A preparation method of malte extract

Abstract

The application belongs to the technical field of traditional Chinese medicines, and particularly relates to a preparation method of a Mailuoshutong extract. The Mailuoshutong extract is prepared from twelve kinds of raw medicinal materials including Astragalus membranaceus, honeysuckle, Phellodendron amurense, Atractylodes lancea, Coix seed, figwort, angelica, radix paeoniae alba, licorice, leech, scorpion and centipede. The preparation method is characterized in that: firstly, the three kinds of precious animal medicinal materials, i.e. leech, scorpion and centipede, are filtered through microfiltration and ultrafiltration, and the stench of the animal medicinal materials is effectively removed through a freeze-drying process, so that the amount of the dry extract powder is reduced, the dosage is reduced on the premise of ensuring that all components of the animal medicinal materials are extracted into the medicine, and the taste is improved. The honeysuckle is used in a backward way for volatile oil extraction, so that the content of the Mailuoshutong extract medicinal components and the volatile oil yield are improved, the operation process tends to be simple, continuous and efficient, the product stability can be improved, and the product quality is ensured.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a method for preparing a traditional Chinese medicine extract, and more particularly to a method for preparing a meridian-clearing extract. Background Technology

[0002] The prescription for the Meridian Relaxing Preparation is derived from traditional Chinese medicine formulas, including Dang Gui Bu Xue Tang, Shao Yao Gan Cao Tang, Si Miao Yong An Tang, and Zhi Jing San. The prescription is made from twelve Chinese herbs: Astragalus membranaceus, Lonicera japonica, Phellodendron chinense, Atractylodes lancea, Coix lacryma-jobi, Scrophularia ningpoensis, Angelica sinensis, Paeonia lactiflora, Glycyrrhiza uralensis, Hirudo medicinalis, Scorpio, and Scolopendra subspinipes. It has the effects of clearing heat and detoxifying, removing blood stasis and unblocking the meridians, and eliminating dampness and reducing swelling. It is mainly used for thrombophlebitis caused by damp-heat obstructing the meridians, and lower limb swelling, pain, dark red skin, or cord-like structures caused by non-acute deep vein thrombosis. This formula uses Astragalus membranaceus and Lonicera japonica as the principal herbs, which invigorate qi and promote diuresis, clear heat and detoxify, purge yin fire, detoxify muscles, clear foulness, and treat accumulated toxins. Phellodendron chinense, Atractylodes lancea, Coix lacryma-jobi, Angelica sinensis, Paeonia lactiflora, and Scrophularia ningpoensis are the assistant herbs, which clear heat and remove dampness, nourish blood, relieve spasms and cramps, harmonize the blood and relieve pain, soften hardness and dissipate nodules, reduce swelling and detoxify, and promote unobstructed blood flow. Leech, scorpion, and centipede are the adjuvant herbs, which invigorate blood and remove blood stasis, attack toxins and dissipate nodules, and unblock the meridians and relieve pain. Glycyrrhiza uralensis is the guiding herb to harmonize the effects of all the herbs. The combined effects of these herbs work synergistically to clear heat and detoxify, resolve blood stasis and unblock the meridians, promote diuresis and reduce swelling. The formula is potent and has achieved good clinical efficacy.

[0003] The product line includes various dosage forms such as Mailuoshutong Granules, Mailuoshutong Granules (sugar-free), and Mailuoshutong Pills (concentrated pills). Mailuoshutong Granules obtained a new drug certificate (Class III new drug of traditional Chinese medicine) and production license in 1998; Mailuoshutong Granules (sugar-free) obtained a supplementary application approval in 2012; and Mailuoshutong Pills (concentrated pills) obtained a drug registration approval in 2009. All of these products are exclusively produced in China and are the first traditional Chinese medicine approved for the treatment of thrombophlebitis. The launch of this series of products filled the market gap for traditional Chinese medicine drugs for treating damp-heat stagnation in the meridians, both domestically and internationally.

[0004] CN1201787C discloses a drug for treating thrombophlebitis, CN103933410A discloses the medicinal use of a traditional Chinese medicine composition and its preparation method, and CN101618161B discloses a traditional Chinese medicine composition for treating thrombophlebitis and its preparation method. The extraction and preparation methods of the above patent documents for the "Mailuoshutong" are as follows: steam distillation is used to extract volatile oil, cyclodextrin is added for inclusion, and cyclodextrin inclusion complex is obtained; the remaining medicinal materials are added with 1 / 2 of the prescription amount of animal medicinal materials and the residue after extracting volatile oil for water extraction and alcohol precipitation, and the extract is concentrated under reduced pressure and dried to obtain extract powder; the remaining 1 / 2 of the prescription amount of animal medicinal materials is pulverized into powder of the required particle size, and the extract powder, volatile oil inclusion complex and appropriate amounts of different kinds of pharmaceutical excipients are added to prepare a suitable dosage form. CN110123968A discloses a method for preparing a vascular smoothing preparation. The technical solution of this patent document is mainly based on the conventional extraction and preparation method of vascular smoothing in the above-mentioned patent document, and uses a double extraction method (alcohol reflux and water decoction) to extract three kinds of animal medicinal materials separately. The remaining extraction and preparation methods are the same as the above methods.

[0005] Existing methods for preparing pulmonase preparations have many drawbacks and shortcomings. For example, honeysuckle is added simultaneously with other herbs for volatile oil extraction, but chlorogenic acid in honeysuckle is easily destroyed under prolonged heating. In the original preparation method, half of the prescribed amount of animal herbs is used directly as animal powder without extraction, which not only increases the dosage for patients but also leads to poor patient compliance due to the strong fishy smell of the animal herbs. While using a dual extraction method to extract animal herbs separately solves the problems of large dosage and strong fishy smell, the effective components in animal herbs are not limited to water-soluble and alcohol-soluble components. The dual extraction method cannot completely extract the effective components from animal herbs, especially since these three types of animal herbs are precious and rare, which leads to resource waste and affects the efficacy of the preparation. Summary of the Invention

[0006] To address the shortcomings and deficiencies of existing technologies, this invention provides a method for preparing a blood vessel smoothing extract. By improving the original blood vessel smoothing composition extraction method, three kinds of precious animal medicinal materials are pulverized, mixed with water, and extracted. The extract is then further filtered using microfiltration and ultrafiltration. The filtrate is then freeze-dried into a freeze-dried powder, which effectively removes the fishy and foul odor of the animal medicinal materials and reduces the amount of extract powder. While ensuring the extraction of all components of the animal medicinal materials for medicinal use, the dosage is reduced and the taste is improved.

[0007] This invention also extracts the volatile oil from honeysuckle using a post-processing method, which increases the content of the key active ingredients and the extraction yield of volatile oil in the meridian-clearing extract. This makes the operation process simpler, more continuous, and more efficient, and can improve product stability, ensure product quality, and thus guarantee the clinical efficacy of the product.

[0008] The technical solution of the present invention is as follows:

[0009] A method for preparing a meridian-soothing extract, wherein the meridian-soothing extract is made from 12 raw medicinal materials including Astragalus membranaceus, Lonicera japonica, Phellodendron chinense, Atractylodes lancea, Scrophularia ningpoensis, Angelica sinensis, Paeonia lactiflora, Coix lacryma-jobi, Glycyrrhiza uralensis, Scolopendra subspinipes, Buthus martensii, and Hirudo medicinalis. The method includes pulverizing the three animal-derived medicinal materials (Scolopendra subspinipes, Buthus martensii, and Hirudo medicinalis), adding water and stirring for extraction, centrifuging to obtain a supernatant and precipitate, microfiltration and ultrafiltration of the supernatant followed by freeze-drying to obtain a fine powder, and then extracting the precipitate by boiling in water; extracting the volatile oils from Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, Paeonia lactiflora, and Lonicera japonica by water distillation followed by decoction in water; and extracting the Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, and Glycyrrhiza uralensis by boiling in water.

[0010] Preferably, the extraction method of the traditional Chinese medicine composition includes the following steps:

[0011] 1) Take three animal medicinal materials: centipede, leech, and scorpion. Crush them, add purified water, stir, mix well, centrifuge, and collect the supernatant and precipitate separately for later use.

[0012] 2) Take the supernatant from step 1), filter it through a microporous membrane, collect the filtrate, ultrafilter it, collect the retentate, freeze-dry it to obtain freeze-dried animal medicinal powder for later use;

[0013] 3) Take four raw medicinal materials: Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, and Paeonia lactiflora. Add 6-12 times the amount of purified water and distill to extract the volatile oil for 5-6 hours. Then add Lonicera japonica and continue to extract the volatile oil for 1-2 hours to obtain the volatile oil. Add cyclodextrin to encapsulate the volatile oil to prepare the cyclodextrin encapsulation complex for later use. The distilled aqueous solution and the residue are also for later use.

[0014] 4) Take the four raw medicinal materials of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, and Glycyrrhiza uralensis, along with the precipitate from step 1) and the dregs from step 2), mix them well, add 8-12 times the amount of water, decoct twice, each time for 1-3 hours, filter the decoction, concentrate under reduced pressure to obtain concentrated liquid, and set aside for later use.

[0015] 5) Take the concentrated solution from step 4) and combine it with the aqueous solution after distillation from step 3). Concentrate under reduced pressure to obtain an extract with a relative density of 1.12-1.20 at 60°C. Add ethanol to make the alcohol content reach 60%-80%. Refrigerate for 24-48 hours. Recover the ethanol and concentrate to obtain an extract with a relative density of 1.15-1.25 at 60°C. Dry the extract into a fine powder to obtain the extract powder for later use.

[0016] 6) Take the freeze-dried animal medicinal material powder from step 2), the volatile oil cyclodextrin inclusion complex from step 3), and the dry powder of the extract from step 5, mix them well, and you will get the fine powder of the Meridian Soothing Extract.

[0017] Preferably, in step 1), the amount of water added is 5-12 times the amount of the medicinal materials, and the mixture is stirred for 5-36 hours;

[0018] Preferred step 1) Add water in an amount 10 times that of the medicinal materials and stir for 24-36 hours.

[0019] Preferably, the ultrafiltration membrane in step 2) has a molecular weight cutoff of 1000-10000 Da, and the retentate obtained by ultrafiltration is retained to 0.25-0.4 times the weight of the animal medicinal material.

[0020] Preferably, the ultrafiltration membrane in step 2) has a molecular weight cutoff of 6000-10000 Da, and the retentate obtained from ultrafiltration is retained to 0.25-0.3 times the weight of the animal medicinal material.

[0021] Preferably, the freeze-drying curve in step 1) is as follows:

[0022]

[0023] Further preferred, the freeze-drying curve in step 1) is as follows:

[0024]

[0025] Preferably, in step 3), after distilling 8 times the amount of water to extract volatile oil from Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, and Paeonia lactiflora for 6 hours, honeysuckle is added to extract volatile oil for 1 hour.

[0026] Preferably, in step 5), ethanol is added to make the alcohol content reach 70%, and the mixture is refrigerated for 36 hours.

[0027] Preferably, the drying process described in step 5) is atmospheric pressure drying, reduced pressure drying, or fluidized bed drying; further including atmospheric pressure drying in an oven, vacuum belt drying, spray drying, etc.

[0028] The Meridian Relaxant Extract is made from the following raw medicinal materials in parts by weight:

[0029] Astragalus membranaceus 300-700 parts by weight, Lonicera japonica 300-700 parts by weight, Phellodendron chinense 100-400 parts by weight

[0030] Atractylodes lancea 100-400 parts by weight, Scrophularia ningpoensis 300-700 parts by weight, Angelica sinensis 100-400 parts by weight

[0031] White peony root 100-400 parts by weight, coix seed 300-700 parts by weight, licorice root 50-100 parts by weight

[0032] Centipede 10-40 parts by weight, whole scorpion 50-100 parts by weight, leech 180-280 parts by weight

[0033] Preferably, the meridian-clearing extract is made from the following raw medicinal materials in parts by weight:

[0034] Astragalus membranaceus 500 parts by weight, honeysuckle 500 parts by weight, and phellodendron chinense 250 parts by weight

[0035] Atractylodes lancea 250 parts by weight, Scrophularia ningpoensis 500 parts by weight, Angelica sinensis 250 parts by weight

[0036] White peony root 250 parts by weight, coix seed 500 parts by weight, licorice root 83 parts by weight

[0037] Centipede 20 parts by weight, whole scorpion 83 parts by weight, leech 250 parts by weight

[0038] Preferably, the meridian-clearing extract is made from the following raw medicinal materials in parts by weight:

[0039] Astragalus membranaceus 416.5 parts by weight, Lonicera japonica 416.5 parts by weight, Phellodendron chinense 208.5 parts by weight

[0040] Atractylodes lancea 208.5 parts by weight, Scrophularia ningpoensis 416.5 parts by weight, Angelica sinensis 208.5 parts by weight

[0041] White peony root 208.5 parts by weight, coix seed 416.5 parts by weight, licorice root 69 parts by weight

[0042] Centipede 16.5 parts by weight, whole scorpion 69 parts by weight, leech 208.5 parts by weight

[0043] It should be noted that the extraction method of the present invention can be applied to preparations of the Meridian Soothing Agent, and if necessary, pharmaceutical excipients can be added to the extract to prepare preparations that are clinically acceptable.

[0044] The technical advantages of the preparation method of the meridian-soothing extract described in this invention are as follows:

[0045] 1. The preparation method of this invention uses a stirring method to extract three precious animal medicinal materials: leeches, centipedes, and scorpions. This method is closer to the preparation of raw medicinal powders, avoiding the waste of resources caused by using only alcohol-soluble and water-soluble components. It also improves the strong fishy smell caused by using raw animal medicinal powders. The dry powder obtained by the extraction and purification process of this invention is significantly less than the freeze-dried powder obtained by existing technologies, which reduces the dosage of the preparation, improves the effectiveness of the preparation, and enhances patient compliance.

[0046] 2. The present invention uses a post-processing method to extract volatile oil from honeysuckle, which effectively increases the extraction yield compared to existing technologies. This ensures that the volatile oil extracted from the medicinal materials containing volatile components in the prescription is more comprehensive, and also protects the chlorogenic acid component in honeysuckle, which is easily destroyed by prolonged heating, thus significantly improving the retention rate of medicinal components.

[0047] To verify the stability and feasibility of the preparation process of the *Meridian-Clearing Extract* of this invention, the inventors conducted comparative experiments on the determination of the content of key pharmacodynamic components and an evaluation of its fishy odor. It should be noted that the *Meridian-Clearing Extract* selected for the pharmacodynamic experiments of this invention is a sample obtained using a representative preparation method of this invention. Due to space limitations, the experiments and results involving samples obtained using other preparation methods included in this invention are not exhaustively listed here.

[0048] Experimental Example 1: Comparative Study on the Determination of the Content of Marker Pharmacological Components

[0049] To verify the effect of the technical solution of this invention on increasing the content of chlorogenic acid, a key pharmacodynamic component in the formulation, appropriate amounts of dextrin, aspartame, sodium hydroxypropyl starch, and other excipients were added to the fine powder of the extract prepared in Examples 1-3 of this invention. The mixture was then stirred, granulated, and dried to produce 10 kg of granules. The chlorogenic acid content of the granules prepared by different extraction methods was determined, and the method for determining chlorogenic acid content is as follows:

[0050] Chromatographic conditions and system suitability test: Octadecylsilane-bonded silica gel was used as the packing material; acetonitrile: 0.4% phosphoric acid solution = 10:90 was used as the mobile phase; evaporative light scattering detector was used for detection; the detection wavelength was 327 nm; the theoretical plate number calculated based on the chlorogenic acid peak should not be less than 1000.

[0051] Preparation of the reference solution: Accurately weigh an appropriate amount of chlorogenic acid reference standard, add methanol to prepare a solution containing 0.05 mg per ml. Shake well to obtain the solution.

[0052] Preparation of the test solution: Accurately weigh 1g of sample and place it in a stoppered conical flask. Add 50ml of 50% methanol, weigh again, sonicate for 30min, cool, and weigh again. Make up the weight loss with 50% methanol, shake well, filter, and add an appropriate amount of the filtrate to a brown volumetric flask to obtain the test sample solution.

[0053] For the assay, 20 μl of the reference solution and the test solution were injected separately, and the content of chlorogenic acid in the samples was calculated using the external standard two-point method and logarithmic equation. The results are shown in Table 1.

[0054] Table 1. Determination of chlorogenic acid content using different extraction methods

[0055]

[0056] Experiment Example 2: Evaluation Test of Fishy Odor

[0057] Ten adults (5 men and 5 women) aged 20-35 were selected as volunteers to form a taste evaluation team. The granules prepared in Example 1 and Comparative Examples 1-2 were evaluated separately. Each sample was evaluated three times by the evaluation team. After rinsing their mouths, the volunteers tasted the granules prepared by different methods, leaving them in their mouths for 30 seconds before spitting them out. The fishy or unpleasant odor was evaluated based on the taste assessment at 0 seconds and 30 seconds, and scored according to the evaluation criteria in Table 2. Higher scores indicated a poorer taste. Each volunteer tested independently, with a 2-minute interval between each sample.

[0058] Table 2. Grading Table of Fishy and Off-Smell Odor Evaluation Standards by Taste Evaluation Group

[0059]

[0060] Example 1 and Comparative Examples 1-2 are granules obtained using the same parts by weight of raw medicinal materials but different preparation methods; Example 1 is a granule prepared using the method of the present invention, while Comparative Examples 1-2 are granules prepared using existing technology. The evaluation results are shown in Table 3.

[0061] Table 3 Taste Evaluation Scores

[0062]

[0063] The above results indicate that, compared with existing technologies, the method for preparing the Mailuoshutong extract of the present invention can remove the fishy and foul odor of animal medicinal materials to a greater extent, improve patient medication compliance, and effectively avoid the loss of honeysuckle active ingredients, which is conducive to the full realization of the clinical value of Mailuoshutong. Detailed Implementation

[0064] The technical solution of the present invention will be described in detail below through specific embodiments; however, those skilled in the art should know that the embodiments do not limit the present invention in any way.

[0065] Example 1: Preparation of Pulsifying Extract

[0066] Astragalus membranaceus 5000g, Lonicera japonica 5000g, Phellodendron chinense 2500g, Atractylodes lancea 2500g

[0067] Scrophularia ningpoensis 5000g, Angelica sinensis 2500g, Paeonia lactiflora 2500g, Coix lacryma-jobi 5000g

[0068] Licorice root 830g, centipede 200g, scorpion 830g, leech 2500g

[0069] 1) Take three animal medicinal materials: centipede, leech, and scorpion. Crush them, add 10 times the amount of purified water, stir for 36 hours, mix well, centrifuge, and collect the supernatant and precipitate separately for later use.

[0070] 2) Take the supernatant from step 1), filter it through a 0.22 μm filter membrane, collect the filtrate, and then ultrafilter it through an ultrafiltration membrane with a molecular weight cutoff of 8000 Da to about 1 L. Collect the retentate, freeze-dry it according to the following freezing curve to obtain freeze-dried animal medicinal powder for later use.

[0071]

[0072] 3) Take four raw medicinal materials: Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, and Paeonia lactiflora. Add 8 times the amount of purified water and distill to extract the volatile oil for 6 hours. Then add Lonicera japonica and continue to extract the volatile oil for 1 hour. Collect 9.1 ml of volatile oil and add 90 g of β-cyclodextrin to form a volatile oil cyclodextrin inclusion complex for later use. The distilled aqueous solution and the residue are also for later use.

[0073] 4) Take the four raw medicinal materials of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, and Glycyrrhiza uralensis, along with the precipitate from step 1) and the dregs from step 2), mix them well, add 10 times the amount of water, decoct twice, 2 hours each time, filter the decoction, concentrate under reduced pressure to obtain concentrated liquid, and set aside for later use.

[0074] 5) Take the concentrated liquid from step 4) and combine it with the aqueous solution after distillation in step 3). Concentrate under reduced pressure to a paste with a relative density of 1.12 at 60°C. Add ethanol to make the alcohol content reach 70%. Refrigerate for 36 hours. Recover the ethanol and concentrate to a paste with a relative density of 1.25 at 60°C. Vacuum belt dry to obtain a fine powder to obtain the extract powder for later use.

[0075] 6) Take the freeze-dried animal medicinal material powder from step 2), the volatile oil cyclodextrin inclusion complex from step 3), and the dry powder of the extract from step 5, mix them well, and you will get 3.32 kg of fine powder of the Meridian Soothing Extract.

[0076] Example 2: Preparation of Meridian Soothing Extract

[0077] Astragalus membranaceus 5000g, Lonicera japonica 5000g, Phellodendron chinense 2500g, Atractylodes lancea 2500g

[0078] Scrophularia ningpoensis 5000g, Angelica sinensis 2500g, Paeonia lactiflora 2500g, Coix lacryma-jobi 5000g

[0079] Licorice root 830g, centipede 200g, scorpion 830g, leech 2500g

[0080] 1) Take three animal medicinal materials: centipede, leech, and scorpion. Crush them, add 12 times the amount of purified water, stir for 24 hours, mix well, centrifuge, and collect the supernatant and precipitate separately for later use.

[0081] 2) Take the supernatant from step 1), filter it through a 0.22 μm filter membrane, collect the filtrate, and then ultrafilter it to 1.2 L through an ultrafiltration membrane with a molecular weight cutoff of 6000 Da. Collect the retentate, freeze-dry it according to the following freezing curve to obtain freeze-dried animal medicinal material powder for later use.

[0082]

[0083] 3) Take four raw medicinal materials: Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, and Paeonia lactiflora. Add 8 times the amount of purified water and distill to extract the volatile oil for 5 hours. Then add Lonicera japonica and continue to extract the volatile oil for 2 hours. Collect 8.9 ml of volatile oil and add 71.2 g of β-cyclodextrin to form a volatile oil cyclodextrin inclusion complex for later use. The distilled aqueous solution and the residue are also for later use.

[0084] 4) Take the four raw medicinal materials of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, and Glycyrrhiza uralensis, along with the precipitate from step 1) and the dregs from step 2), mix them well, add 8 times the amount of water, and decoct twice. The first decoction is for 3 hours, and the second decoction is for 2 hours. Filter the decoction, concentrate it under reduced pressure, and use the concentrated liquid for later use.

[0085] 5) Take the concentrated liquid from step 4) and combine it with the aqueous solution after distillation in step 3). Concentrate under reduced pressure to a paste with a relative density of 1.15 at 60°C. Add ethanol to make the alcohol content reach 60%. Refrigerate for 48 hours. Recover the ethanol and concentrate to a paste with a relative density of 1.20 at 60°C. Vacuum belt dry to obtain a fine powder to obtain the extract powder for later use.

[0086] 6) Take the freeze-dried animal medicinal material powder from step 2), the volatile oil cyclodextrin inclusion complex from step 3), and the dry powder of the extract from step 5, mix them well, and you will get 3.41 kg of fine powder of the Meridian Soothing Extract.

[0087] Example 3: Preparation of Pulse-Clearing Extract

[0088] Astragalus membranaceus 5000g, Lonicera japonica 5000g, Phellodendron chinense 2500g, Atractylodes lancea 2500g

[0089] Scrophularia ningpoensis 5000g, Angelica sinensis 2500g, Paeonia lactiflora 2500g, Coix lacryma-jobi 5000g

[0090] Licorice root 830g, centipede 200g, scorpion 830g, leech 2500g

[0091] 1) Take three animal medicinal materials: centipede, leech, and scorpion. Crush them, add 8 times the amount of purified water, stir for 24 hours, mix well, centrifuge, and collect the supernatant and precipitate separately for later use.

[0092] 2) Take the supernatant from step 1), filter it through a 0.22 μm filter membrane, collect the filtrate, and then ultrafilter it to 1.1 L through an ultrafiltration membrane with a molecular weight cutoff of 10000 Da. Collect the retentate, freeze-dry it according to the following freezing curve to obtain freeze-dried animal medicinal material powder for later use.

[0093]

[0094] 3) Take four raw medicinal materials: Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, and Paeonia lactiflora. Add 8 times the amount of purified water and distill to extract the volatile oil for 3 hours. Then add Lonicera japonica and continue to extract the volatile oil for 4 hours. Collect 7.2 ml of volatile oil and add 72 g of β-cyclodextrin to form a volatile oil cyclodextrin inclusion complex for later use. The distilled aqueous solution and the residue are also for later use.

[0095] 4) Take the four raw medicinal materials of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, and Glycyrrhiza uralensis, as well as the precipitate from step 1) and the dregs from step 2), mix them well, add 12 times the amount of water, and decoct twice. The first decoction is 2 hours and the second decoction is 1 hour. Filter the decoction, concentrate it under reduced pressure, and use the concentrated liquid for later use.

[0096] 5) Take the concentrated liquid from step 4) and combine it with the aqueous solution after distillation in step 3). Concentrate under reduced pressure to a paste with a relative density of 1.20 at 60°C. Add ethanol to make the alcohol content reach 80%. Refrigerate for 24 hours. Recover the ethanol and concentrate to a paste with a relative density of 1.25 at 60°C. Vacuum belt dry to obtain a fine powder to obtain the extract powder for later use.

[0097] 6) Take the freeze-dried animal medicinal material powder from step 2), the volatile oil cyclodextrin inclusion complex from step 3), and the dry powder of the extract from step 5, mix them well, and you will get 3.28 kg of fine powder of the Meridian Soothing Extract.

[0098] Example 4: Preparation of Meridian Soothing Extract

[0099] Astragalus membranaceus 4165g, Lonicera japonica 4165g, Phellodendron chinense 2085g, Atractylodes lancea 2085g

[0100] Scrophularia ningpoensis 4165g, Angelica sinensis 2085g, Paeonia lactiflora 2085g, Coix lacryma-jobi 4165g

[0101] Licorice root 690g, centipede 165g, scorpion 690g, leech 2085g

[0102] 1) Take three animal medicinal materials: centipede, leech, and scorpion. Crush them, add 10 times the amount of purified water, stir for 36 hours, mix well, centrifuge, and collect the supernatant and precipitate separately for later use.

[0103] 2) Take the supernatant from step 1), filter it through a 0.22 μm filter membrane, collect the filtrate, and then ultrafilter it through an ultrafiltration membrane with a molecular weight cutoff of 8000 Da to 750 ml. Collect the retentate and freeze-dry it according to the following freezing curve to obtain freeze-dried animal medicinal powder for later use.

[0104]

[0105] 3) Take four raw medicinal materials: Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, and Paeonia lactiflora. Add 8 times the amount of purified water and distill to extract the volatile oil for 6 hours. Then add Lonicera japonica and continue to extract the volatile oil for 1 hour. Collect 7.7 ml of volatile oil and add 80 g of β-cyclodextrin to form a volatile oil cyclodextrin inclusion complex for later use. The distilled aqueous solution and the residue are also for later use.

[0106] 4) Take the four raw medicinal materials of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, and Glycyrrhiza uralensis, along with the precipitate from step 1) and the dregs from step 2), mix them well, add 10 times the amount of water, decoct twice, 2 hours each time, filter the decoction, concentrate under reduced pressure to obtain concentrated liquid, and set aside for later use.

[0107] 5) Take the concentrated liquid from step 4) and combine it with the aqueous solution after distillation in step 3). Concentrate under reduced pressure to a paste with a relative density of 1.10 at 60°C. Add ethanol to make the alcohol content reach 70%. Refrigerate for 36 hours. Recover the ethanol and concentrate to a paste with a relative density of 1.21 at 60°C. Vacuum belt dry to obtain a fine powder to obtain the extract powder for later use.

[0108] 6) Take the freeze-dried animal medicinal material powder from step 2), the volatile oil cyclodextrin inclusion complex from step 3), and the dry powder of the extract from step 5, mix them well, and you will get 2.65 kg of fine powder of the Meridian Soothing Extract.

[0109] Example 5: Preparation of the Meridian Soothing Extract

[0110] Astragalus membranaceus 3000g, Lonicera japonica 3000g, Phellodendron chinense 1000g, Atractylodes lancea 1000g

[0111] Scrophularia ningpoensis 3000g, Angelica sinensis 1000g, Paeonia lactiflora 1000g, Coix lacryma-jobi 3000g

[0112] 500g licorice root, 100g centipede, 500g scorpion, 1800g leech

[0113] 1) Take three animal medicinal materials: centipede, leech, and scorpion. Crush them, add 5 times the amount of purified water, stir for 36 hours, mix well, centrifuge, and collect the supernatant and precipitate separately for later use.

[0114] 2) Take the supernatant from step 1), filter it through a 0.22 μm filter membrane, collect the filtrate, and then ultrafilter it to 600 ml through an ultrafiltration membrane with a molecular weight cutoff of 8000 Da. Collect the retentate and freeze-dry it according to the following freezing curve to obtain freeze-dried animal medicinal material powder for later use.

[0115]

[0116] 3) Take four raw medicinal materials: Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, and Paeonia lactiflora. Add 8 times the amount of purified water and distill to extract the volatile oil for 6 hours. Then add Lonicera japonica and continue to extract the volatile oil for 1 hour. Collect 4.3 ml of volatile oil and add 35 g of β-cyclodextrin to form a volatile oil cyclodextrin inclusion complex for later use. The distilled aqueous solution and the residue are also for later use.

[0117] 4) Take the four raw medicinal materials of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, and Glycyrrhiza uralensis, along with the precipitate from step 1) and the dregs from step 2), mix them well, add 10 times the amount of water, decoct twice, 2 hours each time, filter the decoction, concentrate under reduced pressure to obtain concentrated liquid, and set aside for later use.

[0118] 5) Take the concentrated liquid from step 4) and combine it with the aqueous solution after distillation in step 3). Concentrate under reduced pressure to a paste with a relative density of 1.10 at 60°C. Add ethanol to make the alcohol content reach 70%. Refrigerate for 48 hours. Recover the ethanol and concentrate to a paste with a relative density of 1.15 at 60°C. Vacuum dry to obtain a fine powder to obtain the extract powder for later use.

[0119] 6) Take the freeze-dried animal medicinal material powder from step 2), the volatile oil cyclodextrin inclusion complex from step 3), and the dry powder of the extract from step 5, mix them well, and you will get 1.80 kg of fine powder of the Meridian Soothing Extract.

[0120] Example 6: Preparation of the Meridian Soothing Extract

[0121] Astragalus membranaceus 7000g, Lonicera japonica 7000g, Phellodendron chinense 4000g, Atractylodes lancea 4000g

[0122] Scrophularia ningpoensis 7000g, Angelica sinensis 4000g, Paeonia lactiflora 4000g, Coix lacryma-jobi 7000g

[0123] Licorice root 1000g, centipede 400g, scorpion 1000g, leech 2800g

[0124] 1) Take three animal medicinal materials: centipede, leech, and scorpion. Crush them, add 12 times the amount of purified water, stir for 5 hours, mix well, centrifuge, and collect the supernatant and precipitate separately for later use.

[0125] 2) Take the supernatant from step 1), filter it through a 0.22 μm filter membrane, collect the filtrate, and then ultrafilter it to 1.5 L through an ultrafiltration membrane with a molecular weight cutoff of 8000 Da. Collect the retentate, freeze-dry it according to the following freezing curve to obtain freeze-dried animal medicinal powder for later use.

[0126]

[0127] 3) Take four raw medicinal materials: Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, and Paeonia lactiflora. Add 8 times the amount of purified water and distill to extract the volatile oil for 6 hours. Then add Lonicera japonica and continue to extract the volatile oil for 1 hour. Collect 13.4 ml of volatile oil and add 107 g of β-cyclodextrin to form a volatile oil cyclodextrin inclusion complex for later use. The distilled aqueous solution and the residue are also for later use.

[0128] 4) Take the four raw medicinal materials of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, and Glycyrrhiza uralensis, along with the precipitate from step 1) and the dregs from step 2), mix them well, add 10 times the amount of water, decoct twice, 2 hours each time, filter the decoction, concentrate under reduced pressure to obtain concentrated liquid, and set aside for later use.

[0129] 5) Take the concentrated liquid from step 4) and combine it with the aqueous solution after distillation in step 3). Concentrate under reduced pressure to an extract with a relative density of 1.15 at 60°C. Add ethanol to make the alcohol content reach 65%. Refrigerate for 36 hours. Recover the ethanol and concentrate to an extract with a relative density of 1.23 at 60°C. Spray dry to obtain the extract powder for later use.

[0130] 6) Take the freeze-dried animal medicinal material powder from step 2), the volatile oil cyclodextrin inclusion complex from step 3), and the dry powder of the extract from step 5, mix them well, and you will get 4.65 kg of fine powder of the Meridian Soothing Extract.

[0131] Preparation of Meridian-Soothing Granules in Comparative Example 1

[0132] Astragalus membranaceus 5000g, Lonicera japonica 5000g, Phellodendron chinense 2500g, Atractylodes lancea 2500g

[0133] Scrophularia ningpoensis 5000g, Angelica sinensis 2500g, Paeonia lactiflora 2500g, Coix lacryma-jobi 5000g

[0134] Licorice root 830g, centipede 200g, scorpion 830g, leech 2500g

[0135] 1) Take honeysuckle, atractylodes, scrophularia, angelica, and white peony root and place them in a multi-functional extraction tank for steam distillation for 7 hours to obtain 6.8 ml of volatile oil. Add anhydrous ethanol, mix well, and obtain an ethanol volatile oil solution. Store in a sealed container.

[0136] 2) Take Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, Glycyrrhiza uralensis, and half the amount of leech, centipede, and scorpion obtained from distillation. Add water and decoct twice, for 1.5 hours and 1 hour respectively. Combine the two decoctions, filter, and combine the distilled liquids. Concentrate the liquids, cool them, and add ethanol to a concentration of 60%. Let it stand for more than 12 hours to allow it to fully precipitate. Filter the leaves, recover the ethanol, and concentrate under reduced pressure to an extract with a relative density of 1.30. Dry the extract under vacuum to obtain a dry extract.

[0137] 3) Crush the remaining 1 / 2 of the leeches, centipedes, and scorpions into fine powder, mix with the dry paste obtained in step 2) to obtain 5.15 kg of dry matter, add an appropriate amount of sugar powder and dextrin and mix well; add ethanol as a wetting agent to make a soft material, put it into a fluidized bed dryer to dry, and spray the volatile oil obtained in step 1) to obtain the meridian-relieving granules.

[0138] Comparative Example 2: Preparation of Meridian-Soothing Granules

[0139] Astragalus membranaceus 5000g, Lonicera japonica 5000g, Phellodendron chinense 2500g, Atractylodes lancea 2500g

[0140] Scrophularia ningpoensis 5000g, Angelica sinensis 2500g, Paeonia lactiflora 2500g, Coix lacryma-jobi 5000g

[0141] Licorice root 830g, centipede 200g, scorpion 830g, leech 2500g

[0142] 1) After cleaning, washing, sterilizing and drying the three animal medicinal materials, namely leeches, centipedes and scorpions, they are then pulverized by an ultra-micro pulverizer to make the average particle size of the powder less than 1μm.

[0143] 2) Extract the volatile oil from honeysuckle, atractylodes, scrophularia, angelica, and white peony root with 8 times the amount of water for 7 hours, and collect 6.5 ml of volatile oil. Add the residue to astragalus, phellodendron, coix seed, and licorice with 10 times the amount of water and decoct twice, 2 hours each time. Combine the decoctions, filter, concentrate to a relative density of 1.20, add ethanol to a concentration of 60%, precipitate for 24 hours, and collect the supernatant. Concentrate under reduced pressure to recover the ethanol to a relative density of 1.30 to obtain the extract. Dry the extract into a fine powder under vacuum.

[0144] 3) Mix the ultrafine powder obtained in step 1) with the fine powder obtained in step 2) for a total of 6.8 kg, add an appropriate amount of granulation liquid, mix and stir to granulate, dry, granulate, spray in the volatile oil obtained in step 2), mix well to obtain the meridian-relieving granules.

Claims

1. A method for preparing a meridian-clearing extract, characterized in that, Includes the following steps: 1) Take three animal medicinal materials: centipede, leech, and scorpion. Crush them, add purified water, stir, mix well, centrifuge, and collect the supernatant and precipitate separately for later use. 2) Take the supernatant from step 1), filter it through a microporous membrane, collect the filtrate, and then ultrafilter it through an ultrafiltration membrane with a molecular weight cutoff of 6000-10000 Da. Collect the retentate and freeze-dry it according to the following freeze-drying curve to obtain freeze-dried animal medicine powder for later use. ； 3) Take four raw medicinal materials: Angelica sinensis, Atractylodes lancea, Scrophularia ningpoensis, and Paeonia lactiflora. Add 6-12 times the amount of purified water and distill to extract the volatile oil for 5-6 hours. Then add Lonicera japonica and continue to extract the volatile oil for 1-2 hours to obtain the volatile oil. Add cyclodextrin to encapsulate the volatile oil to prepare the cyclodextrin encapsulation complex for later use. The distilled aqueous solution and the residue are also for later use. 4) Take the four raw medicinal materials of Astragalus membranaceus, Phellodendron chinense, Coix lacryma-jobi, and Glycyrrhiza uralensis, along with the precipitate from step 1) and the dregs from step 2), mix them well, add 8-12 times the amount of water, decoct twice, each time for 1-3 hours, filter the decoction, concentrate under reduced pressure to obtain concentrated liquid, and set aside for later use. 5) Take the concentrated solution from step 4) and combine it with the aqueous solution after distillation from step 3). Concentrate under reduced pressure to an extract with a relative density of 1.1-1.2 at 60°C. Add ethanol to make the alcohol content 60%-80%. Refrigerate for 24-48 hours. Recover the ethanol and concentrate to an extract with a relative density of 1.15-1.25 at 60°C. Dry the extract into a fine powder to obtain the extract powder for later use. 6) Take the freeze-dried animal medicinal material powder from step 2), the volatile oil cyclodextrin inclusion complex from step 3), and the dry powder of the extract from step 5, mix them well, and you will get the fine powder of the Meridian Soothing Extract.

2. The preparation method according to claim 1, characterized in that, Step 1) Add 5-12 times the amount of purified water and stir for 5-36 hours.

3. The preparation method according to claim 1, characterized in that, Step 2) The retentate obtained by ultrafiltration is retained to 0.25-0.3 times the weight of the animal medicinal material.

4. The preparation method according to claim 1, characterized in that, Step 2) The freeze-drying curve is as follows: 。 5. The preparation method according to claim 1, characterized in that, In step 3), angelica, atractylodes, scrophularia, and white peony are distilled with 8 times the amount of water for 6 hours to extract volatile oil, and then honeysuckle is added to extract volatile oil for 1 hour.

6. The preparation method according to claim 1, characterized in that, Step 5) Add ethanol to make the alcohol content 70%, and refrigerate for 36 hours.

7. The preparation method according to any one of claims 1-6, characterized in that, The aforementioned Meridian-Soothing Extract is made from the following raw medicinal materials: Astragalus membranaceus 300-700 parts by weight, Lonicera japonica 300-700 parts by weight, Phellodendron chinense 100-400 parts by weight Atractylodes lancea 100-400 parts by weight, Scrophularia ningpoensis 300-700 parts by weight, Angelica sinensis 100-400 parts by weight White peony root 100-400 parts by weight, coix seed 300-700 parts by weight, licorice root 50-100 parts by weight Centipede 10-40 parts by weight, whole scorpion 50-100 parts by weight, leech 180-280 parts by weight.

8. The preparation method according to claim 7, characterized in that, The aforementioned Meridian-Soothing Extract is made from the following raw medicinal materials: Astragalus membranaceus 500 parts by weight, honeysuckle 500 parts by weight, and phellodendron chinense 250 parts by weight Atractylodes lancea 250 parts by weight, Scrophularia ningpoensis 500 parts by weight, Angelica sinensis 250 parts by weight White peony root 250 parts by weight, coix seed 500 parts by weight, licorice root 83 parts by weight Centipede 20 parts by weight, whole scorpion 83 parts by weight, leech 250 parts by weight.

9. The preparation method according to claim 7, characterized in that, The aforementioned Meridian-Soothing Extract is made from the following raw medicinal materials: Astragalus membranaceus 416.5 parts by weight, Lonicera japonica 416.5 parts by weight, Phellodendron chinense 208.5 parts by weight Atractylodes lancea 208.5 parts by weight, Scrophularia ningpoensis 416.5 parts by weight, Angelica sinensis 208.5 parts by weight White peony root 208.5 parts by weight, coix seed 416.5 parts by weight, licorice root 69 parts by weight Centipede 16.5 parts by weight, whole scorpion 69 parts by weight, leech 208.5 parts by weight.

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