A traditional Chinese medicine compound preparation for treating chronic liver disease, and its preparation method and application

Abstract

The present invention discloses a traditional Chinese medicine compound preparation for treating chronic liver disease, as well as its preparation method and application. The raw materials of the effective ingredients of the traditional Chinese medicine compound preparation include astragalus, raw oyster, polygonatum, seaweed, poria, salvia miltiorrhiza, zedoaria, raw turtle shell, kelp, phyllanthus urinaria, sophora flavescens, bupleurum, cyperus rotundus, vinegar-cured corydalis, and Panax notoginseng. The traditional Chinese medicine compound preparation of the present invention is mainly used for chronic liver disease and liver fibrosis, and is symptomatic. It has the effects of promoting blood circulation and removing blood stasis, removing dampness and resolving phlegm, softening and dispersing hard masses, and has good absorption effect, significant efficacy, no toxic side effects and clinical adverse reactions. It has a high cure rate for liver fibrosis as clinically verified.

Description

Technical Field

[0001] The present invention belongs to the field of traditional Chinese medicine, and specifically relates to a traditional Chinese medicine compound preparation for treating chronic liver disease, a preparation method thereof, and applications thereof. In particular, it relates to a traditional Chinese medicine compound preparation for treating chronic liver disease and liver fibrosis, a preparation method thereof, and applications thereof. Background Art

[0002] Chronic liver disease refers to lesions that occur in the liver, with chronic hepatitis and cirrhosis being the most common. The main pathological changes are liver function impairment and liver fibrosis. Liver fibrosis is a key pathological link in the development of various chronic liver diseases. It is a reversible stage in the progression of chronic hepatitis to cirrhosis. It is the body's repair response to various chronic liver injuries and the common pathological basis of all chronic liver diseases. Liver fibrosis can progress to cirrhosis, liver failure, and primary liver cancer, and patients ultimately die from end-stage diseases related to chronic liver disease. Liver fibrosis is the early clinical stage of cirrhosis and liver cancer. Therefore, its prevention and treatment can significantly reduce the morbidity and mortality of cirrhosis and liver cancer and improve patients' quality of life. How to inhibit liver fibrosis and prevent the disease from further developing into cirrhosis and liver cancer has become a research hotspot both domestically and internationally.

[0003] The fundamental treatment strategy for chronic liver disease and liver fibrosis is a combination of etiological treatment and anti-fibrotic therapy. However, due to poor liver targeting, short half-life, and toxic side effects caused by drug accumulation in other tissues, drug efficacy remains low. Currently, there are no clinically available anti-fibrotic chemical or biological drugs for the treatment of liver fibrosis. Therefore, identifying effective drugs to block, delay, and reverse the onset and progression of liver fibrosis is an urgent issue.

[0004] The research team of the present inventor has been engaged in the clinical and scientific research of chronic liver disease for a long time, and has rich clinical experience. They are particularly good at treating liver fibrosis with remarkable results. The present inventor believes that the description of the pathogenesis of accumulation syndrome in the "Inner Canon of Medicine" is consistent with the pathology of liver fibrosis. For example, "Lingshu. The Origin of All Diseases" believes that pathogenic factors invade the human body, and combined with internal injuries, worry and anger, or irregular diet and daily life, lead to "the failure of warming qi to function, blood coagulation and accumulation inside, and the obstruction of body fluids, which persist and do not go away, and accumulation is formed". When external evils such as "damp-heat epidemic toxins" and "poisonous insect poisons" invade the liver, or when injured by alcohol and food, they do not heal for a long time, gradually leading to dysfunction of the liver, spleen, and kidneys. The entanglement of qi, blood, and body fluids causes the meridians to stagnate, so that the yang qi cannot flow smoothly, causing blood coagulation inside and unable to dissipate, and the infusion of body fluids also becomes stagnant, eventually leading to the deposition of phlegm dampness and blood stasis, which is caused by the obstruction of the liver meridians. Therefore, "phlegm dampness" and "blood stasis" are the key to the pathogenesis of liver fibrosis. Based on this basic disease characteristic, a Chinese medicine compound preparation for treating chronic liver disease is prepared according to the clinical method of promoting blood circulation and removing blood stasis, dispelling dampness and resolving phlegm, and softening and dispersing hard masses according to the theory of TCM differentiation of syndromes. Most doctors focus on using blood circulation promoting and removing blood stasis drugs, but if only blood circulation promoting and removing blood stasis drugs are used, there are many drawbacks of consuming qi and damaging yin, and even breaking up blood stasis and causing bleeding. The liver is yin in nature and should be used with yang, so the use of drugs should be soft instead of rigid. In the treatment of liver fibrosis, dispersing hard masses and causing fullness instead, so on the basis of using drugs that promote blood circulation and dispersing hard masses, products that invigorate qi and strengthen the spleen, nourish yin and soften the liver should be added. Based on this, mainly for patients with chronic liver disease and liver fibrosis, the present invention is specially proposed. Summary of the Invention

[0005] In order to make up for the deficiencies of the existing technology, the present invention provides a traditional Chinese medicine compound preparation for treating chronic liver disease. The raw materials of the effective ingredients of the traditional Chinese medicine compound preparation include astragalus, raw oyster, polygonatum, seaweed, poria, salvia miltiorrhiza, zedoaria, raw turtle shell, kelp, phyllanthus urinaria, sophora flavescens, bupleurum, cyperus rotundus, vinegar-preserved corydalis, and Panax notoginseng.

[0006] Preferably, the weight proportions of the raw materials of the active ingredients of the Chinese herbal compound preparation of the present invention are:

[0007] 20-40 parts of Astragalus, 20-40 parts of raw oyster, 10-30 parts of Polygonatum, 10-30 parts of seaweed,

[0008] 10-30 parts of Poria cocos, 10-30 parts of Salvia miltiorrhiza, 10-30 parts of Curcuma zedoaria, 10-30 parts of raw turtle shell,

[0009] 10-30 parts of kelp, 10-30 parts of phyllanthus, 10-30 parts of sophora flavescens, 5-20 parts of bupleurum,

[0010] 5-20 parts of Cyperus rotundus, 5-20 parts of vinegar-soaked Corydalis, and 5-20 parts of Panax notoginseng.

[0011] Preferably, the raw material composition and weight proportions of the active ingredients of the Chinese herbal compound preparation of the present invention are:

[0012] 30 parts of Astragalus, 30 parts of raw oyster, 20 parts of Polygonatum, 15 parts of seaweed,

[0013] 15 parts of Poria cocos, 15 parts of Salvia miltiorrhiza, 15 parts of Curcuma zedoaria, 15 parts of raw turtle shell,

[0014] 15 parts of Kelp, 15 parts of Phyllanthus urinaria, 15 parts of Sophora flavescens, 10 parts of Bupleurum,

[0015] 10 parts of Cyperus rotundus, 10 parts of vinegar-cured Corydalis, and 10 parts of Panax notoginseng.

[0016] On the other hand, the present invention also provides a method for preparing the Chinese medicine compound preparation, which comprises the following process steps:

[0017] (1) preparing 15 kinds of medicinal materials according to the weight ratio;

[0018] (2) Mix the six medicinal materials, including Astragalus, Salvia miltiorrhiza, Curcuma zedoaria, Cyperus rotundus, Corydalis yanhusuo, and Panax notoginseng, and grind them into powder using a universal grinder. Then, mix them evenly using a trough mixer and pass them through a 100-mesh sieve.

[0019] (3) Add 10 times the amount of water to the raw oyster, polygonatum, seaweed, poria, raw turtle shell, kelp, phyllanthus, sophora flavescens, and bupleurum, and boil twice, the first time for 1.5 hours and the second time for 1.0 hours. Combine the decoctions, filter, and concentrate the filtrate into a thick paste with a relative density of 1.30-1.35 at 60°C.

[0020] (4) The fine powder obtained in step (2) and the thick paste obtained in step (3) are mixed evenly with a trough mixer, and pellets are made using a fully automatic speed-controlled Chinese medicine pill making machine, polished, dried in a hot air circulation oven, and bottled.

[0021] Preferably, the Chinese medicine compound preparation prepared by the method of the present invention is a pill.

[0022] Preferably, in step (4) of the present invention, each 10 pills weigh 0.39 g.

[0023] Preferably, the bottling in step (4) of the present invention is 120 g / bottle.

[0024] In another aspect, the present invention also provides a use of the Chinese medicine compound preparation in the preparation of a treatment for chronic liver disease.

[0025] Preferably, the chronic liver disease described in the present invention is chronic liver disease liver fibrosis.

[0026] The medicinal properties of the Chinese medicinal compound preparation used in the present invention are as follows:

[0027] Astragalus: Sweet and slightly warm in nature. It enters the lung, spleen, liver, and kidney meridians. It tonifies qi and strengthens the spleen, elevates yang and lifts deficient qi, strengthens the defensive system, promotes diuresis and reduces swelling, nourishes blood and produces body fluids, relieves stagnation and relieves numbness, heals sores and promotes tissue regeneration, and expels toxins and pus. It primarily treats qi deficiency and fatigue, qi deficiency in the middle, chronic diarrhea and rectal prolapse; lung qi deficiency, cough, wheezing, and shortness of breath; qi and blood deficiency, difficult sores and ulcers; internal heat and thirst, blood deficiency and sallow complexion; qi deficiency and blood stasis, pain and numbness. Modern pharmacology indicates that astragalus can prevent hepatic glycogen depletion. Experimental studies have shown that it has a protective effect against hepatitis in mice, possibly through regulating intracellular cAMP and cGMP, enhancing cellular physiological metabolism. It also promotes serum and liver protein turnover, promoting protein metabolism. It can also enhance immunity and stress resistance, improve cardiac function, lower blood pressure, and regulate blood sugar, improving hemodynamics in related vascular diseases.

[0028] Raw oysters are salty and slightly cold in nature. They enter the liver, gallbladder, and kidney meridians. They have calming and soothing effects, suppressing yang and replenishing yin, softening and dispersing lumps, and astringing and constricting properties. They are used to treat restlessness, palpitations, and insomnia; hyperactivity of liver yang, dizziness, goiters, masses, and accumulations; spontaneous sweating, night sweats, spermatorrhea, metrorrhagia, and leukorrhea; stomachache and heartburn. Modern pharmacology indicates that oysters participate in a wide range of metabolic processes in the human body, exhibiting antiarrhythmic effects, protecting liver cells, and combating fatty liver disease.

[0029] Polygonatum sibiricum: Sweet and neutral in nature. It enters the spleen, lung, and kidney meridians. Its primary effects are to nourish qi and yin, moisten the lungs and benefit the kidneys, and tonify the spleen. It is primarily used to treat spleen and stomach deficiency, fatigue, dry mouth and poor appetite, internal heat and thirst, dry cough due to lung deficiency, chronic cough caused by exertion, dizziness due to kidney deficiency, soreness of the waist and knees, premature graying of hair, internal heat and thirst.

[0030] Seaweed: Bitter, salty, and cold in nature. It enters the kidney, liver, and stomach meridians. It softens and dissipates lumps, eliminates phlegm, and promotes diuresis and reduces swelling. "Compendium of Materia Medica Chongyuan" states: "Seaweed, with its bitter and salty flavor and cold and cleansing properties, is primarily used to treat lumps both inside and outside the meridians."

[0031] Poria cocos: Sweet, mild, and neutral in nature. It enters the heart, lung, spleen, and kidney meridians. It promotes diuresis, dispelling dampness, strengthening the spleen, and calming the mind. It is primarily used to treat edema, dysuria; cough due to phlegm and fluid retention, dizziness and palpitations; diarrhea due to spleen deficiency, loss of appetite, loose stools, and vomiting; palpitations, restlessness, insomnia, and forgetfulness. The Materia Medica states: "Avoid using rice vinegar." The Origin of Medicine states: "If urination is frequent or frequent consumption is harmful to the eyes; if excessive sweating is caused, consumption can damage vital energy and shorten lifespan."

[0032] Danshen (Salvia miltiorrhiza) is bitter and slightly cold in nature. It enters the Heart and Liver meridians. It promotes blood circulation and regulates menstruation, removes blood stasis and relieves pain, cools blood and eliminates carbuncles, and relieves restlessness and calms the mind. The Ben Jing (Classic Classic of Compendium of Materia Medica) states that it "treats evil spirits in the heart and abdomen, rumbling bowels like running water, and accumulation of cold and heat; it dissolves lesions and masses, relieves restlessness and fullness, and replenishes Qi." The Compendium of Materia Medica states that it "activates blood circulation, unblocks the pericardium, and treats hernia pain." Modern medical research has found that Danshen can increase plasmin activity; prolong blood clotting and clotting times; inhibit platelet aggregation; improve hemorheological properties; enhance microcirculation; promote tissue repair and regeneration; inhibit fibroblast proliferation; and protect the liver and improve liver microcirculation.

[0033] Curcuma: Pungent, bitter, and warm in nature. It enters the Liver and Spleen meridians. It has the effects of promoting blood circulation, promoting qi circulation, and relieving pain. It is primarily used to treat abdominal pain caused by blood stasis, hepatosplenomegaly, and abdominal distension and pain; accumulation of blood, amenorrhea caused by blood stasis in women, pain caused by injuries, and food stagnation; amenorrhea caused by qi stagnation and blood stasis; chest and flank pain; abdominal pain and lumps; and stomach and abdominal distension and pain caused by food stagnation.

[0034] Raw turtle shell: Salty and slightly cold in nature. It enters the liver and kidney meridians. It nourishes yin and suppresses yang, reduces fever and eliminates steaming, softens and disperses lumps. It is used for yin deficiency fever, fatigue-induced bone steaming, yin deficiency and yang hyperactivity, dizziness, internal wind movement, spasms in the hands and feet; amenorrhea, scabies and accumulations, and chronic malaria. Ancient texts state, "As for the treatment of accumulations... For example, turtle shell pills treat liver accumulation as fat qi, dry lacquer pills and Pinellia powder treat heart accumulation as hidden liang, and turtle shell pills treat spleen accumulation as abdominal distension. Although the four prescriptions are different, they all enter the viscera of the foot Jueyin, hand Shaoyin, and foot Taiyin. Because turtle shell is specialized in yin qi, it enters the three yin meridians and dispels accumulations, naturally benefiting from the corresponding qi."

[0035] Kelp: Salty in nature and flavor. Enters the liver, stomach, and kidney meridians. Has the functions of softening and dispersing lumps, eliminating phlegm, and promoting diuresis. Used for edema caused by phlegm and fluid retention;

[0036] It can dissipate lumps, eliminate phlegm, and promote diuresis; it is effective for treating goiters, scrofula, testicular swelling and pain, and edema caused by phlegm and fluid retention. "Bielu" (Beilu) states: "It treats twelve types of edema, goiters, gas accumulation, and impotence." Modern pharmacological studies have shown that kelp can inhibit hyperthyroidism and has antihypertensive, blood sugar, lipid-lowering, anticoagulant, and anti-radiation effects.

[0037] Phyllanthus urinaria: Slightly bitter, sweet, and cooling in nature. It enters the liver and spleen meridians. It has heat-clearing, diuretic, eye-improving, and digestive properties. Modern pharmacology suggests that Phyllanthus urinaria has anti-hepatitis B virus (HBV) effects, anti-hepatocellular carcinoma (HCC) effects, and antibacterial properties.

[0038] Sophora flavescens: Bitter in taste and cold in nature, it enters the Heart, Liver, Stomach, Large Intestine, and Bladder meridians. It has the effects of clearing heat, drying dampness, and detoxifying. The "Shennong Bencao Jing" states: "It treats qi stagnation in the heart and abdomen, accumulation of masses, jaundice, residual urine, diuresis, and carbuncle removal." Modern pharmacological research has shown that matrine and oxymatrine have strong inhibitory effects on hepatitis B virus, hepatitis C virus, coxsackie virus, and adenovirus.

[0039] Bupleurum: Acrid and bitter, slightly cold in nature. It enters the liver, gallbladder, and lung meridians. Its primary functions are to dispel heat, relieve liver depression, and elevate yang energy. The "Shennong Bencao Jing" notes: "It has a bitter, neutral flavor and is non-toxic." Modern pharmacological research indicates that Bupleurum has antipyretic, anti-inflammatory, immune-boosting, liver-protective, choleretic, and radiation-resistant properties. It also lowers blood lipids, inhibits gastric acid secretion, fights ulcers, inhibits trypsin, fights pathogens and microorganisms, and has anti-tumor and anti-epileptic properties.

[0040] Cyperus rotundus: Spicy, slightly bitter, slightly sweet, and neutral in nature, it enters the liver, spleen, and triple burner meridians. It has the effects of soothing the liver and relieving depression, regulating qi and relieving fullness, regulating menstruation and relieving pain, and stabilizing pregnancy. Modern pharmacological studies have shown that Cyperus rotundus can significantly increase bile flow, promote bile secretion, and protect liver cells.

[0041] Yuanhu (Rhizoma Corydalis): Also known as Yanhusuo, it is warm in nature and bitter in flavor. It enters the heart, spleen, and liver meridians, promoting blood circulation, promoting qi circulation, and relieving pain. It is mainly used to treat qi stagnation and blood stasis, chest and flank pain, abdominal pain, angina pectoris, amenorrhea, dysmenorrhea, postpartum blood stasis, and swelling and pain caused by falls.

[0042] Panax notoginseng: Warm in nature, sweet with a slightly bitter taste, it enters the liver and stomach meridians, dispersing blood stasis, arresting bleeding, reducing swelling and alleviating pain. It is primarily used to treat hemoptysis, hematemesis, epistaxis, bloody stool, metrorrhagia, traumatic bleeding, stabbing chest and abdominal pain, and swelling and pain from falls. "Compendium of Materia Medica" states that it specifically enters the liver and stomach, and also the heart and large intestine. It is also known as mountain lacquer. Modern pharmacological research indicates that Panax notoginseng can significantly shorten bleeding and clotting times, exhibit antiplatelet aggregation and thrombolytic properties, protect against liver damage and tumors, and promote the proliferation of multifunctional hematopoietic stem cells, exerting a hematopoietic effect.

[0043] Liver fibrosis is a key stage in the progression of chronic liver disease. It refers to the excessive deposition of fibrous connective tissue in liver cells and the diffuse abnormal distribution of the extracellular matrix. It is a chronic pathological change in the liver and a key step in the progression of normal liver tissue to cirrhosis. It is also a key factor affecting the prognosis of chronic liver disease. The inventors have accumulated nearly 30 years of clinical experience and have conducted in-depth research and summary on the disease of liver fibrosis. The treatment of liver fibrosis has achieved good results, delaying the progression of the disease in patients and even reversing the state of liver fibrosis, effectively improving the prognosis of patients with chronic liver disease.

[0044] The inventors believe that the description of the pathogenesis of accumulation syndrome in the Neijing (Inner Canon of Internal Medicine) is consistent with the pathology of liver fibrosis. For example, the Lingshu (Lingshu) states that pathogenic factors invade the human body, coupled with internal injuries, anxiety, anger, or irregular diet and daily living habits, leading to "the inability of warming qi to function, blood clotting and retention, and the stagnant and intractable accumulation of body fluids, which then form accumulations." The Treatise on the Causes and Symptoms of Various Diseases states that "when pathogenic factors are initially absorbed by the various internal organs, accumulations are initially prevented, but they stagnate and become stagnant, forming accumulations." Furthermore, the Jingyue Complete Works states that "accumulation refers to the accumulation of a substance, which gradually develops." Accumulation-related diseases can be caused by alcohol, food, blood, qi, wind, cold, and emotions. "Ji Sheng Fang" states, "People who are prone to worry, worry, joy, and anger are all part of human nature. Excessive worry and anger can harm the five internal organs... and this accumulation can lead to the five accumulations." This disease is often caused by the long-term effects of pathogenic toxins on the liver. Because the liver is responsible for dispersing qi and discharging qi, the liver's physiology is affected by pathogenic factors, leading to disharmony in the liver meridians. Liver disease originates from qi and blood. Qi stagnation and blood stasis lead to a stagnation of qi, blood, and body fluids, causing stagnation in the meridians. This prevents the smooth flow of yang qi, causing blood to clot and become unable to dissipate. The transfusion of body fluids also becomes stagnant, ultimately leading to the accumulation of phlegm-dampness and blood stasis, resulting in liver meridian stasis. Therefore, "phlegm-dampness" and "blood stasis" are key to the pathogenesis of liver fibrosis. In the early stages, pathogenic factors are generally prevalent, with a conflict between the evil and the righteous, while the righteous qi can still resist the evil, representing a syndrome of excess. The later stages of accumulation are characterized by blood stasis in the liver, insufficient qi and yin, forming a syndrome of deficiency in the underlying cause and excess in the superficial cause.

[0045] The Complete Works of Jingyue states that "the key to treating accumulation is to know when to attack or when to supplement, and to distinguish between slow and urgent". The present inventor believes that when treating the real, one should take into account the virtual, and when supplementing the virtual, one should not forget the real, so as to dredge the blood and qi, and regulate them. Most patients with liver fibrosis have poor circulation of qi and blood, which blocks the meridians and consumes the body's vital energy, leading to qi and yin deficiency, accumulation of blood stasis entering the meridians, and both qi and blood stasis. Neither a strong attack nor a slow action can be taken. The liver qi and blood should be dispersed, the masses should be broken up and the masses should be resolved. Pungent and warm drugs are often used to invigorate the blood circulation, but pungent and warm drugs are strong and often injure the yin, so drugs that nourish the yin should be added. The liver is yin in nature and uses yang, so drugs that are used should avoid being too strong and should be soft. In the treatment of liver fibrosis, slow drugs should be used to soften and dissolve the masses. If only blood-activating and stasis-removing drugs are used, there are often disadvantages of consuming qi and injuring the yin, and even breaking up the blood stasis and causing bleeding, while eliminating the masses can cause fullness. In addition, drugs that invigorate qi, invigorate the spleen, nourish the yin and soften the liver should be used. The so-called "yin evil enters the meridians, and the main purpose is to treat it with pungent and warm herbs that enter the blood meridians. Yin governs essence, and if it does not move, it is the root of tranquility, so it is yin... Therefore, it is necessary to use yang products to utilize the body's yin, so that yang can be released, so as to rotate its pungent, dispersing, warming and unblocking power." Therefore, Professor Hu Zhenbin put forward his own views based on many years of clinical experience. He used the clinical methods of promoting blood circulation and removing blood stasis, removing dampness and resolving phlegm, and softening and dispersing nodules in the theory of Chinese medicine differentiation of syndromes to produce a Chinese medicine compound preparation for treating chronic liver disease. Therefore, the present invention prescribes medicine according to the cause of the disease. In the prescription, salvia miltiorrhiza, panax notoginseng and zedoaria are the main herbs that promote blood circulation and remove blood stasis. Turtle shell and oyster are the auxiliary herbs that nourish yin and suppress yang, soften and dispersing nodules, and dispersing nodules without damaging yin. Seaweed and kelp resolve phlegm, soften and dispersing nodules. Seaweed, kelp, bupleurum, cyperus and corydalis are adjuvants. Qi is the leader of blood, and blood circulates when qi moves. Bupleurum and cyperus soothe the liver and regulate qi, while corydalis promotes blood circulation and relieves pain. Phlegm and dampness accumulate over time and turn into heat. Phyllanthus urinaria and Sophora flavescens clear away heat and toxic substances, dispelling exogenous pathogens. Astragalus membranaceus replenishes the middle qi and invigorates qi. Polygonatum sibiricum replenishes qi and nourishes yin, invigorates the spleen and benefits the kidneys. Poria cocos invigorates the spleen and eliminates dampness, dispelling pathogens without harming the body. Phyllanthus urinaria, Sophora flavescens, Astragalus membranaceus, Polygonatum sibiricum, and Poria cocos serve as guiding herbs. The combination of these herbs works together to strengthen the body's qi, dissipate blood stasis, and dissipate stagnation. The Chinese herbal compound preparation of the present invention promotes blood circulation and dredges, invigorates qi and nourishes yin, dredges blood vessels in the liver, clears liver congestion, dissipates blood stasis and dissipates stagnation, promotes the degradation and absorption of liver fibrosis, protects the liver, promotes liver cell regeneration, and lowers portal blood pressure, thus having clinical promotion value.

[0046] Therefore, the medicinal materials selected in the present invention have complementary medicinal properties, and the medicine is used according to the cause of the disease. The combination of the medicines has the effects of strengthening the body, replenishing qi, and dispersing blood stasis and resolving stagnation. By promoting blood circulation and unblocking the meridians, replenishing qi and nourishing yin, dredging the blood vessels in the liver, clearing liver congestion, dispersing blood stasis and resolving stagnation, the present invention promotes the degradation and absorption of liver fibrosis in chronic liver disease, protects the liver, and promotes liver cell regeneration. It has no toxic side effects and has good efficacy.

[0047] Clinically verified, the present invention has a high cure rate for liver fibrosis, good absorption effect, significant therapeutic effect, and no toxic side effects or clinical adverse reactions. The traditional Chinese medicine compound preparation of the present invention can promote the degradation and absorption of liver fibrosis, protect the liver, promote liver cell regeneration, lower portal blood pressure, and effectively improve the patient's prognosis, thus having clinical promotion value.

[0048] The Chinese medicine compound preparation of the present invention is mainly aimed at chronic liver disease and liver fibrosis, and is a symptomatic medicine. It has the effects of strengthening the body and replenishing qi, removing blood stasis and dispersing nodules, promoting qi and relieving pain, has good absorption effect, significant therapeutic effect, no toxic side effects and clinical adverse reactions, and has a high cure rate for liver fibrosis as clinically verified. BRIEF DESCRIPTION OF THE DRAWINGS

[0049] Figure 1 Diagram of the preparation model of Chinese herbal compound preparations.

[0050] Figure 2 Some quality inspection pictures of Chinese herbal compound preparations.

[0051] Figure 3 Finished product sample. DETAILED DESCRIPTION

[0052] The present invention is further described below with reference to specific examples. Unless otherwise specified, all raw materials involved in the following examples are commercially available.

[0053] The present invention will be further described in detail below with reference to the accompanying drawings and examples. The following examples are intended to illustrate the present invention only and are not intended to limit the scope of the invention. Experimental methods in the examples where specific conditions are not specified are generally performed under conventional conditions or as recommended by the manufacturer.

[0054] Example 1 The raw material composition and weight of the active ingredients of the Chinese herbal compound preparation for treating chronic liver disease are as follows:

[0055] 20-40 parts of Astragalus, 20-40 parts of raw oyster, 10-30 parts of Polygonatum, 10-30 parts of seaweed,

[0056] 10-30 parts of Poria cocos, 10-30 parts of Salvia miltiorrhiza, 10-30 parts of Curcuma zedoaria, 10-30 parts of raw turtle shell,

[0057] 10-30 parts of kelp, 10-30 parts of phyllanthus, 10-30 parts of sophora flavescens, 5-20 parts of bupleurum,

[0058] 5-20 parts of Cyperus rotundus, 5-20 parts of Corydalis yanhusuo, and 5-20 parts of Panax notoginseng.

[0059] Example 2 The raw material composition and weight of the active ingredients of the Chinese herbal compound preparation for treating chronic liver disease are as follows:

[0060] 20 parts of Astragalus, 20 parts of raw oyster, 10 parts of Polygonatum, 10 parts of seaweed,

[0061] 10 parts of Poria cocos, 10 parts of Salvia miltiorrhiza, 10 parts of Curcuma zedoaria, 10 parts of raw turtle shell,

[0062] 10 parts of Kelp, 10 parts of Phyllanthus urinaria, 10 parts of Sophora flavescens, 5 parts of Bupleurum root,

[0063] 5 parts of Cyperus rotundus, 5 parts of Corydalis yanhusuo, and 5 parts of Panax notoginseng.

[0064] Example 3 The raw material composition and weight of the active ingredients of the Chinese herbal compound preparation for treating chronic liver disease are as follows:

[0065] 40 parts of Astragalus, 40 parts of raw oyster, 30 parts of Polygonatum, 30 parts of seaweed,

[0066] 30 parts of Poria cocos, 30 parts of Salvia miltiorrhiza, 30 parts of Curcuma zedoaria, 30 parts of raw turtle shell,

[0067] 30 parts of Kelp, 30 parts of Phyllanthus urinaria, 30 parts of Sophora flavescens, 20 parts of Bupleurum root,

[0068] 20 parts of Cyperus rotundus, 20 parts of Corydalis yanhusuo, and 20 parts of Panax notoginseng.

[0069] Example 4 The raw material composition and weight of the active ingredients of the Chinese herbal compound preparation for treating chronic liver disease are as follows:

[0070] 30 parts of Astragalus, 30 parts of raw oyster, 20 parts of Polygonatum, 15 parts of seaweed,

[0071] 15 parts of Poria cocos, 15 parts of Salvia miltiorrhiza, 15 parts of Curcuma zedoaria, 15 parts of raw turtle shell,

[0072] 15 parts of Kelp, 15 parts of Phyllanthus urinaria, 15 parts of Sophora flavescens, 10 parts of Bupleurum,

[0073] 10 parts of Cyperus rotundus, 10 parts of Corydalis yanhusuo, and 10 parts of Panax notoginseng.

[0074] Example 5 The preparation method of the Chinese herbal compound preparation in Examples 1 to 4 comprises the following steps:

[0075] (1) preparing 15 kinds of medicinal materials according to the weight ratio;

[0076] (2) Astragalus, Salvia miltiorrhiza, Curcuma zedoaria, Cyperus rotundus, Corydalis yanhusuo, and Panax notoginseng were mixed and ground into powder using a universal crusher (9FZ-35), then mixed evenly using a trough mixer (CH-50) and passed through a 100-mesh sieve;

[0077] (3) Add 10 times the amount of water to the raw oyster, polygonatum, seaweed, poria, raw turtle shell, kelp, phyllanthus, sophora flavescens, and bupleurum, and boil twice, the first time for 1.5 hours and the second time for 1.0 hours. Combine the decoctions, filter, and concentrate the filtrate into a thick paste with a relative density of 1.30-1.35 at 60°C.

[0078] (4) The fine powder obtained in step (2) and the thick paste obtained in step (3) were mixed uniformly using a trough mixer (CH-50), and pelletized using a fully automatic speed-controlled Chinese medicine pelletizing machine (YUJ-16B) (each 10 pellets weighing 0.39 g), polished, and dried in a hot air circulation oven (CTCI). The resulting product was then bottled (120 g / bottle).

[0079] (5) The preparation model of Chinese medicine compound preparation is shown in the figure Figure 1 Some quality inspection pictures of Chinese herbal compound preparations are shown in the figure below. Figure 2 As shown. The finished product sample is as follows Figure 3 shown.

[0080] The dosage of the Chinese herbal compound preparations in Examples 1 to 4 is: oral administration, about 10 g at a time, twice a day, one hour after meals.

[0081] Example 6 Treatment Case Analysis

[0082] 1. Case selection

[0083] Two hundred inpatients and outpatients diagnosed with hepatitis B liver fibrosis at our hospital between January 2016 and December 2018 were randomly divided into four groups: A, B, C, and D. Group A included 50 patients, including 37 males and 13 females with a mean age of 44.3 years and a disease duration of 2-15 years. Group B included 50 patients, including 40 males and 10 females with a mean age of 43.3 years and a disease duration of 2.5-13 years. Group C included 50 patients, including 41 males and 9 females with a mean age of 42.8 years and a disease duration of 2-14 years. Group D included 50 patients, including 39 males and 11 females with a mean age of 44.5 years and a disease duration of 2.5-15 years. No statistically significant differences in general information were found among the four groups (P>0.05), indicating comparability.

[0084] 2. Groups A, B, C, and D all received entecavir as a basic antiviral treatment. In addition, Group A orally administered the Chinese herbal compound preparation of the present invention (formula in Implementation Plan 4). Group B orally administered silymarin tablets, 2 tablets / time, 3 times / day. The course of treatment for both groups was 1 year. Group C orally administered the Chinese herbal compound preparation of the present invention (formula in Implementation Plan 2). Group D orally administered the Chinese herbal compound preparation of the present invention (formula in Implementation Plan 3).

[0085] 3. Efficacy assessment:

[0086] Related biochemical test indicators: liver function, liver fibrosis index, LSM value, liver, gallbladder, spleen and pancreas color Doppler ultrasound (portal vein diameter (Dpv), spleen thickness, splenic vein diameter (Dsv) value comparison.

[0087] 4. Results

[0088] A clinical study of 200 patients with hepatitis B liver fibrosis found that after treatment, group A (using entecavir combined with the traditional Chinese medicine compound preparation of the present invention (formula in Example 4)) was compared with group B (using entecavir combined with silymarin tablets), group C (using entecavir combined with the traditional Chinese medicine compound preparation of the present invention (formula in Implementation Plan 2)), and group D (using entecavir combined with the traditional Chinese medicine compound preparation of the present invention (formula in Implementation Plan 3)). In terms of liver function (ALT, AST), liver fibrosis indicators (HA, PCIII, IV-C, LN), LSM values, and liver, gallbladder, spleen, and pancreas ultrasound (portal vein diameter (Dpv), spleen thickness, and splenic vein diameter (Dsv) values), group A, group C, and group D were significantly different from group B (P < 0.05). There was a statistically significant difference between Group A and Group C (P < 0.05), and there was no significant difference between Group A and Group D after treatment (P > 0.05). Entecavir combined with the Chinese herbal compound preparation of the present invention can treat chronic liver disease hepatitis B and liver fibrosis, which can not only achieve an antiviral effect, but also enhance the patient's immunity, which is better than conventional liver protection treatment. The two work synergistically and can significantly relieve the patient's symptoms. It has great significance for the long-term development of chronic liver disease and is worthy of clinical promotion and use.

[0089] (1) Changes in liver function of the four groups of patients before and after treatment are shown in Table 1.

[0090] Table 1 Comparison of changes in liver function in the four groups of patients before and after treatment

[0091]

[0092]

[0093] Note: After treatment, there were significant differences between Group A, Group C, and Group D compared with Group B (*P<0.05); there was a statistical difference between Group A and Group C (#P<0.05), and there was no significant difference between Group A and Group D after treatment (ΔP>0.05)

[0094] (2) Changes in serum liver fibrosis indicators in the four groups of patients before and after treatment are shown in Table 2

[0095] Table 2 Comparison of changes in serum liver fibrosis indicators in the four groups of patients before and after treatment

[0096]

[0097] Note: After treatment, there were significant differences between Group A, Group C, and Group D compared with Group B (*P<0.05); there was a statistical difference between Group A and Group C (#P<0.05), and there was no significant difference between Group A and Group D after treatment (ΔP>0.05)

[0098] (3) Comparison of changes in liver stiffness values ​​before and after treatment in the two groups of patients is shown in Table 3.

[0099] Table 3 Comparison of LSM values ​​before and after treatment in the four groups of patients ( kPa)

[0100]

[0101] Note: After treatment, there were significant differences between Group A, Group C, and Group D compared with Group B (*P<0.05); there was a statistical difference between Group A and Group C (#P<0.05), and there was no significant difference between Group A and Group D after treatment (ΔP>0.05)

[0102] (4) The changes of Dpv, spleen thickness and Dsv in the two groups before and after treatment are shown in Table 4

[0103] Table 4 Changes of Dpv, spleen thickness and Dsv in the four groups of patients before and after treatment

[0104]

[0105] Note: After treatment, there were significant differences between Group A, Group C, and Group D compared with Group B (*P<0.05); there was a statistical difference between Group A and Group C (#P<0.05), and there was no significant difference between Group A and Group D after treatment (ΔP>0.05)

[0106] Typical case examples:

[0107] 1. Liang, a 43-year-old male, presented to our hospital's outpatient hepatology department on February 8, 2018, complaining of two weeks of stabbing pain in the right upper abdomen, loss of appetite, a greasy sensation after eating, fatigue, a sallow complexion, occasional abdominal distension, poor appetite and sleep, and normal bowel movements. He had an eight-year history of chronic hepatitis B and had not received antiviral treatment. He had not sought medical attention or treatment during this period. Physical examination revealed a dark red tongue and a thready, stringy pulse. A few scattered spider nevi were visible on the chest and back. The abdomen was soft, with mild tenderness in the right upper abdomen, no rebound tenderness, and a shifting dullness (negative). A two-pair hepatitis B panel performed at our hospital revealed HBsAg (positive), HBeAg (negative), and HBcAb (negative). HBV-DNA quantification: 2.36 x 10∧5. Liver function tests: ALT: 96 U / L, AST: 73 U / L, and TBIL: 18.5 μmol / L. Four liver fibrosis indicators: HA: 270 Lg / L, PIII: 165 Lg / L, IV-C: 190 Lg / L, LN: 159 Lg / L. Color Doppler ultrasound of the liver, gallbladder, pancreas, and spleen revealed multiple intrahepatic nodules and early-stage cirrhosis. Portal vein diameter (Dpv): 12.6 mm, spleen thickness: 43.6 mm, splenic vein diameter (Dsv): 10.3 mm. FibroScan system testing revealed 10.6 kPa. Based on the patient's medical history, symptoms, and ancillary tests, the diagnosis was hepatitis B fibrosis. Treatment was with entecavir dispersible tablets (1 tablet / dose, daily) for antiviral therapy and the traditional Chinese medicine compound preparation of the present invention (formula in Example 4) (10 g / dose, twice daily) for liver protection and anti-fibrosis treatment. Follow-up was conducted every three months. One year later, the patient showed no significant discomfort, had good appetite and sleep, and had normal bowel movements. Hepatitis B testing revealed: HBsAg (+), HBeAg (-), HBcAb (-). HBV DNA quantitative analysis: (-). Liver function tests: ALT: 32 U / L, AST: 41 U / L, TBIL: 9.5 μmol / L. Four liver fibrosis tests: HA: 75 Lg / L, PIII: 63 Lg / L, IV-C: 52 Lg / L, LN: 61 Lg / L. Color Doppler ultrasound of the liver, gallbladder, pancreas, and spleen revealed: slightly increased echogenicity of the liver tissue. Portal vein diameter (Dpv): 7.3 mm, spleen thickness: 28.9 mm, splenic vein diameter (Dsv): 6.3 mm. FibroScan system testing revealed: 7.3 kPa. The results were significant.

[0108] 2. Liang, a 51-year-old female, presented to our hospital's hepatology outpatient clinic on June 3, 2018, complaining of fatigue and loss of appetite over the past six months. She had not sought medical attention or treatment during this time. A hepatitis B two-pair half-test at our hospital revealed HBsAg (positive), HBeAg (negative), and HBcAb (negative). HBV-DNA quantitative analysis: 3.23 x 10∧³. Liver function tests: ALT: 63 U / L, AST: 85 U / L, TBIL: 19.1 μmol / L. Ultrasound of the liver, gallbladder, pancreas, and spleen revealed multiple intrahepatic nodules and early-stage cirrhosis. A FibroScan system revealed 10.3 kPa. Based on the patient's medical history, symptoms, and laboratory tests, a Western medical diagnosis was made: hepatitis B with liver fibrosis. The patient was treated with one entecavir dispersible tablet daily for antiviral therapy, and 10 g of the traditional Chinese medicine compound preparation of the present invention (formula in Example 4) twice daily for liver protection and anti-fibrosis treatment. One year later, the patient showed no significant discomfort, good appetite and sleep, and normal bowel movements. Hepatitis B testing revealed HBsAg (+), HBeAg (-), and HBcAb (-). HBV-DNA quantification: (-). Liver function tests revealed ALT: 21 U / L, AST: 20 U / L, and TBIL: 10.5 μmol / L. Ultrasound examination of the liver, gallbladder, pancreas, and spleen revealed slightly increased echogenicity in the liver tissue. Testing with the FibroScan system revealed a reading of 7.6 kPa. The treatment was effective.

[0109] Comparative test of Example 7 with other formulations

[0110] The raw material composition and weight of the active ingredients of the basic formula of the traditional Chinese medicine compound preparation for treating chronic liver disease are as follows:

[0111] 30 parts of Astragalus, 15 parts of Salvia miltiorrhiza, 10 parts of Panax notoginseng, 15 parts of Curcuma zedoaria,

[0112] 15 parts of Poria cocos, 15 parts of Sargassum, 20 parts of White Peony Roots, and 15 parts of Kelp.

[0113] Case selection

[0114] Compare the therapeutic effects of the basic formula of the Chinese herbal compound preparation for treating chronic liver disease of Example 4 (formula of Implementation Plan 4) and Example 7 (formula of Implementation Plan 7).

[0115] Fifty patients, both inpatients and outpatients at our hospital between January 2016 and December 2018, were selected for group E. They were diagnosed with hepatitis B liver fibrosis, including 37 males and 13 females; the average age was 43.2 years; the disease duration ranged from 3 to 15.5 years. There were no statistically significant differences in general information (P>0.05), indicating comparability. They were given entecavir as a basic antiviral therapy combined with oral administration of the traditional Chinese medicine compound preparation of the present invention (formula in Implementation Plan 7).

[0116] (1) Changes in liver function of the two groups of patients before and after treatment are shown in Table 5.

[0117] Table 5 Comparison of changes in liver function between the two groups of patients before and after treatment

[0118]

[0119] Note: There was a statistically significant difference between group A and group E after treatment (*P<0.05)

[0120] (2) Changes in serum liver fibrosis indicators in the two groups of patients before and after treatment are shown in Table 6

[0121] Table 2 Comparison of changes in serum liver fibrosis indicators between the two groups of patients before and after treatment

[0122]

[0123] Note: There was a statistically significant difference between group A and group E after treatment (*P<0.05)

[0124] (3) Comparison of changes in liver stiffness values ​​before and after treatment in the two groups of patients is shown in Table 7.

[0125] Table 7 Comparison of LSM values ​​before and after treatment in the two groups of patients ( kPa)

[0126]

[0127] Note: There was a statistically significant difference between group A and group E after treatment (*P<0.05)

[0128] (4) The changes of Dpv, spleen thickness and Dsv in the two groups before and after treatment are shown in Table 7

[0129] Table 7 Changes of Dpv, spleen thickness and Dsv in the two groups of patients before and after treatment

[0130]

[0131] Note: There was a statistically significant difference between group A and group E after treatment (*P<0.05)

[0132] Results: The Chinese herbal compound preparation of the present invention (formula in implementation plan 4) had better therapeutic effect than the Chinese herbal compound preparation (formula in implementation plan 7). There were significant differences between the two groups in terms of liver function, liver fibrosis index, LSM value, and liver, gallbladder, spleen and pancreas ultrasound value (P < 0.05).

[0133] The above description is not intended to limit the invention, and the invention is not limited to the above examples. Any changes, modifications, additions or substitutions made by a person skilled in the art within the spirit of the invention shall also fall within the scope of protection of the present invention.

Claims

1. A Chinese medicinal compound preparation for treating hepatitis B liver fibrosis, characterized in that: The raw material composition and weight proportions of the traditional Chinese medicine compound preparation are as follows: 20-40 parts of astragalus, 20-40 parts of raw oyster, 10-30 parts of polygonatum, 10-30 parts of seaweed, 10-30 parts of poria, 10-30 parts of salvia miltiorrhiza, 10-30 parts of zedoaria, 10-30 parts of raw turtle shell, 10-30 parts of kelp, 10-30 parts of phyllanthus, 10-30 parts of sophora flavescens, 5-20 parts of bupleurum, 5-20 parts of cyperus rotundus, 5-20 parts of vinegar corydalis, and 5-20 parts of panax notoginseng.

2. The Chinese medicine compound preparation according to claim 1, characterized in that The raw material composition and weight proportions of the traditional Chinese medicine compound preparation are as follows: 30 parts of astragalus, 30 parts of raw oyster, 20 parts of polygonatum, 15 parts of seaweed, 15 parts of poria, 15 parts of salvia miltiorrhiza, 15 parts of zedoaria, 15 parts of raw turtle shell, 15 parts of kelp, 15 parts of phyllanthus urinaria, 15 parts of sophora flavescens, 10 parts of bupleurum, 10 parts of cyperus rotundus, 10 parts of vinegar corydalis, and 10 parts of panax notoginseng.

3. A method for preparing the Chinese medicine compound preparation according to any one of claims 1 to 2, characterized in that: The method comprises the following process steps: (1) preparing 15 kinds of medicinal materials according to the weight ratio; (2) mixing and crushing the six medicinal materials, namely, astragalus, salvia miltiorrhiza, zedoaria, cyperus rotundus, vinegar corydalis, and Panax notoginseng, into powder using a universal crusher, then mixing evenly using a trough mixer and passing through a 100-mesh sieve; (3) adding 10 times the amount of water to the nine medicinal materials, namely, raw oyster, polygonatum, seaweed, poria, raw turtle shell, kelp, phyllanthus urinaria, sophora flavescens, and bupleurum, and boiling them twice, the first time for 1.5 hours and the second time for 1.0 hours, and then combining them; The decoction is filtered, and the filtrate is concentrated into a thick paste having a relative density of 1.30 to 1.35 at 60° C.; (4) the fine powder obtained in step (2) and the thick paste obtained in step (3) are mixed uniformly with a trough mixer, and pellets are made using a fully automatic speed-controlled Chinese medicine pill making machine, polished, dried in a hot air circulation oven, and bottled; the Chinese medicine compound preparation prepared by the method is a pill; when making the pills in step (4), each 10 pills weigh 0.39 g; and when bottled in step (4), the weight is 120 g per bottle.

4. Use of the Chinese medicinal compound preparation according to any one of claims 1 to 2 in the preparation of a medicament for treating hepatitis B liver fibrosis.

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