A Chinese medicine composition and its preparation and application

Abstract

The present invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for treating post-infectious cough, which is prepared from 5-10 parts of stemonae, 3-9 parts of tuckahoe, 5-10 parts of loquat leaves, 5-10 parts of aster, 10-18 parts of dwarf tea, 5-10 parts of burdock seeds, 3-9 parts of ephedra, 3-9 parts of white peony root, and 1-5 parts of liquorice. The present invention also provides a traditional Chinese medicine compound preparation for treating post-infectious cough, a preparation method thereof, and an application thereof.

Description

Technical Field

[0001] The invention belongs to the technical field of traditional Chinese medicines, and in particular relates to a traditional Chinese medicine composition for treating post-infectious cough, and a preparation and application thereof. Background Art

[0002] Postinfectious cough (PIC) is a cough caused by a cold, in which the acute symptoms have disappeared but the cough is delayed and does not heal. It is self-limiting and the course of the disease usually does not exceed 2 months. After the acute symptoms of a cold disappear, the human body still has a "stubborn cough and a long cough". If the cough persists and does not heal, it will cause trouble to daily life and work. Many patients have a course of illness for several months or even years, which seriously interferes with their normal work, life and study. Western medicine currently mainly uses centrally acting antitussive drugs, oral or nebulized inhaled hormones, the use of antihistamine receptor antagonists, compound preparations and other methods for treatment, but there are still the following problems: (1) The diagnostic procedure is complicated and the cost is high, which increases the financial burden on patients; (2) The large-scale use of antibiotics leads to abuse; (3) There is a lack of effective and safe treatment plans, and the drugs have the risk of excessive side effects.

[0003] The name of cough can be found in Neijing for the earliest time. Suwen points out that cough is caused by "the skin and fur are first affected by evil spirits" and "all the internal organs and six bowels cause cough, not just the lungs". It emphasizes that the pathogenesis should be that the six external evils of cold, heat, dryness, dampness, wind and fire invade the lung system or the internal organs are dysfunctional, resulting in internal injury of the lung system, the lungs lose their ability to descend, and thus the lung qi goes up, impacting the airway and causing cough. Modern Chinese medicine experts believe that post-infectious cough should be classified as "long-term cough and stubborn cough" in Chinese medicine after combining the clinical symptoms of cough. Although the symptoms have been resolved, the external evil has not been eliminated, and the lung's descending function is dysfunctional, so the cough is prolonged and unhealed. Many Chinese medicines have extremely high pharmacological effects such as antiviral, antitussive, phlegm-resolving and lung-moistening, and anti-inflammatory. Traditional Chinese medicine has the advantages of definite efficacy, no obvious adverse reactions, and can be taken for a long time in the treatment of post-infectious cough, and has good application prospects. Summary of the invention

[0004] The purpose of the present invention is to provide a traditional Chinese medicine composition for treating post-infectious cough and its preparation and application.

[0005] The first aspect of the present invention provides a traditional Chinese medicine composition for treating post-infectious cough, which is prepared from the following raw materials in parts by weight: 5-10 parts of Stemona, 3-9 parts of Poria, 5-10 parts of Loquat Leaves, 5-10 parts of Aster, 10-18 parts of Camellia Sinensis, 5-10 parts of Burdock Fruit, 3-9 parts of Ephedra, 3-9 parts of White Peony Root, and 1-5 parts of Licorice.

[0006] In a preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 7-9 parts of Stemona, 4-7 parts of Poria, 7-9 parts of Loquat Leaves, 6-9 parts of Aster, 13-17 parts of Camellia Sinensis, 7-9 parts of Burdock Fruit, 5-7 parts of Ephedra, 5-7 parts of White Peony Root, and 2-4 parts of Licorice.

[0007] In a preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 5 parts of Stemona, 9 parts of Poria, 10 parts of Loquat Leaves, 6 parts of Aster, 10 parts of Camellia Sinensis, 5 parts of Burdock Fruit, 9 parts of Ephedra, 3 parts of White Peony Root, and 2 parts of Licorice.

[0008] In another preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 10 parts of Stemona, 7 parts of Poria, 7 parts of Eriobotrya japonica, 5 parts of Aster tataricus, 13 parts of Camellia ternata, 8 parts of Burdock, 7 parts of Ephedra, 5 parts of White Peony Root, and 5 parts of Licorice.

[0009] In another preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 9 parts of Stemona, 6 parts of Poria, 9 parts of Eriobotrya japonica, 9 parts of Eriobotrya japonica, 9 parts of Aster tataricus, 15 parts of Camellia ternata, 9 parts of Burdock fruit, 6 parts of Ephedra, 6 parts of White Peony Root, and 3 parts of Licorice.

[0010] In another preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 7 parts of Stemona, 4 parts of Poria, 8 parts of Eriobotrya japonica, 10 parts of Aster, 18 parts of Camellia ternata, 10 parts of Burdock, 5 parts of Ephedra, 7 parts of White Peony Root, and 1 part of Licorice.

[0011] In another preferred example, the Chinese medicine composition is made of the following raw materials in parts by weight: 8 parts of Stemona, 3 parts of Poria, 5 parts of Eriobotrya japonica, 7 parts of Aster, 17 parts of Camellia ternata, 7 parts of Burdock, 3 parts of Ephedra, 9 parts of White Peony Root, and 4 parts of Licorice.

[0012] The second aspect of the present invention is to provide a Chinese medicine compound preparation for treating post-infectious cough, wherein the Chinese medicine compound preparation is a decoction, granules, capsules, tablets, oral liquid or syrup with the above Chinese medicine composition as an active ingredient.

[0013] In a preferred embodiment, the Chinese medicine compound preparation is a granule.

[0014] The present invention also provides application of the Chinese medicine composition in preparing medicine for treating post-infectious cough.

[0015] The details of various aspects of the present invention will be described in detail in the following sections. The features, objectives and advantages of the present invention will become more apparent through the following description and the claims. DETAILED DESCRIPTION

[0016] The Chinese medicinal materials used by the inventors in the process of preparing the pharmaceutical composition of the present invention have the following sources: Stemona, the dried tubers of Stemona erecta (Miq.) Miq., Stemona ajaponica (Bl.) Miq. or Stemona tuberosa Lour. of the Stemonaceae family. Poria, the dried sclerotium of the fungus Poria cocos (Schw.) Wolf of the Polyporaceae family. Loquat leaves, the dried leaves of Eriobotrya japonica (Thunb.) Lindl. of the Rosaceae family. Aster, the dried roots and rhizomes of Aster tataricus Lf of the Asteraceae family. Dwarf tea, the dried whole herb of Ardisia japonica (Thunb.) Blume of the Myrsinaceae family. Arctium lappa, the dried mature fruit of Arctium lapppa L. of the Asteraceae family. Ephedra, the dried herbaceous stems of Ephedra sinicaStapf, Ephedra intermediaSchrenk et CAMey. or Ephedra equisetinaBge. of the Ephedraceae family. White peony, the dried root of Paeonialactiflora Pall. of the Ranunculaceae family. Licorice, the dried roots and rhizomes of Glycyrrhiza uralensisFisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabraL. of the Leguminosae family.

[0017] Based on many years of clinical practice experience, the inventor believes that the six exogenous pathogens can all become the pathogenic factors of this disease. Cough after infection belongs to the category of "long-term cough and stubborn cough" in traditional Chinese medicine. Although the superficial symptoms have been resolved, the exogenous pathogens have not been eliminated, and the lung's descending function is disordered, so the cough is prolonged and unhealed. The Chinese medicine composition of the present invention contains a total of ten Chinese medicines. Among them, Stemona is the main medicine, moistening the lungs and relieving cough. Ayam tea resolves phlegm and relieves cough, clears dampness and heat; loquat leaves clear the lungs and relieve cough, descend the adverse and stop vomiting; Aster moistens the lungs and relieves qi, eliminates phlegm and relieves cough; Poria strengthens the spleen and promotes water, cultivates the soil and produces gold; the above four flavors are all ministers, helping the main medicine to enhance the antitussive effect. Ephedra sweats and dispels cold, promotes lung and relieves asthma, and disperses the wind evil that clings to the lungs. Burdock seeds disperse wind and heat, promote lung and detoxify and relieve throat, and enhance the effect of dispersing wind evil together with ephedra; white peony nourishes blood and regulates menstruation, restrains yin and stops sweating to prevent ephedra from dispersing too much, and the above three flavors are all adjuvants. Licorice nourishes the spleen and replenishes qi, clears away heat and detoxifies, removes phlegm and relieves cough, and harmonizes various medicines. At the same time, most of the ingredients in the prescription are honey-roasted slices, which can replenish qi and regulate the middle and enhance the cough-relieving effect. The combination of various medicines has the effects of moistening the lungs, resolving phlegm, relieving cough, clearing heat, and strengthening the spleen, with both attack and supplement, so as to achieve the functions of clearing dampness and heat, moistening the lungs, resolving phlegm and relieving cough.

[0018] The pharmaceutical composition of the present invention can be prepared according to the conventional method in the art, for example: add 10 times the amount of water to nine herbs such as Stemona tuberosa, boil them twice, each time for 1.5 hours, filter, combine the filtrate, and concentrate the filtrate under reduced pressure to a clear paste; centrifuge, and continue to concentrate the supernatant under reduced pressure to an extract with a relative density of 1.20 to 1.30, and dry it to obtain the extract.

[0019] The Chinese medicine composition of the present invention is easy to use, has a definite curative effect, has little side effects, is low in cost, can be taken for a long time, and has good clinical curative effect for treating post-infectious cough. In view of the long course of the disease, even up to several months or even several years, it seriously interferes with the daily life of the patient. At present, the therapeutic effects of hormones, antihistamines and the like are different, and there are limitations such as complicated diagnostic procedures, high costs and large side effects, so the Chinese medicine composition of the present invention has good clinical application prospects.

[0020] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are intended only to illustrate the present invention and are not intended to limit the scope of the present invention. The experimental methods in the following examples without specifying specific conditions are usually performed under normal conditions or according to the conditions recommended by the manufacturer. Unless otherwise stated, all percentages, ratios, proportions, or parts are by weight.

[0021] Unless otherwise defined, all professional 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 methods of the present invention. The preferred implementation methods and materials described herein are for demonstration purposes only.

[0022] The above features mentioned in the present invention or the features mentioned in the embodiments can be combined in any way. All the features disclosed in this patent specification can be used in combination with any combination form, and each feature disclosed in the specification can be replaced by any alternative feature that can provide the same, equal or similar purpose. Therefore, unless otherwise specified, the disclosed features are only general examples of equal or similar features.

[0023] Embodiment 1

[0024] Take 5g of Stemona, 9g of Poria, 10g of Loquat Leaf, 6g of Aster, 10g of Camellia Sinensis, 5g of Burdock Fructus, 9g of Ephedra, 3g of White Peony Root, and 2g of Licorice.

[0025] The preparation method is as follows: add 10 times the amount of water to nine herbs including Stemona bulbs, decoct twice, each time for 1.5 hours, filter the decoction, and concentrate the filtrate under reduced pressure to a clear paste; centrifuge, and continue to concentrate the supernatant under reduced pressure to an extract with a relative density of 1.20 to 1.30, dry, add auxiliary materials to granulate, and the extract is obtained.

[0026] The method of administration is as follows: dissolve the granules in water and administer orally.

[0027] Embodiment 2

[0028] Take 10g of Stemona, 7g of Poria, 7g of Loquat Leaf, 5g of Aster, 13g of Camellia Sinensis, 8g of Burdock Fructus, 7g of Ephedra, 5g of White Peony Root, and 5g of Licorice.

[0029] The preparation method and administration method are the same as in Example 1.

[0030] Embodiment 3

[0031] Take 9g of Stemona, 6g of Poria, 9g of Loquat Leaf, 9g of Aster, 15g of Camellia Sinensis, 9g of Burdock Fructus, 6g of Ephedra, 6g of White Peony Root, and 3g of Licorice.

[0032] The preparation method and administration method are the same as in Example 1.

[0033] Embodiment 4

[0034] Take 7g of Stemona, 4g of Poria, 8g of Loquat Leaf, 10g of Aster, 18g of Camellia Sinensis, 10g of Burdock Fructus, 5g of Ephedra, 7g of White Peony Root, and 1g of Licorice.

[0035] The preparation method and administration method are the same as in Example 1.

[0036] Embodiment 5

[0037] Take 8g of Stemona, 3g of Poria, 5g of Loquat Leaf, 7g of Aster, 17g of Camellia Sinensis, 7g of Burdock Fructus, 3g of Ephedra, 9g of White Peony Root, and 4g of Licorice.

[0038] The preparation method and administration method are the same as in Example 1.

[0039] Example 6 Animal experiment on the treatment of post-infectious cough with a Chinese medicine composition

[0040] Experimental animals: SD rats

[0041] Experimental drugs: The Chinese medicine composition was prepared according to Example 3. Experimental methods: 4-week-old, male, SD rats were used as model animals. After one week of adaptive feeding, they were randomly divided into a normal group, a model group, and a medication group. The animals were placed in a whole-body exposure atomization system and ventilated at a certain airflow rate. A metal fumigation box (sawdust cigarette) was placed in the exposure box and ignited for fumigation. The smoke was smoked for 60 minutes every day for 12 consecutive days. The normal group was only ventilated without smoke stimulation. After the fumigation, the rats were weighed. On the 12th, 13th, 14th, 16th, and 19th days, except for the rats in the normal group, the rest of the rats were lightly anesthetized and dripped with 0.4mg / ml lipopolysaccharide (LPS) solution through the nose. The administration volume was 10μl / 10g, and the normal group was replaced with physiological saline. Starting from the 14th day, each group of rats was gavage-administered according to the experimental design every day for 7 consecutive days. At the same time, the rats were placed in a transparent and closed exposure box on the 14th, 15th, 17th, 18th, and 20th days for 10-4 mol / L capsaicin solution was sprayed at an output atomization rate of 0.037 ml / min to stimulate cough, 15 min each time, once a day. The number of coughs and cough latency were recorded when stimulating cough on the 14th and 20th days.

[0042] The specific observation and inspection indicators during the test include the following:

[0043] (1) Cough frequency and cough latency

[0044] On the first day (14d) and the last day (20d) of oral administration, the rats were placed in a transparent closed exposure box 1 hour after administration and inhaled with a 10-4 mol / L capsaicin solution to induce coughing for 15 minutes. After the spraying was completed, the aerosol in the exposure box was evacuated for the first 2 minutes. Two minutes later, the time of the first cough (cough latency) and the number of coughs within 15 minutes were observed.

[0045] (2) Bronchoalveolar lavage fluid cytology

[0046] The left lung of the rat was ligated with a thread, and a 1 ml syringe was connected to the endotracheal tube. 1 ml of normal saline was injected each time for perfusion. The normal saline was withdrawn and collected. The perfusion and extraction were repeated 3 times. Part of the alveolar lavage fluid was taken for detection of the total white blood cell count, neutrophil ratio, eosinophil ratio, lymphocyte ratio, etc. using an automatic cell biochemical detector.

[0047] (3) Detection of cytokine and neuropeptide expression in bronchoalveolar lavage fluid

[0048] After the last administration and the completion of the cough test, the rats in each group were deeply anesthetized, and the alveolar lavage fluid was obtained. The lavage fluid was stored at -80°C, and the ELISA kit method was subsequently used to detect the expression levels of cytokines (IL-4, IFN-γ, TNF-α) and neuropeptides (SP, NKA, CGRP) in the alveolar lavage fluid.

[0049] (4) Lung tissue pathology

[0050] After bronchoalveolar lavage, the ligature was cut off, and the lung tissues of rats in each group were quickly removed and weighed to calculate the organ coefficient. Then, the right upper lobe lung tissue was trimmed and the appropriate-sized tissue blocks from the same part of the lung were uniformly taken and fixed overnight in 10% paraformaldehyde. The sections were embedded in paraffin and stained with H&E. The morphological structure and inflammatory cell infiltration of the lungs and trachea were observed under a light microscope.

[0051] Statistical methods: SPSS 21.0 for Windows statistical software was used for statistical analysis. One-way-classification ANOVA was used for quantitative data, and t-test was used for pairwise comparison. P < 0.05 was used as the criterion for statistically significant difference. Count data were expressed by rate and composition ratio, and x-test was used for comparison. 2 P < 0.05 was considered as the criterion for statistical significance.

[0052] Experimental results: As shown in Table 1, after 7 days of continuous administration, the capsaicin solution stimulated rats to cough. Compared with the model group, the Chinese medicine composition could significantly reduce the number of coughs (P < 0.01).

[0053] As shown in Table 2: 20 days after the establishment of the post-infection cough model rats, the alveolar lavage fluid was collected for cytological detection. Compared with the rats in the normal group, the white blood cell count (WBC) (P < 0.01), neutrophil count (NEUT) (P < 0.01), lymphocyte count (LYMPH) (P < 0.01) and monocyte count (MONO) (P < 0.05) of the model group rats were significantly increased. At the same time, the lymphocyte ratio (LYMPH%) (P < 0.05) in the alveolar lavage fluid of the model group rats was significantly reduced. After 7 days of administration of the Chinese medicine composition, compared with the model group, the Chinese medicine composition significantly downregulated the white blood cell count (WBC) (P < 0.05), neutrophil count (NEUT) (P < 0.05) and lymphocyte count (LYMPH) (P < 0.05) in the alveolar lavage fluid.

[0054] As shown in Table 3: Compared with the rats in the normal group, the inflammatory factor IFN-γ (P < 0.05) in the bronchoalveolar lavage fluid of the rats in the model group was significantly reduced, IL-4 (P < 0.001) and TNF-α (P < 0.01) were significantly increased; cough-related factors SP (P < 0.01), CGRP1 (P < 0.05) and NKA (P < 0.01) were significantly increased. After 7 days of treatment with the Chinese medicine composition, the level of inflammatory factor IL-4 in the bronchoalveolar lavage fluid of the rats with cough model after infection was significantly reduced (P < 0.01), and the level of IFN-γ was significantly increased (P < 0.05); the levels of cough-related factors CGRP1 (P < 0.05) and SP (P < 0.01) were significantly reduced.

[0055] Pathological histological examination showed that the model group animals had mild to mild degeneration / necrosis of small bronchial mucosal epithelial cells (12 / 12), mild to mild interstitial monomorphonuclear cell infiltration (12 / 12), and mild to moderate alveolar macrophage aggregation (12 / 12) in the lungs compared with the normal group. Although some animals in the normal group also had the above lesions, the model animals had more pathological changes and more severe lesions. It is considered that the above changes are related to modeling. Compared with the model group, the Chinese medicine combination group had similar lesion levels and numbers of small bronchial mucosal epithelial cells degeneration / necrosis and interstitial monomorphonuclear cell infiltration in each group, but the degree of alveolar macrophage aggregation in the lungs of rats in the Chinese medicine combination group was reduced.

[0056] The above test results show that under the present test conditions, the Chinese medicine composition has an antitussive effect on SD rats with post-infection cough.

[0057] Table 1 Results of cough latency and cough frequency

[0058]

[0059] Note: Compared with the normal group, * Indicates P < 0.05; ** Indicates P < 0.01.

[0060] Compared with the model group, # Indicates P < 0.05; ## Indicates P < 0.01.

[0061] Table 2 Cytological examination of bronchoalveolar lavage fluid

[0062]

[0063] Note: Compared with the normal group, * indicates P < 0.05; ** indicates P < 0.01.

[0064] Compared with the model group, # indicates P < 0.05.

[0065] Table 3 Detection of inflammatory factors and cough factors in lung lavage fluid

[0066]

[0067] Note: Compared with the normal group, * indicates P < 0.05; ** indicates P < 0.01.

[0068] Compared with the model group, # indicates P < 0.05; ## indicates P < 0.01.

[0069] Example 7 Comparative Study of Chinese Medicine Composition and Literature Prescription

[0070] Experimental animals: SPF guinea pigs

[0071] Experimental drugs: Chinese medicine composition prepared according to Example 3

[0072] Literature prescription: Platycodon grandiflorum, ephedra, aster, stemona, radix scutellariae, apricot kernel, dwarf tea, houttuynia cordata, loquat leaf. Prepared according to the method disclosed in the literature (a pharmaceutical composition for treating cough and asthma, its preparation method and use - 201710486890.5).

[0073] Experimental methods: After the animal adaptability observation, the guinea pigs were randomly divided into a normal group, a model group, a Chinese medicine combination group, and a literature prescription group. The guinea pigs in the model group, the Chinese medicine combination group, and the literature prescription group were all subjected to a post-infection cough model by aerosol inhalation of citric acid. The modeling method was as follows: the guinea pigs were placed in a whole-body aerosol exposure system, and a 17.5% volume fraction citric acid solution was sprayed at a speed of 5L / min for 6min. The guinea pigs in the Chinese medicine combination group and the literature prescription group were given the corresponding drugs by gavage, and the normal group and the model group were given distilled water once a day for 7 consecutive days. One hour after the last administration, the guinea pigs in the model group, the Chinese medicine combination group, and the literature prescription group were placed in a whole-body aerosol exposure system, and a 17.5% volume fraction citric acid solution was sprayed at a speed of 5L / min for 6min. The incubation period of coughing in the guinea pigs and the number of coughs within 6min were observed and recorded.

[0074] Statistical methods: SPSS 21.0 for Windows statistical software was used for statistical analysis. Count data were expressed by rate and composition ratio, and x 2 P < 0.05 was considered as the criterion for statistical significance.

[0075] Experimental results: As shown in Table 4, after 7 days of continuous administration, compared with the model group, the Chinese medicine combination and the literature prescription significantly reduced the number of coughs and prolonged the cough latency, and there was a statistical difference (P < 0.01). The cough suppression rate of the Chinese medicine combination and the literature prescription reached more than 50%, but compared with the literature prescription, the Chinese medicine combination had a more significant effect in reducing the number of coughs and prolonging the cough latency, and the cough suppression rate was also higher, proving that the treatment effect of the Chinese medicine combination is better than that of the literature prescription.

[0076] Table 4 Results of guinea pig cough latency and cough frequency within 6 minutes

[0077]

[0078] Note: Compared with the normal group, * indicates P < 0.05; ** indicates P < 0.01.

[0079] Compared with the model group, the drug group#" , means P<0.05," ##" Indicates P<0.01.

[0080] Example 8 Comparative Study of Chinese Medicine Combination and Separated Prescriptions

[0081] Experimental animals: SPF Hartley guinea pigs

[0082] Experimental drugs: Chinese medicine composition prepared according to Example 3

[0083] The composition of prescription 1: Poria 6g, loquat leaf 9g, Aster 9g, Dwarf Camellia 15g, Burdock Fructus 9g, Ephedra 6g, White Peony 6g, Licorice 3g.

[0084] The composition of prescription 2: 9g of Stemona japonica, 9g of loquat leaf, 9g of Aster tataricus, 15g of Camellia oleifera, 9g of Arctium lappa, 6g of Ephedra sinica, 6g of White Peony Root, and 3g of Licorice.

[0085] The composition of prescription 3: 9g of Stemona japonica, 6g of Poria cocos, 9g of Aster tataricus, 15g of Camellia sinensis, 9g of Arctium lappa, 6g of Ephedra sinica, 6g of White Peony Root, and 3g of Licorice.

[0086] The composition of prescription 4: 9g of Stemona, 6g of Poria, 9g of Loquat Leaf, 15g of Camellia Sinensis, 9g of Burdock Fruit, 6g of Ephedra, 6g of White Peony Root, and 3g of Licorice.

[0087] The composition of prescription 5: 9g of Stemona japonica, 6g of Poria cocos, 9g of loquat leaf, 9g of Aster tataricus, 9g of Arctium lappa, 6g of Ephedra sinica, 6g of White Peony Root, and 3g of Licorice.

[0088] The composition of prescription 6: 9g of Stemona, 6g of Poria, 9g of Loquat Leaf, 9g of Aster, 15g of Camellia sinensis, 6g of Ephedra, 6g of White Peony Root, and 3g of Licorice.

[0089] The composition of prescription 7: 9g of Stemona bulbs, 6g of Poria cocos, 9g of loquat leaves, 9g of Aster tataricus, 15g of Camellia sinensis, 9g of Burdock fruit, 6g of White Peony Root, and 3g of Licorice.

[0090] The composition of prescription 8: 9g of Stemona japonica, 6g of Poria cocos, 9g of loquat leaf, 9g of Aster tataricus, 15g of Camellia sinensis, 9g of Burdock fruit, 6g of Ephedra sinica, and 3g of Licorice.

[0091] The composition of prescription 9: 9g of Stemona bulbs, 6g of Poria cocos, 9g of loquat leaves, 9g of Aster tataricus, 15g of Camellia sinensis, 9g of Arctium lappa, 6g of Ephedra sinica, and 6g of White Peony Root.

[0092] Preparation method of the split prescription medicine: prepare it according to the method of Example 1.

[0093] Experimental methods: After the animal adaptability observation, the guinea pigs were randomly divided into a normal group, a model group, a Chinese medicine combination group, and each disassembled prescription group (disassembled prescription 1, disassembled prescription 2, disassembled prescription 3, disassembled prescription 4, disassembled prescription 5, disassembled prescription 6, disassembled prescription 7, disassembled prescription 8, and disassembled prescription 9). The guinea pigs in the model group, the Chinese medicine combination group, and each disassembled prescription group were stimulated by nasal drops of lipopolysaccharide, smoke, and capsaicin atomization to construct a guinea pig model of post-infection cough. The animals were placed in a whole-body exposure atomization system and ventilated at a certain airflow rate. A metal fumigation box (sawdust cigarette) was placed in the exposure box and ignited for fumigation. The smoke was smoked for 30 minutes per day, once a day, for 10 consecutive days, and they were free to eat and drink. The normal group was only ventilated without smoke stimulation. After the fumigation, the rats were weighed. On the 11th, 14th, and 17th days, all guinea pigs except the normal group were given 0.4 mg / ml lipopolysaccharide (LPS) solution through the nose after light anesthesia, with a volume of 10 μl / 10 g. The normal group was given saline instead. On the 12th, 13th, 15th, 16th, and 18th days, the guinea pigs were placed in a cough-inducing asthma instrument with 1×10 -4 mol / L capsaicin solution was stimulated by aerosol inhalation for 3 minutes. The guinea pigs in the Chinese medicine combination group and each disassembled prescription group were given the corresponding drugs by gavage, and the normal group and the model group were given distilled water, once a day, for 7 consecutive days. 24 hours after the last administration, the guinea pigs were placed in a closed bell jar of a multifunctional cough-inducing and wheezing instrument, and aerosol inhalation of capsaicin solution was used for 3 minutes. Starting from the first loud cough determined by the instrument, the time of coughing and the number of coughs within 8 minutes were recorded (including the number of coughs recorded manually within 3 minutes of aerosol inhalation).

[0094] Statistical methods: SPSS 21.0 for Windows statistical software was used for statistical analysis. Count data were expressed by rate and composition ratio, and x 2 Test. P<0.05 was used as the criterion for statistical difference. Experimental results: As shown in Table 5, compared with the model group, the Chinese medicine combination and each separated prescription significantly reduced the number of coughs and prolonged the cough latency, with statistical difference (P<0.01). However, the therapeutic effect of any separated prescription with one less medicine was not as good as that of the Chinese medicine combination, and there was statistical difference (P<0.01).

[0095] Table 5 Results of guinea pig cough latency and cough frequency within 8 minutes

[0096]

[0097] Note: Compared with the normal group, the model group #" , means P<0.05," ##" Indicates P<0.01.

[0098] Compared with the model group, "*" indicates P < 0.05, and "**" indicates P < 0.01.

[0099] Example 9 Clinical Comparative Study of Traditional Chinese Medicine Composition and Dioxin Hydrochloride Tablets

[0100] 1. Clinical Data and Methods

[0101] 1.1 Research subjects

[0102] All patients with post-infectious cough who visited the outpatient department of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (Shandong Provincial Hospital of Traditional Chinese Medicine).

[0103] 1.2 Diagnostic criteria

[0104] 1.2.1 Western medicine diagnostic criteria

[0105] With reference to the Guidelines for the Diagnosis and Treatment of Cough (2021 Edition), the most common causes were selected as follows: (1) Cough secondary to a previous respiratory tract infection; (2) After the acute symptoms of respiratory tract infection disappear, the cough persists for 3 to 8 weeks; (3) It manifests as an irritating dry cough or coughing up a small amount of white mucus, usually lasting 3 to 8 weeks, and no abnormalities are found in chest X-ray examinations; (4) Pulmonary function tests are normal; (5) Cough caused by other causes is excluded.

[0106] 1.2.2 TCM syndrome diagnostic criteria

[0107] With reference to the TCM section on cough mentioned in the "Standards for Diagnosis and Efficacy of TCM Internal Medicine Diseases" and the 2021 edition of the "Guidelines for Diagnosis and Treatment of Cough", the diagnostic criteria for cough after wind-evil-hidden lung infection were formulated: Main symptoms: paroxysmal cough, cough accompanied by itchy throat, dry cough or little sputum, and difficulty in expectoration. Concomitant symptoms: (1) No obvious cold or heat in the body; (2) Often induced by cold or hot air, odor, and laughing; (3) Exogenous infection often induces aggravation or recurrence of cough. Tongue and pulse: Pale red tongue with thin white fur. Pulse: Stringy or slippery. Patients with the above main symptoms + 1 or more of the concomitant symptoms can be diagnosed by referring to the tongue and pulse.

[0108] 1.2.3 Inclusion criteria: (1) Age ranged from 18 to 65 years (excluding those aged 18 and 65 years); (2) Met the diagnostic criteria for post-infectious cough; (3) Cough onset duration ≥ 3 weeks and ≤ 8 weeks; (4) Met the TCM diagnostic and differentiation criteria for cough-wind evil in the lungs; (5) Cough VAS score ≥ 60 mm (0-100 mm scale); (6) Subjects gave informed consent and signed the informed consent form.

[0109] 1.2.4 Exclusion criteria: (1) patients with cough variant asthma (CVA), upper airway cough syndrome (UACS), eosinophilic bronchitis (EB), gastroesophageal reflux cough (GERC), chronic bronchitis and other causes of cough; (2) patients with body temperature (axillary) ≥ 37.3°C; (3) patients with abnormalities such as lung infection, tuberculosis, tumor, pleural effusion, etc. on chest X-ray; (4) patients with other respiratory diseases such as pneumonia, bronchial asthma, bronchiolitis, bronchopneumonia, respiratory allergies, etc.; (5) patients with FeNO> 30 ppb; (6) patients with nasal diseases such as rhinitis, sinusitis symptoms or postnasal drip; (7) patients using A Patients with drug-induced cough caused by CEI, ARB antihypertensive drugs, β-blockers, mycophenolate mofetil, nitrofurantoin, propofol, leflunomide, simvastatin, γ-interferon, omeprazole and other drugs; (8) Patients with serious underlying diseases such as cardiovascular disease, kidney disease, liver disease, blood system disease, nervous system and neuromuscular disease, metabolic and endocrine system disease, immunosuppression (including immunosuppression caused by the use of immunosuppressants or HIV infection), who are determined by the researchers to be ineligible for inclusion in the study; (9) Patients whose clinical test indicators (BUN, Cr, ALT, etc.) exceed 1.5 times the upper limit of the normal reference value or whose white blood cell count in blood routine examination is greater than 12×10 9 / L; serum creatinine>upper limit of normal reference value; urine protein>+; blood white blood cells<3.0×10 9 / L or>10.0×10 9 / L; and / or neutrophil (N) classification >80%; (10) patients with severe multiple organ failure; (11) pregnant, pregnant or lactating women; (12) patients who are unable to cooperate, such as those suffering from mental illness; (13) patients who are allergic to the drugs involved in the trial; (14) patients who have participated in other drug clinical trials or taken other research drugs in the past three months.

[0110] 1.2.5 Sample size estimation

[0111] Refer to the relevant formulas of the 6th edition of "Medical Statistics" for calculation. From the perspective of effectiveness, according to statistical requirements, a superiority test was used, a two-sided test, α = 0.05, β = 0.2, and the expected average effective rate was 0.90. The estimated number of cases was 126. Considering the dropout factor, it was decided that this trial would have 140 cases, 70 in the Chinese medicine group and 70 in the Western medicine group.

[0112] 1.2.6 Ethical Review

[0113] This study has been reviewed by the Ethics Committee of the Affiliated Hospital of Shandong University of Traditional Chinese Medicine (Shandong Provincial Hospital of Traditional Chinese Medicine) and has been granted the ethics number ChiCTR220035.

[0114] 1.3 Drug treatment Western medicine group: given dioxetine hydrochloride tablets, specifications of 5mg*100 tablets. Oral, adults take 5mg orally once, 3 times a day.

[0115] Chinese medicine group: The Chinese medicine composition of the present invention was administered and taken with boiled water, 1 bag at a time, 3 times a day, half an hour after meals.

[0116] The Chinese medicine composition is prepared according to the dosage of implementation three and is produced by Suzhou Wusongjiang Pharmaceutical Co., Ltd. All medicinal materials are added with 10 times the amount of water, decocted twice, each time for 1.5 hours, the decoction is filtered, and the filtrate is concentrated under reduced pressure to a clear paste; centrifuged, the supernatant is further concentrated under reduced pressure to an extract with a relative density of 1.20 to 1.30, dried, and added with auxiliary materials to form granules. The granules are taken with boiled water, 1 bag at a time, 3 times a day, half an hour after meals.

[0117] Both groups were treated for 14 days.

[0118] 1.4 Observation indicators

[0119] The cough severity of each group of patients was scored before and after treatment. The scoring method recommended by the "Guidelines for the Diagnosis and Treatment of Cough (2021 Edition)" and the simple cough severity score table (cough evaluation test, CET) were used. The efficacy was evaluated according to the efficacy index, and the efficacy index = (total score before treatment - total score after treatment) ÷ total score before treatment. ① Marked effect: symptoms improved significantly, and the syndrome score decreased by ≥70% compared with before treatment; ② Effective: symptoms improved, and the syndrome score decreased by ≥30% and <70% compared with before treatment; ③ Ineffective: symptoms did not improve, and the syndrome score decreased by <30% compared with before treatment; ④ Aggravated: symptoms worsened, and the syndrome score decreased by <0% compared with before. Statistical methods: SPSS21.0 for windows statistical software was used for statistical analysis. The counting data were expressed by rate and constituent ratio, and x was used. 2 P < 0.05 was considered as the criterion for statistical significance.

[0120] 2. Results

[0121] As shown in Table 6, a total of 140 cases of post-infection cough were collected, with 70 cases in the traditional Chinese medicine group and 70 cases in the western medicine group. The total effective rate of the traditional Chinese medicine group was 94.29%, which was significantly higher than that of the western medicine group, with statistical difference (P<0.05).

[0122] Table 6 Comparison of clinical efficacy between the two groups / case

[0123]

[0124] The various aspects of the present invention have been described above. However, it should be understood that, without departing from the spirit of the present invention, equivalent changes and modifications may be made by those skilled in the art, and the changes and modifications also fall within the scope of the appended claims of the present application.

Claims

1. A Chinese medicine composition for treating post-infectious cough, characterized in that: The invention is prepared from the following raw materials in parts by weight: 5-10 parts of stemonae, 3-9 parts of tuckahoe, 5-10 parts of loquat leaves, 5-10 parts of aster, 10-18 parts of dwarf camellia, 5-10 parts of burdock seeds, 3-9 parts of ephedra, 3-9 parts of white peony root and 1-5 parts of liquorice.

2. The Chinese medicine composition according to claim 1, characterized in that The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 7-9 parts of stemonae, 4-7 parts of tuckahoe, 7-9 parts of loquat leaves, 6-9 parts of aster, 13-17 parts of dwarf camellia, 7-9 parts of burdock, 5-7 parts of ephedra, 5-7 parts of white peony root and 2-4 parts of liquorice.

3. The Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 5 parts of stemonae, 9 parts of tuckahoe, 10 parts of loquat leaves, 6 parts of aster, 10 parts of dwarf camellia, 5 parts of burdock fruits, 9 parts of ephedra, 3 parts of white peony root and 2 parts of liquorice.

4. The Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 10 parts of stemonae, 7 parts of tuckahoe, 7 parts of loquat leaves, 5 parts of aster, 13 parts of dwarf camellia, 8 parts of burdock seeds, 7 parts of ephedra, 5 parts of white peony root and 5 parts of liquorice.

5. The Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 9 parts of stemonae, 6 parts of tuckahoe, 9 parts of loquat leaves, 9 parts of aster, 15 parts of dwarf camellia, 9 parts of burdock seeds, 6 parts of ephedra, 6 parts of white peony root and 3 parts of liquorice.

6. The Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 7 parts of stemona, 4 parts of tuckahoe, 8 parts of loquat leaves, 10 parts of aster, 18 parts of dwarf camellia, 10 parts of burdock fruits, 5 parts of ephedra, 7 parts of white peony root and 1 part of liquorice.

7. The Chinese medicine composition according to claim 1, characterized in that: The traditional Chinese medicine composition is prepared from the following raw materials in parts by weight: 8 parts of stemona, 3 parts of tuckahoe, 5 parts of loquat leaves, 7 parts of aster, 17 parts of dwarf camellia, 7 parts of burdock, 3 parts of ephedra, 9 parts of white peony root and 4 parts of liquorice.

8. A Chinese medicinal compound preparation for treating post-infectious cough, characterized in that: The Chinese medicine compound preparation is a decoction, granule, powder, capsule, tablet or oral liquid with the Chinese medicine composition described in claim 1 or 2 or 3 or 4 or 5 or 6 as the active ingredient.

9. The Chinese medicinal compound preparation according to claim 8, characterized in that: The Chinese medicine compound preparation is a granule.

10. Use of the Chinese medicine composition as claimed in claim 1 or 2 or 3 or 4 or 5 or 6 or 7 in the preparation of a medicament for treating post-infectious cough.

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