A traditional Chinese medicine composition, preparation, application, and preparation method for treating chronic hepatitis B virus-related cirrhosis.

Abstract

This invention relates to the field of traditional Chinese medicine, and discloses a traditional Chinese medicine composition, preparation, application, and preparation method for treating chronic hepatitis B virus-related cirrhosis. The active ingredients of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 1-10 parts of stir-fried Bupleurum chinense, 5-15 parts of stir-fried Citrus aurantium, 8-16 parts of stir-fried Paeonia lactiflora, 5-15 parts of stir-fried Citrus reticulata peel, 5-15 parts of Curcuma zedoaria, 10-20 parts of Sedum sarmentosum, 15-25 parts of Hedyotis diffusa, and 1-10 parts of raw Glycyrrhiza uralensis. This traditional Chinese medicine composition and preparation possess good safety and high practicality, and have good efficacy in treating HBV-related cirrhosis (liver stagnation and toxin obstruction syndrome).

Description

Technical Field

[0001] This invention relates to the field of traditional Chinese medicine, specifically to a traditional Chinese medicine composition, preparation, application, and preparation method for treating postoperative gastrointestinal reactions in patients with malignant tumors. Background Technology

[0002] Hepatitis B virus (HBV)-related cirrhosis is a progressive liver disease caused by persistent chronic hepatitis B virus (HBV) infection. Clinically, it typically manifests as extensive hepatocellular necrosis, liver structural destruction, and fibrosis, ultimately leading to cirrhosis. HBV-related cirrhosis is a crucial stage in the natural course of chronic hepatitis B (CHB) and a major cause of serious complications such as liver failure, portal hypertension, and liver cancer, posing a serious threat to public health.

[0003] The pathogenesis of HBV-related cirrhosis is complex, involving direct or indirect viral-induced hepatocellular damage and inflammatory responses, abnormal immune system reactions, and changes in the liver microenvironment. Persistent HBV infection leads to hepatocellular damage and necrosis, the formation of fibrous septa within the liver, and the gradual accumulation of extracellular matrix such as collagen in liver tissue, ultimately resulting in cirrhosis. While the host's immune response helps clear the virus to some extent, its overactivity can also exacerbate hepatocellular damage, further promoting the activation of hepatic stellate cells (HSCs), thereby causing fibrosis.

[0004] Liver fibrosis is caused by the transformation of hepatic stellate cells into a myofibroblast-like activated state. These cells synthesize and secrete large amounts of collagen, inhibiting its degradation, thereby leading to excessive deposition of the extracellular matrix. In addition to viral infection, gut microbiota dysbiosis, abnormal bile acid metabolism, and angiogenesis also play important roles in the progression of HBV-related cirrhosis.

[0005] Although the term "HBV-related cirrhosis" does not appear in ancient Chinese medicine literature, analysis of its pathogenesis and symptoms reveals many similarities between it and traditional disease names. For example, symptoms such as hypochondriac pain, jaundice, abdominal distension, and liver cirrhosis are recorded in Chinese medicine literature, providing important clues for tracing the understanding of the pathological mechanism of this disease by ancient physicians.

[0006] Traditional Chinese medicine (TCM) considers the liver to be the organ that "stores blood," and impaired liver qi circulation is often a cause of disease. In the early stages of cirrhosis, liver qi stagnation typically manifests as symptoms such as hypochondriac pain and abdominal distension, while weakness of liver and spleen function and poor blood circulation are the main reasons for the aggravation of symptoms. Traditional TCM pathogenesis theory, through the differentiation of qi, blood, body fluids, and organ function, reveals the pathological process of cirrhosis, especially the three major pathological changes of "qi stagnation, blood stasis, and dampness," which interact and ultimately lead to damage to liver structure and functional failure.

[0007] Currently, the main approach to treating HBV-related cirrhosis in Western medicine is through antiviral drugs, such as entecavir, to inhibit viral replication and slow disease progression. However, while existing drug therapies control the virus, they cannot address the liver inflammation and subsequent fibrosis caused by viral infection. Furthermore, antiviral therapy typically requires long-term use and may be accompanied by adverse reactions, resulting in less than ideal efficacy.

[0008] Traditional Chinese medicine (TCM) has unique advantages in treating HBV-related cirrhosis. TCM emphasizes holistic regulation, focusing on methods such as soothing the liver and detoxifying, removing blood stasis and unblocking the meridians, and replenishing qi and nourishing blood. It has significant effects in regulating liver function, improving blood circulation, and slowing down liver fibrosis. According to TCM theory, the treatment of cirrhosis should focus on soothing the liver and relieving stagnation, removing blood stasis and detoxifying, and promoting the flow of qi and blood to restore normal liver function. Summary of the Invention

[0009] During clinical practice, the applicant observed that HBV-related cirrhosis patients often experienced emotional symptoms alongside typical liver disease symptoms such as hypochondriac pain, including depression, irritability, anxiety, and restlessness. The reason for this is that HBV is a "latent pathogenic virus" that thrives in the liver meridian, nesting in the yin aspect of the body and residing in the blood. When at rest, it lies hidden in the blood; when active, it flows along the meridians to the spleen, subtly aligning with the liver's "yin in substance but yang in function" nature—hence its "liver-loving" nature—making it highly contagious. The liver governs the vital energy of spring, which is associated with growth and development. Belonging to the element of wood in the Five Elements theory, it embodies the natural cycle of growth. When external pathogenic factors invade the liver, its ascending and dispersing nature is suppressed, leading to stagnation of qi. This stagnation of qi results in emotional distress and imbalance, as stated in the *Danxi Xinfa*: "When qi and blood are in harmony, no disease arises; but when there is stagnation, all diseases arise." Furthermore, the increased pressure of modern society means that early signs of illness may include depression, anxiety, and lethargy. When external pathogenic factors accumulate over time, they become pathogenic toxins. As stated in the "Essential Prescriptions of the Golden Chamber," "Toxins are the accumulation of pathogenic factors that cannot be resolved." In the early stages, pathogenic toxins spread like wildfire, and the body's vital energy rises up to fight against them. The struggle between the body's vital energy and pathogenic factors leads to the lingering and persistent nature of latent pathogenic toxins. They remain trapped in the liver for a long time, gradually causing the liver to lose its function of dispersing and draining, disrupting the ascending and descending of the middle jiao, and causing the flow of qi to become obstructed. This leads to qi stagnation and blood stasis, and the combination of stasis and heat further exacerbates dampness and turbidity. This cycle repeats itself, and the liver loses its supple and moist quality. The collaterals become withered, and the liver gradually deteriorates, manifesting as "fat qi" and "abdominal qi." Symptoms include pain in the hypochondrium and masses under the ribs. This is the "liver accumulation" among the five visceral diseases described in the "Classic of Difficult Issues."

[0010] The applicant pointed out that the symptoms and pathogenesis of HBV-related cirrhosis are closely related to "liver stagnation" and "toxic pathogens." Based on this analysis, the applicant proposed that "liver qi stagnation and internal obstruction of toxic stasis" is the main pathogenesis of HBV-related cirrhosis, and "liver stagnation and toxic obstruction syndrome" is an important stage in the development of HBV-related cirrhosis. The *Treatise on the Spleen and Stomach* states, "Qi is the root of spirit." The *Suwen* (Plain Questions) states, "The mechanism of life and death lies in the ascending and descending of qi." "When the flow of qi ceases, the spirit perishes; when the ascending and descending cease, qi becomes isolated and endangered." Life activities are fundamentally based on the ascending, descending, entering, and exiting of qi, and early-stage cirrhosis is most commonly characterized by liver qi stagnation. Therefore, the first step in treating cirrhosis should be to regulate qi. Professor Chen believes that this disease originates from external invasion of HBV virus pathogens, which lurk in the liver meridians. Furthermore, due to the root cause of qi stagnation, the liver's inability to regulate qi leads to poor blood circulation, causing blood to pool and stagnate. Once stagnation and turbidity form, they further obstruct the smooth flow of liver qi, leading to the mutual binding of qi stagnation, toxins, and blood stasis. The obstruction of qi and blood circulation worsens daily, and disharmony among the internal organs gradually intensifies, ultimately causing pathogenic factors to penetrate from the qi to the blood, from the symptoms to the root cause, resulting in a prolonged and intractable malignant transformation. Furthermore, if the toxins formed in the body in the early stages are not resolved in time, toxins such as hepatitis viruses accumulate in the liver over a long period. The liver is the organ that stores blood; if it fails to regulate qi and blood flow, qi stagnation and blood stasis occur, leading to the accumulation of stagnant toxins. Over time, liver yin is depleted, yin and blood become insufficient, liver vessels are damaged, and the liver loses its suppleness and function, further accumulating into turbidity. This gradual accumulation leads to an irreversible qualitative change, exacerbating the primary disease and promoting the development of liver cancer. Therefore, for HBV-related cirrhosis, the applicant formulated a "Liver-Soothing and Detoxifying Decoction" to soothe the liver, relieve depression, clear heat and detoxify, and remove blood stasis and unblock the meridians. The main purpose is to restore the liver's function of regulating the flow of qi, cut off the spread of the epidemic toxin, and eliminate the opportunity for the formation of masses, thereby achieving the purpose of treatment.

[0011] This invention addresses the shortcomings of existing technologies by providing a traditional Chinese medicine composition, preparation, application, and preparation method for treating chronic hepatitis B virus-related cirrhosis. The traditional Chinese medicine composition exhibits good efficacy against liver stagnation and toxin obstruction syndrome in HBV-related cirrhosis, with no observed adverse reactions and high safety.

[0012] To achieve the above objectives, the present invention adopts the following technical solution:

[0013] A traditional Chinese medicine composition for treating chronic hepatitis B virus (HBV)-related cirrhosis, wherein the effective components of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 4-8 parts of stir-fried Bupleurum chinense, 7-11 parts of stir-fried Citrus aurantium, 10-14 parts of stir-fried Paeonia lactiflora, 7-11 parts of stir-fried Citrus reticulata, 7-11 parts of Curcuma zedoaria, 13-17 parts of Sedum sarmentosum, 18-22 parts of Hedyotis diffusa, and 3-7 parts of raw Glycyrrhiza uralensis.

[0014] Preferably, the active ingredient raw materials of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 6 parts of stir-fried Bupleurum chinense, 9 parts of stir-fried Citrus aurantium, 12 parts of stir-fried Paeonia lactiflora, 9 parts of stir-fried Citrus reticulata peel, 9 parts of Curcuma zedoaria, 15 parts of Sedum sarmentosum, 20 parts of Hedyotis diffusa, and 5 parts of raw Glycyrrhiza uralensis.

[0015] Furthermore, the present invention also provides a traditional Chinese medicine composition for treating chronic hepatitis B virus-related cirrhosis, wherein the traditional Chinese medicine composition comprises the aforementioned traditional Chinese medicine composition and / or pharmaceutical excipients.

[0016] Preferably, the traditional Chinese medicine composition is in the form of tablets, granules, capsules, ointments, or liquids.

[0017] Furthermore, the present invention also provides the application of the aforementioned traditional Chinese medicine composition or the aforementioned traditional Chinese medicine composition preparation in combination with entecavir in the preparation of a drug for treating chronic hepatitis B virus-related cirrhosis.

[0018] Preferably, this application is used to treat HBV-related cirrhosis with liver stagnation and toxicity, including:

[0019] Improve liver function indicators, liver stiffness value, four liver fibrosis markers, and HBV-DNA viral load;

[0020] In addition, it improves the patient's TCM symptoms, which include stabbing pain in the hypochondrium, pain that does not move, abdominal distension, hardness upon palpation, lumps under the ribs, purplish-brown lips, poor appetite and insomnia.

[0021] Furthermore, the present invention also provides a method for preparing the aforementioned traditional Chinese medicine composition, which comprises the following steps: weighing all medicinal materials in proportion, decocting and concentrating them, or preparing them into a formulation in an appropriate dosage form.

[0022] Furthermore, the present invention also provides a drug kit for treating chronic hepatitis B virus (HBV)-related cirrhosis-liver stagnation syndrome, comprising:

[0023] First component: the traditional Chinese medicine composition or the traditional Chinese medicine composition preparation described above;

[0024] Second component: entecavir or a pharmaceutically acceptable salt thereof.

[0025] Preferably, the first and second components are packaged in the same outer packaging and accompanied by instructions to patients to administer the medication according to the following periodic procedure: the Chinese medicine composition is taken orally twice daily, each time corresponding to 150 mL of concentrated decoction or an equal amount of solid preparation, one hour after breakfast and dinner respectively; entecavir is taken continuously at 0.5 mg daily for the entire course of treatment; one course of treatment is 3 months of continuous use, followed by a 3-month break and then another 3 months of continuous use, with 2 courses of treatment per year.

[0026] Furthermore, the present invention also provides the application of the aforementioned drug kit in the preparation of a drug for treating chronic hepatitis B virus-related cirrhosis, the application of which is used to treat HBV-related cirrhosis with liver stagnation and toxicity obstruction, including:

[0027] Improve liver function indicators, liver stiffness value, four liver fibrosis markers, and HBV-DNA virus quantification;

[0028] Moreover, improve the traditional Chinese medicine (TCM) syndromes of the patients, and the TCM syndromes include stabbing pain in the hypochondrium with fixed pain location, abdominal fullness with a hard feeling on palpation, mass in the hypochondrium under the costal margin, purplish-brown lips, and reduced appetite with insomnia.

[0029] The requirements of the present invention and the analysis of the composition are as follows:

[0030] The liver is a rigid organ and likes to be smooth. Liver depression leads to qi stagnation and blood stasis, and the accumulation of toxic pathogens, which will turn into mass over time. Just as stated in "Medical Records of Clinical Practice Guidelines": "Depression leads to qi stagnation, which will turn into heat over time, and heat depression leads to collateral stasis and qi obstruction." Shugan Jiedu Decoction uses Bupleuri Radix as the monarch drug, which is slightly bitter and cold, and can soothe the liver and relieve depression with its gentle and ascending nature. Aurantii Fructus Immaturus and Citri Reticulatae Pericarpium regulate qi and soothe the middle, helping the liver qi to flow smoothly; Paeoniae Radix Rubra and Rhizoma Curcumae promote blood circulation to remove blood stasis and break up masses and eliminate accumulations; Sedi Herba and Herba Salviae Chinensis clear heat and detoxify, directly reducing the stagnant toxins in the liver and gallbladder. Licorice Root is used as an assistant drug to harmonize all the drugs. The whole formula follows the principle of "unblocking the wood when it is stagnant", and through the three methods of soothing liver qi, promoting blood circulation to remove blood stasis, and clearing turbid toxins simultaneously, it can improve symptoms such as hypochondriac pain, abdominal distension, and purple and dull tongue. Clinical observations show improvement in liver fibrosis indicators, reflecting the treatment concept of "when the dredging and discharging functions return to normal, the toxins and blood stasis will disappear by themselves" for treating the liver.

[0031] Bupleuri Radix is slightly bitter and cold, and enters the liver, gallbladder, and triple energizer meridians. "The Explanation of the Properties and Efficacies of Medicinal Herbs Prepared by Lei Gong" says about Bupleuri Radix: "It dredges the stagnation of liver wood, promotes the elimination of the old and the generation of the new." Bupleuri Radix can not only regulate the stagnation of liver qi but also promote the ascending of the qi of Shaoyang meridian. Its ascending function can make the clear yang qi reach all parts of the body, and its dredging power can dredge the qi stagnation in the triple energizer, promoting the metabolism of qi, blood, and body fluids. In the formula, Bupleuri Radix is used for its functions of regulating liver qi, soothing liver depression, and guiding the drug into the liver meridian.

[0032] Fructus Aurantii Immaturus Praeparatus is bitter, pungent, and slightly cold, and enters the spleen, stomach, and large intestine meridians. "Supplementary Records of Famous Physicians" says about Fructus Aurantii Immaturus: "It eliminates phlegm and masses in the chest and hypochondrium, expels retained fluid, breaks up firm masses, relieves fullness and distension, treats acute stuffiness and pain in the epigastrium, adverse qi, and pain in the hypochondrium due to wind." Fructus Aurantii Immaturus Praeparatus can relieve symptoms such as distending pain in the hypochondrium and emotional depression caused by liver qi stagnation. Zhu Danxi often used it in combination with Cyperi Rhizoma and Perillae Folium Viride to treat hypochondriac pain caused by liver qi stagnation. In the formula, it is used for its functions of regulating qi and soothing the middle, promoting qi movement and relieving distension.

[0033] Paeoniae Radix Rubra Praeparatus is slightly cold in nature and bitter in taste, and belongs to the liver and spleen meridians. "Collected Annotations to the Classic of Materia Medica" says: "It eliminates blood stasis, breaks up firm accumulations, scatters evil blood, and relieves pain." This medicine is red in color and enters the liver, and is good at dredging collaterals and promoting the flow of qi. It can not only disperse the stasis in nutrient blood but also scatter the stagnation of static blood, especially known for clearing the stagnant heat in the liver meridian. In the formula, it is used for its functions of clearing heat and cooling blood, promoting blood circulation to remove blood stasis, and reducing swelling and relieving pain.

[0034] Citri Reticulatae Pericarpium Praeparatus is bitter, pungent, and warm, and enters the spleen, lung, and liver meridians. Citri Reticulatae Pericarpium can regulate qi and strengthen the spleen, warm and dry dampness. When combined with Fructus Aurantii Immaturus, it enhances the effects of soothing liver qi and replenishing qi and strengthening the spleen. While soothing the liver, it also takes into account strengthening the spleen, just as stated in "Synopsis of the Golden Chamber": "When liver disease is detected, it is known that the liver will transmit to the spleen, so the spleen should be strengthened first", achieving the goal of treating both the liver and the spleen.

[0035] Curcuma zedoaria, bitter, pungent, and warm in nature, enters the liver and spleen meridians. The *Ben Cao Tong Xuan* (Comprehensive Treatise on Materia Medica) states that Curcuma zedoaria "specifically targets the liver, breaking up accumulated blood stasis." For this reason, physicians throughout history have not discussed its blood-activating effects, but only its ability to break up blood stasis and eliminate accumulations. The *Ben Cao Yan Yi* (Extended Meaning of Materia Medica) states that it can "treat various pains in the heart and abdomen, food stagnation, and abdominal masses." In summary, its clinical applications show that it has the effects of breaking up blood stasis, promoting qi circulation, eliminating accumulations, and relieving pain, especially effective in treating various accumulations of qi and abdominal masses. It is commonly used to soothe the liver, regulate qi, activate blood circulation, and remove blood stasis, improving symptoms such as hypochondriac pain and abdominal masses caused by liver stagnation and blood stasis. The formula utilizes its effects of breaking up blood stasis, promoting qi circulation, eliminating accumulations, and relieving pain.

[0036] Sedum sarmentosum, with a sweet, bland, and slightly sour taste, is cool in nature and enters the liver, gallbladder, and small intestine meridians. Its functions include clearing heat and detoxifying, promoting diuresis and relieving jaundice, and soothing the liver and relieving depression. Its cool nature clears damp-heat from the liver and gallbladder, while its sweet and bland taste promotes diuresis and eliminates damp-heat pathogens through urination. It is suitable for jaundice and hypochondriac pain caused by damp-heat accumulation in the liver and gallbladder. This formula utilizes its heat-clearing, diuretic, and detoxifying properties.

[0037] *Scutellaria baicalensis* has a bitter and pungent taste, is slightly cold in nature, and enters the liver and spleen meridians. It can clear damp-heat in the liver meridian and detoxify the liver and gallbladder, making it suitable for jaundice, hypochondriac pain, and bitter taste in the mouth caused by damp-heat accumulation in HBV-related cirrhosis. It can also invigorate blood circulation, remove blood stasis, and dredge the qi and blood of the liver meridian, improving hypochondriac pain and dull complexion caused by qi stagnation and blood stasis. Additionally, it can soften and disperse nodules, relieving hepatosplenomegaly. The formula utilizes its heat-clearing, detoxifying, blood-activating, and nodule-softening properties.

[0038] Licorice root, sweet in taste and slightly cold in nature, enters the heart, lung, spleen, and stomach meridians, playing the role of the "elder" in this formula. Its sweet and mild nature harmonizes the middle jiao, regulating the pungent and dispersing properties of Bupleurum and Aurantium, and counteracting the bitter and cold properties of Sedum sarmentosum and Hedyotis diffusa that harm the stomach. Furthermore, its sweet and mild properties unblock the meridians, soothing the liver and relieving acute pain, and promoting the flow of qi and blood. The entire formula utilizes its sweet and neutral harmonizing power to soothe the liver and detoxify without harming the root cause, and to resolve blood stasis and dissipate nodules without leaving any adverse effects.

[0039] Modern pharmacological studies of the Chinese herbal composition of the present invention:

[0040] Bupleurum: Bupleurum is one of the core drugs in traditional Chinese medicine for treating liver diseases. Its main components include saikosaponins, quercetin, and isorhamnetin, which have hepatoprotective effects, alleviate depressive mood, reduce inflammation, and inhibit cancer cell growth. Studies have found that saikosaponins enhance the body's fibrinolytic function and achieve anti-fibrotic effects by regulating the expression levels of plasminogen activator inhibitor (PAI) and tissue-type plasminogen activator (TPA) and increasing the TPA / PAI ratio. As a key active ingredient, saikosaponins can significantly delay the pathological progression of liver fibrosis through multi-target regulation by enhancing the body's ability to metabolize malondialdehyde (MDA), effectively reducing its serum level, and inhibiting abnormal activation of hepatic stellate cells. The results of Liu et al.'s research show that isorhamnetin helps reduce the levels of AST, ALT, and hydroxyproline in mice, alleviating problems such as inflammatory infiltration, hepatocyte swelling and necrosis caused by chronic injury, and also inhibiting inflammation-induced hepatocyte autophagy and apoptosis. Quercetin can slow the progression of liver fibrosis, and its mechanism is related to the inhibition of HSC activation and the regulation of TGF-β1 / Smads and PI3K / Akt signaling pathways.

[0041] Fried Bitter Orange Peel: Bitter orange peel is one of the commonly used qi-regulating herbs in traditional Chinese medicine. Studies have found that bitter orange peel has effects such as promoting gastrointestinal motility, anti-inflammation, anti-oxidation, and regulating blood lipids. Naringin, as the main active ingredient of bitter orange peel, can effectively reduce the oxidative stress induced by cyclophosphamide, alleviate the inflammatory response triggered by it, and also has a good effect on improving hepatocyte dysfunction. In addition, the study by Wang Siwei et al. showed that bitter orange peel extract significantly improved liver oxidative damage, inflammatory infiltration, and organelle dysfunction in carbon tetrachloride-induced liver fibrosis mice by inhibiting the NF-κB / NLRP3 inflammasome pathway.

[0042] Red peony root: The main active ingredient of red peony root is total paeoniflorin, which has multiple clinical values, including protecting the liver, reducing inflammation, and anti-oxidation. Studies have shown that total paeoniflorin can exert an anti-hepatic fibrosis effect by blocking the TGF-β / Smads signaling pathway in the process of liver fibrosis, thereby improving cirrhosis. In addition, studies have also indicated that red peony root shows significant therapeutic effects in liver injury, and its mechanism may be related to reducing malondialdehyde (MDA) levels.

[0043] Dried tangerine peel (Chenpi): The effects of dried tangerine peel on the liver are mainly manifested in anti-oxidation, anti-inflammation, anti-fibrosis, regulation of lipid metabolism, promotion of detoxification, and improvement of liver function. Elshazly et al., in their study of hesperidin in dried tangerine peel, found that hesperidin exhibited a significant hepatoprotective effect on a dimethylnitrosamine-induced rat model of liver fibrosis and inhibited the activation of hepatocellular carcinoma cells (HSCs), thereby delaying the progression of fibrosis. Zeng Bing et al., through animal experimental models, observed that the cardioactive component of dried tangerine peel extract, hesperidin enzyme, has a significant hepatoprotective effect and can effectively improve the pathological process of liver fibrosis.

[0044] Curcuma zedoaria: The main components of Curcuma zedoaria include volatile oils and curcuminoids. Related studies have shown that curcumol can significantly upregulate the phosphorylation levels of receptor-interacting protein kinases 1 and 3. Based on this, it can induce necrosis of HSCs, inhibit HSC migration and adhesion, and downregulate the expression levels of key fibrinogenic enzymes, thereby achieving anti-fibrosis. Furthermore, Curcuma zedoaria extract, by selectively inhibiting the Hedgehog and GEF / GDIβ-Rho-related kinase dual pathway nodes, not only significantly reduced serum transaminase levels but also effectively reduced the production levels of hyaluronic acid and procollagen.

[0045] Sedum sarmentosum: Sedum sarmentosum is the dried whole herb of the Crassulaceae plant Sedum sarmentosum. Modern pharmacological studies have found that Sedum sarmentosum has unique advantages in the treatment of HBV-related cirrhosis. Sedum sarmentosum can exert an anti-liver fibrosis effect by downregulating the expression of B-cell lymphoma 2, while promoting the expression of Bcl-2-related X protein and caspase 3, and inducing apoptosis of hepatic stellate cells. In addition, the alcoholic extract of Sedum sarmentosum can significantly improve the survival rate of mice in a lipopolysaccharide / D-galactosamine-induced acute liver injury model. Its mechanism of action may be related to the upregulation of microRNA-124 expression and the inhibition of the activity of Hedgehog and high-mobility group box B1 signaling pathways.

[0046] Hedyotis diffusa: Hedyotis diffusa has antioxidant, anti-inflammatory, and anti-tumor effects. Animal experiments by Chen Peng et al. have confirmed that total phenolic acids from Hedyotis diffusa can improve acute liver injury through multiple targets, including enhancing tissue antioxidant capacity, protecting cell membranes from free radical attack, and reducing lipid peroxidation damage.

[0047] Licorice: Modern pharmacological studies have found that licorice has anti-inflammatory, antiviral, and anti-hepatic effects. Its main components include glycyrrhizic acid, glycyrrhetinic acid, and glycyrrhizin. Related studies have shown that glycyrrhizic acid can inhibit HSC activation, downregulate CTGF and MMP2 / 9 protein expression, and reduce the production of type I / III collagen mRNA, thereby exerting anti-hepatocyte apoptosis and anti-hepatic fibrosis effects. Glycyrrhetinic acid can inhibit inflammatory responses, oxidative stress, and cell damage by regulating multiple signaling pathways such as nuclear factor E2-related factor 2 / antioxidant response element (Nrf2 / ARE), thus exerting a hepatoprotective effect.

[0048] The traditional Chinese medicine composition and its preparation for treating chronic hepatitis B virus-related cirrhosis provided by this invention have good safety and high practicality, and show good efficacy in treating HBV-related cirrhosis (liver stagnation and toxin obstruction syndrome).

[0049] 1) It can effectively improve liver function indicators, liver stiffness value, four liver fibrosis items, and HBV-DNA viral load;

[0050] 2) It can improve the TCM symptoms of patients with HBV-related cirrhosis and liver stagnation and toxicity, especially in terms of stabbing pain in the hypochondrium, pain that does not move, abdominal distension, hardness upon palpation, mass under the ribs, purplish-brown lips, poor appetite, insomnia, shortness of breath and fatigue. Attached Figure Description

[0051] Figure 1 To compare the aspartate aminotransferase (AST) levels before and after treatment in two groups of patients.

[0052] Figure 2 To compare the alanine aminotransferase (ALT) levels before and after treatment in two groups of patients.

[0053] Figure 3 This study compares serum total bilirubin (TBIL) levels before and after treatment in two groups of patients.

[0054] Figure 4 The study compared the liver stiffness (LSM) index between the two groups of patients before and after treatment.

[0055] Figure 5 This study compares the hyaluronic acid (HA) levels before and after treatment in two groups of patients.

[0056] Figure 6 To compare the levels of laminin (LN) before and after treatment in two groups of patients.

[0057] Figure 7 This study compares the levels of type III procollagen N-terminal peptide (PⅢNP) before and after treatment in two groups of patients.

[0058] Figure 8 To compare the levels of type IV collagen (CⅣ) before and after treatment in two groups of patients.

[0059] Figure 9 This study compares the levels of chronic hepatitis B virus deoxyribonucleic acid (HBV-DNA) before and after treatment in two groups of patients.

[0060] Figure 10 This study compares the scores of various TCM syndromes before and after treatment in the control group.

[0061] Figure 11 The scores of various TCM syndromes were compared before and after treatment in the experimental group.

[0062] Figure 12 The total scores of TCM syndromes were compared between the two groups of patients before and after treatment.

[0063] Figure 13 To compare the overall efficacy of TCM syndromes in two groups of subjects. Detailed Implementation

[0064] Combined with the embodiments of the present invention, the technical solutions in the embodiments will be clearly and completely described. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. All other embodiments obtained by those of ordinary skill in the art based on the embodiments of the present invention without creative efforts shall fall within the protection scope of the present invention.

[0065] Research on the beneficial effects of the present invention:

[0066] I. Research materials and methods

[0067] (I) Research materials

[0068] 1. Research objects

[0069] The experimental objects of this study were all from the outpatient and inpatient departments of the Department of Gastroenterology and the Department of Infectious Diseases of the Provincial Tongde Hospital Affiliated to Zhejiang Chinese Medical University. The enrollment time was from July 2023 to September 2024. All the patients who visited the doctor met the diagnostic criteria for HBV-related liver cirrhosis (syndrome of liver depression and toxin stasis).

[0070] 2. Diagnostic criteria and syndrome differentiation criteria

[0071] (1) Western medicine diagnostic criteria

[0072] The diagnostic criteria for HBV-related liver cirrhosis were drawn up by referring to the "Guidelines for the Diagnosis and Treatment of Liver Cirrhosis" formulated by the Chinese Liver Disease Society of the Chinese Medical Association in 2019 and the "Guidelines for the Prevention and Treatment of Chronic Hepatitis B" formulated by the Chinese Liver Disease Society of the Chinese Medical Association in 2022:

[0073] ① Currently positive for HBsAg, or negative for HBsAg, positive for anti-HBc, and with a clear history of chronic HBV infection (previous HBsAg positive for >6 months), and excluding other etiologies.

[0074] ② The liver biopsy pathology conforms to the manifestations of liver cirrhosis.

[0075] ③ Meeting 2 or more of the following 5 items, and excluding non-cirrhotic portal hypertension:

[0076] a. Imaging examination shows signs of liver cirrhosis and / or portal hypertension;

[0077] b. Endoscopic examination shows esophageal and gastric varices;

[0078] c. Liver stiffness measurement (LSM) conforms to liver cirrhosis (when ALT < 1×ULN, LSM ≥ 12.0 kPa; when 1×ULN < ALT < 5×ULN, LSM ≥ 17.0 kPa);

[0079] d. Blood biochemistry tests showed decreased albumin levels (<35g / L) and / or prolonged PT (>3s longer than control);

[0080] e. A complete blood count shows a platelet count <100×10⁻⁶. 9 / L etc.

[0081] Diagnosis confirmation: Based on the above criteria, if condition ① is met, and condition ② or ③ is also met, a comprehensive diagnosis of HBV-related cirrhosis can be made.

[0082] (2) Traditional Chinese Medicine diagnostic criteria

[0083] Based on the "Consensus on the Diagnosis and Treatment of Liver Cirrhosis with Integrated Traditional Chinese and Western Medicine (2011 Edition)" and the 2002 edition of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs (Trial Implementation)," a classification standard for HBV-related liver cirrhosis with liver stagnation and toxicity obstruction syndrome was formulated, and a TCM syndrome scoring table was created.

[0084] Main symptoms: ① Stabbing pain in the hypochondrium, with no shifting location; ② Abdominal distension, hard to the touch; ③ Mass under the ribs; ④ Purplish-brown lips.

[0085] Secondary symptoms: ① fatigue and weight loss; ② shortness of breath and weakness; ③ poor appetite and insomnia; ④ irritability and insomnia.

[0086] Tongue appearance: The tongue is swollen and large with a white coating.

[0087] Pulse characteristics: Thready and hesitant or wiry and slippery.

[0088] The syndrome type is determined by the presence of two primary symptoms, one secondary symptom, tongue appearance, and a reference pulse (a thin, hesitant, or slippery pulse).

[0089] 3. Inclusion criteria

[0090] (1) Age 18-80 years old, gender not limited;

[0091] (2) Meets the diagnostic criteria for HBV-related cirrhosis;

[0092] (3) Meets the diagnostic criteria for liver stagnation and toxicity obstruction syndrome;

[0093] (4) No contraindications for use in the study;

[0094] (5) If you agree to participate in this study, you may take medication as prescribed by your doctor.

[0095] 4. Exclusion Criteria

[0096] (1) Cirrhosis caused by other causes, including those with hepatitis B or other hepatitis virus infections, alcoholic cirrhosis, autoimmune cirrhosis, primary biliary cirrhosis, schistosomiasis cirrhosis, etc.

[0097] (2) Patients with serious primary diseases of the cardiovascular, renal and hematopoietic systems, as well as mental illnesses;

[0098] (3) Pregnant or breastfeeding women; persons with disabilities as defined by law;

[0099] (4) Those who are unwilling to accept research measures or have other reasons for not being able to cooperate;

[0100] (5) Those with a known or suspected history of allergy to or severe adverse reactions to traditional Chinese medicine;

[0101] (6) Individuals who participated in other clinical trials within 3 months prior to enrollment;

[0102] (7) History of malignant tumors;

[0103] (8) Accompanied by diseases that may affect the appearance of the tongue and pulse, such as hemangioma, varicose veins of the lower extremities, tongue lesions, etc.;

[0104] (9) Other situations in which the researchers believe that it is not appropriate for them to participate in this trial, including those who have received traditional Chinese medicine treatment within the past two weeks.

[0105] 5. Rejection criteria and dropout criteria

[0106] (1) Those who are mistakenly included because they do not meet the inclusion criteria, cannot cooperate to complete the trial, violate the drug use regulations and clinical trial protocol, or undergo other drug trials during the trial period shall be excluded.

[0107] (2) Cases that were dropped due to incomplete data, inability to perform statistical analysis, serious adverse reactions, special physiological changes that made it unsuitable to continue the trial, loss to follow-up, or voluntary withdrawal were all considered dropout cases.

[0108] 6. Criteria for Termination

[0109] (1) A serious adverse event related to the investigational drug occurs;

[0110] (2) The researchers believe that continuing the trial may cause harm to the subjects;

[0111] (3) Subjects may request early termination of the treatment trial for various reasons;

[0112] 7. Ethical requirements

[0113] This study has been approved by the relevant ethical authorities (Ethical Review No. 2023-030, Zhejiang University of Traditional Chinese Medicine Affiliated Provincial Tongde Hospital), and all participants have been informed of the relevant risks.

[0114] (II) Research Methods

[0115] 1. Sample size estimation

[0116] This is a clinical study, designed according to the principles of randomized controlled trials. The final treatment efficacy rate in both the experimental and control groups is the outcome measure of this study. The sample size was calculated using the following formula:

[0117]

[0118] Based on the principle of statistical sample size, let α = 0.05, and the power be 90%, then Z α =1.96, Z β =1.28. Based on a literature review of the disease, the expected effective rate is 80% in the experimental group and 60% in the control group, i.e., P1=0.9, P2=0.6. Calculated... n =43 cases. Based on the requirements of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines" and the patient's medical history, the expected dropout rate was 10%, therefore the final calculation was... n 1 = n 2 =48 cases, a total of 96 subjects need to be included.

[0119] 2. Grouping method

[0120] Subjects collected from this study between July 2023 and September 2024 were randomly assigned to groups using a random number table generated by SPSS 26.0 statistical software.

[0121] 3. Treatment Plan

[0122] (1) Experimental group

[0123] The patient was treated with a modified Shugan Jiedu Decoction (6g of stir-fried Bupleurum chinense, 9g of stir-fried Citrus aurantium, 12g of stir-fried Paeonia lactiflora, 9g of stir-fried Citrus reticulata peel, 9g of Curcuma zedoaria, 15g of Sedum sarmentosum, 20g of Hedyotis diffusa, and 5g of Glycyrrhiza uralensis). The decoction was prepared by the pharmaceutical preparation room of Zhejiang University of Traditional Chinese Medicine Affiliated Provincial Tongde Hospital. Each dose was decocted into 150mL x 2 bags, taken orally one hour after breakfast and dinner, respectively. Western medicine treatment included entecavir (0.5mg x 21 tablets, Suzhou Dongrui Pharmaceutical Co., Ltd., National Drug Approval Number: H20100129) 0.5mg orally, one tablet daily. One course of treatment consisted of three consecutive months of continuous use, followed by a three-month break, and then another three-month continuous use. Two courses of treatment were administered annually.

[0124] (2) Control group

[0125] Entecavir (0.5mg x 21 tablets, Suzhou Dongrui Pharmaceutical Co., Ltd., National Drug Approval Number: H20100129) 0.5mg orally, one tablet daily. One course of treatment is 3 months of continuous use. After a 3-month break, continue taking the medication for another 3 months. Two courses of treatment are required annually.

[0126] 4. Observation Indicators

[0127] (1) General observation indicators:

[0128] Baseline information such as gender and age was recorded immediately after enrollment. The pre-treatment gender and age distributions of the two groups were compared to determine for statistical significance. Pre-enrollment liver function indicators, liver stiffness values, four liver fibrosis markers, HBV-DNA viral load, and TCM syndrome scores were recorded using two independent samples. t The statistical test was performed to compare the severity of the patients' conditions and the presence of symptoms before enrollment to determine if there were any statistically significant differences.

[0129] (2) Liver function indicators

[0130] The levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (TBIL) were measured at weeks 0 and 24 of treatment.

[0131] (3) Four indicators of liver fibrosis

[0132] The changes in hyaluronic acid (HA), laminin (LN), procollagen III N-terminal peptide (PⅢNP), and type IV collagen (CⅣ) were monitored at weeks 0 and 24 of treatment.

[0133] (4) Liver stiffness index

[0134] Liver stiffness values ​​were measured using a liver function shear wave quantification ultrasound diagnostic instrument (FibroScan) at weeks 0 and 24 of treatment.

[0135] (5) HBV-DNA viral quantitative indicators

[0136] Changes in HBV-DNA viral quantitative indicators were detected at week 0 and week 24 of treatment.

[0137] (6) Indicators of TCM syndrome efficacy

[0138] A TCM syndrome scale was developed based on the 2002 edition of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicine Drugs (Trial Implementation)". Each symptom was scored using a four-level grading system according to its severity (Level 0: None; Level I: Mild symptoms, not affecting daily life; Level II: Obvious symptoms, partially affecting daily life; Level III: Severe symptoms, significantly affecting work and life). Primary symptoms were scored at 0, 2, 4, or 6 points, and secondary symptoms at 0, 1, 2, or 3 points.

[0139] (7) Safety observation indicators:

[0140] General physical examination items: blood pressure, heart rate, heart rhythm, and respiration, with one examination before and one after treatment.

[0141] Relevant examinations included: routine blood tests; coagulation function tests; liver and kidney function tests; electrocardiogram; chest X-ray and abdominal ultrasound. These examinations were performed once before and after each course of treatment to observe for any toxic side effects. All of the above were recorded by the physician acting as the investigator.

[0142] The safety evaluation criteria were formulated with reference to the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines": Grade I: Safe, no adverse reactions were observed during the treatment period; Grade II: Relatively safe, adverse reactions that occurred did not require special treatment, and the trial administration could continue; Grade III: There is a certain degree of safety risk, adverse reactions have occurred during the trial, and symptomatic treatment is required, but the subject can continue to participate in the clinical trial after improvement; Grade IV: The serious adverse reactions experienced by the subject prevented the continuation of the clinical trial.

[0143] 5. Evaluation Criteria

[0144] (1) Evaluation criteria for TCM syndrome differentiation and treatment efficacy

[0145] Calculated using the Nimodipine method:

[0146] The efficacy index = (pre-treatment score - post-treatment score) / pre-treatment score × 100%.

[0147] ① Clinical cure: The main symptoms and signs have disappeared or basically disappeared, and the efficacy index is ≥95%;

[0148] ②Significant effect: Major symptoms and signs are significantly improved, with 70% ≤ efficacy index < 95%;

[0149] ③ Effective: Major symptoms and signs show significant improvement, with 30% ≤ efficacy index < 70%;

[0150] ④ Ineffective: The main symptoms and signs do not improve significantly, or even worsen, and the efficacy index is <30%.

[0151] Overall effective rate = (number of cured cases + number of cases with significant effect + number of effective cases) / total number of cases × 100%.

[0152] (2) Safety evaluation standards

[0153] Formulated with reference to the 2002 edition of the "Guiding Principles for Clinical Research of New Traditional Chinese Medicines (Trial Implementation)":

[0154] ① Grade I: Safe, no adverse reactions occurred during treatment;

[0155] ② Grade II: Relatively safe. If adverse reactions occur, no special treatment is required, and subsequent drug therapy can be administered.

[0156] ③ Level III: There are safety issues. Certain adverse reactions occurred during the test. After appropriate treatment, subsequent tests can be carried out.

[0157] ④ Grade IV: Serious adverse reactions occur, and the clinical trial needs to be terminated.

[0158] 6. Statistical methods

[0159] SPSS 26.0 was used to analyze and process the data in this study. Quantitative data that conformed to a normal distribution were analyzed using... t Tests were performed; the chi-square test was used for count data; the rank-sum test was used for non-normally distributed measurement data and ordinal data. The descriptive method for the analysis results was selected based on the distribution characteristics: normally distributed data were described using the mean. ± standard deviation s The values ​​are indicated by , and non-normally distributed data are presented as the median and interquartile range M (P25, P75). The statistical significance level is set at α = 0.05. P <0.05 indicates a statistically significant difference in the test results; P >0.05, indicating no statistically significant difference in the test results.

[0160] II. Research Results

[0161] (a) Patient information included

[0162] This study enrolled 96 patients from July 2023 to September 2024, who were randomly divided into an experimental group and a control group, with 48 patients in each group. In the experimental group, 3 patients were excluded because they could not complete the questionnaire, and 2 patients dropped out due to changes in residence for work reasons. In the control group, 4 patients were excluded because they could not complete the questionnaire, and 1 patient dropped out due to personal refusal. Ultimately, 43 patients from each group completed the study, with an overall dropout rate of 10.4%. (See Table 1 for details)

[0163] Table 1 Completion status of the two groups of patients

[0164]

[0165] (II) Comparison of general data

[0166] 1. Gender comparison

[0167] This study included 55 males and 31 females. The experimental group consisted of 28 males and 15 females (male-to-female ratio 1.87:1), while the control group consisted of 27 males and 16 females (male-to-female ratio 1.69:1). There was no statistically significant difference in gender composition between the experimental and control groups. P (>0.05), indicating comparability between groups. (See Table 2 for details)

[0168] Table 2 Comparison of gender between the two groups of patients

[0169]

[0170] Note: The chi-square test was used to compare the sex ratios between the two patient groups.

[0171] 2. Age comparison

[0172] The oldest patient included in this study was 79 years old, and the youngest was 39 years old. The age distribution of the experimental group ranged from 39 to 71 years, with a mean age of (56.86 ± 9.93) years. The age distribution of the control group ranged from 42 to 79 years, with a mean age of (57.00 ± 9.21) years. No statistically significant differences were found between the experimental and control groups in age or age distribution. P (>0.05), indicating comparability between groups. (See Table 3 for details)

[0173] Table 3 Comparison of ages between the two groups of patients

[0174]

[0175] Note: The comparison of the mean age of the two groups of patients used an independent sample. t test

[0176] 3. Observe the baseline comparison of indicators

[0177] Statistical analysis was performed on the liver function (AST, ALT, TBIL), four indicators of liver fibrosis (HA, LN, PⅢNP, IV-C), liver stiffness value (LSM), HBV-DNA viral load, and total TCM syndrome score of the two groups of patients before treatment. The results indicated that there were no statistically significant differences in the clinical data between the groups. P (>0.05), making them comparable. (See Table 4 for details)

[0178] Table 4 Comparison of observation indicators between the two groups of cases before treatment

[0179]

[0180] Note: Comparison of observational indicators between the two groups of patients used independent samples. t test

[0181] (III) Comparison of efficacy and safety

[0182] 1. Comparison of various liver function indicators before and after treatment

[0183] The liver function indicators (AST, ALT, TBIL) of both groups of patients before and after treatment were found to be normal and homogeneous in variance. Independent samples were used. t Tests showed that after the treatment course, the levels of AST, ALT, and TBIL in both groups decreased significantly compared to before treatment, and the differences were statistically significant. P <0.05); In intergroup comparisons, the experimental group showed a more significant decrease in AST, ALT, and TBIL levels after treatment compared to the control group, and the differences were statistically significant. P <0.05). (See Table 5 for details) Figures 1-3 )

[0184] This indicates that both treatment regimens improved liver function indicators in patients with HBV-related cirrhosis, but the combination of entecavir and Shugan Jiedu Decoction was more effective than entecavir alone. From a Traditional Chinese Medicine perspective, Bupleurum, Citrus aurantium, and Citrus reticulata have the effects of soothing the liver, relieving depression, regulating qi, and relieving stagnation in the middle jiao, thus improving liver qi and blood circulation and reducing the burden on the liver. Sedum sarmentosum and Paeonia lactiflora clear heat, cool blood, and detoxify, effectively reducing the inflammatory response in patients. Curcuma zedoaria and Hedyotis diffusa invigorate blood, regulate qi, clear heat, and detoxify, improving liver microcirculation, reducing hepatocyte damage, and promoting liver function recovery. From a modern pharmacological perspective, studies show that saikosaponin B2 in Bupleurum can significantly alleviate lipopolysaccharide / galactosamine-induced serum ALT and AST levels in mice and reduce liver damage by inhibiting inflammatory factors (TNF-α, IL-1β, IL-6) and improving energy metabolism. Citrus aurantium extract can reduce the infiltration of inflammatory cells in the liver and reduce damage to liver tissue. In addition, Sedum sarmentosum has also been shown to significantly reduce serum AST and ALT levels.

[0185] Table 5. Comparison of ALT, AST, and TBIL levels before and after treatment in the two groups of patients.

[0186]

[0187] Note: Comparisons of ALT, AST, and TBIL levels before and after treatment in both groups of patients were performed using... t test.

[0188] 2. Comparison of LSM values ​​before and after treatment

[0189] The LSM values ​​of both groups of patients before and after treatment were found to be normal and homogeneous in variance, using independent samples. t Tests showed that after the treatment course, LSM levels in both groups decreased compared to before treatment, and the difference was statistically significant. P <0.05); In intergroup comparison, the LSM level decreased more significantly in the experimental group than in the control group after treatment, and the difference was statistically significant. P <0.05). (See Table 6 for details) Figure 4 )

[0190] Table 6 Comparison of LSM indices before and after treatment in the two groups of patients

[0191]

[0192] Note: Comparison of LSM levels before and after treatment in both groups of patients was performed using... t test.

[0193] 3. Comparison of four liver fibrosis indicators before and after treatment

[0194] The four liver fibrosis indicators (HA, LN, PⅢNP, CⅣ) of both groups of patients before and after treatment were found to be normal and homogeneous in variance. Independent samples were used. t Tests showed that after the treatment course, the levels of HA, LN, PⅢNP, and CⅣ in both groups decreased compared to before treatment, and the differences were statistically significant. P <0.05); In intergroup comparisons, the levels of HA, LN, PⅢNP, and IV-C decreased more significantly in the experimental group than in the control group after treatment, and the differences were statistically significant. P <0.05). (See Table 7 for details) Figures 5-8 )

[0195] Table 7 Comparison of four liver fibrosis indicators (HA, LN, PⅢNP, CⅣ) before and after treatment in the two groups of patients.

[0196]

[0197] Note: Comparison of the four liver fibrosis indicators (HA, LN, PⅢNP, CⅣ) before and after treatment in both groups of patients was conducted using... t test.

[0198] Comparative analysis of LSM and four liver fibrosis markers (HA, LN, PⅢNP, CⅣ) showed that both treatment regimens could improve liver stiffness and the four liver fibrosis markers in patients with HBV-related cirrhosis. However, the efficacy of entecavir combined with Shugan Jiedu Decoction was superior to entecavir alone. The formation of liver fibrosis in HBV-related cirrhosis patients is initially due to the invasion of pathogenic toxins, which linger in the liver meridians, causing stagnation of Qi and blood, leading to blood stasis. Body fluids accumulate as phlegm due to abnormal Qi transformation. The phlegm and blood stasis become intertwined in the liver meridians, further obstructing the ascending and descending of Qi in the liver meridians. This is the root cause of the persistent and difficult-to-cure nature of liver fibrosis. Stir-fried Bupleurum chinense relieves stagnation of Qi in the liver and gallbladder, allowing the liver to relax. Stir-fried Citrus aurantium works synergistically with Bupleurum chinense, one ascending and the other descending, regulating the Qi mechanism of the middle Jiao. When the liver Qi flows smoothly, the spleen can function properly, preventing the internal generation of phlegm and dampness, thus cutting off the source of fibrosis. Stir-fried Citrus reticulata regulates Qi and strengthens the spleen, allowing the earth element to "reach its proper place," ensuring the source of Qi and blood production, nourishing the liver, making it supple and moist, and relieving the spasm of the liver meridians. Stir-fried Paeonia lactiflora and Curcuma zedoaria directly enter the liver meridians, promoting blood circulation and eliminating blood stasis to dissipate masses. Sedum sarmentosum and Lysimachia christinae clear away epidemic toxins and prevent the regeneration of toxins and blood stasis. The entire formula, through regulating Qi, resolving blood stasis, and clearing toxins, uses the principle of "unblocking" and "softening" to treat the meridians, restoring the liver meridians to their "supple and smooth" nature, and naturally eliminating fibrosis masses. In modern pharmacology, turmeric can exert its anti-hepatic fibrosis effect by inhibiting the TGF-β1 / Smad signaling pathway, reducing collagen fiber deposition, and improving hepatocyte inflammatory damage. Saikosaponin D, one of the most pharmacologically active components of Bupleurum chinense, can reverse the epithelial-mesenchymal transition (EMT) to the EMT process, thus exerting its anti-hepatic fibrosis effect. Sedum sarmentosum can also inhibit the proliferation activity of hepatocytes (HSCs), ultimately exerting its anti-fibrotic biological effect. Furthermore, Paeonia lactiflora has also been shown to slow the progression of hepatic fibrosis by reducing the synthesis and deposition of collagen fibers in liver tissue.

[0199] 4. Comparison of HBV-DNA levels before and after treatment

[0200] The HBV-DNA levels in both groups of patients before and after treatment were found to be normal and homogeneous in variance, using independent samples. t Tests showed that after the treatment course, the HBV-DNA levels in both groups decreased compared to before treatment, and the difference was statistically significant. P <0.05); In intergroup comparison, the HBV-DNA level in the experimental group decreased more significantly than that in the control group after treatment, and the difference was statistically significant. P <0.05). (See Table 8 for details) Figure 9 )

[0201] This indicates that both treatment regimens can improve HBV-DNA levels in patients with HBV-related cirrhosis, but the efficacy of entecavir combined with Shugan Jiedu Decoction is superior to entecavir alone. The latent hepatitis B virus within the liver meridians, with toxicity and blood stasis intertwined, is a key pathogenesis for persistent viral replication. The formula contains Sedum sarmentosum and Hedyotis diffusa, which are highly effective at clearing heat and detoxifying. The *Compendium of Materia Medica* states that Sedum sarmentosum "detoxifies the epidemic and benefits the liver and gallbladder," while Hedyotis diffusa detoxifies and disperses nodules, degrading the latent epidemic toxins within the liver. Fried Bupleurum chinense soothes the liver and guides the medicine into the liver meridian, aiding in the outward expulsion of the toxins; Curcuma zedoaria and fried Paeonia lactiflora invigorate blood and remove blood stasis, improving liver meridian obstruction and preventing the mutual accumulation of toxins and blood stasis. Glycyrrhiza uralensis harmonizes the other herbs, tonifies qi, and supports the body's defenses against toxins. The entire formula clears the epidemic toxins to inhibit replication, soothes the liver meridians to expel the toxins, and resolves blood stasis to strengthen the body's foundation, embodying the TCM treatment principle of "removing the toxins and restoring health." Saikosaponin C exerts its anti-HBV effect by upregulating IL-6 expression, inhibiting the activity of hepatocyte nuclear factors HNF1α and HNF4α, and blocking the transcription process of HBV pregenomic RNA. In addition, glycyrrhizic acid exerts its anti-HBV effect through multiple pathways, including inhibiting the secretion of hepatitis B virus surface antigen, regulating immune cell activity, and inducing interferon production.

[0202] Table 8 Comparison of HBV-DNA levels before and after treatment in the two groups of patients

[0203]

[0204] Note: Comparisons of HBV-DNA levels before and after treatment in both groups were conducted using... t test.

[0205] 5. Comparison of TCM syndrome differentiation and treatment efficacy

[0206] The results showed that the TCM syndrome scores of the two groups of patients did not conform to normality before and after treatment; therefore, the rank-sum test was used. Before treatment, there were no statistically significant differences in the TCM syndrome scores between the experimental group and the control group. P >0.05); After the course of treatment, the scores of all TCM syndromes in the experimental group decreased compared with those before treatment, and the differences were statistically significant. P <0.05); In the control group, the incidence of stabbing pain in the hypochondrium, fixed pain location, abdominal distension, hardness upon palpation, palpable mass under the ribs, purplish-brown lips, fatigue, and emaciation was statistically significant compared to before treatment. P <0.05), while shortness of breath, fatigue, irritability, insomnia, and poor appetite were not statistically significant compared to before treatment ( P >0.05). In intergroup comparisons, the experimental group showed significantly greater improvement than the control group in areas such as fixed pain location, abdominal distension and hardness upon palpation, palpable mass under the ribs, purplish-brown lips, shortness of breath and fatigue, poor appetite and insomnia after treatment, which was statistically significant. P <0.05), but there was no statistically significant difference in fatigue, weight loss, irritability, and insomnia. P >0.05).

[0207] By examining whether the total TCM syndrome scores of both groups of patients before and after treatment met the requirements of normality and homogeneity of variance, independent samples were used. t Test. After the course of treatment, the total TCM syndrome scores of both groups of patients decreased compared with those before treatment, and the difference was statistically significant. P <0.05); In intergroup comparison, the total TCM syndrome score of the experimental group decreased more significantly than that of the control group after treatment, and the difference was statistically significant. P <0.05). (See Table 9 for details) Figures 10-12 )

[0208] Table 9 Comparison of TCM syndrome scores before and after treatment in the two groups of patients (M(P25, P75))

[0209]

[0210] Table 9 (Continued) Comparison of TCM syndrome scores before and after treatment in the two groups of patients (M(P25, P75))

[0211]

[0212] Note: The rank-sum test was used to compare the scores of various TCM syndromes before and after treatment in both groups of patients; the total scores of TCM syndromes were compared using... t test.

[0213] 6. Comparison of overall efficacy of traditional Chinese medicine

[0214] After 24 weeks of treatment, the total effective rate of TCM syndrome differentiation in the experimental group was 93.02%, while that in the control group was 72.09%. The difference in the total effective rate of TCM syndrome differentiation between the two groups was statistically significant. P <0.05). (See Table 10 for details) Figure 13 )

[0215] Table 10 Comparison of TCM syndrome improvement rates between the two groups of patients ( n )

[0216]

[0217] Note: Chi-square analysis was used to compare the improvement rates of TCM syndromes between the two groups of patients.

[0218] 7. Comparison of safety and adverse reactions

[0219] During the 24-week clinical observation period, all patients had stable vital signs, and no significant abnormalities were observed in routine blood tests, liver and kidney function indicators, or electrocardiogram results. No adverse events were observed.

[0220] The foregoing description of embodiments of the present invention, through which those skilled in the art are able to implement or use the present invention, will be readily apparent to those skilled in the art. Various modifications to these embodiments will be readily apparent to those skilled in the art. The general principles defined herein may be implemented in other embodiments without departing from the spirit or scope of the invention. Therefore, the present invention is not to be limited to the embodiments shown herein, but is to be accorded the widest scope consistent with the principles and novelty disclosed herein.

Claims

1. A drug kit for treating chronic hepatitis B virus-related cirrhosis with liver stagnation and toxicity obstruction, characterized in that, include: First component: a traditional Chinese medicine composition or a preparation made from the traditional Chinese medicine composition; Second component: entecavir or a pharmaceutically acceptable salt thereof; The effective components of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 4-8 parts of stir-fried Bupleurum chinense, 7-11 parts of stir-fried Citrus aurantium, 10-14 parts of stir-fried Paeonia lactiflora, 7-11 parts of stir-fried Citrus reticulata peel, 7-11 parts of Curcuma zedoaria, 13-17 parts of Sedum sarmentosum, 18-22 parts of Hedyotis diffusa, and 3-7 parts of raw Glycyrrhiza uralensis.

2. The drug kit according to claim 1, characterized in that, The effective components of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 6 parts of stir-fried Bupleurum chinense, 9 parts of stir-fried Citrus aurantium, 12 parts of stir-fried Paeonia lactiflora, 9 parts of stir-fried Citrus reticulata peel, 9 parts of Curcuma zedoaria, 15 parts of Sedum sarmentosum, 20 parts of Hedyotis diffusa, and 5 parts of raw Glycyrrhiza uralensis.

3. The drug kit according to claim 1, characterized in that, The traditional Chinese medicine composition preparation is in the form of tablets, granules, capsules, ointments, or liquids.

4. The drug kit according to claim 1, characterized in that, The first and second components are packaged in the same outer packaging and accompanied by instructions for patients to administer the medication according to the following cyclical procedure: The herbal composition is taken orally twice daily, each time corresponding to 150 mL of concentrated decoction or an equivalent amount of solid preparation, one hour after breakfast and dinner, respectively; Entecavir is taken continuously at 0.5 mg daily for the entire course of treatment; one course of treatment is 3 months of continuous use, followed by a 3-month break, and then another 3 months of continuous use, with 2 courses of treatment per year.

5. The drug kit according to claim 1, characterized in that, The preparation method of the traditional Chinese medicine composition is to weigh all the medicinal materials in proportion, decoct and concentrate them, or prepare them into a formulation in an appropriate dosage form.

6. The use of the pharmaceutical kit according to any one of claims 1-5 in the preparation of a drug for treating chronic hepatitis B virus-related cirrhosis.

7. The application according to claim 6, characterized in that, This application is used to treat HBV-related cirrhosis with liver stagnation and toxicity, including: Improve liver function indicators, liver stiffness value, four liver fibrosis parameters, and HBV-DNA viral load; In addition, it improves the patient's TCM symptoms, which include stabbing pain in the hypochondrium, pain that does not move, abdominal distension, hardness upon palpation, lumps under the ribs, purplish-brown lips, poor appetite and insomnia.

8. The use of a traditional Chinese medicine composition or a preparation of the traditional Chinese medicine composition in combination with entecavir in the preparation of a drug for treating chronic hepatitis B virus-related cirrhosis; the effective components of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 4-8 parts of stir-fried Bupleurum chinense, 7-11 parts of stir-fried Citrus aurantium, 10-14 parts of stir-fried Paeonia lactiflora, 7-11 parts of stir-fried Citrus reticulata peel, 7-11 parts of Curcuma zedoaria, 13-17 parts of Sedum sarmentosum, 18-22 parts of Hedyotis diffusa, and 3-7 parts of raw Glycyrrhiza uralensis.

9. The application according to claim 8, characterized in that, The effective components of the traditional Chinese medicine composition are composed of the following raw materials in parts by weight: 6 parts of stir-fried Bupleurum chinense, 9 parts of stir-fried Citrus aurantium, 12 parts of stir-fried Paeonia lactiflora, 9 parts of stir-fried Citrus reticulata peel, 9 parts of Curcuma zedoaria, 15 parts of Sedum sarmentosum, 20 parts of Hedyotis diffusa, and 5 parts of raw Glycyrrhiza uralensis.

10. The application according to claim 8, characterized in that, The traditional Chinese medicine composition preparation is in the form of tablets, granules, capsules, ointments, or liquids.

Images