Application of traditional Chinese medicine composition in preparation of medicine for preventing and treating cough variant asthma

By regulating inflammatory factors in cough variant asthma, especially IL-4, IL-10 and TGF-β1, through a combination of traditional Chinese medicine, the problems of large side effects in Western medicine treatment and lack of prevention and treatment methods in traditional Chinese medicine have been solved, thus achieving effective prevention and treatment of cough variant asthma.

CN119258134APending Publication Date: 2025-01-07JIANGSU KANION PHARMA CO LTD
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Patent Information

Application Number
CN202410785032.0
Authority / Receiving Office
CN · China
Patent Type
Applications(China)
Current Assignee / Owner
Filing Date
2024-06-18
Publication Date
2025-01-07

AI Technical Summary

Technical Problem

Current Western medicine treatments for cough variant asthma suffer from problems such as misdiagnosis, missed diagnosis, significant side effects, and poor patient compliance. Traditional Chinese medicine treatments lack effective prevention and treatment methods and struggle to effectively regulate inflammatory factor levels and reduce the frequency of coughing.

Method used

The traditional Chinese medicine composition includes houttuynia cordata, honeysuckle, red peony root, mugwort leaf and peppermint, which regulates the level of inflammatory factors in serum, especially IL-4, IL-10 and TGF-β1, and reduces the frequency of coughing. It is prepared into various dosage forms such as decoction, tablets and capsules, and is administered orally, by spray inhalation and other methods.

Benefits of technology

It significantly reduces cough frequency, regulates inflammatory factor levels, reduces the number of coughs, increases IL-10 and TGF-β1 levels, and reduces the frequency and severity of cough variant asthma attacks.

✦ Generated by Eureka AI based on patent content.
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Abstract

The invention relates to the technical field of traditional Chinese medicine, in particular to application of a traditional Chinese medicine composition in preparation of a medicine for preventing and treating cough variant asthma. 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 the influence of the composition on the expression levels of IL-4, 1L-10 and TGF-beta 1 in the serum of rats. Experimental results show that the traditional Chinese medicine composition can obviously relieve the cough variant asthma symptom of rats, and the cough frequency of the rats is obviously reduced; the traditional Chinese medicine composition can reduce the level of an inflammatory factor IL-4 in serum of rats and improve the levels of anti-inflammatory factors IL-10 and TGF-beta1 in the serum, so that the medicine has a good function of treating cough variant asthma.
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Description

Technical Field

[0001] The invention relates to the technical field of traditional Chinese medicines, and in particular to application of a traditional Chinese medicine composition in preparing medicines for preventing and treating cough variant asthma. Background Art

[0002] Cough variant asthma (CVA) is a chronic cough with cough as the main or only symptom and is difficult to improve for a long time (usually >8 weeks). It is a special form of asthma. In addition to being related to one's own genetics, the onset of CVA is also affected by allergens and environmental factors. With the deterioration of air quality, high urbanization and high industrialization, adverse environmental impacts are becoming increasingly serious.

[0003] For Western medical diagnosis, since cough is the only and main symptom of the disease, a variety of auxiliary examinations are required clinically. Therefore, in the early stages of the disease, the CVA diagnostic criteria are not met and it can only be classified as a chronic cough, which often leads to misdiagnosis, missed diagnosis, and incorrect treatment. These reasons may cause some CAV patients to eventually develop into typical bronchial asthma.

[0004] Western medicine treats CVA similarly to asthma, but only for CVA attacks, mainly for the chronic inflammatory lesions of the airways of cough variant asthma, and takes the form of long-term inhaled glucocorticoids and bronchodilators for treatment. Hormone drugs can cause certain adverse reactions to the digestive tract, growth and development, etc. during use, and the compliance of hormone drugs is poor. The irregular inhalation method of patients and their resistance to hormone drugs make it difficult to guarantee the treatment effect.

[0005] Most Western medicine treatments are only symptomatic, but prevention of CVA is particularly important. It is necessary not only to avoid exposure to inducing factors in the environment, but also to ensure the steady-state balance of the body's own internal environment and immunity. In TCM diagnosis, CVA is mainly manifested by itchy throat, irritating dry cough, severe cough, cough at night and early morning, and colds, cold air, dust and oil smoke can easily induce or aggravate coughs. These manifestations of CVA completely correspond to the manifestations of "wind evil in the lungs" in TCM cough, and "wind evil in the lungs" is the core of CVA symptoms.

[0006] TCM believes that chronic airway inflammation in cough variant asthma is related to "wind and phlegm", with cough as the main symptom, and is characterized by airway hyperresponsiveness. Therefore, Chinese patent medicines or prescriptions such as Compound Fresh Bamboo Sap Oral Liquid, Ma Xing Shi Gan Tang, and Modified Xiao Qing Long Tang are often used to treat cough variant asthma. TCM has a complete theoretical system for the overall onset, etiology, pathogenesis, treatment, and prevention of CVA. In terms of treatment, multiple drugs and multiple targets are used for treatment, and damage to the body is minimized; in terms of prevention, Chinese medicine has unique advantages in adjusting the overall living conditions of patients and relieving minor symptoms. It can eliminate "hidden wind" when CVA is not onset, and can reduce the number and duration of CVA. Therefore, it is necessary to further develop more effective Chinese medicines for the prevention and treatment of cough variant asthma. Summary of the invention

[0007] In view of this, the technical problem to be solved by the present invention is to provide an application of a Chinese medicine composition in the preparation of a medicament for preventing and treating cough variant asthma.

[0008] The present invention provides the use of a Chinese medicine composition in preparing a medicine for preventing and treating cough variant asthma;

[0009] 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 leaf, and 3-15 parts of mint.

[0010] In the present invention, the prevention and treatment of cough variant asthma includes: regulating the level of inflammatory factors and / or reducing the number of coughs.

[0011] During the onset of cough variant asthma, the level of inflammatory factors often increases abnormally. This increase may be closely related to the severity of airway inflammation. The present invention has found that the Chinese medicine composition as described above can regulate the level of inflammatory factors, especially the level of inflammatory factors in serum. Inflammatory factors such as IL-4, IL-10 and TGF-β1 are closely related to the occurrence and development of cough variant asthma. In the invention, the inflammatory factors include at least one of IL-4, IL-10 and TGF-β1. The regulation includes: increasing the levels of IL-10, TGF-β1 and / or reducing the level of IL-4.

[0012] Cough variant asthma is a type of asthma with cough as the main symptom or the only symptom, and reducing the number of coughs is the basis of cough variant asthma. The Chinese medicine composition of the present invention can reduce the number of coughs and reduce the frequency of coughs, which is specifically manifested as a reduction in the number of coughs per unit time.

[0013] In the present invention, the cough variant asthma is cough variant asthma caused by allergy. The allergen of the allergy is ovalbumin.

[0014] In an embodiment of the present invention, the mass fractions of each component 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, and 3-10 parts of mint. Furthermore, the mass fractions of each component 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, and 3-5 parts of mint.

[0015] Optionally, the mass proportions 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.

[0016] Optionally, the mass proportions 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.

[0017] Optionally, the mass proportions 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.

[0018] The composition of the present invention can be directly ground into powder, or it can be an extract obtained by conventional means in the art. The composition can be directly ground into powder by conventional methods, or it can be an extract obtained by conventional means, so as to be made into different dosage forms, obtain better therapeutic effects and be more conducive to the preparation of modern pharmaceutical dosage forms.

[0019] In an embodiment of the present invention, the preparation method of the Chinese medicine composition comprises:

[0020] Step A: weighing Chinese medicinal materials according to the weight ratio of the raw materials;

[0021] Step B: extracting honeysuckle with 6-12 times the amount of 50%-80% ethanol, filtering the extract, recovering the ethanol, drying and crushing to obtain a dry paste powder;

[0022] Step C: add 3-12 times of water to Houttuynia cordata, Artemisia argyi and mint to extract volatile oil, add coarse powder of red peony root to the residue, add 6-12 times of water to boil, filter the extract to obtain a clear paste, add ethanol with a concentration of more than 90% to 60% to 80% alcohol, precipitate with alcohol, let stand, recover ethanol from the supernatant to obtain a thick paste, dry and crush to obtain dry paste powder;

[0023] Step D: Mix the volatile oil and the two dry paste powders.

[0024] Furthermore, the method for preparing the Chinese medicine composition comprises the following steps:

[0025] Step A: Add 12 times the amount of 50% ethanol to honeysuckle, reflux extract twice, each time for 0.5 hours, filter, combine the filtrate, 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 crush to obtain alcohol-extracted dry extract powder;

[0026] Step B: add 8 times the amount of water to Houttuynia cordata, Artemisia argyi and mint, extract volatile oil by steam distillation for 5 hours, filter the extract and set aside;

[0027] Step C: grinding and inclusion of 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;

[0028] Step D: after extracting the volatile oil, the residue is combined with red peony root, 10 times the amount of water is added, extraction is performed twice, each time for 1 hour, the extract is combined with the oil extraction liquid, filtered, the filtrate is concentrated under reduced pressure to a clear paste with a relative density of 1.02-1.05, cooled to room temperature, 95% ethanol is added to make the alcohol content reach 70%, and the mixture is allowed to stand for more than 12 hours. The supernatant of the alcohol precipitation is reduced in pressure to recover ethanol and concentrated to a thick paste with a relative density of 1.25-1.30, dried under reduced pressure, and crushed to obtain a water-extracted dry extract powder; the alcohol-extracted dry extract powder, the volatile oil inclusion compound and the water-extracted dry extract powder are mixed.

[0029] The present invention also provides a medicine for preventing and treating cough variant asthma, which comprises 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 wormwood leaf, and 3-15 parts of mint.

[0030] The dosage forms of the drug of the present invention include, but are not limited to, decoctions, tablets, capsules, granules, pills, injections, decoctions, suspensions, dispersions, syrups, suppositories, gels, aerosols, patches and / or oral solutions.

[0031] In some embodiments provided by the present invention, the capsule is a hard capsule or a soft capsule.

[0032] In some embodiments provided herein, the tablet is an oral tablet or an oral tablet.

[0033] Oral tablets refer to tablets for oral administration. Most of the drugs in such tablets are absorbed through the gastrointestinal tract to exert their effects, and some of the drugs in tablets exert their effects locally in the gastrointestinal tract. In some embodiments provided by the present invention, the oral tablets are ordinary compressed tablets, dispersible tablets, effervescent tablets, chewable tablets, coated tablets or sustained-release tablets.

[0034] 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.

[0035] The medicine described in the present invention also includes other medicines for preventing and treating cough variant asthma, and the other medicines for preventing and treating cough variant asthma include: at least one of budesonide, fluticasone, prednisone, dexamethasone, salmeterol, formoterol, salbutamol, terbutaline, montelukast sodium, zafirlukast, cetirizine, loratadine, aminophylline, and ipratropium bromide.

[0036] In the present invention, in the medicine, the Chinese medicine composition and other therapeutic agents may exist independently of each other or may exist in combination, and the present invention does not limit this.

[0037] Furthermore, the present invention also provides a method for preventing and treating cough variant asthma, which comprises administering the drug of the present invention.

[0038] The administration methods of the drug include, but are not limited to, oral administration, spray inhalation, rectal administration, nasal administration, buccal administration, vaginal administration, topical administration. Or non-enteral administration, such as subcutaneous, intravenous, intramuscular, intraperitoneal, intrathecal, intraventricular, intrasternal or intracranial injection or infusion; or administration via an explanted reservoir. Preferably, the administration method is oral administration and / or aerosol inhalation.

[0039] In the present invention, when the medicine includes a Chinese medicine composition and other therapeutic agents, two or more medicines can be administered simultaneously or sequentially, and the present invention is not limited to this.

[0040] 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.

[0041] In the present invention, when the medicine includes a 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 is not limited to this.

[0042] For example, the administration frequency of two or more of the drugs 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.

[0043] In the present invention, the medicine includes a Chinese medicine composition, and the dosage is not less than the effective dose. If the medicine includes a Chinese medicine composition and other therapeutic agents, the dosage of the Chinese medicine composition is lower than the effective dose, or not lower than the effective dose; the dosage of other therapeutic agents is lower than the effective dose, or not lower than the effective dose.

[0044] 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 preventive or therapeutic effective amount of a drug will vary depending on the specific drug selected (e.g., considering the efficacy, 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, and other factors, but can still be routinely determined by those skilled in the art.

[0045] In the present invention, the prevention and treatment includes prevention and / or treatment, which is a preventive and therapeutic measure for cough variant asthma. This includes a method for preventing the occurrence of cough variant asthma, the purpose of which is to prevent, slow down (reduce) undesirable physiological changes or lesions in the treated subject, and the beneficial or desired clinical results include but are not limited to avoiding the occurrence of cough variant asthma, alleviating the symptoms of cough variant asthma, reducing the degree of cough variant asthma, stabilizing the state of cough variant asthma (i.e., not worsening), delaying or slowing the progression of cough variant asthma, improving or alleviating the state of cough variant asthma, 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.

[0046] In the present invention, the object of prevention and treatment is a human or a mammal, and the mammal includes bovines, equines, ovines, swine, canines, felines, rodents, and primates. The rodent is a mouse and / or a rat.

[0047] The Chinese medicine composition of the present invention comprises 5-30 parts of houttuynia, 5-30 parts of honeysuckle, 5-20 parts of red peony root, 3-15 parts of wormwood and 3-15 parts of mint. The present invention finds the effect of the composition on the expression levels of IL-4, 1L-10 and TGF-β1 in rat serum. The experimental results show that the Chinese medicine composition of the present invention can significantly alleviate the symptoms of rat cough variant asthma, and the number of rat coughs is significantly reduced; it can reduce the level of inflammatory factor IL-4 in rat serum and increase the levels of anti-inflammatory factors IL-10 and TGF-β1 in serum, indicating that the drug of the present invention has a good function of treating cough variant asthma. DETAILED DESCRIPTION

[0048] The present invention provides the use of a Chinese medicine composition in the preparation of a medicine for preventing and treating cough variant asthma. Those skilled in the art can refer to the content of this article and appropriately improve the process parameters to achieve it. It should be particularly noted that all similar replacements and modifications are obvious to those skilled in the art, and they are all considered to be included in the present invention. The method and application of the present invention have been described through preferred embodiments, and relevant personnel can obviously modify or appropriately change and combine the method and application of this article without departing from the content, spirit and scope of the present invention to realize and apply the technology of the present invention.

[0049] The test materials used in the present invention are all common commercial products and can be purchased in the market.

[0050] The present invention will be further described below in conjunction with embodiments:

[0051] Example 1 Preparation of Chinese medicine composition granules

[0052] Ratio of raw materials: Houttuynia cordata: 750g, honeysuckle 750g, red peony root 450g, wormwood leaf 300g, mint 150g.

[0053] Step A: adding 12 times the amount of 50% ethanol to honeysuckle, reflux extraction twice, each time for 0.5 hour, filtering, combining the filtrate, reducing pressure (-0.07MPa~-0.09MPa, 65℃~75℃) to recover ethanol and concentrate to a thick paste with a relative density of 1.20~1.25 (65℃), reducing pressure drying (-0.07MPa~-0.09MPa, 60℃~65℃), crushing, and obtaining alcohol-extracted dry extract powder;

[0054] Step B: add 8 times the amount of water to Houttuynia cordata, Artemisia argyi and mint, and extract volatile oil by steam distillation for 5 hours. Filter the extract and store it in another container for later use;

[0055] Step C: grinding and inclusion of the obtained volatile oil with 10 times the amount of β-cyclodextrin and 20 times the amount of water for 20 minutes, drying the inclusion compound (55° C.), and crushing to obtain a volatile oil inclusion compound;

[0056] Step D: after extracting the volatile oil, the 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 liquid, 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%, and the mixture is allowed to stand for more than 12 hours. The supernatant of the alcohol precipitation is decompressed (-0.07MPa to -0.09MPa, 65°C to 75°C) to recover 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 to reduce the pressure (-0.07MPa to -0.09MPa, 75°C) to dry, and pulverize to obtain a water-extracted dry extract powder.

[0057] 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.

[0058] Experimental Example 2 Therapeutic effect of Chinese medicine composition on cough variant asthma

[0059] 1. Experimental Materials

[0060] 1.1 Animals

[0061] 60 SPF SD rats, healthy males, with a body weight of 180-200g.

[0062] 1.2 Drugs

[0063] The three intermediates prepared in Example 1 were from Jiangsu Kangyuan Pharmaceutical Co., Ltd.

[0064] Budesonide: produced by Chia Tai Tianqing Pharmaceutical Group, batch number: 20220909.

[0065] Ovalbumin (OVA): Sigma-Aldrich, catalog number SLCP1458.

[0066] Aluminum hydroxide adjuvant: Biolon Corporation, product number: KX0210054.

[0067] Capsaicin: Solebao Company, product number: N8490.

[0068] 1.3 Instruments and reagents

[0069] Refrigerator (Siemens, model: BCD-265); electronic balance (METTLER TOLEDO, model: ME204); purified water instrument (Millipore, Germany, model: Milli-QPlus); animal weight scale (Shanghai Xiangchuan Electronic Scale Co., Ltd., model: ACX-SC-DA); multifunctional microplate reader (Molecular Devices, model: SpectraMax M2); IL-4, 1L-10, TGF-β1 ELISA detection kit (Wuhan Boster Biotechnology Co., Ltd.); sodium pentobarbital (Sigma-Aldrich, cat. no. 57-33-0); sodium chloride injection (Shaanxi Shengao Animal Pharmaceutical Co., Ltd.)

[0070] 2. Dosage design

[0071] The clinical daily dosage of the Chinese medicine composition is 72g of crude drug / day. According to the body surface area conversion method, the equivalent dose for rats is 72g of crude drug / 60kg×6.2=7.44g of crude drug / kg. The high, medium and low doses are 14.88, 7.44 and 3.72g of crude drug / kg respectively.

[0072] 3. Experimental Methods

[0073] 3.1 Establishment of cough variant asthma animal model

[0074] Sensitization: After 1 week of adaptive feeding, rats were randomly divided into 6 groups according to body weight, namely, blank group, model group, high-, medium- and low-dose groups of Chinese medicine combination and positive drug group, with 10 rats in each group. Starting from the 8th day, except for the blank group, rats in other groups were intraperitoneally injected with 0.2 mL of 2 mg ovalbumin (OVA) and 100 mg aluminum hydroxide gel suspension. Three weeks after the first sensitization (day 29), the rats were sensitized again with the same dose and volume. Rats in the blank group were sensitized twice with an equal amount of normal saline intraperitoneally.

[0075] Challenge: 3 weeks after the second sensitization (50th day), except for the normal group, which was challenged with saline nebulization, the model group, the high, medium and low dose groups of the Chinese medicine composition and the positive drug group were challenged with 1% ovalbumin (OVA) every other day for 20 minutes, for a total of 7 times. The model was successfully established when the rats developed coughing symptoms but no other symptoms such as wheezing were observed.

[0076] 3.2 Drug intervention

[0077] Three weeks after the second sensitization (day 50), rats in each group were gavaged 30 minutes before atomization for a total of 2 weeks, twice a day. The blank group and the model group were given an equal amount of distilled water. The Chinese medicine composition was given 14.88, 7.44, and 3.72 g of crude drug / (kg·d) in the high, medium, and low dose groups, respectively. The positive drug group was given 1.2 mg / (kg·d) of budesonide suspension for inhalation.

[0078] 4. Detection indicators

[0079] 4.1 Rat cough sensitivity assay

[0080] After 24 hours of stimulation, cough sensitivity of each rat was measured and the number of coughs was recorded. Capsaicin solution was used to induce coughing in rats of each group in turn, with each atomization time of 60 seconds, and then the atomization was stopped for another 60 seconds, and the number of coughs of each rat was observed and recorded for 2 minutes.

[0081] 4.2 ELISA method to detect the levels of IL-4, 1L-10 and TGF-β1 in rat serum

[0082] After the last administration, the rats were fasted for 24 h (free access to water), and after being weighed and anesthetized, 4 mL of blood was collected from the abdominal aorta. After standing for 1 h, the blood was centrifuged at 2000 r / min for 10 min at 4°C with a centrifugal radius of 8 cm to separate the serum and store it below -20°C.

[0083] The ELISA method was used to determine the levels of serum IL-4, IL-10, and TGF-β1, and the operation was carried out strictly according to the instructions of the kit.

[0084] 5. Experimental Results

[0085] 5.1 Comparison of cough frequency among rats in each group

[0086] The results of the comparison of the number of coughs in rats are shown in Table 1. Compared with the blank group, the number of coughs in the model group was significantly increased, and there was a statistically significant difference between the two groups (P<0.001). Compared with the model group, the number of coughs in the positive drug group, the medium dose group and the high dose group was significantly reduced (P<0.001, P<0.05, P<0.001).

[0087] Table 1 Comparison of cough frequency in rats ( n=10)

[0088] Group dose Number of coughs Blank group — 2.6±0.7*** Model Group — 11.7±1.34 Positive drug group 1.2mg / kg 6.7±0.67*** Low dose group 3.72g crude drug / kg 11.6±1.17 Medium dose group 7.44g crude drug / kg 10.7±1.06* High dose group 14.88g crude drug / kg 7.6±1.26***

[0089] Note: Compared with the model group, *P<0.05, **P<0.01, ***P<0.001

[0090] 5.2 Detection of serum inflammatory factors in rats with cough variability

[0091] The results of serum ELISA test are shown in Table 2. Compared with the blank group, the serum IL-4 content of rats in the model group was significantly increased (P<0.001), and the serum IL-10 and TGF-β1 contents were significantly decreased, which were statistically significant (P<0.001, P<0.01). Compared with the model group, the serum IL-4 content of rats in the medium and high dose groups of the Chinese medicine composition was significantly decreased (P<0.01, P<0.001), the serum IL-10 content of rats in the high dose group was significantly increased (P<0.01), and the serum TGF-β1 content of rats in the medium and high dose groups was significantly increased (P<0.05, P<0.001).

[0092] Table 2 Effects of serum inflammatory factors on rats with cough variant asthma ( n=10)

[0093] Group dose IL-4 (ng / L) IL-10 (ng / L) TGF-β1(ng / L) Blank group — 12.28±3.93*** 30.04±1.83*** 28.68±1.69** Model Group — 51.24±4.34 25.69±1.46 26.41±1.59 Positive drug group 1.2mg / kg 37.24±2.83*** 29.04±3.29** 28.55±2.34* Low dose group 3.72g crude drug / kg 52.84±4.49 26.29±1.40 28.27±2.93 Medium dose group 7.44g crude drug / kg 45.61±5.31** 25.88±3.2 29.33±3.08* High dose group 14.88g crude drug / kg 38.55±3.78*** 28.19±2.27** 30.52±2.79***

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

[0095] 6. Experimental conclusion

[0096] The experimental results show that the sample prepared according to Example 1 of the present invention can significantly reduce the number of rat coughs at high and medium doses, inhibit the expression of rat serum IL-4, and promote the expression of serum IL-10 and TGF-β1, indicating that the drug of the present invention has a good function in treating cough variant asthma.

[0097] 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 cough variant asthma; 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 cough variant asthma includes: regulating the level of inflammatory factors and / or reducing the frequency of coughing.

3. The use according to claim 2, characterized in that: The inflammatory factors include at least one of IL-4, IL-10 and TGF-β1.

4. The use according to claim 2 or 3, characterized in that: The inflammatory factors are inflammatory factors in serum.

5. The use according to claim 2, characterized in that: The regulation includes: increasing the levels of IL-10 and TGF-β1 and / or decreasing the level of IL-4.

6. The use according to claim 1, characterized in that: The cough variant asthma is cough variant asthma caused by allergies.

7. The use according to any one of claims 1 to 6, characterized in that: The preparation method of the Chinese medicine composition comprises: Step A: weighing Chinese medicinal materials according to the weight ratio of the raw materials; Step B: extracting honeysuckle with 6-12 times the amount of 50%-80% ethanol, filtering the extract, recovering the ethanol, drying and crushing to obtain a dry paste powder; Step C: add 3-12 times of water to Houttuynia cordata, Artemisia argyi and mint to extract volatile oil, add coarse powder of red peony root to the residue, add 6-12 times of water to boil, filter the extract to obtain a clear paste, add ethanol with a concentration of more than 90% to 60% to 80% alcohol, precipitate with alcohol, let stand, recover ethanol from the supernatant to obtain a thick paste, dry and crush to obtain dry paste powder; Step D: Mix the volatile oil and the two dry paste powders.

8. The use according to claim 7, characterized in that: The method for preparing the Chinese medicine composition comprises the following steps: Step A: Add 12 times the amount of 50% ethanol to honeysuckle, reflux extract twice, each time for 0.5 hours, filter, combine the filtrate, 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 crush to obtain alcohol-extracted dry extract powder; Step B: add 8 times the amount of water to Houttuynia cordata, Artemisia argyi and mint, extract volatile oil by steam distillation for 5 hours, filter the extract and set aside; Step C: grinding and inclusion of 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; Step D: after extracting the volatile oil, the 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 liquid, filtered, and the filtrate is concentrated under reduced pressure to a clear paste with a relative density of 1.02-1.05, cooled to room temperature, 95% ethanol is added to make the alcohol content reach 70%, and the mixture is allowed to stand for more than 12 hours, and the ethanol is recovered from the supernatant of the alcohol precipitation under reduced pressure and concentrated to a thick paste with a relative density of 1.25-1.30, and the mixture is dried under reduced pressure and crushed to obtain a water-extracted dry extract powder; and the alcohol-extracted dry extract powder, the volatile oil inclusion compound and the water-extracted dry extract powder are mixed.

9. A drug for preventing and treating cough variant asthma, 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 8, characterized in that Other drugs for preventing and treating cough variant asthma are also included, and the other drugs for preventing and treating cough variant asthma include: at least one of budesonide, salbutamol, terbutaline, aminophylline, fluticasone, aspirin, chlorpheniramine, cetirizine, montelukast, dextromethorphan, pentoxyverine, benproperine, narcotine or cough syrup.