阅读说明：本技术 保肝中药组合物及其提取物和制药用途 (Liver-protecting traditional Chinese medicine composition, extract and pharmaceutical application thereof ) 是由 高月求 单俊杰 孙学华 李曼 陈彦旭 周振华 高亚婷 麻浩 张鑫 徐锐 聂丹 于 2018-08-03 设计创作，主要内容包括：本申请涉及保肝中药组合物及其提取物和制药用途。其中,所述中药组合物含有以下组分：巴戟天、灵芝、黄芪、猫爪草、苦参和丹参。所述中药组合物及其提取物具有抗肝损伤和免疫调节的作用,可用于治疗肝脏疾病,例如慢性乙型肝炎、非酒精性脂肪性肝炎、酒精性脂肪性肝炎、肝纤维化、代偿期肝硬化、肝癌(尤其是慢性乙型肝炎导致的原发性肝癌)及药物或毒物等引发的肝损伤,也可用作疫苗佐剂或免疫调节剂。(The application relates to a liver-protecting traditional Chinese medicine composition, an extract and a pharmaceutical application thereof. Wherein, the traditional Chinese medicine composition comprises the following components: morinda officinalis, Ganoderma lucidum, Astragalus membranaceus, Ranunculus ternatus, Sophora flavescens and Salvia miltiorrhiza. The Chinese medicinal composition and the extract thereof have the effects of resisting liver injury and regulating immunity, can be used for treating liver diseases, such as chronic hepatitis B, non-alcoholic steatohepatitis, hepatic fibrosis, compensatory liver cirrhosis, liver cancer (especially primary liver cancer caused by chronic hepatitis B) and liver injury caused by medicaments or poisons, and can also be used as vaccine adjuvants or immunomodulators.)

1. A traditional Chinese medicine composition comprises the following components: morinda officinalis, Ganoderma lucidum, Astragalus membranaceus, Ranunculus ternatus, Sophora flavescens and Salvia miltiorrhiza.

2. The traditional Chinese medicine composition of claim 1, wherein the weight ratio of each component is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis and 10-20 parts of salvia miltiorrhiza;

preferably, the weight ratio of each component is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 15 parts of radix sophorae flavescentis and 15 parts of salvia miltiorrhiza.

3. A Chinese medicinal composition according to claim 1 or 2, which further comprises one or more (e.g. 2-10, such as 2-6, such as 2, 3, 4, 5 or 6) of the following components: herba Epimedii, rehmanniae radix, Atractylodis rhizoma, pericarpium Citri Reticulatae viride, herba Sedi, radix Puerariae, semen Hoveniae, flos Puerariae Lobatae, herba Lycopi, rhizoma Wenyujin Concisa, carapax Trionycis preparata, herba Dendrobii, Pseudobulbus Cremastrae Seu pleiones, herba abri, Curcumae rhizoma and herba Scutellariae Barbatae;

preferably, the traditional Chinese medicine composition further comprises the following components: herba Epimedii, rehmanniae radix, Atractylodis rhizoma and pericarpium Citri Reticulatae viride; further preferably, the weight ratio of each component is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 10-30 parts of herba epimedii, 5-15 parts of rehmannia, 10-30 parts of bighead atractylodes rhizome and 5-10 parts of pericarpium citri reticulatae viride; further preferably, the weight ratio of each component is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 15 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 15 parts of herba epimedii, 10 parts of rehmannia, 15-30 parts of bighead atractylodes rhizome and 9-10 parts of pericarpium citri reticulatae viride;

preferably, the traditional Chinese medicine composition further comprises the following components: stringy stonecrop herb and kudzuvine root; further preferably, the weight ratio of each component is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 15-30 parts of stringy stonecrop herb and 15-30 parts of kudzu root; further preferably, the weight ratio of each component is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 10 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 30 parts of stringy stonecrop herb and 30 parts of radix puerariae;

preferably, the traditional Chinese medicine composition further comprises the following components: herba Sedi, radix Puerariae, semen Hoveniae and flos Puerariae Lobatae; further preferably, the weight ratio of each component is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 15-30 parts of stringy stonecrop herb, 15-30 parts of radix puerariae, 15-30 parts of hovenia dulcis thunb and 10-20 parts of pueraria flowers; further preferably, the weight ratio of each component is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 10 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 30 parts of stringy stonecrop herb, 30 parts of radix puerariae, 30 parts of hovenia dulcis thunb and 15 parts of pueraria flower;

preferably, the traditional Chinese medicine composition further comprises the following components: herba Lycopi, rhizoma Wenyujin Concisa, carapax Trionycis preparata and herba Dendrobii; further preferably, the weight ratio of each component is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 10-20 parts of herba lycopi, 10-20 parts of rhizoma curcumae longae, 10-20 parts of roasted turtle shell and 10-20 parts of dendrobium nobile; further preferably, the weight ratio of each component is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 10 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 15 parts of herba lycopi, 15 parts of rhizoma curcumae longae, 15 parts of roasted turtle shell and 15 parts of dendrobium;

preferably, the traditional Chinese medicine composition further comprises the following components: pseudobulbus Cremastrae Seu pleiones, herba abri, Curcumae rhizoma, Atractylodis rhizoma and herba Scutellariae Barbatae; further preferably, the weight ratio of each component is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 5-10 parts of edible tulip, 15-30 parts of abrus cantoniensis hance, 5-10 parts of curcuma zedoary, 20-30 parts of bighead atractylodes rhizome and 10-20 parts of sculellaria barbata; further preferably, the weight ratio of each component is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 10 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 6 parts of edible tulip, 15 parts of abrus cantoniensis hance, 6 parts of curcuma zedoary, 15 parts of bighead atractylodes rhizome and 15 parts of sculellaria barbata.

4. A traditional Chinese medicine extract A is prepared by the following method:

mixing the components of the Chinese medicinal composition defined in any one of claims 1-3, and decocting in water to obtain a water decoction; preferably, the volume of water added is 5-20 times (in L: Kg) the weight of the components (e.g., 5, 10, 15 or 20 times);

concentrating the water decoction to obtain a concentrated solution, namely the traditional Chinese medicine extract A;

preferably, before decocting with water, the method also comprises the step of crushing the components; further preferably, after the pulverization, a step of sieving (for example, a 20-mesh sieve) is further included;

preferably, before concentration, the method further comprises the step of filtering and/or centrifuging the water decoction;

preferably, the method further comprises the step of drying (e.g. freeze drying) the concentrate.

5. A traditional Chinese medicine extract B is prepared by the following method:

adding ethanol into the concentrated solution defined in claim 4, standing for precipitation for 12-72h (such as 12h, 24h, 36h, 48h or 72 h); preferably, the volume of ethanol added is 1-10 times (e.g., 2, 3, 5, 8, or 10 times) the volume of the concentrate;

collecting supernatant, and concentrating to obtain the Chinese medicinal extract B;

preferably, a centrifugation step is further included before collecting the supernatant after standing and precipitating;

preferably, after concentration, a drying step is also included.

6. A traditional Chinese medicine extract C is prepared by the following method:

adding ethanol into the concentrated solution defined in claim 4, standing for precipitation for 12-72h (such as 12h, 24h, 36h, 48h or 72 h); preferably, the volume of ethanol added is 1-10 times (e.g., 2, 3, 5, 8, or 10 times) the volume of the concentrate;

collecting precipitate, dissolving in water (total volume of water is 1-3 times (L: Kg) of the weight of the medicinal materials), dialyzing the part with molecular weight cutoff of more than 1000Da, and concentrating to obtain Chinese medicinal extract B;

preferably, after concentration, a drying step is also included.

7. A pharmaceutical composition comprising a herbal composition according to any one of claims 1-3 or a herbal extract according to any one of claims 4-6, and optionally one or more pharmaceutically acceptable carriers or excipients;

preferably, it is in the form of decoction, oral liquid, medicated tea, medicated wine, granule, tablet, capsule, powder, pill or extract.

8. An adjuvant or immunomodulator comprising a Chinese medicinal composition according to any of claims 1 to 3, a Chinese medicinal extract according to any of claims 4 to 6 or a pharmaceutical composition according to claim 7.

9. A combination comprising a herbal composition according to any one of claims 1 to 3, a herbal extract according to any one of claims 4 to 6 or a pharmaceutical composition according to claim 7, and one or more antiviral agents; preferably, the antiviral drug is a nucleoside antiviral drug; preferably, the antiviral drug is selected from entecavir, tenofovir, telbivudine, adefovir and lamivudine, preferably entecavir.

10. Use of a Chinese medicinal composition according to any one of claims 1 to 3, a Chinese medicinal extract according to any one of claims 4 to 6, a pharmaceutical composition according to claim 7 or a combination according to claim 9 in the manufacture of a medicament for the treatment of liver injury or liver disease;

preferably, the liver disease is selected from chronic hepatitis (e.g. chronic hepatitis b), non-alcoholic steatohepatitis, liver fibrosis, compensatory cirrhosis, liver cancer (especially primary liver cancer caused by chronic hepatitis b);

preferably, the liver injury is drug or poison induced liver injury.

11. Use of a Chinese medicinal composition according to any one of claims 1 to 3, a Chinese medicinal extract according to any one of claims 4 to 6 or a pharmaceutical composition according to claim 7 as an adjuvant or immunomodulator.

Technical Field

The application relates to the field of traditional Chinese medicines, in particular to a traditional Chinese medicine composition with effects of resisting liver injury and regulating immunity, which mainly comprises morinda officinalis, lucid ganoderma, astragalus membranaceus, ternate buttercup root, radix sophorae flavescentis and salvia miltiorrhiza. The Chinese medicinal composition can be used for treating liver diseases, such as chronic hepatitis B, non-alcoholic steatohepatitis, hepatic fibrosis, compensatory cirrhosis or liver cancer (especially primary liver cancer caused by chronic hepatitis B), and can also be used as a vaccine adjuvant or immunomodulator.

Background

The liver is an important organ for maintaining metabolism of a human body, and plays an important role in various physiological functions such as biosynthesis, biotransformation, detoxification, secretion, immunity and the like. However, when the liver is infected by virus, poisons, careless administration, bad eating habits or other pathogenic reasons, liver damage such as viral hepatitis, non-alcoholic and alcoholic liver diseases, liver fibrosis, liver cirrhosis, liver cancer, drug hepatitis and the like may result in liver damage caused by liver function impairment.

According to traditional Chinese medicine, the liver belongs to one of five internal organs, and the main physiological functions of the liver are blood storage, qi dispersion, tendon and claw governing, eyes opening, and gallbladder exterior and interior. The liver stores blood and regulates blood volume, and the article on Su Wen & Wuzang Generation states that the lying blood of the deceased belongs to the liver, the liver can be seen by blood, the feet can move and the palm can be held by blood, and the fingers can be taken by blood. Pathologically, such as liver blood deficiency and liver failure to store blood, frequent symptoms of tiredness, hypodynamia, fatigue intolerance, binocular dryness, blurred vision, hematemesis, hematochezia, epistaxis, etc. The liver governs smoothing flow of qi and blood, and regulates qi and blood, so as to ensure the normal operation of viscera. If the liver qi is depressed and the qi movement is not smooth, qi stagnation and blood stasis occur; the digestive and absorptive functions of the spleen and stomach are closely related to the function of the liver to dredge and discharge. For example, liver qi failing to regulate and discharge can affect the digestion of spleen and stomach, resulting in the occurrence of the pathological changes of dyspepsia. Except for symptoms of liver-qi depression such as distending pain in chest and hypochondrium, irritability and the like, symptoms of eructation, nausea, vomiting, abdominal distension and diarrhea are often caused. The liver and gallbladder are in exterior-interior relationship, and whether the function of liver smoothing flow is normal or not directly affects the secretion and excretion of bile, if it is normal, bile circulates normally; on the contrary, bile may flow upwards or overflow to cause pathological changes, such as bitter taste in mouth and jaundice. Liver stores blood and kidney stores essence, liver blood depends on the nourishment of kidney essence, kidney essence is continuously filled with essence transformed from liver blood, and essence and blood are bred mutually, so the theory of homology of liver and kidney is provided. Pathologically, the pathological changes of kidney essence and liver blood often affect each other, such as kidney essence deficiency, which can cause liver blood deficiency; deficiency of liver blood can also cause kidney essence deficiency, and symptoms such as soreness and pain of waist and back, spermatorrhea, tinnitus, blurred vision, dizziness and dry eyes can occur. When liver yang is hyperactivity or liver fire is hyperactivity, kidney yin can be exhausted, resulting in kidney yin deficiency. Ascending, descending, transportation and transformation of the spleen and stomach depend on the function of liver qi to regulate and drain. The liver stores blood, the spleen governs blood and governs transportation and transformation to become the source of qi and blood generation, and the liver and spleen coordinate with each other to complete normal blood circulation. In the pathological aspect, if the liver qi stagnation and the flow of qi are disturbed, the ascending, descending, transporting and transforming functions of the spleen and stomach are impaired, the symptoms will appear: "disharmony between liver and stomach"; the syndrome of disharmony between the liver and spleen. After qi generation, fullness in chest and hypochondrium, abdominal distention, anorexia, nausea, vomiting, lassitude, asthenia and abnormal stool are common in clinic. Conversely, spleen disease also affects the liver. For example, spleen-qi deficiency, blood deficiency and source of transformation; or spleen failing to control blood and losing excessive blood, resulting in liver blood deficiency. For instance, spleen failing to transport and water retention may cause retention of dampness and heat in the body, which may lead to jaundice due to stagnation of damp-heat in the liver and gallbladder. Therefore, liver diseases transmitting spleen, spleen diseases and liver, liver and spleen two organs are affected each other pathologically. Heart governs blood, liver stores blood, blood vessels are full, heart governs blood and liver stores blood. The liver qi develops and the lung qi descends, which cooperate with each other to maintain the normal function of qi. In conclusion, the liver and gallbladder are connected, the spleen and stomach are communicated, the upper part is the heart and lung, the lower part is the kidney water, the triple energizer is unobstructed, and people can calm the liver, so that modern students can study the treatment method of liver diseases, focus on conditioning the spleen and stomach, nourish water and wood, smoothen qi activity and regulate yin and yang, and the aim of curing the liver diseases can be achieved.

According to the traditional Chinese medicine, exogenous damp-heat or epidemic toxin, internal injury, emotion, diet, overstrain and the like are main causes of chronic liver diseases, the disease location of the chronic liver diseases is mainly in the liver, and the chronic liver diseases usually relate to spleen and kidney, gallbladder, stomach, triple energizer and other internal organs. The nature of the disease is marked by deficiency and excess, and the nature is mixed with deficiency and excess. Because the etiology, pathogenesis, location and disease nature of chronic liver disease are complicated and changeable, and the condition of chronic liver disease is difficult to heal, the relationship between the excess pathogenic factors of dampness, heat, stasis and toxin and the deficiency of the healthy qi of liver, spleen and kidney should be distinguished, so that people should be concerned during treatment, the body resistance can be correctly treated, the pathogenic factors can be eliminated, and the balance of yin and yang, qi and blood and the functions of viscera can be mainly adjusted.

Under the guidance of the theory of traditional Chinese medicine, the inventor proves that the kidney tonifying, spleen strengthening, dampness removing and blood circulation invigorating are basic treatment methods for treating chronic hepatitis B, non-alcoholic steatohepatitis, hepatic fibrosis (compensatory cirrhosis), primary liver cancer caused by hepatitis B and other chronic liver diseases through long-term clinical and modern pharmacological research, so that the traditional Chinese medicine composition is obtained, and the application is completed.

Disclosure of Invention

Thus, in one aspect, the present application provides a Chinese medicinal composition comprising the following components: morinda officinalis, Ganoderma lucidum, Astragalus membranaceus, Ranunculus ternatus, Sophora flavescens and Salvia miltiorrhiza. In some preferred embodiments, the weight ratio of the components is: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis and 10-20 parts of salvia miltiorrhiza. In some preferred embodiments, the weight ratio of the components is: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 15 parts of radix sophorae flavescentis and 15 parts of salvia miltiorrhiza.

In the prescription, the morinda officinalis is used as a monarch drug for warming yang, tonifying kidney and tonifying kidney yin; the lucid ganoderma and the astragalus are used as ministers to tonify qi and strengthen spleen, and the liver and kidney are tonified simultaneously, the innate and the acquired are harmonized simultaneously, and the spleen and the kidney are tonified simultaneously; radix sophorae flavescentis and radix ranunculi ternati are used for assisting in clearing heat, promoting diuresis and detoxifying so as to eliminate remaining pathogens; the salvia miltiorrhiza is used for promoting qi and blood circulation and guiding the drugs to the meridians. The whole formula is combined, the kidney and the spleen are used as the basis for treating diseases, the heat clearing and the dampness removing are used as the targets for treating the diseases, the symptoms and root causes are treated, the qi circulation and the blood circulation are both considered, the constitution is fixed, the vitality is restored, the damp toxin is cleared, the diseases are relieved, and the diseases are cured.

In certain preferred embodiments, the Chinese medicinal composition further comprises one or more (e.g., 2-10, e.g., 2-6, e.g., 2, 3, 4, 5, or 6) of the following components: herba Epimedii, rehmanniae radix, Atractylodis rhizoma, pericarpium Citri Reticulatae viride, herba Sedi, radix Puerariae, semen Hoveniae, flos Puerariae Lobatae, herba Lycopi, rhizoma Wenyujin Concisa, carapax Trionycis preparata, herba Dendrobii, Pseudobulbus Cremastrae Seu pleiones, herba abri, Curcumae rhizoma and herba Scutellariae Barbatae.

In certain preferred embodiments, the Chinese medicinal composition further comprises the following components: herba Epimedii, rehmanniae radix, Atractylodis rhizoma and pericarpium Citri Reticulatae viride. In some preferred embodiments, the weight ratio of the components is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 10-30 parts of herba epimedii, 5-15 parts of rehmannia, 10-30 parts of bighead atractylodes rhizome and 5-10 parts of pericarpium citri reticulatae viride. In some preferred embodiments, the weight ratio of the components is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 15 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 15 parts of herba epimedii, 10 parts of rehmannia, 15-30 parts of bighead atractylodes rhizome and 9-10 parts of pericarpium citri reticulatae viride.

Pharmacological research proves that the preparation can obviously improve symptoms of Balb/C liver injury model mouse liver swelling caused by ConA and LPS, inhibit hepatocyte necrosis and inflammatory cell aggregation, increase division and proliferation of hepatocytes, obviously promote hepatocyte proliferation, and effectively inhibit secretion of hepatitis B virus antigens HBsAg and HBeAg, has obvious immunoregulation effect, for example, has obvious proliferation promoting activity on splenocytes of mice, can promote proliferation of T cells and B cells, and can promote splenocytes of mice to secrete IFN-gamma and TNF- α.

In certain preferred embodiments, the Chinese medicinal composition further comprises the following components: herba Sedi and radix Puerariae. In some preferred embodiments, the weight ratio of the components is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 15-30 parts of stringy stonecrop herb and 15-30 parts of kudzu root. In some preferred embodiments, the weight ratio of the components is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 10 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 30 parts of stringy stonecrop herb and 30 parts of radix puerariae.

Pharmacological research shows that the preparation can promote liver cell proliferation, has obvious immunoregulation effect, for example, has obvious proliferation promoting activity on mouse spleen cells, and can promote proliferation of T cells and B cells. In clinical tests, the prescription can obviously improve the liver function of a patient with nonalcoholic steatohepatitis, reduce the blood fat level and improve the liver/spleen CT value grading. Can be used for treating liver diseases (such as nonalcoholic steatohepatitis) and liver injury (especially drug or poison induced liver injury), and can be used as immunological adjuvant or immunomodulator.

In certain preferred embodiments, the Chinese medicinal composition further comprises the following components: herba Sedi, radix Puerariae, semen Hoveniae and flos Puerariae Lobatae. In some preferred embodiments, the weight ratio of the components is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 15-30 parts of stringy stonecrop herb, 15-30 parts of radix puerariae, 15-30 parts of hovenia dulcis thunb and 10-20 parts of pueraria flowers. In some preferred embodiments, the weight ratio of the components is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 10 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 30 parts of stringy stonecrop herb, 30 parts of radix puerariae, 30 parts of hovenia dulcis thunb and 15 parts of pueraria flowers.

Pharmacological research shows that the preparation can promote liver cell proliferation, has obvious immunoregulation effect, for example, has obvious proliferation promoting activity on mouse spleen cells, and can promote proliferation of T cells and B cells. In clinical tests, the traditional Chinese medicine composition can obviously reduce ALT, AST, GGT and total cholesterol levels of patients with alcoholic steatohepatitis, and obviously improve symptoms of weakness, anorexia and the like in traditional Chinese medicine symptoms. Can be used for treating liver diseases (such as alcoholic fatty hepatitis) and liver injury (especially liver injury caused by drug or poison), and can be used as immunological adjuvant or immunomodulator.

In certain preferred embodiments, the Chinese medicinal composition further comprises the following components: herba Lycopi, rhizoma Wenyujin Concisa, carapax Trionycis preparata, and herba Dendrobii. In some preferred embodiments, the weight ratio of the components is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 10-20 parts of herba lycopi, 10-20 parts of rhizoma curcumae longae, 10-20 parts of roasted turtle shell and 10-20 parts of dendrobium. In some preferred embodiments, the weight ratio of the components is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 10 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 15 parts of herba lycopi, 15 parts of rhizoma curcumae longae, 15 parts of roasted turtle shell and 15 parts of dendrobium.

Pharmacological research shows that the preparation can promote liver cell proliferation, has obvious immunoregulation effect, for example, has obvious proliferation promoting activity on mouse spleen cells, and can promote proliferation of T cells and B cells. In clinical tests, the HBeAg level of a hepatic fibrosis patient can be obviously reduced, and the fatty inflammation grading is improved. In addition, the CTP score of patients with hepatitis B cirrhosis in the compensation stage can be obviously reduced, and the CLDQ score is improved. Can be used for treating liver diseases (such as hepatic fibrosis and liver cirrhosis compensation period) and liver injury (especially drug or toxic induced liver injury), and can be used as immunologic adjuvant or immunomodulator.

In certain preferred embodiments, the Chinese medicinal composition further comprises the following components: pseudobulbus Cremastrae Seu pleiones, herba abri, Curcumae rhizoma, Atractylodis rhizoma and herba Scutellariae Barbatae. In some preferred embodiments, the weight ratio of the components is as follows: 15-35 parts of morinda officinalis, 10-20 parts of lucid ganoderma, 25-35 parts of astragalus membranaceus, 10-20 parts of ternate buttercup root, 10-20 parts of radix sophorae flavescentis, 10-20 parts of salvia miltiorrhiza, 5-10 parts of edible tulip, 15-30 parts of abrus cantoniensis hance, 5-10 parts of curcuma zedoary, 20-30 parts of bighead atractylodes rhizome and 10-20 parts of sculellaria barbata. In some preferred embodiments, the weight ratio of the components is as follows: 30 parts of morinda officinalis, 15 parts of lucid ganoderma, 30 parts of astragalus membranaceus, 15 parts of ternate buttercup root, 10 parts of radix sophorae flavescentis, 15 parts of salvia miltiorrhiza, 6 parts of edible tulip, 15 parts of abrus cantoniensis hance, 6 parts of curcuma zedoary, 15 parts of bighead atractylodes rhizome and 15 parts of sculellaria barbata.

Pharmacological research shows that the preparation can promote liver cell proliferation, has obvious immunoregulation effect, for example, has obvious proliferation promoting activity on mouse spleen cells, and can promote proliferation of T cells and B cells. In clinical tests, the prescription can remarkably prolong the life cycle of patients with primary liver cancer, reduce the recurrence rate and improve the main traditional Chinese medicine symptoms of the patients after primary liver cancer operation. Can be used for treating liver diseases (such as liver cancer, especially primary liver cancer caused by chronic hepatitis B) and liver injury (especially liver injury caused by drug or poison), and can be used as immunological adjuvant or immunomodulator.

In another aspect, the present application provides a herbal extract a, which is prepared by the following method:

mixing the above Chinese medicinal materials, and decocting in water to obtain decoction;

and concentrating the water decoction to obtain a concentrated solution, namely the traditional Chinese medicine extract A.

In certain preferred embodiments, the volume of water added is 5-20 times (in L: Kg) the weight of the component (e.g., 5, 10, 15, or 20 times).

In certain preferred embodiments, the method further comprises the step of comminuting the components prior to decocting in water.

In certain preferred embodiments, after comminution, a sieving (e.g., 20 mesh) step is also included.

In certain preferred embodiments, the method further comprises the step of filtering and/or centrifuging the water decoction prior to concentration.

In certain preferred embodiments, the method further comprises the step of drying (e.g., freeze drying) the concentrate.

In another aspect, the present application provides a chinese herbal extract B, which is prepared by the following method:

adding ethanol into the concentrated solution, standing and precipitating for 12-72h (such as 12h, 24h, 36h, 48h or 72 h);

collecting supernatant, and concentrating to obtain the Chinese medicinal extract B.

In certain preferred embodiments, the volume of ethanol added is 1 to 10 times (in L: Kg) the volume of the concentrate (e.g., 2, 3, 5, 8, or 10 times).

In certain preferred embodiments, a centrifugation step is included after the standing pellet and before the supernatant is collected.

In certain preferred embodiments, after concentration, a drying step is also included.

In another aspect, the present application provides a chinese herbal extract C, which is prepared by the following method:

adding ethanol into the concentrated solution, standing and precipitating for 12-72h (such as 12h, 24h, 36h, 48h or 72 h);

collecting precipitate, dissolving in water for several times, dialyzing the part with cut-off molecular weight greater than 1000Da, and concentrating to obtain the Chinese medicinal extract B.

In certain preferred embodiments, the volume of ethanol added is 1-10 times (e.g., 2, 3, 5, 8, or 10 times) the volume of the concentrate.

In certain preferred embodiments, the total volume of water added is 1-3 times the weight of the herb (in L: kg)).

In certain preferred embodiments, after concentration, a drying step is also included.

In another aspect, the present application provides a pharmaceutical composition comprising the aforementioned herbal composition or herbal extract, and optionally one or more pharmaceutically acceptable carriers or excipients.

The pharmaceutically acceptable carrier refers to a diluent, adjuvant, excipient, or vehicle with which the therapeutic agent is administered and which is, within the scope of sound medical judgment, suitable for contact with the tissues of humans and/or other animals without excessive toxicity, irritation, allergic response, or other problem or complication commensurate with a reasonable benefit/risk ratio.

Pharmaceutically acceptable carriers that may be employed in the pharmaceutical compositions of the present application include, but are not limited to, sterile liquids, such as water and oils, including those of petroleum, animal, vegetable or synthetic origin, such as peanut oil, soybean oil, mineral oil, sesame oil and the like.

Water is an exemplary carrier when the pharmaceutical composition is administered intravenously. Physiological saline and aqueous dextrose and glycerol solutions can also be employed as liquid carriers, particularly for injectable solutions. Suitable pharmaceutical excipients include starch, glucose, lactose, sucrose, gelatin, maltose, chalk, silica gel, sodium stearate, glycerol monostearate, talc, sodium chloride, dried skim milk, glycerol, propylene glycol, water, ethanol and the like. The pharmaceutical composition may also optionally contain minor amounts of wetting agents, emulsifying agents, or pH buffering agents.

Oral formulations may contain standard carriers such as pharmaceutical grades of mannitol, lactose, starch, magnesium stearate, sodium saccharine, cellulose, magnesium carbonate and the like. Examples of suitable pharmaceutically acceptable carriers are described in Remington's pharmaceutical sciences (1990).

The pharmaceutical compositions of the present application may act systemically and/or locally. For this purpose, they may be administered by a suitable route, for example by injection, intravenous, intraarterial, subcutaneous, intraperitoneal, intramuscular or transdermal administration; or by oral, buccal, nasal, transmucosal, topical, in the form of ophthalmic preparations or by inhalation.

For these routes of administration, the pharmaceutical compositions of the present application may be administered in a suitable dosage form. Such dosage forms include, but are not limited to, tablets, capsules, lozenges, hard candies, decoctions, oral liquids, powders, teas, vinuses, granules, pills, extracts, sprays, creams, ointments, suppositories, gels, pastes, lotions, ointments, aqueous suspensions, injectable solutions, elixirs, syrups. In certain preferred embodiments, the pharmaceutical composition may be formulated into decoction, oral liquid, tea, wine, granule, tablet, capsule, powder, pill or extract.

In another aspect, the present application provides a combination comprising the aforementioned herbal composition, herbal extract or pharmaceutical composition, and one or more antiviral drugs.

In certain preferred embodiments, the antiviral drug is a nucleoside antiviral drug. In certain preferred embodiments, the antiviral agent is selected from the group consisting of entecavir, tenofovir, telbivudine, adefovir, and lamivudine, preferably entecavir.

In another aspect, the present application provides an adjuvant or immunomodulator comprising the aforementioned Chinese medicinal composition, Chinese medicinal extract or pharmaceutical composition.

The adjuvant refers to a substance capable of non-specifically enhancing an immune response to an antigen, which is injected into a body prior to or together with the antigen, and can enhance the immune response of the body to the antigen or change the type of immune response.

The immunomodulator is a preparation capable of regulating, balancing and recovering the immune function of an organism, and commonly used immunomodulators comprise three types of immune promoters, immune inhibitors and immune bidirectional regulators.

In another aspect, the present application provides a use of the aforementioned Chinese medicinal composition, Chinese medicinal extract, pharmaceutical composition or combination for the preparation of a medicament for treating liver injury or liver disease.

In another aspect, the present application provides the aforementioned Chinese medicinal composition, Chinese medicinal extract, pharmaceutical composition or combination for treating liver injury or liver disease.

In another aspect, the present application provides a method for treating liver injury or liver disease, comprising the step of administering to an individual in need thereof an effective amount of the aforementioned herbal composition, herbal extract, pharmaceutical composition or combination.

By effective is meant an amount of the compound that will alleviate to some extent one or more of the symptoms of the disease being treated upon administration. The dosage of the herbal composition, herbal extract or pharmaceutical composition described herein depends primarily on the severity of the subject, disorder or condition being treated, the rate of administration and the judgment of the prescribing physician. Generally, the effective dose is 130-. In some cases, dosage levels not higher than the lower limit of the aforesaid range may be sufficient, while in other cases still larger doses may be employed without causing any harmful side effects, provided that the larger dose is first divided into several smaller doses to be administered throughout the day.

By treating (treating) is meant reversing, alleviating, inhibiting the progression of, or preventing one or more symptoms of the disease or symptoms.

The subject includes a human or non-human animal. Exemplary human individuals include individuals with a disease (e.g., a disease described herein), referred to as patients, or normal individuals. Such non-human animals include all vertebrates, such as non-mammals (e.g., birds, amphibians, reptiles) and mammals, such as non-human primates, livestock, and/or domesticated animals (e.g., sheep, dogs, cats, cows, pigs, etc.).

In certain preferred embodiments, the liver disease is selected from chronic hepatitis (e.g., chronic hepatitis b), non-alcoholic steatohepatitis, liver fibrosis, compensatory liver cirrhosis, liver cancer (particularly primary liver cancer resulting from chronic hepatitis b).

In certain preferred embodiments, the liver injury is drug or poison induced liver injury.

The use of the aforementioned traditional Chinese medicine composition, traditional Chinese medicine extract or pharmaceutical composition as an adjuvant or immunomodulator.

Advantageous effects of the invention

The application provides a traditional Chinese medicine composition with effects of resisting liver injury and regulating immunity, which mainly comprises morinda officinalis, lucid ganoderma, astragalus membranaceus, ternate buttercup root, radix sophorae flavescentis and salvia miltiorrhiza. The Chinese medicinal composition has the effects of treating liver diseases, resisting liver injury and regulating immunity. Pharmacological studies have shown that, in certain preferred embodiments, the Chinese medicinal composition of the present application has significant effects of resisting liver inflammation injury and oxidative injury, promoting hepatocyte regeneration, inhibiting HBsAg and HBeAg secretion of hepatocytes, and to some extent, inhibiting hepatitis B virus replication. Can be used for treating liver diseases, such as chronic hepatitis (such as chronic hepatitis B), non-alcoholic steatohepatitis, hepatic fibrosis, compensatory liver cirrhosis or liver cancer (especially primary liver cancer caused by chronic hepatitis B), and resisting liver injury (especially drug or toxic induced liver injury), and can also be used as immunomodulator or vaccine adjuvant.

Drawings

FIG. 1 shows the pathological effect analysis of the compound dry extract prepared in example 21 on the liver injury of the ConA-induced mice.

Detailed Description

Embodiments of the present invention will be described in detail below with reference to examples, but those skilled in the art will appreciate that the following examples are only illustrative of the present invention and should not be construed as limiting the scope of the present invention. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products commercially available.