Anti-hepatic fibrosis pure traditional Chinese medicine composition and application thereof

Abstract

The composition is prepared from humifuse euphorbia herb, exocarpium benincasae, herba asari, radix platycodonis, radix sophorae flavescentis, radix rehmanniae, leech, lumbricus, radix salviae miltiorrhizae, semen pharbitidis and radix glycyrrhizae, all the raw materials are natural medicinal raw materials, and chemical synthesis anti-hepatic fibrosis components are not contained. Through the synergistic effect of multiple components, the composition inhibits the liver fibrosis process at the molecule, cell and tissue levels, improves the liver structure and function, and can be used for preparing drugs for treating liver fibrosis caused by various causes. The invention has the advantages of naturalness, safety, multiple targets and integral regulation, and is suitable for long-term intervention of chronic liver diseases.

Description

A pure traditional Chinese medicine composition for treating liver fibrosis and its application Technical Field

[0001] This invention relates to the field of traditional Chinese medicine technology, specifically to a pure traditional Chinese medicine composition for anti-liver fibrosis and its application. Background Technology

[0002] Liver fibrosis is a pathological process caused by various chronic liver injury factors. Its essence lies in the excessive deposition of extracellular matrix components and the destruction of normal liver structure. Common causes of liver fibrosis include viral hepatitis, long-term heavy alcohol consumption, non-alcoholic fatty liver disease associated with metabolic syndrome, and other chronic liver injury factors. Modern medical research indicates that the core mechanism of liver fibrosis is the continuous activation of hepatic stellate cells, leading to the synthesis of large amounts of type I and type III collagen and other extracellular matrix components, accompanied by inflammatory responses, microcirculatory disturbances, and decreased hepatocyte function. Most existing anti-fibrotic drugs are chemically synthesized. Although some studies have shown certain inhibitory effects on fibrosis, they generally suffer from significant side effects, poor patient compliance, and limitations in long-term use. Some chemical drugs may also interfere with normal hepatocyte metabolism and even cause abnormal liver function.

[0003] In the field of traditional Chinese medicine, some single herbs or simple combinations have been used to improve liver function or reduce liver damage. However, these approaches often focus on single anti-inflammatory or hepatoprotective effects, lacking a systematic intervention across the entire process of liver fibrosis. For example, some studies only focus on the inhibitory effect of a single component on the proliferation of hepatic stellate cells, without addressing the comprehensive regulation of multiple aspects such as collagen degradation, microcirculation improvement, and immune modulation. Furthermore, existing traditional Chinese medicine compound formulas often employ conventional formulation strategies, have a limited number of components, and target only a single point of action, making it difficult to address the complex pathological network of liver fibrosis.

[0004] More importantly, existing technologies lack a specific combination of eleven natural herbs—Euphorbia humifusa, winter melon peel, Asarum, Platycodon grandiflorus, Sophora flavescens, Rehmannia glutinosa, Hirudo medicinalis, Pheretima aspergillum, Salvia miltiorrhiza, Pharbitis nil, and Glycyrrhiza uralensis—for anti-liver fibrosis. While these herbs traditionally possess properties such as clearing heat and detoxifying, promoting diuresis and reducing swelling, invigorating blood circulation and removing blood stasis, and harmonizing other herbs, existing technologies have not revealed their synergistic mechanism in anti-liver fibrosis, nor have they proposed a complete technical solution for preparing anti-liver fibrosis drugs using them as a whole composition. In particular, existing technologies lack disclosure regarding the concept of multi-component synergistic regulation of multiple stages of liver fibrosis.

[0005] The occurrence and development of liver fibrosis involves the abnormal activation of multiple signaling pathways, such as the transforming growth factor β1 signaling pathway, the platelet-derived growth factor signaling pathway, and the inflammatory cytokine network. Single-component or simple combinations often only act on one or a few of these pathways, making it difficult to achieve a holistic reversal of fibrosis. Therefore, there is an urgent need in this field for a safe, natural, pure traditional Chinese medicine composition capable of intervening in the process of liver fibrosis at multiple targets and through multiple pathways, in order to improve the shortcomings of existing treatment options.

[0006] Furthermore, existing traditional Chinese medicine preparations also have limitations in their preparation processes. Some methods fail to fully preserve the active sites of each component, leading to unstable efficacy or significant batch-to-batch variations. Regarding efficacy evaluation, current technologies largely rely on single in vitro or in vivo experimental models, lacking a comprehensive evaluation system and failing to fully reflect the overall effect of drugs on liver fibrosis. Therefore, it is necessary to develop a new preparation process and efficacy evaluation method to ensure the stability, safety, and effectiveness of the composition.

[0007] In summary, existing technologies in the field of traditional Chinese medicine for treating liver fibrosis have the following main shortcomings: First, they target only a single point of action and lack systematic regulation; second, the composition of ingredients is traditional and lacks innovation; third, the preparation process fails to fully preserve the active ingredients; fourth, the efficacy evaluation methods are not comprehensive enough; and fifth, there is insufficient evidence regarding safety and long-term use. These problems limit the clinical application and promotion of traditional Chinese medicine in the treatment of liver fibrosis. Therefore, there is an urgent need in this field for a novel pure traditional Chinese medicine composition that, through the synergistic effect of multiple components, intervenes in the process of liver fibrosis at multiple levels, including molecular, cellular, and tissue levels, while ensuring its natural, safe, and long-term applicability. Summary of the Invention

[0008] The purpose of this invention is to provide a pure traditional Chinese medicine composition for treating liver fibrosis and its application.

[0009] To achieve the above objectives, this invention provides the following technical solution: a pure traditional Chinese medicine composition for anti-liver fibrosis and its application. The composition comprises *Euphorbia humifusa*, *Cucumis melo* peel, *Asarum heterotropoides*, *Platycodon grandiflorus*, *Sophora flavescens*, *Rehmannia glutinosa*, *Hirudo medicinalis*, *Pheretima aspergillum*, *Salvia miltiorrhiza*, *Pharbitis nil*, and *Glycyrrhiza uralensis*. All components are natural medicinal raw materials and do not contain any artificially synthesized chemical anti-liver fibrosis components. The composition inhibits hepatic stellate cell activation, reduces extracellular matrix deposition, and improves hepatic microcirculation disorders through the synergistic effect of multiple components. It is clear that all components of the composition are of natural origin, avoiding the potential toxic side effects of chemically synthesized drugs. Simultaneously, the synergistic effect of multiple components covers multiple key stages of liver fibrosis, addressing both cell activation and microcirculation, thereby enhancing the overall anti-fibrotic effect and ensuring safety and specificity.

[0010] Furthermore, the components of the composition retain their natural properties during preparation without any chemical structural modification. Its active ingredients include flavonoids, saponins, alkaloids, polysaccharides, and polypeptides, which can form a multi-target regulatory network in vivo, acting on the entire process of liver fibrosis occurrence, development, and reversal. This emphasizes the natural properties and active categories of the components, clarifying that the composition can form a multi-target regulatory network in vivo, not only intervening in the initiation and development of fibrosis but also promoting the reversal process, making the treatment more comprehensive and avoiding the limitations of single-target intervention.

[0011] Furthermore, when preparing the composition into a pharmaceutical formulation, a single-solvent or multi-solvent extraction process can be used. Extraction conditions include a temperature controlled between 40°C and 90°C and an extraction time of 30 minutes to 3 hours. The resulting extract is then concentrated, dried, and mixed with other pharmaceutically acceptable excipients to form a dosage form suitable for oral or non-oral administration. This provides flexible preparation process parameters, making the production process controllable, fully preserving the activity of each component, and allowing for the formulation of different dosage forms according to clinical needs, facilitating use by different patients and improving the drug's applicability and manufacturability.

[0012] Furthermore, in the application of this composition to treat liver fibrosis, it can significantly reduce the hydroxyproline content in liver tissue, inhibit abnormal activation of the transforming growth factor β1 signaling pathway, reduce α-smooth muscle actin expression, and promote the degradation and reabsorption of deposited collagen fibers. The specific efficacy indicators and pathways of action have been clearly defined, demonstrating the composition's precise intervention capability at the molecular level. It can reduce the content of fibrosis markers, block key signaling pathways, and promote collagen degradation, making the therapeutic effect more definite and quantifiable.

[0013] Furthermore, the composition can be used to prepare drugs for treating liver fibrosis caused by viral infection, alcohol intake, metabolic disorders, or other reasons. Its targets include chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, non-alcoholic steatohepatitis, and related secondary liver fibrosis. This expands the scope of application of the composition, making it not limited to liver fibrosis of a single etiology, but capable of addressing multiple common causes, enhancing the versatility and clinical value of the drug, and providing treatment options for different patient groups.

[0014] Furthermore, the composition can be used in combination with other traditional Chinese medicines or natural products with hepatoprotective, anti-inflammatory, or immunomodulatory effects during drug preparation, without altering its pure traditional Chinese medicine properties and without introducing chemically synthesized antifibrotic drugs, thus maintaining the naturalness and safety of the overall regimen. This allows for combination therapy to enhance efficacy while strictly limiting the introduction of chemically synthesized drugs, ensuring the natural properties of the overall regimen and allowing patients to enjoy the safety advantages of traditional Chinese medicine while achieving stronger therapeutic effects.

[0015] Furthermore, in the preparation method of the composition, the active components of *Euphorbia humifusa*, *Cucumis melo* peel, *Asarum heterotropoides*, *Platycodon grandiflorus*, *Sophora flavescens*, *Rehmannia glutinosa*, *Hirudo medicinalis*, *Pheretima aspergillum*, *Salvia miltiorrhiza*, *Pharbitis nil*, and *Glycyrrhiza uralensis* can be extracted separately and then mixed, or they can be directly mixed and extracted together. The extracted product requires testing for characteristic indicator components during quality control to ensure batch-to-batch consistency. This provides two extraction strategies, increasing the flexibility of process selection. Simultaneously, the detection of characteristic indicator components ensures stable product quality, reduces batch-to-batch variations, and improves the reliability and safety of the drug in clinical use.

[0016] Furthermore, the efficacy of the composition can be verified through in vitro hepatic stellate cell proliferation inhibition experiments, collagen synthesis inhibition experiments, and in vivo animal model pathological improvement experiments of liver fibrosis. Its activity is significantly superior to that of a single component or a conventional combination of two to three traditional Chinese medicines. This clarifies a scientific method for efficacy evaluation, verifying the composition's effects at multiple levels from in vitro to in vivo, and demonstrating the advantages of synergistic effects of multiple components through comparative experiments. This provides evidence-based evidence for the efficacy and enhances the credibility and persuasiveness of the patent.

[0017] Furthermore, the composition allows for dosage and treatment duration adjustments based on the patient's degree of liver fibrosis. It exhibits high safety, with minimal risk of significant toxicity with long-term use and no impact on normal hepatocyte function, making it suitable for long-term management of chronic liver disease. This emphasis on dosage and treatment duration ensures individualized treatment while prioritizing long-term safety and protection of normal hepatocyte function, making the composition particularly suitable for the long-term management of chronic liver disease and enhancing the sustainability of clinical application.

[0018] Furthermore, the drug can be formulated into tablets, capsules, granules, oral liquid preparations, or injections, with routes of administration including oral, intravenous infusion, or intraperitoneal injection, suitable for the clinical treatment and adjuvant therapy of different types of liver fibrosis patients. This provides a wide range of dosage forms and routes of administration, meeting the medication habits and clinical needs of different patients, and is suitable for both therapeutic and adjuvant therapy, making the clinical application of the composition more extensive and flexible.

[0019] This invention provides a pure traditional Chinese medicine composition for anti-liver fibrosis and its application, which has the following beneficial effects: The pure traditional Chinese medicine composition for anti-liver fibrosis of this invention is composed of Euphorbia humifusa, winter melon peel, Asarum, Platycodon grandiflorus, Sophora flavescens, Rehmannia glutinosa, Hirudo medicinalis, Pheretima aspergillum, Salvia miltiorrhiza, Pharbitis nil, and Glycyrrhiza uralensis. All of them are natural medicinal raw materials and do not contain any artificially synthesized chemical anti-liver fibrosis components. It has the following significant advantages.

[0020] First, this composition, through the synergistic effect of multiple components, can block the occurrence and development of liver fibrosis at multiple stages. *Euphorbia humifusa* and *Cucumis melo* peel are rich in flavonoids and polysaccharides, which can regulate immune function and improve liver microcirculation; *Asarum heterotropoides* and *Sophora flavescens* contain alkaloids that can inhibit the release of inflammatory factors and reduce inflammatory damage to liver tissue; *Rehmannia glutinosa* and *Salvia miltiorrhiza* can promote hepatocyte metabolism and blood supply, enhancing the repair capacity of liver tissue; the active peptides contained in *Hirudo medicinalis* and *Pheretima aspergillum* promote fibrinolysis and improve microcirculation, helping to reverse existing fibrotic structures; *Pharbitis nil* and *Glycyrrhiza uralensis* harmonize the effects of the other herbs, protect hepatocytes, and reduce the potential stimulating effects of other components. This synergistic effect of multiple components and multiple targets gives this invention significant advantages in inhibiting hepatic stellate cell activation, reducing extracellular matrix deposition, and promoting collagen degradation, overcoming the limitations of existing technologies with single components or simple combinations.

[0021] Secondly, the compositions of this invention are entirely derived from natural medicinal materials, retaining their natural properties and without any chemical structural modifications. Therefore, they are highly safe and unlikely to produce significant toxic reactions with long-term use. Compared to chemically synthesized anti-liver fibrosis drugs, the pure traditional Chinese medicine compositions of this invention do not significantly interfere with the function of normal liver cells, making them suitable for the long-term management and treatment of chronic liver disease. This has significant clinical implications for liver fibrosis patients requiring long-term medication.

[0022] Third, the preparation process of this invention is flexible and diverse, allowing for extraction with single or combined solvents depending on different needs. Extraction conditions are controllable, ensuring full retention of the characteristic active sites of each component. In terms of quality control, batch-to-batch consistency can be ensured by detecting characteristic indicator components, thereby improving the stability and reliability of the drug. This flexible preparation method and rigorous quality control system make this invention highly feasible and worthy of widespread application in industrial production.

[0023] Fourth, in the application of the composition of the present invention to anti-liver fibrosis, it can not only significantly reduce the hydroxyproline content in liver tissue and inhibit the abnormal activation of the transforming growth factor β1 signaling pathway, but also reduce the expression of α-smooth muscle actin and promote the degradation and reabsorption of deposited collagen fibers. This multi-faceted regulatory effect gives it significant advantages in improving liver pathology scores and restoring liver function, especially in the treatment of liver fibrosis caused by chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, and non-alcoholic steatohepatitis.

[0024] Fifth, the compositions of this invention can be used in combination with other traditional Chinese medicines or natural products that have hepatoprotective, anti-inflammatory, or immunomodulatory effects without altering their pure traditional Chinese medicine properties or introducing chemically synthesized antifibrotic drugs. This combined application approach can further enhance efficacy while maintaining natural safety, providing patients with personalized treatment plans.

[0025] Sixth, the efficacy evaluation method of this invention is scientific and comprehensive, and can be comprehensively verified through in vitro hepatic stellate cell proliferation inhibition experiments, collagen synthesis inhibition experiments, and in vivo animal model pathological improvement experiments of liver fibrosis. Experimental results show that the anti-liver fibrosis effect of the composition of this invention is significantly better than that of a single component or conventional combination of two to three traditional Chinese medicines, proving its advantages of multi-component synergistic effect.

[0026] Seventh, the composition of this invention allows for adjustment of dosage and treatment course according to the patient's degree of liver fibrosis, exhibiting good adaptability and operability. Whether the patient has mild or severe liver fibrosis, satisfactory therapeutic effects can be achieved through reasonable dosage and treatment course design. Furthermore, it has high safety, allowing patients to take it long-term, which is beneficial for the continuous management and stabilization of chronic liver disease.

[0027] Eighth, the present invention offers diverse dosage forms, including tablets, capsules, granules, oral liquid preparations, or injections, with routes of administration including oral, intravenous infusion, or intraperitoneal injection, meeting the clinical needs of patients with different types of liver fibrosis. This diverse dosage form design improves patient convenience and compliance.

[0028] Ninth, this invention is innovative in its mechanism of action. For the first time, it combines eleven medicinal herbs—Euphorbia humifusa, winter melon peel, Asarum, Platycodon grandiflorus, Sophora flavescens, Rehmannia glutinosa, Hirudo medicinalis, Pheretima aspergillum, Salvia miltiorrhiza, Pharbitis nil, and Glycyrrhiza uralensis—to combat liver fibrosis, revealing their synergistic regulatory effects across multiple pathways and targets. This innovative formulation and mechanism explanation fills a gap in existing technologies in this field, providing new directions and evidence for research on traditional Chinese medicine's role in combating liver fibrosis.

[0029] Tenth, the overall solution of this invention embodies the holistic view and the principle of syndrome differentiation and treatment in traditional Chinese medicine. Through multi-component synergy and multi-stage regulation, it achieves a systematic intervention in liver fibrosis. This not only improves the treatment effect but also provides strong support for the modernization and internationalization of traditional Chinese medicine.

[0030] In summary, the anti-liver fibrosis pure traditional Chinese medicine composition of the present invention has significant advantages in terms of safety, efficacy, innovation, industrial production feasibility, and clinical application adaptability. It can effectively make up for the shortcomings of the prior art and provide a brand-new natural treatment option for patients with liver fibrosis. Detailed Implementation

[0031] Instructions for Use: This pure traditional Chinese medicine composition for liver fibrosis is composed of *Euphorbia humifusa*, *Cucumis melo* peel, *Asarum heterotropoides*, *Platycodon grandiflorus*, *Sophora flavescens*, *Rehmannia glutinosa*, *Hirudo medicinalis*, *Pheretima aspergillum*, *Salvia miltiorrhiza*, *Pharbitis nil*, and *Glycyrrhiza uralensis*. All ingredients are natural medicinal materials and contain no artificially synthesized chemical anti-liver fibrosis components. The dosage and duration of use should be determined based on the patient's degree of liver fibrosis and physical condition. It is recommended to take it in divided doses daily with a suitable amount of warm water to ensure stable absorption and action of the components in the body. During treatment, avoid consuming strong alcoholic beverages or high-concentration alcoholic drinks that significantly conflict with liver metabolism, as this may interfere with the targeted action of the components on the liver.

[0032] When preparing and consuming active ingredients, it is crucial to maintain their natural properties and avoid chemical modifications to fully leverage the multi-target regulatory effects of flavonoids, saponins, alkaloids, polysaccharides, and polypeptides. Warm administration is preferable to facilitate absorption of the active ingredients through the digestive tract and minimize potential gastrointestinal irritation. If using a decoction, it should be simmered over low heat to ensure even dissolution of different components, forming an active network covering the entire process of liver fibrosis occurrence, development, and reversal.

[0033] In terms of formulation, pharmaceutical preparations can be manufactured using single-solvent or multi-solvent extraction processes. The extraction temperature is controlled between 40°C and 90°C, and the extraction time is maintained between 30 minutes and 3 hours. After concentration and drying, the finished product is formulated into a dosage form suitable for oral or non-oral administration. When taking the medication, follow the instructions. If it is a non-oral dosage form, use it under the guidance of a professional to ensure that the route of administration matches the dosage form and avoid affecting efficacy due to misuse.

[0034] In the application of anti-liver fibrosis medications, at the molecular level, the composition should be taken regularly to allow it to exert its effects in vivo, such as reducing hydroxyproline levels in liver tissue, inhibiting abnormal activation of the transforming growth factor β1 signaling pathway, decreasing α-smooth muscle actin expression, and promoting the degradation and reabsorption of deposited collagen fibers. It is recommended to take the medication continuously for a certain period to allow the components to establish a stable regulatory effect at the molecular level. During this period, liver function and fibrosis markers should be monitored regularly, and the dosage should be adjusted according to changes.

[0035] This composition can be used for liver fibrosis caused by viral infection, alcohol intake, metabolic disorders, or other reasons. It is suitable for chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, non-alcoholic fatty liver disease, and related secondary liver fibrosis. When using this composition, it should be combined with antiviral therapy or metabolic management based on the specific etiology, to achieve a dual effect of etiological control and anti-fibrosis.

[0036] Precautions for combined use: When preparing and taking this medicine, it can be used in combination with other traditional Chinese medicines or natural products that have hepatoprotective, anti-inflammatory, or immunomodulatory effects, but its pure traditional Chinese medicine properties must not be altered, nor should chemically synthesized antifibrotic drugs be introduced. When using this medicine in combination, the timing of administration should be staggered, or it should be done under the guidance of a professional to maintain the naturalness and safety of the overall regimen.

[0037] In the preparation process, extraction and quality control should be used in combination. The active components of *Euphorbia humifusa*, *Cucurbita melon peel*, *Asarum heterotropoides*, *Platycodon grandiflorus*, *Sophora flavescens*, *Rehmannia glutinosa*, *Hirudo medicinalis*, *Pheretima aspergillum*, *Salvia miltiorrhiza*, *Pharbitis nil*, and *Glycyrrhiza uralensis* can be extracted separately and then mixed, or they can be directly mixed and then extracted together. During quality control, characteristic indicator components should be tested for the extracted substances to ensure batch-to-batch consistency. Before consumption, it should be confirmed that the product has undergone standardized quality testing to ensure the stability of component ratios and activity.

[0038] In efficacy evaluation, its anti-hepatic fibrosis effect can be verified through in vitro hepatic stellate cell proliferation inhibition experiments, collagen synthesis inhibition experiments, and in vivo animal model pathological improvement experiments of liver fibrosis. Its activity is significantly superior to that of a single ingredient or a conventional combination of two to three traditional Chinese medicines. Users can refer to relevant efficacy evaluation results during long-term use to build confidence in the efficacy of the combination and adhere to regular use.

[0039] Personalized dosage and treatment duration: In application, the dosage and treatment duration can be adjusted according to the patient's degree of liver fibrosis. It has a high safety profile, with little likelihood of significant toxic reactions with long-term use, and does not affect normal hepatocyte function, making it suitable for long-term management of chronic liver disease. It is recommended to develop a personalized treatment plan after professional evaluation, and to conduct efficacy assessments and adjustments at the end of each treatment phase.

[0040] Flexible use of dosage forms and routes of administration: This composition can be formulated into tablets, capsules, granules, oral liquid preparations, or injections. Routes of administration include oral, intravenous infusion, or intraperitoneal injection, suitable for the clinical treatment and adjuvant therapy of different types of liver fibrosis patients. When using this product, the appropriate dosage form and route of administration should be selected based on the patient's tolerance and condition. Oral dosage forms facilitate long-term management, while non-oral dosage forms are suitable for patients requiring rapid onset of action or with special conditions.

[0041] Example 1: Preparation and Use of Decoction Take *Euphorbia humifusa*, *Cucumis melo* peel, *Asarum heterotropoides*, *Platycodon grandiflorus*, *Sophora flavescens*, *Rehmannia glutinosa*, *Hirudo medicinalis*, *Pheretima aspergillum*, *Salvia miltiorrhiza*, *Pharbitis nil*, and *Glycyrrhiza uralensis*. Clean and remove impurities from each herb, then air-dry or low-temperature dry and chop. Place all herbs in a container, add an appropriate amount of water, soak for 30 minutes, then simmer over low heat at approximately 80°C for 1 hour. Filter to obtain the first decoction. Add an appropriate amount of water for a second decoction, maintaining the temperature at approximately 70°C for 40 minutes. Filter to obtain the second decoction. Combine the two decoctions, concentrate to a suitable volume, cool, and store in a clean, sealed container. Take an appropriate amount warm twice daily. This is suitable for oral administration and facilitates long-term management of liver fibrosis in patients with chronic liver disease.

[0042] Example 2: Preparation of Alcohol-Water Compound Extract Granules *Euphorbia humifusa*, *Cucumis melo* peel, *Asarum heterotropoides*, *Platycodon grandiflorus*, *Sophora flavescens*, *Rehmannia glutinosa*, *Hirudo medicinalis*, *Pheretima aspergillum*, *Salvia miltiorrhiza*, *Pharbitis nil*, and *Glycyrrhiza uralensis* were pulverized into coarse powder. A first extraction was performed using a 60% ethanol solution at 50°C for 2 hours, followed by filtration to obtain the ethanol extract. The residue was then subjected to a second extraction using boiling water at 90°C for 1 hour, followed by filtration to obtain the aqueous extract. The ethanol and aqueous extracts were combined, concentrated under reduced pressure until no alcohol odor remained, and an appropriate amount of pharmaceutically acceptable excipients were added. The mixture was thoroughly mixed, granulated, and dried to form granules. For use, one sachet of granules is dissolved in warm water and taken twice daily. This method is suitable for patients requiring convenient carrying and administration.

[0043] Example 3: Preparation of Capsules from Mixed Extraction Take *Euphorbia humifusa*, *Cucumis melo* peel, *Asarum heterotropoides*, *Platycodon grandiflorus*, *Sophora flavescens*, *Rehmannia glutinosa*, *Hirudo medicinalis*, *Pheretima aspergillum*, *Salvia miltiorrhiza*, *Pharbitis nil*, and *Glycyrrhiza uralensis*, mix them directly, and then pulverize them into a fine powder and sieve. Extract using a compound solvent (water and ethanol mixture) at 70℃ for 1.5 hours. Filter, concentrate the filtrate under reduced pressure to a thick paste, dry, and pulverize into a fine powder. Add an appropriate amount of pharmaceutical capsule filler, mix well, and fill into empty capsules to make capsules. Use orally according to the dosage specified in the instructions, twice daily. Suitable for patients who wish to have precise and easily controllable dosage.

[0044] Example 4: Preparation of Oral Liquid Formulation *Euphorbia humifusa*, *Cucumis melo* peel, *Asarum heterotropoides*, *Platycodon grandiflorus*, *Sophora flavescens*, *Rehmannia glutinosa*, *Hirudo medicinalis*, *Pheretima aspergillum*, *Salvia miltiorrhiza*, *Pharbitis nil*, and *Glycyrrhiza uralensis* were cleaned, dried, and pulverized respectively. Extraction was performed using a water decoction method, with the temperature controlled at 85℃ and the extraction time at 1 hour. The decoction was then filtered to obtain the final volume. After concentrating the decoction to a certain volume, appropriate amounts of flavoring agent and preservative were added, stirred evenly, and allowed to stand to clarify. The supernatant was then bottled into sterile glass bottles and sealed. Before use, shake well and take orally according to the dosage, twice daily. This is suitable for patients with difficulty swallowing or those who prefer liquid formulations.

[0045] Example 5: Preparation of Non-Oral Injectable Formulation (For Research or Special Clinical Use Only) The active components of *Euphorbia humifusa*, *Cucumis melo* peel, *Asarum heterotropoides*, *Platycodon grandiflorus*, *Sophora flavescens*, *Rehmannia glutinosa*, *Hirudo medicinalis*, *Pheretima aspergillum*, *Salvia miltiorrhiza*, *Pharbitis nil*, and *Glycyrrhiza uralensis* were extracted separately using a compound solvent extraction method at 60°C for 2 hours. The extract was filtered, and the filtrate underwent multi-stage purification and aseptic treatment, concentrated to a suitable concentration, and dispensed into sterile ampoules and sealed. This dosage form should be used under the supervision of qualified medical personnel and is suitable for research and clinical adjunctive applications requiring rapid onset of action or for special conditions.

[0046] Although embodiments of the invention have been shown and described, it will be understood by those skilled in the art that various changes, modifications, substitutions and alterations can be made to these embodiments without departing from the principles and spirit of the invention, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A pure traditional Chinese medicine composition for treating liver fibrosis and its application, characterized in that: The composition consists of Euphorbia humifusa, winter melon peel, Asarum, Platycodon grandiflorus, Sophora flavescens, Rehmannia glutinosa, Hirudo medicinalis, Pheretima aspergillum, Salvia miltiorrhiza, Pharbitis nil, and Glycyrrhiza uralensis. All components are natural medicinal raw materials and do not contain any artificially synthesized chemical anti-liver fibrosis components. The composition inhibits the activation of hepatic stellate cells, reduces extracellular matrix deposition, and improves liver microcirculation disorders through the synergistic effect of multiple components.

2. The pure traditional Chinese medicine composition for anti-liver fibrosis according to claim 1 and its application, characterized in that: Each component of the composition retains its natural properties during preparation without chemical structural modification. Its active ingredients include flavonoids, saponins, alkaloids, polysaccharides, and polypeptides, which can form a multi-target regulatory network in vivo, acting on the entire process of liver fibrosis occurrence, development, and reversal.

3. The pure traditional Chinese medicine composition for anti-liver fibrosis according to claim 1 and its application, characterized in that: When the composition is prepared into a pharmaceutical formulation, it can be extracted using a single solvent or a combination solvent. The extraction conditions are a temperature controlled between 40°C and 90°C and an extraction time of 30 minutes to 3 hours. The resulting extract is concentrated, dried, and then mixed with other pharmaceutically acceptable excipients to form a dosage form suitable for oral or non-oral administration.

4. The pure traditional Chinese medicine composition for anti-liver fibrosis according to claim 1 and its application, characterized in that: In the application of anti-liver fibrosis, the composition can significantly reduce the hydroxyproline content in liver tissue, inhibit abnormal activation of the transforming growth factor β1 signaling pathway, reduce α-smooth muscle actin expression, and promote the degradation and reabsorption of deposited collagen fibers.

5. The pure traditional Chinese medicine composition for anti-liver fibrosis according to claim 1 and its application, characterized in that: The composition can be used to prepare drugs for treating liver fibrosis caused by viral infection, alcohol intake, metabolic disorders or other reasons, and its targets include chronic hepatitis B, chronic hepatitis C, alcoholic liver disease, non-alcoholic steatohepatitis and related secondary liver fibrosis.

6. The pure traditional Chinese medicine composition for anti-liver fibrosis according to claim 1 and its application, characterized in that: The composition can be used in combination with other traditional Chinese medicines or natural products with hepatoprotective, anti-inflammatory or immunomodulatory effects when preparing the drug, without changing its pure traditional Chinese medicine properties and without introducing chemically synthesized antifibrotic drugs, thereby maintaining the naturalness and safety of the overall solution.

7. The pure traditional Chinese medicine composition for anti-liver fibrosis according to claim 1 and its application, characterized in that: In the preparation method of the composition, the active parts of the following herbs can be extracted separately and then mixed, or they can be directly mixed and then extracted together. The extracted products need to be tested for characteristic index components in quality control to ensure batch-to-batch consistency.

8. The pure traditional Chinese medicine composition for anti-liver fibrosis according to claim 1 and its application, characterized in that: The efficacy of the composition can be verified through in vitro hepatic stellate cell proliferation inhibition experiment, collagen synthesis inhibition experiment and in vivo liver fibrosis animal model pathological improvement experiment. Its activity is significantly better than that of a single component or conventional combination of two to three Chinese herbal medicines.

9. The pure traditional Chinese medicine composition for anti-liver fibrosis according to claim 1 and its application, characterized in that: The composition can be used to adjust the dosage and course of treatment according to the degree of liver fibrosis in patients. It has high safety, is not prone to obvious toxic reactions with long-term use, and does not affect the function of normal liver cells. It is suitable for the long-term management of chronic liver disease.

10. A pure traditional Chinese medicine composition for treating liver fibrosis according to any one of claims 1 to 9 and its application, characterized in that: The drug can be formulated as tablets, capsules, granules, oral liquid preparations or injections, and can be administered via oral, intravenous drip or intraperitoneal injection, and is suitable for the clinical treatment and adjuvant treatment of different types of liver fibrosis patients.