Medicine for treating and / or preventing chronic bronchitis

Abstract

The invention relates to application of a traditional Chinese medicine composition in preparation of a medicine for treating and / or preventing chronic bronchitis. The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 300 to 400 parts of cordia dichotoma fruits, 100 to 200 parts of Chinese dates, 150 to 200 parts of pericarpium papaveris, 50 to 100 parts of liquorice, 10 to 50 parts of hollyhock seeds, 10 to 50 parts of cucumber seeds, 10 to 50 parts of cydonia oblonga seeds, 50 to 100 parts of almonds, 50 to 100 parts of pericarpium papaveris, 10 to 50 parts of tragacanth gum, 10 to 50 parts of liquorice extract and 10 to 50 parts of Arabic gum.

Description

Technical Field

[0001] This application belongs to the field of pharmaceutical technology, and specifically relates to a traditional Chinese medicine composition for treating or preventing chronic bronchitis. Background Art

[0002] Chronic bronchitis (CB) is a chronic non-specific inflammation of the trachea, bronchial mucosa and its surrounding tissues caused by infectious or non-infectious factors. This disease is clinically common and prone to occur in the elderly population, with characteristics such as a long course and repeated attacks. The progression of the disease can also be complicated by obstructive emphysema, cor pulmonale, etc., and chronic obstructive pulmonary disease is a secondary disease of this disease.

[0003] The pathogenesis of chronic bronchitis is not yet clear and may be the result of the long-term interaction of multiple factors. Most clinical treatments focus on prevention first and treatment second, and the main purpose is to relieve symptoms, prevent the occurrence of complications and slow down the progression of the disease. Western medicine treats this disease mainly with antibiotics and anti-infections, and the short-term treatment effect is obvious. However, due to the easy recurrence of chronic bronchitis and the majority of patients being the elderly population, if antibiotics are frequently used, sensitive bacteria in the body can be inhibited, while the bacteria and fungi that are not inhibited will take the opportunity to multiply in large numbers, causing dysbacteriosis. This will cause great obstacles to subsequent treatment. In addition, certain side effects such as liver and kidney damage also limit the wide range of its clinical applications.

[0004] Traditional Chinese medicine treatment of chronic bronchitis has the characteristics of overall regulation and multi-target intervention, high treatment safety, and broad application prospects. The prescription of Respirov Syrup has the efficacy of relieving cough and resolving phlegm, and can be used to treat cough and sore throat. The treatment advantages and molecular mechanisms of this medicine in the treatment of respiratory diseases are not yet clear and need to be explored in depth and systematically. The research on chronic bronchitis is particularly important. Summary of the Invention

[0005] One or more embodiments of this application provide the use of a traditional Chinese medicine composition in the preparation of a drug for treating and / or preventing chronic bronchitis or its complications or secondary diseases, wherein the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:

[0006]

[0007] In one or more embodiments, the traditional Chinese medicine composition is prepared from the following raw materials in parts by weight:

[0008]

[0009] In one or more embodiments, the traditional Chinese medicine composition consists of the water extract of the following raw materials in parts by weight:

[0010]

[0011] In one or more embodiments, the traditional Chinese medicine composition is composed of water extracts of traditional Chinese medicinal materials in the following parts by weight:

[0012]

[0013] In one or more embodiments, the traditional Chinese medicine composition is prepared by the following method:

[0014]

[0015] Take the raw materials in the above parts by weight, crush them into coarse powder, decoct with water 1, 2 or 3 times, each time for 1 hour, filter, combine the filtrates, concentrate into a thick paste, and dry the thick paste to obtain the product.

[0016] In one or more embodiments, the traditional Chinese medicine composition is prepared by the following method:

[0017]

[0018] Take the raw materials in the above parts by weight, crush them into coarse powder, decoct with water 1, 2 or 3 times, each time for 1 hour, filter, combine the filtrates, concentrate into a thick paste, and dry the thick paste to obtain the product.

[0019] In one or more embodiments, 900 parts by weight of powdered sugar is added to the thick paste to make granules, and then dried to obtain the product.

[0020] In one or more embodiments, the complication is obstructive emphysema.

[0021] In one or more embodiments, the complication is cor pulmonale.

[0022] In one or more embodiments, the secondary disease is chronic obstructive pulmonary disease.

[0023] The fruit of Cordia dichotoma Forst.f. is the dried ripe fruit of Cordia dichotoma Forst.f. of the family Boraginaceae.

[0024] The fruit of Chinese jujube is the dried ripe fruit of Ziziphus jujuba Mill.var.inermis (Bunge) Rehd. of the family Rhamnaceae.

[0025] The pericarp of opium poppy is the dried ripe pericarp of Papaver somniferum L. of the family Papaveraceae.

[0026] Licorice is the dried root of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., or Glycyrrhiza glabra L. of the Leguminosae family.

[0027] The seeds of hollyhock are from the seeds of Althaea rosea (L.) Cavan. of the Althaea genus in the Malvaceae family.

[0028] Cucumber seeds are the seeds of Cucumis sativus L. of the Cucurbitaceae family.

[0029] Quince seeds are the seeds of Cydonia oblonga Mill. of the Cydonia genus in the Rosaceae family.

[0030] Bitter almond kernels are the dried and mature seeds of Amygdalus communis L. of the Rosaceae family.

[0031] Poppy seeds are the seeds of Papaver somniferum L. of the Papaver genus in the Papaveraceae family.

[0032] Tragacanth gum is the dried gum mucus extracted from Astragalus gummifer Labill. of the Leguminosae family.

[0033] Licorice extract is an extract made by decocting and extracting Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat., or Glycyrrhiza glabra L. of the Leguminosae family.

[0034] Arabic gum is a dried gummy exudate obtained from the branches of Acacia Senegal (Linne) Willdenow of the Acacia genus in the Leguminosae family or similar tree species of the same genus. Description of the Drawings

[0035] Figure 1 Indicates the changes in body weight of mice in each group in Example 2.

[0036] Figure 2 Indicates the pathological changes in the lung tissues of mice in each group in Example 3.

[0037] Figure 3 Indicates the results of the histopathological scores of each group in Example 3.

[0038] Figure 4 Indicates the results of the Masson trichrome stained lung tissue sections of each group in Example 4.

[0039] Figure 5 Indicates the results of the histopathological scores of each group in Example 4.

[0040] Figure 6 Indicates the SOD levels of each group in Example 5.

[0041] Figure 7 Indicates the MDA levels of each group in Example 5.

[0042] Figure 8 Indicates the IL-6 level in the bronchoalveolar lavage fluid in Example 6.

[0043] Figure 9 Indicates the analysis result of TNF-α in the bronchoalveolar lavage fluid in Example 6 using one-way ANOVA. Detailed implementation manners

[0044] The following examples are used to illustrate the technical solutions of the present application in detail, but are not used to limit the scope of the present application.

[0045] Preparation of the traditional Chinese medicine composition in Example 1

[0046] The prescription of Respisitan Hot Sensation consists of 12 traditional Chinese medicinal materials, namely 350 g of Cordia dichotoma fruit, 140 g of jujube, 168 g of poppy shell, 84 g of licorice, 28 g of Althaea rosea seeds, 28 g of cucumber seeds, 21 g of Cydonia oblonga seeds, 84 g of almond, 84 g of poppy seeds, 21 g of tragacanth gum, 21 g of licorice extract, and 21 g of gum arabic.

[0047] The preparation method of the traditional Chinese medicine composition is as follows: Grind the above 12 medicinal materials into coarse powder, decoct with water for 3 times, each time for 1 hour, filter, combine the filtrates, concentrate into a thick paste (hereinafter referred to as "composition extract"), and dry.

[0048] Construction of the animal model in Example 2

[0049] 2.1 Construction of the LPS (lipopolysaccharide) / CS (smoke) - induced chronic bronchitis model

[0050] 2.1.1 Animal grouping and treatment

[0051] 70 SPF male C57BL / 6 mice (8 weeks old) were provided by the Animal Center of Xinjiang Medical University. The mice were housed in a specific pathogen-free room with a constant temperature of (21 ± 2) °C, a humidity of (50% ± 10%), and a 12-hour light / dark cycle.

[0052] Wild-type C57BL / 6 mice were adaptively fed for 7 days and randomly divided into 7 groups (10 mice in each group): normal control group (control group), LPS / CS-induced chronic bronchitis model group (model group), 0.87 mg / g composition extract treatment group (Re low dose), 1.74 mg / g composition extract treatment group (Re medium dose), 3.48 mg / kg composition extract treatment group (Re high dose), 0.35 mg / g Maxing Zhike tablets treatment group (Ma), and 10 mg / kg roflumilast treatment group (ROF).

[0053] Mice in the control group were housed in a SPF air chamber. The chronic bronchitis mouse model group was established by intranasally instilling 20 μg / 50 μL LPS into mice and exposing the mice to CS. Briefly, 20 μg LPS was dissolved in 50 μL distilled water and intranasally instilled into mice on the 1st and 15th days of the experiment. From the 2nd to 14th days and 16th to 42nd days, the mice were exposed to cigarette smoke (six cigarettes / 30 minutes) (self-made smoking chamber 0.64 m × 0.44 m × 0.40 m) for 2 hours per day, 6 days per week for 6 weeks. Mice were orally administered the composition extract solution or Maxing Zhike tablets (0.35 mg / kg), roflumilast (10 mg / kg) 1 hour before cigarette smoke exposure from the 28th to 42nd days. Mice in the control group were simultaneously orally administered distilled water (0.2 mL / mouse). On the 43rd day, whole blood, bronchoalveolar lavage fluid (BALF), and lung tissue of each group of mice were collected for further study.

[0054] 2.2 Sample collection

[0055] 2.2.1 Collection of mouse blood

[0056] Twenty-four hours after the last administration of mice, blood was collected by orbital puncture. The collected mouse blood was placed in a 1.5 mL EP tube and allowed to stand overnight, then centrifuged at 3000 rpm at 4°C for 15 min, and the supernatant was stored at -80°C for later use.

[0057] 2.2.2 Collection of mouse bronchoalveolar lavage fluid (BALF)

[0058] Four mice were randomly selected from each group. The mice were fixed on a foam board and the chest cavity was opened to expose the trachea. A 1 mL syringe needle was slowly and gently inserted into the trachea of the mice and fixed. 0.8 mL PBS was slowly pushed into the lungs of the mice along the trachea, and about 1 mL BALF was recovered after two perfusions. The collected BALF samples were kept on ice and centrifuged at 1000 rpm at 4°C for 15 min. The supernatant of each tube of BALF was collected into a separate 1.5 mL EP tube and stored at -80°C for later use.

[0059] 2.2.3 Collection of mouse lung tissue

[0060] Six mice were randomly selected from each group to collect lung tissues for subsequent experiments. The mice were fixed on a foam board, and the chest wall was cut open to expose the thoracic cavity. The left lung was placed in pre-prepared 4% paraformaldehyde for histological examination, and the right lung was wrapped in tin foil, placed on ice, and then transferred to a liquid nitrogen tank for later use.

[0061] 2.3 Sample processing

[0062] 2.3.1 The specific steps for H&E staining of mouse lung tissues are as follows:

[0063] The collected mouse lung tissues were fixed in 4% paraformaldehyde for 48 h for subsequent H&E staining.

[0064] 1) Dehydration

[0065] The process of replacing the water contained in tissues or cells with a dehydrating agent is called tissue dehydration. Currently, alcohol is mostly used for dehydration, but alcohol can easily harden and embrittle tissues. Therefore, when using it, it is usually from low concentration to high concentration, and the concentration series is generally 65%, 75%, 85%, 95%, and 100%.

[0066] 2) Clearing

[0067] After the tissue has been treated with a series of alcohols, xylene is used for clearing. The operation steps are as follows:

[0068] ① Xylene I: 30 min.

[0069] ② Xylene II: 30 min.

[0070] 3) Wax infiltration

[0071] The process of impregnating the tissue, which has been completely cleared by the clearing agent, into molten paraffin at about 65 °C is called wax infiltration. The operation steps are as follows:

[0072] ① Paraffin I: 1 h.

[0073] ② Paraffin II: 2 h.

[0074] ③ Paraffin III: 2 h.

[0075] 4) Embedding

[0076] Place the specimen to be embedded on the embedding mold, pour in the wax, making sure there are no air bubbles. Then place the corresponding embedding cassette on top of the mold. Put the embedded mold on a cold table. After the wax block on the cold table has cooled, remove the mold, trim the excess wax from the edges, and place them in order on an ice box for sectioning.

[0077] 5) Sectioning

[0078] First, freeze the wax block at -20°C for about 20 minutes. Turn on the microtome in advance and set the temperature to about 45°C. Fix the paraffin block on the specimen holder. Select the coarse adjustment to trim the specimen to its largest surface. Select the fine adjustment and the section thickness, and then cut the section. When cutting the section, first cut a few slices, hold them up with the brush in the left hand, and then while turning the right hand, gently pull with the left hand. Sometimes, you can also gently blow on the section to flatten it. Use forceps to pick up the section and place it on the water surface. After flattening, pick up the section. Write the number on it and drain the water vertically on the glass slide.

[0079] 6) Baking the section

[0080] Before staining the paraffin section, bake the section at 65°C for 30 minutes to 1 hour.

[0081] 7) Dewaxing

[0082] ① Xylene I: 10 minutes.

[0083] ② Xylene II: 10 minutes.

[0084] 8) Rehydration

[0085] ① Absolute ethanol I: 1 minute.

[0086] ② Absolute ethanol II: 1 minute.

[0087] ③ 95% ethanol I: 1 minute.

[0088] ④ 95% ethanol II: 1 minute.

[0089] ⑤ 85% ethanol: 1 minute.

[0090] ⑥ 75% ethanol: 1 minute.

[0091] ⑦ Water washing: 2 minutes.

[0092] 9) Staining

[0093] ① Hematoxylin: 5 - 10 minutes.

[0094] ② Differentiation: Decolorize with 0.5 - 1% hydrochloric acid alcohol (prepared with 70% alcohol) for a short time. Control under the microscope until the cell nucleus and nuclear chromatin are clear, about 10 seconds.

[0095] ③ Water washing: 1 - 8 minutes. (Blue returning)

[0096] ④ Eosin: 1 minute.

[0097] ⑤ Water washing: 30 seconds.

[0098] 10) Dehydration

[0099] ① 75% ethanol: 20 seconds.

[0100] ② 85% ethanol: 30 seconds.

[0101] ③ 95% ethanol I: 1 min.

[0102] ④ 95% ethanol II: 1 min.

[0103] ⑤ Absolute ethanol I: 1 min.

[0104] ⑥ Absolute ethanol II: 1 min.

[0105] 11) Transparency

[0106] ① Xylene I: 5 min.

[0107] ② Xylene II: 5 min.

[0108] 12) Mounting

[0109] Mount with neutral balsam.

[0110] 13) Microscopic examination

[0111] After the sections are air-dried, observe and record under the microscope.

[0112] 2.3.2 The specific steps for Masson staining of mouse lung tissue are as follows:

[0113] 1) Deparaffinize the above paraffin sections routinely to water.

[0114] 2) Stain with the prepared Weigert iron hematoxylin staining solution for 5 - 10 min.

[0115] 3) Differentiate with acidic ethanol differentiating solution for 5 - 15 s, then wash with water.

[0116] 4) Blue with Masson bluing solution for 3 - 5 min, then wash with water. Wash with distilled water for 1 min.

[0117] 5) Stain with Ponceau fuchsin staining solution for 5 - 10 min.

[0118] 6) During the above operation process, prepare a weak acid working solution according to the ratio of distilled water: acid solution = 2:1, and wash with the weak acid working solution for 1 min.

[0119] 7) Wash with phosphomolybdic acid working solution for 1 - 2 min. Wash with the prepared weak acid working solution for 1 min.

[0120] 8) Directly place it in the aniline blue staining solution and stain for 1 - 2 min. Wash with the prepared weak acid working solution for 1 min.

[0121] 9) Dehydrate quickly with 95% ethanol for 2 - 3 s, dehydrate with absolute ethanol 3 times, 5 - 10 s each time.

[0122] 10) Xylene transparency for 3 times, 1 - 2 min each time, and seal with neutral balsam.

[0123] 2.3.3 Detection of MDA and SOD in mouse serum

[0124] Centrifuge the collected mouse blood at 3000 rpm and 4 °C for 30 minutes, collect the supernatant of each tube separately into a single 1.5 mL Eppendorf tube, and store at -80 °C for subsequent detection of indicators.

[0125] 1) Detection of MDA

[0126] ① Standard tubes: Take 0.02 mL of standards with 8 different concentrations and add them to 1.5 mL Eppendorf tubes with standard numbers respectively.

[0127] Sample tubes: Take 0.02 mL of the sample to be measured and add it to a 1.5 mL Eppendorf tube.

[0128] Control tubes: Take 0.02 mL of the sample to be measured and add it to a 1.5 mL Eppendorf tube.

[0129] ② Add 0.02 mL of Reagent 1 to each tube in Step ①.

[0130] ③ Add 0.6 mL of Reagent 2 application solution to each tube in Step ②.

[0131] ④ Add 0.2 mL of Reagent 3 application solution to the standard tubes and measurement tubes in Step ③, and add 0.2 mL of 50% acetic acid to the control tubes.

[0132] ⑤ Tie the mouth of the Eppendorf tube tightly with plastic wrap, mix well, and make a small hole in the plastic wrap, then place it in a 100 °C water bath for 40 min.

[0133] ⑥ Cool to room temperature with running water and centrifuge at 9569×g for 10 min.

[0134] ⑦ Use a micropipette to take 0.25 mL of the supernatant to the enzyme - linked immunosorbent assay (ELISA) plate. (Do not add the precipitate to the ELISA plate)

[0135] ⑧ Measure the OD value at 532 nm on an ELISA reader.

[0136] 2) Detection of SOD

[0137] ① Control blank wells: Take 5 μL of PBS (0.01 M, pH 7.4) and add it to the control blank wells.

[0138] Control wells: Take 5 μL of PBS (0.01 M, pH 7.4) and add it to the control wells.

[0139] Measurement wells: Take 5 μL of the sample and add it to the measurement wells.

[0140] ② Add 90 μL of Reagent 1 application solution to each well in Step ①.

[0141] ③ Add 30 μL of enzyme working solution to the assay and control wells in Step ②.

[0142] Add 30 μL of non - enzyme working solution to the control blank well.

[0143] ④ Shake the plate on the microplate reader for 10 s, cover with a plastic film, and incubate at 37 °C for 50 min.

[0144] ⑤ Add 180 μL of chromogenic reagent to each well in Step ④.

[0145] ⑥ Shake the plate on the microplate reader for 10 s, let it stand at room temperature for 10 min, and measure the absorbance of each well at 550 nm using the microplate reader.

[0146] 2.3.4 Detection of IL - 6 and TNF - α in mouse BALF

[0147] Centrifuge the collected BALF at 1000 rpm at 4 °C for 15 min, collect the supernatant of each tube of BALF into a separate 1.5 mL Eppendorf tube, and store it at - 80 °C for subsequent detection of inflammatory factor expression.

[0148] 1) Detection of IL - 6

[0149] ① Set the standard wells, blank wells, and sample wells respectively. Add 100 μL of serially diluted standard product to the standard wells, 100 μL of standard product & sample diluent to the blank wells, and 100 μL of the sample to be tested to the remaining wells. Cover the microplate with a plastic film and incubate at 37 °C for 90 minutes.

[0150] ② Discard the liquid in the wells by flicking, without washing. Add 100 μL of biotinylated antibody working solution to each well, cover the microplate with a plastic film, and incubate at 37 °C for 1 hour.

[0151] ③ Discard the liquid in the wells by flicking, and pat dry on a clean absorbent paper. Add 350 μL of washing solution to each well, soak for 1 minute, aspirate or flick off the liquid in the microplate, and pat dry. Repeat this washing step 3 times.

[0152] ④ Add 100 μL of enzyme conjugate working solution to each well, cover the microplate with a plastic film, and incubate at 37 °C for 30 minutes.

[0153] ⑤ Discard the liquid in the wells by flicking, wash the plate 5 times, with the method the same as in Step 3.

[0154] ⑥ Add 90 μL of substrate solution (TMB) to each well, cover the microplate with a plastic film, and incubate at 37 °C in the dark for about 15 minutes.

[0155] ⑦ Add 50 μL of stop solution to each well to terminate the reaction.

[0156] ⑧Immediately measure the optical density (OD value) of each well at a wavelength of 450 nm using an enzyme-labeled instrument.

[0157] 2) TNF-α detection

[0158] Same method as above

[0159] result

[0160] 1. Observation of general signs of mice

[0161] 1) Blank control group: The mice had normal activities, large food intake, quick reactions, stable breathing, shiny fur, and normal skin and mucous membrane color.

[0162] 2) CS / LPS group: During the fumigation, the mice became agitated at first and then became quiet. In the later stage of fumigation, the mice tended to gather in piles, breathing rapidly, and wheezing could be heard. Some mice experienced hair loss, ate less, and lost a significant amount of weight. Their skin and mucous membranes were redder than those of normal mice.

[0163] 3) Groups treated with extract of the combination: The above changes of mice in the treated group were significantly improved. The weight changes of mice in each group were as follows: Figure 1 shown.

[0164] Example 3: The extract of the composition improves the inflammatory cell infiltration in the lungs of mice with chronic bronchitis induced by CS / LPS

[0165] In order to evaluate the effect of the extract of the combined composition on the lungs and cellular inflammatory cell infiltration in mice with chronic bronchitis, the lung tissues of each group of mice were stained with H&E and scored for histopathology. Microscopic observation results showed that the cilia of the airway mucosa of the mice in the CS / LPS group were significantly reduced, the cilia were collapsed and adhered, the airway wall was significantly thickened, the inflammatory cells around the airway increased, the alveolar wall was thickened, and the alveolar cavity was shrunken. The pathological results were consistent with chronic bronchitis, and the above pathological changes in the lung tissues of the mice in each group that were given the extract of the combined composition were improved. The results are as follows: Figure 2 Shown are hematoxylin and eosin (H&E) staining of lung tissues (scale bars 100 μm / 200 μm).

[0166] The results of histopathological scoring of each group are as follows Figure 3 As shown, the degree of inflammation of mouse lung tissue was scored by analyzing the inflammatory cell infiltration of mouse lung tissue, alveolar wall thickening, alveolar cavity collapse, bronchial epithelial thickening and degeneration, and surrounding fibrosis (n=4). Histopathological scoring: 1) Inflammatory cell infiltration: none-0 points, mild-1 point, moderate-2 points, severe-3 points. 2) Alveolar wall thickening and alveolar cavity collapse: none-0 points, mild-1 point, moderate-2 points, severe-3 points, 3) Bronchial epithelial thickening and degeneration, surrounding fibrosis: none-0 points, mild-1 point, moderate-2 points, severe-3 points.

[0167] One-way analysis of variance was used. Compared with the model group, *P < 0.05, **P < 0.01, ***P < 0.0005, ****P < 0.0001. Compared with the model group, #P < 0.0001 for the control group. It was shown that the composition extract could improve the infiltration of inflammatory cells in the lungs of mice with chronic bronchitis induced by CS / LPS.

[0168] Compared with the control group, the lung tissues of the CS / LPS group had obvious inflammatory manifestations, including thickening of the bronchial wall, infiltration of inflammatory cells, etc. However, under the treatment of the composition extract, the above conditions were significantly improved, and the composition extract significantly inhibited the lung structure damage caused by CS / LPS. Among them, the high-dose composition extract treatment group had a more significant curative effect. The curative effect could be clearly seen with Maxing Zhike Tablets and roflumilast, further confirming the clinical anti-inflammatory treatment effect of this medicine.

[0169] Example 4 Composition extract improves collagen fiber deposition around the airway wall of mice with chronic bronchitis induced by CS / LPS

[0170] The persistent airway inflammation in chronic bronchitis leads to the deposition of collagen fibers around the airway, thereby reducing the elasticity of lung tissue and further exacerbating the inflammation. To determine the effect of the composition extract on treating CS / LPS-induced lung tissue fibrosis, lung tissue sections were stained with Masson's trichrome. As Figure 4 shown, only a small amount of collagen deposition was detected in the lung tissues of the control group mice. Representative histopathological sections of collagen deposition (blue) in the lungs (scale bar 100 μm / 200 μm). Compared with the control group, a large amount of collagen was observed around the bronchi and blood vessels in the CS / LPS group mice, confirming the fibrosis of the lung tissue induced by CS / LPS. After treatment with the composition extract, compared with the CS / LPS group, the collagen deposition around the airway wall in the administration group was significantly reduced, and it was more significant at high doses. In addition, after treatment with Maxing Zhike Tablets and roflumilast, a significant reduction in collagen deposition around the blood vessels and bronchi was observed. The composition extract was superior to Maxing Zhike Tablets and roflumilast in improving lung collagen deposition in mice with chronic bronchitis.

[0171] The results of the histopathological scores of each group are as Figure 5 shown. The lung tissues were stained with Masson, and the quantitative analysis of collagen deposition (n = 3 mice in each group). To test for group differences, one-way analysis of variance was used. Compared with the model group, P < 0.05, **P < 0.01, ***P < 0.0005, ****P < 0.0001. Compared with the model group, #P < 0.0001 for the control group. It was shown that the composition extract inhibited the collagen fiber deposition around the airway wall of mice with chronic bronchitis induced by CS / LPS /

[0172] Example 5: The extract of the composition improves the serum oxidative stress level in CS / LPS-induced chronic bronchitis mice. SOD is an important antioxidant enzyme that scavenges superoxide anion radicals in vivo and can protect cells from oxygen free radical damage. MDA is a metabolite of lipid peroxidation caused by oxygen free radical damage to tissues or cells. The level of MDA in serum and tissues reflects the severity of the body's exposure to free radicals and is a sensitive indicator for measuring the body's free radical metabolism. The experimental results showed that compared with the control group, the SOD level in CS / LPS group mice was significantly decreased (P < 0.0001). After administration of the extract of the composition, the SOD level in each group of mice increased correspondingly, and the high-dose group had a more significant curative effect. The SOD level in the Maxing Zhike Tablets and roflumilast groups also increased correspondingly, and the high-dose curative effect of the extract of the composition was better than that of Maxing Zhike Tablets and roflumilast groups (see Figure 6 ). Compared with the control group, the MDA level in CS / LPS group mice increased (P < 0.01). After treatment with the extract of the composition, the MDA level decreased, and the high-dose had a significant curative effect. The experimental results were consistent with those of SOD (see Figure 7 ). Among them, to test the group differences, one-way analysis of variance was used. Compared with the model group, P < 0.05, **P < 0.01, ***P < 0.0005, ****P < 0.0001, and compared with the model group, #P < 0.0001 for the control group, indicating that the extract of the composition improves the serum oxidative stress level in CS / LPS-induced chronic bronchitis mice.

[0173] Example 6: The extract of the composition improves the recruitment of inflammatory factors in the airways of CS / LPS-induced chronic bronchitis mice

[0174] CS has been shown to induce the production of inflammatory mediators such as ROS, cytokines (TNF-α and IL-6), etc., leading to lung inflammation. LPS can accelerate the in vivo inflammatory response. Therefore, we investigated whether administration of the extract of the composition could improve CS / LPS-induced chronic bronchitis in mice. The results showed that compared with the control group mice, the levels of TNF-α and IL-6 in the bronchoalveolar lavage fluid (BALF) of CS / LPS-treated mice increased significantly. The extract of the composition, Maxing Zhike Tablets, and ROF treatment significantly inhibited the secretion of inflammatory factors in CS / LPS-exposed mice.

[0175] Figure 8 Indicates the level of IL-6 in the bronchoalveolar lavage fluid. Figure 9The analysis results of TNF-α in bronchoalveolar lavage fluid were shown by one-way ANOVA. Compared with the model group, P < 0.05, **P < 0.01, ***P < 0.0005, ****P < 0.0001 in the administration group, and P < 0.0001 in the control group compared with the model group. It was indicated that the extract of the composition improved the recruitment of inflammatory factors in bronchoalveolar lavage fluid of mice with CS / LPS-induced chronic bronchitis.

[0176] These results indicated that the extract of the composition had anti-inflammatory activity in a mouse model of CS / LPS-induced chronic bronchitis.

Claims

1. Use of a traditional Chinese medicine composition in the preparation of a medicament for treating and / or preventing chronic bronchitis or its complications or sequelae, wherein the traditional Chinese medicine composition is prepared from raw materials in the following parts by weight:

2. The use according to claim 1, wherein the traditional Chinese medicine composition is prepared from raw materials in the following parts by weight:

3. The use according to claim 1, wherein the traditional Chinese medicine composition consists of water extracts of raw materials in the following parts by weight:

4. The use according to claim 1, wherein the traditional Chinese medicine composition consists of water extracts of Chinese medicinal materials in the following parts by weight:

5. The use according to claim 1, wherein the traditional Chinese medicine composition is prepared by the following method: Take the raw materials in the above parts by weight, crush them into coarse powder, decoct with water 1, 2 or 3 times, each time for 1 hour, filter, combine the filtrates, concentrate into a thick paste, and dry the thick paste to obtain the product.

6. The use according to claim 1, wherein the traditional Chinese medicine composition is prepared by the following method: Take the raw materials in the above parts by weight, crush them into coarse powder, decoct with water 1, 2 or 3 times, each time for 1 hour, filter, combine the filtrates, concentrate into a thick paste, and dry the thick paste to obtain the product.

7. The use according to claim 5 or 6, wherein 900 parts by weight of powdered sugar is added to the thick paste, granulated, and dried to obtain the product.

8. The use according to claim 1, wherein the complication is obstructive emphysema.

9. The use according to claim 1, wherein the complication is cor pulmonale.

10. The use according to claim 1, wherein the sequela is chronic obstructive pulmonary disease.

Images