A traditional Chinese medicine composition for treating chronic pancreatitis

Abstract

The present application relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for treating chronic pancreatitis, which is composed of the following raw medicinal materials by weight: 20-40 parts of raw astragalus, 20-40 parts of dark plum, 20-40 parts of chicken gizzard, 10-20 parts of white peony root, 10-20 parts of red peony root, 4-8 parts of prepared aconite, 4-8 parts of dried ginger, 10-20 parts of cassia twig, 4-8 parts of coptis, 10-20 parts of scutellaria, 10-20 parts of giant knotweed, and 6-12 parts of costus. The traditional Chinese medicine composition is in accordance with the principle of "monarch, minister, assistant and guide" of traditional Chinese medicine, and the raw materials are common traditional Chinese medicines. The traditional Chinese medicine composition is simple, inexpensive and effective, has a significant effect on chronic pancreatitis, and has a broad market prospect. Through preliminary basic research, the effect and mechanism of the traditional Chinese medicine composition in improving pancreatic fibrosis are determined, providing an effective treatment method for the clinical treatment of chronic pancreatitis.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, in particular to a traditional Chinese medicine composition for treating chronic pancreatitis. BACKGROUND

[0002] Chronic pancreatitis is a progressive and irreversible inflammatory and fibrotic disease of the pancreas, and the clinical manifestations are mainly pain, impairment of pancreatic endocrine and exocrine function, and other secondary manifestations. Preliminary diagnosis needs laboratory examination and imaging examination, and definite diagnosis needs pathological examination of pancreatic tissue. Chronic pancreatitis is divided into three types according to pathological changes: chronic calcified pancreatitis, chronic obstructive pancreatitis and chronic inflammatory pancreatitis. The diagnosis and treatment guidelines issued by the Chronic Pancreatitis Committee of the Pancreatic Disease Professional Committee of the Chinese Medical Association divide the disease into five stages: 0 (subclinical stage), asymptomatic; 1 (without pancreatic insufficiency): repeated abdominal pain or acute pancreatitis; 2 (partial pancreatic insufficiency): pancreatic endocrine or exocrine dysfunction; 3 (complete pancreatic insufficiency): simultaneous occurrence of pancreatic endocrine and exocrine dysfunction; 4 (painless end stage): simultaneous occurrence of pancreatic endocrine and exocrine dysfunction, and no pain symptoms. At present, the treatment strategies commonly used by Western medicine are early use of pancreatic enzyme replacement and antioxidant therapy, mid-term endoscopic minimally invasive therapy, and late-stage surgical resection or decompression to relieve pain, but the early drug therapy cannot substantially reverse or reduce pancreatic fibrosis, and patients urgently need a truly effective drug to block or slow down the progression of the disease. Therefore, it is a hot spot in the field of pancreatic diseases to explore drugs that can improve pancreatic fibrosis.

[0003] Pancreatic fibrosis is progressive and irreversible during the course of chronic pancreatitis, and existing treatment methods are only to solve or relieve the clinical symptoms of chronic pancreatitis, and cannot fundamentally reverse or delay the development of pancreatic fibrosis. Therefore, screening drugs that can improve pancreatic fibrosis from natural drugs or synthetic drugs is the key in the field of chronic pancreatitis research at present.

[0004] Under the guidance of the theory of Chinese medicine characteristics, the traditional Chinese medicine composition formed by combining and matching natural drugs has good clinical efficacy in many types of fibrotic diseases, and there are also related clinical reports of traditional Chinese medicine treatment of chronic pancreatitis in China. However, there is no report on a clinically effective, inexpensive and safe traditional Chinese medicine composition at present. SUMMARY

[0005] The purpose of the present application is to provide a traditional Chinese medicine composition for treating chronic pancreatitis, to clarify its therapeutic effect of improving pancreatic fibrosis, and to clarify its mechanism of action, thereby providing an effective treatment method for the clinical treatment of chronic pancreatitis. The present application combines the diagnosis and treatment of chronic pancreatitis patients in the department of gastroenterology to summarize the experience and induce a clinically effective, inexpensive and safe traditional Chinese medicine composition.

[0006] In a first aspect, the present application provides a Chinese medicine composition for treating chronic pancreatitis, which is composed of raw medicinal materials in the following proportions by weight: 20-40 parts of Radix Astragali, 20-40 parts of Fructus Mume, 20-40 parts of Endothelium Corii Asini, 10-20 parts of Radix Paeoniae Alba, 10-20 parts of Radix Paeoniae Rubra, 4-8 parts of Aconiti Praeparatae, 4-8 parts of Rhizoma Zingiberis Recens, 10-20 parts of Ramulus Cinnamomi, 4-8 parts of Rhizoma Coptidis, 10-20 parts of Radix Scutellariae, 10-20 parts of Rhizoma Polygoni Cuspidati, and 6-12 parts of Radix Aucklandiae.

[0007] Further, the Chinese medicine composition for treating chronic pancreatitis is composed of Chinese medicine raw medicinal materials in the following proportions by weight:

[0008] 30-40 parts of Radix Astragali, 30-40 parts of Fructus Mume, 30-40 parts of Endothelium Corii Asini, 15-20 parts of Radix Paeoniae Alba, 15-20 parts of Radix Paeoniae Rubra, 6-8 parts of Aconiti Praeparatae, 6-8 parts of Rhizoma Zingiberis Recens, 15-20 parts of Ramulus Cinnamomi, 6-8 parts of Rhizoma Coptidis, 15-20 parts of Radix Scutellariae, 15-20 parts of Rhizoma Polygoni Cuspidati, and 9-12 parts of Radix Aucklandiae.

[0009] Further, the Chinese medicine composition for treating chronic pancreatitis is composed of Chinese medicine raw medicinal materials in the following proportions by weight:

[0010] In a third aspect, the present application provides a Chinese medicine preparation using the Chinese medicine composition for treating chronic pancreatitis as described above as an active ingredient, which is prepared into a common dosage form in pharmacy by using a conventional preparation method in the field.

[0011] Further, the dosage form of the Chinese medicine preparation is a decoction, a tablet, a capsule, a granule, a pill, an oral liquid or a syrup.

[0012] Further, the Chinese medicine preparation further comprises a pharmaceutically acceptable excipient.

[0013] In a fourth aspect, the present application provides use of the Chinese medicine composition as described above in the preparation of a medicine for treating chronic pancreatitis.

[0014] In a fifth aspect, the present application provides use of the Chinese medicine preparation as described above in the preparation of a medicine for treating chronic pancreatitis.

[0015] Further, the traditional Chinese medicine composition can improve the weight loss of chronic pancreatitis mice, atrophy of pancreas, obviously relieve atrophy of acinar cells in pancreas tissue, reduce the content of collagen fibers in the pathological state of chronic pancreatitis, obviously reduce the content of fibronectin (Fibronectin I) and collagen (Collagen I) in the pancreas tissue of CP mice, reduce the degree of pancreatic fibrosis, obviously down-regulate the gene expression level of collagen type I, collagen type III and fibronectin in the pancreas tissue of CP mice, affect the expression balance of Timps / MMPs related genes, and then reduce the degree of pancreatic fibrosis, and obviously reduce the content of hydroxyproline, which is an essential amino acid of collagen in the pancreas tissue of CP mice, indicating that the degree of pancreatic fibrosis is reduced.

[0016] In the prescription, Huangqi supplements qi and invigorates the spleen, makes qi strong and blood flow, Wumei softens the liver and relieves urgency, stops pain and diarrhea, both of which are used together, the liver and spleen are adjusted, and tonifying and astringing are applied, which are the monarch drugs. Jineijin invigorates the stomach and promotes digestion, and can also disperse accumulation and distention; the same use of Chishabaoshao nourishes blood and blood, dredges collaterals and stops pain, assists the monarch drug in adjusting the liver and spleen, and is the minister drug. With the use of Fuzi, Ganjiang and Guizhi, the yang is dredged, the cold is stopped and the pain is relieved; Huanglian, Huangqin and Huozhang are used to clear heat and purge fire, and the two groups of drugs make the cold and heat harmonious, the yin and yang balanced, and are the assistant drugs. Muxiang is used to dredge qi, stop pain, invigorate the spleen and promote digestion, and is used as a complementary drug. The whole prescription is used together, the cold and heat are used together, the attack and tonification are applied, the liver and spleen are adjusted, and the functions of tonifying qi, invigorating the spleen, softening the liver and dredging collaterals, and regulating cold and heat are achieved.

[0017] The present application has the advantages that:

[0018] The traditional Chinese medicine composition of the present application is compatible with the principle of "monarch, minister and assistant" of traditional Chinese medicine, the raw materials are common traditional Chinese medicines, it is simple, economical and effective, has significant efficacy on chronic pancreatitis, and has a broad market prospect. Through preliminary basic research, the effect and mechanism of the traditional Chinese medicine composition in improving pancreatic fibrosis are clarified, which provides an effective treatment method for clinical treatment of chronic pancreatitis, and also provides a theoretical basis for researchers engaged in screening of traditional Chinese medicine monomers for treating chronic pancreatitis. BRIEF DESCRIPTION OF DRAWINGS

[0019] Figure 1 . The line graph of the weight change of mice;

[0020] Figure 2 . The ratio of the weight of the pancreas of mice;

[0021] Figure 3 . HE & Masson staining;

[0022] Figure 4 . Fibrosis-related protein indicators;

[0023] Figure 5 . Expression level of fibrosis-related genes;

[0024] Figure 6 . Pancreatic tissue hydroxyproline content. DETAILED DESCRIPTION

[0025] The specific embodiments of the present application are described in detail below with reference to the following examples.

[0026] Example 1: Traditional Chinese medicine composition of the present application

[0027] Composed of the following raw medicinal materials by weight: Radix Astragali 20 parts, Fructus Mume 20 parts, Endo-Scapus Galli 20 parts, Radix Paeoniae Alba 10 parts, Radix Paeoniae Rubra 10 parts, Prepared Aconiti Lateralis Radix 4 parts, Rhizoma Zingiberis Recens 4 parts, Ramulus Cinnamomi 10 parts, Rhizoma Coptidis 4 parts, Radix Scutellariae 10 parts, Rhizoma Polygoni Cuspidati 10 parts, Radix Aucklandiae 6 parts.

[0028] Example 2: Traditional Chinese medicine composition of the present application

[0029] Composed of the following raw medicinal materials by weight: Radix Astragali 25 parts, Fructus Mume 25 parts, Endo-Scapus Galli 25 parts, Radix Paeoniae Alba 12 parts, Radix Paeoniae Rubra 12 parts, Prepared Aconiti Lateralis Radix 5 parts, Rhizoma Zingiberis Recens 5 parts, Ramulus Cinnamomi 12 parts, Rhizoma Coptidis 5 parts, Radix Scutellariae 12 parts, Rhizoma Polygoni Cuspidati 12 parts, Radix Aucklandiae 8 parts.

[0030] Example 3: Traditional Chinese medicine composition of the present application

[0031] Composed of the following raw medicinal materials by weight: Radix Astragali 30 parts, Fructus Mume 30 parts, Endo-Scapus Galli 30 parts, Radix Paeoniae Alba 15 parts, Radix Paeoniae Rubra 15 parts, Prepared Aconiti Lateralis Radix 6 parts, Rhizoma Zingiberis Recens 6 parts, Ramulus Cinnamomi 15 parts, Rhizoma Coptidis 6 parts, Radix Scutellariae 15 parts, Rhizoma Polygoni Cuspidati 15 parts, Radix Aucklandiae 9 parts.

[0032] Example 4: Traditional Chinese medicine composition of the present application

[0033] Composed of the following raw medicinal materials by weight: Radix Astragali 35 parts, Fructus Mume 30 parts, Endo-Scapus Galli 30 parts, Radix Paeoniae Alba 18 parts, Radix Paeoniae Rubra 18 parts, Prepared Aconiti Lateralis Radix 7 parts, Rhizoma Zingiberis Recens 7 parts, Ramulus Cinnamomi 18 parts, Rhizoma Coptidis 7 parts, Radix Scutellariae 18 parts, Rhizoma Polygoni Cuspidati 18 parts, Radix Aucklandiae 10 parts.

[0034] Example 5: Traditional Chinese medicine composition of the present application

[0035] Composed of the following raw medicinal materials by weight: Radix Astragali 40 parts, Fructus Mume 30 parts, Endo-Scapus Galli 30 parts, Radix Paeoniae Alba 20 parts, Radix Paeoniae Rubra 20 parts, Prepared Aconiti Lateralis Radix 8 parts, Rhizoma Zingiberis Recens 8 parts, Ramulus Cinnamomi 20 parts, Rhizoma Coptidis 8 parts, Radix Scutellariae 20 parts, Rhizoma Polygoni Cuspidati 20 parts, Radix Aucklandiae 12 parts.

[0036] Example 6: Preparation of decoction

[0037] The conventional preparation method of traditional Chinese medicine decoction is adopted, i.e. the raw medicinal materials are weighed according to the proportion by weight, and then boiled with water to prepare the decoction.

[0038] Example 7: Preparation of tablets / capsules

[0039] Weigh each Chinese herbal raw material according to the weight ratio, grind it into a fine powder, decoct it, concentrate it under reduced pressure to obtain an extract, dry and pulverize the extract into granules, add pharmaceutical excipients, and compress it into tablets or capsules.

[0040] Example 8: Preparation of Granules

[0041] Weigh each Chinese herbal medicine raw material according to the weight ratio, grind it into a fine powder, decoct it, concentrate it under reduced pressure to obtain an extract, and dry and pulverize the extract to make granules.

[0042] Example 9: Preparation of pills

[0043] Weigh each Chinese herbal medicine raw material according to the weight ratio, grind it into a fine powder, decoct it, take the supernatant, and concentrate it into a thick extract; add appropriate pharmaceutical excipients (white sugar, honey, benzopropionic acid or ethylparaben, etc.) to make pills.

[0044] Example 10: Animal Experiment

[0045] I. Experimental Methods

[0046] C57BL / 6J mice were randomly divided into three groups: a normal control group (CON), a disease model group (CP), and a disease model group plus a traditional Chinese medicine (TCM) combination gavage treatment group (CP+QMKL). All three groups were fed at room temperature. The latter two groups (CP and CP+QMKL) were intraperitoneally injected with PBS-dissolved thymol at a dose of 50 μg / kg for 4 weeks, three days a week, six times a day, with one-hour intervals. The last group (CP+QMKL) was given a TCM solution (compound granules dissolved in double-distilled water) once daily by gavage starting from the second week, at a dose of 2 g / kg (clinical patient dosage × animal equivalent dose ratio). After 4 weeks, pancreatic tissue was collected from the mice. Pancreatic head tissue was stained with HE and Masson staining, and pancreatic tail tissue was used for quantitative PCR, Western blotting, and ELISA experiments.

[0047] II. Results and Analysis

[0048] 1. A traditional Chinese medicine composition improved weight loss and pancreatic atrophy in mice with chronic pancreatitis.

[0049] Observe the line graph of mouse body weight change ( Figure 1 It can be seen that the body weight of the CP group was significantly lower than that of the CON group, while the average body weight of the CP+QMKL group was higher than that of the CP group during the modeling period. Observation of the pancreas-body weight ratio histogram ( Figure 2 It can be seen that the pancreas-to-body weight ratio in the CP group was significantly lower than that in the CON group, while the pancreas-to-body weight ratio in the CP+QMKL group was higher than that in the CP group. It can be inferred that the traditional Chinese medicine combination can improve the weight loss and pancreatic atrophy in mice with chronic pancreatitis.

[0050] 2. Traditional Chinese medicine composition improves pancreatic fibrosis in mice with chronic pancreatitis.

[0051] (1) Pathological section staining results (HE & Masson staining)

[0052] Pathological slide image ( Figure 3 The results show that the traditional Chinese medicine composition can significantly alleviate the atrophy of acinar cells in pancreatic tissue and reduce the content of collagen fibers in the pathological state of chronic pancreatitis.

[0053] (2) Western blot assay

[0054] Results of Western blot assay ( Figure 4 The results showed that the traditional Chinese medicine composition significantly reduced the content of fibronectin I and collagen I in the pancreatic tissue of CP mice, thus alleviating the degree of pancreatic fibrosis.

[0055] (3) Real-time quantitative nucleic acid amplification detection experiment (qPCR)

[0056] Results of real-time quantitative nucleic acid amplification detection experiment ( Figure 5 The traditional Chinese medicine composition significantly downregulated the gene expression levels of type I and type III collagen and fibronectin in the pancreatic tissue of CP mice, affected the expression balance of Timps / MMPs-related genes, and thus reduced the degree of pancreatic fibrosis.

[0057] (4) Enzyme-linked immunosorbent assay (ELISA)

[0058] Results of enzyme-linked immunosorbent assay (ELISA) Figure 6 The results showed that the traditional Chinese medicine composition significantly reduced the content of hydroxyproline, an essential amino acid for collagen, in the pancreatic tissue of CP mice, indicating that the degree of pancreatic tissue fibrosis was reduced.

[0059] The preferred embodiments of the present invention have been described in detail above, but the present invention is not limited to the embodiments described. Those skilled in the art can make various equivalent modifications or substitutions without departing from the spirit of the present invention, and these equivalent modifications or substitutions are all included within the scope defined by the claims of this application.

Claims

1. A traditional Chinese medicine composition for treating chronic pancreatitis, characterized in that, The raw medicinal materials are composed of the following components by weight: Radix Astragali 20-40 parts, Fructus Mume 20-40 parts, Endothelium Corneum Gigeriae Galli 20-40 parts, Radix Paeoniae Alba 10-20 parts, Radix Paeoniae Rubra 10-20 parts, Preparata Aconiti 4-8 parts, Rhizoma Zingiberis 4-8 parts, Ramulus Cinnamomi 10-20 parts, Rhizoma Coptidis 4-8 parts, Radix Scutellariae 10-20 parts, Rhizoma Polygoni Cuspidati 10-20 parts, Radix Aucklandiae 6-12 parts.

2. The traditional Chinese medicine composition for treating chronic pancreatitis according to claim 1, characterized in that, The raw medicinal materials are composed of the following components by weight: Radix Astragali 30-40 parts, Fructus Mume 30-40 parts, Endothelium Corneum Gigeriae Galli 30-40 parts, Radix Paeoniae Alba 15-20 parts, Radix Paeoniae Rubra 15-20 parts, Preparata Aconiti 6-8 parts, Rhizoma Zingiberis 6-8 parts, Ramulus Cinnamomi 15-20 parts, Rhizoma Coptidis 6-8 parts, Radix Scutellariae 15-20 parts, Rhizoma Polygoni Cuspidati 15-20 parts, Radix Aucklandiae 9-12 parts.

3. The traditional Chinese medicine composition for treating chronic pancreatitis according to claim 1, characterized in that, The raw medicinal materials are composed of the following components by weight: Radix Astragali 30 parts, Fructus Mume 30 parts, Endothelium Corneum Gigeriae Galli 30 parts, Radix Paeoniae Alba 15 parts, Radix Paeoniae Rubra 15 parts, Preparata Aconiti 6 parts, Rhizoma Zingiberis 6 parts, Ramulus Cinnamomi 15 parts, Rhizoma Coptidis 6 parts, Radix Scutellariae 15 parts, Rhizoma Polygoni Cuspidati 15 parts, Radix Aucklandiae 9 parts.

4. A Chinese medicine preparation comprising the Chinese medicine composition for treating chronic pancreatitis according to any one of claims 1 to 3 as an active ingredient, characterized in that, The traditional Chinese medicine preparation is prepared into a common dosage form in pharmacy by using a conventional preparation method in the art.

5. The traditional Chinese medicine preparation according to claim 4, characterized in that, The dosage form of the traditional Chinese medicine preparation is a decoction, a tablet, a capsule, a granule, a pill, an oral liquid or a syrup.

6. Use of the traditional Chinese medicine composition according to any one of claims 1-3 in the preparation of a medicament for treating chronic pancreatitis.

7. Use of the traditional Chinese medicine preparation according to claim 4 or 5 in the preparation of a medicament for treating chronic pancreatitis.

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