Use of herbal medicine composition in the manufacture of a medicament for treating cough asthma

Abstract

Provided is a herbal medicine composition made from Scutellaria Baicalensis, Bouquet, Qianhuo, Angelica Root, Bupleurum Root, Quercus Root, Cnidium Root, Kikkomang, Poria Cocos, Platycodon Root, and Licorice Root, which can reduce the frequency of coughing in a guinea pig model of cough asthma, lower the proportion of eosinophils in bronchoalveolar lavage fluid, and lower the serum eosinophil cationic protein level, and thus has preventive and therapeutic effects on cough asthma.

Description

[Technical field]

[0001] The present invention relates to a new use of a herbal composition, specifically to the use of the herbal composition in preparing a medicament for treating cough asthma, which belongs to the technical field of herbal medicine. [Background technology]

[0002] Cough variant asthma (CVA) is also known as cough-type asthma, and was previously called allergic bronchitis, allergic cough, and hidden asthma. Symptoms include repeated dry coughs accompanied by an itchy throat and occasional small amounts of white phlegm that are difficult to cough up. The cough is generally sudden and spasmodic, and when the cough is severe, the patient may be unable to catch their breath or hold their breath. Other symptoms include a low voice and shortness of breath. Some patients experience severe coughing at night, which has a serious impact on sleep.

[0003] Cough-variant asthma is characterized by chronic cough. In modern medicine, the trigger is mostly airway irritation (such as smoke, cold air, and allergens), cough is its only expression, and it may not be accompanied by asthma, and the treatment is thought to be almost the same as asthma. In clinical Chinese medicine, it is classified as "cough", "whining symptom", "wind cough", "lung paralysis", "pharyngeal origin cough", etc., and sometimes classified as "asthma symptom". The symptoms of cough-variant asthma can also be classified as "cough" and "internal injury cough" for differential treatment. This disease often belongs to the category of "evil real and positive deficiency" (excess of evil energy reduces the body's immune system) and "deficiency real and mixed" (excess of evil energy and reduced immune system at the same time). Evil real is mainly phlegm dampness and phlegm heat accumulated in the lungs, and liver fire affects the lungs, and positive deficiency is mainly lung yin deficiency, lung and spleen both deficiency, and lung and kidney both deficiency. In terms of treatment, it is necessary to take into consideration the three organs - the lungs, spleen and kidneys - by dispelling evil and stopping the cough, while at the same time reinforcing the positive and making up for the deficiency.

[0004] Because the mechanism and pathogenesis of cough asthma are not yet fully understood, many scholars believe that it is consistent with the mechanism of typical asthma disease, that is, airway allergic inflammation, so the current treatment is basically symptomatic. Common treatment methods for cough asthma include environmental prevention and hormone therapy. In the acute phase, it is controlled with Western medicine, and in the remission phase, it is treated with a combination of Chinese medicine and Western medicine.

[0005] The following is a dialectical classification system for common cough symptoms in traditional Chinese medicine.

[0006] (1) The chills attack the lungs. The cough is heavy, the phlegm is thin and white, there is chills and fever, and no sweating. The tongue coating is thin and white, and both the floating and fast pulses are observed.

[0007] (2) Wind-heat attacks the lungs. There is coughing and shortness of breath, thick, white or yellow phlegm, sore throat and raspy cough, or fever, intolerance to cold, slight thirst, red tip of tongue, thin white or yellow coating, and superficial, rapid pulse.

[0008] (3) Dryness damages the lungs. There is a dry, hacking cough without phlegm, difficulty in expectorating phlegm, dry nose and pharynx, and dry mouth. The tip of the tongue is red, coated with a thin yellow coating, there is little saliva, and the pulse is thin as a thread, but beats powerfully and rapidly.

[0009] (4) Phlegm-heat accumulates in the lungs. There is coughing and shortness of breath, the phlegm is copious, thick, yellow, irritable, hot and dry mouth, the tongue is red and coated with a yellow coating, the pulse feels like a ball rolling in a plate, and the pulse beats rapidly.

[0010] (5) Liver Fire attacks the Lungs. Coughing causes suffocation, accompanied by hiccups, chest pain when coughing, and in severe cases hemoptysis. The tongue is red, with a thin yellow coating, there is scanty saliva, and the pulse is tense, strong, regular, and rapid.

[0011] (6) Phlegm and dampness are accumulated in the lungs. Coughing is heavy, with a lot of white phlegm, and is severe in the morning. There is chest discomfort, epigastric distension, and poor appetite. The tongue is white, and the pulse feels like a ball rolling in a plate.

[0012] (7) Lung Yin deficiency. Prolonged cough, scanty expectoration, difficulty in expectorating, sticky phlegm, bloody phlegm, dry throat, dry mouth, fever in the palms and soles of the feet, red tongue, scanty coating, thread-like pulse, but strong and rapid beat.

[0013] (8) Lung qi deficiency. The illness continues for a long time, the cough is low-pitched and asthmatic, the phlegm is thin and white, the appetite is poor, the breath is short, the breath is short, the energy is low, there is sweating, and the patient is weak to cold. The tongue is red and coated with white paint, and the pulse is weak.

[0014] Yang Deyi (Yang Deyi, Treating 57 Cases of Cough Varicose Veins with Ephedra He Jing Bang Baidu Powder [J], Jiangxi Traditional Chinese Medicine, 2006(7):32) used Ephedra Herb and Ephedra Root He Jing Bang Baidu Powder to treat 57 cases of cough variant asthma, with remarkable therapeutic effects. Ephedrine, the main active ingredient in Ephedra Herb, can affect multiple systems in the body and can cause serious side effects on the cardiovascular and central nervous systems (Side Effects of Ephedrine and Related Research Status [J], Foreign Medical Chinese Medicine, Chinese Medicine, 2005,27(3):155-156). Liu Xiaoshuai et al. (An experimental study of the anti-inflammatory mechanism of nitric oxide synthase-nitric oxide pathway by Jingbosan [J]. Shizhen Guoyi Guoyi, 2008,19(12):3014-3015.) used ovalbumin-induced mouse asthma model and carrageenan-induced rat pleurisy model to observe the changes in NOS, iNOS activity, and NO content in rat pleural exudate and mouse lung tissue homogenate after Jingbosan treatment, and investigated the anti-inflammatory mechanism of Jingbosan. Jingbo granules are a combination of Jingjie, Fangfeng, Qianhuo, Angelica dahurica, Bupleurum Root, Cnidium Officinale, Kikko, Platycodon grandiflorum, and Licorice, which promote sweating and have a clearing effect, can clear cold and phlegm, remove dirt accumulated in the lungs, and stop coughing. It is known to have a good effect on a series of symptoms when used for external cold and wind. Cough variant can also be triggered or aggravated by external cold and wind, and in actual clinical application, it was found that cough variant is a new indication for Jingfang Granules, and in particular, it is more effective for cold cough caused by the accumulation of phlegm and dampness in the lungs, as the cough syndrome is thought to be caused by cold and wind attacks the lungs, and these clinical experiences have provided support for the further development and use of this product. Currently, there have been no reports on the prescription of Jingfang Granules that can be used for cough variant. Summary of the Invention [Problem to be solved by the invention]

[0015] The main object of the present invention is to provide a herbal composition prepared using Qiang Huo, Angelica Root, Poria Cocos, Bouquet, Scutellaria Root, Cnidium Root, Platycodon Root, Bupleurum Root, Oryza Root, and Licorice Root. [Means for solving the problem]

[0016] The present invention further develops the use of the conventional product, Jingbou Granules.

[0017] The present inventors have studied the treatment of cough variant asthma with Jingbo Granules and found that Jingbo Granules are significantly effective for cough variant asthma and can be used as a drug by patients. The formulation of Jingbo Granules used in the present invention does not contain Ephedra Herb or Ephedra Root, which eliminates the side effects caused by Ephedra Herb and Ephedra Root and reduces safety risks.

[0018] One of the objects of the present invention is to provide a herbal medicine composition mainly consisting of Scutellaria Baicalensis, Fangfeng Root, Qiang Huo, Angelica Root, Bupleurum Root, Cnidium Root, Anemone Root, Poria Cocos Root, Platycodon Root and Licorice Root, that is, the herbal medicine composition is mainly produced from the following raw materials: 5 to 30 parts by weight of Jinghuan, 5 to 30 parts by weight of windbreak, 5 to 30 parts by weight of Qinghui, Dokatsu 5-30 parts by weight, Saiku 3-25 parts by weight, Qianhu 3-25 parts by weight, 5 to 30 parts by weight of Chinese cabbage, 3 to 25 parts by weight of Mantis annua, 5 to 30 parts by weight of Bokum, Bellflower 3~25 parts by weight, licorice 1~10 parts by weight.

[0019] Preferably, the herbal composition is mainly made of the following raw materials: 10~20 parts by weight of Jinghu, 10~20 parts by weight of windbreak, 10~20 parts by weight of Qinghui Dokatsu 10~20 parts by weight, Saiku 3~20 parts by weight, Qianhu 3~20 parts by weight 10 to 20 parts by weight of Cucumber, 3 to 20 parts by weight of Mantis chinensis, 10 to 25 parts by weight of Bulong Bellflower 3-20 parts by weight, licorice 1-8 parts by weight.

[0020] More preferably, the herbal composition is mainly made from the following raw materials: 15 parts by weight of Jinghu, 15 parts by weight of windbreak, 15 parts by weight of Qianghu, Dokatsu 15 parts by weight, Saiba 15 parts by weight, Qianhu 15 parts by weight, 15 parts by weight of Cucumber, 15 parts by weight of Mantis annua, 15 parts by weight of Boulong, 15 parts by weight of bellflower, 5 parts by weight of licorice.

[0021] Another object of the present invention is to provide a use of said herbal composition in preparing a medicament for treating cough variant asthma.

[0022] The cough variant asthma of the present invention has a main clinical symptom of coughing, mainly a long-term persistent dry cough, and is often caused by inhalation of irritating odors (paint, gasoline, perfume, pollen, etc.), chills, contact with allergens, strenuous exercise, and respiratory infections, but some patients develop asthma without any trigger. Cough variant asthma often occurs at night and early in the morning, and is most commonly seen in spring and autumn.

[0023] The clinical characteristics of the cough variant of the present invention are as follows: There is chronic cough without cause for more than 2 months, paroxysmal dry irritation cough, or a small amount of white foamy sputum. The condition may worsen when inhaling chemical odors such as smoke, paint, and dichlorvos. Various antibiotics have been used but have been ineffective, and no obvious abnormalities were found in radiography or CT scans. 40% of patients may have symptoms of allergic rhinitis such as sneezing and runny nose, and many doctors outside China call it allergic rhinitis-bronchitis.

[0024] The cough variant of the present invention is classified according to the type of symptoms in Chinese medicine into cold and howling, heat and howling, external cold and internal heat type, and lung full and kidney deficiency type.

[0025] Cough variant asthma (CVA), also known as cough-type asthma, was previously known as allergic bronchitis, allergic cough, or hidden asthma. Symptoms include repeated dry coughs accompanied by an itchy throat and occasional small amounts of white phlegm that are difficult to cough up. The cough is generally sudden and spasmodic, and severe coughing can cause symptoms such as shortness of breath, shortness of breath, low voice, and shortness of breath.

[0026] A further object of the present invention is to Step A is to distill Scutellaria Baicalensis, Fangfeng, Qiang Huo, Angelica Root, Chinese Husk, Cnidium Officinalis, and Citrus Fruit Extraction Method to Extract Volatile Oil, and Prepare Distillation Residue, Distillation Cnidium Officinalis, and Citrus Fruit Extraction Method for Use; Step B is to prepare the distilled Cnidium officinalis and Cnidium husk aqueous solution obtained in step A into a 10-40% ethanol solution for use; Step C is to mix the Poria cocos, the distilled Cnidium officinalis and the residue of the husk obtained in step A, and leach and extract the mixture with the ethanol solution obtained in step B, and prepare the leachate for use;

[0027] Step D is to add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk residue obtained in step A, and boil them, concentrating the boiled liquid for use; and step E, mixing and concentrating the infusion obtained in step C with the decoction obtained in step D, and adding the volatile oil obtained in step A to obtain the herbal composition.

[0028] Preferably, the method comprises the steps of: Step A is to distill Scutellaria Baicalensis, Fangfeng, Qiang Huo, Angelica Root, Chinese Husk, Cnidium Officinalis, and Citrus Fruit Extraction Method to Extract Volatile Oil, and Prepare Distillation Residue, Distillation Cnidium Officinalis, and Citrus Fruit Extraction Method for Use; Step B is to prepare the distilled Cnidium officinalis and Cnidium husk aqueous solution obtained in step A into a 15-30% ethanol solution for use; Step C is to mix the Poria cocos, the distilled Cnidium officinalis and the residue of the husk obtained in step A, and leach and extract the mixture with the ethanol solution obtained in step B, and prepare the leachate for use; Step D is to add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk residue obtained in step A, and boil them, concentrating the boiled liquid for use; and step E, mixing and concentrating the infusion obtained in step C and the decoction obtained in step D, and adding the volatile oil obtained in step A to obtain the herbal medicine composition.

[0029] More preferably, the method comprises the steps of: Step A is to distill Scutellaria Baicalensis, Fangfeng, Qiang Huo, Angelica Root, Chinese Husk, Cnidium Officinalis, and Citrus Fruit Extraction Method to Extract Volatile Oil, and Prepare Distillation Residue, Distillation Cnidium Officinalis, and Citrus Fruit Extraction Method for Use; Step B is to prepare the distilled Cnidium officinalis and Cnidium husk aqueous solution obtained in step A into a 25% ethanol solution for use; Step C is to mix the Poria cocos, the distilled Cnidium officinalis and the residue of the husk obtained in step A, and leach and extract the mixture with the ethanol solution obtained in step B, and prepare the leachate for use; Step D is to add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk residue obtained in step A, and boil them, concentrating the boiled liquid for use; and step E, mixing the decoction obtained in step C with the ointment obtained in step D to concentrate it into a ointment, and adding the volatile oil obtained in step A to obtain the herbal medicine composition.

[0030] A further object of the present invention is to provide a herbal medicine preparation having the above-mentioned herbal medicine composition, i.e., a clinically acceptable dosage form prepared by directly adding pharmaceutical acceptable auxiliary materials to the herbal medicine composition through conventional processes.

[0031] Preferably, the clinically acceptable oral formulation is one or more of a pill, a capsule, a tablet, a granule, and a liquid oral formulation;

[0032] More preferably, the oral formulation is a granule. Effect of the Invention

[0033] Compared with the prior art, the present invention has significant technical advantages.

[0034] The herbal composition of the present invention can significantly reduce the cough frequency of guinea pig models of cough variant asthma and reduce the eosinophil rate in their bronchoalveolar lavage fluid (BALF). According to another embodiment of the present invention, it is found that the herbal composition of the present invention can significantly reduce the cough frequency of rats with cough variant asthma and lower the serum eosinophil cationic protein level. Eosinophil cationic protein (ECP) is a toxic protein released after EOS activation that damages the airway epithelium, leading to allergic pathological changes such as airway spasm and mucosal edema, and resulting in high airway reactivity. The herbal composition of the present invention is clinically safe and has a remarkable effect on the treatment of cough variant asthma. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0035] Example of the invention In order to verify the efficacy of the herbal medicine composition of the present invention on cough asthma, the inventors conducted animal test studies, and only some experimental models are described below as examples. However, the inventors also conducted pharmacological experimental studies on other cough asthma symptoms described in the specification, and the results showed that the composition of the present invention can achieve the same or similar effects, so they will not be described in detail here.

[0036] In addition, all of the experimental studies below were conducted after demonstrating the safety of the drugs through acute and long-term toxicity tests, and the drug dosages used in the experimental studies were all within the safe dosage range.

[0037] Production Example 1: Production of granules Prescription Jinghu 75g Windproof 75g Qianghu 75g Dokatsu 75g Saihu 75g Qianhu 75g 75g of Senkyu, 75g of Mango husk, 75g of Bokul, 75g of Kikyo, 25g of licorice

[0038] Manufacturing method Step A: Extract volatile oils from Atractylodes sieboldii, Acanthus persica, Atractylodes chinensis, Anemone ulmoides, Oryza sativa, Cnidium rhizome, and Anemone husk through distillation, and prepare the distillation dregs, distilled Cnidium rhizome, and anemone husk aqueous solution for use. Step B: The distilled aqueous solution of Cnidium officinalis and Citrus husk obtained in Step A is prepared into a 25% ethanol solution for use. Step C: Poria cocos, the distilled Cnidium officinalis and the husk residue obtained in Step A are mixed and extracted with the ethanol solution obtained in Step B, and the infusion is prepared for use. Step D: Add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk Residue obtained in Step A, and decoctate them twice for 1.5 hours each. The two decoctions are combined, filtered, and concentrated into a paste for use. Step E: The decoction obtained in Step C and the ointment obtained in Step D are mixed, allowed to stand, and filtered to concentrate into a ointment. An appropriate amount of sucrose is added, mixed uniformly, granulated, dried, and the volatile oil obtained in Step A is added, and mixed uniformly to obtain a Chinese herbal medicine composition.

[0039] Production Example 2 Production of granules Prescription Jinghu 10g Windproof 10g Qianghu 12g Dokatsu 12g Saihu 5g Qianhu 5g 12g of Chinese cucumber, 5g of quince, 20g of bellflower, 5g of bellflower, 3g of licorice

[0040] The manufacturing method was the same as in Example 1.

[0041] Production Example 3: Production of granules Prescription Jinghu 30g Windproof 5g Qianghu 30g Dokatsu 5g Saihu 25g Qianhu 3g Cucumber 30g, Conch husk 3g, Bulyo 30g, Kikyo 3g, Licorice 10g

[0042] The manufacturing method was the same as in Example 1.

[0043] Production Example 4 Production of oral liquid Prescription Jinghu 5g Windproof 30g Qianghu 5g Dokatsu 30g Saihu 3g Qianhu 25g 5g of Chinese cabbage, 25g of quince, 5g of Japanese bellflower, 25g of bellflower, 1g of licorice;

[0044] Manufacturing method Step A: Extract volatile oils from Atractylodes sieboldii, Acanthus persica, Atractylodes chinensis, Anemone ulmoides, Oryza sativa, Cnidium rhizome, and Anemone husk through distillation, and prepare the distillation dregs, distilled Cnidium rhizome, and anemone husk aqueous solution for use. Step B: The distilled aqueous solution of Cnidium officinalis and Citrus husk obtained in Step A is made into a 10% ethanol solution for use. Step C: Poria cocos, the distilled Cnidium officinalis and the husk residue obtained in Step A are mixed together, and then extracted with the ethanol solution obtained in Step B, and the infusion is prepared for use. Step D: Add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk Residue obtained in Step A, and decoctate them twice for 1.5 hours each. The two decoctions are combined, filtered, and concentrated into a paste for use. Step E: The decoction obtained in step C and the ointment obtained in step D are mixed, allowed to stand, and filtered to concentrate into a ointment. An appropriate amount of sucrose is added and mixed uniformly, the volatile oil obtained in step A is added and mixed uniformly, and water is added until the volume reaches 1000 ml to obtain a Chinese herbal medicine composition.

[0045] Production Example 5 Production of syrup Prescription Jinghu 20g Windproof 10g Qianghu 20g Dokatsu 10g Saihu 20g Qianhu 3g Cucumber 20g, Conch husk 3g, Bokuri 25g, Kikyo 3g, Licorice 8g

[0046] Manufacturing method Step A: Extract volatile oils from Atractylodes sieboldii, Acanthus persica, Atractylodes chinensis, Anemone ulmoides, Oryza sativa, Cnidium rhizome, and Anemone husk through distillation, and prepare the distillation dregs, distilled Cnidium rhizome, and anemone husk aqueous solution for use. Step B: The distilled aqueous solution of Cnidium officinalis and Citrus husk obtained in Step A is made into a 40% ethanol solution for use. Step C: Poria cocos, the distilled Cnidium officinalis and the residue of husk obtained in Step A are mixed, and then leached and extracted with the ethanol solution obtained in Step B, and the leachate is prepared for use. Step D: Add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk Residue obtained in Step A, and decoctate them twice for 1.5 hours each. The two decoctions are combined, filtered, and concentrated into a paste for use. Step E: The decoction obtained in step C and the ointment obtained in step D are mixed, allowed to stand, and filtered to concentrate into a ointment. An appropriate amount of sucrose is added and mixed uniformly. The volatile oil obtained in step A and 500 ml of simple syrup are added, mixed uniformly, allowed to stand, filtered, and water is added until the total volume reaches 1000 ml to obtain a Chinese herbal medicine composition.

[0047] Preparation Example 6 Preparation of tablets Prescription Jinghu 10g Windproof 20g Qianghu 10g Dokatsu 20g Saihu 3g Qianhu 20g 10g of Chinese cucumber, 20g of coconut husk, 10g of bellflower, 20g of bellflower, 1g of licorice

[0048] Manufacturing method Step A: Extract volatile oils from Atractylodes sieboldii, Acanthus persica, Atractylodes chinensis, Anemone ulmoides, Oryza sativa, Cnidium rhizome, and Anemone husk through distillation, and prepare the distillation dregs, distilled Cnidium rhizome, and anemone husk aqueous solution for use. Step B: The distilled aqueous solution of Cnidium officinalis and Citrus husk obtained in Step A is made into a 15% ethanol solution for use. Step C: Poria cocos, the distilled Cnidium officinalis and the husk residue obtained in Step A are mixed together, and then leached and extracted with the ethanol solution obtained in Step B, and the leachate is prepared for use. Step D: Add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk Residue obtained in Step A, and decoctate them twice for 1.5 hours each. The two decoctions are combined, filtered, and concentrated into a paste for use. Step E: The decoction obtained in step C and the ointment obtained in step D are mixed, allowed to stand, filtered and concentrated into a ointment, an appropriate amount of sucrose is added, mixed uniformly, granulated, dried, the volatile oil obtained in step A is added, mixed uniformly, granulated, an appropriate amount of auxiliary materials are added, mixed uniformly, and compressed into tablets to obtain a Chinese herbal medicine composition.

[0049] Production Example 7 Production of Capsules Prescription Jinghu 20g Windproof 10g Qianghu 20g Dokatsu 10g Saihu 20g Qianhu 3g Cucumber 20g, Conch husk 3g, Bokuri 25g, Kikyo 3g, Licorice 8g

[0050] Step A: Extract volatile oils from Atractylodes sieboldii, Acanthus persica, Atractylodes chinensis, Anemone ulmoides, Oryza sativa, Cnidium rhizome, and Anemone husk through distillation, and prepare the distillation dregs, distilled Cnidium rhizome, and anemone husk aqueous solution for use. Step B: The distilled aqueous solution of Cnidium officinalis and Citrus husk obtained in Step A is made into a 30% ethanol solution for use. Step C: Poria cocos, the distilled Cnidium officinalis and the husk residue obtained in Step A are mixed together, and then leached and extracted with the ethanol solution obtained in Step B, and the leachate is prepared for use. Step D: Add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk Residue obtained in Step A, and decoctate them twice for 1.5 hours each. The two decoctions are combined, filtered, and concentrated into a paste for use. Step E: The decoction obtained in step C and the ointment obtained in step D are mixed, allowed to stand, and filtered to concentrate into a ointment, and an appropriate amount of sucrose is added, mixed uniformly, granulated, and dried, and the volatile oil obtained in step A is added, mixed uniformly, granulated, dried, pulverized, and filled into capsules to obtain a Chinese herbal medicine composition.

[0051] Preparation Example 8 Preparation of pills Formulation: Jinghu 10g Windproof 20g Qianghu 10g Dokatsu 20g Saihu 3g Qianhu 20g 10g of Chinese cucumber, 20g of coconut husk, 10g of bellflower, 20g of bellflower, 1g of licorice

[0052] Manufacturing method Step A: Extract volatile oils from Atractylodes sieboldii, Acanthus persica, Atractylodes chinensis, Anemone ulmoides, Oryza sativa, Cnidium rhizome, and Anemone husk through distillation, and prepare the distillation dregs, distilled Cnidium rhizome, and anemone husk aqueous solution for use. Step B: The distilled aqueous solution of Cnidium officinalis and Citrus husk obtained in Step A is made into a 25% ethanol solution for use. Step C: Poria cocos, the distilled Cnidium officinalis and the husk residue obtained in Step A are mixed together, and then leached and extracted with the ethanol solution obtained in Step B, and the leachate is prepared for use. Step D: Add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk Residue obtained in Step A, and decoctate them twice for 1.5 hours each. The two decoctions are combined, filtered, and concentrated into a paste for use. Step E: The decoction obtained in step C and the ointment obtained in step D are mixed, allowed to stand, and filtered to concentrate into a ointment, and an appropriate amount of sucrose is added, mixed uniformly, granulated, and dried, and the volatile oil obtained in step A is added, mixed uniformly, dried, crushed, sieved, and 40-60g of refined honey and an appropriate amount of water are added, and the mixture is made into pills, and dried to obtain a Chinese herbal medicine composition.

[0053] Production Example 9: Production of plaster Prescription Jinghu 75g Windproof 75g Qianghu 75g Dokatsu 75g Saihu 75g Qianhu 75g 75g of Senkyu, 75g of Mango husk, 75g of Bokul, 75g of Kikyo, 25g of licorice

[0054] Manufacturing method

[0055] Step A: Extract volatile oils from Atractylodes sieboldii, Acanthus persica, Atractylodes chinensis, Anemone ulmoides, Oryza sativa, Cnidium rhizome, and Anemone husk through distillation, and prepare the distillation dregs, distilled Cnidium rhizome, and anemone husk aqueous solution for use. Step B: The distilled aqueous solution of Cnidium officinalis and Citrus husk obtained in Step A is made into a 25% ethanol solution for use. Step C: Poria cocos, the distilled Cnidium officinalis and the husk residue obtained in Step A are mixed together, and then leached and extracted with the ethanol solution obtained in Step B, and the leachate is prepared for use. Step D: Add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk Residue obtained in Step A, and decoctate them twice for 1.5 hours each. The two decoctions are combined, filtered, and concentrated into a paste for use. Step E: The decoction obtained in Step C and the ointment obtained in Step D are mixed, allowed to stand, and filtered to concentrate into a ointment. The volatile oil obtained in Step A is added and mixed uniformly to obtain a herbal medicine composition.

[0056] Efficacy Example 1: Effect of the herbal medicine composition of the present invention on guinea pig models of cough asthma 1 material 1.1 Animals Regular guinea pigs, 60 males and 60 females, half each, 60-90 days old, body mass (300±30)g The experimental animals were provided by the New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd. and were reared for one week prior to the experiment.

[0057] 1.2 Drugs and Reagents 1.2.1 Drugs

[0058] Example 1 Granules Nimahe Jingbo Haidokusan, prescription and composition ratio as described in the literature (Yang Deyi. Treatment of 57 cases of cough asthma with Nimahe Jingbo Haidokusan [J]. Jiangxi Chinese Medicine, 2006(7):32-32)

[0059] Ovalbumin (OVA) (GBCBIO Technologies, Rod No. A20199006-59)

[0060] Aluminum hydroxide dry powder (Tianjin Huirui Chemical Technology Co., Ltd., Rod No.: 20201209)

[0061] Capsaicin (Sigma, USA, Rod No.: 20200401)

[0062] 1.2.2 Dosage for guinea pigs Example 1 Granules: 3.6 g / kg high dose, 1.8 g / kg medium dose, 0.9 g / kg low dose

[0063] Nima Gojing anti-septic poison powder: 1.8g / kg.

[0064] 1.3 Main Reagents Hematoxylin and eosin were from Wuhan Dr. De Biotechnology Co., Ltd.

[0065] 2. Grouping, model creation and administration 2.1 Grouping After the animals were adaptively reared for one week, they were randomly divided into normal control group, model control group, Nimanhe Jingbo Haidokusan group, and low, medium, and high dose groups of Example 1 Granules, with 10 animals per group, according to body mass.

[0066] 2.2 Model Creation The experimental animals were randomly divided into a normal control group, a model control group, high, medium and low dose groups of Example 1 Granules, and a Nimanhe Jingbo Haidokusan group.

[0067] Modeling animals were smoked for 30 min daily from days 1 to 28. On day 15, each guinea pig was injected with 1 mL of 20 g / L OVA and 200 mg of aluminum hydroxide suspension. On day 22, each guinea pig was boosted once by injecting 1 mL of 20 g / L OVA and 200 mg of aluminum hydroxide suspension. From day 29, aerosol challenge with 10 g / L OVA was performed once daily for 7 consecutive days. The normal control group was given the same volume of saline.

[0068] All animals were housed in a normal environment, on a 12h / 12h light cycle, and had free access to water and granular feed. The smoking box and the method of use are as follows. The smoking box is a stainless steel custom-made box with the length, width, and height of 100cm × 60cm × 60cm. The cigarettes used in our laboratory are "Hongbai" filter cigarettes (Hongta Tobacco Co., Ltd.; flue-cured tobacco, tar content 10mg, nicotine content in smoke 0.7mg, carbon monoxide content in smoke 12mg). The cigarettes were lit in the smoking box, 10 cigarettes at a time, and after the cigarettes were lit, the smoke was discharged into the smoking box by manual operation using a 300mL syringe and a three-way pipe until the cigarettes burned out.

[0069] 2.3 Treatment The administration began on the day of the aerosol challenge on day 29, and 10 ml / kg of the drug corresponding to each administration group was administered intragastrically once daily for 7 consecutive days. The normal control group and the model control group were given the same amount of purified water.

[0070] 2.4 Sampling and detection 2.4.1 Cough susceptibility detection (CRS). 2.4.2 Percentage of eosinophils in bronchoalveolar lavage fluid

[0071] 2.5 Statistical methods The analysis was performed using SPSS19.0 statistical software.

[0072]

number

[0073] After testing for homogeneity of variance, analysis of variance was used for comparisons between multiple groups, and the LSD method was used for pairwise comparisons. P < 0.05 indicated a statistically significant difference.

[0074] 3. Inspection items 3.1 CRS measurement in each group of guinea pigs The cough sensitivity of the airway was determined by the capsaicin cough stimulation test. Using a whole-body plethysmograph (Buxco Electronics), the guinea pigs were placed in a body scan box on the second day after the last aerosol challenge with 10 g / L OVA, and the number of coughs in the guinea pigs was observed and recorded for 5 min after nebulizing 10-4 mol / L capsaicin solution for 2 min.

[0075] 3.2 Measurement of the percentage of eosinophils in bronchoalveolar lavage fluid of guinea pigs in each group After the stimulation test was completed, the bronchoalveolar cavity was washed three times with 2 mL of phosphate buffered saline (PBS) to collect bronchoalveolar lavage fluid (BALF). 200uL of the collected BALF was taken and centrifuged at 3000r / min for 10 min, the supernatant was transferred, red blood cell lysis solution was added, and the mixture was centrifuged at 3000r / min for 10 min, the supernatant was transferred, an equal volume of PBS was added, and the mixture was dropped onto a slide and stained with hematoxylin-iosin (HE). The number of eosinophils per 200 cells in consecutive fields was counted under a microscope, and the percentage of eosinophils was calculated.

[0076] 4. Results and Conclusions 4.1 CRS measurement in each group of guinea pigs From the results in Table 1, compared with the normal control group, the number of coughs in the model control group increased significantly, with a statistically significant difference (P<0.05).

[0077] The frequency of coughs in the treatment group was significantly lower than that in the model control group, and the frequency of coughs in the medium and high dose groups of the granules of Example 1 was significantly reduced compared to the model control group, with statistically significant differences (P<0.05 or P<0.01).

[0078] Compared with the Nima He Jingbo Haidokusan group, the frequency of coughing was significantly reduced in the high dose group of Example 1 Granules, with a statistically significant difference (P<0.05).

[0079] The above experimental results show that Jingfang Granules can suppress the coughing reaction in guinea pigs and have antitussive effects, and the antitussive effect has a certain relationship with the dose of the granules.

[0080] [Table 1]

[0081] Note: Compared with the normal control group, #P<0.05, ##P<0.01. Compared with the model control group, *P<0.05, **P<0.01. Compared with the Nimahekeibohaidokusan group, △P<0.05, △△P<0.01.

[0082] 4.2 Measurement of the percentage of eosinophils in bronchoalveolar lavage fluid of guinea pigs in each group From the results in Table 2, the proportion of eosinophils in the model control group was significantly increased compared with the normal control group, and the difference was statistically significant (P<0.05).

[0083] Compared with the model control group, the percentage of eosinophils was significantly decreased in the four treatment groups, all of which had statistically significant differences (P<0.05 or P<0.01).

[0084] Compared with the Nima He Jing Bo Haidoku San group, the high dose group of Example 1 Granules showed a remarkable decrease in the proportion of eosinophils, with a statistically significant difference (P<0.05).

[0085] [Table 2]

[0086] Note: Compared with the normal control group, #P<0.05, ##P<0.01. Compared with the model control group, *P<0.05, **P<0.01. Compared with the Nimahekeibohaidokusan group, △P<0.05, △△P<0.01.

[0087] From the above, the herbal medicine composition of the present invention can significantly reduce the number of coughs in the CVA guinea pig model and reduce the proportion of eosinophils in bronchoalveolar lavage fluid (BALF).The above experimental results show that the herbal medicine composition of the present invention can achieve the purpose of treating cough variant asthma.

[0088] Efficacy Example 2: Effect of the herbal medicine composition of the present invention on rats with cough asthma 1 material 1.1 Animals 6-week-old male clean grade SD rats, body mass (220±20)g The experimental animals were provided by the New Drug Pharmacology Center of Lunan Pharmaceutical Group Co., Ltd. and were kept for one week for adaptation before the experiment.

[0089] 1.2 Drugs

[0090] Example 1 Granules; Jingbosan, ingredients and manufacturing method described in the literature (Liu Xiaoshuai et al., Experimental study of the anti-inflammatory mechanism of nitric oxide synthase-nitric oxide pathway by Jingbosan [J]. Shizhen Guoyi Guoyi, 2008, 19(12): 3014-3015.)

[0091] Ovalbumin (OVA) (GBCBIO Technologies, Rod No. A20199006-59)

[0092] Aluminum hydroxide dry powder (Tianjin Huirui Chemical Technology Co., Ltd., Rod No.: 20201209)

[0093] Capsaicin (Sigma, USA, Rod No.: 20200401)

[0094] 1.2.2 Dosage in rats Example 1 Granules: 3.6 g / kg high dose, 1.8 g / kg medium dose, 0.9 g / kg low dose

[0095] Jing bansan: 2.5g / kg

[0096] 2. Grouping, model creation and administration The model was created using the method of sensitization by co-stimulation of egg protein and aluminum hydroxide. Except for 8 rats in the normal control group, the remaining rats were subcutaneously injected with 1 mL of saline containing 1 mg of prepared egg protein and 10 mg of aluminum hydroxide. Ten points were taken on both hind paws, groin, waist, back, and neck, and 0.05 mL was subcutaneously injected at each point, and 0.5 mL was intraperitoneally injected, for a total of 1 mL injection, and the injection was repeated once on the 8th day to strengthen the sensitization. From the 15th day, the rats were placed in a sealed organic glass cover, and the saline containing 1% egg protein solution was ultrasonically atomized to stimulate the rats for 20 minutes to induce asthma. The obvious contraction of the rat abdominal muscles was considered positive, and the appearance of symptoms of airway spasm such as deeper and faster breathing indicated that the model was successfully created.

[0097] The rats that were successfully modeled were randomly divided into 5 groups (model control group, high, medium, and low dose groups of the granules of Example 1, and the Jingbo-Shan group) of 8 rats each. The low, medium, and high doses of the granules of Example 1 were 0.9 g / kg, 1.8 g / kg, and 3.6 g / kg, respectively, and the dose of the Jingbo-Shan group was 2.5 g / kg, dissolved in purified water, and administered at a dose of 10 mL / kg. The normal control group and the model control group were intragastrically administered with an equal volume of purified water. The administration was continued for 13 days.

[0098] 3. Indicator Testing 3.1 Measuring cough frequency 3.2 Measurement of serum eosinophil cationic protein (ECP) content

[0099] 3.3 Statistical methods The analysis was performed using SPSS19.0 statistical software.

[0100]

number

[0101] After testing for homogeneity of variance, analysis of variance was used for comparisons between multiple groups, and the LSD method was used for pairwise comparisons. P<0.05 indicates statistical significance.

[0102] 4.Results 4.1 Comparison of cough frequency measurements in rats of each group From the 13th day after administration, rats in each group were placed in a sealed box and inhaled 1×10 −4 mol / L capsaicin solution by spray within 5 minutes, after which the number of coughs was recorded and counted.

[0103] [Table 3]

[0104] Note: Compared to the normal control group, # P < 0.05, ## P<0.01. Compared with the model control group, *P<0.05, **P<0.01. Compared with the thorn-proof group, △ P < 0.05, △△ P<0.01.

[0105] Compared with the normal control group, the number of coughs in the model control group increased significantly, with a statistically significant difference (P<0.01). Compared with the model control group, the number of coughs in the low, medium, and high dose groups of Example 1 Granules decreased significantly, with a statistically significant difference (P<0.05, P<0.01). Compared with the Jingbosan group, the number of coughs in the medium and high dose groups of Example 1 Granules decreased obviously, with a statistically significant difference (P<0.05, P<0.01).

[0106] The above experimental results showed that Keibo Granules could suppress the coughing reaction in rats, had the effect of suppressing cough in cough asthma, and had a superior cough suppressant effect to Keibo San.

[0107] 4.2 Comparison of serum ECP content in rats of each group On the 14th day of the experiment, the animals were killed, and 5 mL of blood was collected from the abdominal aorta, left at 4°C, centrifuged at 2000 r / min for 10 min, and the serum was separated and stored at -20°C. The measurement was performed strictly according to the instruction manual of the ECP ELISA kit.

[0108] [Table 4]

[0109] Note: Compared to the normal control group, # P < 0.05, ## P<0.01. Compared with the model control group, *P<0.05, **P<0.01. Compared with the thorn-proof group, △ P < 0.05, △△ P<0.01.

[0110] Compared with the normal control group, the serum ECP content of the model control group was significantly increased (P<0.01); in each administration group, after treatment, compared with the model control group, the serum ECP content of the high-dose group in Example 1 Granules was obviously reduced (P<0.05, P<0.01), and the serum ECP reduction effect of the high-dose group in Example 1 Granules was better than that of the anti-asthma group (P<0.05, P<0.01). The above test results show that Jingfang Granules can reduce the body's ECP level and alleviate the allergic reaction symptoms of cough asthma.

Claims

1. Use of a Chinese herbal medicine composition comprising Scutellaria Baicalensis, Boufu Root, Qianhuo Root, Angelica Root, Bupleurum Root, Cnidium Officinale, Anemone Root, Poria Root, Platycodon Root, and Licorice Root in the manufacture of a medicament for treating cough asthma.

2. The use according to claim 1, characterized in that the cough asthma is any one of the following types: cold wheezing, hot wheezing, external cold internal heat type, and lung fullness and kidney deficiency type.

3. 2. The use according to claim 1, characterized in that it reduces the percentage of eosinophils in bronchoalveolar lavage fluid (BALF) and serum eosinophil cationic protein levels in patients with cough asthma.

4. The herbal medicine composition contains, as its main raw materials: The use described in any one of claims 1 to 3, characterized in that it is produced from 5 to 30 parts by weight of Scutellaria Root, 5 to 30 parts by weight of Bouquet of Flowering Plant, 5 to 30 parts by weight of Qiang Huo, 5 to 30 parts by weight of Angelica Root, 3 to 25 parts by weight of Bupleurum Root, 3 to 25 parts by weight of Qiang Huo, 5 to 30 parts by weight of Cnidium Root, 3 to 25 parts by weight of Kikko Root, 5 to 30 parts by weight of Poria Root, 3 to 25 parts by weight of Platycodon Root, and 1 to 10 parts by weight of Licorice.

5. The herbal medicine composition contains, as its main raw materials: The use according to claim 4, characterized in that it is made from 10-20 parts by weight of Scutellaria Root, 10-20 parts by weight of Fangfeng Root, 10-20 parts by weight of Qiang Huo, 10-20 parts by weight of Angelica Root, 3-20 parts by weight of Bupleurum Root, 3-20 parts by weight of Qiang Huo, 10-20 parts by weight of Cnidium Root, 3-20 parts by weight of Kii Root, 10-25 parts by weight of Poria Root, 3-20 parts by weight of Platycodon Root, and 1-8 parts by weight of Licorice Root.

6. The herbal medicine composition contains, as its main raw materials: The use described in claim 5, characterized in that it is made from 15 parts by weight of Scutellaria Root, 15 parts by weight of Fangfeng Root, 15 parts by weight of Qiang Huo, 15 parts by weight of Angelica Root, 15 parts by weight of Bupleurum Root, 15 parts by weight of Qiang Huo, 15 parts by weight of Cnidium Root, 15 parts by weight of Kikko Root, 15 parts by weight of Poria Root, 15 parts by weight of Platycodon Root, and 5 parts by weight of Licorice Root.

7. The method for producing the herbal medicine composition includes: Step A is to distill Scutellaria Baicalensis, Scutellaria Baicalensis, Scutellaria Baicalensis, Angelica Root, Oriental Green Tea, Cnidium Officinalis, and Anemone Root to extract volatile oils, and prepare the distillation residue, the distillation Cnidium Officinalis, and the aqueous solution of Anemone Root for use; Step B is to prepare the distilled aqueous solution of Cnidium officinalis and Cnidium husk obtained in step A into a 10-40% ethanol solution for use; Step C is to mix the Poria cocos, the distilled Cnidium officinalis and the residue of the husk obtained in step A, and leach and extract the mixture with the ethanol solution obtained in step B, and prepare the leachate for use; Step D is to add water to the Bupleurum Root, Platycodon Root, Licorice Root, and the distilled Scutellaria Root, Bougainvillea Root, Qiang Huo, Angelica Root, and Chinese Husk residue obtained in step A, and boil them, and concentrate the boiled liquid for use; Step E: mixing and concentrating the infusion obtained in step C and the decoction obtained in step D, and adding the volatile oil obtained in step A to obtain the herbal composition; Including, Preferably, in step B, the distilled aqueous solution of Cnidium officinalis and Cnidium husk obtained in step A is prepared into a 15-30% ethanol solution for use; More preferably, in step B, the distilled aqueous solution of Cnidium officinalis and Cnidium husk obtained in step A is prepared into a 25% ethanol solution for use; Use according to any one of claims 1 to 3.

8. The use according to claim 7, characterized in that the herbal composition does not contain or contains one or more pharma-ceutically acceptable pharmaceutical excipients.

9. The use according to claim 8, characterized in that the herbal composition is made into one or more of tablets, oral liquids, capsules, pills, granules, and liquid oral formulations.

Images