A traditional Chinese medicine composition for treating non-alcoholic fatty liver disease and a preparation method thereof

Abstract

The application provides a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, which comprises the following raw materials in parts by weight: 4-15 parts of yujin, 15-25 parts of chaisu, 5-15 parts of chuanmiao, 10-20 parts of huangqi, 5-15 parts of danshen, 1-12 parts of muxiang, 4-12 parts of shanzha, 3-15 parts of huaihua, 5-15 parts of jigucao and 5-25 parts of zexie. The prescription of the traditional Chinese medicine composition for treating non-alcoholic fatty liver disease is composed of all the traditional Chinese medicines, which are balanced and compatible. The traditional Chinese medicine composition can soothe the liver and regulate qi, promote blood circulation to remove blood stasis, and guide all the drugs to the liver and gallbladder by yujin, chaisu and chuanmiao. Danshen, huangqi, shanzha and muxiang are used to invigorate the spleen, remove dampness, digest food accumulation, and invigorate the spleen, remove dampness, soothe the liver and benefit the gallbladder. Huaihua and jigucao are used to strengthen the effects of clearing heat and removing dampness, and dissipating stagnation. Zexie can remove phlegm and dampness, remove water, clear the latent fire of the liver and kidney, and all the drugs can jointly achieve the effects of soothing the liver and regulating qi, clearing and removing phlegm and dampness, activating blood to remove turbidity, and removing blood stasis and stagnation.

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, and in particular to a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease and its preparation method. Background Technology

[0002] Nonalcoholic fatty liver disease (NAFLD) is a metabolic stress-induced liver disease characterized by hepatocellular steatosis and lipid deposition in individuals without a history of excessive alcohol consumption. It has a high incidence rate and is highly dangerous, serving as a crucial link in the progression to liver fibrosis, cirrhosis, and even hepatocellular carcinoma (HCC). It is also one of the most significant global public health issues of the 21st century. In recent years, the incidence of NAFLD has been increasing annually, and the age of onset is gradually becoming younger, seriously threatening the health of the Chinese population.

[0003] Nonalcoholic fatty liver disease (NAFLD) is a modern medical term, not recorded in traditional Chinese medicine literature. Based on its clinical manifestations, TCM categorizes it under terms such as "accumulation," "hypochondriac pain," "abdominal distension," "phlegm turbidity," and "dampness obstruction." The causes are often attributed to excessive consumption of rich, fatty foods, obesity, alcoholism, exposure to damp-heat toxins, emotional imbalances, or prolonged illness leading to physical weakness. Its pathogenesis involves impaired liver function, spleen dysfunction, kidney essence deficiency, internal accumulation of damp-heat, phlegm turbidity, and blood stasis, ultimately resulting in the mutual binding of phlegm, dampness, and blood stasis, obstructing the liver's meridians and leading to fatty liver. Although the disease is located in the liver, its underlying pathogenesis involves multiple organs, including the liver, spleen, and kidneys. Consensus on Integrated Traditional Chinese and Western Medicine Treatment of NAFLD (Chinese Association of Integrated Traditional and Western Medicine Digestive Diseases Professional Committee. Consensus on Integrated Traditional Chinese and Western Medicine Treatment of Non-Alcoholic Fatty Liver Disease [J]. Chinese Journal of Integrated Traditional and Western Medicine, 2011, 31(2): 155-158) The syndrome types are divided into liver qi stagnation syndrome, liver qi stagnation and spleen deficiency syndrome, phlegm-dampness obstruction syndrome, damp-heat accumulation syndrome, and phlegm-stagnant syndrome. The main treatment measures are to actively control the risk factors for disease progression, such as changing lifestyle, exercise therapy and adjusting diet, controlling blood sugar and blood lipids, and avoiding the use of hepatotoxic drugs. At present, Western medicine for the treatment of NAFLD mainly uses drugs that simply lower blood sugar and lipids, such as statins, metformin, and aspirin. However, the pathology of non-alcoholic fatty liver disease is not only about lowering blood sugar and lipids, but also includes the damage to liver function caused by intrahepatic fat infiltration. Although Western medicine treatment alone has a certain therapeutic effect, its single effect often produces side effects and damages liver and kidney function. In recent years, traditional Chinese medicine has conducted extensive research on the prevention and treatment of NAFLD and has made certain progress. It has gained a deeper understanding of the pathogenesis, treatment methods, and medications for NAFLD, and the treatment has become more diversified, showing broad prospects.

[0004] Traditional Chinese medicine (TCM) treatment for NAFLD primarily focuses on tonifying Qi and strengthening the spleen, dispelling dampness and promoting blood circulation. For example, Chinese patent CN103800352A discloses a compound preparation of effective TCM ingredients for treating non-alcoholic fatty liver disease, composed of geniposide and chlorogenic acid. Many similar TCM compositions exist for treating non-alcoholic fatty liver disease, but they all have drawbacks, such as excessive ingredients, difficulty in sourcing raw materials, high cost, crude preparation processes, unclear pharmacodynamic material basis, and slow onset of action. Therefore, there is an urgent need for a drug that has a significant therapeutic effect on non-alcoholic fatty liver disease, fewer ingredients, and no side effects. Summary of the Invention

[0005] In view of this, the technical problem to be solved by the present invention is to provide a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, and the traditional Chinese medicine composition provided by the present invention has good therapeutic effect on non-alcoholic fatty liver disease.

[0006] This invention provides a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, and its preparation method, based on the principles of syndrome differentiation and treatment. The composition has clear active ingredients, a well-defined mechanism of action, few impurities, significant therapeutic effects, small dosage, and no side effects.

[0007] This invention provides a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, comprising the following raw materials in parts by weight:

[0008] Turmeric 4-15 parts, vinegar-processed Bupleurum 15-25 parts, Ligusticum chuanxiong 5-15 parts, Astragalus membranaceus 10-20 parts, Salvia miltiorrhiza 5-15 parts, Aucklandia lappa 1-12 parts, Crataegus pinnatifida 4-12 parts, Sophora japonica 3-15 parts, Abrus precatorius 5-15 parts, Alisma plantago-aquatica 5-25 parts.

[0009] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by the present invention includes 4 to 15 parts by weight of turmeric; specifically, it can be 4 parts by weight, 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 11 parts by weight, 12 parts by weight, 13 parts by weight, 14 parts by weight, or 15 parts by weight; or any point value between the above two.

[0010] The turmeric in this invention has the effects of promoting blood circulation, relieving pain, promoting bile secretion and reducing jaundice, regulating qi and relieving depression, and soothing the liver and promoting bile secretion.

[0011] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by the present invention includes 15 to 25 parts by weight of vinegar-processed Bupleurum chinense; specifically, it can be 15 parts by weight, 16 parts by weight, 17 parts by weight, 18 parts by weight, 19 parts by weight, 20 parts by weight, 21 parts by weight, 22 parts by weight, 23 parts by weight, 24 parts by weight, or 25 parts by weight; or any value between the above two.

[0012] This invention relates to vinegar-processed Bupleurum, which has the effects of purging heat from the exterior, soothing the liver and relieving depression, and raising Yang Qi.

[0013] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by the present invention includes 5 to 15 parts by weight of Ligusticum chuanxiong; specifically, it can be 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 11 parts by weight, 12 parts by weight, 13 parts by weight, 14 parts by weight, or 15 parts by weight; or any point value between the above two.

[0014] This invention relates to Ligusticum chuanxiong, which has the effects of regulating qi and relieving stagnation, enhancing immunity, and improving microcirculation.

[0015] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by the present invention includes 10 to 20 parts by weight of Astragalus membranaceus; specifically, it can be 10 parts by weight, 11 parts by weight, 12 parts by weight, 13 parts by weight, 14 parts by weight, 15 parts by weight, 16 parts by weight, 17 parts by weight, 18 parts by weight, 19 parts by weight, 20 parts by weight; or any value between the above two.

[0016] This invention relates to Astragalus membranaceus, which has the functions of tonifying the spleen and replenishing qi, promoting diuresis and reducing swelling, reducing blood viscosity, and protecting the liver.

[0017] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by the present invention includes 5 to 15 parts by weight of Salvia miltiorrhiza; specifically, it can be 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 11 parts by weight, 12 parts by weight, 13 parts by weight, 14 parts by weight, or 15 parts by weight; or any point value between the above two.

[0018] This invention relates to Danshen, which has the effects of promoting blood circulation, removing blood stasis, improving microcirculation disorders, and altering blood rheology.

[0019] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by the present invention includes 1 to 12 parts by weight of costus root; specifically, it can be 1 part by weight, 2 parts by weight, 3 parts by weight, 4 parts by weight, 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 11 parts by weight, or 12 parts by weight; or any point value between the above two.

[0020] This invention relates to costus root, which has the functions of promoting qi circulation, relieving pain, and alleviating liver qi stagnation.

[0021] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by the present invention includes 4 to 12 parts by weight of hawthorn; specifically, it can be 4 parts by weight, 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 11 parts by weight, 12 parts by weight; or any value between the above two.

[0022] This invention relates to hawthorn, which has the functions of aiding digestion, strengthening the stomach, promoting qi circulation, dispersing blood stasis, clearing turbidity, and lowering lipids.

[0023] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by the present invention comprises 3 to 15 parts by weight of Sophora japonica flowers; specifically, it can be 3 parts by weight, 4 parts by weight, 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 11 parts by weight, 12 parts by weight, 13 parts by weight, 14 parts by weight, or 15 parts by weight; or any value between the above two.

[0024] This invention relates to Sophora japonica flowers, which have the effects of cooling the blood and stopping bleeding, clearing liver heat, stopping bleeding and lowering blood pressure.

[0025] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by the present invention includes 5 to 15 parts by weight of *Heliotropium indicum*; specifically, it can be 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 11 parts by weight, 12 parts by weight, 13 parts by weight, 14 parts by weight, or 15 parts by weight; or any value between the above two.

[0026] This invention relates to *Chicken Bone Grass*, which has the functions of promoting diuresis and relieving jaundice, clearing heat and detoxifying, and soothing the liver and relieving pain.

[0027] The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease provided by this invention includes 5 to 25 parts by weight of Alisma plantago-aquatica; specifically, it can be 5 parts by weight, 6 parts by weight, 7 parts by weight, 8 parts by weight, 9 parts by weight, 10 parts by weight, 11 parts by weight, 12 parts by weight, 13 parts by weight, 14 parts by weight, 15 parts by weight, 16 parts by weight, 17 parts by weight, 18 parts by weight, 19 parts by weight, 20 parts by weight, 21 parts by weight, 22 parts by weight, 23 parts by weight, 24 parts by weight, or 25 parts by weight; or any value between the above two.

[0028] This invention contains Alisma plantago-aquatica, which promotes diuresis, eliminates dampness, clears heat, resolves turbidity, and lowers lipids.

[0029] In some embodiments, the traditional Chinese medicine composition for treating non-alcoholic fatty liver disease comprises the following raw materials in parts by weight:

[0030] Turmeric 4-15 parts, vinegar-processed Bupleurum 15-25 parts, Ligusticum chuanxiong 5-15 parts, Astragalus membranaceus 10-20 parts, Salvia miltiorrhiza 5-15 parts, Aucklandia lappa 1-12 parts, Crataegus pinnatifida 4-12 parts, Sophora japonica 3-15 parts, Abrus precatorius 5-15 parts, Alisma plantago-aquatica 5-15 parts;

[0031] In one embodiment, the traditional Chinese medicine composition for treating non-alcoholic fatty liver disease comprises the following raw materials in parts by weight:

[0032] Turmeric 9 parts, vinegar-processed Bupleurum 20 parts, Ligusticum chuanxiong 10 parts, Astragalus membranaceus 15 parts, Salvia miltiorrhiza 10 parts, Aucklandia lappa 6 parts, Crataegus pinnatifida 8 parts, Sophora japonica 8 parts, Abrus precatorius 10 parts, Alisma plantago-aquatica 12 parts;

[0033] In one embodiment, the traditional Chinese medicine composition for treating non-alcoholic fatty liver disease comprises the following raw materials in parts by weight:

[0034] 15 parts of turmeric, 25 parts of vinegar-processed Bupleurum, 15 parts of Ligusticum chuanxiong, 20 parts of Astragalus membranaceus, 15 parts of Salvia miltiorrhiza, 1 part of Aucklandia lappa, 4 parts of hawthorn, 3 parts of Sophora japonica, 15 parts of Abrus precatorius, and 5 parts of Alisma plantago-aquatica.

[0035] In one embodiment, the traditional Chinese medicine composition for treating non-alcoholic fatty liver disease comprises the following raw materials in parts by weight:

[0036] 4 parts turmeric, 15 parts vinegar-processed Bupleurum, 5 parts Ligusticum chuanxiong, 10 parts Astragalus membranaceus, 5 parts Salvia miltiorrhiza, 12 parts Aucklandia lappa, 12 parts Crataegus pinnatifida, 15 parts Sophora japonica, 5 parts Abrus precatorius, 15 parts Alisma plantago-aquatica

[0037] This invention selects a variety of traditional Chinese medicines with significant effects in soothing the liver and regulating qi, clearing phlegm and dampness, and promoting blood circulation and eliminating turbidity. Through rational combination, the components produce a synergistic effect, which not only has the effects of soothing the liver and relieving depression, lowering blood lipids and blood sugar, and improving fibrosis, but also protects liver cells and promotes liver cell regeneration. It shows significant efficacy, especially for liver qi stagnation type, liver qi stagnation and spleen deficiency type, and damp-heat stagnation type. In this formula, turmeric, vinegar-processed Bupleurum, and Ligusticum chuanxiong are the principal herbs, which soothe the liver and regulate qi, and guide the other herbs directly to the liver and gallbladder. The assistant herbs Salvia miltiorrhiza, Astragalus membranaceus, Crataegus pinnatifida, and Aucklandia lappa are added to strengthen the spleen and eliminate dampness, digest food stagnation and promote qi circulation and dispel blood stasis. The adjuvant herbs Sophora japonica and Abrus precatorius are added to enhance the effects of clearing heat and eliminating dampness and dispelling stagnation. Alisma plantago-aquatica is added to eliminate phlegm and dampness, promote water metabolism, and clear the latent fire in the liver and kidneys. It is especially effective for those with obesity and hyperlipidemia. The combined effects of these herbs are to soothe the liver and regulate qi, clear phlegm and dampness, promote blood circulation and eliminate turbidity, and relieve stagnation. Experimental results show that the traditional Chinese medicine composition provided by this invention can effectively reduce intraperitoneal fat accumulation and liver deposition in NAFLD model rats. Simultaneously, it can significantly improve liver function, reduce serum ALT and AST levels in NAFLD rats, and the therapeutic effect is significantly dose-dependent. It also corrects lipid and glucose metabolism disorders, reduces serum TC, TG, and FBG levels, and exhibits a certain dose-dependent trend.

[0038] This composition not only has the effects of soothing the liver and relieving depression, lowering blood lipids, lowering blood sugar, and improving fibrosis, but also shows significant efficacy, especially for liver qi stagnation type, liver qi stagnation and spleen deficiency type, and damp-heat stagnation type. Pharmacodynamic experiments have confirmed that the traditional Chinese medicine composition prepared by this invention has significant efficacy, high bioavailability, and stable and reliable quality. This traditional Chinese medicine composition can be prepared into different dosage forms according to patient needs, and is convenient to carry and easy to take.

[0039] The present invention discloses a method for preparing a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease as described in any one of the above claims, comprising the following steps:

[0040] S1) Astragalus and Alisma were extracted by water reflux, filtered, and concentrated to obtain a thick extract; the thick extract was precipitated with ethanol, the ethanol was recovered, and the extract was concentrated to obtain a clear extract; the clear extract was freeze-dried to obtain extract A;

[0041] S2) Ligusticum chuanxiong and Bupleurum chinense were decocted in water to obtain a decoction and a first volatile oil. The decoction was concentrated to obtain a clear extract. The clear extract was dissolved in acid, the pH was adjusted, the temperature was maintained, and the mixture was filtered. After the precipitate was dissolved, the pH was adjusted, ethanol was added to dissolve it, and the mixture was filtered. The filtrate was purified through a first macroporous resin to obtain extract B.

[0042] S3) Sophora japonica flowers, turmeric and water chestnut extract by steam distillation to obtain the second volatile oil and residue;

[0043] Hawthorn, salvia miltiorrhiza and the above-mentioned drug residues were extracted by water reflux, concentrated, precipitated with ethanol, and the supernatant was purified by second macroporous resin column to obtain extract C.

[0044] S4) The first and second volatile oils were dissolved in a solvent and encapsulated with β-cyclodextrin to obtain volatile oil inclusion complexes, which are extracts D;

[0045] S5) Chicken bone grass was extracted by water flash extraction, followed by extraction with ethanol. The extract was concentrated to obtain a clear extract, which was then purified by column chromatography to obtain extract E.

[0046] S6) Mix extract A, extract B, extract C, extract D and extract E to obtain the final product.

[0047] The preparation method of extract A includes:

[0048] Astragalus and Alisma are extracted using water reflux extraction, filtered, and concentrated to obtain a thick extract; the extraction is performed 2-3 times, preferably three times; the extraction temperature is 45-55℃, the material-to-liquid ratio for each extraction is 1:6-10, and the extraction time for each extraction is 5-7 hours. More preferably, the extraction includes: first, adding 10 times the amount of water, soaking at 50℃ for 40 minutes, and extracting for 3 hours; second, adding 8 times the amount of water and extracting for 2 hours; and third, adding 6 times the amount of water and extracting for 1 hour.

[0049] The thick paste was precipitated with ethanol, the ethanol was recovered, and the paste was concentrated to obtain a clear paste; the clear paste was freeze-dried to obtain extract A.

[0050] The decoctions were combined, filtered, and concentrated under reduced pressure to a thick paste with a relative density of 1.25 (60°C). Ethanol was added to bring the alcohol content to 60%, and the mixture was precipitated for 20-24 hours. The ethanol was recovered, and the concentrate was concentrated to a clear paste with a relative density of 1.18 (60°C). The concentrate was freeze-dried and pulverized into a fine powder to obtain extract A. The preferred mesh size of the fine powder is 120 mesh.

[0051] The preparation methods of extract B include:

[0052] Ligusticum chuanxiong and Bupleurum chinense were decocted in water to obtain a decoction and a first volatile oil. The decoction was concentrated to obtain a clear extract. The clear extract was dissolved in acid, the pH was adjusted, the mixture was kept warm, filtered, and the precipitate was dissolved. After adjusting the pH, ethanol was added to dissolve the precipitate, and the mixture was filtered. The filtrate was purified through a first macroporous resin to obtain extract B.

[0053] Take Ligusticum chuanxiong and Bupleurum chinense (processed with vinegar), grind them into coarse powder, add them to an aqueous solution with pH 7.0 and decoct 1-2 times; collect the volatile oil at the same time; preferably, the ratio of the decoction material to the liquid is 1:(10-12); the decoction time is 1-2 hours each time; more preferably, add 12 times the amount of water for the first time and decoct for 2 hours, add 10 times the amount of water for the second time and decoct for 1 hour, combine the decoctions, and store the volatile oil in a separate container.

[0054] The relative density of the ointment is 1.15 (60℃).

[0055] The pH was adjusted to 3.5 with 2 mol / L hydrochloric acid solution, and the mixture was kept at 65°C for 1 hour. After filtration, the precipitate was mixed with 7 times its volume of water, and the pH was adjusted to 6.5 with 3% NaOH solution. An equal volume of 95% ethanol was added, and the mixture was stirred to dissolve the precipitate. The mixture was then filtered, and the filtrate was concentrated to a solid-liquid ratio of 1:3. The filtrate was then passed through the treated macroporous resin. The first macroporous resin was AB-8 macroporous resin.

[0056] The resin purification process specifically includes: eluting with water, discarding the eluent, then eluting with 40% ethanol and collecting the eluent.

[0057] In some embodiments, elution is performed with 4 column volumes of water, the eluent is discarded, and then elution is performed with 8 column volumes of 40% ethanol, and the ethanol eluent is collected.

[0058] After collecting the ethanol eluent, the solution was concentrated under reduced pressure until a relative density of 1.20 (60℃) was obtained. The solution was then dried under cold conditions and pulverized into a fine powder to obtain extract B.

[0059] The preparation methods of extract C include:

[0060] Sophora japonica flowers, turmeric, and costus root were extracted by steam distillation to obtain a second volatile oil and residue. The steam distillation time was 4-6 hours; the ratio of the total amount of Sophora japonica flowers, turmeric, and costus root to water was 1:(10-12).

[0061] In one specific embodiment of the present invention, Sophora japonica flowers, Curcuma longa, and Aucklandia lappa are taken, crushed into coarse powder, and 12 times the amount of water is added. The mixture is then steam distilled for 5 hours to extract the volatile oil. The volatile oil is stored separately, and the residue is kept for later use.

[0062] Hawthorn, salvia miltiorrhiza, and the above-mentioned residues were extracted by water reflux, concentrated, precipitated with ethanol, and the supernatant was purified by second-large-pore resin column to obtain extract C.

[0063] Hawthorn, salvia miltiorrhiza, and the above-mentioned medicinal residues were extracted by water reflux; the extraction temperature was 90~105℃, the number of extractions was 2~3 times; the material-to-liquid ratio for each extraction was 1:7~9; and the extraction time for each extraction was 1~3 hours.

[0064] The optimal extraction method is to extract three times, with each extraction using 8 times the amount of water. Specifically, the extraction times are 3 hours, 2 hours, and 1 hour, respectively. The extracts are combined and concentrated to a relative density of 1.18 (60°C). Ethanol is added to achieve an alcohol content of 60%, and the mixture is precipitated for 20-24 hours. The supernatant is collected, and the precipitate is washed twice with 60% ethanol. The supernatant and washings are combined and the mixture is recovered until there is no alcohol odor.

[0065] Dilute with water to 4 times the amount of medicinal material, and then place on a treated HPD-722 macroporous resin column.

[0066] The resin purification process specifically includes: elution with water at a rate of 8 ml / min, discarding the eluent, followed by elution with 5-6 column volumes of 50% ethanol, collecting the eluent, and then elution with 2-3 column volumes of 30% ethanol, collecting the eluent, and combining the eluents.

[0067] In one specific implementation,

[0068] Elute with 8 column volumes of purified water at a rate of 8 ml / min, and discard the eluent. Elute with 6 column volumes of 50% ethanol, collect the eluent, and then elute with 3 column volumes of 30% ethanol, collect the eluent, and combine the eluents.

[0069] Combine the eluents, recover until no alcohol odor remains, freeze-dry, and pulverize into a fine powder to obtain extract C.

[0070] The first and second volatile oils were dissolved in a solvent and encapsulated with β-cyclodextrin to obtain volatile oil inclusion complexes, which are extracts D.

[0071] The solvent used in this invention is ethanol. The β-cyclodextrin inclusion complex comprises: dissolving the first volatile oil and the second volatile oil in ethanol, adding them dropwise to an aqueous solution of β-cyclodextrin, stirring at 40°C for 4-5 hours, refrigerating at 5°C for 20-24 hours, filtering, and vacuum drying the precipitate at 35-40°C for 4-5 hours.

[0072] In the β-cyclodextrin aqueous solution, the mass-to-volume ratio of β-cyclodextrin to water is 1:5 (g / ml), and the volume-to-mass ratio of volatile oil to β-cyclodextrin is 1:7 (ml / g).

[0073] The preparation methods of extract E include:

[0074] Chicken bone grass was extracted using water flash extraction, followed by ethanol extraction. The extract was concentrated to obtain a clear extract, which was then purified by column chromatography to obtain extract E.

[0075] The flash extraction time and voltage of the present invention are 8 minutes and 120V. The ethanol extraction includes: using 70% ethanol, adjusting the pH to 5.0, and letting it stand for 20-24 hours.

[0076] In one preferred embodiment of the present invention: the herb *Heliotropium indicum* is crushed and water is added, the voltage is controlled at 120 V, flash extraction is performed for 8 min, ethanol is added to the extract to make the ethanol concentration 70%, the pH of the extract is adjusted to 5.0, the extract is allowed to stand for 24 hours, the ethanol is recovered, and the extract is concentrated under reduced pressure to a clear extract with a relative density of 1.10 (50℃).

[0077] The extract was then purified by column chromatography to obtain extract E. The column purification was performed using a neutral alumina column with a particle size of 100-200 mesh, and eluted with 50% ethanol.

[0078] Extracts A, B, C, D, and E are mixed to obtain the final product. This invention does not limit the specific method of mixing described above; methods well-known to those skilled in the art are acceptable.

[0079] This invention provides the use of any one of the traditional Chinese medicine compositions for treating non-alcoholic fatty liver disease in the preparation of a medicament for treating non-alcoholic fatty liver disease.

[0080] This invention provides a medicament for treating non-alcoholic fatty liver disease, comprising the traditional Chinese medicine composition for treating non-alcoholic fatty liver disease described in the above technical solution.

[0081] The present invention also includes excipients or ingredients commonly used in the pharmaceutical field.

[0082] The dosage forms described in this invention include, but are not limited to, one or more of the following: granules, decoctions, powders, oral liquids, tablets, pills, ointments, or capsules.

[0083] This invention presents a traditional Chinese medicine composition for the prevention and treatment of non-alcoholic fatty liver disease (NAFLD). The formula employs a balanced combination of warming and cooling herbs. Turmeric, vinegar-processed Bupleurum, and Ligusticum chuanxiong are used to soothe the liver and regulate qi, promoting blood circulation and dispersing blood stasis, guiding the other herbs directly to the liver and gallbladder. The addition of Salvia miltiorrhiza, Astragalus membranaceus, Crataegus pinnatifida, and Aucklandia lappa aims to strengthen the spleen and eliminate dampness, digesting food stagnation while simultaneously strengthening the spleen, resolving dampness, soothing the liver, and promoting bile secretion. The addition of Sophora japonica and Abrus precatorius enhances the effects of clearing heat, eliminating dampness, and dispersing stagnation. Furthermore, Alisma plantago-aquatica eliminates phlegm, promotes diuresis, clears latent heat in the liver and kidneys. The combined effects of these herbs are to soothe the liver and regulate qi, clear phlegm and dampness, invigorate blood circulation, eliminate turbidity, and resolve stagnation. It can effectively improve clinical symptoms and signs, reduce liver function and blood lipid levels, and effectively prevent the progression of NAFLD. Animal experiments have demonstrated good efficacy, with no toxic side effects after long-term use, effectively avoiding the use of strong side effects from herbs such as rhubarb, Coptis chinensis, and peach kernel in current conventional traditional Chinese medicine formulas.

[0084] The traditional Chinese medicine composition provided by this invention can significantly reduce liver index; it can significantly reduce serum TC, TG, and FBG levels. The traditional Chinese medicine composition has a good regulatory effect on lipid disorders in NAFLD rats.

[0085] The traditional Chinese medicine composition disclosed in this invention can effectively reduce intraperitoneal fat accumulation, decrease liver wet weight and liver index in NAFLD model rats, and reduce fat deposition in the liver. At the same time, it can significantly improve liver function [1], reduce serum ALT and AST levels in NAFLD rats, and the therapeutic effect is significantly dose-related. It corrects lipid and glucose metabolism disorders, reduces serum TC, TG and FBG levels, and has a certain dose-related trend. The results show that the traditional Chinese medicine composition has a definite therapeutic effect on NAFLD, and its mechanism of action may be related to reducing hepatocyte fat deposition, improving liver function and correcting glucose and lipid metabolism disorders. Attached Figure Description

[0086] Figure 1 The effect of liver index on each group of rats;

[0087] Figure 2 The effect on blood lipid levels in NAFLD rats;

[0088] Figure 3 To investigate the effects of ALT and AST levels in the serum of NAFLD rats. Detailed Implementation

[0089] This invention provides a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease and its preparation method. Those skilled in the art can refer to the content of this document and appropriately modify the process parameters to achieve the desired result. It should be particularly noted that all similar substitutions and modifications are obvious to those skilled in the art and fall within the scope of protection of this invention. The method and application of this invention have been described through preferred embodiments. Those skilled in the art can obviously make modifications or appropriate alterations and combinations to the method and application described herein without departing from the content, spirit, and scope of this invention to realize and apply the technology of this invention.

[0090] In this application, the term "and / or" describes the relationship between related objects, indicating that three relationships can exist. For example, A and / or B can represent: A existing alone, A and B existing simultaneously, or B existing alone. A and B can be singular or plural.

[0091] In this application, "at least one" means one or more, and "more than one" means two or more. "At least one of the following" or similar expressions refer to any combination of these items, including any combination of single or multiple items.

[0092] It should be understood that in the various embodiments of this application, the order of the above processes does not imply the order of execution. Some or all steps may be executed in parallel or sequentially. The execution order of each process should be determined by its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of this application.

[0093] The numerical ranges and parameters involved in this invention have been presented as accurately as possible to the relevant values ​​in the specific embodiments. However, any numerical value inevitably contains standard deviations due to individual test methods. Therefore, unless otherwise expressly stated, it should be understood that all numerical ranges or specific data used in this disclosure may have a reasonable deviation within a certain range, for example, within 1% or 0.5%.

[0094] The embodiments and comparative examples of this invention describe some examples, in which the embodiments illustrate certain implementations of the invention. However, this does not mean that the effects of the invention can only be achieved in these examples.

[0095] To further illustrate the present invention, the following describes in detail, with reference to embodiments, a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease and its preparation method.

[0096] Example 1: The composition of the present invention

[0097] Formula: Turmeric 9 parts, Vinegar-processed Bupleurum 20 parts, Ligusticum chuanxiong 10 parts, Astragalus membranaceus 15 parts, Salvia miltiorrhiza 10 parts, Aucklandia lappa 6 parts, Crataegus pinnatifida 8 parts, Sophora japonica 8 parts, Abrus precatorius 10 parts, Alisma plantago-aquatica 12 parts

[0098] Preparation method:

[0099] 1. A method for preparing a traditional Chinese medicine extract A for treating non-alcoholic fatty liver disease:

[0100] Take 15 parts of Astragalus membranaceus and 12 parts of Alisma plantago-aquatica, and extract them three times under reflux. For the first extraction, add 10 times the amount of water, soak at 50℃ for 40 minutes, and extract for 3 hours. For the second extraction, add 8 times the amount of water and extract for 2 hours. For the third extraction, add 6 times the amount of water and extract for 1 hour. Combine the decoctions, filter, concentrate under reduced pressure to a thick paste with a relative density of 1.25 (60℃), add ethanol to make the alcohol content reach 60%, precipitate with alcohol for 24 hours, recover the ethanol, and concentrate to a clear paste with a relative density of 1.18 (60℃). Freeze-dry the concentrate and pulverize it into a fine powder to obtain extract A.

[0101] 2. A method for preparing a traditional Chinese medicine extract B for treating non-alcoholic fatty liver disease:

[0102] Take 10 parts of Ligusticum chuanxiong and 20 parts of Bupleurum chinense (processed with vinegar), grind them into coarse powder, add an aqueous solution with pH 7.0 and decoct twice (collecting volatile oil at the same time). For the first decoction, add 12 times the amount of water and decoct for 2 hours. For the second decoction, add 10 times the amount of water and decoct for 1 hour. Combine the decoctions, store the volatile oil separately, and concentrate the decoction to a clear extract with a relative density of 1.15 (60℃). Adjust the pH to 3.5 with 2 mol / L hydrochloric acid solution, keep warm at 65℃ for 1 hour, filter, and add 7 times the amount of water to the precipitate. Stir well, adjust the pH to 6.5 with 3% NaOH solution, add an equal volume of 95% ethanol, stir to dissolve, filter, concentrate the filtrate to a solid-liquid ratio of 1:3, pass through the treated AB-8 macroporous resin, elute with 4 column volumes of water, discard the eluent, then elute with 8 column volumes of 40% ethanol, collect the ethanol eluent, concentrate under reduced pressure to a relative density of 1.20 (60℃), cool and dry, and pulverize into a fine powder to obtain extract B.

[0103] 3. A method for preparing a traditional Chinese medicine extract C for treating non-alcoholic fatty liver disease:

[0104] Take 8 parts of Sophora japonica flowers, 9 parts of Curcuma longa, and 6 parts of Aucklandia lappa flowers, grind them into coarse powder, add 12 times the amount of water, and extract by steam distillation for 5 hours. Collect the volatile oil; store the volatile oil in a separate container, and keep the residue for later use.

[0105] Take 8 parts hawthorn and 10 parts salvia miltiorrhiza, and extract them three times with the above-mentioned dregs of sophora japonica, turmeric, and costus root by reflux with water. Each time, the amount of water added is 8 times the volume of the herb, and the extraction time is 3 hours, 2 hours, and 1 hour, respectively. Combine the extracts and concentrate them to a relative density of 1.18 (60℃). Add ethanol to make the alcohol content reach 60%, and precipitate for 24 hours. Collect the supernatant, wash the precipitate twice with 60% ethanol, combine the supernatant and washings, and recover until there is no alcohol odor. Dilute with water to 4 times the volume of the herb, and load it onto a pre-treated HPD-722 macroporous resin column. Elute with 8 column volumes of purified water at a rate of 8 ml / min, and discard the eluent. Then elute with 6 column volumes of 50% ethanol, collect the eluent, and then elute with 3 column volumes of 30% ethanol, collect the eluent, combine the eluents, and recover until there is no alcohol odor. Freeze-dry and pulverize into a fine powder to obtain extract C.

[0106] 4. A method for preparing a traditional Chinese medicine extract D for treating non-alcoholic fatty liver disease:

[0107] Dissolve the volatile oil from step "3" and the volatile oil from step "2" in an equal volume of ethanol, and add the solution dropwise to a β-cyclodextrin aqueous solution. Stir at 40°C for 5 hours, refrigerate at 5°C for 24 hours, filter, and vacuum dry the precipitate at 40°C for 5 hours to obtain the volatile oil inclusion complex. Crush the precipitate into a fine powder to obtain extract D. (Wherein, the mass-to-volume ratio of β-cyclodextrin to water in the β-cyclodextrin aqueous solution is 1:5 (g / ml), and the volume-to-mass ratio of volatile oil to β-cyclodextrin is 1:7 (ml / g).

[0108] 5. A method for preparing a traditional Chinese medicine extract E for treating non-alcoholic fatty liver disease:

[0109] Take 10 parts of *Heliotropium indicum*, grind it into coarse powder, add 30 times the amount of water, control the voltage at 120 V, and perform flash extraction for 8 minutes. Add ethanol to the extract to make the ethanol concentration 70%, adjust the pH of the solution to 5.0, let it stand for 24 hours, recover the ethanol, and concentrate under reduced pressure to a clear extract with a relative density of 1.10 (50℃). Place the extract on a neutral alumina column (100-200 mesh) and elute with 50% ethanol. Collect the eluent and concentrate it to a clear extract with a relative density of 1.18 (60℃). Freeze-dry the concentrate and grind it into fine powder to obtain extract E.

[0110] 6. Preparation of a traditional Chinese medicine extract composition for treating non-alcoholic fatty liver disease

[0111] The extract powders prepared in steps (1), (2), (3), (4), and (5) are mixed evenly to obtain the traditional Chinese medicine composition of the present invention.

[0112] Example 2: Composition of the present invention

[0113] Formula: Turmeric 9 parts, Vinegar-processed Bupleurum 20 parts, Ligusticum chuanxiong 10 parts, Astragalus membranaceus 15 parts, Salvia miltiorrhiza 10 parts, Aucklandia lappa 6 parts, Crataegus pinnatifida 8 parts, Sophora japonica 8 parts, Abrus precatorius 10 parts, Alisma plantago-aquatica 12 parts

[0114] Preparation method:

[0115] 1. A method for preparing a traditional Chinese medicine extract A for treating non-alcoholic fatty liver disease:

[0116] Take 15 parts of Astragalus membranaceus and 12 parts of Alisma plantago-aquatica, and extract them three times under reflux. For the first extraction, add 8 times the amount of water, soak at 50℃ for 40 minutes, and extract for 3 hours. For the second extraction, add 8 times the amount of water and extract for 2 hours. For the third extraction, add 6 times the amount of water and extract for 1 hour. Combine the decoctions, filter, concentrate under reduced pressure to a thick paste with a relative density of 1.20 (60℃), add ethanol to make the alcohol content reach 60%, precipitate with alcohol for 24 hours, recover the ethanol, and concentrate to a clear paste with a relative density of 1.15 (60℃). Freeze-dry the concentrate and pulverize it into a fine powder to obtain extract A.

[0117] 2. A method for preparing a traditional Chinese medicine extract B for treating non-alcoholic fatty liver disease:

[0118] Take 10 parts of Ligusticum chuanxiong and 20 parts of Bupleurum chinense (processed with vinegar), grind them into coarse powder, add them to an aqueous solution with pH 7.5 and decoct twice (collecting the volatile oil at the same time). For the first decoction, add 10 times the amount of water and decoct for 2 hours. For the second decoction, add 8 times the amount of water and decoct for 1 hour. Combine the decoctions, store the volatile oil separately, and concentrate the decoction to a clear extract with a relative density of 1.17 (60℃). Adjust the pH to 3.7 with 2 mol / L hydrochloric acid solution, keep warm at 65℃ for 1 hour, filter, and add 7 times the amount of water to the precipitate and stir well. The pH was adjusted to 6.2 with 3% NaOH solution, and an equal volume of 95% ethanol was added. The mixture was stirred to dissolve the solution, filtered, and the filtrate was concentrated to a solid-liquid ratio of 1:3.5. The solution was then passed through the treated AB-8 macroporous resin and eluted with 4 column volumes of water. The eluent was discarded, and the solution was eluted with 8 column volumes of 40% ethanol. The ethanol eluent was collected, concentrated under reduced pressure, and concentrated to a relative density of 1.22 (60°C). The solution was then dried under cold conditions and pulverized into a fine powder to obtain extract B.

[0119] 3. A method for preparing a traditional Chinese medicine extract C for treating non-alcoholic fatty liver disease:

[0120] Take 8 parts of Sophora japonica flowers, 9 parts of Curcuma longa, and 6 parts of Aucklandia lappa, grind them into coarse powder, add 9 times the amount of water, and extract by steam distillation for 3 hours. Collect the volatile oil; store the volatile oil in a separate container, and keep the residue for later use.

[0121] Take 8 parts hawthorn and 10 parts salvia miltiorrhiza, and extract them three times with the above-mentioned dregs of sophora japonica, turmeric, and costus root by reflux with water. Each time, the amount of water added is 10 times the volume of the herb, and the extraction time is 3 hours, 2 hours, and 1 hour, respectively. Combine the extracts and concentrate them to a relative density of 1.17 (60℃). Add ethanol to make the alcohol content reach 60%, and precipitate for 24 hours. Collect the supernatant, wash the precipitate twice with 65% ethanol, combine the supernatant and washings, and recover until there is no alcohol odor. Dilute with water to 4 times the volume of the herb, and load it onto a pre-treated HPD-722 macroporous resin column. Elute with 9 column volumes of purified water at a rate of 10 ml / min, and discard the eluent. Then elute with 6 column volumes of 50% ethanol, collect the eluent, and then elute with 3 column volumes of 30% ethanol, collect the eluent, combine the eluents, and recover until there is no alcohol odor. Freeze-dry and pulverize into a fine powder to obtain extract C.

[0122] 4. A method for preparing a traditional Chinese medicine extract D for treating non-alcoholic fatty liver disease:

[0123] Dissolve the volatile oil from step "3" and the volatile oil from step "2" in an equal volume of ethanol, and add the solution dropwise to a β-cyclodextrin aqueous solution. Stir at 42°C for 5 hours, refrigerate at 5°C for 24 hours, filter, and vacuum dry the precipitate at 40°C for 5 hours to obtain the volatile oil inclusion complex. Crush the precipitate into a fine powder to obtain extract D. (Wherein, the mass-to-volume ratio of β-cyclodextrin to water in the β-cyclodextrin aqueous solution is 1:8 (g / ml), and the volume-to-mass ratio of volatile oil to β-cyclodextrin is 1:7.5 (ml / g).

[0124] 5. A method for preparing a traditional Chinese medicine extract E for treating non-alcoholic fatty liver disease:

[0125] Take 10 parts of *Heliotropium indicum*, grind it into coarse powder, add 28 times the amount of water, control the voltage at 120 V, and perform flash extraction for 8 minutes. Add ethanol to the extract to make the ethanol concentration 70%, adjust the pH of the solution to 5.0, let it stand for 24 hours, recover the ethanol, and concentrate under reduced pressure to a clear extract with a relative density of 1.14 (50℃). Place the extract on a neutral alumina column (100-200 mesh) and elute with 52% ethanol. Collect the eluent and concentrate it to a clear extract with a relative density of 1.16 (60℃). Freeze-dry the concentrate and grind it into fine powder to obtain extract E.

[0126] 6. Preparation of a traditional Chinese medicine extract composition for treating non-alcoholic fatty liver disease

[0127] The extract powders prepared in steps (1), (2), (3), (4), and (5) are mixed evenly to obtain the traditional Chinese medicine composition of the present invention.

[0128] Example 3: Composition of the present invention

[0129] Formula: Turmeric 15 parts, Vinegar-processed Bupleurum 25 parts, Ligusticum chuanxiong 15 parts, Astragalus membranaceus 20 parts, Salvia miltiorrhiza 15 parts, Aucklandia lappa 1 part, Crataegus pinnatifida 4 parts, Sophora japonica 3 parts, Abrus precatorius 15 parts, Alisma plantago-aquatica 5 parts

[0130] Preparation method:

[0131] 1. A method for preparing a traditional Chinese medicine extract A for treating non-alcoholic fatty liver disease:

[0132] Take 20 parts of Astragalus membranaceus and 5 parts of Alisma plantago-aquatica, and extract them three times under reflux. For the first extraction, add 9 times the amount of water, soak at 50℃ for 40 minutes, and extract for 3 hours. For the second extraction, add 7 times the amount of water and extract for 2 hours. For the third extraction, add 5 times the amount of water and extract for 1 hour. Combine the decoctions, filter, concentrate under reduced pressure to a thick paste with a relative density of 1.25 (60℃), add ethanol to make the alcohol content reach 60%, precipitate with alcohol for 24 hours, recover the ethanol, and concentrate to a clear paste with a relative density of 1.18 (60℃). Freeze-dry the concentrate and pulverize it into a fine powder to obtain extract A.

[0133] 2. A method for preparing a traditional Chinese medicine extract B for treating non-alcoholic fatty liver disease:

[0134] Take 15 parts of Ligusticum chuanxiong and 25 parts of Bupleurum chinense (processed with vinegar), grind them into coarse powder, add them to an aqueous solution with pH 7.0 and decoct twice (collecting the volatile oil at the same time). For the first decoction, add 10 times the amount of water and decoct for 2 hours. For the second decoction, add 8 times the amount of water and decoct for 1 hour. Combine the decoctions, store the volatile oil separately, and concentrate the decoction to a clear extract with a relative density of 1.18 (60℃). Adjust the pH to 4.0 with 2 mol / L hydrochloric acid solution, keep warm at 65℃ for 1 hour, filter, and add 7 times the amount of water to the precipitate and stir well. The pH was adjusted to 6.8 with 3% NaOH solution, and an equal volume of 95% ethanol was added. The mixture was stirred to dissolve the ethanol, filtered, and the filtrate was concentrated to a solid-liquid ratio of 1:3.5. The filtrate was then passed through the treated AB-8 macroporous resin and eluted with 4 column volumes of water. The eluent was discarded, and the solution was eluted with 8 column volumes of 40% ethanol. The ethanol eluent was collected, concentrated under reduced pressure, and concentrated to a relative density of 1.25 (60°C). The solution was then dried under cold conditions and pulverized into a fine powder to obtain extract B.

[0135] 3. A method for preparing a traditional Chinese medicine extract C for treating non-alcoholic fatty liver disease:

[0136] Take 3 parts of Sophora japonica flowers, 15 parts of Curcuma longa, and 1 part of Aucklandia lappa, grind them into coarse powder, add 12 times the amount of water, and extract by steam distillation for 5 hours. Collect the volatile oil; store the volatile oil in a separate container, and keep the residue for later use.

[0137] Take 4 parts hawthorn and 15 parts salvia miltiorrhiza, along with the above-mentioned dregs of sophora japonica, turmeric, and costus root. Extract three times by reflux with water, each time adding 9 times the volume of water. The extraction times are 3 hours, 2 hours, and 1 hour, respectively. Combine the extracts and concentrate to a relative density of 1.17 (60℃). Add ethanol to achieve an alcohol content of 65%, and precipitate for 24 hours. Collect the supernatant, wash the precipitate twice with 65% ethanol, combine the supernatant and washings, and recover until no alcohol odor remains. Dilute with water to 4 times the volume of the medicinal materials, and load onto a pre-treated HPD-722 macroporous resin column. Elute with 8 column volumes of purified water at a rate of 6 ml / min, discarding the eluent. Elute again with 6 column volumes of 50% ethanol, collecting the eluent. Elute again with 3 column volumes of 30% ethanol, collecting the eluent. Combine the eluents and recover until no alcohol odor remains. Freeze-dry and pulverize into a fine powder to obtain extract C.

[0138] 4. A method for preparing a traditional Chinese medicine extract D for treating non-alcoholic fatty liver disease:

[0139] Dissolve the volatile oil from step "3" and the volatile oil from step "2" in an equal volume of ethanol, and add the solution dropwise to a β-cyclodextrin aqueous solution. Stir at 40°C for 5 hours, refrigerate at 5°C for 24 hours, filter, and vacuum dry the precipitate at 40°C for 6 hours to obtain the volatile oil inclusion complex. Pulverize the precipitate into a fine powder to obtain extract D. (Wherein, the mass-to-volume ratio of β-cyclodextrin to water in the β-cyclodextrin aqueous solution is 1:4 (g / ml), and the volume-to-mass ratio of volatile oil to β-cyclodextrin is 1:5 (ml / g).

[0140] 5. A method for preparing a traditional Chinese medicine extract E for treating non-alcoholic fatty liver disease:

[0141] Take 15 parts of *Abrus precatorius*, grind it into coarse powder, add 30 times the amount of water, control the voltage at 120 V, and perform flash extraction for 7 minutes. Add ethanol to the extract to make the ethanol concentration 75%, adjust the pH of the solution to 4.0, let it stand for 24 hours, recover the ethanol, and concentrate under reduced pressure to a clear extract with a relative density of 1.13 (50℃). Place the extract on a neutral alumina column (100-200 mesh) and elute with 50% ethanol. Collect the eluent and concentrate it to a clear extract with a relative density of 1.15 (60℃). Freeze-dry the concentrate and grind it into fine powder to obtain extract E.

[0142] 6. Preparation of a traditional Chinese medicine extract composition for treating non-alcoholic fatty liver disease

[0143] The extract powders prepared in steps (1), (2), (3), (4), and (5) are mixed evenly to obtain the traditional Chinese medicine composition of the present invention.

[0144] Example 4: Composition of the present invention

[0145] Formula: Curcuma longa 4 parts, Bupleurum chinense (processed with vinegar) 15 parts, Ligusticum chuanxiong 5 parts, Astragalus membranaceus 10 parts, Salvia miltiorrhiza 5 parts, Aucklandia lappa 12 parts, Crataegus pinnatifida 12 parts, Sophora japonica 15 parts, Abrus precatorius 5 parts, Alisma plantago-aquatica 15

[0146] Preparation method:

[0147] 1. A method for preparing a traditional Chinese medicine extract A for treating non-alcoholic fatty liver disease:

[0148] Take 10 parts of Astragalus membranaceus and 15 parts of Alisma plantago-aquatica, and extract them three times under reflux. For the first extraction, add 10 times the amount of water, soak at 60℃ for 30 minutes, and extract for 2 hours. For the second extraction, add 8 times the amount of water and extract for 2 hours. For the third extraction, add 6 times the amount of water and extract for 1 hour. Combine the decoctions, filter, concentrate under reduced pressure to a thick paste with a relative density of 1.20 (60℃), add ethanol to make the alcohol content reach 70%, precipitate with alcohol for 24 hours, recover the ethanol, and concentrate to a clear paste with a relative density of 1.15 (60℃). Freeze-dry the concentrate and pulverize it into a fine powder to obtain extract A.

[0149] 2. A method for preparing a traditional Chinese medicine extract B for treating non-alcoholic fatty liver disease:

[0150] Take 5 parts of Ligusticum chuanxiong and 15 parts of Bupleurum chinense (processed with vinegar), grind them into coarse powder, add an aqueous solution with pH 6.5 and decoct twice (collecting volatile oil at the same time). For the first decoction, add 12 times the amount of water and decoct for 2 hours. For the second decoction, add 10 times the amount of water and decoct for 1 hour. Combine the decoctions, store the volatile oil separately, and concentrate the decoction to a clear extract with a relative density of 1.15 (60℃). Adjust the pH to 3.5 with 2 mol / L hydrochloric acid solution, keep warm at 65℃ for 1 hour, filter, and add 7 times the amount of water to the precipitate and stir well. Adjust the pH to 6.0 with 2.5% NaOH solution, add an equal volume of 95% ethanol, stir to dissolve, filter, concentrate the filtrate to a solid-liquid ratio of 1:2.5, pass it through the treated AB-8 macroporous resin, elute with 4 column volumes of water, discard the eluent, then elute with 7 column volumes of 50% ethanol, collect the ethanol eluent, concentrate under reduced pressure to a relative density of 1.18 (60℃), cool and dry, and pulverize into a fine powder to obtain extract B.

[0151] 3. A method for preparing a traditional Chinese medicine extract C for treating non-alcoholic fatty liver disease:

[0152] Take 15 parts of Sophora japonica flowers, 4 parts of Curcuma longa, and 12 parts of Aucklandia lappa, grind them into coarse powder, add 10 times the amount of water, and extract by steam distillation for 4 hours. Collect the volatile oil; store the volatile oil in a separate container, and keep the residue for later use.

[0153] Take 12 parts hawthorn and 5 parts salvia miltiorrhiza, and extract them three times with the above-mentioned dregs of sophora japonica, turmeric, and costus root by reflux with water. Each time, the amount of water added is 10 times the volume of the herb, and the extraction time is 2 hours, 2 hours, and 1 hour, respectively. Combine the extracts and concentrate them to a relative density of 1.16 (60℃). Add ethanol to make the alcohol content reach 60%, and precipitate for 24 hours. Collect the supernatant, wash the precipitate twice with 65% ethanol, combine the supernatant and washings, and recover until there is no alcohol odor. Dilute with water to 4 times the amount of the herb, and load it onto a pre-treated HPD-722 macroporous resin column. Elute with 9 column volumes of purified water at a rate of 7 ml / min, and discard the eluent. Then elute with 7 column volumes of 40% ethanol, collect the eluent, and then elute with 3 column volumes of 40% ethanol, collect the eluent, combine the eluents, and recover until there is no alcohol odor. Freeze-dry and pulverize into a fine powder to obtain extract C.

[0154] 4. A method for preparing a traditional Chinese medicine extract D for treating non-alcoholic fatty liver disease:

[0155] Dissolve the volatile oil from step "3" and the volatile oil from step "2" in an equal volume of ethanol, and add the solution dropwise to a β-cyclodextrin aqueous solution. Stir at 40°C for 4 hours, refrigerate at 5°C for 24 hours, filter, and vacuum dry the precipitate at 40°C for 5 hours to obtain the volatile oil inclusion complex. Pulverize the precipitate into a fine powder to obtain extract D. (Wherein, the mass-to-volume ratio of β-cyclodextrin to water in the β-cyclodextrin aqueous solution is 1:6 (g / ml), and the volume-to-mass ratio of volatile oil to β-cyclodextrin is 1:8 (ml / g).

[0156] 5. A method for preparing a traditional Chinese medicine extract E for treating non-alcoholic fatty liver disease:

[0157] Take 5 parts of *Heliotropium indicum*, grind it into coarse powder, add 25 times the amount of water, control the voltage at 120 V, and perform flash extraction for 6 minutes. Add ethanol to the extract to make the ethanol concentration 75%, adjust the pH of the solution to 5.0, let it stand for 24 hours, recover the ethanol, and concentrate under reduced pressure to a clear extract with a relative density of 1.08 (50℃). Place the extract on a neutral alumina column (100-200 mesh) and elute with 40% ethanol. Collect the eluent and concentrate it to a clear extract with a relative density of 1.18 (60℃). Freeze-dry the concentrate and grind it into fine powder to obtain extract E.

[0158] 6. Preparation of a traditional Chinese medicine extract composition for treating non-alcoholic fatty liver disease

[0159] The extract powders prepared in steps (1), (2), (3), (4), and (5) are mixed evenly to obtain the traditional Chinese medicine composition of the present invention.

[0160] Example 5

[0161] The specific compositions of the thrombolytic and collateral-clearing tablets, the composition of Chinese patent CN201310597025.X, and the atorvastatin calcium tablets used in the experimental groups in this embodiment are as follows:

[0162] The formula for Xiaoshuan Tongluo tablets is as follows: Chuanxiong 287g, Danshen 215g, Huangqi 431g, Zexie 144g, Sanqi 144g, Huaihua 72g, Guizhi 144g, Yujin 144g, Muxiang 72g, Bingpian 5.7g, Shanzha 144g.

[0163] The formula of patent CN201310597025.X is as follows: 30 parts of Coptis chinensis, 20 parts of Picrorhiza scrophulariiflora, 30 parts of Panax notoginseng, 20 parts of Salvia miltiorrhiza, 15 parts of Pueraria lobata, 15 parts of Atractylodes macrocephala, 30 parts of Paeonia lactiflora, 20 parts of Poria cocos, 15 parts of Bupleurum chinense, 15 parts of Angelica sinensis, 30 parts of Nelumbo nucifera leaf, 30 parts of Coix lacryma-jobi, 30 parts of Benincasa hispida seed, 20 parts of Phragmites communis rhizome, 15 parts of Platycodon grandiflorus, 15 parts of Lepidium apetalum, 15 parts of Eriobotrya japonica leaf, 15 parts of Fritillaria cirrhosa, 12 parts of Lycium barbarum, 12 parts of Cassia tora seed, 12 parts of Alisma plantago-aquatica, 10 parts of Prunus persica kernel, and 5 parts of Morus alba leaf.

[0164] Atorvastatin calcium tablets contain atorvastatin calcium, chemically named [R-(R′, R′)]-2-(4-fluorophenyl)-bd-dihydroxy-5-(1-methylethyl)-3-phenyl-4-[(aniline)carbonyl]-1-hydro-pyrrole-1-heptanoic acid calcium trihydrate.

[0165] Example 6: Tablets of the present invention

[0166] Take the traditional Chinese medicine composition described in Example 1, add an appropriate amount of maltodextrin and sucrose (maltodextrin: sucrose = 1.7:1), mix evenly, compress into tablets.

[0167] Example 7: Capsule Formulation of the Present Invention

[0168] Take the traditional Chinese medicine composition described in Example 2, add an appropriate amount of starch, mix evenly, wet granulate, dry, granulate, and fill into capsules to make capsules.

[0169] Example 8: Granules of the present invention

[0170] Take the traditional Chinese medicine composition described in Example 3, add dextrin, lactose, etc., mix evenly, and dry granulate to make granules.

[0171] Example 9 Missing square group

[0172] 10 parts of turmeric, 10 parts of chuanxiong rhizome, 15 parts of astragalus root, 10 parts of salvia root, 8 parts of costus root, 10 parts of hawthorn fruit, 9 parts of sophora flower, and 12 parts of alisma rhizome.

[0173] Preparation method:

[0174] 1. A method for preparing a traditional Chinese medicine extract A for treating non-alcoholic fatty liver disease:

[0175] Take 15 parts of Astragalus membranaceus and 12 parts of Alisma plantago-aquatica, and extract them three times under reflux. For the first extraction, add 10 times the amount of water, soak at 50℃ for 40 minutes, and extract for 3 hours. For the second extraction, add 8 times the amount of water and extract for 2 hours. For the third extraction, add 6 times the amount of water and extract for 1 hour. Combine the decoctions, filter, concentrate under reduced pressure to a thick paste with a relative density of 1.28 (60℃), add ethanol to make the alcohol content reach 60%, precipitate with alcohol for 24 hours, recover the ethanol, and concentrate to a clear paste with a relative density of 1.19 (60℃). Freeze-dry the concentrate and pulverize it into a fine powder to obtain extract A.

[0176] 2. A method for preparing a traditional Chinese medicine extract B for treating non-alcoholic fatty liver disease:

[0177] Take 10 parts of Ligusticum chuanxiong, grind it into coarse powder, add it to a pH 7.0 aqueous solution and decoct twice (collecting the volatile oil at the same time). For the first decoction, add 12 times the amount of Ligusticum chuanxiong and decoct for 2 hours. For the second decoction, add 10 times the amount of water and decoct for 1 hour. Combine the decoctions, store the volatile oil separately, and concentrate the decoction to a clear extract with a relative density of 1.18 (60℃). Adjust the pH to 3.5 with 2 mol / L hydrochloric acid solution, keep warm at 65℃ for 1 hour, filter, add 7 times the amount of water to the precipitate and stir well. Adjust the pH to 6.5 with 3% NaOH solution, add an equal volume of 95% ethanol, stir to dissolve, filter, concentrate the filtrate to a solid-liquid ratio of 1:3, pass it through the treated AB-8 macroporous resin, elute with 4 column volumes of water, discard the eluent, then elute with 8 column volumes of 40% ethanol, collect the ethanol eluent, concentrate under reduced pressure to a relative density of 1.25 (60℃), cool and dry, and pulverize into a fine powder to obtain extract B.

[0178] 3. A method for preparing a traditional Chinese medicine extract C for treating non-alcoholic fatty liver disease:

[0179] Take 9 parts of Sophora japonica flowers, 10 parts of Curcuma longa, and 8 parts of Aucklandia lappa flowers, grind them into coarse powder, add 12 times the amount of water, and extract by steam distillation for 5 hours. Collect the volatile oil; store the volatile oil in a separate container, and keep the residue for later use.

[0180] Take 10 parts hawthorn and 10 parts salvia miltiorrhiza, and extract them three times with the above-mentioned dregs of sophora japonica, turmeric, and costus root by reflux with water. Each time, the amount of water added is 8 times the volume of the herb, and the extraction time is 3 hours, 2 hours, and 1 hour, respectively. Combine the extracts and concentrate them to a relative density of 1.20 (60℃). Add ethanol to make the alcohol content reach 60%, and precipitate for 24 hours. Collect the supernatant, wash the precipitate twice with 60% ethanol, combine the supernatant and washings, and recover until there is no alcohol odor. Dilute with water to 4 times the volume of the herb, and load it onto a pre-treated HPD-722 macroporous resin column. Elute with 8 column volumes of purified water at a rate of 8 ml / min, and discard the eluent. Then elute with 6 column volumes of 50% ethanol, collect the eluent, and then elute with 3 column volumes of 30% ethanol, collect the eluent, combine the eluents, and recover until there is no alcohol odor. Freeze-dry and pulverize into a fine powder to obtain extract C.

[0181] 4. A method for preparing a traditional Chinese medicine extract D for treating non-alcoholic fatty liver disease:

[0182] Dissolve the volatile oil from step "3" and the volatile oil from step "2" in an equal volume of ethanol, and add the solution dropwise to a β-cyclodextrin aqueous solution. Stir at 40°C for 5 hours, refrigerate at 5°C for 24 hours, filter, and vacuum dry the precipitate at 40°C for 5 hours to obtain the volatile oil inclusion complex. Crush the precipitate into a fine powder to obtain extract D. (Wherein, the mass-to-volume ratio of β-cyclodextrin to water in the β-cyclodextrin aqueous solution is 1:5 (g / ml), and the volume-to-mass ratio of volatile oil to β-cyclodextrin is 1:7 (ml / g).

[0183] 5. Preparation of a traditional Chinese medicine extract composition for treating non-alcoholic fatty liver disease

[0184] The extract powders prepared in steps (1), (2), (3), and (4) are mixed evenly to obtain the traditional Chinese medicine composition of the present invention.

[0185] Example 10: Replacement group

[0186] 5 parts turmeric, 15 parts vinegar-processed Bupleurum, 7 parts Ligusticum chuanxiong, 10 parts Astragalus membranaceus, 8 parts Salvia miltiorrhiza, 4 parts Aucklandia lappa, 6 parts hawthorn, 5 parts Sophora japonica, 8 parts Abrus precatorius, and 10 parts Alisma plantago-aquatica.

[0187] Preparation method:

[0188] 1. A method for preparing a traditional Chinese medicine extract A for treating non-alcoholic fatty liver disease:

[0189] Take 10 parts of Astragalus membranaceus and 10 parts of Alisma plantago-aquatica, and extract them three times under reflux. For the first extraction, add 10 times the amount of water, soak at 50℃ for 40 minutes, and extract for 3 hours. For the second extraction, add 8 times the amount of water and extract for 2 hours. For the third extraction, add 6 times the amount of water and extract for 1 hour. Combine the decoctions, filter, concentrate under reduced pressure to a thick paste with a relative density of 1.25 (60℃), add ethanol to make the alcohol content reach 60%, precipitate with alcohol for 24 hours, recover the ethanol, and concentrate to a clear paste with a relative density of 1.18 (60℃). Freeze-dry the concentrate and pulverize it into a fine powder to obtain extract A.

[0190] 2. A method for preparing a traditional Chinese medicine extract B for treating non-alcoholic fatty liver disease:

[0191] Take 7 parts of Ligusticum chuanxiong and 15 parts of Bupleurum chinense (processed with vinegar), grind them into coarse powder, add them to an aqueous solution with pH 7.0 and decoct twice (collecting the volatile oil at the same time). For the first decoction, add 12 times the amount of water and decoct for 2 hours. For the second decoction, add 10 times the amount of water and decoct for 1 hour. Combine the decoctions, store the volatile oil separately, and concentrate the decoction to a clear extract with a relative density of 1.15 (60℃). Adjust the pH to 3.5 with 2 mol / L hydrochloric acid solution, keep warm at 65℃ for 1 hour, filter, and add 7 times the amount of water to the precipitate and stir. Mix well, adjust the pH to 6.5 with 3% NaOH solution, add an equal volume of 95% ethanol, stir to dissolve, filter, concentrate the filtrate to a material-to-liquid ratio of 1:3, pass through the treated AB-8 macroporous resin, elute with 4 column volumes of water, discard the eluent, then elute with 8 column volumes of 40% ethanol, collect the ethanol eluent, concentrate under reduced pressure to a relative density of 1.20 (60℃), cool and dry, and pulverize into a fine powder to obtain extract B.

[0192] 3. A method for preparing a traditional Chinese medicine extract C for treating non-alcoholic fatty liver disease:

[0193] Take 5 parts of Sophora japonica flowers, 5 parts of Curcuma longa, and 4 parts of Aucklandia lappa, grind them into coarse powder, add 12 times the amount of water, and extract by steam distillation for 5 hours. Collect the volatile oil; store the volatile oil in a separate container, and keep the residue for later use.

[0194] Take 6 parts hawthorn and 8 parts salvia miltiorrhiza, and extract them three times with the above-mentioned dregs of sophora japonica, turmeric, and costus root by reflux with water. Each time, the amount of water added is 8 times the volume of the herb, and the extraction time is 3 hours, 2 hours, and 1 hour, respectively. Combine the extracts and concentrate them to a relative density of 1.18 (60℃). Add ethanol to make the alcohol content reach 60%, and precipitate for 24 hours. Collect the supernatant, wash the precipitate twice with 60% ethanol, combine the supernatant and washings, and recover until there is no alcohol odor. Dilute with water to 4 times the volume of the herb, and load it onto a pre-treated HPD-722 macroporous resin column. Elute with 8 column volumes of purified water at a rate of 8 ml / min, and discard the eluent. Then elute with 6 column volumes of 50% ethanol, collect the eluent, and then elute with 3 column volumes of 30% ethanol, collect the eluent, combine the eluents, and recover until there is no alcohol odor. Freeze-dry and pulverize into a fine powder to obtain extract C.

[0195] 4. A method for preparing a traditional Chinese medicine extract D for treating non-alcoholic fatty liver disease:

[0196] Dissolve the volatile oil from step "3" and the volatile oil from step "2" in an equal volume of ethanol, and add the solution dropwise to a β-cyclodextrin aqueous solution. Stir at 40°C for 5 hours, refrigerate at 5°C for 24 hours, filter, and vacuum dry the precipitate at 40°C for 5 hours to obtain the volatile oil inclusion complex. Crush the precipitate into a fine powder to obtain extract D. (Wherein, the mass-to-volume ratio of β-cyclodextrin to water in the β-cyclodextrin aqueous solution is 1:5 (g / ml), and the volume-to-mass ratio of volatile oil to β-cyclodextrin is 1:7 (ml / g).

[0197] 5. A method for preparing a traditional Chinese medicine extract E for treating non-alcoholic fatty liver disease:

[0198] Take 8 parts of *Heliotropium indicum*, grind it into coarse powder, add 30 times the amount of water, control the voltage at 120 V, and perform flash extraction for 8 minutes. Add ethanol to the extract to make the ethanol concentration 70%, adjust the pH of the solution to 5.0, let it stand for 24 hours, recover the ethanol, and concentrate under reduced pressure to a clear extract with a relative density of 1.10 (50℃). Place the extract on a neutral alumina column (100-200 mesh) and elute with 50% ethanol. Collect the eluent and concentrate it to a clear extract with a relative density of 1.18 (60℃). Freeze-dry the concentrate and grind it into fine powder to obtain extract E.

[0199] 6. Preparation of a traditional Chinese medicine extract composition for treating non-alcoholic fatty liver disease

[0200] The extract powders prepared in steps (1), (2), (3), (4), and (5) are mixed evenly to obtain the traditional Chinese medicine composition of the present invention.

[0201] 1 Experimental Materials

[0202] 1.1 Test Drugs

[0203] The traditional Chinese medicine composition, the original traditional Chinese medicine composition, and the patent preparation of CN201310597025.X are provided by Jilin Xiuzheng Pharmaceutical New Drug Development Co., Ltd.

[0204] 1.2 Experimental Animals

[0205] 42 male SPF-grade SD rats were used, with the animal production license number SCXK (Ji)-2020-0002. The maintenance feed for SPF rats was provided by Changchun Yisi Laboratory Animal Technology Co., Ltd.

[0206] 1.3 Reagents

[0207] Fasting blood glucose (FBG) kit, alanine aminotransferase (ALT) kit, aspartate aminotransferase (AST) kit, triglyceride (TG) kit, and total cholesterol (TC) kit were purchased from Nanjing Jiancheng Bioengineering Institute.

[0208] 2 Experimental Methods

[0209] Forty-two 6-week-old male SD rats were adaptively fed for 3 days. 6 rats were randomly selected as the blank group, and given 10 mL / kg of normal saline by gavage, while the remaining rats were given an equal amount of high-sugar and high-fat emulsion by gavage to establish a rat model of non-alcoholic fatty liver disease (NAFLD). After 8 weeks, all animals were anesthetized with ether, and venous blood was collected to obtain serum for TC detection. According to the TC values, the modeled rats were randomly divided into a model group, a simvastatin group (8 mg / kg), the CN201310597025.X patent preparation group (1250 mg / kg), a high-dose traditional Chinese medicine composition group (2500 mg / kg) and a low-dose traditional Chinese medicine composition group (1250 mg / kg). After grouping, modeling-related administration was performed in the morning and therapeutic administration was performed in the afternoon. The normal control group and the model control group were given an equal volume of pure water, with an administration volume of 10 mL / kg. Administration was continued for 6 weeks, during which all rats were fed with standard diet.

[0210] 3 Observation and Determination of Indicators

[0211] 3.1 General Conditions

[0212] During the experiment, the behavior, mental state, hair, and excrement of rats in each group were observed.

[0213] 3.2 Fasting Blood Glucose (FBG) Detection

[0214] Before the last administration, animals in each group were fasted but allowed free access to water for 12 hours, then blood was collected from the tail vein to determine fasting blood glucose (FBG).

[0215] 2.3 Detection of biochemical indicators in serum

[0216] Animals in each group were fasted for 12 hours after the last administration but allowed free access to water. Blood was collected intravenously after anesthesia, and serum was separated by centrifugation at 3500 r / min for 15 min. Liver function tests, including alanine aminotransferase (ALT) and aspartate aminotransferase (AST), as well as blood lipid levels of triglycerides (TG) and total cholesterol (TC), were measured.

[0217] 2.4 Organ Coefficient

[0218] The rat was euthanized by dislocation, and its liver was harvested, weighed, and its organ coefficient was calculated. Organ coefficient = (Wet organ mass (g) / Body mass (g)) × 100%

[0219] 3. Statistical methods

[0220] All experimental data are expressed in terms of... ±s indicates statistical analysis using SPSS 11.5 software, and t-tests were used for comparisons between groups.

[0221] 4. Experimental Results

[0222] 4.1 General Situation

[0223] During the experiment, the control group rats showed good growth and activity, with glossy fur, high energy, and no abnormalities in their excrement. The model group rats were lethargic, with tangled and dull fur, preferred to huddle together and lie curled up, and had loose, foul-smelling feces. The simvastatin group and the drug-treated group showed better activity and glossy fur than the model control group; only a few exhibited sluggish movement, dull fur, and diarrhea.

[0224] 4.2 Effects on liver index

[0225] Compared with the control group, the liver index in the model group was significantly increased (P<0.001); compared with the model group, the liver index in the high-dose group of the traditional Chinese medicine composition was significantly decreased (P<0.01); compared with the patented preparation group (CN201310597025.X), the liver index in the high-dose group of the traditional Chinese medicine composition was significantly decreased (P<0.05). See Table 1 for details. Figure 1 ; Figure 1 The effect of liver index on each group of rats; such as Figure 1 As shown, the traditional Chinese medicine composition can effectively reduce intraperitoneal fat accumulation, decrease liver wet mass and liver index in NAFLD model rats, reduce fat deposition in the liver, and improve liver function. Its effects are significantly superior to patented preparations, unavailable formulas, and alternative preparations.

[0226] Table 1 Comparison of liver index among rats in each group ( ±S)

[0227]

[0228] Note: Compared with the blank group, ▲▲▲ P < 0.001; compared with the model group, *** P<0.001, ** P<0.01; compared with the formulation group of patent CN201310597025.X, △ P<0.05, △△ P<0.01.

[0229] 4.2 Effects on blood lipid levels in NAFLD rats

[0230] Compared with the control group, the serum levels of TC, TG, and FBG in the model group were significantly increased (P<0.001); compared with the model group, the serum levels of TC, TG, and FBG in each treatment group were significantly decreased to varying degrees (P<0.05, P<0.01, P<0.001). Compared with the patented formulation group (CN201310597025.X), the serum levels of TC, TG, and FBG in the high- and low-dose groups of the traditional Chinese medicine composition were significantly decreased to varying degrees (P<0.05, P<0.01, P<0.001). This indicates that the traditional Chinese medicine composition has a good regulatory effect on lipid dyslipidemia in NAFLD rats. See Table 2 for details. Figure 2 , Figure 2 To investigate the effects on blood lipid levels in NAFLD rats; such as Figure 2 As shown, the traditional Chinese medicine composition has a good regulatory effect on dyslipidemia in NAFLD rats. Its effect is significantly better than that of patented preparations, unavailable prescriptions, and alternative preparations.

[0231] Table 2 Effects on blood lipid levels in NAFLD rats (mmol / L) ±S)

[0232]

[0233] Note: Compared with the blank group, ▲▲▲ P < 0.001; compared with the model group, *** P<0.001, * P<0.05; compared with the formulation group of patent CN201310597025.X, △ P<0.05, △△ P<0.01, △△△ P<0.001.

[0234] 4.3 Comparison of serum ALT and AST levels in NAFLD rats

[0235] Compared with the blank group, the serum ALT and AST levels of rats were significantly increased (P<0.001); compared with the model group, the serum ALT and AST levels of rats in each treatment group were significantly decreased to varying degrees (P<0.05, P<0.001); compared with the patented preparation group of CN201310597025.X, the serum ALT and AST levels of rats in the high- and low-dose groups of the traditional Chinese medicine composition were significantly decreased to varying degrees (P<0.05, P<0.01, P<0.001).

[0236] Table 3 Comparison of serum ALT and AST levels in NAFLD rats ( ±S)

[0237]

[0238] Note: Compared with the blank group, ▲▲▲ P < 0.001; compared with the model group, *** P<0.001, * P<0.05; compared with the formulation group of patent CN201310597025.X, △ P<0.05, △△ P<0.01, △△△ P<0.001.

[0239] The results are as follows Figure 3 The above, Figure 3 To investigate the effects of ALT and AST levels in the serum of NAFLD rats, such as Figure 3 As shown, the traditional Chinese medicine composition reduced serum ALT and AST levels in NAFLD rats and corrected lipid metabolism disorders. Its effect was significantly superior to patented preparations, unavailable formulas, and alternative preparations.

[0240] The above results show that the traditional Chinese medicine composition disclosed in this invention can effectively reduce intraperitoneal fat accumulation, decrease liver wet weight and liver index in NAFLD model rats, and reduce fat deposition in the liver. It can also significantly improve liver function. [1] The herbal composition reduced serum ALT and AST levels in rats with NAFLD, with a significant dose-related therapeutic effect. It also corrected lipid and glucose metabolism disorders, reducing serum TC, TG, and FBG levels, showing a certain dose-related trend. These results indicate that the herbal composition has a definite therapeutic effect on NAFLD, and its mechanism of action may involve reducing hepatocyte fat deposition, improving liver function, and correcting glucose and lipid metabolism disorders.

[0241] It is related to disorder. Its effect is significantly better than patented formulations, missing formulations, and alternative formulations.

[0242] 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 traditional Chinese medicine composition for treating non-alcoholic fatty liver disease, characterized in that, The raw materials for the medicine are: Turmeric 4-15 parts, vinegar-processed Bupleurum 15-25 parts, Ligusticum chuanxiong 5-15 parts, Astragalus membranaceus 10-20 parts, Salvia miltiorrhiza 5-15 parts, Aucklandia lappa 1-12 parts, Crataegus pinnatifida 4-12 parts, Sophora japonica 3-15 parts, Abrus precatorius 5-15 parts, Alisma plantago-aquatica 5-25 parts.

2. The traditional Chinese medicine composition according to claim 1, characterized in that, The raw materials for the medicine are: Turmeric 9 parts, vinegar-processed Bupleurum 20 parts, Ligusticum chuanxiong 10 parts, Astragalus membranaceus 15 parts, Salvia miltiorrhiza 10 parts, Aucklandia lappa 6 parts, Crataegus pinnatifida 8 parts, Sophora japonica 8 parts, Abrus precatorius 10 parts, Alisma plantago-aquatica 12 parts; or 15 parts of turmeric, 25 parts of vinegar-processed Bupleurum, 15 parts of Ligusticum chuanxiong, 20 parts of Astragalus membranaceus, 15 parts of Salvia miltiorrhiza, 1 part of Aucklandia lappa, 4 parts of hawthorn, 3 parts of Sophora japonica, 15 parts of Abrus precatorius, and 5 parts of Alisma plantago-aquatica. or 4 parts turmeric, 15 parts vinegar-processed Bupleurum, 5 parts Ligusticum chuanxiong, 10 parts Astragalus membranaceus, 5 parts Salvia miltiorrhiza, 12 parts Aucklandia lappa, 12 parts Crataegus pinnatifida, 15 parts Sophora japonica, 5 parts Abrus precatorius, and 15 parts Alisma plantago-aquatica.

3. A method for preparing a traditional Chinese medicine composition for treating non-alcoholic fatty liver disease as described in any one of claims 1 to 2, characterized in that, The process includes the following steps: S1) Astragalus membranaceus and Alisma plantago-aquatica are extracted by water reflux, filtered, and concentrated to obtain a thick extract; the thick extract is precipitated with ethanol, the ethanol is recovered, and the extract is concentrated to obtain a clear extract; the clear extract is freeze-dried to obtain extract A; S2) Ligusticum chuanxiong and Bupleurum chinense were decocted in water to obtain a decoction and a first volatile oil. The decoction was concentrated to obtain a clear extract. The clear extract was dissolved in acid, the pH was adjusted, the temperature was maintained, and the mixture was filtered. After the precipitate was dissolved, the pH was adjusted, ethanol was added to dissolve it, and the mixture was filtered. The filtrate was purified through a first macroporous resin to obtain extract B. S3) Sophora japonica flowers, turmeric and water chestnut extract by steam distillation to obtain the second volatile oil and residue; Hawthorn, salvia miltiorrhiza and the above-mentioned drug residues were extracted by water reflux, concentrated, precipitated with ethanol, and the supernatant was purified by second macroporous resin column to obtain extract C. S4) The first and second volatile oils were dissolved in a solvent and encapsulated with β-cyclodextrin to obtain volatile oil inclusion complexes, which are extracts D; S5) Chicken bone grass was extracted by water flash extraction, followed by extraction with ethanol. The extract was concentrated to obtain a clear extract, which was then purified by column chromatography to obtain extract E. S6) Mix extract A, extract B, extract C, extract D and extract E to obtain the final product.

4. The preparation method according to claim 3, characterized in that, The extraction temperature of S1) is 45~55℃, and the number of extractions is 2~3 times; the material-to-liquid ratio of each extraction is 1:6~10; the extraction time is 5~7h; the relative density of the thick paste at 60℃ is 1.25; the ethanol is 60% ethanol; and the relative density of the clear paste at 60℃ is 1.

18.

5. The preparation method according to claim 3, characterized in that, The material-to-liquid ratio in S2) is 1:(10~12); the number of decoctions is 1~2; the time for each decoction is 1~2 hours; the relative density of the extract at 60℃ is 1.15; the first macroporous resin is AB-8 macroporous resin; the resin purification specifically includes: elution with water, discarding the eluent, and then elution with 40% ethanol, collecting the eluent.

6. The preparation method according to claim 3, characterized in that, The steam distillation extraction time in S3) is 4-6 hours; The extraction temperature is 90~105℃, and the number of extractions is 2~3; the material-to-liquid ratio for each extraction is 1:7~9; the extraction time for each extraction is 1~3 hours; and the ethanol used is 60% ethanol. The second macroporous resin is HPD-722 macroporous resin. The resin purification specifically includes: elution with water at a rate of 8 ml / min, discarding the eluent, then eluting with 5-6 column volumes of 50% ethanol, collecting the eluent, then eluting with 2-3 column volumes of 30% ethanol, collecting the eluent, and combining the eluents.

7. The preparation method according to claim 3, characterized in that, The solvent in S4) is ethanol, and the β-cyclodextrin inclusion complex includes: dissolving the first volatile oil and the second volatile oil in ethanol, adding them dropwise to a β-cyclodextrin aqueous solution, stirring at 40°C for 4-5 hours, refrigerating at 5°C for 20-24 hours, filtering, and vacuum drying the precipitate at 35-40°C for 4-5 hours. In the β-cyclodextrin aqueous solution, the mass-to-volume ratio of β-cyclodextrin to water is 1 g: 5 ml, and the volume-to-mass ratio of volatile oil to β-cyclodextrin is 1 mL: 7 g.

8. The preparation method according to claim 3, characterized in that, The flash extraction time in S5) is 8 minutes, and the voltage is 120V; The ethanol extraction includes: using 70% ethanol, adjusting the pH to 5.0, and letting it stand for 20-24 hours; The column purification was performed using a neutral alumina column with a particle size of 100-200 mesh; elution was performed using 50% ethanol.

9. The use of the traditional Chinese medicine composition for treating non-alcoholic fatty liver disease according to any one of claims 1 to 2 in the preparation of a medicament for treating non-alcoholic fatty liver disease.

10. A drug for treating non-alcoholic fatty liver disease, characterized in that, The traditional Chinese medicine composition for treating non-alcoholic fatty liver disease as described in any one of claims 1 to 2 is included.

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