Traditional Chinese medicine composition for treating hepatic fibrosis and preparation method thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicines, and particularly provides a traditional Chinese medicine composition for treating hepatic fibrosis and a preparation method thereof. According to the invention, astragalus membranaceus, vinegar-processed curcuma zedoary, salvia miltiorrhiza, moutan bark, radix paeoniae rubra, angelica sinensis, curcuma aromatica, fructus amomi, bran-fried atractylodes macrocephala koidz, poria cocos, fingered citron, vinegar-processed bupleurum chinense and honey-fried licorice root are adopted as raw materials and are subjected to proper weight proportioning; wherein the astragalus membranaceus is a monarch drug, and the vinegar curcuma zedoary, the salvia miltiorrhiza, the moutan bark, the red paeony root, the angelica sinensis, the radix curcumae, the fructus amomi and the bran-fried rhizoma atractylodis macrocephalae are The vinegar bupleurum chinense, fingered citron and poria cocos are used as adjuvant drugs, and the liquorice is used as conductant drug; all the medicines are combined to achieve the effects of replenishing qi to invigorate the spleen, soothing the liver, regulating qi and promoting blood circulation to remove blood stasis. Under the synergistic effect of all the medicine components, the traditional Chinese medicine composition has a good curative effect on liver fibrosis, especially liver fibrosis common clinically with liver depression, spleen deficiency and blood stasis syndromes, and is small in toxic and side effect and worthy of clinical application and popularization.

Description

Technical Field

[0001] This invention belongs to the field of traditional Chinese medicine technology, specifically relating to a traditional Chinese medicine composition for treating liver fibrosis and its preparation method. Background Technology

[0002] Liver fibrosis is a reversible pathological phenomenon resulting from the excessive deposition of fibrous connective tissue in the liver after repeated exacerbations of various chronic liver diseases, and it is the inevitable path to cirrhosis. Given that modern medicine has not yet developed any clinically applicable chemical or biological drugs for treating liver fibrosis, Western medicine primarily uses antiviral drugs and hepatoprotective and enzyme-lowering drugs to treat the common chronic hepatitis B-related liver fibrosis in my country. While this etiological treatment can slow the progression of liver fibrosis to some extent by inhibiting HBV replication and promoting hepatocyte repair, it is difficult to achieve good control over the final outcome of the disease, especially in reversing existing cirrhosis, where significant therapeutic limitations remain.

[0003] With the deepening of research in recent years, traditional Chinese medicine (TCM) has demonstrated unique advantages and occupies an important position in the treatment of liver fibrosis due to its fewer adverse reactions, lower cost, and multi-target efficacy. Clinically, the combination of antiviral drugs and TCM has become a major strategy and research focus for treating liver fibrosis and even cirrhosis caused by hepatitis B. Summary of the Invention

[0004] To address the aforementioned problems in the existing technology, this invention provides a traditional Chinese medicine composition for treating liver fibrosis with good anti-hepatic fibrosis efficacy and few toxic side effects, as well as its preparation method.

[0005] The technical solution adopted in this invention is as follows: The first aspect of this invention provides a traditional Chinese medicine composition for treating liver fibrosis, comprising the following raw material components: 10-20 parts by weight of Astragalus membranaceus, 4-8 parts by weight of Curcuma zedoaria (processed with vinegar), 5-15 parts by weight of Salvia miltiorrhiza, 5-15 parts by weight of Paeonia suffruticosa, 5-15 parts by weight of Paeonia lactiflora, 4-8 parts by weight of Angelica sinensis, 5-15 parts by weight of Curcuma longa, 4-8 parts by weight of Amomum villosum, 5-15 parts by weight of Atractylodes macrocephala (processed with wheat bran), 8-16 parts by weight of Poria cocos, 4-8 parts by weight of Citrus medica, 4-8 parts by weight of Bupleurum chinense (processed with vinegar), and 1-5 parts by weight of Glycyrrhiza uralensis (processed with honey).

[0006] The raw material components of the traditional Chinese medicine composition for treating liver fibrosis are further preferably: Astragalus membranaceus 14-16 parts by weight, Curcuma zedoaria (processed with vinegar) 5-7 parts by weight, Salvia miltiorrhiza 8-12 parts by weight, Paeonia suffruticosa 8-12 parts by weight, Paeonia lactiflora 8-12 parts by weight, Angelica sinensis 5-7 parts by weight, Curcuma longa 8-12 parts by weight, Amomum villosum 5-7 parts by weight, Atractylodes macrocephala (stir-fried with wheat bran) 8-12 parts by weight, Poria cocos 10-14 parts by weight, Citrus medica 5-7 parts by weight, Bupleurum chinense (processed with vinegar) 5-7 parts by weight, Glycyrrhiza uralensis (processed with vinegar) 2-4 parts by weight.

[0007] The raw material components of the traditional Chinese medicine composition for treating liver fibrosis are further preferably: Astragalus membranaceus 15 parts by weight, Curcuma zedoaria (processed with vinegar) 6 parts by weight, Salvia miltiorrhiza 10 parts by weight, Paeonia suffruticosa 10 parts by weight, Paeonia lactiflora 10 parts by weight, Angelica sinensis 6 parts by weight, Curcuma longa 10 parts by weight, Amomum villosum 6 parts by weight, Atractylodes macrocephala (stir-fried with wheat bran) 10 parts by weight, Poria cocos 12 parts by weight, Citrus medica 6 parts by weight, Bupleurum chinense (processed with vinegar) 6 parts by weight, Glycyrrhiza uralensis (processed with vinegar) 3 parts by weight.

[0008] A second aspect of this invention provides a method for preparing the aforementioned traditional Chinese medicine composition for treating liver fibrosis, comprising the following steps: (1) Take Astragalus membranaceus, Curcuma zedoaria, Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Angelica sinensis, Curcuma longa, Amomum villosum and Atractylodes macrocephala stir-fried with wheat bran according to the weight parts, and after ultra-fine pulverization, obtain ultra-fine powder of each Chinese medicine; (2) Take the remaining raw material components according to the weight parts, crush them, and mix them thoroughly to obtain the Chinese medicine mixed powder; (3) Add water to the mixed powder of Chinese medicine obtained in step (2), and perform water extraction to obtain water extract; (4) The aqueous extract obtained in step (3) is filtered and concentrated to obtain a concentrate; (5) The concentrate described in step (4) is dried and ultra-finely pulverized in sequence, and then each of the traditional Chinese medicine ultra-fine powders described in step (1) is added and mixed thoroughly to obtain the traditional Chinese medicine composition for treating liver fibrosis.

[0009] In step (1), the particle size of each of the Chinese herbal medicine ultrafine powders is 1200-1800 mesh.

[0010] In step (3), the mass ratio of the mixed Chinese medicine powder to the added water is 1:2-1:6.

[0011] In step (3), the water extraction treatment time is 2-4 hours; In step (4), the concentration is carried out under reduced pressure to a thick paste with a relative density of 1.31-1.34; In step (5), the drying temperature is 80-160℃.

[0012] In step (5), the particle size of the ultrafine powder obtained after ultrafine grinding is 1200-1800 mesh.

[0013] The application of the aforementioned traditional Chinese medicine composition in the preparation of drugs for treating liver fibrosis.

[0014] Astragalus membranaceus (Huang Qi) is sweet in taste and warm in nature. It tonifies Qi and strengthens the exterior, promotes diuresis and eliminates toxins, drains pus, and promotes tissue regeneration. It is used for Qi deficiency and fatigue, poor appetite and loose stools, Qi sinking, chronic diarrhea and rectal prolapse, hematochezia and metrorrhagia, spontaneous sweating due to exterior deficiency, edema due to Qi deficiency, carbuncles that are difficult to heal, chronic ulcers that do not heal, anemia and chlorosis, internal heat and thirst; proteinuria in chronic nephritis, and diabetes.

[0015] Curcuma zedoaria has a pungent and bitter taste, and is warm in nature. It promotes qi circulation, breaks up blood stasis, eliminates stagnation, and relieves pain. It is used for abdominal masses, amenorrhea due to blood stasis, abdominal distension and pain due to food stagnation; and early-stage cervical cancer.

[0016] Salvia miltiorrhiza, sweet in taste and slightly cold in nature. It removes blood stasis and relieves pain, invigorates blood circulation and regulates menstruation, clears the heart and relieves irritability. It is used for irregular menstruation, amenorrhea and dysmenorrhea, abdominal masses, chest and abdominal pain, hot arthralgia, sores and swelling, insomnia due to heart palpitations; hepatosplenomegaly, and angina pectoris.

[0017] Moutan bark is bitter and pungent in taste, and slightly cold in nature. It clears heat and cools the blood, promotes blood circulation and removes blood stasis. It is used for febrile diseases with rashes, hematemesis and epistaxis, night fever and morning coolness, bone steaming without sweating, amenorrhea and dysmenorrhea, carbuncles and boils, and injuries from falls and blows.

[0018] Red peony root, bitter in taste and slightly cold in nature. It clears heat and cools the blood, disperses blood stasis and relieves pain. It is used for febrile diseases with rashes, hematemesis and epistaxis, red and swollen eyes, liver stagnation and hypochondriac pain, amenorrhea and dysmenorrhea, abdominal masses and pain, traumatic injuries, carbuncles and sores.

[0019] Angelica sinensis, sweet and pungent in taste, and warm in nature. It nourishes and invigorates blood, regulates menstruation and relieves pain, and moistens the intestines to promote bowel movements. It is used for blood deficiency and chlorosis, dizziness and palpitations, irregular menstruation, amenorrhea and dysmenorrhea, abdominal pain due to deficiency and cold, constipation due to intestinal dryness, rheumatic pain, injuries from falls, carbuncles and sores. Angelica sinensis infused in wine invigorates blood and regulates menstruation. It is used for amenorrhea and dysmenorrhea, rheumatic pain, and injuries from falls.

[0020] Turmeric, pungent and bitter in taste, and cold in nature. It invigorates blood circulation and relieves pain, regulates qi and relieves depression, clears the heart and cools the blood, and promotes bile secretion and reduces jaundice. It is used for qi stagnation and blood stasis, stabbing pain in the chest and hypochondrium, chest pain, irregular menstruation, amenorrhea and dysmenorrhea, breast distension and pain, delirium due to febrile diseases, epilepsy and mania, hematemesis and epistaxis due to blood heat, retrograde menstruation, damp-heat in the liver and gallbladder, jaundice and dark urine, and gallbladder distension and hypochondriac pain.

[0021] Amomum villosum, pungent in taste and warm in nature. It resolves dampness, invigorates the spleen and stomach, warms the middle jiao and stops diarrhea, regulates qi and calms the fetus. It is used for dampness obstructing the middle jiao, stagnation of spleen and stomach qi, epigastric fullness and lack of appetite, spleen and stomach deficiency and cold, vomiting and diarrhea, morning sickness, and threatened abortion.

[0022] Stir-fried Atractylodes macrocephala with wheat bran has a bitter and sweet taste and is warm in nature. It strengthens the spleen and replenishes qi, dries dampness and promotes diuresis, stops sweating, and calms the fetus. It is used for spleen deficiency with poor appetite, abdominal distension and diarrhea, phlegm retention with dizziness and palpitations, edema, spontaneous sweating, and threatened abortion. Wild Atractylodes macrocephala strengthens the spleen, harmonizes the stomach, and calms the fetus. It is used for spleen deficiency with poor appetite, loose stools, and threatened abortion.

[0023] The present invention has the following beneficial effects: This invention provides a traditional Chinese medicine composition for treating liver fibrosis. It uses Astragalus membranaceus, Curcuma zedoaria (processed with vinegar), Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Angelica sinensis, Curcuma longa, Amomum villosum, Atractylodes macrocephala (processed with wheat bran), Poria cocos, Citrus medica, Bupleurum chinense (processed with vinegar), and Glycyrrhiza uralensis (processed with roasted) as raw materials in appropriate weight ratios. Astragalus membranaceus is the principal herb; Curcuma zedoaria (processed with vinegar), Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Angelica sinensis, Curcuma longa, Amomum villosum, and Atractylodes macrocephala (processed with wheat bran) are the assistant herbs; Bupleurum chinense (processed with vinegar), Citrus medica, and Poria cocos are the adjuvant herbs; and Glycyrrhiza uralensis is the guiding herb. The formula heavily utilizes Astragalus membranaceus to invigorate Qi and strengthen the spleen, promoting blood circulation. The combined use of Curcuma zedoaria (processed with vinegar) and the principal herb Astragalus membranaceus can invigorate Qi and resolve blood stasis, often leading to the disappearance of lesions before they become apparent. Because Astragalus membranaceus combined with Curcuma zedoaria replenishes Qi without causing stagnation, and its attacking effect does not harm the body's vital energy, the two herbs complement each other, promoting circulation while replenishing, and replenishing while promoting circulation, achieving synergistic effects. Salvia miltiorrhiza is a key herb for treating blood stasis syndrome; when combined with Curcuma zedoaria, it enhances the effects of promoting blood circulation and removing blood stasis. Paeonia suffruticosa invigorates blood without causing further bleeding, cools the blood without leaving stasis; when combined with Paeonia lactiflora, it can clear heat and stagnation in the liver meridian and also promote blood circulation, remove blood stasis, and relieve pain. Angelica sinensis combined with Salvia miltiorrhiza and Curcuma zedoaria ensures that removing blood stasis does not harm the body's vital energy. Curcuma longa is pungent and bitter, promoting blood circulation and removing blood stasis to relieve pain, soothing the liver and regulating Qi to relieve depression, and also clearing the heart, cooling the blood, promoting bile secretion, and reducing jaundice. Amomum villosum is pungent... This herb, with its warming and aromatic properties, can warm the middle jiao (spleen and stomach), dispel dampness, invigorate the spleen and stimulate appetite, and also regulate qi and stop vomiting. When combined with the chief herb, Astragalus membranaceus, stir-fried Atractylodes macrocephala enhances its qi-tonifying and spleen-strengthening effects. When combined with the chief herb, Bupleurum chinense, and the vinegar-processed Bupleurum chinense, it assists in tonifying qi and raising yang, and guides the other herbs to the liver meridian. When combined with Bupleurum chinense, Citrus medica enhances its liver-soothing and qi-regulating effects. Furthermore, this herb enters the spleen and stomach meridians, regulating qi and relieving pain; its bitter and warm nature dries dampness and resolves phlegm, and when combined with Poria cocos, it strengthens the middle jiao and dispels dampness. When combined with the assistant herb, stir-fried Atractylodes macrocephala, they mutually enhance the spleen-strengthening and dampness-removing effects. Licorice root has the function of tonifying qi, harmonizing the middle jiao, and coordinating the effects of the other herbs. The combined effects of these herbs are to tonify qi and strengthen the spleen, soothe the liver and regulate qi, and promote blood circulation and remove blood stasis.

[0024] The pharmaceutical composition of this invention exhibits a significant protective effect against liver fibrosis caused by spleen deficiency and blood stasis, through the synergistic effect of the aforementioned drug components. It not only effectively reduces pathological damage and inflammatory response of hepatocytes but also significantly reduces the deposition of collagen fibers in the liver, thereby comprehensively improving the degree of liver fibrosis. Through research on the potential mechanism of the traditional Chinese medicine composition in treating liver fibrosis, the inventors of this application discovered that the composition may exert its effects by simultaneously acting on key signaling pathways such as PI3K-Akt, MAPK, NF-κB, and TGF-β. These pathways are closely related to multiple mechanisms, including inhibiting inflammation, blocking fibrosis progression, improving oxidative stress, and balancing immune responses, thereby achieving comprehensive regulation of the pathological network of liver fibrosis. Furthermore, the traditional Chinese medicine composition of this invention may also affect the interaction between cells and the extracellular matrix, thereby intervening in the fibrosis process through multiple targets and inhibiting abnormal extracellular matrix deposition. Clinical results demonstrate that the traditional Chinese medicine composition of this invention has good efficacy in treating liver fibrosis, especially for the clinically common liver fibrosis caused by liver stagnation, spleen deficiency, and blood stasis, with few toxic side effects, making it worthy of clinical promotion and application. Detailed Implementation

[0025] To make the objectives, technical solutions, and advantages of this invention clearer, the technical solutions of this invention will be described in detail below. Obviously, the described embodiments are merely some embodiments of this invention, and not all embodiments. Based on the embodiments of this invention, all other implementation methods obtained by those skilled in the art without creative effort are within the scope of protection of this invention.

[0026] Unless otherwise specified, all reagents involved in the specific embodiments of this invention are commercially available products and can be purchased through commercial channels.

[0027] In the following examples, 1 part by weight represents 1g.

[0028] Example 1 This embodiment provides a traditional Chinese medicine composition for treating liver fibrosis, the raw material components of which include: Astragalus membranaceus 15 parts by weight, Curcuma zedoaria (processed with vinegar) 6 parts by weight, Salvia miltiorrhiza 10 parts by weight, Paeonia suffruticosa 10 parts by weight, Paeonia lactiflora 10 parts by weight, Angelica sinensis 6 parts by weight, Curcuma longa 10 parts by weight, Amomum villosum 6 parts by weight, Atractylodes macrocephala (stir-fried with wheat bran) 10 parts by weight, Poria cocos 12 parts by weight, Citrus medica 6 parts by weight, Bupleurum chinense (processed with vinegar) 6 parts by weight, Glycyrrhiza uralensis (processed with vinegar) 3 parts by weight.

[0029] The preparation method of the traditional Chinese medicine composition for treating liver fibrosis includes the following steps: (1) Take Astragalus membranaceus, Curcuma zedoaria, Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Angelica sinensis, Curcuma longa, Amomum villosum and Atractylodes macrocephala stir-fried with wheat bran according to the weight parts, and after ultra-fine pulverization, obtain ultra-fine powder of each Chinese medicine with a particle size of 1500 mesh. (2) Take the remaining raw material components according to the weight parts, crush them, and mix them thoroughly to obtain the Chinese medicine mixed powder; (3) Add 4 times the mass of water to the Chinese herbal medicine mixture obtained in step (2) and perform reflux extraction for 3 hours to obtain the aqueous extract; (4) After filtering the aqueous extract described in step (3), concentrate it under reduced pressure to a thick paste with a relative density of 1.33, which is the concentrate; (5) The concentrate described in step (4) is first dried at 120°C and then ultra-finely pulverized to obtain ultra-fine powder with a particle size of 1500 mesh. Then, the ultra-fine powder of each Chinese medicine described in step (1) is added and mixed thoroughly to obtain the Chinese medicine composition for treating liver fibrosis.

[0030] Example 2 This embodiment provides a traditional Chinese medicine composition for treating liver fibrosis, the raw material components of which include: Astragalus membranaceus 10 parts by weight, Curcuma zedoaria (processed with vinegar) 8 parts by weight, Salvia miltiorrhiza 5 parts by weight, Paeonia suffruticosa 15 parts by weight, Paeonia lactiflora 5 parts by weight, Angelica sinensis 8 parts by weight, Curcuma longa 5 parts by weight, Amomum villosum 8 parts by weight, Atractylodes macrocephala (stir-fried with wheat bran) 5 parts by weight, Poria cocos 16 parts by weight, Citrus medica 4 parts by weight, Bupleurum chinense (processed with vinegar) 8 parts by weight, Glycyrrhiza uralensis (processed with vinegar) 1 part by weight.

[0031] The preparation method of the traditional Chinese medicine composition for treating liver fibrosis includes the following steps: (1) Take Astragalus membranaceus, Curcuma zedoaria, Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Angelica sinensis, Curcuma longa, Amomum villosum and Atractylodes macrocephala stir-fried with wheat bran according to the weight parts, and after ultra-fine pulverization, obtain ultra-fine powder of each Chinese medicine with a particle size of 1200 mesh. (2) Take the remaining raw material components according to the weight parts, crush them, and mix them thoroughly to obtain the Chinese medicine mixed powder; (3) Add 6 times the mass of water to the Chinese herbal medicine mixture obtained in step (2) and perform reflux extraction for 2 hours. Repeat the reflux extraction 3 times and combine the extracts to obtain the aqueous extract. (4) After filtering the aqueous extract described in step (3), concentrate it under reduced pressure to a thick paste with a relative density of 1.31, which is the concentrate; (5) The concentrate described in step (4) is first dried at 80°C and then ultra-finely pulverized to obtain ultra-fine powder with a particle size of 1200 mesh. Then, the ultra-fine powder of each Chinese medicine described in step (1) is added and mixed thoroughly to obtain the Chinese medicine composition for treating liver fibrosis.

[0032] Example 3 This embodiment provides a traditional Chinese medicine composition for treating liver fibrosis, the raw material components of which include: Astragalus membranaceus 20 parts by weight, Curcuma zedoaria (processed with vinegar) 4 parts by weight, Salvia miltiorrhiza 15 parts by weight, Paeonia suffruticosa 5 parts by weight, Paeonia lactiflora 15 parts by weight, Angelica sinensis 4 parts by weight, Curcuma longa 15 parts by weight, Amomum villosum 4 parts by weight, Atractylodes macrocephala (stir-fried with wheat bran) 15 parts by weight, Poria cocos 8 parts by weight, Citrus medica 8 parts by weight, Bupleurum chinense (processed with vinegar) 4 parts by weight, Glycyrrhiza uralensis (processed with vinegar) 5 parts by weight.

[0033] The preparation method of the traditional Chinese medicine composition for treating liver fibrosis includes the following steps: (1) Take Astragalus membranaceus, Curcuma zedoaria, Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Angelica sinensis, Curcuma longa, Amomum villosum and Atractylodes macrocephala stir-fried with wheat bran according to the weight parts, and after ultra-fine pulverization, obtain ultra-fine powder of each Chinese medicine with a particle size of 1800 mesh. (2) Take the remaining raw material components according to the weight parts, crush them, and mix them thoroughly to obtain the Chinese medicine mixed powder; (3) Add 6 times the mass of water to the Chinese herbal medicine mixture obtained in step (2) and perform reflux extraction for 4 hours. The reflux extraction is repeated twice. Combine the extracts to obtain the aqueous extract. (4) After filtering the aqueous extract described in step (3), concentrate it under reduced pressure to a thick paste with a relative density of 1.34, which is the concentrate; (5) The concentrate described in step (4) is first dried at 160°C and then ultra-finely pulverized to obtain ultra-fine powder with a particle size of 1800 mesh. Then, the ultra-fine powder of each Chinese medicine described in step (1) is added and mixed thoroughly to obtain the Chinese medicine composition for treating liver fibrosis.

[0034] Example 4 This embodiment provides a traditional Chinese medicine composition for treating liver fibrosis, the raw material components of which include: Astragalus membranaceus 14 parts by weight, Curcuma zedoaria (processed with vinegar) 7 parts by weight, Salvia miltiorrhiza 8 parts by weight, Paeonia suffruticosa 12 parts by weight, Paeonia lactiflora 8 parts by weight, Angelica sinensis 7 parts by weight, Curcuma longa 8 parts by weight, Amomum villosum 7 parts by weight, Atractylodes macrocephala (stir-fried with wheat bran) 8 parts by weight, Poria cocos 14 parts by weight, Citrus medica 5 parts by weight, Bupleurum chinense (processed with vinegar) 7 parts by weight, Glycyrrhiza uralensis (processed with vinegar) 2 parts by weight.

[0035] The preparation method of the traditional Chinese medicine composition for treating liver fibrosis includes the following steps: (1) Take Astragalus membranaceus, Curcuma zedoaria, Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Angelica sinensis, Curcuma longa, Amomum villosum and Atractylodes macrocephala stir-fried with wheat bran according to the weight parts, and after ultra-fine pulverization, obtain ultra-fine powder of each Chinese medicine with a particle size of 1500 mesh. (2) Take the remaining raw material components according to the weight parts, crush them, and mix them thoroughly to obtain the Chinese medicine mixed powder; (3) Add 6 times the mass of water to the Chinese herbal medicine mixture obtained in step (2) and perform reflux extraction for 3 hours. The reflux extraction is repeated twice. Combine the extracts to obtain the aqueous extract. (4) After filtering the aqueous extract described in step (3), concentrate it under reduced pressure to a thick paste with a relative density of 1.33, which is the concentrate; (5) The concentrate described in step (4) is first dried at 120°C and then ultra-finely pulverized to obtain ultra-fine powder with a particle size of 1500 mesh. Then, the ultra-fine powder of each Chinese medicine described in step (1) is added and mixed thoroughly to obtain the Chinese medicine composition for treating liver fibrosis.

[0036] Example 5 This embodiment provides a traditional Chinese medicine composition for treating liver fibrosis, the raw material components of which include: Astragalus membranaceus 16 parts by weight, Curcuma zedoaria (processed with vinegar) 5 parts by weight, Salvia miltiorrhiza 12 parts by weight, Paeonia suffruticosa 8 parts by weight, Paeonia lactiflora 12 parts by weight, Angelica sinensis 5 parts by weight, Curcuma longa 12 parts by weight, Amomum villosum 5 parts by weight, Atractylodes macrocephala (stir-fried with wheat bran) 12 parts by weight, Poria cocos 10 parts by weight, Citrus medica 7 parts by weight, Bupleurum chinense (processed with vinegar) 5 parts by weight, Glycyrrhiza uralensis (processed with vinegar) 4 parts by weight.

[0037] The preparation method of the traditional Chinese medicine composition for treating liver fibrosis includes the following steps: (1) Take Astragalus membranaceus, Curcuma zedoaria, Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Angelica sinensis, Curcuma longa, Amomum villosum and Atractylodes macrocephala stir-fried with wheat bran according to the weight parts, and after ultra-fine pulverization, obtain ultra-fine powder of each Chinese medicine with a particle size of 1500 mesh. (2) Take the remaining raw material components according to the weight parts, crush them, and mix them thoroughly to obtain the Chinese medicine mixed powder; (3) Add 4 times the mass of water to the Chinese herbal medicine mixture obtained in step (2) and perform reflux extraction for 4 hours. The reflux extraction is repeated twice. Combine the extracts to obtain the aqueous extract. (4) After filtering the aqueous extract described in step (3), concentrate it under reduced pressure to a thick paste with a relative density of 1.34, which is the concentrate; (5) The concentrate described in step (4) is first dried at 120°C and then ultra-finely pulverized to obtain ultra-fine powder with a particle size of 1500 mesh. Then, the ultra-fine powder of each Chinese medicine described in step (1) is added and mixed thoroughly to obtain the Chinese medicine composition for treating liver fibrosis.

[0038] Example 6 The only difference between this embodiment and Embodiment 1 is the preparation method.

[0039] The preparation method of the traditional Chinese medicine composition for treating liver fibrosis includes the following steps: (1) Take each drug component by weight, and after ultra-fine grinding, obtain each Chinese medicine ultra-fine powder with a particle size of 1500 mesh; (2) Mix the ultrafine powders of each Chinese herbal medicine thoroughly to obtain a mixed powder of Chinese herbal medicine; (3) Add 4 times the mass of water to the Chinese herbal medicine mixture obtained in step (2) and perform reflux extraction for 4 hours. The reflux extraction is repeated twice. The extracts are combined to obtain the Chinese herbal medicine composition for treating liver fibrosis.

[0040] Example 7 The only difference between this embodiment and Embodiment 1 is the preparation method.

[0041] The preparation method of the traditional Chinese medicine composition for treating liver fibrosis includes the following steps: (1) Take each drug component by weight, dry and then pulverize to obtain each Chinese medicine powder with a particle size of 100 mesh; (2) Mix all the Chinese herbal powders thoroughly to obtain a mixed Chinese herbal powder; (3) Add 2 times the mass of water to the Chinese herbal medicine mixture obtained in step (2) and decoct for 2 hours. Repeat the decoction twice and combine the decoction liquid to obtain the Chinese herbal medicine composition for treating liver fibrosis.

[0042] Experimental Example This study included cases of chronic hepatitis B with liver fibrosis (liver stagnation and spleen deficiency with blood stasis syndrome) treated at the Liver Disease Center of a traditional Chinese medicine hospital from January 2024 to September 2025. Patients were required to complete a 24-week standardized follow-up and have complete clinical data. Based on whether they received combined treatment with the traditional Chinese medicine composition described in this invention, they were divided into an observation group or a control group.

[0043] 1. Treatment plan (1) Control group: The first-line drug tenofovir was administered orally for antiviral treatment.

[0044] (2) Observation group: In addition to the control group, the Chinese medicine composition described in Example 7 of this invention was administered orally, 200ml each time, once in the morning and once in the evening, taken warm after meals.

[0045] 2. Treatment course and visitation plan Both treatment courses lasted 24 weeks. Each participant underwent blood tests, liver and kidney function tests, HBV-DNA tests, liver stiffness (LSM) measurements, spleen thickness, and portal vein diameter before treatment and after the 24-week observation period.

[0046] 3. Efficacy evaluation criteria Based on the 2023 Guidelines for the Diagnosis and Treatment of Liver Cirrhosis with Integrated Traditional Chinese and Western Medicine, the 2022 Traditional Chinese Medicine Treatment Protocol for Accumulation (Compensated Stage of Liver Cirrhosis), the 2019 Guidelines for the Diagnosis and Treatment of Liver Fibrosis with Integrated Traditional Chinese and Western Medicine, and the 2018 Expert Consensus on the Diagnosis of Liver Fibrosis using Transient Elastography, and in conjunction with clinical practice, the following efficacy evaluation criteria are formulated: Significant effect: At the end of the treatment course, ① LSM decreased by ≥30%; ② hepatosplenomegaly remained stable or shrank, with no percussion or tenderness; ③ liver function returned to normal.

[0047] Effective: At the end of the treatment course, ① LSM decreased by ≥10%; ② hepatosplenomegaly remained stable without significant percussion or tenderness; ③ liver function improved by >50% but not completely normal.

[0048] Ineffective: Those who do not meet the above improvement criteria or whose condition worsens by the end of the treatment course.

[0049] 4. Case completion status Data was collected based on patients' outpatient medical records and, according to relevant inclusion and exclusion criteria, a total of 100 cases were obtained. Patients treated with tenofovir alafenamide alone served as the control group (n=50), while patients receiving combined treatment with the traditional Chinese medicine composition described in Example 1 of this invention served as the observation group (n=50). To reduce the impact of confounding factors on the research results, this study used propensity score matching (PSM) to balance the baseline characteristics of the observation and control groups. Based on the calculated propensity scores, a 1:1 nearest neighbor matching method was used for pairing, with a caliper value set at 0.150. The matching results showed that out of the initial 50 pairs, 42 pairs were successfully matched (matching success rate 84.0%), including 42 fuzzy matches and 0 perfect matches. Eight cases (16.0%) failed to match due to propensity score differences exceeding the caliper value or a lack of suitable partners. Furthermore, according to the balance test, the difference in standard means of each variable after matching is significantly closer to 0, and no variable has an SMD > 0.25. It can be considered that the variables have reached equilibrium after matching and the differences are small.

[0050] 5. Baseline comparison after PSM The results of general data comparison showed that, after matching, there were no significant differences between the control group and the observation group in terms of gender composition and age (P>0.05), indicating that the two groups of patients were well comparable in terms of baseline demographic characteristics. See Table 1 for details.

[0051] Table 1 - Comparison of general data between the two groups after matching 6. Statistical results of therapeutic efficacy indicators (1) Comparison of liver stiffness values ​​(E value), APRI scores, and FIB-4 index between the two groups after matching Intergroup comparison: Before treatment, there were no statistically significant differences between the control group and the observation group in liver stiffness (E value), APRI score, and FIB-4 index (P>0.05), indicating that the two groups were comparable. After treatment, there were still no statistically significant differences between the control group and the observation group in liver stiffness (E value), APRI score, and FIB-4 index (P>0.05). See Table 2 for details.

[0052] Intra-group comparisons: For liver stiffness (E value), intra-group comparisons showed no statistically significant change in E value before and after treatment in the control group (P=0.134), while the E value in the observation group was significantly lower after treatment than before treatment (P<0.001), indicating a significant and statistically significant effect of the observation group in improving liver fibrosis. For APRI scores, intra-group comparisons showed a significant decrease in the APRI index after treatment in the control group compared to before treatment (P=0.015), and a similar significant decrease in the APRI index in the observation group after treatment (P=0.027), both statistically significant. For FIB-4 index, intra-group comparisons showed no statistically significant change in the FIB-4 index before and after treatment in the control group (P=0.054), and no statistically significant change in the FIB-4 index in the observation group before and after treatment (P=0.191).

[0053] Table 2 - Comparison of matched liver stiffness values ​​(E value), APRI score, and FIB-4 index (2) Comparison of liver function data between the two groups after matching Intergroup comparison: Before treatment, there were no statistically significant differences in total bilirubin, AST, and ALT between the control group and the observation group (P>0.05), indicating that the two groups were comparable. Regarding total bilirubin, after treatment, the observation group showed significantly higher levels than the control group (P=0.039). There were no statistically significant differences in AST and ALT between the two groups after treatment (P>0.05). See Table 3 for details.

[0054] Within-group comparisons: Regarding total bilirubin, there was no statistically significant change in total bilirubin before and after treatment in either the control or observation group (P>0.05). Regarding AST, both the control and observation groups showed a significant decrease in AST after treatment compared to before treatment (P<0.05). Regarding ALT, there was no statistically significant change in ALT before and after treatment in the control group (P=0.1), while the observation group showed a significant decrease in ALT after treatment compared to before treatment (P=0.024).

[0055] Table 3 - Comparison of liver function between the two groups after matching (3) Comparison of serological indicators between the two groups after matching Intergroup comparison: Before treatment, there were no statistically significant differences in platelet count and creatinine between the control group and the observation group (P>0.05), indicating that the two groups were comparable. After treatment, there were no statistically significant differences in platelet count between the two groups (P>0.05). After treatment, creatinine levels in the observation group were significantly lower than those in the control group, and the difference was statistically significant (P=0.003). See Table 4 for details.

[0056] Within-group comparisons: Regarding platelets, the platelet count in the control group increased significantly after treatment compared to before treatment (P=0.016), while there was no statistically significant change in platelet count in the observation group (P=0.293). Regarding creatinine, there was no change in creatinine before and after treatment in the control group (P=1.000), while creatinine in the observation group decreased significantly after treatment compared to before treatment (P=0.002), which was statistically significant.

[0057] Table 4 - Comparison of serological indicators between the two groups after matching (4) Comparison of imaging indicators between the two groups after matching Intergroup comparison: Before treatment, there were no statistically significant differences in spleen thickness and portal vein width between the control group and the observation group (P>0.05), indicating that the two groups were comparable. After treatment, there were no statistically significant differences in spleen thickness and portal vein width between the two groups (P>0.05). See Table 5 for details.

[0058] Intragroup comparisons: Regarding spleen thickness, there was no statistically significant change in spleen thickness before and after treatment in the control group (P=0.443), while the spleen thickness in the observation group was significantly reduced after treatment compared to before treatment (P=0.016), which was statistically significant. Regarding portal vein width, there was no statistically significant change before and after treatment in either the control or observation group (P>0.05).

[0059] Table 5 - Comparison of two sets of imaging indicators after matching (5) Comparison of HBV DNA in the two groups after matching Before treatment: There was no statistically significant difference in HBV DNA positivity rate between the control group and the observation group (P>0.05), indicating that the two groups were comparable. See Table 6 for details.

[0060] Post-treatment: The difference in HBV DNA positivity rates between the two groups was statistically significant (χ²). 2 =3.977, P=0.046), the HBV DNA negative rate in the observation group was significantly higher than that in the control group.

[0061] Table 6 - Comparison of HBV DNA from the two groups after matching (6) Evaluation results of efficacy in the two matched groups In the control group of 42 patients, 24 (57.14%) showed no effect, 8 (19.05%) showed significant effect, and 10 (23.81%) showed effect, with a total effective rate of 42.86% (18 / 42). In the observation group of 42 patients, 6 (14.29%) showed no effect, 17 (40.48%) showed significant effect, and 19 (45.24%) showed effect, with a total effective rate of 85.71% (36 / 42). The difference in clinical efficacy between the two groups was statistically significant (χ²). 2 =16.833 (P<0.001), the clinical efficacy of the observation group was significantly better than that of the control group. See Table 7.

[0062] Table 7 - Results of efficacy evaluation in the two groups after matching 7. Safety and adverse reaction monitoring Before and after treatment, no significant abnormalities were observed in laboratory safety indicators such as blood routine and renal function in either group of patients. No drug-related adverse events, such as vomiting, rash, or other discomfort, occurred in either group of patients.

[0063] The traditional Chinese medicine composition of this invention is more effective than tenofovir alafenamide alone in reducing liver stiffness (LSM), spleen thickness, and APRI score in patients with chronic hepatitis B liver fibrosis (liver stagnation and spleen deficiency with blood stasis syndrome), improving liver function and increasing HBV DNA seroconversion rate, and has good safety.

Claims

1. A traditional Chinese medicine composition for treating liver fibrosis, characterized in that, The raw material components include: Astragalus membranaceus 10-20 parts by weight, Curcuma zedoaria (processed with vinegar) 4-8 parts by weight, Salvia miltiorrhiza 5-15 parts by weight, Paeonia suffruticosa 5-15 parts by weight, Paeonia lactiflora 5-15 parts by weight, Angelica sinensis 4-8 parts by weight, Curcuma longa 5-15 parts by weight, Amomum villosum 4-8 parts by weight, Atractylodes macrocephala (processed with wheat bran) 5-15 parts by weight, Poria cocos 8-16 parts by weight, Citrus medica 4-8 parts by weight, Bupleurum chinense (processed with vinegar) 4-8 parts by weight, and Glycyrrhiza uralensis (processed with vinegar) 1-5 parts by weight.

2. The traditional Chinese medicine composition for treating liver fibrosis according to claim 1, characterized in that, The raw material components include: Astragalus membranaceus 14-16 parts by weight, Curcuma zedoaria (processed with vinegar) 5-7 parts by weight, Salvia miltiorrhiza 8-12 parts by weight, Paeonia suffruticosa 8-12 parts by weight, Paeonia lactiflora 8-12 parts by weight, Angelica sinensis 5-7 parts by weight, Curcuma longa 8-12 parts by weight, Amomum villosum 5-7 parts by weight, Atractylodes macrocephala (processed with wheat bran) 8-12 parts by weight, Poria cocos 10-14 parts by weight, Citrus medica 5-7 parts by weight, Bupleurum chinense (processed with vinegar) 5-7 parts by weight, and Glycyrrhiza uralensis (processed with vinegar) 2-4 parts by weight.

3. The traditional Chinese medicine composition for treating liver fibrosis according to claim 1 or 2, characterized in that, The raw material components include: Astragalus membranaceus 15 parts by weight, Curcuma zedoaria (processed with vinegar) 6 parts by weight, Salvia miltiorrhiza 10 parts by weight, Paeonia suffruticosa 10 parts by weight, Paeonia lactiflora 10 parts by weight, Angelica sinensis 6 parts by weight, Curcuma longa 10 parts by weight, Amomum villosum 6 parts by weight, Atractylodes macrocephala (stir-fried with wheat bran) 10 parts by weight, Poria cocos 12 parts by weight, Citrus medica 6 parts by weight, Bupleurum chinense (processed with vinegar) 6 parts by weight, and Glycyrrhiza uralensis (processed with vinegar) 3 parts by weight.

4. The method for preparing the traditional Chinese medicine composition for treating liver fibrosis according to any one of claims 1-3, characterized in that, Includes the following steps: (1) Take Astragalus membranaceus, Curcuma zedoaria, Salvia miltiorrhiza, Paeonia suffruticosa, Paeonia lactiflora, Angelica sinensis, Curcuma longa, Amomum villosum and Atractylodes macrocephala stir-fried with wheat bran according to the weight parts, and after ultra-fine pulverization, obtain ultra-fine powder of each Chinese medicine; (2) Take the remaining raw material components according to the weight parts, crush them, and mix them thoroughly to obtain the Chinese medicine mixed powder; (3) Add water to the mixed powder of Chinese medicine obtained in step (2), and perform water extraction to obtain water extract; (4) The aqueous extract obtained in step (3) is filtered and concentrated to obtain a concentrate; (5) The concentrate described in step (4) is dried and ultra-finely pulverized in sequence, and then each of the traditional Chinese medicine ultra-fine powders described in step (1) is added and mixed thoroughly to obtain the traditional Chinese medicine composition for treating liver fibrosis.

5. The method for preparing the traditional Chinese medicine composition for treating liver fibrosis according to claim 4, characterized in that, In step (1), the particle size of each of the Chinese herbal medicine ultrafine powders is 1200-1800 mesh.

6. The method for preparing the traditional Chinese medicine composition for treating liver fibrosis according to claim 4, characterized in that, In step (3), the mass ratio of the mixed Chinese medicine powder to the added water is 1:2-1:

6.

7. The method for preparing the traditional Chinese medicine composition for treating liver fibrosis according to claim 4, characterized in that, In step (3), the water extraction process takes 2-4 hours.

8. The method for preparing the traditional Chinese medicine composition for treating liver fibrosis according to claim 4, characterized in that, In step (4), the concentration is carried out under reduced pressure to a thick paste with a relative density of 1.31-1.

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9. The method for preparing the traditional Chinese medicine composition for treating liver fibrosis according to claim 4, characterized in that, In step (5), the drying temperature is 80-160℃; the particle size of the ultrafine powder obtained after ultrafine pulverization is 1200-1800 mesh.

10. The use of the traditional Chinese medicine composition according to any one of claims 1-3 or the traditional Chinese medicine composition prepared by the method according to any one of claims 4-9 in the preparation of a medicament for treating liver fibrosis.

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