Application of traditional Chinese medicine composition in preparation of medicine for preventing and treating chronic obstructive pulmonary disease and / or emphysema

Abstract

The invention relates to the technical field of traditional Chinese medicines, in particular to application of a traditional Chinese medicine composition in preparation of medicines for preventing and treating chronic obstructive pulmonary diseases and / or emphysema. The traditional Chinese medicine composition is prepared from 5-30 parts of herba houttuyniae, 5-30 parts of honeysuckle flowers, 5-20 parts of radix paeoniae rubra, 3-15 parts of folium artemisiae argyi and 3-15 parts of herba menthae. The invention finds that the composition can obviously improve FVC, FEV0.3 and PEF of rats, obviously reduce the level of inflammatory factors IL-17, increase the content of serum alpha1-AT of the rats after molding, prevent progressive destruction of alveolar walls, reduce the content of serum HA and PCIII of the rats and delay the disease progress of emphysema on smoked and LPS composite replication COPD models and elastinase-induced emphysema model rats. Therefore, the traditional Chinese medicine composition disclosed by the invention has a good effect of treating the chronic obstructive pulmonary disease.

Description

Technical Field

[0001] The present invention relates to the technical field of traditional Chinese medicines, and in particular to the use of a traditional Chinese medicine composition in preparing medicines for preventing and treating chronic obstructive pulmonary disease and / or emphysema. Background Art

[0002] Chronic obstructive pulmonary disease (COPD) is a common, preventable, and treatable chronic airway inflammatory disease. Its main symptoms include chronic cough, sputum production, and difficulty breathing. These symptoms can gradually worsen and affect patients' daily lives. COPD is often associated with long-term exposure to harmful particles or gases, such as smoking, air pollution, and occupational dust exposure.

[0003] Pulmonary emphysema, also known as obstructive emphysema, is a chronic lung disease characterized by persistent, abnormally high air volume, overinflation, and airway wall damage. This condition is primarily caused by long-term exposure to cigarette smoke and other environmental pollutants, as well as genetic factors, leading to a decrease in airway elasticity distal to the bronchioles. Emphysema is primarily classified as alveolar emphysema and interstitial emphysema, with the former being more common.

[0004] There is a close association between chronic obstructive pulmonary disease (COPD) and emphysema. In most cases, emphysema is caused by COPD. The persistent airflow limitation and airway obstruction caused by COPD can further trigger the pathological changes of emphysema, such as airway wall destruction and excessive expansion of lung tissue. However, not all emphysema is caused by COPD. In some cases, emphysema can exist as an independent disease without the other characteristics of COPD. In addition, in addition to COPD, other diseases such as bronchial asthma and bronchiectasis may also lead to the occurrence of emphysema.

[0005] In the stable stage of COPD and emphysema, drug therapy is the core treatment method. Commonly used drugs include bronchodilators (such as β2 receptor agonists, anticholinergic drugs), anti-inflammatory drugs (such as corticosteroids) and phosphodiesterase inhibitors. These drugs can effectively relieve symptoms, improve respiratory function, and reduce the risk of acute exacerbations. It can be seen that the current drugs for the treatment of COPD and emphysema are mainly hormones and antibiotics, but the side effects of these drugs are always a problem that cannot be ignored. In recent years, with the deepening of medical research, the treatment plan for COPD has also been evolving. The field of traditional Chinese medicine should actively intervene in the prevention and treatment of chronic obstructive pulmonary disease and develop symptomatic prescriptions. Summary of the Invention

[0006] In view of this, the technical problem to be solved by the present invention is to provide a use of a traditional Chinese medicine composition in the preparation of a medicament for preventing and treating chronic obstructive pulmonary disease and / or emphysema.

[0007] The present invention provides the use of a traditional Chinese medicine composition in preparing a medicament for preventing and treating chronic obstructive pulmonary disease and / or preventing and treating emphysema;

[0008] The traditional Chinese medicine composition comprises the following raw materials in parts by weight: 5-30 parts of houttuynia cordata, 5-30 parts of honeysuckle, 5-20 parts of red peony root, 3-15 parts of wormwood leaf, and 3-15 parts of mint.

[0009] In the present invention, the prevention and treatment of chronic obstructive pulmonary disease includes improving lung function and / or inhibiting the level of inflammatory factors.

[0010] Pulmonary function tests play a crucial role in the assessment and management of chronic obstructive pulmonary disease (COPD). FVC (forced vital capacity), FEV0.3 (the expiratory flow at 30 percent of forced expiratory volume in one second), and PEF (peak expiratory flow) are all crucial parameters in pulmonary function testing and are crucial for assessing the severity of COPD patients' condition, formulating treatment plans, and monitoring their progress. Experiments in the present invention have demonstrated that the aforementioned Chinese herbal composition can improve patients' FVC, FEV0.3, and / or PEF.

[0011] In the pathogenesis of chronic obstructive pulmonary disease (COPD), a wide variety of inflammatory factors are involved, including but not limited to interleukins (IL), tumor necrosis factor (TNF), transforming growth factor (TGF), and chemokines. These inflammatory factors interact with each other and jointly influence the occurrence and development of COPD. Experiments in the present invention have shown that the traditional Chinese medicine composition described above can suppress the levels of inflammatory factors, particularly inflammatory factor levels in serum. More specifically, the inflammatory factor described in the present invention is IL-17.

[0012] In the present invention, the chronic obstructive pulmonary disease (COPD) that can be treated by the Chinese medicine composition is COPD caused by harmful gases and lung inflammation. In some embodiments, the harmful gases are cigarette smoke, and the lung inflammation is inflammation caused by LPS.

[0013] In the present invention, the prevention and treatment of emphysema includes preventing the destruction of alveolar walls and / or improving the process of pulmonary fibrosis.

[0014] Alveoli are the basic functional units of the lungs, responsible for gas exchange. Damage to the alveolar walls leads to a series of pathophysiological changes. First, the damaged alveolar walls lose their original elasticity and tension, preventing the alveoli from maintaining their normal shape and structure. This can cause the alveoli to enlarge, deform, and even rupture and fuse, forming large bullous structures. Therefore, alveolar wall destruction is a key step in the pathogenesis of emphysema. Experiments in the present invention have demonstrated that the aforementioned Chinese herbal composition can prevent alveolar destruction.

[0015] α1-AT is the most important broad-spectrum protease inhibitor in human plasma, inhibiting the activity of multiple serine proteases. Its primary function is to protect normal cells and organs from protease damage. When α1-AT is deficient or its activity is reduced, protease activity may increase, potentially leading to damage to the alveolar wall and other tissues. In the present invention, preventing alveolar wall damage involves suppressing α1-AT levels.

[0016] As emphysema progresses, damaged lung tissue may undergo a series of repair and remodeling processes. During this process, fibroblasts may become overactive, leading to abnormal deposition of extracellular matrix and the subsequent formation of pulmonary fibrosis. Hyaluronidase and type III procollagen play an important role in pulmonary fibrosis and can be used as important indicators for assessing the degree of pulmonary fibrosis and monitoring the progression of the disease. Experiments in the present invention have shown that the traditional Chinese medicine composition described above can improve the progression of pulmonary fibrosis, and the improvement includes inhibiting the levels of HA and / or PC III.

[0017] In the present invention, the emphysema is caused by increased protease activity or decreased anti-lytic activity.

[0018] In an embodiment of the present invention, the weight percentages of the components in the traditional Chinese medicine composition are: 5-25 parts of houttuynia cordata, 5-25 parts of honeysuckle, 5-15 parts of red peony root, 3-10 parts of wormwood leaf, and 3-10 parts of mint. Furthermore, the weight percentages of the components in the traditional Chinese medicine composition are: 15-25 parts of houttuynia cordata, 15-25 parts of honeysuckle, 10-15 parts of red peony root, 5-10 parts of wormwood leaf, and 3-5 parts of mint.

[0019] Optionally, the mass parts of each component in the traditional Chinese medicine composition are: 20 parts of houttuynia cordata, 20 parts of honeysuckle, 12 parts of red peony root, 8 parts of artemisia argyi, and 4 parts of mint.

[0020] Optionally, the mass parts of each component in the traditional Chinese medicine composition are: 15 parts of houttuynia cordata, 15 parts of honeysuckle, 12 parts of red peony root, 7 parts of artemisia argyi, and 7 parts of mint.

[0021] Optionally, the mass parts of each component in the traditional Chinese medicine composition are: 10 parts of houttuynia cordata, 10 parts of honeysuckle, 8 parts of red peony root, 4 parts of artemisia argyi, and 4 parts of mint.

[0022] The composition of the present invention can be directly ground into powder or can be an extract prepared by conventional means in the art. The composition can be directly ground into powder by conventional methods or can be an extract prepared by conventional means to prepare different dosage forms, obtain better therapeutic effects and be more conducive to the preparation of modern pharmaceutical dosage forms.

[0023] In an embodiment of the present invention, the preparation method of the Chinese medicine composition comprises:

[0024] Step A: Weigh the Chinese medicinal materials according to the weight ratio of the raw materials;

[0025] Step B: extracting honeysuckle with 6-12 times the amount of 50% to 80% ethanol, filtering the extract, recovering the ethanol, drying and crushing to obtain a dry paste powder;

[0026] Step C: adding 3-12 times of water to Houttuynia cordata, Artemisia argyi, and mint to extract volatile oil, adding coarse red peony root powder to the medicinal residue, adding 6-12 times of water to boil, filtering the extract to obtain a clear paste, adding 90% or more ethanol to an alcohol content of 60% to 80%, precipitating with alcohol, standing, recovering ethanol from the supernatant to obtain a thick paste, drying and pulverizing to obtain a dry paste powder;

[0027] Step D: Mix the volatile oil and the two dry paste powders.

[0028] Furthermore, the preparation method of the Chinese medicine composition comprises the following steps:

[0029] Step A: Add 12 times the amount of 50% ethanol to honeysuckle, reflux extract twice, each time for 0.5 hours, filter, combine the filtrates, recover the ethanol under reduced pressure and concentrate to a thick paste with a relative density of 1.20 to 1.25, dry under reduced pressure, and grind to obtain the alcohol-extracted dry extract powder;

[0030] Step B: Add 8 times the amount of water to Houttuynia cordata, Artemisia argyi, and mint, and extract the volatile oil by steam distillation for 5 hours. Filter the extract and set aside;

[0031] Step C: grinding and inclusion-compounding the obtained volatile oil with 10 times the amount of β-cyclodextrin and 20 times the amount of water for 20 minutes, drying and crushing the inclusion compound to obtain a volatile oil inclusion compound;

[0032] Step D: combining the medicinal residue after volatile oil extraction with red peony root, adding 10 times the amount of water, extracting twice, each time for 1 hour, combining the extract with the oil extraction medicinal solution, filtering, and concentrating the filtrate under reduced pressure to a clear paste with a relative density of 1.02 to 1.05, cooling to room temperature, adding 95% ethanol to make the alcohol content reach 70%, standing for more than 12 hours, recovering ethanol from the supernatant of the alcohol precipitation under reduced pressure and concentrating to a thick paste with a relative density of 1.25 to 1.30, drying under reduced pressure, and pulverizing to obtain a water-extracted dry extract powder; and mixing the alcohol-extracted dry extract powder, the volatile oil inclusion compound, and the water-extracted dry extract powder.

[0033] The present invention also provides a drug for preventing and treating chronic obstructive pulmonary disease and / or preventing and treating emphysema, which includes pharmaceutically acceptable excipients and the following raw materials in parts by weight: 5-30 parts of houttuynia cordata, 5-30 parts of honeysuckle, 5-20 parts of red peony root, 3-15 parts of mugwort, and 3-15 parts of mint.

[0034] The dosage forms of the drug of the present invention include, but are not limited to, decoctions, granules, capsules, tablets, oral liquids, pills, tinctures, syrups, suppositories, gels, sprays and / or injections.

[0035] In some embodiments provided herein, the capsule is a hard capsule or a soft capsule.

[0036] In some embodiments provided herein, the tablet is an oral tablet or buccal tablet.

[0037] Oral tablets are tablets for oral administration. Most of the drugs in these tablets are absorbed through the gastrointestinal tract to exert their effects, while some drugs in other tablets exert their effects locally in the gastrointestinal tract. In some embodiments provided herein, the oral tablets are conventional compressed tablets, dispersible tablets, effervescent tablets, chewable tablets, coated tablets, or sustained-release tablets.

[0038] The pharmaceutically acceptable excipients include one or a mixture of two or more of fruit powder, edible flavors, sweeteners, acidulants, fillers, lubricants, preservatives, suspending agents, edible pigments, diluents, emulsifiers, disintegrants or plasticizers.

[0039] The drugs described in the present invention also include other drugs for preventing and treating chronic obstructive pulmonary disease and / or preventing and treating emphysema, and the other drugs for preventing and treating chronic obstructive pulmonary disease and / or preventing and treating emphysema include: at least one of aminophylline, dexamethasone, prednisone, ambroxol hydrochloride, methylprednisolone, budesonide, fluticasone, salbutamol sulfate or antibiotics.

[0040] In the present invention, the Chinese medicine composition and other therapeutic agents in the medicine may exist independently of each other or may exist in combination, and the present invention does not impose any limitation on this.

[0041] Furthermore, the present invention also provides a method for preventing and treating chronic obstructive pulmonary disease and / or preventing and treating emphysema, which comprises administering the drug of the present invention.

[0042] The drug can be administered by methods including, but not limited to, oral administration, spray inhalation, rectal administration, nasal administration, buccal administration, vaginal administration, and topical administration. Alternatively, parenteral administration can be employed, such as subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal, intraventricular, intrasternal, or intracranial injection or infusion; or administration via an externally implanted reservoir. Preferably, the drug is administered orally and / or by aerosol inhalation.

[0043] In the present invention, when the medicine includes a traditional Chinese medicine composition and other therapeutic agents, two or more medicines can be administered simultaneously or sequentially, and the present invention does not limit this.

[0044] For example, the Chinese medicine composition in the medicine is administered no longer than 6 hours, preferably no longer than 5 hours, more preferably no longer than 4 hours, even more preferably no longer than 3 hours, more preferably no longer than 2 hours and most preferably no longer than 1 hour before the administration of other therapeutic agents and / or no longer than 6 hours, preferably no longer than 5 hours, more preferably no longer than 4 hours, even more preferably no longer than 3 hours, more preferably no longer than 2 hours and most preferably no longer than 1 hour after the administration of other therapeutic agents.

[0045] In the present invention, when the medicine includes a traditional Chinese medicine composition and other therapeutic agents, the administration frequency of two or more medicines may be the same or different, and the present invention does not limit this.

[0046] For example, the administration frequency of two or more drugs in the drug is independently selected from 4 times / day, 3 times / day, 2 times / day or 1 time / day, wherein the administration frequency of the Chinese medicine composition is 4 times / day, 3 times / day, 2 times / day or 1 time / day.

[0047] In the present invention, the medicament includes a traditional Chinese medicine composition, and the dosage administered is not less than the effective dose. If the medicament includes a traditional Chinese medicine composition and other therapeutic agents, the dosage of the traditional Chinese medicine composition is either less than or not less than the effective dose; the dosage of the other therapeutic agents is either less than or not less than the effective dose.

[0048] In the present invention, the effective dose includes a "therapeutically effective amount" or a "prophylactically effective amount", which refers to an amount that is sufficient to treat or prevent a patient's disease but low enough to avoid serious side effects (at a reasonable benefit / risk ratio) within the scope of reasonable medical judgment. The prophylactic or therapeutically effective amount of a drug will vary depending on factors such as the specific drug selected (for example, considering the potency, effectiveness and half-life of the drug), the selected route of administration, the disease to be prevented or treated, the severity of the disease to be prevented or treated, the age, size, weight and physical illness of the patient to be prevented or treated, the medical history of the patient to be prevented or treated, the duration of prevention or treatment, the nature of concurrent therapy, the desired preventive or therapeutic effect, etc., but can still be routinely determined by those skilled in the art.

[0049] In the present invention, the prevention and treatment include prevention and / or treatment, which are preventive and therapeutic measures for chronic obstructive pulmonary disease and / or prevention and treatment of emphysema. This includes methods for preventing the occurrence of chronic obstructive pulmonary disease and / or prevention and treatment of emphysema, the purpose of which is to prevent, slow down (reduce) unwanted physiological changes or lesions in the treatment subject, and beneficial or desired clinical results include but are not limited to avoiding the occurrence of chronic obstructive pulmonary disease and / or prevention and treatment of emphysema, alleviating the symptoms of chronic obstructive pulmonary disease and / or prevention and treatment of emphysema, reducing the degree of chronic obstructive pulmonary disease and / or prevention and treatment of emphysema, stabilizing the state of chronic obstructive pulmonary disease and / or prevention and treatment of emphysema (i.e., not worsening), delaying or slowing the progression of chronic obstructive pulmonary disease and / or prevention and treatment of emphysema, improving or alleviating the state of chronic obstructive pulmonary disease and / or prevention and treatment of emphysema, and alleviating (whether partially or completely), whether detectable or undetectable. Subjects in need of treatment include subjects who already have a condition or disease, as well as subjects who are susceptible to a condition or disease or subjects who intend to prevent a condition or disease.

[0050] In the present invention, the objects of prevention and treatment are humans or mammals, and the mammals include bovines, equines, ovines, porcines, canines, felines, rodents, and primates. The rodents are mice and / or rats.

[0051] The traditional Chinese medicine composition of the present invention comprises 5-30 parts of houttuynia cordata, 5-30 parts of honeysuckle, 5-20 parts of red peony root, 3-15 parts of mugwort, and 3-15 parts of mint. The present invention has discovered the effects of the composition on rats in a COPD model replicated by a combination of smoke and LPS and an elastase-induced emphysema model. Experimental results show that at 14.88, 7.44, and 3.72 g of crude drug / kg, the traditional Chinese medicine composition can significantly improve the rats' forced vital capacity (FVC), forced expiratory volume (FEV0.3), and positive force (PEF), significantly reduce the level of the inflammatory factor IL-17, increase the serum α1-AT content of rats after modeling, prevent progressive destruction of the alveolar wall, reduce the levels of HA and PCIII in rat serum, and delay the progression of emphysema. This demonstrates that the traditional Chinese medicine composition of the present invention has a good therapeutic effect on chronic obstructive pulmonary disease. DETAILED DESCRIPTION

[0052] The present invention provides the use of a Chinese medicine composition in the preparation of a medicament for preventing and treating chronic obstructive pulmonary disease and / or emphysema. Those skilled in the art can refer to the contents of this invention and appropriately improve the process parameters to achieve the desired effect. It should be noted that all similar substitutions and modifications are obvious to those skilled in the art and are considered to be included in the present invention. The methods and applications of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the methods and applications herein without departing from the content, spirit and scope of the present invention to implement and apply the technology of the present invention.

[0053] The test materials used in the present invention are all common commercial products and can be purchased in the market.

[0054] Unless otherwise specified, the following experiments were conducted under conventional conditions or those recommended by the manufacturer. All APIs, excipients, reagents, and instruments used, unless the manufacturer is specified, are commercially available. Unless otherwise specified, all percentages, ratios, proportions, and parts are by weight.

[0055] Unless otherwise defined, all technical and scientific terms used herein have the same meanings as those familiar to those skilled in the art. In addition, any methods and materials similar or equivalent to those described herein can be applied to the present invention. The present invention is further described below with reference to the following examples:

[0056] Example 1 Preparation of Chinese medicine composition granules

[0057] Raw material ratio: Houttuynia cordata: 750g, honeysuckle 750g, red peony root 450g, mugwort 300g, mint 150g.

[0058] Step A: adding 12 times the amount of 50% ethanol to honeysuckle, refluxing and extracting twice, each time for 0.5 hours, filtering, combining the filtrates, and recovering the ethanol under reduced pressure (-0.07MPa to -0.09MPa, 65°C to 75°C) and concentrating to a thick paste with a relative density of 1.20 to 1.25 (65°C), drying under reduced pressure (-0.07MPa to -0.09MPa, 60°C to 65°C), and pulverizing to obtain a dry extract powder of the alcohol extraction part;

[0059] Step B: Add 8 times the amount of water to Houttuynia cordata, Artemisia argyi, and mint, and extract the volatile oil by steam distillation for 5 hours. The extract is filtered and stored in a separate container for later use;

[0060] Step C: The obtained volatile oil is ground and included with 10 times the amount of β-cyclodextrin and 20 times the amount of water for 20 minutes, and the inclusion compound is dried (55° C.) and crushed to obtain a volatile oil inclusion compound;

[0061] Step D: After extracting the volatile oil, the medicinal residue is combined with red peony root, 10 times the amount of water is added, and extraction is performed twice, each time for 1 hour. The extract is combined with the oil extraction medicinal solution, filtered, and the filtrate is concentrated under reduced pressure (-0.07MPa to -0.09MPa, 75°C to 85°C) to a clear paste with a relative density of 1.02 to 1.05 (70°C), cooled to room temperature, and 95% ethanol is added to make the alcohol content reach 70%. The mixture is allowed to stand for more than 12 hours. The supernatant of the alcohol precipitation is reduced pressure (-0.07MPa to -0.09MPa, 65°C to 75°C) to recover the ethanol and concentrate to a thick paste with a relative density of 1.25 to 1.30 (65°C), and an appropriate amount of dextrin is added, dried under reduced pressure (-0.07MPa to -0.09MPa, 75°C), and pulverized to obtain a dry extract powder of the water extraction part.

[0062] The above three intermediates (dry extract powder of alcohol extraction part, volatile oil inclusion compound, dry extract powder of water extraction part) are mixed with appropriate amount of dextrin and stevioside, and dry granulated to prepare 1000g granules.

[0063] Example 2 Effect of Chinese herbal composition on COPD induced by smoke and LPS

[0064] 1. Experimental Materials

[0065] 1.1 Animals

[0066] SD rats, SPF grade, male, weighing 150-170 g were purchased.

[0067] Breeding environment: room temperature 20-26℃, relative humidity controlled at 40-70%, and breeding density of 5 per cage.

[0068] 1.2 Medication

[0069] Chinese medicine composition, three intermediates prepared according to the method of Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.;

[0070] Aminophylline tablets, product of Tianjin Lisheng Pharmaceutical Co., Ltd., batch number: 2103005; specifications: 0.1g / tablet, 100 tablets / bottle.

[0071] 1.3 Reagents

[0072] Lipopolysaccharide toxin (LPS): SIGMA, specification: 100 mg / vial, batch number 039M4004V;

[0073] 0.9% sodium chloride solution, Chenxin Pharmaceutical Co., Ltd., specification: 100 ml / bottle, batch number: 2101282721;

[0074] Chloral hydrate, Shanghai Sinopharm Chemical Reagent Co., Ltd., specification: 250 g / bottle, batch number: 20200320;

[0075] IL-17 ELISA detection kit, Shanghai Yuanye Biotechnology Co., Ltd., specification: 96T, batch number: E-15278.

[0076] 1.4 Instruments

[0077] electronic balance (Sartorius Scientific Instruments, model: BSA224S-CW);

[0078] R415-Pro ​​small animal ventilator, Shenzhen Ruiwode Life Science Technology Co., Ltd.;

[0079] PowerLab8 / 35 biological signal acquisition system, manufactured by ADInstruments, Australia;

[0080] CENTRFUGE5840 refrigerated centrifuge, Eppendorf;

[0081] FLEX-STION3 microplate reader from MD.

[0082] 2. Dosage design

[0083] The daily dosage of the Chinese herbal medicine composition is 72 g of the crude drug per day. Based on the body surface area conversion method, the equivalent dose for rats is 72 g / 60 kg x 6.2 = 7.44 g of crude drug per kg. This equivalent dose is considered the medium dose, with the high, medium, and low doses being 14.88, 7.44, and 3.72 g of crude drug per kg, respectively. Administration is by oral gavage at 1 mL / 100 g once daily.

[0084] The daily dosage of aminophylline tablets is 0.6g / day. According to the body surface area conversion method, the equivalent dose for rats is 0.6g / 60kg×6.2=0.062g / kg.

[0085] 3. Experimental Methods

[0086] SD rats were adaptively fed for 5 days with free access to feed and water and randomly divided into a normal group, a model group, a positive drug (aminophylline tablets) group, and a high-, medium-, and low-dose group of the Chinese medicine composition, with 10 rats in each group.

[0087] On days 1 and 14, rats were injected with 200 μg / 200 μL of endotoxin via the trachea. From days 2 to 30 (except day 14), rats were exposed to 5% cigarette smoke (front door brand) for 1 hour / day, twice daily, to establish a COPD model. A normal control group received a similar tracheal instillation of normal saline without smoke on days 1 and 14. The normal and model control groups were given double-distilled water, different doses of the Chinese herbal composition (14.88, 7.44, and 3.72 g crude drug / kg), and aminophylline tablets (10 ml / kg) orally once daily for 30 days. Thirty minutes after the last dose, rats were anesthetized with 10% chloral hydrate 0.35 g / kg intraperitoneally for specimen collection.

[0088] Test indicators: ① Pulmonary function tests are important for determining airflow limitation. Rats were anesthetized with chloral hydrate, and the neck skin was longitudinally incised to expose the trachea. An inverted "T"-shaped incision was made beneath the cricoid cartilage. An endotracheal tube connected to a three-way switch was inserted. One end was connected to an animal ventilator and the other end to a biosignal acquisition system to measure respiratory parameters. Parameters such as forced vital capacity (FVC), forced expiratory volume in 0.3 seconds (FEV0.3), FEV0.3 / FVC, and peak expiratory flow (PEF) were measured. ② Serum IL-17 levels.

[0089] 4 Test results

[0090] 4.1 Effects on respiratory parameters of rats

[0091] The results showed that FVC, FEV0.3, FEV0.3 / FVC, and PEF in the model group were significantly lower than those in the normal group (P < 0.001, P < 0.001, P < 0.05, P < 0.001), indicating successful modeling. FVC, FEV0.3, and PEF in the high- and medium-dose groups of the Chinese herbal composition were significantly improved compared to the model group (P < 0.001, P < 0.05, P < 0.01). FVC and PEF in the low-dose group of the Chinese herbal composition were significantly improved compared to the model group (P < 0.05). The results are shown in Table 1.

[0092] Table 1 Effects on lung function in rats with chronic obstructive pulmonary disease

[0093] Group n FVC (ml) FEV0.3 (ml) FEV0.3 / FVC (%) PEF (ml / s) Normal group 10 4.97±0.77*** 3.96±0.72*** 80.10±10.18* 1.15±0.20*** Model Group 10 2.58±0.46 1.68±0.70 64.04±20.84 0.73±0.15 Positive drug group 10 4.09±0.82*** 3.09±0.90*** 75.64±15.59 1.06±0.22*** High-dose group 10 3.93±0.74*** 3.01±0.71*** 76.57±10.81 1.07±0.23*** Medium dose group 10 3.45±0.96* 2.34±0.45* 71.06±17.47 1.01±0.21** Low-dose group 10 2.99±0.39* 2.05±0.65 68.47±19.22 0.91±0.18*

[0094] Note: Compared with the model group, *P<0.05, **P<0.01, ***P<0.001.

[0095] 4.2 Effects on the levels of inflammatory factors in rat serum

[0096] Compared with the normal group, the serum IL-17 level in the model group rats was significantly increased (P < 0.001). Compared with the model group, the serum IL-17 level in the rats in the high-dose, medium-dose, and low-dose groups of the Chinese medicine composition was significantly decreased (P < 0.001). The results are shown in Table 2.

[0097] Table 2 Effects on the serum inflammatory factor IL-17 level in rats with chronic obstructive pulmonary disease

[0098] Group n IL-17 (pg / ml) Normal group 10 10.12±0.88*** Model Group 10 41.26±6.65 Positive drug group 10 13.57±1.24*** High-dose group 10 14.43±1.85*** Medium dose group 10 17.73±1.92*** Low-dose group 10 22.65±2.87***

[0099] Note: Compared with the model group, ***P<0.001.

[0100] 5. Experimental Conclusion

[0101] The Chinese medicine composition can significantly improve FVC, FEV0.3, and PEF, and significantly reduce the level of inflammatory factors, suggesting that the Chinese medicine composition has the effect of alleviating lung inflammation and emphysema.

[0102] Example 3 Effect of Chinese medicine composition on elastase-induced emphysema

[0103] 1. Experimental Materials

[0104] 1.1 Animals

[0105] SD rats, SPF grade, male, weighing 200-240 g were purchased.

[0106] Breeding environment: room temperature 20-26℃, relative humidity controlled at 40-70%, and breeding density of 5 per cage.

[0107] 1.2 Medication

[0108] Chinese medicine composition, three intermediates prepared according to the method of Example 1, Jiangsu Kangyuan Pharmaceutical Co., Ltd.;

[0109] Dexamethasone tablets, Guangdong Nanguo Pharmaceutical Co., Ltd., batch number: 210304; specifications: 0.75 mg / tablet, 100 tablets / bottle.

[0110] 1.3 Reagents

[0111] Elastase (porcine pancreas), Beijing Biolab Technology Co., Ltd., 1 g / vial, batch number 20210518;

[0112] 0.9% sodium chloride solution, Chenxin Pharmaceutical Co., Ltd., specification: 100 ml / bottle, batch number: 2101282721;

[0113] Chloral hydrate, Shanghai Sinopharm Chemical Reagent Co., Ltd., specification: 250 g / bottle, batch number: 20200320;

[0114] Rat α1-antitrypsin (α1-AT) ELISA kit, Hangzhou Zhenyoupin Biotechnology Co., Ltd., specification: 96T, batch number: 20210907;

[0115] Rat hyaluronidase (HAase) ELISA kit, Hangzhou Zhenyoupin Biotechnology Co., Ltd., specification: 96T, batch number: 20210908;

[0116] Rat type III procollagen (PCIII) ELISA kit, Hangzhou Zhenyoupin Biotechnology Co., Ltd., specification: 96T, batch number: 20210910.

[0117] 1.4 Instruments

[0118] electronic balance (Sartorius Scientific Instruments, model: BSA224S-CW);

[0119] CENTRFUGE5840 refrigerated centrifuge, Eppendorf;

[0120] FLEX-STION3 microplate reader from MD.

[0121] 2. Dosage design

[0122] The daily dosage of the Chinese herbal medicine composition is 72 g of the crude drug per day. Based on the body surface area conversion method, the equivalent dose for rats is 72 g / 60 kg x 6.2 = 7.44 g of crude drug per kg. This equivalent dose is considered the medium dose, with the high, medium, and low doses being 14.88, 7.44, and 3.72 g of crude drug per kg, respectively. Administration is by oral gavage at 1 mL / 100 g once daily.

[0123] The daily dosage of dexamethasone tablets is 2.25 mg / day. According to the body surface area conversion method, the equivalent dose for rats is 2.25 / 60 kg×6.2=0.2325 mg / kg.

[0124] 3. Experimental Methods

[0125] Select 60 SD rats, male, according to body weight, randomly divided into 6 groups, 10 in each group. The 6 groups are respectively a normal group, a model group, a Chinese medicine composition different low, medium and high dose groups (14.88, 7.44, 3.72g crude drug / kg), and a positive control group (dexamethasone 0.2325mg / kg). Adopt elastase intratracheal instillation method to replicate the experimental rat emphysema model. Anesthetize the rats with 10% chloral hydrate intraperitoneal injection, expose the trachea, take 0.5ml (200U / kg) of porcine pancreatic elastase solution with a 1ml syringe, slowly instill in the trachea, immediately set the rats upright and shake them to make them evenly distributed, suture the incision, and complete the operation, and sterilize the incision. The normal control group is operated on by the same method, and normal saline is instilled into the trachea at 0.4ml / kg. Start administration on the second day after operation, once a day, for 4 consecutive weeks.

[0126] Detection indicators: Determination of α1-AT, HA and PC III in serum.

[0127] 4 Test results

[0128] After elastase modeling, the serum α1-AT content of rats was significantly decreased compared with the normal group, while the serum HA and PCIII contents were significantly increased (P<0.001). After administration of the Chinese medicine composition, the serum α1-AT content of rats in the high-, medium-, and low-dose groups was significantly increased compared with the model group, while the HA and PCIII contents were significantly decreased (P<0.001, P<0.01, and P<0.05).

[0129] Table 3. Contents of α1-AT, HA and PC III in serum

[0130] Group Number of samples α1-AT content (g / L) HA content (ng / ml) PCIII content (μg / L) Normal group 10 1.87±0.14*** 145.45±15.58*** 104.85±5.57*** Model Group 10 1.22±0.11 231.55±19.52 150.65±10.49 Positive drug group 10 1.73±0.11*** 180.85±12.74*** 128.45±11.54*** High-dose group 10 1.69±0.15*** 184.55±20.95*** 130.15±12.55*** Medium dose group 10 1.62±0.15*** 202.85±17.84** 132.65±13.58** Low-dose group 10 1.53±0.13*** 208.65±19.98* 138.65±14.19*

[0131] Note: Compared with the model group, *p<0.05, **p<0.01, ***p<0.001

[0132] 5. Experimental Conclusion

[0133] The Chinese medicine composition can increase the serum α1-AT content of rats after modeling, prevent the progressive destruction of alveolar walls, reduce the serum HA and PCIII contents of rats, and delay the disease progression of emphysema.

[0134] The above are only preferred embodiments of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principles of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. Use of a Chinese medicine composition in the preparation of a drug for preventing and treating chronic obstructive pulmonary disease and / or emphysema; The Chinese medicine composition comprises the following raw materials in parts by weight: 5-30 parts of houttuynia cordata, 5-30 parts of honeysuckle, 5-20 parts of red peony root, 3-15 parts of wormwood leaves, and 3-15 parts of mint.

2. The use according to claim 1, characterized in that: The prevention and treatment of chronic obstructive pulmonary disease includes improving lung function and / or inhibiting the level of inflammatory factors.

3. The use according to claim 2, characterized in that: The improving lung function includes improving FVC, FEV0.3 and / or PEF.

4. The use according to claim 2, characterized in that: The inflammatory factor is IL-17.

5. The use according to any one of claims 1 to 4, characterized in that: The chronic obstructive pulmonary disease is a chronic obstructive pulmonary disease caused by harmful gases and lung inflammation.

6. The use according to claim 1, characterized in that: The prevention and treatment of emphysema includes preventing the destruction of alveolar walls and / or improving the progress of pulmonary fibrosis.

7. The use according to claim 1, characterized in that: The prevention of alveolar wall destruction includes inhibiting the level of α1-AT, and the improvement of pulmonary fibrosis progression includes inhibiting the level of HA and / or PC III.

8. The use according to claim 6 or 7, characterized in that: The pulmonary emphysema is caused by increased protease activity or decreased anti-lytic activity.

9. A drug for preventing and treating chronic obstructive pulmonary disease and / or emphysema, comprising pharmaceutically acceptable excipients and the following raw materials in parts by weight: 5-30 parts of Houttuynia cordata, 5-30 parts of Honeysuckle, 5-20 parts of Red Peony Root, 3-15 parts of Artemisia argyi, and 3-15 parts of mint.

10. The drug according to claim 9, characterized in that It also includes other drugs for preventing and treating chronic obstructive pulmonary disease and / or preventing and treating emphysema, and the other drugs for preventing and treating chronic obstructive pulmonary disease and / or preventing and treating emphysema include: at least one of aminophylline, dexamethasone, prednisone, ambroxol hydrochloride, methylprednisolone, budesonide, fluticasone, salbutamol sulfate or antibiotics.