LU504091B1

LU504091B1 - Traditional chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with chb and nafld, preparation method thereof and combined therapeutic drug

Info

Publication number: LU504091B1
Application number: LU504091A
Authority: LU
Inventors: Minghao Liu
Original assignee: The First Affiliated Hospital Of Henan Univ Of Chinese Medicine
Priority date: 2023-04-27
Filing date: 2023-04-27
Publication date: 2023-10-27

Abstract

Disclosed are a traditional Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with CHB and NAFLD, a preparation method thereof and a combined therapeutic drug, to solve the technical problems of poor curative effect, mutual antagonism of drug side effects and lack of targeted treatment of patients with CHB and NAFLD in the prior art. The traditional Chinese medicine preparation is composed of Rhizoma Polygoni Cuspidati, Radix Salviae Miltiorrhizaea, Radix Curcumae, Sargassum, Fructus Crataegi, Phyllanthus urinaria and vinegar processed Radix Bupleur. The traditional Chinese medicine preparation of that invention has wide source of raw materials, low price and no toxic or side effect; the raw material components support each other and have scientific compatibility, have the effects of clearing away heat and toxic materials, eliminating phlegm and dampness, and are used for enhancing the antiviral efficacy of entecavir in patients with CHB complicated with NAFLD.

Description

DESCRIPTION LU504091

TRADITIONAL CHINESE MEDICINE PREPARATION FOR ENHANCING

ANTIVIRAL EFFICACY OF ENTECAVIR COMBINED WITH CHB AND NAFLD,

PREPARATION METHOD THEREOF AND COMBINED THERAPEUTIC DRUG

TECHNICAL FIELD

The invention relates to the technical field of drugs for treating liver diseases, and in particular to a traditional Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with CHB and NAFLD, a preparation method thereof and a combined therapeutic drug.

BACKGROUND

The incidence of Chronic hepatitis B (CHB) complicated with Nonalcoholic fatty liver disease (NAFLD) is 15%-27%, and it has an increasing trend, which is more harmful and more prone to cirrhosis than patients with CHB alone.

At present, the clinical application of nucleoside analogues in patients with simple

CHB has a good virological response. Entecavir, as a first-line drug, has a wide range of clinical applications and definite curative effects, but it has hidden dangers of aggravating liver fibrosis. Statins are the main treatment for NAFLD, and the frequent occurrence of side effects such as liver damage also limits its application in CHB complicated with NAFLD.

However, for patients with CHB complicated with NAFLD, the efficacy of the above therapies is not good, and the side effects of drugs are antagonistic to each other. Due to the existence of double liver damage causes, the use of drugs with side effects of liver damage is avoided, and the treatment of CHB complicated with NAFLD faces many challenges.

SUMMARY LU504091

The technical problem to be solved by the invention is to provide a traditional

Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with

CHB and NAFLD, a preparation method thereof and a combined therapeutic drug, so as to solve the technical problems of poor curative effect, mutual antagonism of drug side effects and lack of targeted treatment of patients with CHB and NAFLD in the prior art.

In order to solve the technical problems, the invention adopts the following technical schemes.

The invention provides a traditional Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with CHB and NAFLD, and it is prepared from the following bulk drugs in parts by weight: 13-16 parts of Rhizoma Polygoni Cuspidati, 13-16 parts of Radix Salviae

Miltiorrhizaea, 8-12 parts of Radix Curcumae, 18-22 parts of Sargassum, 13-16 parts of

Fructus Crataegi, 13-16 parts of Phyllanthus urinaria and 13-16 parts of vinegar processed Radix Bupleur.

Preferably, it is prepared from the following raw materials: parts of Rhizoma Polygoni Cuspidati, 15 parts of Radix Salviae Miltiorrhizaea, 10 parts of Radix Curcumae, 20 parts of Sargassum, 15 parts of Fructus Crataegi, 15 parts of Phyllanthus urinaria and 15 parts of vinegar processed Radix Bupleur.

The invention provides a preparation method of the traditional Chinese medicine preparation for enhancing the antiviral efficacy of entecavir combined with CHB and

NAFLD, including the following steps: (1) weighing the raw materials according to a proportion for later use; (2) distilling Radix Curcumae and vinegar processed Radix Bupleur, and collecting volatile components; (3) mixing Rhizoma Polygoni Cuspidati, Radix Salviae Miltiorrhizaea, Sargassum,

Fructus Crataegi and Phyllanthus urinaria with residues obtained in the previous step, adding water to decoct for 0. 5-1 h, filtering to obtain filtrate, adding water to decoct the filter residue again, repeating for 1-2 times, and mixing the filtrates;

(4) concentrating the filtrates obtained in the previous step under reduced pressutg)504091 into paste, drying it under reduced pressure, pulverizing it, mixing the volatile components obtained in the step (2) evenly, and making into granules; pharmaceutically acceptable drug carriers or auxiliary components may also be added as needed to improve its acceptability or commercialization. Of course, other dosage forms, such as tablet, pill, powder, decoction, etc., may also be made by using the existing technology according to the above-mentioned drug formula.

Preferably, in the step (3), an amount of water added each time is 1-2 times of a volume of the solid materials to be decocted.

Based on the research of clinical practice, it is found that patients with CHB complicated with NAFLD should reasonably choose antiviral and lipid-reducing and liver-protecting drugs according to the disease activity, course of disease and drug efficacy, that is, both antiviral and lipid-reducing and liver-protecting treatments should be taken into account. Therefore, the present invention further provides a combined therapeutic drug for CHB complicated with NAFLD, which includes, in parts by weight, 100-150 parts of the traditional Chinese medicine preparation prepared by the above method or a dosage/dosage form with equivalent active ingredients, 0.5-1 part of entecavir dispersible tablet or other dosage forms with equivalent active ingredients.

Mechanism analysis of CHB complicated with NAFLD in this invention:

CHB complicated with NAFLD is a common clinical disease, but there is no such disease name in traditional Chinese medicine classics. Based on long-term research and clinical experience, the inventor gradually realized that according to its etiology and clinical manifestations, it belongs to the categories of hypochondriac pain, liver obsession and liver addiction. The body feels the evil of damp-heat and epidemic poison, which lies in the liver collaterals, the liver body is cut down, the yin and blood are gradually consumed, and the liver body loses its softness and gradually declines. In addition, overeating of fat and sweet foods and emotional disorder lead to liver stagnation, spleen and stomach weakness, and dereliction of duty in transportation, which leads to dampness and phlegm, qi stagnation and blood stasis, and phlegm and blood stasis are intertwined in the liver, resulting in lingering illness and difficulty in healing. Therefore, "phlegm, dampness, heat and poison" are the basic pathologicbl504091 characteristics of this disease. Based on this, it is believed that its treatment should be "clearing away heat and toxic materials, resolving phlegm and eliminating dampness" to help clear away "epidemic poison".

Principles of syndrome differentiation and prescription of traditional Chinese medicine preparation of the present invention: in view of the fact that a large number of fat droplets in CHB combined with NAFLD are deposited in hepatocytes, which affects the therapeutic effect of antiviral drugs and reduces the antiviral effect of entecavir, it is necessary to improve the degree of liver steatosis and treat NAFLD at the same time of antiviral treatment. The pathogenesis of

NAFLD is that phlegm, dampness and blood stasis are combined in the liver, and the treatment should be combined with eliminating phlegm and dampness, and promoting blood circulation. The pathogenesis of CHB complicated with NAFLD is that phlegm, dampness, heat and toxin are combined in the liver, and the treatment should be to clear away heat and toxic materials, eliminate phlegm and eliminate dampness. There are significant differences between the two treatments. Therefore, on the basis of treating the original prescription of NAFLD (China invention patent document CN102106992B), the invention re-composes the prescription according to the pathogenesis of CHB complicated with NAFLD:

Rhizoma Polygoni Cuspidati is added to clear away heat and promote diuresis, and

Rhizoma Alismatis that is only beneficial to disinhibit water and percolate dampness is removed; Phyllanthus urinaria with strong heat-clearing and detoxicating effects is added, and Semen Cassiae and Silybum marianum with weak liver-clearing effects are removed; the dosage of Sargassum is increased to strengthen the effect of eliminating phlegm; the liver heat of this disease is obvious, and the catharsis effect of Radix Bupleur is too strong, which is easy to produce dry fire and aggravate liver heat. However, after the

Radix Bupleur is treated with vinegar, its catharsis is reduced, and the sour taste relates to the liver meridian, so the dose is slightly increased to strengthen the effect of introducing meridians. The taste of Radix Curcumae is pungent, so it should be slightly reduced, so as to avoid its pungent dispersing and activating qi too much, which will tutrt/504091 fire into yin.

Therefore, the prescription is composed of Rhizoma Polygoni Cuspidati, Radix

Salviae Miltiorrhizaea, Radix Curcumae, Sargassum, Fructus Crataegi, Phyllanthus urinaria and vinegar processed Radix Bupleur. In the prescription, hizoma Polygoni

Cuspidati may clear away heat and promote diuresis, Radix Salviae Miltiorrhizaea may promote blood circulation and remove blood stasis, cool blood and calm nerves, and they are both sovereign drugs; Radix Curcumae promotes blood circulation to relieve pain, promotes qi circulation to relieve depression, and Sargassum eliminates phlegm, promotes diuresis, softens hardness and eliminates phlegm, and all of them are minister drugs; Fructus Crataegi dispels stagnation and removes blood stasis, and Phyllanthus urinaria clears away heat and detoxifies, which are all assistant drugs; vinegar processed Radix Bupleur soothes the liver and regulates qi, and introduces medicine into the liver meridian as envoy drugs.

Among the above raw materials:

Rhizoma Polygoni Cuspidati: the fibrous roots are removed, washed, sliced and dried in the sun; it is used for clearing heat and promoting diuresis, eliminating phlegm and removing blood stasis.

Radix Salviae Miltiorrhizaea: the fibrous roots and soil of it are removed and it is dried in the sun, and it has the effects of promoting blood circulation, regulating menstruation, cooling blood, eliminating carbuncle and calming the nerves.

Radix Curcumae: the fibrous roots of it is removed and it is dried in the sun; it has the effects of promoting blood circulation, promoting qi circulation, relieving pain, relieving depression, clearing heart, benefiting gallbladder, relieving jaundice and cooling blood.

Sargassum: impurities are removed from the Sargassum, then it is rinsed the slightly with water, slightly aired, cut into sections, and dried in the sun; It has the effects of softening and hardening, eliminating phlegm, promoting diuresis and relieving swelling.

Fructus Crataegi: it is cleaned, sliced and dried; it has the effects of promotirig/504091 digestion, promoting qi circulation and removing blood stasis.

Phyllanthus urinaria: impurities are removed from it, then it is washed clean, slightly moistened until soft, cut into sections, and dried in the sun; It has the effects of clearing away heat and toxic materials, invigorating spleen and resolving food stagnation, clearing liver and improving eyesight.

Vinegar processed Radix Bupleur.

Radix Bupleur slices are mixed with vinegar, stir-fried with slow fire until the vinegar is completely absorbed and slightly dried, and dried in the sun; it has the effects of dispersing fever, soothing the liver, relieving depression, rising yang and lifting depression.

Compared with the prior art, the invention has the following main beneficial technical effects. 1. The prescription of the traditional Chinese medicine preparation is scientific, and the raw material components support each other, so that the traditional Chinese medicine preparation has the effects of clearing away heat and toxic materials, eliminating phlegm and eliminating dampness, is used for enhancing the antiviral efficacy of entecavir in patients with CHB complicated with NAFLD, and has achieved good results through clinical application. 2. The traditional Chinese medicine preparation of that invention has wide source of raw materials, low price and no toxic or side effect; clinical research shows that it may promote the antiviral effect of entecavir in CHB and NAFLD. 3. The combined therapeutic drug of the invention combines Chinese and western medicines, complements each other, has obvious curative effect, low treatment cost and is easily accepted by patients.

BRIEF DESCRIPTION OF THE FIGURES LU504091

FIG. 1 is a comparison chart of ALT levels of two groups of patients before and after treatment.

FIG. 2 is a comparison chart of AST levels of two groups of patients before and after treatment.

FIG. 3 is a comparison chart of TG levels of two groups of patients before and after treatment.

FIG. 4 is a comparison chart of GLU levels of two groups of patients before and after treatment.

FIG. 5 is a comparison chart of CAP levels of two groups of patients before and after treatment.

FIG. 6 is a comparison chart of FFA levels of two groups of patients before and after treatment.

FIG. 7 is a comparison chart of HBV-DNA levels of two groups of patients before and after treatment.

DESCRIPTION OF THE INVENTION

Specific embodiments of the present invention will be described below with reference to the drawings and embodiments, but the following embodiments are only used to illustrate the present invention in detail and do not limit the scope of the present invention in any way.

Unless otherwise specified, the instruments and equipment involved in the following embodiments are all conventional instruments and equipment. Unless otherwise specified, the reagents involved are all conventional reagents on the market. Unless otherwise specified, the test methods involved are all conventional methods.

Embodiment 1 A traditional Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with CHB and NAFLD

It is prepared from the following medicines: 15 Kg of Rhizoma Polygoni CuspidatiJ504091

Kg of Radix Salviae Miltiorrhizaea, 10 Kg of Radix Curcumae, 20 Kg of Sargassum, 15 Kg of Fructus Crataegi, 15 Kg of Phyllanthus urinaria and 15 Kg of vinegar processed

Radix Bupleur.

Its preparation method is as follows: (1) weighing the raw materials according to a proportion for later use; (2) distilling Radix Curcumae and vinegar processed Radix Bupleur, and collecting volatile components; (3) mixing Rhizoma Polygoni Cuspidati, Radix Salviae Miltiorrhizaea, Sargassum,

Fructus Crataegi and Phyllanthus urinaria with residues obtained in the previous step, adding water to decoct for 0. 5-1 h, filtering to obtain filtrate, adding water to decoct the filter residue again, repeating for 1-2 times, and mixing the filtrates; (4) concentrating the filtrates obtained in the previous step under reduced pressure into paste, drying it under reduced pressure, pulverizing it, mixing the volatile components obtained in the step (2) evenly, and making into granules.

Embodiment 2 A traditional Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with CHB and NAFLD

The difference from Embodiment 1 is that: it is prepared from the following medicines: 14 Kg of Rhizoma Polygoni Cuspidati, 16 Kg of Radix Salviae Miltiorrhizaea, 9 Kg of Radix Curcumae, 22 Kg of Sargassum, 14

Kg of Fructus Crataegi, 16 Kg of Phyllanthus urinaria and 13 Kg of vinegar processed

Radix Bupleur.

Embodiment 3 A traditional Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with CHB and NAFLD

The difference from Embodiment 1 is that: it is prepared from the following medicines: 16 Kg of Rhizoma Polygoni Cuspidati, 13 Kg of Radix Salviae Miltiorrhizaea, 11 Kg of Radix Curcumae, 18 Kg of Sargassum, 15 Kg of Fructus Crataegi, 13 Kg of Phyllanthus urinaria and 16 Kg of vinegar processed

Radix Bupleur.

Clinical trial cases

1. Criteria for selecting patient cases LU504091

All patients diagnosed with chronic hepatitis B combined with nonalcoholic fatty liver disease are regarded as the criteria for selecting cases.

Among them, the diagnostic criteria are as follows: (1) Diagnostic criteria of western medicine (formulated with reference to Diagnostic

Criteria for Chronic Hepatitis B (2015 Edition) and Diagnostic Guidelines for

Nonalcoholic Fatty Liver Disease in China (2010 Revision Edition))

Anyone who has the following items may be diagnosed as chronic hepatitis B complicated with nonalcoholic fatty liver disease. 1) Chronic hepatitis B with HBeAg positive or HBeAg negative accompanied by elevated transaminase and HBV-DNA positive was diagnosed as chronic HBV infection by pathological examination of liver tissue inflammation caused by HBV infection. 2) No history of drinking or alcohol consumption, the equivalent amount of alcohol is less than 140 g per week for men and less than 70 g per week for women. 3) Specific diseases of fatty liver caused by drug-induced liver disease, chronic viral hepatitis C, autoimmune liver disease, total parenteral nutrition and sinusoidal degeneration of liver are excluded. 4) In addition to the clinical manifestations of primary diseases, there may be non-specific symptoms and signs such as fatigue, dyspepsia, dull pain in liver area, hepatosplenomegaly, etc. 5) There may be components related to metabolic syndrome such as overweight and/or visceral obesity, elevated fasting blood sugar, dyslipidemia, hypertension, etc. 6) Serum transaminase and y-glutamyltranspeptidase levels are slightly to moderately increased (<5 times higher than the normal level), and alanine aminotransferase (ALT) is usually increased. 7) The instantaneous transient elastography of liver shows that the CAP value of liver fat detection was = 238 db/m. (2) Diagnostic criteria of TCM syndromes

With reference to the Terminology of Clinical Diagnosis and Treatment of Traditional

Chinese Medicine issued by the State Bureau of Quality and Technical Supervision, the

Clinical Guiding Principles of New Chinese Medicine formulated by National MedicaU504091

Products Administration and the dialectical criteria of the National Planning Textbook of

Traditional Chinese Medicine in the Twelfth Five-Year Plan of General Higher Education, the basic syndrome and concurrent symptoms of phlegm-dampness and blood stasis are determined according to the pathogenesis characteristics and symptom changes of

CHB complicated with NAFLD.

Syndrome of phlegm-dampness and blood stasis

Main symptoms: right hypochondriac discomfort/dull pain/swelling pain.

Secondary symptoms: fatigue, abdominal distension, heavy limb fatigue, dizziness, bitter and sticky mouth, unpleasant or loose stools, dull tongue with petechiae and ecchymosis, thin and white fur, exposed hypoglossal vein, thin or heavy pulse. Among them, the diagnosis may be made with two main symptoms and secondary symptoms. 2. Treatment regimen

Patients in the treatment group take orally the traditional Chinese medicine granules prepared in Embodiment 1 combined with entecavir dispersible tablets.

Patients in the control group take entecavir dispersible tablets orally.

The traditional Chinese medicine granules prepared in Embodiment 1 are taken twice a day, with 6 g each time.

Entecavir dispersible tablets are taken once a day, one tablet each time, and each tablet is 0.5 mg.

The course of treatment is 3 months, and the statistical effect is obtained after the course of treatment. 3. Safety evaluation standard

Grade |: safe without any adverse reaction.

Grade II: relatively safe. If there are adverse reactions, the drug may be continued without any treatment.

Grade Ill: there are safety problems and moderate adverse reactions, and the drug may be continued after treatment.

Grade IV: the test is suspended due to adverse reactions.

4. Statistical treatment LU504091

Patients are randomly divided into treatment group (32 cases), including 27 males and 5 females, aged between 28 and 53 (median 38.00); control group (32 cases), including 28 males and 4 females, aged between 28 and 63 (median 39.50). There is no difference in the distribution of patients in gender and age between the treatment group and the control group (P>0.05), and there is no significant difference in ALT, AST, TG,

GLU, CAP, FFA and HBV-DNA between the two groups before treatment, which is comparable.

Detection indexes: ALT (alanine aminotransferase), AST (aspartate aminotransferase), TG (triglyceride), GLU (glucose), CAP value of liver fat content, FFA (free fatty acid) and HBV-DNA (hepatitis B virus gene) are observed in both groups before and after treatment.

Statistical methods: all data are processed by SPSS19.0 statistical analysis software, and the data are described by mean standard+deviation (* ts). T-test is performed for those whose data conform to normal distribution (Shapiro-Wilk test) and homogeneity of variance; non-normal distribution is analyzed by rank sum test, and chi-square test is used to classify disordered data. P<0.05 is considered statistically significant, and P<0.01 is considered statistically significant. 5. Test result

All patients in the treatment group do not have any adverse reactions.

The levels of ALT, AST, TG, GLU and CAP in the two groups do not conform to the normal distribution after the treatment. The rank sum test of nonparametric test is used for analysis. The specific results are shown in Table 1 and FIG. 1-FIG. 5.

Table 1 Comparison of ALT, AST, TG, GLU and CAP levels between the two groups/504091 before and after treatment (* +s)

C TG GLU

Befo

Treat re 117.50+48 | 64.95+41 | 2.12+0 | 5.94+0 | 307.61+3 rea treat |.95 71 64 84 4.26 ment | 3 ment grou | 2 After p treat 45.70+41. | 37.93+23 | 1.43+0 | 5.55+0 | 258.52+3 79 .92 51 75 7.76 ment

Befo re 189.42+26 | 92.01+11 | 2.01+0 | 6.181 | 293.0013

Note: After treatment, the levels of ALT, AST, TG, GLU and CAP in the two groups are compared, P>0.05.

The results show that there is no significant difference in the levels of ALT, AST, TG,

GLU and CAP between the two groups after the course of treatment (P>0.05), but after treatment, the levels of serum ALT, AST, TG and GLU and the CAP value of liver fat content in the treatment group show a decreasing trend compared with the control group.

After the treatment, the FFA and HBV-DNA levels of the two groups of patients do not conform to the normal distribution. The rank sum test of nonparametric test is used for analysis. The specific results are shown in Table 2 and FIG. 6-FIG. 7.

Table 2 Comparison of FFA and HBV-DNA levels between the two groups before aridJ504091 after treatment (* ts) treatment treatment

Note: all HBV-DNA data are further statistically analyzed after natural logarithmic conversion to reduce errors; A indicates the comparison of FFA level between the two groups after treatment, P<0.05; < indicates the comparison of HBV-DNA levels between the two groups after treatment, P<0.01.

The results show that there is statistically significant difference in FFA level between the two groups after the treatment (P<0.05), and there is significant difference between

HBV-DNA levels.

To sum up, the whole prescription of the traditional Chinese medicine granule has the effects of clearing away heat and toxic materials, eliminating phlegm and dampness, may reduce the plasma FFA level of patients with CHB and NAFLD, improve liver fat deposition, and improve the antiviral effect of entecavir on patients with CHB and

NAFLD.

Typical case 1

Yang, male, 35 years old, from Luoyang, Henan Province, complained that he has an intermittent discomfort in the right hypochondrium for half a year and it aggravated for one week. Current medical history: the patient suffered from right hypochondriac discomfort after heavy physical labor six months ago, which was not taken seriously and treated. After being tired again one week ago, the right hypochondriac discomfort became worse, accompanied by abdominal fullness. The tongue is dark red, the coating is thin and yellow, the sublingual vein is exposed, and the pulse is smooth. Past historiJ504091 no drinking history. The examination: 5 markers of hepatitis B: HBsAg (+), HBsAb(-),

HBeAg(+), HBeAb(-) and HBCAB (+); HBV-DNA: 6.17x10* IU/mL; liver function:

ALT135U/L, AST 69.3 U/L; blood lipid: TG3.01 mmol/L, FFA 0.99 mmol/L; instantaneous elasticity test of liver: CAP289dB/m, E3.7 kPa, suggesting that liver steatosis is = 34% and liver hardness is in FO stage. Traditional Chinese medicine diagnosis: liver stagnation, phlegm-dampness block and toxic heat syndrome; western medicine diagnosis: 1. chronic hepatitis B; 2. non-alcoholic fatty liver disease. Western medicine is given entecavir dispersible tablets, orally taken, 0.5 mg/time, once a day. The treatment method of the invention: eliminating phlegm and dampness, clearing away heat and toxic materials; specific prescription: the traditional Chinese medicine granules prepared in

Embodiment 1 are taken twice a day, 6 g each time, with warm boiled water and taken for 30 days.

Second diagnosis: right hypochondriac discomfort is less than before, and abdominal fullness is less; after 60 doses were taken again, the right hypochondriac discomfort was obviously relieved, and abdominal fullness did not appear again.

HBV-DNA: not detected; liver function: ALT60.2U/L, AST 34 U/L; blood lipid: TG1.23 mmol/L, FFA 0.48 mmol/L; detection of instantaneous elasticity of liver: CAP255 dB/m,

E4.0 kPa, suggesting that hepatic steatosis is = 11% and the liver hardness is in FO stage.

Typical case 2

Ma, a 37-year-old male from Dancheng County, Henan Province, complained of intermittent right flank discomfort for 8 years, aggravated by 5 days. Current medical history: eight years ago, hepatitis B was found in physical examination, right hypochondriac discomfort appeared intermittently, HBV-DNA, 5 markers of hepatitis B and liver function were ominous, and no antiviral treatment was performed. One year ago, color Doppler ultrasound showed diffuse changes in liver parenchyma (1. Fatty liver 2. Chronic hepatitis). After the patient caught a cold five days ago, he felt that the right hypochondriac discomfort was aggravated. After Lianhua Qingwen Capsule is taken, he recovered from the cold, but the right hypochondriac discomfort did not abate,

accompanied with bitter mouth, and there was no obvious discomfort in other aspect&U504091 with dull tongue, thin and greasy fur and thin pulse. Past history: no drinking history. The examination: 5 markers of hepatitis B: HBsAg (+), HBsAb(-), HBeAg(+), HBeAb(-) and

HBCAB (+); HBV-DNA: 3.89x10° IU/mL; liver function: ALT94U/L, AST 62U/L; blood lipid:

TG1.66 mmol/L, FFA 0.69 mmol/L; instantaneous elasticity test of liver: CAP322 dB/m,

E6.2 kPa, suggesting that liver steatosis is = 67% and liver hardness is in FO-F1 stage.

Traditional Chinese medicine diagnosis: liver stagnation, phlegm-dampness block syndrome. Western medicine diagnosis: 1. chronic hepatitis B; 2. non-alcoholic fatty liver disease. Western medicine was given entecavir dispersible tablets, taken orally, 0.5 mg/time, once a day. The treatment method of the invention: eliminating phlegm and dampness, clearing away heat and toxic materials. Specific prescription: the traditional

Chinese medicine granules prepared in Embodiment 1 are taken twice a day, one bag each time, with a weight of 6 g for each bag, and it is taken with warm boiled water for 15 days.

Second diagnosis: the right hypochondriac discomfort was relieved and the bitter taste disappeared. The previous prescription is used continuously. After it is taken for more than 2 months, the discomfort in the right hypochondrium is obviously relieved.

HBV-DNA: < 1.0x102 IU/mL; liver function: ALT25.4U/L, AST 20.4 U/L; blood lipid:

TG0.70 mmol/L, FFA 0.45 mmol/L; instantaneous elasticity test of liver: CAP290 dB/m,

E6.0 kPa, suggesting that liver steatosis is = 34% and liver hardness is in FO-F1 stage.

Typical case 3

Wang, male, 35 years old, from Zhengzhou, Henan Province, complained of intermittent dull pain in his right flank for 1 year and aggravated for 3 days. Current medical history: 1 year ago, the patient went to the community hospital for abdominal color Doppler ultrasound because of dull pain in his right hypochondria, which showed fatty liver. The patient didn't pay attention to it and didn't treat it. Three days ago, due to long-term overtime and staying up late, the patient suffered from dull pain in the right hypochondrium frequently, and the stool was sticky, once or twice a day. The patient went to the local hospital to check the liver function: ALT99.3U/L, AST 22.1U/L; so he went to our hospital for treatment. Tongue pulse: red tongue, yellow greasy fur, tortuous sublingual vein, and number of pulse strings. Past history: the history of hepatitis IBJ504091 (HBsAg, HBeAb, and HBcAD test positive) was 6 years, without antiviral treatment, and no drinking history. The examination shows: 5 markers of hepatitis B: HBsAg(+),

HBsAb(-), HBeAg(+), HBeAb(-) and HBCAB (+); HBV-DNA: 3.67x107 IU/mL: blood lipid:

TG2.51 mmol/L, FFA 0.55 mmol/L; instantaneous elasticity test of liver: CAP346 dB/m,

E7.3 kPa, suggesting that liver steatosis is = 67%, and liver hardness is in F2 stage.

Traditional Chinese medicine diagnosis: liver stagnation, phlegm-dampness block and toxic heat syndrome. Western medicine diagnosis: 1. chronic hepatitis B; 2. non-alcoholic fatty liver disease. Western medicine was given entecavir dispersible tablets, taken orally, 0.5 mg/time, once a day. The treatment method of the invention: eliminating phlegm and dampness, clearing away heat and toxic materials. Specific prescription: the traditional Chinese medicine granules prepared in Embodiment 1 are taken twice a day, one bag each time, with a weight of 6 g for each bag, and taken with warm boiled water for 14 days.

Second diagnosis: the dull pain in the right hypochondrium is less than before, and the stool is sticky, once or twice a day. After the drug is taken for more than 2 months, the dull pain in the right hypochondrium was obviously relieved and the stool was formed, once or twice a day. HBV-DNA: not detected; liver function: ALT18.1U/L, AST 20.3 U/L; blood lipid: TG1.94 mmol/L, FFA 0.32 mmol/L; instantaneous elasticity test of liver:

CAP269 dB/m, E6.6 kPa, suggesting that liver steatosis is = 34% and liver hardness is in

FO-F1 stage.

Typical case 4

Guo, a 41-year-old male from Xiangcheng City, Henan Province, complained of intermittent right flank discomfort for 13 years, which aggravated for half a month.

Current medical history: 13 years ago, hepatitis B (HBsAg, HBeAg and HBcAb test positive) was found during physical examination due to right hypochondriac discomfort, and since then the related items of hepatitis B were examined every year. There was no abnormality in liver function and HBV-DNA was not detected; no antiviral treatment was given. Five years ago, color Doppler ultrasound showed: mild fatty liver; no treatment.

Half a month ago, due to the excessive grief caused by the death of relatives, the discomfort in the right hypochondrium increased, the tongue was reddish, the fur was/504091 white and greasy, the hypoglossal vein was exposed, and the pulse was thin. Past history: no drinking history. The examination shows: 5 markers of hepatitis B: HBsAg(+),

HBsAb(-), HBeAg(+), HBeAb(-) and HBCAB (+); HBV-DNA: 9.13x108 IU/mL; blood lipid:

TG1.39 mmol/L, FFA 0.86 mmol/L; instantaneous elasticity test of liver: CAP247 dB/m,

ES.7 kPa, suggesting that liver steatosis is = 11% and liver hardness is in FO stage.

Chinese medicine granules prepared in Embodiment 1 are taken twice a day, one bag for each time, with a weight of 6 g each bag, and it is taken with warm boiled water for 14 days. The patient is asked to adjust his mood.

Second diagnosis: right hypochondriac discomfort relieved; after the drug is taken for more than 2 months, the right hypochondriac discomfort was obviously relieved.

HBV-DNA: not detected; liver function: ALT29.1U/L, AST 22.8 U/L; blood lipid: TG1.23 mmol/L, FFA 0.52 mmol/L; instantaneous elasticity test of liver: CAP201 dB/m, E4.9 kPa, suggesting that liver steatosis is less than 11%, and liver hardness is in FO stage.

Typical case 5

Li, male, 38 years old, from Taikang County, Henan Province, suffered from intermittent right flank discomfort for 2 years. Chief complaint: two years ago, the patient went to the local hospital for color Doppler ultrasound because of right hypochondriac discomfort, showing fatty liver. The patient paid no attention to and didn’t treat. Current medical history: intermittent right hypochondriac discomfort, lethargy, narcolepsy, defecation, reddish tongue, and thin white greasy fur. Past history: the history of hepatitis

B was 17 years, and no review and antiviral treatment were given; no drinking history.

The examination shows: 5 markers of hepatitis B: HBsAg(+), HBsAb(-), HBeAg(+),

HBeAb(-) and HBCAB (+); HBV-DNA: 6.00x10° IU/mL; blood lipid: TG1.75 mmol/L, FFA 0.65 mmol/L; instantaneous elasticity test of liver: CAP317 dB/m, E6.2 kPa, suggesting that liver steatosis is = 67% and liver hardness is in FO-F1 stage. Traditional Chinedé/504091 medicine diagnosis: liver stagnation, phlegm-dampness block syndrome. Western medicine diagnosis: 1. chronic hepatitis B; 2. non-alcoholic fatty liver disease. Western medicine was given entecavir dispersible tablets, taken orally, 0.5 mg/time, once a day.

The treatment method of the invention: eliminating phlegm and dampness, clearing away heat and toxic materials. Specific prescription: the traditional Chinese medicine granules prepared in Embodiment 1 are taken twice a day, 6 g each time, taken with warm boiled water. The drug is taken for one month.

Second diagnosis: right hypochondriac discomfort relieved. After the drug was taken for more than one month, the right hypochondriac discomfort was obviously relieved.

HBV-DNA: not detected; liver function: ALT16U/L, AST 15U/L; blood lipid: TG1.69 mmol/L, FFA 0.30 mmol/L; instantaneous elasticity test of liver: CAP275 dB/m, E4.7 kPa, suggesting that liver steatosis is = 34% and liver hardness is in FO stage.

The present invention has been described in detail with reference to the attached drawings and embodiments. However, those skilled in the technical field may understand that various specific parameters in the above embodiments may be changed to form a plurality of specific embodiments without departing from the spirit of the present invention, and they are common variation ranges of the present invention, and will not be described in detail here.

Claims

CLAIMS LU504091

1. A traditional Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with CHB and NAFLD, characterized in that, it is prepared from the following bulk drugs in parts by weight: 13-16 parts of Rhizoma Polygoni Cuspidati, 13-16 parts of Radix Salviae Miltiorrhizaea, 8-12 parts of Radix Curcumae, 18-22 parts of Sargassum, 13-16 parts of Fructus Crataegi, 13-16 parts of Phyllanthus urinaria and 13-16 parts of vinegar processed Radix Bupleur.

2. The traditional Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with CHB and NAFLD according to claim 1, characterized in that, it is prepared from the following raw materials: parts of Rhizoma Polygoni Cuspidati, 15 parts of Radix Salviae Miltiorrhizaea, 10 parts of Radix Curcumae, 20 parts of Sargassum, 15 parts of Fructus Crataegi, 15 parts of Phyllanthus urinaria and 15 parts of vinegar processed Radix Bupleur.

3. The traditional Chinese medicine preparation for enhancing antiviral efficacy of entecavir combined with CHB and NAFLD according to claim 1, characterized in that, a processing method of the vinegar processed Radix Bupleur comprises the following steps: mixing Radix Bupleur slices with vinegar, stir-frying with slow fire until the vinegar is completely absorbed and slightly dried, and drying in the sun or air.

4. A preparation method of the traditional Chinese medicine preparation for enhancing the antiviral efficacy of entecavir combined with CHB and NAFLD according to claim 1, comprising the following steps: (1) weighing the raw materials according to a proportion according to claim 1 for later use;

(2) distilling Radix Curcumae and vinegar processed Radix Bupleur, and collectirig/504091 volatile components; (3) mixing Rhizoma Polygoni Cuspidati, Radix Salviae Miltiorrhizaea, Sargassum, Fructus Crataegi and Phyllanthus urinaria with residues obtained in the previous step, adding water to decoct for 0. 5-1 h, filtering to obtain filtrate, adding water to decoct the filter residue again, repeating for 1-2 times, and mixing the filtrates; (4) concentrating the filtrates obtained in the previous step under reduced pressure into paste, drying under reduced pressure, pulverizing, mixing the volatile components obtained in the step (2) evenly, and making into granules.

5. The preparation method according to claim 4, characterized in that, in the step (3), an amount of water added each time is 1-2 times of a volume of the solid materials to be decocted.

6. Drug for use in treatment of CHB and NAFLD, characterized in that, by weight, the drug comprises 100 to 150 parts of a traditional Chinese medicine preparation prepared according to claim 5, or the drug comprises a dose/dosage form with an effective component equivalent thereto, 0.5 to 1 part of entecavir dispersible tablets, or the drug comprises other dosage forms with an effective component equivalent thereto.