterized in that, In step 2), the extraction pressure is 0.5 MPa, the extraction temperature is 5°C, and the extraction time is 8 h.

8. The preparation method of the subcritical extract of spider lily and jujube seed compound according to claim 1, characterized in that, In step 3), the conditions for vacuum distillation are: vacuum degree 0.08~0.09MPa, temperature 5℃.

9. The preparation method of the spider-scented jujube seed compound subcritical extract according to claim 5, characterized in that, The volume ratio of liquid butane to ethanol is 5~10:0.5~2.

10. The subcritical extract of jujube seed compound prepared by the method according to any one of claims 1-9.