Traditional Chinese medicine composition for SARS-CoV-2 infection rehabilitation period and preparation method and application thereof

Abstract

The invention discloses a traditional Chinese medicine composition for SARS-CoV-2 infection convalescence as well as a preparation method and application of the traditional Chinese medicine composition. The traditional Chinese medicine composition is prepared from the following traditional Chinese medicine raw materials in parts by weight: 1-20 parts of semen sinapis; 1-20 parts of fructus perillae; 1-20 parts of semen raphani; 1-20 parts of fritillary bulb; 1-20 parts of perilla frutescens; 1-20 parts of platycodon grandiflorum; 1-20 parts of apricot kernel; 1-20 parts of radix puerariae; 1-20 parts of exocarpium citri rubrum; 1-20 parts of poria cocos; and 1-20 parts of licorice. The raw materials in the formula are all traditional Chinese medicines with homology of medicine and food, and have very high safety; the traditional Chinese medicine composition has obvious effects on relieving asthma, relieving cough, reducing sputum, expanding airway and enhancing immunity aiming at the symptoms such as breathing obstruction, vital capacity decline, cough, chest distress, breath promotion, weakness and the like, has an obvious effect of improving lung functions, and is a pure traditional Chinese medicine rehabilitation medicine which is safe and effective to SARS-CoV-2 infection.

Description

Technical Field

[0001] The present invention relates to the field of traditional Chinese medicine, and in particular to a traditional Chinese medicine composition for the recovery period of SARS-CoV-2 infection, and a preparation method and application thereof. Background Art

[0002] Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is highly contagious and highly variable. It is mainly transmitted through aerosols in confined spaces. After viral infection, the main clinical manifestations are fever, cough, chest tightness, and fatigue. A few patients also have symptoms such as nasal congestion, runny nose, sore throat, myalgia, and diarrhea. Severe patients often experience dyspnea and / or hypoxemia one week after onset. In severe cases, they can rapidly progress to acute respiratory distress syndrome, septic shock, difficult-to-correct metabolic acidosis and coagulation disorders, and multiple organ failure. Even after being treated and out of danger, patients will still have a variety of clinical symptoms for a long period of time. After the acute phase of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, some symptoms can last for several months and involve almost all organ systems, including loss of sensation (taste and smell), cough, persistent fatigue, cardiopulmonary symptoms (myocarditis, pulmonary fibrosis, etc.), cognitive and mental disorders (brain fog, memory loss), and metabolic dysfunction. This is because SARS-CoV-2 invades host cells mainly through the viral spike protein subunit binding to the cell's angiotensin-converting enzyme 2 (ACE2) receptor, which is widely present in multiple organs or tissues throughout the body, including the lungs, heart, gastrointestinal tract, nasal mucosa, neurons, and vascular endothelium. It can cause systemic multi-system damage including arrhythmia, heart failure, ischemic stroke, and the nervous system, and the virus can exist in the body for several months. There is no specific drug for the treatment of SARS-CoV-2 infection, and symptomatic treatment is the main treatment. Traditional Chinese medicine believes that SARS-CoV-2 infection belongs to "dampness and poison epidemic" and "cold and damp epidemic". Dampness belongs to yin evil, which can easily hurt yang qi, block qi mechanism, and is lingering and difficult to resolve.

[0003] In the treatment of SARS-CoV-2 infection, traditional Chinese medicine has played a great role, and Qingfei Paidu Decoction, Huashi Baidu Decoction, Xuanfei Baidu Decoction, Jinhua Qinggan Granule, etc. have achieved good therapeutic effects. However, some serious patients have a long recovery period, and it is necessary to study solutions for the recovery period after SARS-CoV-2 infection in order to achieve better therapeutic effects. Summary of the invention

[0004] In order to solve the problems mentioned in the background technology, the present invention provides a traditional Chinese medicine composition for the recovery period of SARS-CoV-2 infection, and a preparation method and application thereof. The symptoms of the recovery period after SARS-CoV-2 infection are mainly respiratory obstruction, decreased vital capacity, cough, chest tightness, shortness of breath, fatigue, etc.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] The first aspect of the present invention provides a Chinese medicine composition for the recovery period of SARS-CoV-2 infection, which is prepared by the following Chinese medicine raw materials in parts by weight: 1-20 parts of mustard seeds; 1-20 parts of perilla seeds; 1-20 parts of radish seeds; 1-20 parts of Fritillaria; 1-20 parts of Perilla; 1-20 parts of Platycodon; 1-20 parts of Apricot kernel; 1-20 parts of Pueraria root; 1-20 parts of Tangerine peel; 1-20 parts of Poria; 1-20 parts of Licorice. The raw materials in the prescription are all Chinese medicinal materials with medicinal and edible properties, and have high safety. This prescription is used as a basic prescription for rehabilitation medication in the recovery period after SARS-CoV-2 infection.

[0007] Preferably, the Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 5-20 parts of mustard seeds; 5-20 parts of perilla seeds; 5-20 parts of radish seeds; 5-20 parts of Fritillaria; 5-20 parts of Perilla; 5-20 parts of Platycodon; 5-20 parts of Apricot kernel; 5-20 parts of Pueraria root; 5-20 parts of Tangerine peel; 5-20 parts of Poria; and 5-15 parts of Licorice.

[0008] More preferably, the Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 10-15 parts of mustard seeds; 10-15 parts of perilla seeds; 10-15 parts of radish seeds; 10-15 parts of Fritillaria; 10-15 parts of Perilla; 10-15 parts of Platycodon; 10-15 parts of Apricot; 5-10 parts of Pueraria; 5-10 parts of Tangerine peel; 5-10 parts of Poria; and 5-10 parts of Licorice.

[0009] Furthermore, for lung function impairment characterized by cough and phlegm-dampness blocking the lungs, the Chinese medicine composition, in addition to the basic prescription, also includes the following Chinese medicinal raw materials in parts by weight: 1-20 parts of Pinellia, 1-20 parts of Ephedra, 1-20 parts of Paris polyphylla, and 1-20 parts of Cinnamon twig.

[0010] Furthermore, for lung function impairment characterized by persistent wheezing and damp-heat attacking the surface, the Chinese medicine composition, in addition to the basic prescription, also includes the following Chinese medicinal raw materials in parts by weight: 1-20 parts of Angelica sinensis, 1-20 parts of Sophora flavescens, and 1-20 parts of Angelica dahurica.

[0011] Furthermore, for lung function impairment characterized by chest tightness, fatigue and lung fluid deficiency, the Chinese medicine composition, in addition to the basic prescription, also includes the following Chinese medicine raw materials in parts by weight: 1-20 parts of ginseng, 1-20 parts of polygonatum, 1-20 parts of wolfberry, and 1-20 parts of eucommia leaves.

[0012] The technical solution adopted by the present invention also includes a preparation of the Chinese medicine composition, and the dosage form of the Chinese medicine composition is: oral liquid, granules, dripping pills, capsules and tablets.

[0013] The second aspect of the present invention provides a method for preparing a Chinese medicine composition for the recovery period of SARS-CoV-2 infection, wherein all the raw materials in the Chinese medicine composition are weighed and mixed according to their weight, extracted multiple times with water or a water / ethanol system, and the ethanol concentration is 10-70%, the extracts are filtered and combined, and concentrated under reduced pressure to form an extract, or spray-dried to obtain a raw material drug, and the extract or raw material drug is added with excipients to prepare a clinically acceptable dosage form, including oral solution, granules, pills, capsules and tablets.

[0014] In some specific embodiments, the method for preparing the oral liquid of the above dosage form is to dissolve the above extract or raw material drug in an appropriate amount of sterile pure water, adjust to an appropriate volume, and then add flavoring agents, preservatives, etc. to prepare an oral liquid.

[0015] In some specific embodiments, the preparation method of the granules of the above dosage form is to mix the above raw materials with an appropriate amount of pharmaceutical excipients, wet them with ethanol of a certain concentration, granulate them, and obtain granules after drying.

[0016] In some specific embodiments, the preparation method of the above-mentioned dosage form of the dropping pills is to mix the above-mentioned raw materials with an appropriate amount of pharmaceutical excipients, use solid dispersion technology, heat to melt, drip into an immiscible cooling liquid, wash off the surface cooling liquid after cooling, and obtain the dropping pills after drying.

[0017] In some specific embodiments, the method for preparing the capsule of the above dosage form is to prepare the above raw materials and appropriate amounts of pharmaceutical excipients such as diluents, glidants, disintegrants, etc. into uniform powder or granules, and fill them into hollow capsules to obtain capsules.

[0018] In some specific embodiments, the tablet preparation method of the above dosage form is to mix the above raw materials with an appropriate amount of pharmaceutical excipients to make a soft material, then sieve through a 16-mesh sieve to make granules, dry and granulate, add a glidant and a disintegrant to mix evenly, and press to obtain tablets.

[0019] The third aspect of the present invention provides a use of the above-mentioned traditional Chinese medicine composition in the preparation of rehabilitation medicines, health products and foods for the recovery period after SARS-CoV-2 infection.

[0020] Solution

[0021] According to traditional Chinese medicine, SARS-CoV-2 infection is caused by dampness, which first attacks the lungs. Therefore, the pathogenic factors mainly invade the lungs, and severe cases are often accompanied by breathing difficulties. Even after the acute onset period, since lung function has been damaged, the treatment should be based on the principles of warming the lungs and resolving phlegm, relieving cough and asthma, and strengthening the body and eliminating evil.

[0022] The composition of this basic prescription draws on the classic prescriptions "Sanzi Yangqin Decoction" and "Xingsu Powder", that is, the three herbs of "Sanzi Yangqin Decoction" - mustard seeds, perilla seeds, and radish seeds - are added with the five herbs of "Xingsu Powder" - perilla, platycodon, apricot kernel, poria, and licorice, supplemented with kudzu root, fritillaria, and tangerine peel, etc. It has the functions of clearing away heat and resolving phlegm, moistening the lungs and relieving cough, and also has the effects of relieving asthma, relieving muscles and releasing exterior, and lowering qi and digestion. It has better effects than the original prescriptions "Sanzi Yangqin Decoction" and "Xingsu Powder".

[0023] In the Sanzi Yangqin Decoction, Perilla seeds are pungent, warm, and belong to the lung meridian. They can lower qi and resolve phlegm, relieve cough and asthma, and moisten the intestines and relieve constipation; Mustard seeds are pungent, warm, and belong to the lung meridian. They can dissipate phlegm and promote qi, disperse stagnation, dredge meridians, and relieve pain; Radish seeds are pungent, sweet, and neutral, and belong to the lung, spleen, and stomach meridians. They can help digestion and dissipate bloating, lower qi and resolve phlegm. The combination of the three seeds can help resolve phlegm, smooth qi, and relieve asthma and cough.

[0024] Xingsu powder is mainly used to treat cold and dry external attack, lung qi stagnation, and phlegm and dampness internal obstruction. The original prescription has 11 herbs, and this prescription is modified to use 5 of them. Among them, perilla leaf is pungent and warm without being dry, and it can release the exterior and promote lung qi, so that the cold and dry evil can be eliminated from the exterior; apricot kernel is descending and moistening, and it can promote lung qi to relieve cough. Platycodon grandiflorum promotes and descends lung qi, relieves cough and resolves phlegm. Poria is sweet and flat in nature, and it can penetrate dampness and promote diuresis, calm the mind and promote body fluid, and moisturize the spleen and lungs. Licorice harmonizes all the herbs. All the herbs are used together, and they can disperse and promote lung qi to resolve cold and dryness, resolve phlegm and regulate qi to cure cough.

[0025] The root of Pueraria in this prescription is pungent and cool, dispels wind, nourishes body fluids, and moistens tendons and veins. It can dispel the evil of Yingwei, and relieve the symptoms of high fever, loss of body fluids, and limb pain after SARS-CoV-2 invades the upper part of the lungs; Fritillaria has a bitter and cold taste and enters the lungs and heart meridians, and enters the lungs to clear and resolve phlegm, dissipate knots and relieve depression. It can clear the lungs and promote qi, regulate qi, disperse body fluids, make the airway smooth, and restore normal breathing without phlegm; Tangerine peel has a pungent and bitter taste, is warm in nature, and enters the lungs and spleen meridians, which can regulate qi and relieve fullness, dry dampness and resolve phlegm, and has a unique therapeutic effect on cough and phlegm caused by lung injury.

[0026] In summary, the combination of the above-mentioned prescriptions and medicines can achieve the functions of promoting lung function and resolving phlegm, relieving cough and asthma, dispelling cold and dampness, and relieving exterior symptoms and expelling wind. The new prescription not only has the effects of the original prescriptions "Sanzi Yangqin Decoction" and "Xingsu San", but also has better efficacy, and can significantly improve the related symptoms after SARS-CoV-2 infection.

[0027] Compared with the prior art, the beneficial effects of the present invention are as follows: the present invention provides a Chinese medicine composition and a preparation method thereof, which can effectively improve the symptoms of respiratory obstruction, decreased vital capacity, cough, chest tightness, shortness of breath, fatigue and the like caused by lung function damage. At the same time, since it is mainly composed of Chinese medicines with the same origin as medicine and food, it provides a safer treatment scheme for improving lung function compared with chemical drugs and other Chinese medicines, and can be taken for a long time. The product of the present invention has been proved by animal pharmacodynamic tests to have significant effects in relieving asthma, relieving cough and reducing phlegm, airway dilation and enhancing immunity. It has also been clinically verified to have a significant effect on improving lung function in patients infected with SARS-CoV-2. Studies have shown that the new formula not only maintains the original efficacy of "Sanzi Yangqin Decoction" and "Xingsu Powder", but also has better animal efficacy and clinical treatment effects than the original prescriptions. DETAILED DESCRIPTION

[0028] The technical solutions in the embodiments of the present invention are described clearly and completely below. Obviously, the described embodiments are only 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.

[0029] Example 1

[0030] Preparation of the basic Chinese medicine composition raw material JC1 of the present invention: 6000g of mustard seeds, 9000g of perilla seeds, 9000g of radish seeds, 3000g of fritillaria, 6000g of perilla, 6000g of platycodon, 9000g of apricot kernel, 2000g of kudzu root, 6000g of tangerine peel, 10000g of poria, 3000g of liquorice, the above drugs are combined, heated and boiled with 700L and 600L of water respectively, and extracted twice, each time for 1 hour, filtered and combined the filtrate, concentrated under reduced pressure to an appropriate volume, and spray-dried to obtain the basic raw material medicine, which is numbered JC1.

[0031] Example 2

[0032] Preparation of raw material JC2 of the basic Chinese medicine composition of the present invention: 100g of mustard, 100g of perilla seed, 100g of radish seed, 20g of fritillaria, 200g of perilla, 200g of platycodon, 200g of apricot, 200g of kudzu root, 200g of tangerine peel, 200g of poria, 100g of liquorice, the above drugs are combined, and extracted twice with 20L and 18L of 10% ethanol by heating and reflux, each time for 1 hour, and the filtrate is combined after filtration, concentrated under reduced pressure to an appropriate volume, and spray-dried to obtain the product, which is numbered JC2.

[0033] Example 3

[0034] Preparation of raw material JC3 of the basic Chinese medicine composition of the present invention: 100g of mustard, 100g of perilla seed, 100g of radish seed, 100g of fritillaria, 100g of perilla, 100g of platycodon, 100g of apricot, 100g of kudzu root, 100g of tangerine peel, 100g of poria and 100g of liquorice. The above drugs are combined, and extracted twice with 11L and 9L of 60% ethanol by heating and reflux, each time for 1hr, and the filtrates are combined after filtration, concentrated under reduced pressure to an appropriate volume, and spray-dried to obtain the product, which is numbered JC3.

[0035] Comparative Example 1

[0036] Preparation of Sanzi Yangqin Decoction raw material medicine SZ: 18000g of mustard seeds, 27000g of perilla seeds, and 27000g of radish seeds. After combining the above three herbs, they are heated and boiled with 720L and 600L of water respectively, and extracted twice for 1 hr each time. After filtering, the filtrates are combined, concentrated under reduced pressure to an appropriate volume, and spray-dried to obtain the raw material medicine, which is numbered SZ.

[0037] Comparative Example 2

[0038] Preparation of Xingsu Powder API XS: 6000g of Perilla, 9000g of Apricot, 6000g of Processed Pinellia, 10000g of Poria, 3000g of Licorice, 6000g of Peucedanum, 6000g of Platycodon, 6000g of Citrus aurantium, 6000g of Tangerine Peel, 6000g of Ginger, 2000g of Jujube. The above drugs are combined, heated and boiled with 660L and 520L of water respectively, and extracted twice for 1 hr each time. The filtrates are combined after filtration, concentrated under reduced pressure to an appropriate volume, and spray-dried to obtain the API, numbered XS.

[0039] Example 4

[0040] The invention discloses a raw material medicine JCT1 of a Chinese medicine composition for treating cough and phlegm-dampness obstructing the lungs: 100g of mustard, 100g of perilla seed, 100g of radish seed, 100g of fritillaria, 100g of perilla, 100g of platycodon, 100g of apricot kernel, 100g of kudzu root, 100g of tangerine peel, 100g of tuckahoe, 100g of liquorice, 100g of pinellia tuber, 100g of ephedra, 100g of parsley and 100g of cassia twig. The above medicines are combined, and the mixture is extracted twice by heating and refluxing with 15L and 12L of 20% ethanol successively, each time for 1 hour, and the filtrates are combined after filtration, and the ethanol is recovered under reduced pressure and spray-dried to obtain the mixture, which is numbered as JCT1.

[0041] Example 5

[0042] The invention discloses a raw material medicine JCT2 for a Chinese medicine composition for treating cough and phlegm-dampness obstructing the lungs: 100 g of mustard seeds, 100 g of perilla seeds, 100 g of radish seeds, 100 g of fritillaria, 100 g of perilla, 100 g of platycodon, 100 g of apricot kernel, 100 g of kudzu root, 100 g of tangerine peel, 100 g of poria, 100 g of liquorice, 50 g of pinellia tuber, 50 g of ephedra, 50 g of paridis and 50 g of cassia twig. The above medicines are combined, and the raw materials are extracted twice by heating and refluxing with 13 L and 10 L of 40% ethanol, respectively, for 1 hour each time. The filtrates are combined after filtration, the ethanol is recovered under reduced pressure, and the mixture is spray-dried to obtain the raw material medicine, which is numbered as JCT2.

[0043] Example 6

[0044] The invention discloses a raw material medicine JCT3 of a Chinese medicine composition for treating cough and phlegm-dampness obstructing the lungs: 100g of mustard, 100g of perilla seed, 100g of radish seed, 100g of fritillaria, 100g of perilla, 100g of platycodon, 100g of apricot kernel, 100g of kudzu root, 100g of tangerine peel, 100g of tuckahoe, 100g of liquorice, 100g of pinellia tuber, 100g of ephedra, 100g of parsley and 100g of cassia twig. The above medicines are combined, and the mixture is extracted twice by heating and refluxing with 12L and 9L of 60% ethanol successively, each time for 1hr, and the filtrates are combined after filtration, and the ethanol is recovered under reduced pressure and spray-dried to obtain the mixture, which is numbered as JCT3.

[0045] Example 7

[0046] The preparation method of the raw material medicine JCC1 of the Chinese medicine composition for the symptoms of wheezing and damp-heat attacking the exterior of the body includes: 100g of mustard seeds, 100g of perilla seeds, 100g of radish seeds, 100g of fritillaria, 100g of perilla, 100g of platycodon, 100g of apricot kernel, 100g of kudzu root, 100g of tangerine peel, 100g of poria, 100g of liquorice, 100g of angelica, 100g of sophora flavescens, 100g of angelica dahurica, the above medicines are combined, and the extraction is carried out twice by heating and refluxing with 14L and 11L of 60% ethanol successively, each time for 1hr, the filtrates are combined after filtration, the ethanol is recovered under reduced pressure, and the mixture is spray-dried to obtain the mixture, which is numbered as JCC1.

[0047] Example 8

[0048] The preparation method of the raw material medicine JCC2 of the Chinese medicine composition for persistent wheezing and damp-heat attacking the exterior syndrome of the present invention is as follows: 200g of mustard seeds, 200g of perilla seeds, 200g of radish seeds, 100g of fritillaria, 100g of perilla, 100g of platycodon, 100g of apricot kernel, 200g of kudzu root, 100g of tangerine peel, 100g of poria, 100g of liquorice, 10g of angelica, 10g of sophora flavescens and 10g of angelica dahurica. The above medicines are combined, and the mixture is heated and refluxed with 15L and 12L of 50% ethanol for extraction twice, each time for 1hr, and the filtrates are combined after filtration, and the ethanol is recovered under reduced pressure and spray-dried to obtain the product, which is numbered as JCC2.

[0049] Example 9

[0050] The preparation method of the raw material medicine JCC3 of the Chinese medicine composition for wheezing and damp-heat attacking the exterior syndrome of the present invention includes: 10g of mustard seed, 10g of perilla seed, 10g of radish seed, 200g of fritillaria, 200g of perilla, 200g of platycodon, 200g of apricot kernel, 200g of kudzu root, 200g of tangerine peel, 200g of poria, 200g of liquorice, 100g of angelica, 50g of sophora flavescens, 170g of angelica dahurica, the above medicines are combined, and the extraction is carried out twice by heating and refluxing with 16L and 12L of 70% ethanol successively, each time for 1hr, the filtrate is combined after filtering, the ethanol is recovered under reduced pressure, and the product is obtained after spray drying, which is numbered JCC3.

[0051] Example 10

[0052] The invention discloses a raw material medicine JCX1 for a Chinese medicine composition for treating chest tightness, fatigue and deficiency of lung fluid: 200 g of mustard, 200 g of perilla seed, 200 g of radish seed, 200 g of fritillaria, 200 g of perilla, 200 g of platycodon, 200 g of apricot, 200 g of kudzu root, 200 g of tangerine peel, 200 g of poria, 200 g of liquorice, 200 g of ginseng, 200 g of polygonatum, 200 g of wolfberry and 200 g of eucommia. The above medicines are combined, and the mixture is heated and boiled with 30 L and 24 L of water respectively for extraction twice, each time for 1 hour. The filtrates are combined after filtration, concentrated under reduced pressure to an appropriate volume, and spray-dried to obtain the mixture, which is numbered as JCX1.

[0053] Embodiment 11

[0054] The preparation method of the raw material medicine JCX2 of the Chinese medicine composition for chest tightness, fatigue and lung fluid deficiency of the present invention includes: 100g of mustard, 100g of perilla seed, 100g of radish seed, 100g of fritillaria, 100g of perilla, 100g of platycodon, 100g of apricot, 100g of kudzu root, 100g of tangerine peel, 100g of poria, 100g of liquorice, 50g of ginseng, 50g of polygonatum, 50g of wolfberry and 50g of eucommia. The above medicines are combined, and the mixture is extracted twice by heating and reflux with 13L and 10L of 60% ethanol, respectively, for 1 hour each time. The filtrates are combined after filtration, the ethanol is recovered under reduced pressure, and the mixture is spray-dried to obtain the product, which is numbered as JCX2.

[0055] Example 12

[0056] The invention discloses a raw material medicine JCX3 for a Chinese medicine composition for treating chest tightness, fatigue and deficiency of lung fluid: 100 g of mustard, 100 g of perilla seed, 200 g of radish seed, 100 g of fritillaria, 200 g of perilla, 200 g of platycodon, 200 g of apricot kernel, 200 g of kudzu root, 200 g of tangerine peel, 200 g of poria, 30 g of liquorice, 200 g of ginseng, 200 g of polygonatum, 200 g of wolfberry fruit and 200 g of eucommia leaf. The above medicines are combined, and the mixture is extracted twice by heating and refluxing with 25 L and 20 L of 40% ethanol, respectively, for 1 hour each time. The filtrates are combined after filtration, the ethanol is recovered under reduced pressure, and the mixture is spray-dried to obtain the mixture, which is numbered as JCX3.

[0057] Example 13

[0058] Preparation of oral liquid: Take 100 g of the raw material JC1 of Example 1, add 2000 mL of water to dissolve, fill into 200 10 mL oral liquid bottles, and obtain after sterilization.

[0059] Embodiment 14

[0060] Preparation of granules: Take 10000 g of the raw materials JC1, SZ and XS of Example 1, Comparative Example 1 and Comparative Example 2, respectively, add 15000 g of dextrin, wet granulate with appropriate amount of ethanol, dry below 80°C, granulate, and package them in bags of 6 g each, and obtain them, numbered KJC1, KSZ and KXS respectively, for subsequent experiments.

[0061] Embodiment 15

[0062] Preparation of dropping pills: Take 100 g of the raw material JCT3 of Example 6, add 400 g of PEG6000 to evenly disperse the drug, heat and melt, place in a dropping pill machine, drop into dimethyl silicone oil coolant, wash off the dimethyl silicone oil on the surface after cooling, and dry to obtain the pellets.

[0063] Example 16

[0064] Preparation of capsules: Take 100 g of the raw material JCC2 in Example 8, add 150 g of dextrin and 150 g of microcrystalline cellulose and mix well, then add appropriate amount of ethanol to make a soft material, granulate with a 16-mesh sieve, sieve the whole with a 20-mesh sieve, mix with a small amount of talcum powder after drying, and put into the selected empty capsule to obtain.

[0065] Embodiment 17

[0066] Preparation of tablets: Take 100 g of the raw material JCX1 of Example 10, add 100 g of microcrystalline cellulose and 50 g of starch, mix well, add ethanol to make a soft material, granulate and dry, add 10 g of magnesium stearate and 10 g of micropowder silica gel, mix well and press into tablets of a certain specification.

[0067] Embodiment 18

[0068] Asthma relief experiment

[0069] Preparation of sensitizer: Take 2g of acetylcholine chloride and 0.1g of histamine phosphate, add water and mix well, and make up to 100ml.

[0070] Animal modeling: guinea pigs were placed in a glass bell jar and sprayed with a mixture of 2% acetylcholine chloride and 0.1% histamine phosphate at a pressure of 400 mmHg for 15 seconds. The asthma induction latency was observed, and guinea pigs whose asthma attack, breathing difficulties, and convulsions and collapse were within 120 seconds from the start of spraying were selected as test animals. The blank control group was treated with physiological saline instead of the sensitizer.

[0071] Test method: Take JC1, SZ and XS raw materials in Example 1, Comparative Example 1 and Comparative Example 2, take 88 model guinea pigs and randomly divide them into 11 groups, 8 in each group: (1) blank control group; (2) JC1 low-dose group 100 mg / kg; (3) JC1 medium-dose group 200 mg / kg; (4) JC1 high-dose group 400 mg / kg; (5) SZ low-dose group 100 mg / kg; (6) SZ medium-dose group 200 mg / kg; (7) SZ high-dose group 400 mg / kg; (8) XS low-dose group 100 mg / kg; (9) XS medium-dose group 200 mg / kg; (10) XS high-dose group 400 mg / kg; (11) positive drug aminophylline 150 mg / kg.

[0072] The above guinea pigs were fed with drugs for 4-5 days. 1.5 hours after the last gavage (the aminophylline group was intraperitoneally injected with 150ul of aminophylline 30 minutes before the induction of asthma), the guinea pigs were placed in a glass bell jar one by one for atomization inhalation. The asthma incubation period of each animal and the number of falls within 120 seconds were recorded. The obtained data were analyzed using SPSS11.0 statistical analysis software. The quantitative data were expressed as mean ± standard deviation. The quantitative comparison was performed using one-way analysis of variance.

[0073] The experimental results are shown in Table 1 below.

[0074] Table 1 Effects of Chinese herbal extracts on the antiasthmatic effect in guinea pigs

[0075]

[0076] Note: Compared with the blank control group *P<0.05; **P<0.01; ***P<0.001

[0077] The statistical results in Table 1 show that compared with the blank control group, the high-dose SZ group, the high-dose XS group and the JC1 group were significantly different from the aminophylline group, among which the high-dose SZ and XS groups and the low-dose JC1 group were significantly different from the blank group (P<0.05); the medium-dose JC1 group and the aminophylline group were significantly different from the blank group (P<0.01); the high-dose JC1 group was extremely significantly different from the blank group (P<0.001).

[0078] It can be seen from this that the basic prescription of the present invention has better antiasthmatic effect than Sanzi Yangqin Decoction and Xingsu Powder.

[0079] Embodiment 19

[0080] Cough Suppression Experiment

[0081] Experimental method: Take JC1, SZ and XS raw materials in Example 1, Comparative Example 1 and Comparative Example 2, take 110 healthy mice and randomly divide them into 11 groups, with 10 mice in each group: (1) blank control group; (2) JC1 low-dose group 100 mg / kg; (3) JC1 medium-dose group 200 mg / kg; (4) JC1 high-dose group 400 mg / kg; (5) SZ low-dose group 100 mg / kg; (6) SZ medium-dose group 200 mg / kg; (7) SZ high-dose group 400 mg / kg; (8) XS low-dose group 100 mg / kg; (9) XS medium-dose group 200 mg / kg; (10) XS high-dose group 400 mg / kg; (11) positive drug kebiqing group 15 mg / kg.

[0082] After 3 days of conventional feeding, the mice were gavaged and administered once a day for three consecutive days. One hour after the last administration, a cotton ball was placed in a large beaker, 1 mL of 25% concentrated ammonia was drawn with a syringe and injected into the cotton ball. The mice in each group were placed in the large beaker, and the coughing action of the mice was observed (open mouth, abdominal muscle contraction, sometimes coughing), and the cough latency of the mice (the time from the mouse being placed in the large beaker to the occurrence of coughing) and the number of coughs within 180 seconds were immediately recorded.

[0083] The test results are shown in Table 2 below.

[0084] Table 2 Effects of Chinese herbal extracts on antitussive effect in mice

[0085]

[0086] Note: Compared with the blank control group *P<0.05; **P<0.01; ***P<0.001

[0087] The results in Table 2 show that in terms of prolonging the cough latency of mice, compared with the blank control group, the low-dose JC1 group, the high-dose SZ and XS groups had significant differences (*P<0.05); the medium-dose JC1 group and the positive control group had significant differences (**P<0.01); and the high-dose JC1 group had extremely significant differences (***P<0.001).

[0088] In terms of reducing the number of coughing times within 3 minutes in mice, compared with the blank control group, the JC1 low-dose group, the SZ medium- and high-dose groups, and the XS medium- and high-dose groups all had significant differences (*P<0.05); the JC1 medium-dose group and the positive control group had significant differences (**P<0.01); and the JC1 high-dose group had extremely significant differences (***P<0.001).

[0089] It can be seen from this that the basic prescription of the present invention has better antitussive effect than Sanzi Yangqin Decoction and Xingsu Powder.

[0090] Embodiment 20

[0091] Expectorant experiment

[0092] Experimental method: Take the Chinese medicinal raw materials JC3 and JCT3 in Example 3 and Example 6, and take 80 healthy Kunming male mice, and randomly divide them into 8 groups, with 10 mice in each group: (1) blank control group; (2) JC3 low-dose group 100 mg / kg; (3) JC3 medium-dose group 200 mg / kg; (4) JC3 high-dose group 400 mg / kg; (5) JCT3 low-dose group 100 mg / kg; (6) JCT3 medium-dose group 200 mg / kg; (7) JCT3 high-dose group 400 mg / kg; (8) positive drug ammonium chloride group 500 mg / kg.

[0093] After 3 days of conventional feeding, the drug was administered by gavage. The drug was administered once a day for three consecutive days. The mice were fasted for 12 hours before the experiment, but water was not allowed. One hour after the last administration, 0.5 ml of 0.25% phenol red saline solution was injected intraperitoneally. After 30 minutes, the mice were killed by cervical dislocation and fixed on the operating board in the supine position. The skin of the neck was cut open, the trachea was separated, and the tracheal segment from the thyroid cartilage to the tracheal bifurcation was taken. The tracheal segment was placed in 1.5 mL of 5% sodium bicarbonate solution, ultrasonicated for 30 minutes, centrifuged at 2000 r / min for 5 minutes, and the supernatant was taken. The OD value was measured at 546 nm on an enzyme marker, and a standard curve was made with phenol red. The phenol red content (μg / ml) was calculated according to the standard curve, and statistical processing was performed.

[0094] The test results are shown in Table 3 below.

[0095] Table 3 Effects of Chinese herbal extracts on expectorant effect in mice

[0096]

[0097] Note: Compared with the control group *P<0.05; **P<0.01; P<0.001.

[0098] The experimental results in Table 3 show that compared with the control group, the respiratory tract phenol red excretion of the Chinese medicine JC3 medium-dose group and JCT3 low-dose group increased significantly, with a significant difference (P<0.05); the respiratory tract phenol red excretion of the Chinese medicine JC3 high-dose group, JCT3 medium-dose group and positive drug group increased significantly, with a significant difference (P<0.01); the respiratory tract phenol red excretion of the Chinese medicine JCT3 high-dose group increased significantly, with an extremely significant difference (P<0.001).

[0099] It can be seen that at the same dose, the expectorant effect of JCT3 is better than that of JC3.

[0100] Embodiment 21

[0101] Airway dilation test—Schultz-Dale response

[0102] Experimental method: Take the Chinese medicinal raw materials JC3 and JCC1 in Example 3 and Example 7, take sensitized guinea pigs to make tracheal slice specimens, a total of 48, and randomly divide them into 8 groups, 6 slices in each group: (1) blank control group; (2) JC3 low-dose group 100 mg / L; (3) JC3 medium-dose group 200 mg / L; (4) JC3 high-dose group 400 mg / L; (5) JCC1 low-dose group 100 mg / L; (6) JCC1 medium-dose group 200 mg / L; (7) JCC1 high-dose group 400 mg / L; (8) positive drug isoproterenol control group 1.0 μmol / L.

[0103] The isolated guinea pig trachea was immersed in a fully oxygenated 37℃ Ringer's solution, and a 1g / L ovalbumin concentration was added to model. After the isolated trachea contraction reaction stopped, 10mM BaCl2 was added to make the reaction reach the maximum. The relative value of the ovalbumin contraction amplitude was calculated based on this maximum value. The guinea pig isolated trachea administration group was given the low-dose group of Chinese medicine JC3 and JCC1 100mg / L, the medium-dose group 200mg / L, and the high-dose group 400mg / L, respectively, for 10 minutes. The guinea pig isolated trachea blank control group was given 0.9% normal saline, and the contraction amplitude of the guinea pig trachea was compared. The results showed that each dose group of Chinese medicine had a significant inhibitory effect on the Schultz-Dale reaction of the guinea pig isolated trachea.

[0104] The experimental results are shown in Table 4 below.

[0105] Table 4 Effects of Chinese herbal extracts on contraction of isolated guinea pig trachea

[0106]

[0107] Note: Compared with the blank control group *P<0.05; **P<0.01; ***P<0.001

[0108] The results in Table 4 showed that compared with the blank control group, the medium-dose group of Chinese medicine JC3 and the low-dose group of JCC1 had a significant inhibitory effect on the Schultz-Dale reaction of the isolated guinea pig trachea (*P<0.05), the high-dose group of Chinese medicine JC3 and the medium-dose group of JCC1 had a significant inhibitory effect on the Schultz-Dale reaction of the isolated guinea pig trachea (*P<0.01), and the high-dose group of JCC1 had a very significant inhibitory effect on the Schultz-Dale reaction of the isolated guinea pig trachea (*P<0.001), indicating that both Chinese medicine JC3 and JCC1 may have the effect of inhibiting the release of allergic mediators and antagonizing the airway contraction caused by allergic mediators, and at the same dose, the efficacy of JCC1 is better than that of JC3.

[0109] Embodiment 22

[0110] Immunity enhancement experiment - mouse carbon clearance experiment

[0111] Experimental method: Take the Chinese medicinal raw materials JC3 and JCX2 in Example 3 and Example 11, and take 80 healthy Kunming mice, half of which are male and half are female, and randomly divide them into 8 groups, with 10 mice in each group: (1) blank control group; (2) JC3 low-dose group 100 mg / kg; (3) JC3 medium-dose group 200 mg / kg; (4) JC3 high-dose group 400 mg / kg; (5) JCX2 low-dose group 100 mg / kg; (6) JCX2 medium-dose group 200 mg / kg; (7) JCX2 high-dose group 400 mg / kg; (8) positive drug levamisole group 50 mg / kg.

[0112] After 3 days of conventional feeding, the rats were given drugs by gavage, once a day, for three consecutive days. The blank control group was given saline solution. 30 minutes after the last administration, 0.05-0.1 ml / 10 g body weight of India ink diluted 4 times with saline was injected into the tail vein of each rat. 20 μl of blood was collected from the orbital vein 1 minute and 5 minutes later, added to 2 ml of 0.1% NaCO3 solution and shaken well. The color was measured at 680 nm by spectrophotometer, the optical density (OD) was measured, and the clearance index (K) was calculated. The experimental results are shown in Table 5 below:

[0113] Table 5 Effects of Chinese herbal extracts on carbon clearance index in mice

[0114]

[0115] Note: Compared with the blank control group *P<0.05; **P<0.01; ***P<0.001

[0116] The results in Table 5 show that compared with the blank control group, the carbon clearance index of mice in the JC3 medium-dose group and the JCX2 low-dose group increased significantly (*P<0.05); the carbon clearance index of mice in the JC3 high-dose group, the JCX2 medium-dose group and the positive control levamisole group increased significantly (**P<0.01); the carbon clearance index of mice in the JCX2 high-dose group increased extremely significantly (**P<0.001), indicating that the prescription has the effect of enhancing immunity, and at the same dose, the efficacy of JCX2 is better than that of JC3.

[0117] Embodiment 23

[0118] Spirometry test

[0119] 480 adult cases who recovered about one month after SARS-CoV-2 infection were randomly selected, including 260 males and 220 females, aged 23 to 53 years old. It was clinically confirmed that the clinical symptoms of fever and cough in all cases had disappeared, but there were symptoms of chest tightness and shortness of breath. They were randomly divided into 4 groups, each with 120 cases, one of which was given a placebo, and the other three groups were given the granules KJC1, KSZ and KXS in Example 14, respectively. The vital capacity was measured one month and two months after recovery, respectively. The test results are shown in Table 6 below:

[0120] Table 6 Comparison of vital capacity between the two groups at different recovery periods

[0121]

[0122] Note: Compared with the placebo group, *P<0.05, **P<0.01

[0123] The results in Table 6 show that compared with the placebo group, the lung function of the KJC1, KSZ and KXS groups after two months of recovery was significantly improved, and their vital capacity was significantly increased compared with the placebo group and before medication. Among them, there were significant differences between the KSZ and KXS groups and the placebo group and before medication (*P<0.05), and there was a very significant difference between the KJC1 group and the placebo group and before medication (**P<0.01), indicating that the prescription has a good recovery and improvement effect on the decline in lung function and vital capacity, and at the same dose, the clinical effect of KJC1 is better than that of KSZ and KXS.

[0124] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be considered exemplary and non-restrictive in all respects, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims be included in the present invention.

Claims

1. A Chinese medicine composition for the convalescent period of SARS-CoV-2 infection, characterized in that: The Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 1-20 parts of mustard seeds; 1-20 parts of Perilla seeds; 1-20 parts of radish seeds; Fritillaria 1-20 parts; 1-20 parts of Perilla; Platycodon grandiflorum 1-20 parts; 1-20 servings of almonds; 1-20 parts of Pueraria root; 1-20 parts of orange peel; Poria 1-20 parts; 1-20 parts of licorice.

2. A Chinese medicine composition for the convalescent period of SARS-CoV-2 infection according to claim 1, characterized in that: The Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 5-20 parts of mustard seeds; 5-20 parts of perilla seeds; 5-20 portions of radish seeds; 5-20 parts of Fritillaria; 5-20 parts of Perilla; Platycodon grandiflorum 5-20 parts; 5-20 servings of almonds; 5-20 parts of Pueraria root; 5-20 parts of orange peel; Poria 5-20 parts; 5-15 parts of licorice.

3. A Chinese medicine composition for the convalescent period of SARS-CoV-2 infection according to claim 1, characterized in that: The Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 10-15 parts of mustard seeds; 10-15 parts of perilla seeds; 10-15 parts of radish seeds, 10-15 parts of fritillaria, 10-15 parts of perilla, 10-15 parts of platycodon, 10-15 parts of apricot kernel, 5-10 parts of kudzu root, 5-10 parts of tangerine peel, 5-10 parts of poria and 5-10 parts of liquorice.

4. A Chinese medicine composition for the convalescent period of SARS-CoV-2 infection according to claim 1, characterized in that: The Chinese medicine composition also includes the following Chinese medicine raw materials in parts by weight: 1-20 parts of pinellia tuber, 1-20 parts of ephedra, 1-20 parts of parsley, and 1-20 parts of cassia twig.

5. A Chinese medicine composition for the convalescent period of SARS-CoV-2 infection according to claim 1, characterized in that: The Chinese medicine composition further comprises the following Chinese medicine raw materials in parts by weight: 1-20 parts of angelica sinensis, 1-20 parts of sophora flavescens, and 1-20 parts of angelica dahurica.

6. A Chinese medicine composition for the convalescent period of SARS-CoV-2 infection according to claim 1, characterized in that: The Chinese medicine composition further comprises the following Chinese medicine raw materials in parts by weight: 1-20 parts of ginseng, 1-20 parts of polygonatum, 1-20 parts of wolfberry, and 1-20 parts of eucommia leaves.

7. A Chinese medicine composition for the convalescent period of SARS-CoV-2 infection according to any one of claims 1 to 6, characterized in that: The dosage form of the Chinese medicine composition is oral liquid, granules, dripping pills, capsules and tablets.

8. Use of the Chinese medicine composition according to any one of claims 1 to 6 in the preparation of rehabilitation medicines, health products and foods for the recovery period of SARS-CoV-2 infection.

9. A method for preparing the Chinese medicine composition for the convalescent period of SARS-CoV-2 infection according to claim 7, characterized in that: All the raw materials in the traditional Chinese medicine composition are weighed and mixed according to their weight, extracted multiple times with water or a water / ethanol system, with an ethanol concentration of 10-70%, the extracts are filtered and combined, and concentrated under reduced pressure to form an extract, or spray-dried to obtain the raw material drug, and the extract or raw material drug is added with excipients to prepare clinically acceptable dosage forms, including oral liquid, granules, dripping pills, capsules and tablets.

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