Pharmaceutical composition for treating post-infection cough and preparation method thereof

Abstract

The invention provides a pharmaceutical composition for treating cough after infection and a preparation method of the pharmaceutical composition. The pharmaceutical composition comprises the following raw materials in parts by weight: 15-32 parts of reed stems and 15-24 parts of emblic leafflower fruits. The pharmaceutical composition disclosed by the invention has the effects of clearing heat, promoting salivation, expelling phlegm and stopping coughing on the basis of Thailand traditional medical theories or traditional Chinese medicine theories, is safe and non-toxic, has no obvious adverse reaction, and has a good treatment effect on cough after infection.

Description

Technical Field

[0001] The present invention relates to the field of pharmaceutical technology, and in particular to a pharmaceutical composition for treating post-infectious cough and a preparation method thereof. Background Art

[0002] Post-infectious cough (PIC) refers to a disease with cough as the main symptom after the acute symptoms of respiratory tract infection disappear. It is often manifested as repeated attacks of irritating cough, itchy throat, or expectoration. It is induced or aggravated by cold air and activities. It usually lasts for 3-8 weeks. It is one of the most common causes of subacute cough, accounting for 38.0%-66.5% of subacute cough. At present, Western medicine has not yet fully clarified the etiology and pathogenesis of post-infectious cough, and there is no specific diagnosis and treatment standard. It is believed that the disease is self-limiting, and mild cases can be left untreated. Severe cases are treated with antihistamines and antitussives or hormones. However, these drugs have many side effects, not only nausea, loss of appetite, dry mouth, constipation and other adverse reactions, but also easy to recur after stopping the drug, the overall efficacy is poor, and even develops into refractory cough, which has an impact on the patient's work and life that cannot be ignored.

[0003] Compound methoxyphenamine (prescription drug) is a first-line compound antitussive drug, which is commonly used in clinical treatment of post-infection cough. It is composed of methoxyphenamine hydrochloride, aminophylline, noscapine, and chlorpheniramine maleate. Among them, methoxyphenamine hydrochloride is a β2 receptor blocker; noscapine can inhibit cough caused by lung stretch reflex. Excessive doses will produce an effect of stimulating breathing, which will not stop coughing, but will aggravate cough symptoms; aminophylline can inhibit bronchospasm, reduce bronchial mucosal swelling, relieve cough, and make sputum easier to cough up, but it is easy to interact with many drugs; chlorpheniramine maleate is a histamine receptor antagonist with strong drowsiness side effects. This drug cannot be used in combination with other antitussive and expectorant drugs, anti-cold drugs, antihistamines, and sedatives. It has no obvious antipyretic effect on low-grade fever associated with post-infection cough, and its treatment has limitations.

[0004] Traditional Thai medicine believes that the human body is composed of four elements (earth, water, fire, and wind), and most diseases are caused by the imbalance of the four elements. "Samutthan Vinijchai" records that coughs are usually related to the imbalance of wind, fire, and water. "Wind" dominates the respiratory system. After infection, it may cause excessive activity of the wind element, causing persistent coughing; excessive "fire" may cause inflammation and heat in the body, aggravating cough symptoms; "Water" is the liquid part of the human body. It is distributed throughout the body through the wind element, which helps to control the balance of the fire element. Thai medicine prescribes and uses medicines based on the efficacy of the taste of the medicine and the imbalanced elements. "The Six Flavors of Thai Medical Diagnosis Classic" states: "Sweet, sour, and moist overcome wind, bitter, sweet, and astringent overcome fire, and pungent and bitter overcome water." Therefore, Thai medicine can use sweet, sour, moist, bitter, astringent, and pungent flavors to treat coughs after infection. The "Taiyi Classics·Ten Flavors" states: "Astringent is astringent, sweet is muscle-tonifying, toxic is detoxifying, bitter enters the blood, pungent is dispersing, moisturizing enters the tendons, fragrant is calming, salty enters the skin, sour is phlegm-resolving, and light is removing dampness"; the "Taiyi Materia Medica·Pharmaceuticals" states: "Pungent and hot are used to treat wind; pungent and sour are used to treat stagnation; sweet and cool are used to treat thirst." Therefore, the herbs selected by Thai medicine for the treatment of PIC have the following characteristics: sweet can nourish the muscles, sweet and cool can treat thirst, such as licorice; sour can resolve phlegm and treat stagnation, such as emblica; moisturizing can enter the tendons and strengthen the tendons and bones, such as Chuanxiong and costusroot; bitter can enter the blood, clear heat and promote fluid production, such as reed stems; astringent is astringent, such as terminalia chebula; pungent is dispersing and treats wind, such as dried tangerine peel and cloves. Modern research shows that many Thai cough medicines have pharmacological effects such as clearing heat, relieving cough, resolving phlegm, and anti-inflammatory, and have no obvious adverse reactions, and are unique in treating post-infectious cough.

[0005] Modern Chinese medicine experts classify PIC into the categories of "cough", "long-term cough" and "stubborn cough" according to the symptoms and characteristics of PIC's stubborn and irritating cough. They believe that the main pathogenesis of PIC is that the remaining pathogens are not completely eliminated and linger in the lungs, resulting in the failure of the lungs to descend, the cough not being cured, the loss of the lung's qi and yin, the deficiency of the lung's qi and yin, the inability to expel the pathogens, and the long-term cough not being cured. The corresponding treatment principle is to nourish yin and clear away heat, promote body fluid and stop cough. "Huangdi Neijing·Suwen·Kelun" says: "All the five internal organs and six bowels cause cough, not just the lungs", emphasizing that cough is not only a symptom of lung disease, but may also be caused by lesions of other internal organs. Therefore, in treatment, it is not limited to the use of drugs for the lung meridian, but should pay attention to syndrome differentiation and treatment. The history of TCM treatment of cough can be traced back to more than two thousand years ago. In practice, it has accumulated relatively rich theories and experience, and still has certain advantages for modern clinical treatment of cough. From the perspective of short-term effects, TCM treatment can alleviate symptoms, shorten the course of the disease, and has no obvious adverse reactions; from the perspective of long-term effects, TCM treatment can effectively adjust the patient's constitution and reduce the frequency of attacks, and has a good application prospect.

[0006] The understanding of the human body in traditional Thai medicine is different from that in Chinese medicine. For example, Thai medicine believes that the human body is composed of basic elements. Although the theories of Chinese and Thai medicine are not exactly the same, the understanding and application of herbal medicine are relatively similar. For example, the properties and flavors of the herbs selected by traditional Thai medicine for the treatment of cough can correspond to the four properties and flavors of Chinese medicine, including sour astringent and astringent, belonging to the liver meridian; bitter clears away heat and relieves qi reversal, belonging to the heart meridian; sweet tonic, harmonizes the medicinal properties, belonging to the spleen meridian; pungent dispersing, promoting qi and blood circulation, belonging to the lung meridian; astringent and sour medicines have similar effects, but sour is mainly astringent, while astringent is mainly astringent. It can be seen that the selection of prescriptions and drugs by Thai medicine is relatively close to that of Chinese medicine, and the taste of medicine will also be added or subtracted according to different symptoms. For example, for cough caused by wind-heat, Thai medicine will mainly choose bitter and astringent medicines, which is similar to the selection of heat-clearing and wind-removing medicines by Chinese medicine. There have also been examples of Chinese and Thai medicines being used together in the finished medicines registered by the Thai Food and Drug Administration. Therefore, the present invention proposes a pharmaceutical composition for treating post-infectious cough based on Chinese and Thai medical theories and provides a preparation method thereof. Summary of the invention

[0007] In view of the technical problems mentioned in the background technology, the present invention provides a pharmaceutical composition for treating post-infectious cough and a preparation method thereof.

[0008] The technical solution adopted by the present invention to solve its technical problem is:

[0009] A pharmaceutical composition for treating post-infectious cough, comprising the following raw materials in parts by weight:

[0010] 15-32 parts of reed stems and 15-24 parts of emblica.

[0011] As a further technical solution of the present invention, the raw materials also include 10-20 parts of mulberry leaves, 10-16 parts of terminalia chebula, 8-12 parts of tangerine peel and 5-10 parts of liquorice.

[0012] As a further technical solution of the present invention, the following raw materials are included in parts by weight:

[0013] 24 parts of reed stems, 12 parts of emblica fruits, 16 parts of mulberry leaves, 12 parts of terminalia chebula, 8 parts of dried orange peels and 8 parts of liquorice.

[0014] As a further technical solution of the present invention, the reed stem is one of reed stem and reed root or a mixture of the two.

[0015] Another object of the present invention is to provide a method for preparing a pharmaceutical composition for treating post-infectious cough, comprising the following steps:

[0016] The raw material components are weighed according to the ratio, and each raw material component is mixed with water and heated for leaching. The heating leaching includes decocting with high heat and then decocting with low heat, and the two leaching solutions are combined and concentrated to obtain the product.

[0017] As a further technical solution of the present invention, the weight ratio of the raw material components to water is 1:8-12.

[0018] As a further technical solution of the present invention, the time for decocting over high heat is 10-20 minutes, and the time for decocting over low heat is 30-40 minutes.

[0019] As a further technical solution of the present invention, the slow-cooking is repeated at least twice, and the liquid from each slow-cooking is combined; during the second slow-cooking, the amount of water added is 8-12 times the mass of the raw material components.

[0020] As a further technical solution of the present invention, before the raw materials are heated and soaked, the raw material components are soaked, and the soaking time is 20-40 minutes.

[0021] Beneficial effects of the present invention:

[0022] The invention provides a pharmaceutical composition for treating cough after infection. According to Thai medical theory, in the pharmaceutical composition, reed stems are cool in nature and can clear lung heat; emblica seeds are sour, astringent, bitter and cool, can relieve throat, moisten dryness and relieve cough; mulberry leaves are light and cool, can relieve fever, relieve throat and moisten dryness; terminalia chebula seeds are sour, astringent and bitter, can moisten throat and eliminate phlegm; tangerine peel is aromatic, bitter and slightly spicy, can promote qi and relieve depression; licorice is sweet and bitter, can moisten throat, relieve cough and eliminate phlegm; all the medicines are used together to clear lung heat, promote body fluid, relieve throat, eliminate phlegm and relieve cough. From the perspective of traditional Chinese medicine theory, in the pharmaceutical composition provided by the present invention, reed stems are sweet and cold, clear away heat and purge fire, promote fluid production and quench thirst, while emblica fructus is sweet, sour, astringent and cool, clears heat and cools blood, promotes fluid production and relieves cough. Reed and emblica fructus are used to clear heat and relieve cough, and are the main medicines; mulberry leaves are sweet, bitter and cold, clear the lungs and moisten dryness, that is, help to dispel heat evil; terminalia chebula is bitter, sour, astringent and flat, can astringe the lungs and relieve cough, reduce fire and relieve sore throat, and help relieve cough, and both are ministerial medicines; tangerine peel is bitter, pungent and warm, regulates qi, dries dampness and resolves phlegm, and is an adjuvant; licorice is sweet and flat, removes phlegm and relieves cough, and harmonizes various medicines, and is a guiding medicine; the whole formula has the effects of clearing heat and promoting fluid production, nourishing yin and moistening dryness, and removing phlegm and relieving cough.

[0023] Reed stems are tender stems of the grass family reed, and reed roots are rhizomes of reeds. The two come from the same plant and have similar effects. Reed stems are good at clearing lung heat, while reed roots are good at promoting fluid production and quenching thirst, with a slight emphasis on one. At present, there is no supply of reed stems in the drug market. In clinical practice, reed stems and reed roots are often mixed, or reed roots are used to replace reed stems. Therefore, the reed stems described in the pharmaceutical composition of the present invention are tender stems of the grass family reed, or rhizomes (reed roots) of reed, or a mixture of the two.

[0024] In the pharmaceutical composition, reed stems are non-toxic, reed roots, emblica, mulberry leaves, tangerine peel, and licorice are all included in the list of dual-purpose medicines and foods announced by the National Health Commission, and are dual-purpose medicines and foods. Terminalia chebula is one of the Chinese medicines that can be used as health foods announced by the National Health Commission; in 2021, the Thai Ministry of Health issued the "Plant Tea" Notice [Notification of the Ministry of Public Health, Thailand (No. 426) BE2564 (2021) Re: Tea Infusion], which stipulates that 201 plants can be used as tea, including emblica, mulberry leaves, licorice, etc. In summary, the pharmaceutical composition provided by the present invention is highly safe and can be taken with confidence.

[0025] The pharmaceutical composition (reed stem, emblica fruit, mulberry leaf, terminalia chebula, tangerine peel, liquorice) provided by the present invention has the effects of clearing away heat, promoting the production of body fluid, removing phlegm and relieving cough, and is safe and non-toxic, has no obvious adverse reactions, and has a good therapeutic effect on post-infectious cough. In addition, the decoction of the pharmaceutical composition has a slightly sour and sweet taste, is smooth in the throat, has no irritation, can be taken for a long time, and the preparation method is simple and easy to operate.

[0026] Animal experiments have shown that the pharmaceutical composition of the present invention has a significant antitussive effect, can take effect within 1 hour for LPS-induced fever, and continuously exerts a cooling effect, has a definite antipyretic and antipyretic effect, is fast-acting and strong, and has a significantly better effect than positive drugs; the pharmaceutical composition can not only significantly improve clinical symptoms, but also has outstanding advantages in enhancing the body's anti-inflammatory properties, and can reduce cough sensitivity by improving airway neurogenic inflammation; in addition, it also has a certain therapeutic effect on lung damage caused by PIC. BRIEF DESCRIPTION OF THE DRAWINGS

[0027] Figure 1 This is a diagram of the construction process of the PIC rat model in an embodiment of the present invention.

[0028] Figure 2 This is the rectal temperature of rats in each group 1 hour after LPS-induced fever on the 4th day.

[0029] Figure 3 This is the rectal temperature of rats in each group 3 hours after LPS-induced fever on the 4th day.

[0030] Figure 4 This is the rectal temperature of rats in each group 1 hour after LPS-induced fever on the 7th day.

[0031] Figure 5 This is the rectal temperature of rats in each group 3 hours after LPS-induced fever on the 7th day.

[0032] Figure 6 The cough times of rats in each group after administration on the 4th day.

[0033] Figure 7 This is the cough latency period of rats in each group after administration on the 4th day.

[0034] Figure 8 The cough times of rats in each group after administration on the 7th day.

[0035] Fig. 9 This is the cough latency period of rats in each group after administration on the 7th day.

[0036] Fig.10 is the total number of white blood cells in the blood of rats in each group.

[0037] Fig.11 is the percentage of neutrophils in the blood of rats in each group.

[0038] Fig.12 The lung tissue pathological morphology of rats in each group.

[0039] Fig.13 is the TNF-α content in BALF of rats in each group.

[0040] Fig.14 is the IL-8 content in BALF of rats in each group.

[0041] Fig.15 is the SP content in BALF of rats in each group.

[0042] Fig.16 is the CGRP content in BALF of rats in each group. DETAILED DESCRIPTION

[0043] In order to make the purpose, technical solution and advantages of the embodiments of the present invention clearer, the technical solution in the embodiments of the present invention will be clearly and completely described below in conjunction with the drawings in the embodiments of the present invention. Obviously, the described embodiments are part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0044] The present invention provides a pharmaceutical composition for treating post-infectious cough, which comprises the following raw materials in parts by weight:

[0045] 15-32 parts of reed stems and 15-24 parts of emblica.

[0046] In this embodiment, the raw materials further include 10-20 parts of mulberry leaves, 10-16 parts of terminalia chebula, 8-12 parts of dried tangerine peels and 5-10 parts of liquorice.

[0047] In this embodiment, the reed stem is one of reed stem and reed root, or a mixture of the two.

[0048] Another object of the present invention is to provide a method for preparing a pharmaceutical composition for treating post-infectious cough, comprising the following steps:

[0049] The raw material components are weighed according to the ratio, and each raw material component is mixed with water and heated for leaching. The heating leaching includes decocting with high heat and then decocting with low heat, and the two leaching liquids are combined and concentrated to obtain the product.

[0050] In this embodiment, the weight ratio of the raw material components to water is 1:8-12.

[0051] In this embodiment, the high heat decocting time is 10-20 minutes, and the low heat decocting time is 30-40 minutes.

[0052] In this embodiment, the slow-cooking is repeated at least twice, and the liquid from each slow-cooking is combined; during the second slow-cooking, the amount of water added is 8-12 times the mass of the raw material components.

[0053] In this embodiment, before the raw materials are heated and soaked, the raw material components are soaked, and the soaking time is 20-40 minutes.

[0054] Embodiment 1

[0055] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 30 g of reed stems and 20 g of emblica fruit; a preparation method for the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing the reed stems and emblica fruit, soaking them in water for 20 minutes, first decocting them over high heat for 20 minutes, then decocting them over low heat for 30 minutes, and filtering to obtain a medicinal liquid; the weight ratio of the raw material components to the water is 1:12; (b) adding water to the medicinal residue in step (a), first decocting them over high heat for 20 minutes, then decocting them over low heat for 30 minutes, collecting the two medicinal liquids, combining and concentrating them, and the amount of water added is 12 times the mass of the raw material components.

[0056] Embodiment 2

[0057] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 15 g of reed stems and 15 g of emblica fruit; a preparation method for the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing the reed stems and emblica fruit, soaking them in water for 30 minutes, first decocting them over high heat for 10 minutes, then decocting them over low heat for 30 minutes, and filtering to obtain a medicinal liquid; the weight ratio of the raw material components to water is 1:10; (b) adding water to the medicinal residue in step (a), first decocting them over high heat for 10 minutes, then decocting them over low heat for 30 minutes, collecting the two medicinal liquids, combining and concentrating them, and the amount of water added is 10 times the mass of the raw material components.

[0058] Embodiment 3

[0059] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 30 g of reed stems and 15 g of emblica fruit; a preparation method for the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing the reed stems and emblica fruit, soaking them in water for 40 minutes, first decocting them over high heat for 10 minutes, then decocting them over low heat for 40 minutes, and filtering to obtain a medicinal liquid; the weight ratio of the raw material components to water is 1:8; (b) adding water to the medicinal residue in step (a), first decocting them over high heat for 10 minutes, then decocting them over low heat for 40 minutes, collecting the two medicinal liquids, combining and concentrating them, and the amount of water added is 8 times the mass of the raw material components.

[0060] Embodiment 4

[0061] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 32 g of reed stems and 24 g of emblica; a preparation method for the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing the reed stems and emblica, soaking in water for 30 minutes, first decocting over high heat for 15 minutes, then decocting over low heat for 35 minutes, and filtering to obtain a medicinal liquid; the weight ratio of the raw material components to water is 1:10; (b) adding water to the medicinal residue in step (a), first decocting over high heat for 15 minutes, then decocting over low heat for 35 minutes, collecting the two medicinal liquids, combining and concentrating, and the amount of water added is 10 times the mass of the raw material components.

[0062] Embodiment 5

[0063] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 20 g of reed stem, 15 g of emblica fruit, 12 g of dried tangerine peel and 6 g of liquorice; a preparation method for the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing reed stem, emblica fruit and other drugs, soaking in water for 30 minutes, first decocting over high heat for 15 minutes, then decocting over low heat for 30 minutes, filtering to obtain a medicinal liquid; the weight ratio of the raw material components to water is 1:10; (b) adding water to the medicinal residue in step (a), first decocting over high heat for 15 minutes, then decocting over low heat for 30 minutes, collecting the two medicinal liquids, combining and concentrating, and the amount of water added is 10 times the mass of the raw material components.

[0064] Embodiment 6

[0065] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 24g of reed stem, 18g of emblica fruit, 12g of mulberry leaf, 10g of tangerine peel and 6g of liquorice; a preparation method of the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing reed stem, emblica fruit and other drugs, soaking in water for 30min, first decocting over high heat for 10min, then decocting over low heat for 30min, filtering to obtain a medicinal liquid; the weight ratio of the raw material components to water is 1:12; (b) adding water to the medicinal residue in step (a), first decocting over high heat for 10min, then decocting over low heat for 30min, collecting the two medicinal liquids, combining and concentrating, and the amount of water added is 12 times the mass of the raw material components.

[0066] Embodiment 7

[0067] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 30g of reed stem, 20g of emblica fruit, 20g of mulberry leaf, 15g of terminalia chebula, 10g of dried orange peel and 5g of liquorice; a preparation method of the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing reed stem, emblica fruit and other drugs, soaking in water for 20min, first decocting over high heat for 20min, then decocting over low heat for 30min, filtering to obtain a medicinal liquid; the weight ratio of the raw material components to water is 1:12; (b) adding water to the medicinal residue in step (a), first decocting over high heat for 20min, then decocting over low heat for 30min, collecting the two medicinal liquids, combining and concentrating, and the amount of water added is 12 times the mass of the raw material components.

[0068] Embodiment 8

[0069] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 15g of reed stem, 15g of emblica fruit, 10g of mulberry leaf, 10g of terminalia chebula, 10g of dried tangerine peel and 5g of liquorice; a preparation method of the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing drugs such as reed stem and emblica fruit, soaking in water for 30 minutes, first decocting over high heat for 10 minutes, then decocting over low heat for 30 minutes, filtering to obtain a medicinal liquid; the weight ratio of the raw material components to water is 1:10; (b) adding water to the medicinal residue in step (a), first decocting over high heat for 10 minutes, then decocting over low heat for 30 minutes, collecting the two medicinal liquids, combining and concentrating, and the amount of water added is 10 times the mass of the raw material components of the medicine.

[0070] Embodiment 9

[0071] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 24g of reed stem, 12g of emblica fruit, 12g of mulberry leaf, 8g of terminalia chebula, 8g of dried orange peel and 8g of liquorice; a preparation method of the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing reed stem, emblica fruit and other drugs, soaking in water for 40min, first decocting over high heat for 10min, then decocting over low heat for 40min, filtering to obtain a medicinal liquid; the weight ratio of the raw material components to water is 1:8; (b) adding water to the medicinal residue in step (a), first decocting over high heat for 10min, then decocting over low heat for 40min, collecting the two medicinal liquids, combining and concentrating, and the amount of water added is 8 times the mass of the raw material components.

[0072] Embodiment 10

[0073] A pharmaceutical composition for treating post-infectious cough, comprising the following raw material components: 32g of reed stem, 24g of emblica, 16g of mulberry leaf, 16g of terminalia chebula, 12g of dried tangerine peel and 10g of liquorice; a preparation method of the pharmaceutical composition for treating post-infectious cough, comprising the following steps: (a) mixing drugs such as reed stem and emblica, soaking in water for 30min, first decocting over high heat for 15min, then decocting over low heat for 35min, filtering to obtain a medicinal liquid; the weight ratio of the raw material components to water is 1:10; (b) adding water to the medicinal residue in step (a), first decocting over high heat for 15min, then decocting over low heat for 35min, collecting the two medicinal liquids, combining and concentrating, and the amount of water added is 10 times the mass of the raw material components.

[0074] Test example - drug efficacy study based on animal experiments

[0075] 1. Experimental Methods

[0076] 1.1. Modeling

[0077] Establishment of PIC rat model: 4-week-old male SD rats were placed in a homemade smoke box (40×40×40 cm) and smoked with 8 cigarettes once a day for 30 min each time for 10 consecutive days. The rats were free to eat and drink. On the 4th, 7th, and 10th days, the rats were anesthetized with isoflurane (6 h after smoking) and 0.4 mg mL -1 LPS solution (1 μL g -1 ). On days 5, 6, 8, and 9, rats were given 1×10 -4 mol / L capsaicin solution was atomized once a day for 3 minutes each time. On the 10th day, 2 hours after LPS nasal drops, the model rats were subjected to capsaicin cough stimulation test for verification. If the rats showed characteristic signs such as coughing, accelerated breathing, forward extension of the feet, forward extension of the neck, abdominal muscle contraction, and coughed more than 10 times within 3 minutes, the model was successfully established. Figure 1 shown.

[0078] 1.2. Grouping

[0079] After the rats were adaptively raised for 3 days, 6 rats were randomly selected as the blank group, and the remaining rats were modeled using the above method. After the model was successfully prepared, the rats were randomly divided into a model group, a positive drug group (compound methoxyphenamine suspension), a Chinese medicine composition group 1 (prepared according to Example 2), and a Chinese medicine composition group 2 (prepared according to Example 8).

[0080] 1.3. Drug administration

[0081] The equivalent dose of rats was calculated based on the body surface area according to the second edition of "Experimental Methodology of Traditional Chinese Medicine Pharmacology" and related literature. From the 11th day, oral gavage was started at a dose of 10 mL / kg / d. Each medication group was given the corresponding drug, and the blank group and model group were given an equal volume of normal saline once a day for 7 consecutive days.

[0082] 1.4. Detection indicators and methods

[0083] 1.4.1. Rectal temperature detection

[0084] On the 14th and 17th days, LPS was dripped into the nose of the rats 1 hour after administration, and the rectal temperature of each group was measured 1 hour and 3 hours after the drip, and the data were recorded.

[0085] 1.4.2. Determination of cough frequency and cough latency

[0086] After rectal temperature detection on the 14th and 17th days, capsaicin cough provocation test was performed, and the cough latency and the number of coughs within 5 minutes of each group of rats were recorded.

[0087] 1.4.3. Obtaining materials

[0088] On the 18th day, the rats were anesthetized and the samples were collected. ① After anesthesia, blood was collected from the abdominal aorta for routine blood tests. ② Bronchoalveolar lavage fluid (BALF): The left main bronchus was ligated, and 0.9% sodium chloride injection was slowly injected into the right lung through the right main bronchus. After withdrawal, it was slowly injected again, and repeated 3 times; after collecting BALF, it was centrifuged at 4°C, 3000r / min for 10min, the supernatant was collected, and frozen at -80°C for later use. ③ The left lower lobe was taken, fixed with 4% paraformaldehyde, embedded in conventional paraffin, and sectioned for HE staining.

[0089] 1.4.4. Routine blood test

[0090] A blood cell analyzer was used to perform routine blood tests and determine the total white blood cell count (WBC) and neutrophil percentage (NE%) of rats in each group.

[0091] 1.4.5. Pathological observation of lung tissue

[0092] The lung tissue lesions and inflammatory cell infiltration of rats in each group were observed under an optical microscope.

[0093] 1.4.6. Detection of cytokine and neuropeptide expression in BALF

[0094] The levels of TNF-α, IL-8, SP, and CGRP in BALF of rats in each group were detected according to the instructions of the ELISA kit.

[0095] 2. Experimental results

[0096] 2.1. Effect of Chinese herbal medicine composition on rectal temperature of PIC rats.

[0097] like Figure 2-5 As shown, Figure 2 The rectal temperature of rats in each group after LPS-induced fever for 1 hour after administration on the 4th day was compared with that of the blank group. ### P<0.001; compared with the model group, * P<0.05, *** P<0.001. Figure 3 The rectal temperature of rats in each group 3 hours after LPS-induced fever on the 4th day. Figure 3 Compared with the blank group, ### P<0.001; compared with the model group, * P<0.05. Figure 4 The rectal temperature of rats in each group 1 hour after LPS-induced fever on the 7th day. Figure 4 Compared with the blank group, ### P<0.001; compared with the model group, *** P<0.001. Figure 5 The rectal temperature of rats in each group induced by LPS for 3 hours after administration on the 7th day. Figure 5 Compared with the blank group, ### P<0.001; compared with the model group, *** P<0.001.

[0098] from Figure 2-5 The results show that: for LPS-induced fever, the Chinese medicine composition of the present invention can take effect within 1 hour and continue to play a cooling effect, has a definite antipyretic and antipyretic effect, has a fast and strong effect, and the effect is significantly better than that of positive drugs.

[0099] 2.2. Effect of Chinese herbal medicine combination on cough sensitivity in PIC rats

[0100] like Figure 6-9 As shown, Figure 6 is the number of coughs of rats in each group after administration on the 4th day. Figure 6 Compared with the blank group, ### P<0.001; compared with the model group, * P<0.05, *** P<0.001. Figure 7is the cough latency of rats in each group after administration on the 4th day. Figure 7 Compared with the blank group, ### P<0.001; compared with the model group, ** P<0.01, *** P<0.001. Figure 8 is the coughing frequency of rats in each group after administration on the 7th day. Figure 8 Compared with the blank group, ### P<0.001; compared with the model group, * P<0.05, *** P<0.001. Fig. 9 is the cough latency of rats in each group after administration on the 7th day. Fig. 9 Compared with the blank group, ### P<0.001; compared with the model group, *** P<0.001.

[0101] from Figure 6-9 The results show that the Chinese medicine compositions 1 and 2 of the present invention have significant therapeutic effects on cough induced by capsaicin solution atomization. The frequency of coughing in rats can be significantly reduced on the 4th day of administration, and the number of coughing continues to decrease after 7 days of administration. Chinese medicine composition 2 can also significantly prolong the latent period of coughing in rats. In summary, it is proved that the pharmaceutical composition of the present invention has a significant antitussive effect.

[0102] 2.3. Effect of Chinese herbal medicine combination on total white blood cell count and neutrophil percentage in PIC rats

[0103] like Figure 10-11 As shown, Fig.10 is the total number of white blood cells in the blood of rats in each group, compared with the blank group, ### P<0.001; compared with the model group, *** P<0.001. Fig.11 is the percentage of neutrophils in the blood of rats in each group, compared with the blank group, ### P<0.001; compared with the model group, ** P<0.01, *** P<0.001.

[0104] The total white blood cell count (WBC) is an important indicator of infection and inflammatory response. Studies have shown that the level of WBC is correlated with the presence of cough after infection, which to some extent reflects the degree of inflammatory response. The inflammatory nature of PIC is mainly characterized by an increase in neutrophils (NE).

[0105] From the above results, it can be seen that compared with the blank group, the WBC in the model group increased significantly, and the NE% increased significantly; compared with the model group, the total white blood cell count in the Chinese medicine combination group decreased significantly, and the neutrophil percentage increased, indicating that the pharmaceutical composition of the present invention has a good inhibitory effect on PIC inflammatory response.

[0106] 2.4. Effect of Chinese medicine composition on lung tissue morphology of PIC rats.

[0107] like Fig.12 As shown, Fig.12 The pathological morphology of lung tissues of rats in each group. Fig.12 In the figure, A. normal group; B. model group; C. positive drug group; D. Chinese medicine composition group 1; E. Chinese medicine composition group 2.

[0108] The lung tissue of rats in the blank group was basically normal, the alveolar wall structure was intact, irregular vacuolar structures were visible, and there were no obvious pathological changes. Compared with the blank group, the alveolar wall in the model group was thickened, the distance between alveoli was significantly widened, and the vacuolar structure was reduced; a large number of inflammatory cells, mainly neutrophil hyperplasia, infiltrated; the bronchial mucosal epithelium fell off in pieces, and the tracheal wall thickened. After treatment with the Chinese medicine composition, the above pathological damage was significantly improved compared with the model group, the alveolar distance was reduced, the tracheal wall thickening was reduced, epithelial cells occasionally fell off, and inflammatory cells were scattered infiltrated, indicating that the pharmaceutical composition of the present invention has a certain therapeutic effect on lung injury caused by PIC.

[0109] 2.5. Effects of Chinese herbal medicine combination on cytokine and neuropeptide levels in BALF of PIC rats

[0110] like Figure 13-16 As shown, Fig.13 is the content of TNF-α in BALF of rats in each group, compared with the blank group, ### P<0.001; compared with the model group, ** P<0.01, *** P<0.001. Fig.14 is the IL-8 content in BALF of rats in each group, compared with the blank group, ### P<0.001; compared with the model group, * P<0.05, *** P<0.001. Fig.15 is the SP content in BALF of rats in each group, compared with the blank group, ### P<0.001; compared with the model group, ** P<0.01, *** P<0.001. Fig.16 is the CGRP content in BALF of rats in each group, compared with the blank group, ### P<0.001; compared with the model group, ***P<0.001.

[0111] It is generally believed that the pathogenesis of PIC is related to inflammatory response. After the pathogen invades the body and is recognized, it causes an immune response, and the body releases cytokines, inducing inflammatory response. Increased cytokines can directly stimulate the receptors to cause cough, and can also cause airway epithelial cell damage, airway hyperresponsiveness, and cough hypersensitivity to indirectly cause cough. Among them, TNF-α and IL-8 are most closely related to the formation of inflammatory response.

[0112] Increased cough sensitivity is also the main cause of PIC, and airway neurogenic inflammation is an important factor causing increased cough sensitivity. Airway neurogenic inflammation characterized by increased neuropeptide substance P (SP) and calcitonin gene-related peptide (CGRP) is an important feature of PIC.

[0113] like Figure 13-16 As shown in the results, compared with the blank group, the inflammatory factors TNF-α, IL-8 and cough-related factors SP and CGRP in the BALF of the model group were significantly increased. Compared with the model group, the levels of TNF-α, IL-8, SP and CGRP in the Chinese medicine composition group were reduced to varying degrees, indicating that the pharmaceutical composition of the present invention has a good therapeutic effect on inflammatory reactions and airway neurogenic inflammation.

[0114] It should be noted that, in this article, the terms "include", "comprises" or any other variations thereof are intended to cover non-exclusive inclusion, so that a process, method, article or device including a series of elements includes not only those elements, but also other elements not explicitly listed, or also includes elements inherent to such process, method, article or device. In the absence of further restrictions, an element defined by the sentence "comprises a ..." does not exclude the existence of other identical elements in the process, method, article or device including the element.

[0115] The above are only preferred embodiments of the present invention, and are not intended to limit the patent scope of the present invention. Any equivalent structure or equivalent process transformation made using the contents of the present invention specification and drawings, or directly or indirectly applied in other related technical fields, are also included in the patent protection scope of the present invention.

Claims

1. A pharmaceutical composition for treating post-infectious cough, characterized in that: According to weight parts, it includes the following raw materials: 15-32 parts of reed stems and 15-24 parts of emblica.

2. A pharmaceutical composition for treating post-infectious cough according to claim 1, characterized in that: The raw materials also include 10-20 parts of mulberry leaves, 10-16 parts of terminalia chebula, 8-12 parts of dried tangerine peels and 5-10 parts of liquorice.

3. A pharmaceutical composition for treating post-infectious cough according to claim 2, characterized in that: According to weight parts, it includes the following raw materials: 24 parts of reed stems, 12 parts of emblica fruits, 16 parts of mulberry leaves, 12 parts of terminalia chebula, 8 parts of dried orange peels and 8 parts of liquorice.

4. A pharmaceutical composition for treating post-infectious cough according to claim 3, characterized in that: The reed stems are one of reed stems and reed roots or a mixture of the two.

5. A method for preparing a pharmaceutical composition for treating post-infectious cough according to any one of claims 1 to 4, characterized in that: The following steps are involved: The raw material components are weighed according to the ratio, and each raw material component is mixed with water and heated for leaching. The heating leaching includes decocting with high heat and then decocting with low heat, and the two leaching solutions are combined and concentrated to obtain the product.

6. The method for preparing a pharmaceutical composition for treating post-infectious cough according to claim 5, characterized in that: The weight ratio of the raw material components to water is 1:8-12.

7. The method for preparing a pharmaceutical composition for treating post-infectious cough according to claim 5, characterized in that: The time for decocting over high heat is 10-20 minutes, and the time for decocting over low heat is 30-40 minutes.

8. The method for preparing a pharmaceutical composition for treating post-infectious cough according to claim 5, characterized in that: The slow-fire decoction is repeated at least twice, and the liquid from each slow-fire decoction is combined; during the second slow-fire decoction, the amount of water added is 8-12 times the mass of the raw material components.

9. The method for preparing a pharmaceutical composition for treating post-infectious cough according to claim 5, characterized in that: Before the raw materials are heated and soaked, the raw material components are soaked for 20-40 minutes.

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