Traditional Chinese medicine composition for treating chronic obstructive pulmonary disease as well as preparation method and application thereof

Abstract

The invention belongs to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating chronic obstructive pulmonary disease and a preparation method and application thereof. Specifically, the traditional Chinese medicine composition for treating the chronic obstructive pulmonary disease is prepared from the following raw materials in parts by weight: 20-40 parts of calyx seu fructus physalis, 20-40 parts of thesium chinense, 10-25 parts of flos farfarae, 10-20 parts of white mulberry root-bark, 30-50 parts of ginseng and 20-40 parts of ligusticum wallichii. The traditional Chinese medicine composition is prepared according to the traditional Chinese medicine thinking, can clear away lung heat without hurting vital energy, reduce phlegm and stasis, dredge lung collaterals, tonify qi and activate blood to treat both symptoms and root causes, and has the effects of resisting inflammation, relieving asthma and improving lung functions, so that the traditional Chinese medicine composition is used for treating the chronic obstructive pulmonary disease. Tests prove that the compound has anti-inflammatory and anti-oxidation effects on the cellular level, and can inhibit the process of the mouse chronic obstructive pulmonary disease induced by cigarette smoke on the animal level, so that the compound has good practical application value.

Description

Technical Field

[0001] The present invention belongs to the technical field of traditional Chinese medicine, and in particular relates to a traditional Chinese medicine composition for treating chronic obstructive pulmonary disease and a preparation method and application thereof. Background Art

[0002] The information disclosed in this background technology section is only intended to enhance the understanding of the overall background of the invention, and should not necessarily be regarded as an admission or any form of suggestion that the information constitutes the prior art already known to a person skilled in the art.

[0003] Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways characterized by persistent airflow limitation. The pathogenesis of COPD is complex, and the currently recognized mechanisms include inflammatory response, oxidative stress, immune disorders, and microbial infection. Western medicine uses glucocorticoids, antibiotics, long-acting β2 receptor agonists, and M receptor blockers as recommended drugs in clinical guidelines, but they can only relieve the symptoms of airflow limitation and cannot inhibit the progression of the disease. In addition, a large number of patients have side effects such as hormone resistance and immunosuppression, and new clinically effective therapeutic drugs need to be developed.

[0004] COPD belongs to the category of "asthma" and "lung distension" in traditional Chinese medicine. It is caused by deficiency of qi and blood in the lung, spleen and kidney, phlegm and blood stasis, and invasion of exogenous pathogens. Phlegm, heat and blood stasis are the main pathological products of this disease. When phlegm and turbidity are generated internally, they become hot, and phlegm and heat damage the collaterals, which hinders blood circulation and causes blood stasis. Traditional Chinese medicine adopts the treatment principle of "clearing heat and removing phlegm, invigorating qi and activating blood circulation", and has a significant effect in treating COPD. Traditional Chinese medicine and its compound (Suzi Jiangqi Pills, Tingbei Capsules, Beimu Gualou Powder, etc.) with this feature are recommended in the guidelines for the treatment of COPD with traditional Chinese medicine. They have unique advantages in controlling the progression and acute exacerbation of COPD by regulating inflammation, oxidative stress and immune response.

[0005] The pathogenesis of COPD is complex, and the pathological mechanisms are multiple and not fully elucidated. Chinese herbal compound treatment has a multi-component, multi-target, and holistic approach, and the treatment principle is perfect and effective. Guided by the treatment principle and modern COPD pharmacological model, developing effective Chinese herbal compound for the treatment of COPD is an effective strategy to achieve its treatment. Summary of the invention

[0006] In view of the problems existing in the above-mentioned prior art, the present invention provides a Chinese medicine composition for treating chronic obstructive pulmonary disease, and a preparation method and application thereof. Specifically. The present invention formulates a prescription based on traditional Chinese medicine thinking, clears lung heat without damaging the body, resolves phlegm and blood stasis and dredges the lung meridian, replenishes qi and activates blood circulation to treat both the symptoms and the root causes, and plays the effects of anti-inflammatory and antiasthmatic, and improving lung function, so as to be used for the treatment of chronic obstructive pulmonary disease. Based on the above research results, the present invention is completed.

[0007] In order to achieve the above-mentioned invention object, the present invention discloses the following technical solutions:

[0008] The first aspect of the present invention provides a Chinese medicine composition for treating chronic obstructive pulmonary disease, which is composed of the following raw materials in parts by weight:

[0009] 20-40 parts of Lantern Festival, 20-40 parts of Herba Lycopodii, 10-25 parts of Coltsfoot Flos, 10-20 parts of Cortex Mori, 30-50 parts of Ginseng, and 20-40 parts of Rhizoma Chuanxiong.

[0010] The second aspect of the present invention provides a method for preparing the above-mentioned Chinese medicine composition, which includes but is not limited to water decoction, water extraction and alcohol precipitation, enzymatic hydrolysis, acid-base extraction and ultrasonic extraction;

[0011] The third aspect of the present invention provides use of the above-mentioned Chinese medicine composition in the preparation of a pharmaceutical preparation for preventing and treating chronic obstructive pulmonary disease.

[0012] A fourth aspect of the present invention provides a pharmaceutical preparation for preventing and treating chronic obstructive pulmonary disease, wherein the pharmaceutical preparation at least comprises the above-mentioned traditional Chinese medicine composition.

[0013] Compared with the prior art, the above one or more technical solutions have achieved the following beneficial effects:

[0014] 1. The Chinese medicine composition provided by the above technical solution has the ability to enhance the activity of quinone reductase in cells and inhibit the production of nitric oxide (NO) in macrophages, indicating that the Chinese medicine composition provided by the present invention has the effect of inhibiting oxidative damage and inflammatory response.

[0015] 2. The Chinese medicine composition provided by the above technical solution can reduce the weight loss and lung damage of mice with chronic obstructive pulmonary disease induced by cigarette smoke, and reduce the inflammatory factors IL-1β, TNF-α and MUC5AC in the bronchoalveolar lavage fluid induced by cigarette smoke. The Chinese medicine composition can reduce the levels of lymphocytes and neutrophils in the blood of mice with chronic obstructive pulmonary disease. Therefore, the Chinese medicine composition provided by the present invention has the function of treating chronic obstructive pulmonary disease, and its activity is better than that of Yupingfeng granules and Tongxuan Lifei pills at the same dose.

[0016] 3. The traditional Chinese medicine compound provided by the above technical solution is simple and efficient, the raw materials are economical and affordable, and the preparation and extraction methods are simple, low-cost, universal, and easy to mass produce, so it has good practical application value. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] The accompanying drawings in the specification, which constitute a part of the present invention, are used to provide a further understanding of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0018] Figure 1 This is a graph showing the effect of the Chinese medicine composition granules prepared in Example 4 of Example 6 of the present invention on the body weight of mice with COPD induced by cigarette smoke.

[0019] Figure 2 This is a graph showing the effect of the Chinese medicine composition granules prepared in Example 4 of Example 6 of the present invention on the lung tissue structure of mice with chronic obstructive pulmonary disease induced by cigarette smoke.

[0020] Figure 3 This is a graph showing the effect of the Chinese medicine composition granules prepared in Example 4 of Example 6 of the present invention on IL-1β, TNF-α and MUC5AC in the bronchoalveolar lavage fluid of mice with chronic obstructive pulmonary disease induced by cigarette smoke. Figure 4 This is a graph showing the effect of the Chinese medicine composition granules prepared in Example 4 of Example 6 of the present invention on lymphocytes and neutrophils in the peripheral blood of mice with chronic obstructive pulmonary disease induced by cigarette smoke. DETAILED DESCRIPTION

[0021] It should be noted that the following detailed descriptions are illustrative and are intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present application belongs.

[0022] It should be noted that the terms used herein are only for describing specific embodiments and are not intended to limit the exemplary embodiments according to the present application. As used herein, unless the context clearly indicates otherwise, the singular form is also intended to include the plural form. In addition, it should be understood that when the terms "comprise" and / or "include" are used in this specification, it indicates the presence of features, steps, operations, devices, components and / or combinations thereof.

[0023] The present invention is further described in conjunction with specific examples. The following examples are only for explaining the present invention and are not intended to limit the content thereof. If the specific experimental conditions are not specified in the examples, they are usually carried out according to conventional conditions or the conditions recommended by the sales company; if not particularly limited in the present invention, they can all be purchased through commercial channels.

[0024] In a typical embodiment of the present invention, a Chinese medicine composition for treating chronic obstructive pulmonary disease is provided, which is composed of the following raw materials in parts by weight:

[0025] 20-40 parts of Lantern Festival, 20-40 parts of Herba Lycopodii, 10-25 parts of Coltsfoot Flos, 10-20 parts of Cortex Mori, 30-50 parts of Ginseng, and 20-40 parts of Rhizoma Chuanxiong.

[0026] The raw materials of the traditional Chinese medicine composition provided by the invention include 20-40 parts of Lantern Festival, wherein the number of raspberries can be 20 parts, 25 parts, 30 parts, 35 parts, 40 parts, or any value between 20 and 40 parts.

[0027] The raw materials of the Chinese medicine composition provided by the present invention include 20-40 parts of herba spatholobi, wherein the parts of cinnamon bark can be 20 parts, 24 parts, 28 parts, 32 parts, 36 parts, 38 parts, 40 parts, or any value between 20 and 40 parts.

[0028] The raw materials of the Chinese medicine composition provided by the present invention include 10-25 parts of coltsfoot flowers, wherein the parts of hawthorn can be 10 parts, 15 parts, 14 parts, 18 parts, 22 parts, 25 parts, or any value between 10-25 parts.

[0029] The raw materials of the Chinese medicine composition provided by the present invention include 10-20 parts of Morus alba bark, wherein the amount of Morus alba bark can be 10 parts, 15 parts, 17 parts, 19 parts, 20 parts, or any value between 10-20 parts.

[0030] The raw materials of the Chinese medicine composition provided by the present invention include 30-50 parts of ginseng, wherein the number of ginseng parts can be 30 parts, 38 parts, 41 parts, 44 parts, 47 parts, 50 parts, or any value between 35-50 parts.

[0031] The raw materials of the Chinese medicine composition provided by the present invention include 20-40 parts of Chuanxiong, wherein the amount of Chuanxiong can be 20 parts, 22 parts, 24 parts, 28 parts, 32 parts, 37 parts, 40 parts, or any value between 20-40 parts.

[0032] In some embodiments, 20-40 parts of Lantern Festival, 20-40 parts of Herba Lycopodii, 10-25 parts of Coltsfoot Flos, 10-20 parts of Morus alba bark, 30-50 parts of Ginseng, and 20-40 parts of Ligusticum chuanxiong.

[0033] In some embodiments, 24-36 parts of Lantern Festival, 25-35 parts of Herba Lycopodii, 12-22 parts of Coltsfoot Flos, 12-19 parts of Morus alba bark, 34-46 parts of Ginseng, and 24-36 parts of Ligusticum chuanxiong.

[0034] In some embodiments, 28-34 parts of Lantern Festival, 29-33 parts of Herba Lycopodii, 14-20 parts of Coltsfoot Flos, 14-18 parts of Morus alba bark, 38-42 parts of Ginseng, and 28-33 parts of Ligusticum chuanxiong.

[0035] In some embodiments, 30 parts of Lantern Festival, 32 parts of Herba Lycopodii, 17 parts of Coltsfoot Flos, 16 parts of Morus alba bark, 41 parts of Ginseng, and 32 parts of Ligusticum chuanxiong.

[0036] The efficacy of each raw material of the Chinese medicine composition of the present invention is as follows:

[0037] Jin Lantern, clears away heat and detoxifies, relieves sore throat and resolves phlegm, promotes diuresis and relieves stranguria; used for sore throat, cough due to lung heat, dysuria, pemphigus; has antibacterial, anti-inflammatory, antiviral and immunomodulatory pharmacological activities. Dried persistent calyx or persistent calyx with fruit belonging to the Solanaceae plant Physalis salkekengi L.

[0038] Thesium chinense Turcz., clears away heat and detoxifies, relieves cough and resolves phlegm, dredges meridians and relieves pain; used for pneumonia cough, sore throat, breast carbuncle, rheumatic pain; has antibacterial, anti-tumor, antioxidant and immune regulation pharmacological activities. The dried whole herb of Thesium chinense Turcz., a plant of the Santalaceae family.

[0039] Tussilago farfara L., moisturizing the lungs and lowering qi, relieves cough and resolves phlegm; used for new and long-term cough, wheezing and coughing with phlegm, and coughing with blood due to fatigue; has antitussive, expectorant, asthma-relieving and anti-inflammatory pharmacological activities. It is the dried flower bud of Tussilago farfara L., a plant of the Asteraceae family.

[0040] Morus alba bark, purging lungs and relieving asthma, promoting diuresis and reducing swelling; used for lung heat, asthma, edema, dysuria, epistaxis and beriberi; has pharmacological activities such as lowering blood sugar, lowering blood pressure, anti-inflammatory and diuretic. The dried root bark of Morus alba L., a plant of the Moraceae family.

[0041] Ginseng, a great supplement of vital energy, restores pulse and consolidates weakness, nourishes the spleen and lungs, promotes the production of body fluids and calms the mind; it is used for weakness and fainting, cold limbs and weak pulse, asthma and cough due to lung deficiency, thirst due to loss of body fluids; it has pharmacological activities such as enhancing immunity, resisting fatigue, anti-oxidation and regulating the central nervous system. The dried root and rhizome of Panax ginseng CAMey., a plant of the Araliaceae family.

[0042] Chuanxiong promotes blood circulation and qi, dispels wind and relieves pain; used for chest pain, heart pain, menstrual disorders, amenorrhea, dysmenorrhea, headache, rheumatism and pain; has pharmacological activities such as improving microcirculation, anti-platelet aggregation, anti-myocardial ischemia and neuroprotection. It is the dried rhizome of the plant Ligusticum chuanxiong Hort., which belongs to the Apiaceae family.

[0043] In the present invention,

[0044] The Chinese lantern clears away heat, detoxifies and relieves sore throat, and is anti-bacterial and anti-inflammatory. The herb Herba Lycoris Radiatae clears the lungs, relieves cough and unclogs the meridians. Together, they can relieve heat in the airways and inhibit inflammatory responses. Both are monarch drugs, specializing in the pathogenesis of heat and toxicity blocking the lungs.

[0045] Coltsfoot flowers moisten the lungs, resolve phlegm and relieve cough, while mulberry bark clears the lungs, relieves asthma and promotes diuresis. The two complement each other and serve as assistant medicines to help the main medicine to descend lung qi and eliminate phlegm.

[0046] Ginseng greatly replenishes vital energy and strengthens the body's disease resistance; Chuanxiong promotes blood circulation, promotes qi and unclogs meridians, and improves pulmonary microcirculation disorders. The two complement each other and serve as adjuvant drugs, which can both strengthen the body and eliminate evil, and promote the circulation of qi and blood.

[0047] The six medicines are used together to clear away lung heat without damaging the body, resolve phlegm and blood stasis and dredge the lung meridians, replenish qi and activate blood circulation to treat both the symptoms and the root causes, thereby achieving the effect of anti-inflammatory and antiasthmatic effects and improving lung function.

[0048] In another specific embodiment of the present invention, a method for preparing the above-mentioned Chinese medicine composition is provided, the method including but not limited to water decoction, water extraction and alcohol precipitation, enzymatic hydrolysis, acid-base extraction and ultrasonic extraction;

[0049] Specifically, the preparation method comprises:

[0050] (1) weighing Lantern Festival, Herba Lycopodii, Herba Coltsfoot, Cortex Mori, Ginseng, and Rhizoma Chuanxiong according to a proportion, and soaking them in a solvent;

[0051] (2) heating and refluxing the material soaked in step (1) for at least two times;

[0052] (3) The extracts extracted in step (2) are combined and concentrated to obtain the product.

[0053] In some embodiments, the solvent in step (1) is water, ethanol or a mixture of the two. Water can be mixed with ethanol in any proportion. Studies have shown that when the solvent is an aqueous solution with a volume fraction of ethanol of 0-70%, the prepared Chinese medicine composition has a better activity in inhibiting inflammatory response and oxidative damage.

[0054] In some embodiments, the volume of the solvent in step (1) is 4-16 times the mass of the raw material.

[0055] In some embodiments, the temperature of the heated reflux extraction is 60-100°C.

[0056] In some embodiments, the concentration method is a reduced pressure concentration method.

[0057] In some embodiments, the Chinese medicine composition obtained after concentration is in a paste-like state with a relative density of 1.08-1.25.

[0058] In another specific embodiment of the present invention, there is provided use of the above-mentioned Chinese medicine composition in the preparation of a pharmaceutical preparation for preventing and treating chronic obstructive pulmonary disease.

[0059] In another specific embodiment of the present invention, a pharmaceutical preparation for preventing and treating chronic obstructive pulmonary disease is provided, wherein the pharmaceutical preparation at least comprises the above-mentioned Chinese medicine composition; further, the pharmaceutical preparation may also comprise pharmaceutically acceptable excipients.

[0060] The pharmaceutical preparation can be prepared into various pharmaceutical dosage forms, preferably oral liquid, decoction, pill, capsule, tablet, powder or granule, etc., which are suitable for practical application.

[0061] In another specific embodiment of the present invention, the pharmaceutically acceptable excipients in the pharmaceutical preparation include, but are not limited to, one or more of diluents, fillers, disintegrants, lubricants, binders, flow agents, complex forming agents, plasticizers, colorants, sweeteners, viscosity enhancers, preservatives or antioxidants; further preferably, they are pharmaceutically acceptable excipients.

[0062] In another specific embodiment of the present invention, the diluent includes but is not limited to sorbitol, mannitol, starch, lactose, powdered or microcrystalline cellulose, dicalcium phosphate, tricalcium phosphate, etc.;

[0063] The fillers include but are not limited to sodium carboxymethyl cellulose, hydroxypropyl cellulose, methyl cellulose, ethyl cellulose, hydroxypropyl methyl cellulose, gelatinized starch, etc.;

[0064] The disintegrant includes but is not limited to dry starch, cross-linked polyvinylpyrrolidone, cross-linked sodium carboxymethyl cellulose, sodium carboxymethyl starch, low-substituted hydroxypropyl cellulose, etc.;

[0065] The lubricant includes but is not limited to magnesium stearate, sodium lauryl sulfate or micro powder silica gel.

[0066] In another specific embodiment of the present invention, a method for preventing and treating chronic obstructive pulmonary disease is provided, the method comprising administering the above-mentioned Chinese medicine composition or the above-mentioned pharmaceutical preparation to a subject.

[0067] The subject refers to an animal that has been the object of treatment, observation or experiment, preferably a human or non-human mammal, such as mouse, rat, monkey, gorilla, dog, etc.

[0068] The "therapeutically effective amount" refers to the amount of active compound or pharmaceutical agent, including the compounds of the present invention, which can elicit the biological or medical response of the tissue system or animal sought by the researcher, veterinarian, doctor or other medical personnel, including the alleviation or partial alleviation of the symptoms of the disease, syndrome, condition or disorder being treated.

[0069] It must be recognized that the optimal dosage and interval of the active ingredients of the present invention are determined by their nature and external conditions such as the form, route and site of administration and the specific mammal to be treated, and this optimal dosage can be determined by conventional techniques.

[0070] In order to enable those skilled in the art to more clearly understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below in conjunction with specific embodiments.

[0071] Embodiment 1:

[0072] The raw material composition is as follows by weight: 30 parts of Chinese lantern, 32 parts of gentiana macrophylla, 17 parts of coltsfoot flower, 16 parts of white mulberry bark, 41 parts of ginseng and 32 parts of chuanxiong.

[0073] Crush the Chinese lantern, lily of the valley, coltsfoot, white mulberry bark and chuanxiong with a grinder, and cut the ginseng into slices. Add distilled water 12 times the mass of the raw materials, soak at room temperature for 2 hours, heat and reflux at 100℃ for 2 hours, and filter to obtain a filtrate; add the same volume of distilled water to the residue, extract for 2 hours, and filter to obtain a filtrate; combine the two filtrates, and reduce the pressure to concentrate to a paste with a relative density of 1.20.

[0074] Embodiment 2:

[0075] The raw material composition is as follows by weight: 30 parts of Chinese lantern, 32 parts of gentiana macrophylla, 17 parts of coltsfoot flower, 16 parts of white mulberry bark, 41 parts of ginseng and 32 parts of chuanxiong.

[0076] Crush the Chinese lantern, lily of the valley, coltsfoot, white mulberry bark and chuanxiong with a grinder, and cut the ginseng into slices. Add 70% (volume fraction) ethanol 15 times the mass of the raw materials, soak at room temperature for 2 hours, heat and reflux at 100°C for 2 hours, and filter to obtain a filtrate; add the same volume of 70% ethanol to the residue, extract for 2 hours, and filter to obtain a filtrate; combine the filtrates, and concentrate under reduced pressure to a paste with a relative density of 1.20.

[0077] Embodiment 3:

[0078] The raw material composition is as follows by weight: 30 parts of Chinese lantern, 32 parts of gentiana macrophylla, 17 parts of coltsfoot flower, 16 parts of white mulberry bark, 41 parts of ginseng and 32 parts of chuanxiong.

[0079] Crush the Chinese lantern, lily of the valley, coltsfoot, white mulberry bark and chuanxiong with a grinder, and cut the ginseng into slices. Add 50% (volume fraction) ethanol, which is 12 times the mass of the raw materials, soak at room temperature for 1.5 hours, heat and reflux at 100°C for 2 hours, and filter to obtain a filtrate; add the same volume of 50% ethanol to the residue, extract for 2 hours, and filter to obtain a filtrate; combine the filtrates, and concentrate under reduced pressure to a paste with a relative density of 1.20.

[0080] Example 4: Preparation of Chinese medicine composition granules

[0081] The extract of the Chinese medicine composition prepared in Example 1 was selected for the preparation of granules. 200 g of the extract of the Chinese medicine composition obtained in Example 1 was taken, heated at 55°C to a viscous flowable state, 200 g of dextrin and extract were added in batches and stirred evenly, pressed into thin sheets, vacuum dried at 70°C for 5 hours, taken out and crushed into powder, passed through a 60-mesh sieve, added with anhydrous ethanol and mixed to prepare a soft material, granulated with a 20-mesh sieve in the soft material, and granulated again after drying through a 20-mesh sieve, and after granulation, passed through an 80-mesh sieve again to remove fine powder, and the granules of the Chinese medicine composition were obtained.

[0082] Example 5: Anti-inflammatory and antioxidant activities of Chinese medicine composition at the cellular level

[0083] Method: The Chinese medicine composition prepared in Examples 1-3 was tested for quinone reductase induction activity. The experiment was divided into a blank group, a positive control group (sulforaphane), a group treated with Example 1 (100 μg / mL), a group treated with Example 2 (100 μg / mL), and a group treated with Example 3 (100 μg / mL), with 3 replicates in each group. Human liver cancer Hepa 1c1c7 cells were inoculated in a 96-well plate, cultured overnight, the original culture medium was discarded, and a complete culture medium containing the corresponding drug concentration was added for induction for 24 hours. The original culture medium was discarded, 30 μL of cell lysis solution was added, and the cells were lysed at 37°C for 15 minutes, and then 170 μL of reaction solution was added to react for 3 minutes and the absorbance at 610 nm was detected to calculate the reductase induction activity. The complete reaction solution was prepared as shown in the table.

[0084] Table 1 Quinone reductase induction activity complete reaction solution formula

[0085]

[0086] The quinone reductase induction activity of each drug-added group was calculated according to the induction rate = (absorbance of drug-added group - absorbance of blank group) / absorbance of blank group * 100%.

[0087] The Chinese medicine compositions prepared in Examples 1-3 were tested for NO generation inhibition activity. The experiment was divided into a blank group, a positive control group (Didox), an Example 1 drug-added group (100 μg / mL), an Example 2 drug-added group (100 μg / mL), and an Example 3 drug-added group (100 μg / mL). Mouse macrophage RAW 264.7 cells were inoculated in a 96-well plate and cultured overnight. The original culture medium was discarded, and a complete culture medium containing the corresponding concentration of drugs and 1 μg / mL of lipopolysaccharide was added. Three replicates were set for each group and induced for 24 hours. 100 μL of supernatant was drawn from each well, and 100 μL of Griess reagent was added to react for 3 minutes before detecting the absorbance at 570 nm to calculate the NO generation inhibition activity. The NO generation inhibition activity of each drug-added group was calculated according to (model group absorbance-drug-added group absorbance) / (model group absorbance-blank group absorbance)*100%.

[0088] The results are shown in Table 2. The Chinese medicine compositions of Examples 1-3 all have quinone reductase induction activity and nitric oxide production inhibition activity, indicating that the Chinese medicine compositions of Examples 1-3 all have oxidative stress and inflammatory response inhibition activity at the cellular level, and the Chinese medicine compositions of Examples 1 and 2 show stronger activity. Among them, the water preparation method used in Example 1 is lower in cost and safer, so the method of Example 1 is selected to prepare the ingredients.

[0089] Table 2 Comparison of the activity of the Chinese medicine composition of Examples 1-3

[0090] Quinone reductase inducing activity NO production inhibitory activity Example 1 83.20％ 33.27％ Example 2 91.86％ 33.64％ Example 3 71.94％ 15.42％

[0091] Example 6: Therapeutic effect of Chinese medicine composition granules on chronic obstructive pulmonary disease induced by cigarette smoke in mice

[0092] Method: The in vivo activity of the Chinese medicine composition granules provided in Example 4 was verified. (3-8 weeks, 180-200 g, purchased from Beijing Weitong Lihua Company). Rats were raised in a growth environment with a 12-h day and night cycle, ensuring free drinking water and regular food. All in vivo experiments were in accordance with the regulations of the Ethics Committee of the School of Pharmacy of Shandong University. Adaptive feeding for one week.

[0093] The experimental animals were divided into three dosage groups: blank control group, model control group, Chinese medicine combination granules, Yupingfeng granules positive control group, and Tongxuan Lifei pills positive control group, with 8 animals in each group. The groups and dosages were determined as follows: (1) blank control group; (2) model control group; (3) Chinese medicine combination granules low-dose group: Model + 0.96 g / kg granules; (4) Chinese medicine combination granules medium-dose group: Model + 1.92 g / kg granules; (5) Chinese medicine combination granules high-dose group: Model + 2.88 g / kg granules; (6) Yupingfeng granules positive control group: Model + 2.88 g / kg Yupingfeng granules; (7) Tongxuan Lifei pills positive control group: Model + 2.88 g / kg Tongxuan Lifei pills. The COPD model of mice was established by cigarette exposure. In the first 8 weeks, all mice except the control group were placed in the C-260 semi-automatic cigarette exposure system (Shanghai Yuyan Scientific Instrument Co., Ltd., China) for cigarette smoke exposure modeling. They were exposed to the cigarette smoke of 6 Hongtashan cigarettes within 1 hour, and each support lasted for 10 minutes. The cigarette smoke flow rate was 40L / h and the fresh air flow rate was 5L / min. In the next 8 weeks, the mice were gavaged according to the grouping. After 4 hours of administration, the mice except the blank control group received cigarette smoke exposure and cigarette smoke exposure once a day. Weigh once a week. After this stage, the mice were killed and lung tissue, blood and bronchoalveolar lavage fluid were collected for subsequent experiments.

[0094] Lung tissue pathology analysis: Lung tissues were fixed in 4% paraformaldehyde for 24 hours, then embedded in paraffin, sectioned, dewaxed and placed in water, fixed on slides, and stained with hematoxylin-eosin. An Olympus BX53 inverted fluorescence microscope was used to observe and capture images to analyze the effects of each drug-addition group on the structure of mouse lung tissue induced by cigarette smoke.

[0095] Collection of alveolar lavage fluid and detection of IL-1β, TNF-α and MUC5AC: The mouse larynx was dissected and the trachea was exposed. 1 mL of PBS buffer was injected into the lungs through the trachea with a syringe, and then aspirated after 30 seconds. This was repeated three times and combined into alveolar lavage fluid. The alveolar lavage fluid was centrifuged at 8000 rpm and 4°C for 10 minutes, and the supernatant was taken to measure the levels of IL-1β, TNF-α and MUC5AC in the alveolar lavage fluid using ELISA kits, and processed and analyzed using GraphPad Prism 8.0 software.

[0096] Complete blood cell count: The orbital blood of mice was collected into ethylenediaminetetraacetic acid (EDTA) anticoagulant tubes (Wuhan Sewell Biotechnology Co., Ltd.). A full-automatic blood cell analyzer (Mindray BC-6800) was used for complete blood cell count analysis to obtain the effects of the Chinese medicine composition granules on lymphocytes and neutrophils in the peripheral blood of mice with chronic obstructive pulmonary disease induced by cigarette smoke, and GraphPad Prism 8.0 software was used for processing and analysis.

[0097] The results are as follows Figure 1 As shown in the figure, the weight of mice in the model group was significantly reduced compared with the blank control group, and the three doses of particles could effectively alleviate the weight loss of mice induced by cigarette smoke, and the effect of medium-dose particles was comparable to that of positive drugs Yupingfeng Granules and Tongxuan Lifei Pills. Figure 2 As shown in the results, the lung tissues of mice in the model group showed obvious typical pathological features of chronic obstructive pulmonary disease compared with the blank group, including inflammatory cell infiltration, thickening of the tracheal wall, and enlarged alveolar damage. Chinese herbal granules can reduce the structural changes of mouse lung tissues in a dose-dependent manner. Figure 3 As shown in the results, cigarette smoke exposure can increase the protein levels of inflammatory factors TNF-α and IL-1β and mucus-related protein MUC5AC in the bronchoalveolar lavage fluid of mice. The three doses of Chinese medicine particles can effectively reduce the levels of inflammatory factors and mucus-related proteins in the bronchoalveolar lavage fluid of mice, indicating that Chinese medicine particles can inhibit the inflammatory response and sputum secretion in chronic obstructive pulmonary disease. Figure 4As shown in the figure, compared with the blank group, the levels of lymphocytes and neutrophils in the peripheral blood of the model group mice were significantly increased, and the three doses of Chinese medicine granules were able to effectively reduce the levels of lymphocytes and neutrophils in the peripheral blood. Therefore, the Chinese medicine granules in Example 4 can alleviate the pathological damage and weight loss of chronic obstructive pulmonary disease, inhibit the occurrence of pulmonary and systemic inflammatory reactions and excessive secretion of sputum. And the Chinese medicine granules in medium doses are equivalent to the positive control drugs Yupingfeng Granules and Tongxuan Lifei Pills, indicating that the Chinese medicine granules in Example 4 have a stronger efficacy in treating chronic obstructive pulmonary disease.

[0098] Example 7: Preparation of Chinese medicine composition tablets

[0099] 50 g of the Chinese medicine composition extract (provided in Example 1) was added with 45 g of corn starch and 15 g of dextrin, and the mixture was fully mixed to prepare granules. The granules were dried and granulated, and an appropriate amount of talcum powder was added and tablets were obtained.

[0100] Example 8: Preparation of Chinese medicine composition capsules

[0101] 50 g of the Chinese medicine composition extract (provided in Example 1) is added with 50 g of starch, 20 g of dextrin and 10 g of microcrystalline cellulose, and the mixture is thoroughly mixed to obtain granules. The granules are dried and granulated, and an appropriate amount of magnesium stearate is added to the granules. The granules are then filled into capsules to obtain the product.

[0102] It should be noted that the above examples are only used to illustrate the technical solution of the present invention rather than to limit it. Although the present invention is described in detail with reference to the given examples, a person skilled in the art may modify or replace the technical solution of the present invention as needed without departing from the spirit and scope of the technical solution of the present invention.

Claims

1. A Chinese medicine composition for treating chronic obstructive pulmonary disease, characterized in that: According to weight parts, it is composed of the following raw materials: 20-40 parts of Lantern Festival, 20-40 parts of Herba Lycopodii, 10-25 parts of Coltsfoot Flos, 10-20 parts of Cortex Mori, 30-50 parts of Ginseng, and 20-40 parts of Rhizoma Chuanxiong.

2. The Chinese medicine composition according to claim 1, characterized in that According to weight parts, it is composed of the following raw materials: 20-40 parts of Chinese lanterns, 20-40 parts of celery, 10-25 parts of coltsfoot flowers, 10-20 parts of white mulberry bark, 30-50 parts of ginseng, and 20-40 parts of ligusticum chuanxiong; Or, 24-36 parts of Lantern Festival, 25-35 parts of Herba Lycopodii, 12-22 parts of Coltsfoot Flos, 12-19 parts of Morus alba bark, 34-46 parts of Ginseng, and 24-36 parts of Ligusticum chuanxiong; Or, 28-34 parts of Lantern Festival, 29-33 parts of Herba Lycopodii, 14-20 parts of Coltsfoot Flos, 14-18 parts of Morus alba bark, 38-42 parts of Ginseng, and 28-33 parts of Ligusticum chuanxiong; Or, 30 parts of Radix Lanternae, 32 parts of Herba Lycopodii, 17 parts of Flos Coltsfoots, 16 parts of Cortex Mori, 41 parts of Radix Ginsengs, and 32 parts of Rhizoma Chuanxiongs.

3. The method for preparing the Chinese medicine composition according to claim 1 or 2, characterized in that: The preparation method comprises water decoction method, water extraction and alcohol precipitation method, enzymolysis method, acid-base leaching method and ultrasonic extraction method.

4. The preparation method according to claim 3, characterized in that: The preparation method comprises: (1) weighing Lantern Festival, Herba Lycopodii, Herba Coltsfoot, Cortex Mori, Ginseng, and Rhizoma Chuanxiong according to a proportion, and soaking them in a solvent; (2) heating and refluxing the material soaked in step (1) for at least two times; (3) The extracts extracted in step (2) are combined and concentrated to obtain the product.

5. The preparation method according to claim 4, characterized in that: In step (1), the solvent is water, ethanol or a mixture of the two; The volume of the solvent in step (1) is 4-16 times the mass of the raw material.

6. The preparation method according to claim 4, characterized in that: The temperature of the heating reflux extraction in step (2) is 60-100°C.

7. The preparation method according to claim 4, characterized in that: The concentration method in step (3) is a reduced pressure concentration method.

8. Use of the Chinese medicine composition according to any one of claims 1 to 3 in the preparation of a pharmaceutical preparation for preventing and treating chronic obstructive pulmonary disease.

9. A pharmaceutical preparation for preventing and treating chronic obstructive pulmonary disease, characterized in that: The pharmaceutical preparation at least comprises the Chinese medicine composition according to any one of claims 1 to 3.

10. The pharmaceutical preparation according to claim 9, characterized in that The pharmaceutical preparation further comprises a pharmaceutically acceptable excipient; The pharmaceutical preparation is oral liquid, decoction, pill, capsule, tablet, powder or granule.

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