New application of pharmaceutical composition in treatment of non-viral hepatic fibrosis and liver cirrhosis

Abstract

The invention relates to a new application of a pharmaceutical composition for treating non-viral hepatic fibrosis and cirrhosis, and belongs to the technical field of pharmaceutical compositions. The invention provides application of a pharmaceutical composition in preparation of a medicine for treating non-viral hepatic fibrosis and liver cirrhosis. The pharmaceutical composition comprises salvia miltiorrhiza, bear gall, American ginseng, egg yolk lecithin, radix bupleuri, schisandra chinensis, polygonum cuspidatum, radix isatidis and oldenlandia diffusa. The pharmaceutical composition provided by the invention is formulated according to treatment rules, monarch, minister, assistant and guide are matched to jointly play the effects of promoting blood circulation to remove blood stasis, soothing liver and regulating qi, softening hardness to dissipate stagnation, eliminating fiber and resisting knot and improving the immunity of the organism, and animal experiments and clinical tests prove that the pharmaceutical composition conforms to the traditional theory of traditional Chinese medicine, embodies the uniqueness of the traditional Chinese medicine for treating both symptoms and root causes, and has a wide application prospect. The traditional Chinese medicine composition can effectively relieve the development of non-viral hepatic fibrosis and liver cirrhosis, and has a remarkable curative effect on eliminating hepatic fibrosis and liver cirrhosis.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical compositions, and particularly relates to a new use of a pharmaceutical composition for treating non-viral liver fibrosis and cirrhosis. Background Art

[0002] Liver fibrosis refers to the diffuse excessive deposition and abnormal distribution of extracellular matrix of hepatocytes (such as collagen, glycoprotein, proteoglycan, etc.). This process is a pathological repair response of the liver to chronic injury, leading to extensive necrosis of hepatocytes, nodular regeneration of surviving hepatocytes, connective tissue hyperplasia and formation of fibrotic septa, and ultimately developing into cirrhosis. The causes of liver fibrosis include viral and non-viral factors. Viral factors mainly refer to the continuous replication of hepatitis B or C virus invading hepatocytes, triggering immune responses and damaging hepatocytes. Non-viral factors include alcohol, drugs, autoimmune responses, etc., which cause liver inflammation, and long-term inflammation leads to fibrosis. Therefore, the pathological change process of non-viral liver fibrosis and cirrhosis is relatively more complex.

[0003] Due to the differences in etiology and pathological changes, the treatments for viral liver fibrosis and non-viral liver fibrosis and cirrhosis also vary. Viral liver fibrosis is mainly treated by antiviral therapy to inhibit virus replication and reduce inflammatory responses. However, the causes of non-viral liver fibrosis and cirrhosis are diverse, and non-viral liver fibrosis caused by different etiologies shows differences in the distribution, density, morphology, etc. of fibrous tissues, which increases the difficulty of treatment.

[0004] TCM believes that non-viral liver fibrosis and cirrhosis are tangible evils, which are mainly related to factors such as dysfunction of the liver's drainage function, poor circulation of qi and blood, liver dysfunction, and invasion of external evils. TCM believes that the liver has a drainage function that can regulate qi and promote the circulation of qi and blood. When the liver's drainage function is dysfunctional, it will lead to qi stagnation and poor circulation of qi and blood, which will in turn cause obstruction of the liver meridians, resulting in local qi and blood stasis in the liver and the formation of blood stasis. Blood stasis is one of the important factors in the formation of liver fibrosis and cirrhosis. It will hinder the normal physiological function of the liver, leading to liver cell necrosis and regeneration disorders. The formation of liver fibrosis and cirrhosis is also closely related to the dysfunction of the internal organs. For example, the spleen is responsible for transportation and transformation. When the spleen fails to function properly, it will cause water retention and phlegm turbidity, which will then form damp-heat toxic evil and invade the liver. The kidney is responsible for water metabolism and reproduction. When the kidney function is dysfunctional, it will lead to water metabolism disorders, the formation of water retention, and further increase the burden on the liver. Long-term drinking, overeating of fatty and sweet foods, exposure to toxic substances and other external evil invasions can damage the liver, leading to endogenous dampness, heat and toxicity, which invade the liver. In addition, emotional frustration and excessive fatigue can also lead to liver qi stagnation, which in turn causes liver fibrosis and cirrhosis. Traditional Chinese medicine believes that positive energy is the basis for the human body to resist external evil and maintain normal physiological functions. When the positive energy is deficient, the body's disease resistance decreases and it is vulnerable to external evil invasion. In the formation of liver fibrosis and cirrhosis, positive energy deficiency is also an important factor. Positive energy deficiency can lead to dysfunction of the internal organs and poor circulation of qi and blood.

[0005] The invention patent with the announcement number CN100482252C, "A pharmaceutical composition for treating hepatitis B", discloses a pharmaceutical composition for treating acute and chronic hepatitis B using the active ingredients of salvia miltiorrhiza, knotweed, oldenlandia diffusa, isatis root and bear bile to fight hepatitis B virus, and is aimed at the treatment of viral hepatitis B. However, there is no report on the use of the pharmaceutical composition for the treatment of non-viral liver fibrosis and cirrhosis. Summary of the invention

[0006] The present invention provides a novel use of a pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis.

[0007] The technical solution of the present invention:

[0008] A pharmaceutical composition is used in the preparation of a drug for treating non-viral liver fibrosis and cirrhosis. The pharmaceutical composition comprises the following components in parts by weight: 14-36 parts of salvia miltiorrhiza, 0.6-1.4 parts of bear bile, 10-30 parts of American ginseng, 0.6-1.4 parts of egg yolk lecithin, 6-28 parts of bupleurum, 4-24 parts of schisandra, 2-12 parts of knotweed, 2-12 parts of isatis root and 6-18 parts of oldenlandia diffusa.

[0009] Further, the pharmaceutical composition comprises the following components in parts by weight: 19-29 parts of Salvia miltiorrhiza, 0.8-1.2 parts of bear bile, 15-25 parts of American ginseng, 0.8-1.2 parts of egg yolk lecithin, 11-21 parts of Bupleurum chinense, 9-19 parts of Schisandra chinensis, 6-8 parts of Polygonum cuspidatum, 4-8 parts of Isatis indigotica, and 9-15 parts of Hedyotis diffusa.

[0010] Further, the pharmaceutical composition comprises the following components in parts by weight: 19-28 parts of Salvia miltiorrhiza, 0.8-1.2 parts of bear bile, 17-25 parts of American ginseng, 0.8-1.2 parts of egg yolk lecithin, 11-14 parts of Bupleurum chinense, 10-19 parts of Schisandra chinensis, 6-8 parts of Polygonum cuspidatum, 4-8 parts of Isatis indigotica, and 10-14 parts of Hedyotis diffusa.

[0011] Further, the pharmaceutical composition comprises the following components in parts by weight: 19-27 parts of Salvia miltiorrhiza, 1.0-1.2 parts of bear bile, 15-20 parts of American ginseng, 0.8-1.2 parts of egg yolk lecithin, 11-13 parts of Bupleurum chinense, 11-19 parts of Schisandra chinensis, 6-8 parts of Polygonum cuspidatum, 4-6 parts of Isatis indigotica, and 13-14 parts of Hedyotis diffusa.

[0012] Further, the dosage form of the drug for treating liver fibrosis and cirrhosis is tablet, granule, capsule, dripping pill, pill, sustained-release preparation or freeze-dried powder preparation.

[0013] Further, the preparation method of the pharmaceutical composition comprises the following steps:

[0014] Step 1: Weigh each component in the pharmaceutical composition according to parts by weight;

[0015] Step 2: Extract American ginseng with 65-85% ethanol at 60-80 °C for 3 times, 1-2 h each time. Filter the extract, recover ethanol under reduced pressure to obtain a liquid extract. The obtained liquid extract is loaded onto D101 macroporous resin, eluted with 40-60% ethanol, collect the eluate, recover ethanol under reduced pressure, concentrate the eluate to a relative density of 1.13-1.33, and then freeze-dry at -40 to -60 °C and pulverize to obtain fine powder I;

[0016] Step 3: Extract Salvia miltiorrhiza with 60-80% ethanol by vacuum reflux extraction at 45-65 °C for 3 times, 1-2 h each time. Collect the filtrate, recover ethanol under reduced pressure at 60-70 °C, concentrate the filtrate to a liquid extract, then freeze-dry at -40 to -60 °C and pulverize to obtain fine powder II;

[0017] Step 4: Extract Bupleurum chinense with 70-80% alkaline ethanol by vacuum reflux extraction at 75-80 °C for 3 times, 1-2 h each time. Collect the filtrate, recover ethanol under reduced pressure at 60-70 °C until the weight of the filtrate is equal to the weight of the crude drug of Bupleurum chinense. Refrigerate at 4 °C for 24-48 h, then take the precipitate and freeze-dry at -40 to -60 °C and pulverize to obtain fine powder III;

[0018] Step 5: Remove the pulp from Schisandra chinensis, take the kernels of Schisandra chinensis for conventional ethanol extraction, collect the extract, and recover ethanol under reduced pressure to obtain a concentrated paste; Polygonum cuspidatum, Hedyotis diffusa, and Isatis indigotica are subjected to conventional combined ethanol extraction, the extract is collected and dried under reduced pressure, and then pulverized to obtain fine powder IV;

[0019] Step 6: Mix the fine powder I, fine powder II, fine powder III, fine powder IV, concentrated paste, finely ground bear bile powder, and egg yolk lecithin obtained in Steps 2 to 5 to obtain the said pharmaceutical composition.

[0020] The administration method of the pharmaceutical composition provided by the present invention for treating liver fibrosis and liver cirrhosis is to take it warm water after meals, 3 times a day, 1.2 grams of the drug prepared by the present invention each time, and 3 months is a treatment course.

[0021] Beneficial effects of the present invention:

[0022] Non-viral liver fibrosis and liver cirrhosis are caused by invasion of qi deficiency and heat toxin, which are caused by tangible pathogenic factors. The pharmaceutical composition of the present invention uses Salvia miltiorrhiza and bear bile powder as the monarch drugs, aiming to promote blood circulation to remove blood stasis and dredge collaterals to relieve pain, effectively improve the qi and blood circulation status of the liver, provide recombinant nutrients and oxygen for hepatocytes, and reduce hepatocyte damage caused by ischemia. Using American ginseng, egg yolk lecithin, Bupleurum chinense, Schisandra chinensis, and Polygonum cuspidatum as ministerial drugs, aiming to cure qi deficiency and excess, and internal heat problems. Total ginsenosides of American ginseng can regulate the immune system, achieve the effect of supplementing qi and nourishing yin, while clearing heat pathogens in the body, promoting the generation of body fluids, and strengthening the healthy qi and consolidating the foundation, enhancing the overall function of the body; aiming at the collateral disease characteristics of non-viral liver fibrosis and liver cirrhosis, through the combination of monarch and ministerial drugs in the present invention, using the synergistic effect of tanshinone IIa and total ginsenosides of American ginseng, qi leading blood circulation is beneficial to promoting qi and blood circulation; at the same time, using the synergistic effect of total saponins of Bupleurum chinense and tanshinone IIa, there is also the effect of promoting qi and activating blood circulation. The pharmaceutical composition of the present invention uses Isatis indigotica and Hedyotis diffusa as adjuvant drugs, aiming to soothe the liver and relieve depression, reduce fever and inflammation, improve sleep, improve the damp-heat symptoms of the liver, achieve the effect of clearing heat and promoting bile, and help reduce the inflammatory reaction of the liver.

[0023] The pharmaceutical composition provided by the present invention is formulated around the treatment principle, with the combination of monarch, ministerial, adjuvant, and guiding drugs, jointly exerting the effects of promoting blood circulation to remove blood stasis, soothe the liver and regulate qi, soften hardness and dissipate nodes, eliminate fibrosis and resist nodules, and improve the body's immunity, thereby comprehensively improving the pathological state of non-viral liver fibrosis and liver cirrhosis. Combining animal experiments and clinical trials confirm that the pharmaceutical composition of the present invention not only conforms to the traditional theory of traditional Chinese medicine, reflecting the unique features of traditional Chinese medicine in treating both the symptoms and the root cause, but also conforms to the modern medicine theory, and can effectively relieve the development of non-viral liver fibrosis and liver cirrhosis, and has a significant effect on eliminating liver fibrosis and liver cirrhosis. Description of the Drawings

[0024] Figure 1 It is a comparison chart of the ALT levels in the sera of mice in each group in Example 7;

[0025] Figure 2 Comparison chart of AST levels in the sera of mice in each group in Example 7;

[0026] Figure 3 Photographs of HE staining of liver tissues of mice in each group in Example 7;

[0027] Figure 4 and Figure 5 Report forms of liver FibroScan diagnostic examinations before and after taking medicine for 3 months for Case One;

[0028] Figure 6 and Figure 7 Report forms of liver FibroScan diagnostic examinations before and after taking medicine for 3 months for Case Two;

[0029] Figure 8 and Figure 9 Report forms of liver FibroScan diagnostic examinations before and after taking medicine for 6 months for Case Three. Detailed implementation manners

[0030] The technical solutions of the present invention will be further described below in conjunction with embodiments, but are not limited thereto. Any modifications or equivalent replacements made to the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention shall be covered within the protection scope of the present invention. The process equipment or devices not specifically noted in the following embodiments are all conventional equipment or devices in the art. Unless otherwise specified, the raw materials used in the embodiments of the present invention can be obtained commercially; unless otherwise specified, the technical means used in the embodiments of the present invention are all conventional means well-known to those skilled in the art.

[0031] Example 1

[0032] This example provides a new use of a pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis.

[0033] The pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis in this example contains the following components in parts by weight: 36 parts of Salvia miltiorrhiza, 1.2 parts of bear bile, 12 parts of American ginseng, 1.2 parts of egg yolk lecithin, 28 parts of Bupleurum chinense, 22 parts of Schisandra chinensis, 10 parts of Polygonum cuspidatum, 12 parts of Isatis tinctoria, and 18 parts of Hedyotis diffusa.

[0034] The preparation method steps of the pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis in this example are as follows:

[0035] Step 1: Weigh each drug component in the pharmaceutical composition according to parts by weight;

[0036] Step 2: 12 parts of American ginseng are extracted 3 times with 85% ethanol at 70°C for 1 hour each time. The extraction solution is filtered, and ethanol is recovered under reduced pressure to obtain a liquid extract. The obtained liquid extract is loaded onto D101 macroporous resin, eluted with 60% ethanol, the eluate is collected, ethanol is recovered under reduced pressure, the eluate is concentrated to a relative density of 1.13 - 1.33 and then freeze-dried at -50°C, and pulverized to obtain fine powder I;

[0037] Step 3: 36 parts of Salvia miltiorrhiza are refluxed under reduced pressure 3 times with 70% ethanol at 60°C for 1.5 hours each time. The filtrate is collected and ethanol is recovered under reduced pressure at 70°C. The filtrate is concentrated to a liquid extract and then freeze-dried at -50°C, and pulverized to obtain fine powder II;

[0038] Step 4: 2% NaOH is used to adjust the pH to obtain alkaline ethanol with a pH of 9. 28 parts of Bupleurum chinense are refluxed under reduced pressure 3 times with 70% alkaline ethanol at 80°C for 1 hour each time. The filtrate is collected and ethanol is recovered under reduced pressure at 50°C until the weight of the filtrate is equal to the weight of the crude drug of Bupleurum chinense. After refrigerating at 4°C for 24 hours, the precipitate is taken and freeze-dried at -40°C, and pulverized to obtain fine powder III;

[0039] Step 5: 22 parts of Schisandra chinensis are removed from the pulp, and the kernels of Schisandra chinensis are subjected to conventional ethanol extraction with 70% ethanol at 70°C. The extraction solution is collected, and ethanol is recovered under reduced pressure to obtain a concentrated paste. 10 parts of Polygonum cuspidatum, 18 parts of Hedyotis diffusa, and 12 parts of Isatis tinctoria are subjected to conventional combined extraction with 70% ethanol at 70°C. The extraction solution is collected and dried under reduced pressure, and pulverized to obtain fine powder IV;

[0040] Step 6: The fine powder I, fine powder II, fine powder III, fine powder IV, concentrated paste, 1.4 parts of bear bile powder ground to 150 meshes, 1.2 parts, and 1.2 parts of egg yolk lecithin obtained in Steps 2 to 5 are mixed evenly. An equal amount of melted polyethylene glycol 6000 is added, and after mixing evenly, a dripping pill preparation of 40 mg per pill is prepared with a dripping pill machine.

[0041] Example 2

[0042] This example provides a new use of a pharmaceutical composition for the treatment of non-viral liver fibrosis and liver cirrhosis.

[0043] The pharmaceutical composition for the treatment of non-viral liver fibrosis and liver cirrhosis in this example contains the following components in parts by weight: 16 parts of Salvia miltiorrhiza, 0.8 part of bear bile, 28 parts of American ginseng, 0.9 part of egg yolk lecithin, 8 parts of Bupleurum chinense, 5 parts of Schisandra chinensis, 4 parts of Polygonum cuspidatum, 4 parts of Isatis tinctoria, and 6 parts of Hedyotis diffusa.

[0044] The preparation method steps of the pharmaceutical composition for the treatment of non-viral liver fibrosis and liver cirrhosis in this example are as follows:

[0045] Step 1: Weigh each drug component in the pharmaceutical composition according to the parts by weight;

[0046] Step 2: 28 parts of American ginseng are extracted 3 times with 70% ethanol at 80°C for 2 hours each time. The extraction solution is filtered, and ethanol is recovered under reduced pressure to obtain a fluid extract. The obtained fluid extract is loaded onto D101 macroporous resin, eluted with 60% ethanol, the eluate is collected, ethanol is recovered under reduced pressure, and the eluate is concentrated to a relative density of 1.13 - 1.33 and then freeze-dried at -50°C and pulverized to obtain fine powder I;

[0047] Step 3: 16 parts of Salvia miltiorrhiza are refluxed under reduced pressure 3 times with 70% ethanol at 50°C for 1.5 hours each time. The filtrate is collected and ethanol is recovered under reduced pressure at 70°C. The filtrate is concentrated to a fluid extract and then freeze-dried at -50°C and pulverized to obtain fine powder II;

[0048] Step 4: 2% NaOH is used to adjust the pH to obtain alkaline ethanol with a pH value of 9. 8 parts of Bupleurum chinense are refluxed under reduced pressure 3 times with 70% alkaline ethanol at 80°C for 1.5 hours each time. The filtrate is collected and ethanol is recovered under reduced pressure at 60°C until the weight of the filtrate is equal to the weight of the crude drug of Bupleurum chinense. After refrigerating at 4°C for 24 hours, the precipitate is taken and freeze-dried at -40°C and pulverized to obtain fine powder III;

[0049] Step 5: 5 parts of Schisandra chinensis are defleshed, and the kernels of Schisandra chinensis are subjected to conventional ethanol extraction with 70% ethanol at 70°C. The extraction solution is collected, and ethanol is recovered under reduced pressure to obtain a concentrated paste. 4 parts of Polygonum cuspidatum, 6 parts of Hedyotis diffusa, and 4 parts of Isatis indigotica are subjected to conventional combined extraction with 70% ethanol at 70°C. The extraction solution is collected and dried under reduced pressure and pulverized to obtain fine powder IV;

[0050] Step 6: The fine powder I, fine powder II, fine powder III, fine powder IV, concentrated paste, 0.6 part of bear bile powder ground to 150 meshes, 0.8 part, and 0.9 part of egg yolk lecithin obtained in Step 2 to Step 5 are mixed evenly. An equal amount of melted polyethylene glycol 6000 is added, and after mixing evenly, it is made into a dripping pill preparation of 40 mg per pill with a dripping pill machine.

[0051] Example 3

[0052] This example provides a new use of a pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis.

[0053] The pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis in this example contains the following components in parts by weight: 18 parts of Salvia miltiorrhiza, 1.0 part of bear bile, 12 parts of American ginseng, 1.0 part of egg yolk lecithin, 18 parts of Bupleurum chinense, 14 parts of Schisandra chinensis, 9 parts of Polygonum cuspidatum, 10 parts of Isatis indigotica, and 10 parts of Hedyotis diffusa.

[0054] The preparation method steps of the pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis in this example are as follows:

[0055] Step 1: Weigh each drug component in the pharmaceutical composition according to the parts by weight;

[0056] Step 2: 12 parts of American ginseng are extracted 3 times with 70% ethanol at 70°C for 2 hours each time. The extraction solution is filtered, and ethanol is recovered under reduced pressure to obtain a liquid extract. The obtained liquid extract is loaded onto D101 macroporous resin, eluted with 60% ethanol, the eluate is collected, ethanol is recovered under reduced pressure, the eluate is concentrated to a relative density of 1.13 - 1.33, and then freeze-dried at -50°C and pulverized to obtain fine powder I;

[0057] Step 3: 18 parts of Salvia miltiorrhiza are refluxed under reduced pressure 3 times with 70% ethanol at 50°C for 1.5 hours each time. The filtrate is collected and ethanol is recovered under reduced pressure at 70°C. The filtrate is concentrated to a liquid extract and then freeze-dried at -50°C and pulverized to obtain fine powder II;

[0058] Step 4: 2% NaOH is used to adjust the pH to obtain alkaline ethanol with a pH value of 9. 18 parts of Bupleurum chinense are refluxed under reduced pressure 3 times with 70% alkaline ethanol at 80°C for 1.5 hours each time. The filtrate is collected and ethanol is recovered under reduced pressure at 60°C until the weight of the filtrate is equal to the weight of the crude drug of Bupleurum chinense. After refrigerating at 4°C for 24 hours, the precipitate is taken and freeze-dried at -40°C and pulverized to obtain fine powder III;

[0059] Step 5: The pulp of 14 parts of Schisandra chinensis is removed, and the kernels of Schisandra chinensis are subjected to conventional ethanol extraction with 70% ethanol at 70°C. The extraction solution is collected, and ethanol is recovered under reduced pressure to obtain a concentrated paste. 9 parts of Polygonum cuspidatum, 10 parts of Hedyotis diffusa, and 10 parts of Isatis indigotica are subjected to conventional combined extraction with 70% ethanol at 70°C. The extraction solution is collected and dried under reduced pressure and pulverized to obtain fine powder IV;

[0060] Step 6: The fine powder I, fine powder II, fine powder III, fine powder IV, concentrated paste, 1.0 part of bear bile powder ground to 150 meshes, and 1.0 part of egg yolk lecithin obtained in Steps 2 to 5 are mixed evenly, an equal amount of melted polyethylene glycol 6000 is added, and after mixing evenly, a dripping pill preparation of 40 mg / pill is prepared with a dripping pill machine.

[0061] Example 4

[0062] This example provides a new use of a pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis.

[0063] The pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis in this example contains the following components in parts by weight: 19 parts of Salvia miltiorrhiza, 0.9 part of bear bile, 18 parts of American ginseng, 1.2 parts of egg yolk lecithin, 6 parts of Bupleurum chinense, 18 parts of Schisandra chinensis, 8 parts of Polygonum cuspidatum, 6 parts of Isatis indigotica, and 15 parts of Hedyotis diffusa.

[0064] The preparation method steps of the pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis in this example are as follows:

[0065] Step 1: Weigh each drug component in the pharmaceutical composition according to the parts by weight;

[0066] Step 2: 18 parts of American ginseng are extracted 3 times with 70% ethanol at 70°C for 2 hours each time. The extraction solution is filtered, and ethanol is recovered under reduced pressure to obtain a liquid extract. The obtained liquid extract is loaded onto D101 macroporous resin, eluted with 60% ethanol, the eluate is collected, ethanol is recovered under reduced pressure, the eluate is concentrated to a relative density of 1.13 - 1.33 and then freeze-dried at -50°C, and pulverized to obtain fine powder I;

[0067] Step 3: 19 parts of Salvia miltiorrhiza are subjected to reduced-pressure reflux extraction 3 times with 70% ethanol at 50°C for 1.5 hours each time. The filtrate is collected and ethanol is recovered under reduced pressure at 70°C. The filtrate is concentrated to a liquid extract and then freeze-dried at -50°C, and pulverized to obtain fine powder II;

[0068] Step 4: 2% NaOH is used to adjust the pH to obtain alkaline ethanol with a pH value of 9. 6 parts of Bupleurum chinense are subjected to reduced-pressure reflux extraction 3 times with 70% alkaline ethanol at 80°C for 1.5 hours each time. The filtrate is collected and ethanol is recovered under reduced pressure at 60°C until the weight of the filtrate is equal to the weight of the crude drug of Bupleurum chinense. After refrigerating at 4°C for 24 hours, the precipitate is taken and freeze-dried at -40°C, and pulverized to obtain fine powder III;

[0069] Step 5: The flesh of 18 parts of Schisandra chinensis is removed, and the kernels of Schisandra chinensis are subjected to conventional ethanol extraction with 70% ethanol at 70°C. The extraction solution is collected, and ethanol is recovered under reduced pressure to obtain a concentrated paste. 8 parts of Polygonum cuspidatum, 15 parts of Hedyotis diffusa, and 6 parts of Isatis indigotica are subjected to conventional combined extraction with 70% ethanol at 70°C. The extraction solution is collected and dried under reduced pressure, and pulverized to obtain fine powder IV;

[0070] Step 6: The fine powder I, fine powder II, fine powder III, fine powder IV, concentrated paste, 0.9 part of bear bile powder ground to 150 meshes, 0.9 part, and 1.2 parts of egg yolk lecithin obtained in Steps 2 to 5 are mixed evenly. An equal amount of melted polyethylene glycol 6000 is added, and after mixing evenly, the mixture is made into a dropping pill preparation of 40 mg per pill with a dropping pill machine.

[0071] Example 5

[0072] This example provides a new use of a pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis.

[0073] The pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis in this example contains the following components in parts by weight: 34 parts of Salvia miltiorrhiza, 1.0 part of bear bile, 19 parts of American ginseng, 1.2 parts of egg yolk lecithin, 28 parts of Bupleurum chinense, 20 parts of Schisandra chinensis, 8 parts of Polygonum cuspidatum, 5 parts of Isatis indigotica, and 15 parts of Hedyotis diffusa.

[0074] The preparation method steps of the pharmaceutical composition for treating non-viral liver fibrosis and liver cirrhosis in this example are as follows:

[0075] Step 1: Weigh each drug component in the pharmaceutical composition according to the parts by weight;

[0076] Step 2: 19 parts of American ginseng are extracted with 70% ethanol at 70°C for 3 times, 2 hours each time. The extraction solution is filtered, and ethanol is recovered under reduced pressure to obtain a fluid extract. The obtained fluid extract is loaded onto D101 macroporous resin, eluted with 60% ethanol, the eluate is collected, ethanol is recovered under reduced pressure, the eluate is concentrated to a relative density of 1.13 - 1.33, freeze-dried at -50°C, and pulverized to obtain fine powder I;

[0077] Step 3: 34 parts of Salvia miltiorrhiza are subjected to reduced pressure reflux with 70% ethanol at 50°C for 3 times, 1.5 hours each time. The filtrate is collected, ethanol is recovered under reduced pressure at 70°C, the filtrate is concentrated to a fluid extract, freeze-dried at -50°C, and pulverized to obtain fine powder II;

[0078] Step 4: 2% NaOH is used to adjust the pH to obtain a basic ethanol with a pH value of 9. 28 parts of Bupleurum chinense are subjected to reduced pressure reflux with 70% basic ethanol at 80°C for 3 times, 1.5 hours each time. The filtrate is collected, ethanol is recovered under reduced pressure at 60°C until the weight of the filtrate is equal to the weight of the crude drug of Bupleurum chinense, refrigerated at 4°C for 24 hours, and the precipitate is taken and freeze-dried at -40°C, and pulverized to obtain fine powder III;

[0079] Step 5: Remove the pulp from 20 parts of Schisandra chinensis, take the kernels of Schisandra chinensis and carry out conventional ethanol extraction with 70% ethanol at 70°C, collect the extraction solution, and recover ethanol under reduced pressure to obtain a concentrated paste; 8 parts of Polygonum cuspidatum, 15 parts of Hedyotis diffusa, and 5 parts of Isatis indigotica are subjected to conventional combined extraction with 70% ethanol at 70°C, the extraction solution is collected and dried under reduced pressure, and pulverized to obtain fine powder IV;

[0080] Step 6: Mix the fine powder I, fine powder II, fine powder III, fine powder IV, concentrated paste, 1.4 parts of bear bile powder ground to 150 meshes, 1.0 part, and 1.2 parts of egg yolk lecithin obtained in Step 2 to Step 5, add an equal amount of melted polyethylene glycol 6000, mix well, and use a dropping pill machine to make dropping pills with a dose of 40 mg per pill.

[0081] Example 6

[0082] This example provides a new use of a pharmaceutical composition for the treatment of non-viral liver fibrosis and liver cirrhosis.

[0083] The pharmaceutical composition for the treatment of non-viral liver fibrosis and liver cirrhosis in this example contains the following components in parts by weight: 26 parts of Salvia miltiorrhiza, 1.1 parts of bear bile, 18 parts of American ginseng, 0.9 part of egg yolk lecithin, 18 parts of Bupleurum chinense, 19 parts of Schisandra chinensis, 6 parts of Polygonum cuspidatum, 5 parts of Isatis indigotica, and 12 parts of Hedyotis diffusa.

[0084] The preparation method steps of the pharmaceutical composition for the treatment of non-viral liver fibrosis and liver cirrhosis in this example are as follows:

[0085] Step 1: Weigh each drug component in the pharmaceutical composition according to parts by weight;

[0086] Step 2: 18 parts of American ginseng are extracted 3 times with 70% ethanol at 70°C for 2 hours each time. The extraction solution is filtered, and ethanol is recovered under reduced pressure to obtain a fluid extract. The obtained fluid extract is loaded onto D101 macroporous resin, eluted with 60% ethanol, the eluate is collected and ethanol is recovered under reduced pressure. The eluate is concentrated to a relative density of 1.13 - 1.33 and then freeze-dried at -50°C and pulverized to obtain fine powder I;

[0087] Step 3: 26 parts of Salvia miltiorrhiza are subjected to reduced pressure reflux extraction 3 times with 70% ethanol at 50°C for 1.5 hours each time. The filtrate is collected and ethanol is recovered under reduced pressure at 70°C. The filtrate is concentrated to a fluid extract and then freeze-dried at -50°C and pulverized to obtain fine powder II;

[0088] Step 4: 2% NaOH is used to adjust the pH to obtain a basic ethanol with a pH of 9. 18 parts of Bupleurum chinense are subjected to reduced pressure reflux extraction 3 times with 70% basic ethanol at 80°C for 1.5 hours each time. The filtrate is collected and ethanol is recovered under reduced pressure at 60°C until the weight of the filtrate is equal to the weight of the crude drug of Bupleurum chinense. After refrigerating at 4°C for 24 hours, the precipitate is taken and freeze-dried at -40°C and pulverized to obtain fine powder III;

[0089] Step 5: 19 parts of Schisandra chinensis have their flesh removed, and the kernels of Schisandra chinensis are subjected to conventional ethanol extraction with 70% ethanol at 70°C. The extraction solution is collected, and ethanol is recovered under reduced pressure to obtain a concentrated paste. 6 parts of Polygonum cuspidatum, 12 parts of Hedyotis diffusa, and 5 parts of Isatis indigotica are subjected to conventional combined extraction with 70% ethanol at 70°C. The extraction solution is collected and dried under reduced pressure and pulverized to obtain fine powder IV;

[0090] Step 6: The fine powder I, fine powder II, fine powder III, fine powder IV, concentrated paste, 1.1 parts of bear bile powder ground to 150 meshes, 1.1 parts, and 0.9 parts of egg yolk lecithin obtained in Steps 2 to 5 are mixed evenly, an equal amount of melted polyethylene glycol 6000 is added, and after mixing evenly, a dripping pill preparation of 40 mg per pill is prepared with a dripping pill machine.

[0091] In the pharmaceutical composition provided by the present invention:

[0092] Salvia miltiorrhiza: It is slightly cold in nature and belongs to the heart meridian. It has the effect of clearing the heart and relieving restlessness, and can improve the symptoms of restlessness and insomnia. Salvia miltiorrhiza can also play a role in cooling blood and dissipating carbuncles. The active ingredients in Salvia miltiorrhiza have anti-inflammatory effects and can reduce the inflammatory response of the liver. During the process of non-viral liver fibrosis and cirrhosis, the inflammatory response is an important promoting factor. Components such as polyphenolic compounds in Salvia miltiorrhiza can inhibit the release of inflammatory mediators and reduce the inflammatory response of liver tissue, thus helping to slow down the process of liver fibrosis. In addition, Salvia miltiorrhiza has the effects of promoting blood circulation to remove blood stasis, dredging meridians and relieving pain. Salvia miltiorrhiza is rich in various antioxidant substances, such as tanshinone and salvianolic acid, which can scavenge free radicals in the body, prevent cell aging, and delay cell senescence. During the process of non-viral liver fibrosis and cirrhosis, oxidative stress reactions can lead to hepatocyte damage and aggravation of fibrosis. The antioxidant effect of Salvia miltiorrhiza can protect hepatocytes from oxidative stress damage, thus helping to protect liver function and delay the progression of cirrhosis. Certain components in Salvia miltiorrhiza can stimulate the proliferation and regeneration of hepatocytes, helping to repair damaged liver tissue. During the process of non-viral liver fibrosis and cirrhosis, the regenerative ability of hepatocytes is severely damaged. By promoting the regeneration of hepatocytes, Salvia miltiorrhiza helps to restore the normal physiological function of the liver and slow down the progression of cirrhosis. Salvia miltiorrhiza can regulate liver metabolic pathways and improve liver function. For example, Salvia miltiorrhiza can promote bile secretion and bilirubin metabolism, etc., thus helping to reduce the burden on the liver and improve the detoxification and excretion functions of the liver. The compounds in Salvia miltiorrhiza can inhibit the activation of hepatic stellate cells and collagen synthesis, thereby reducing the progression of liver fibrosis. The activation of hepatic stellate cells is a key link in the process of liver fibrosis. By inhibiting the activation of hepatic stellate cells, Salvia miltiorrhiza can reduce the synthesis and deposition of collagen, thus helping to slow down the process of liver fibrosis. These effects are helpful for patients with non-viral liver fibrosis and cirrhosis to relieve the condition and improve the quality of life. The mechanism of action of Salvia miltiorrhiza in the treatment of non-viral liver fibrosis and cirrhosis is multi-faceted, including anti-inflammatory, antioxidant, promoting hepatocyte regeneration, improving liver function and anti-fibrosis effects. These effects work together to help slow down the process of liver fibrosis, protect liver function, and improve the quality of life of patients.

[0093] Bear bile: It has the functions of clearing heat and detoxifying, calming endogenous wind and stopping convulsions, and can be used to treat sores and boils caused by heat toxins, coma and convulsions caused by high fever of swelling toxins, and epilepsy convulsions. Bear bile has the function of clearing the liver and improving eyesight, and can be used for red and inflamed eyes caused by liver heat. Bear bile powder has the function of protecting the liver and promoting bile secretion, and can promote the secretion and excretion of bile. Bile is crucial for the normal function of the liver. It helps with the digestion and absorption of fats, reducing the burden on the liver during the digestion process. At the same time, the excretion of bile also helps the liver excrete toxins and waste from the body, contributing to the maintenance of liver health. During the process of non-viral liver fibrosis and cirrhosis, liver function is damaged, and the functions of bile secretion and excretion are weakened. Bear bile powder can create favorable conditions for the recovery of liver function by promoting bile secretion. Bear bile can also be used to treat jaundice caused by damp-heat in the liver meridian. The active ingredient deoxycholic acid in bear bile powder can reduce the inflammatory response of the liver and lower the mortality rate of liver cells. During the process of non-viral liver fibrosis and cirrhosis, continuous inflammatory response is one of the important factors leading to liver cell damage and fibrosis. Through its anti-inflammatory effect, bear bile powder can protect liver cells from inflammatory damage and maintain the normal structure and function of the liver. Bear bile powder has an anti-fibrotic effect and can inhibit the activation of hepatic stellate cells and reduce the deposition of collagen. The activation of hepatic stellate cells is a key link in the process of liver fibrosis. They secrete a large amount of collagen, leading to the proliferation of liver fibrous tissue. By inhibiting the activation of hepatic stellate cells, bear bile powder can delay the process of liver fibrosis, thereby reducing the severity of cirrhosis. Bear bile powder can regulate the immune function of the body and enhance the body's self-protection ability for the liver. During the process of liver fibrosis and cirrhosis, immune dysfunction is also one of the important factors promoting the progression of the disease. By regulating the immune function, bear bile powder helps to restore the immune balance of the body, reduce the immune damage to the liver, and thus protect liver cells. The active ingredients in bear bile powder can promote the microcirculation of the liver, increase hepatic blood flow, and improve the blood supply situation of the liver. Good liver microcirculation is crucial for the transportation of nutrients and the excretion of metabolites, and is essential for maintaining the normal physiological function of the liver. During the process of non-viral liver fibrosis and cirrhosis, liver microcirculation is damaged. Bear bile powder can create favorable conditions for the repair and regeneration of liver cells by improving liver microcirculation. During the treatment of non-viral liver fibrosis and cirrhosis, bear bile powder exerts its effects through multiple mechanisms such as protecting the liver and promoting bile secretion, reducing liver inflammation, anti-fibrosis, regulating immune function, and improving liver microcirculation. These mechanisms work together synergistically to reduce liver damage and fibrosis, promote the repair and regeneration of liver cells, thereby improving the functional state of the liver and delaying the progression of cirrhosis.

[0094] American ginseng: Also known as Panax quinquefolius, it uses the total saponins of American ginseng. It is cold in nature, slightly bitter and sweet in taste, and often has the effects of supplementing qi and nourishing yin, clearing away heat and promoting fluid production, and strengthening healthy qi. Experiments have shown that ginsenoside Rb1 can enhance the body's immunity and protect infected cells. Ginsenoside Rb1 has a significant inhibitory effect on both acute and chronic inflammation. The saponin components in American ginseng can stimulate the proliferation of lymphocytes and improve the body's disease resistance. For patients with non-viral liver fibrosis and cirrhosis, the improvement of immunity helps to reduce the inflammatory reaction of the liver and promote the repair of liver cells.

[0095] Some components in American ginseng have the function of scavenging free radicals, which helps to reduce the oxidative stress response of the liver. Oxidative stress is one of the important mechanisms in the occurrence and development of non-viral liver fibrosis and cirrhosis. The antioxidant effect of American ginseng can protect liver cells from oxidative damage, thus delaying the process of liver fibrosis and cirrhosis. At the same time, immune regulation can also enhance the body's resistance to pathogens and prevent other infections.

[0096] American ginseng saponin Rb1 has the strongest effect in promoting serum albumin synthesis and can enhance the body's immunity. Blood deficiency can cause internal heat. American ginseng is cold in nature and has the effect of nourishing yin and purging fire. It can improve symptoms such as shortness of breath, spontaneous sweating, and weak voice caused by qi deficiency and yin deficiency, and has the effect of tonifying qi. American ginseng can promote the liver to synthesize detoxifying enzymes such as glutathione peroxidase, improving the liver's detoxification function. American ginseng can be used as an appetite enhancer, and its active ingredients can stimulate gastric juice secretion and increase appetite. Patients with non-viral liver fibrosis and cirrhosis often have symptoms of loss of appetite. This effect of American ginseng helps to improve the patient's nutritional status and quality of life. For patients with non-viral liver fibrosis and cirrhosis, the liver's detoxification function is often impaired. This effect of American ginseng helps to remove harmful substances in the body and reduce the burden on the liver. American ginseng can also improve symptoms such as insufficient body fluid, sore throat, and restlessness caused by deficiency heat and restlessness. American ginseng has an inhibitory effect on the central nervous system and can relieve the patient's anxiety and insomnia symptoms. Due to the impact of the disease, patients with non-viral liver fibrosis and cirrhosis often have varying degrees of anxiety and insomnia. The sedative effect of American ginseng helps to improve the patient's mental state and quality of life. Egg yolk lecithin: Known as the third nutrient alongside protein and vitamins, lecithin is the raw material for lipoprotein synthesis, and lipoprotein is the way fat is transported in the body. During the process of non-viral liver fibrosis and cirrhosis, the liver's fat metabolism function is impaired, easily leading to the accumulation of fat in the liver and further increasing the burden on the liver. Egg yolk lecithin can promote the transport of fat in the liver, transfer fat from the liver to outside the liver, reduce the infiltration of fat into liver cells, and thus help improve the liver's fat metabolism status and reduce the burden on the liver. It can enhance immunity and reduce brain atrophy. It is an essential substance for human nutrition. 90% of the exogenous choline required by the human body is provided by lecithin. It can regulate blood lipids, lower cholesterol, protect the liver, enhance immunity, and fight fatty liver. Lecithin has the function of emulsifying and decomposing fats, can promote blood circulation, improve blood lipids and remove peroxides, lower cholesterol and neutral fat in the blood, reduce the retention time of fat on the inner wall of blood vessels, and prevent atherosclerotic changes. It also has the effect of softening the skin and delaying aging. Lecithin is an important component of cell membranes and can maintain the integrity and stability of cell membranes. During the process of non-viral liver fibrosis and cirrhosis, the liver cell membrane is damaged, resulting in a decline in liver cell function. Egg yolk lecithin can replace the damaged phospholipids on the cell membrane in the form of complete molecules, restore the membrane structure, and thus restore the barrier function, detoxification function, and metabolic function of liver cells, etc., promoting liver cell regeneration. Egg yolk lecithin can be converted into phosphatidic acid in the body, and phosphatidic acid can promote the metabolic function of the liver and improve the liver's detoxification ability. During the process of non-viral liver fibrosis and cirrhosis, the liver's detoxification function is damaged and cannot effectively remove harmful substances in the body. Egg yolk lecithin helps to remove toxins and harmful substances in the body and protect liver cells from further damage by promoting the liver's metabolism and detoxification functions.During the process of non-viral liver fibrosis and cirrhosis, the liver undergoes continuous inflammatory reactions. Egg yolk lecithin has an anti-inflammatory effect, which can inhibit the production of inflammatory factors, reduce the inflammatory reactions in the liver, and thus protect hepatocytes from inflammatory damage. Egg yolk lecithin is rich in antioxidants, which can reduce the damage of free radicals to hepatocytes and protect hepatocytes from oxidative stress. In addition, egg yolk lecithin can also enhance the antioxidant capacity of hepatocytes and improve the resistance of hepatocytes, thereby contributing to maintaining the normal physiological functions of the liver. During the treatment of non-viral liver fibrosis and cirrhosis, egg yolk lecithin plays a comprehensive role through multiple mechanisms, such as participating in fat metabolism, repairing cell membranes, promoting liver detoxification function, reducing inflammatory reactions, and protecting hepatocytes.

[0097] Bupleurum: It has the effects of inducing sweating to reduce fever, soothing the liver and relieving depression, regulating qi movement. Traditional Chinese medicine believes that the occurrence of non-viral liver fibrosis and cirrhosis is closely related to stagnation of liver qi and emotional discomfort. As a commonly used Chinese medicinal material, Bupleurum has the effects of soothing the liver and relieving depression, and regulating qi movement. It can relieve the liver function disorder caused by emotional discomfort and stagnation of liver qi by regulating the qi movement of the liver, thus helping to improve the condition of non-viral liver fibrosis and cirrhosis, and lifting yang qi. Modern pharmacological research has confirmed that the active ingredients in Bupleurum can inhibit the overexpression of liver fibrosis-related factors. These factors play a key role in the occurrence and development of non-viral liver fibrosis and cirrhosis. By inhibiting the expression of these factors, Bupleurum can reduce the production and deposition of collagen fibers in the liver, thus slowing down or preventing the process of liver fibrosis. Bupleurum is slightly cold in nature and bitter in taste. It is good at inducing sweating to reduce fever and dispersing Shaoyang pathogens, and can dispel pathogens in the half-exterior and half-interior. It can be used for the fever symptoms of patients with exterior heat sensation. Bupleurum enters the liver meridian and has the effect of soothing the liver and relieving depression. Bupleurum contains saikosaponins, which can reduce plasma cholesterol, alleviate liver damage, and promote bile secretion. Bupleurum also has the effects of protecting liver cells and reducing inflammatory reactions. It can reduce the damage of liver cells by inhibiting the inflammatory reactions in the liver, and promote the repair and regeneration of liver cells. At the same time, Bupleurum can also enhance the antioxidant capacity of liver cells and improve the resistance of liver cells, thus helping to delay the progression of cirrhosis. Bupleurum also has the effect of regulating immune function. It can reduce the damage of the immune system to the liver by regulating the function of the immune system, and promote the repair and regeneration of the liver. At the same time, Bupleurum can also enhance the immune function of the body and improve the resistance of the body to pathogens, thus helping to prevent and treat the complications of non-viral liver fibrosis and cirrhosis. In the process of treating non-viral liver fibrosis and cirrhosis, the pharmacological effects of Bupleurum are not a single pathway, but play a role through multiple mechanisms. These mechanisms cooperate with each other and act on the liver together, helping to improve the functional state of the liver, alleviate the condition of non-viral liver fibrosis and cirrhosis, and thus delay the progression of the disease. The mechanism of action of Bupleurum in the treatment of non-viral liver fibrosis and cirrhosis is multi-faceted, including soothing the liver and relieving depression, regulating qi movement, inhibiting the overexpression of liver fibrosis-related factors, protecting liver cells, reducing inflammatory reactions, and regulating immune function, etc. These mechanisms of action work together to help improve the functional state of the liver, alleviate the condition of non-viral liver fibrosis and cirrhosis, and thus delay the progression of the disease.

[0098] Schisandra chinensis: It has the effects of astringing and fixing colors, replenishing qi and promoting the production of body fluid, and tonifying the kidney and tranquilizing the mind. Schisandra chinensis is the mature fruit of Schisandra sphenanthera. It has an aroma, tastes sour and sweet, is warm in nature, and belongs to the lung, heart, and kidney meridians, with the effects of astringing and arresting sweating, replenishing qi and promoting the production of body fluid, tonifying the kidney and tranquilizing the mind, etc. The active ingredients in Schisandra chinensis, such as schisandrin B, can reduce the damage of hepatocytes and maintain the normal structure and function of hepatocytes. These ingredients can inhibit the lipid peroxidation reaction in hepatocytes, reduce the damage of free radicals to hepatocytes, and thus play a role in protecting hepatocytes. Schisandra chinensis tastes sour and sweet, is warm in nature, enters the lung meridian, and has the effect of astringing and arresting sweating. Schisandra chinensis has the effect of inhibiting the activation of hepatic stellate cells and collagen synthesis. The activation of hepatic stellate cells is a key link in the process of liver fibrosis. They secrete a large amount of collagen, leading to the proliferation of liver fibrous tissue. By inhibiting the activation of hepatic stellate cells and collagen synthesis, Schisandra chinensis can slow down the process of liver fibrosis and has a certain significance for preventing the occurrence of liver cirrhosis. The liver is an important detoxifying organ of the human body. Schisandra chinensis can improve the detoxifying ability of the liver, promote the metabolism and excretion of harmful substances, and reduce the burden on the liver. In the process of non-viral liver fibrosis and liver cirrhosis, the detoxifying function of the liver is often damaged. This effect of Schisandra chinensis helps to restore the normal physiological function of the liver. Schisandra chinensis can stimulate the proliferation and differentiation of hepatocytes and promote the regeneration of hepatocytes. In the process of non-viral liver fibrosis and liver cirrhosis, the regenerative ability of hepatocytes is severely damaged. By promoting the regeneration of hepatocytes, Schisandra chinensis helps to restore the normal structure and function of the liver. In the process of treating non-viral liver fibrosis and liver cirrhosis, the pharmacological effects of Schisandra chinensis are not a single pathway, but play a role through multiple mechanisms. For example, while protecting hepatocytes, Schisandra chinensis can also reduce the level of transaminases and improve liver function; while anti-liver fibrosis, it can also enhance the detoxifying function of the liver and promote the regeneration of hepatocytes. These comprehensive action mechanisms make Schisandra chinensis have unique advantages in the treatment of non-viral liver fibrosis and liver cirrhosis. The mechanism of action of Schisandra chinensis in the treatment of non-viral liver fibrosis and liver cirrhosis is multi-faceted, including protecting hepatocytes, reducing transaminases, anti-liver fibrosis, enhancing the detoxifying function of the liver, and promoting the regeneration of hepatocytes, etc. These action mechanisms work together to help slow down the process of liver fibrosis, protect liver function, and improve the quality of life of patients.

[0099] Polygonum cuspidatum: A plant of the Polygonaceae family, the dried rhizome and roots of Polygonum cuspidatum, slightly bitter in taste and slightly cold in nature, belonging to the liver, gallbladder, and lung meridians. Polygonum cuspidatum has the effect of promoting blood circulation to remove blood stasis. Active ingredients in Polygonum cuspidatum, such as resveratrol, have significant anti-inflammatory effects. They can inhibit the production of inflammatory factors, reduce the inflammatory response of the liver, and thus protect hepatocytes from inflammatory damage. During the process of non-viral liver fibrosis and cirrhosis, continuous inflammatory response is one of the important factors driving the progression of the disease. The anti-inflammatory effect of Polygonum cuspidatum helps to slow down this process and can be used to treat amenorrhea, scalds and burns caused by fire and water, falls and injuries, etc., for the syndrome of stasis obstruction of menstruation. Polygonum cuspidatum can clear heat and promote diuresis, and is commonly used in the treatment of arthralgia and damp-heat jaundice. Polygonum cuspidatum can clear heat and detoxify. Certain components in Polygonum cuspidatum, such as isoorientin, have antioxidant activity and can counteract the damage of free radicals. Free radicals are one of the important inducing factors of liver damage and fibrosis. The antioxidant effect of Polygonum cuspidatum can reduce the generation of free radicals, protect hepatocytes from oxidative stress damage, and thus delay the process of non-viral liver fibrosis and cirrhosis. The extract of Polygonum cuspidatum contains various alkaloid compounds, such as berberrubine, etc. These substances have the effect of directly dissolving fibrinogen and can promote the degradation of liver fibrosis. Liver fibrosis is an inevitable stage of cirrhosis. By promoting the degradation of liver fibrosis, Polygonum cuspidatum helps to improve the texture and function of the liver and slow down the progression of cirrhosis. The active ingredients in Polygonum cuspidatum can regulate the immune function of the body and improve the disease resistance of the body. During the process of non-viral liver fibrosis and cirrhosis, immune dysfunction is also one of the important factors driving the progression of the disease. By regulating the immune function, Polygonum cuspidatum helps to restore the immune balance of the body, reduce the immune damage of the liver, and thus protect hepatocytes. Components such as flavonoid compounds in Polygonum cuspidatum can protect hepatocytes from damage by various harmful factors, such as drugs, alcohol, etc. These components can enhance the antioxidant ability of hepatocytes and improve the resistance of hepatocytes, thus helping to maintain the normal physiological function of the liver. In the process of treating non-viral liver fibrosis and cirrhosis, Polygonum cuspidatum exerts its effects through multiple mechanisms such as anti-inflammatory, antioxidant, promoting the degradation of liver fibrosis, regulating immune function, and protecting hepatocytes. These mechanisms cooperate with each other to jointly reduce the inflammatory response of the liver, protect hepatocytes, promote the degradation of liver fibrosis, thus delaying the progression of cirrhosis and improving the function of the liver.

[0100] Oldenlandia diffusa: Slightly cold in nature, bitter and sweet in taste, with the efficacy of clearing heat and detoxifying. In traditional Chinese medicine theory, liver fibrosis and cirrhosis are often related to the internal accumulation of damp-heat toxin. Oldenlandia diffusa can clear the heat toxin in the body, reduce the inflammatory reaction of the liver, and thus help relieve the condition of liver fibrosis and cirrhosis. Oldenlandia diffusa has the effect of promoting diuresis and reducing swelling, which can promote the excretion of urine and relieve the symptoms of edema in the body. In patients with non-viral liver fibrosis and cirrhosis, due to impaired liver function, it may lead to disorders of water metabolism and symptoms such as ascites. The effect of promoting diuresis and reducing swelling of Oldenlandia diffusa helps to improve these symptoms and relieve the pain of patients. Oldenlandia diffusa also has the efficacy of promoting blood circulation and removing blood stasis, which can improve the blood circulation of the liver and promote the dissipation of blood stasis. During the process of liver fibrosis and cirrhosis, the blood circulation in the liver may be blocked, leading to the formation of blood stasis. The effect of promoting blood circulation and removing blood stasis of Oldenlandia diffusa helps to improve the microcirculation of the liver and reduce liver fibrosis and nodule formation. A variety of chemical components in Oldenlandia diffusa have anti-inflammatory and anti-fibrotic effects. These components can inhibit the inflammatory reaction in the liver, reduce the infiltration of inflammatory cells and the release of inflammatory factors, and thus reduce liver damage. At the same time, they can also inhibit the proliferation of fibrous tissue in the liver and slow down the process of liver fibrosis. Based on the research findings of network pharmacology, the active ingredients of Oldenlandia diffusa in the treatment of non-viral liver fibrosis include stigmasterol, β-sitosterol, quercetin, etc. These components can act on targets such as VEGF, EGFR, HIF-1α, IL-6, etc., and regulate signal pathways such as PI3K / Akt, HIF-1, etc., so as to play an anti-liver fibrosis role. In addition, Oldenlandia diffusa also has multiple effects such as anti-tumor and antioxidant{1}, which also help to improve the functional state of the liver. Isatis root: It has the effects of clearing heat and detoxifying, cooling blood, and relieving sore throat. Isatis root is bitter and cold. Isatis root is rich in a variety of active ingredients, among which isatis root polysaccharide has significant antiviral ability. For liver fibrosis and cirrhosis caused by viral hepatitis, Isatis root can slow down the process of liver fibrosis by inhibiting the replication and transmission of the virus and reducing the damage of the virus to the liver. Isatis root enters the heart and stomach meridians, is good at clearing and resolving excessive heat-toxin, has the same effect of clearing heat and detoxifying as Folium Isatidis, and is more prominent in detoxifying, relieving sore throat, and dissipating nodules. It has the effects of clearing heat and detoxifying. Oxidative stress is one of the important pathogenesis of non-viral liver fibrosis and cirrhosis. The active ingredients in Isatis root have antioxidant effects, which can scavenge free radicals in the body, reduce the damage of oxidative stress to the liver, and protect the structure and function of hepatocytes. Isatis root has the effect of cooling blood and reducing swelling. During the process of non-viral liver fibrosis and cirrhosis, the liver will have a continuous inflammatory reaction. The chemical components in Isatis root have anti-inflammatory effects, which can inhibit the release of inflammatory mediators, reduce the inflammatory reaction of the liver, and protect hepatocytes from further damage. Isatis root is mainly used to treat various syndromes of pestilence and heat-toxin. The antiviral glycoprotein contained in Isatis root can effectively inhibit bacteria and has antiviral effects. Isatis root can promote the regeneration and repair of hepatocytes, increase the protein synthesis ability, and thus improve the function of the liver.In addition, Isatis indigotica Fort. can also reduce fat deposition in the liver, promote bile secretion, and help maintain the normal metabolic function of the liver. Isatis indigotica Fort. can enhance the immune function of the body, improve the phagocytic ability of macrophages, and promote the activation of immune cells, thereby enhancing the body's resistance to pathogens, reducing the chance of infection, and helping to protect the liver from further damage. The active ingredients in Isatis indigotica Fort. can inhibit the activation of hepatic stellate cells and the synthesis of collagen, thereby slowing down the process of liver fibrosis. The activation of hepatic stellate cells is a key link in the process of liver fibrosis. By inhibiting its activation, Isatis indigotica Fort. can reduce the deposition of collagen and help improve the degree of liver fibrosis. In the treatment of non-viral liver fibrosis and cirrhosis, Isatis indigotica Fort. exerts its effects through multiple mechanisms such as antiviral, anti-inflammatory, antioxidant, liver protection, immune regulation, and anti-fibrosis. These mechanisms cooperate with each other to jointly reduce the inflammatory response of the liver, protect hepatocytes, promote the regeneration and repair of hepatocytes, thereby slowing down the process of liver fibrosis and improving the function of the liver.

[0101] Example 7

[0102] Evaluation and research on the effectiveness of the pharmaceutical composition of the present invention on a mouse liver fibrosis model.

[0103] (1) Grouping of experimental animals and administration method

[0104] C57BL / 6 male mice at 8 weeks of age, weighing 20±2 g, of SPF grade (purchased from Beijing Vital River Laboratory Animal Technology Co., Ltd.) were selected and randomly divided into 6 groups, namely blank control group, model group, silybin group (positive control group), low-dose group of pharmaceutical composition, medium-dose group of pharmaceutical composition, and high-dose group of pharmaceutical composition, with 8 mice in each group. Among them, the positive control group was administered silybin at 150 mg / kg body weight / day, and the low-dose group of pharmaceutical composition (6 g / kg of crude drug), medium-dose group of pharmaceutical composition (9 g / kg of crude drug), and high-dose group of pharmaceutical composition (12 g / kg of crude drug) were given intragastric administration once a day for a total of 6 weeks. For every 10 g of weight, 100 μl was administered by gavage, and the control group and the model group were given an equal volume of normal saline by gavage.

[0105] The pharmaceutical composition used in this example is the crude drug prepared according to the component ratio of the pharmaceutical composition provided in Example 1.

[0106] (2) Establishment of CCl4-induced liver fibrosis model

[0107] Blank control group: The mice were only treated with corn oil;

[0108] Model group: The mice were intraperitoneally injected with CCl4 (0.5 ml / kg of 25% CCl4 v / v corn oil solution) every three days for 6 weeks;

[0109] Positive control group: On the basis of the model group, from the 4th week to the 6th week, mice were intragastrically administered with 150 mg / kg of silybin every day;

[0110] Low-dose group of the drug composition: On the basis of the model group, from the 4th week to the 6th week, mice were intragastrically administered with the drug composition at a crude drug concentration of 6 g / kg body weight every day;

[0111] Medium-dose group of the drug composition: On the basis of the model group, from the 4th week to the 6th week, mice were intragastrically administered with the drug composition at a crude drug concentration of 9 g / kg body weight every day;

[0112] High-dose group of the drug composition: On the basis of the model group, from the 4th week to the 6th week, mice were intragastrically administered with the drug composition at a crude drug concentration of 12 g / kg body weight every day;

[0113] 2 hours after the last administration, except for the blank group, each group was intraperitoneally injected with 10% (v:v) concentration of CCl4 dissolved in olive oil (1 ml / kg) once to induce an acute liver injury model; the blank group was intraperitoneally injected with an equal volume of olive oil.

[0114] (3) Sample collection and processing

[0115] 3 hours after the last administration, mice were anesthetized with sodium pentobarbital, sacrificed by orbital blood collection, and the liver was separated for subsequent detection. After the whole blood of the mice was allowed to stand at room temperature for 30 minutes, it was centrifuged at 4°C and 3000 rpm for 15 minutes, and the supernatant was taken to measure liver function indexes (ALT, AST). The same part of the liver of the mice was taken for histopathological examination.

[0116] Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) were detected by using a kit method, which was purchased from Nanjing Jiancheng Bioengineering Research Institute Co., Ltd.

[0117] (4) Detection of serum ALT and AST levels

[0118] In the mouse liver fibrosis model, the changes in the levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in the serum were detected. ALT mainly exists in the cytoplasm of hepatocytes. When the hepatocytes are just damaged, they will swell, and the permeability of the cell membrane will increase accordingly. Then ALT will escape from the hepatocytes and enter the serum. While AST mainly exists in the mitochondria of hepatocytes. Once the hepatocytes are severely damaged and the mitochondrial structure is destroyed, AST will be released into the serum. Therefore, when the liver is damaged, the levels of ALT and AST in the serum will show an upward trend.

[0119] Figure 1 and Figure 2 are respectively the comparison charts of the ALT levels and AST levels of the sera of the mice in each group in Example 7; as Figure 1 andFigure 2 As shown, in the mouse liver fibrosis model, the levels of serum ALT and AST were both significantly increased. However, in the drug composition group and the high-dose group of the model, it could be seen that the levels of serum ALT and AST were both significantly inhibited, and there was a certain concentration-dependence. This indicates that the drug composition has the effect of inhibiting liver injury.

[0120] (5) Observation of pathological changes in liver tissue by HE staining

[0121] To evaluate the pathological changes of liver tissue, the section changes of liver tissue in each group of the mouse liver fibrosis model were further observed by hematoxylin-eosin staining (HE staining). In HE staining, hematoxylin is a basic dye, and the cell nucleus is stained blue because of the acidic DNA present in it; eosin is an acidic dye, which combines with the cation of the amino positive charge of the protein to stain the cytoplasm red.

[0122] Figure 3 It is the HE staining photo of the liver tissue of each group of mice in Example 7; as Figure 3 shown, in the model group, the cell nuclei of some cells were significantly enlarged, and there were many aggregated small blue dot-like cells. The stained small blue dot-like cells are giant cells, which indicates that there are inflammatory or necrotic inflammatory foci in the CCl4 model group. In contrast, in the medium- and high-dose groups of the drug composition, the aggregation of giant cells was significantly reduced, and the size of the cell nuclei was mostly normal, which indicates that the drug composition inhibits the inflammatory infiltration in liver injury.

[0123] Example 8

[0124] This example is an application example of a non-viral liver fibrosis and cirrhosis clinical case. The traditional Chinese medicine composition used is the drop pill preparation prepared according to the component ratio and preparation method of the drug composition provided in Example 1.

[0125] I. Case selection of patients taking this drug composition

[0126] 1. Diagnostic criteria for patients taking this drug composition

[0127] 1.1 Applying traditional Chinese medicine theory, according to the formation mechanism of non-viral liver fibrosis and cirrhosis in traditional Chinese medicine theory, non-viral liver fibrosis and cirrhosis belong to pathogenic factors with form, belonging to qi deficiency and heat toxin invading internally, qi stagnation and blood stasis, qi deficiency, etc. The main clinical manifestations of patients are: loss of appetite, pale tongue with white and slippery coating, deep and thready pulse. According to these traditional Chinese medicine symptoms and the measured value of the transient elastography of the liver in Western medicine, cases that meet the treatment indications of this drug composition are selected as the main patients for the evaluation of the curative effect after taking the medicine.

[0128] 1.2 According to the "Classification, Diagnosis and Treatment Guidelines for Liver Fibrosis and Cirrhosis in China (2020 Edition)", referring to the "Guiding Principles for Clinical Research of New Chinese Medicines (2002 Edition)", based on the elastance modulus scan reports of patients in Class III Grade A hospitals, determine the regular shape of liver fibrosis and cirrhosis. According to the imaging display of the elastance modulus of the patient's liver, determine whether the liver is fibrotic, cirrhotic, or a mixed state. Select patients who meet the criteria for taking this pharmaceutical composition as the main cases and conduct an evaluation of the therapeutic effect after medication.

[0129] 2. Select the main patient population according to the above criteria

[0130] 2.1 Non-viral liver fibrosis and cirrhosis patients who meet the Chinese and Western medicine diagnostic criteria

[0131] 2.2 Aged 20 - 70 years old, both genders are included

[0132] 2.3 Classification index range of non-viral liver fibrosis and cirrhosis patients diagnosed by liver elastance modulus imaging

[0133] 2.3.1 Normal range:

[0134] Elastance modulus value of the liver: 2.4 to 7.0 kPa (or 2.8 to 7.4 kPa).

[0135] 2.3.2 Mild fibrosis: Elastance modulus value of the liver: 7.0 to 9.5 kPa.

[0136] Moderate fibrosis: Elastance modulus value of the liver: 9.5 to 12.5 kPa.

[0137] 2.3.3 Severe fibrosis: Elastance modulus value of the liver 12.5 to 17.5 kPa.

[0138] Cirrhosis: Elastance modulus value of the liver exceeds 17.5 kPa.

[0139] II. Exclusion criteria for inapplicable clinical administration of this pharmaceutical composition

[0140] 1. Patients who do not meet the traditional Chinese medicine syndrome differentiation and diagnostic criteria of this pharmaceutical composition;

[0141] 2. Patients with obvious cardiovascular, liver, kidney and some serious primary diseases of the system;

[0142] 3. Psychiatric patients;

[0143] 4. Patients with allergic constitution or allergic to multiple drugs;

[0144] 5. Patients in critical condition for whom it is impossible to make an accurate evaluation of the effectiveness and safety of this pharmaceutical composition;

[0145] 6. Lactating and pregnant women.

[0146] 3. Safety Assessment

[0147] The patient was examined before and after taking the drug composition:

[0148] 1. General physical examination items;

[0149] 2. Routine blood, urine and stool tests;

[0150] 3. Heart, liver and kidney function tests;

[0151] 4. Changes in the patient’s TCM symptoms, etc.

[0152] IV. Criteria for determining the therapeutic effect of taking this pharmaceutical composition

[0153] Cured: Symptoms diagnosed by clinical Chinese medicine disappeared, and reexamination of liver elastic modulus diagnosed that non-viral liver fibrosis and cirrhosis disappeared.

[0154] Markedly effective: Symptoms diagnosed by clinical Chinese medicine were eliminated, and liver elastic modulus reexamination diagnosed that liver fibrosis and cirrhosis were reduced.

[0155] Effective: Clinical TCM diagnosis of symptoms was alleviated or eliminated, and liver elastic modulus reexamination diagnosed pulmonary fibrosis and cirrhosis without enlargement or increase.

[0156] Ineffectiveness: After taking the modified drug combination regularly, the symptoms diagnosed by clinical Chinese medicine did not improve, and the liver elastic modulus reexamination diagnosed liver fibrosis and cirrhosis continued to increase.

[0157] 5. Method of taking this drug combination and precautions

[0158] 1. Take with warm water after meals, 3 times a day, 80 pills each time, 3 months as a course of treatment.

[0159] 2. It is strictly forbidden to take other drugs of the same type while taking this drug combination.

[0160] 3. Avoid spicy and dry foods, smoking and drinking.

[0161] 4. If you experience any adverse reactions during use, stop taking the medicine immediately.

[0162] VI. Clinical efficacy statistics

[0163] 1. A total of 90 cases were observed taking the drug composition, including 50 males and 40 females. 20 patients aged 18-30 years old, 40 patients aged 31-50 years old, and 30 patients aged 51-70 years old. The 90 patients underwent liver elastic modulus examinations in a tertiary A-level hospital before and after taking the drug, of which 69 cases were diagnosed with alcoholic liver fibrosis, 10 cases with alcoholic liver cirrhosis, and 20 cases with drug-induced liver fibrosis.

[0164] 2. A total of 90 patients were treated with this pharmaceutical composition. For patients with various morphologies shown by FibroScan, after observing one treatment course (three months), 55 patients (61%) were cured, 23 patients (26%) showed marked improvement, and 11 patients (12%) had effective responses. After the treatment (three months of administration), the total effective rate of the 90 patients was 98.8%. The statistical results of the observation items during the clinical administration of this pharmaceutical composition are shown in Table 1.

[0165] Table 1

[0166]

[0167] As shown in Table 1, for one of the formulations of this pharmaceutical composition, the dosage was referred to the results of animal experiments and the maximum dosage was adopted. The results confirmed the true effectiveness of this pharmaceutical composition in the treatment of non-viral liver fibrosis and cirrhosis.

[0168] During the period when this pharmaceutical composition was taken by patients, no toxic or side effects, or adverse reactions occurred or were shown.

[0169] Typical Case 1

[0170] Patient Ding *, male. The patient had a long-term history of heavy drinking. His self-reported symptoms were fatigue, indigestion, discomfort or pain in the right upper abdomen. He was diagnosed with mild liver fibrosis by transient elastography of the liver. The patient continuously took the pharmaceutical composition pills prepared in Example 8 for 3 months, and the above symptoms basically disappeared. The FibroScan diagnostic examination reports before and after the patient took the medicine are as Figure 4 and Figure 5 shown.

[0171] Typical Case 2

[0172] Patient Ding **, female. The patient had a long-term history of taking anti-tuberculosis drugs. Her symptoms were fatigue, indigestion, loss of appetite, abdominal distension, nausea, etc. She was diagnosed with mild liver fibrosis by transient elastography of the liver. The patient continuously took the pharmaceutical composition pills prepared in Example 8 for 3 months, and the above symptoms basically disappeared. The FibroScan diagnostic examination reports before and after the patient took the medicine are as Figure 6 and Figure 7 shown.

[0173] Typical Case 3

[0174] Patient Yu **, female. The patient had a long-term history of heavy drinking. Her symptoms were fatigue, indigestion, loss of appetite, abdominal distension, nausea, fullness, jaundice, skin ecchymosis, etc. She was diagnosed with decompensated liver cirrhosis by transient elastography of the liver. The patient continuously took the pharmaceutical composition pills prepared in Example 8 for 6 months, and the above symptoms basically disappeared. The FibroScan diagnostic examination reports before and after the patient took the medicine are as Figure 8 and Figure 9 shown.

[0175] Those skilled in the art should understand that the above embodiments are merely exemplary embodiments. According to different symptoms of patients, the dosage of the pharmaceutical composition can be arbitrarily selected within the scope of the present invention. Without departing from the spirit and technical scope of this application, various changes, substitutions, and alterations can be made, and its methods and uses are all within the protection scope of this application.

Claims

1. Use of a pharmaceutical composition in the preparation of a medicament for treating non-viral liver fibrosis and liver cirrhosis, characterized in that, The pharmaceutical composition comprises the following components in parts by weight: 14-36 parts of Salvia miltiorrhiza, 0.6-1.4 parts of bear bile, 10-30 parts of American ginseng, 0.6-1.4 parts of egg yolk lecithin, 6-28 parts of Bupleurum chinense, 4-24 parts of Schisandra chinensis, 2-12 parts of Polygonum cuspidatum, 2-12 parts of Isatis indigotica, and 6-18 parts of Hedyotis diffusa.

2. Use of a pharmaceutical composition according to claim 1 in the preparation of a medicament for treating non-viral liver fibrosis and liver cirrhosis, characterized in that, The pharmaceutical composition comprises the following components in parts by weight: 19-29 parts of Salvia miltiorrhiza, 0.8-1.2 parts of bear bile, 15-25 parts of American ginseng, 0.8-1.2 parts of egg yolk lecithin, 11-21 parts of Bupleurum chinense, 9-19 parts of Schisandra chinensis, 6-8 parts of Polygonum cuspidatum, 4-8 parts of Isatis indigotica, and 9-15 parts of Hedyotis diffusa.

3. Use of a pharmaceutical composition according to claim 1 in the preparation of a medicament for treating non-viral liver fibrosis and liver cirrhosis, characterized in that, The pharmaceutical composition comprises the following components in parts by weight: 19-28 parts of Salvia miltiorrhiza, 0.8-1.2 parts of bear bile, 17-25 parts of American ginseng, 0.8-1.2 parts of egg yolk lecithin, 11-14 parts of Bupleurum chinense, 10-19 parts of Schisandra chinensis, 6-8 parts of Polygonum cuspidatum, 4-8 parts of Isatis indigotica, and 10-14 parts of Hedyotis diffusa.

4. Use of a pharmaceutical composition according to claim 1 in the preparation of a medicament for treating non-viral liver fibrosis and cirrhosis, characterized in that, The pharmaceutical composition comprises the following components in parts by weight: 19-27 parts of Salvia miltiorrhiza, 1.0-1.2 parts of bear bile, 15-20 parts of American ginseng, 0.8-1.2 parts of egg yolk lecithin, 11-13 parts of Bupleurum chinense, 11-19 parts of Schisandra chinensis, 6-8 parts of Polygonum cuspidatum, 4-6 parts of Isatis indigotica, and 13-14 parts of Hedyotis diffusa.

5. Use of a pharmaceutical composition according to any one of claims 1-4 in the preparation of a medicament for treating non-viral liver fibrosis and liver cirrhosis, characterized in that, The dosage form of the drug for treating liver fibrosis and cirrhosis is tablet, granule, capsule, dripping pill, pill, sustained release preparation or freeze-dried powder preparation.

6. Use of a pharmaceutical composition according to claim 5 in the preparation of a medicament for treating non-viral liver fibrosis and liver cirrhosis, characterized in that, The preparation method of the pharmaceutical composition comprises the following steps: Step 1: Weigh each component in the pharmaceutical composition according to parts by weight; Step 2: American ginseng is extracted 3 times with 65-85% ethanol at 60-80 °C for 1-2 hours each time. The extraction solution is filtered, and ethanol is recovered under reduced pressure to obtain a liquid extract. The obtained liquid extract is loaded onto D101 macroporous resin, eluted with 40-60% ethanol, the eluate is collected, ethanol is recovered under reduced pressure, and the eluate is concentrated to a relative density of 1.13-1.33 and then freeze-dried at -40 to -60 °C and pulverized to obtain fine powder I; Step 3: Salvia miltiorrhiza is extracted by reduced pressure reflux with 60-80% ethanol at 45-65 °C for 3 times, 1-2 hours each time. The filtrate is collected, ethanol is recovered under reduced pressure at 60-70 °C, the filtrate is concentrated to a liquid extract and then freeze-dried at -40 to -60 °C and pulverized to obtain fine powder II; Step 4: Bupleurum chinense is extracted by reduced pressure reflux with 70-80% alkaline ethanol at 75-80 °C for 3 times, 1-2 hours each time. The filtrate is collected, ethanol is recovered under reduced pressure at 60-70 °C until the weight of the filtrate is equal to the weight of the crude drug of Bupleurum chinense, refrigerated at 4 °C for 24-48 hours, and then the precipitate is taken and freeze-dried at -40 to -60 °C and pulverized to obtain fine powder III; Step 5: The flesh of Schisandra chinensis is removed, and the kernels of Schisandra chinensis are subjected to conventional ethanol extraction. The extraction solution is collected, and ethanol is recovered under reduced pressure to obtain a concentrated paste; Polygonum cuspidatum, Hedyotis diffusa and Isatis indigotica are subjected to conventional combined ethanol extraction, the extraction solution is collected and dried under reduced pressure and pulverized to obtain fine powder IV; Step 6: The fine powder I, fine powder II, fine powder III, fine powder IV, concentrated paste, ground bear bile powder and egg yolk lecithin obtained in Step 2 to Step 5 are mixed evenly to obtain the pharmaceutical composition.

7. Use of a pharmaceutical composition according to claim 6 in the preparation of a medicament for treating non-viral liver fibrosis and liver cirrhosis, characterized in that, The pH value of the alkaline ethanol described in Step 4 is 9.

Images