A traditional Chinese medicine for treating late stage of respiratory virus infection

Abstract

The present invention relates to a Chinese medicine for treating late respiratory viral infection, wherein the Chinese medicine comprises the following raw materials in weight proportions: 280-350 parts of Pseudostellariae Radix, 100-140 parts of Cinnamon Twig, 130-170 parts of White Peony Root, 130-170 parts of Poria, 130-170 parts of Atractylodes Macrocephala, 280-340 parts of Shenqu, 100-140 parts of Morus Album, 100-140 parts of Trichosanthes, 130-170 parts of Houttuynia Cordata, 100-140 parts of Platycodon, 100-140 parts of Fritillariae Thunbergii, and 50-70 parts of Licorice. The prescription has the functions of invigorating Qi and nourishing Yin, clearing away heat and resolving phlegm. It is mainly used for treating the late stage of new coronavirus infection, influenza, common cold, etc., which are caused by disharmony between Ying and Wei, consumption of Qi and injury to Yin, physical weakness, fatigue, spontaneous sweating, fear of wind, cough and sputum, dry throat and sore throat, loss of appetite, pale red tongue, thin white or yellow fur, and floating and weak pulse. The traditional Chinese medicine is easy to take, has significant clinical efficacy, and a simple preparation process, and has a good market application prospect.

Description

Technical Field

[0001] The invention relates to a traditional Chinese medicine for treating late respiratory virus infection, belonging to the field of traditional Chinese medicines. Background Art

[0002] At present, cases of infection with the Omicron strain have replaced the Delta strain as the main epidemic strain. Omicron is milder, but not mild. Omicron is much more contagious than the previous new coronavirus. BA.1 is 10 times more contagious than the original virus and 13 times more contagious than the influenza virus, which means that even if it is likened to a "large flu", the number of people infected may be 10 times that of the flu, which is a fatal blow to the elderly who have not yet been vaccinated and have underlying diseases. Although the individual mortality rate is low, the increase in the mortality rate of the population caused by high transmission cannot be ignored. The shortage of drugs and the difficulty in seeking medical treatment have brought great pressure to medical institutions and medical personnel at all levels across the country. At present, Western medicine mainly treats symptoms. New drugs such as namatevir / ritonavir, azithromycin tablets, hormones, tocilizumab, baricitinib and other drugs are still in the clinical research stage, and the clinical efficacy is still uncertain.

[0003] In view of the basic national conditions of my country, such as a large population base, a large elderly population, and a large rural population, how to protect vulnerable groups and minimize the mortality rate is a major scientific problem that needs to be solved urgently. Practice has proved that traditional Chinese medicine has played an important role in all aspects of disease prevention, treatment and prognosis. It is safe, effective, economical, feasible, and easy to popularize in clinical practice. Experts in Shaanxi Provincial Hospital of Traditional Chinese Medicine, including Chief Physician Xu Jianqin, Chief Physician Mi Liehan, and Deputy Chief Physician Xiao Yang of Shaanxi Provincial Hospital of Traditional Chinese Medicine, believe that this disease has experienced symptoms such as sore throat, chills, fever, sore throat, nasal congestion, cough, and fatigue. After the fever subsides, many patients have long-term sore throat, cough, fatigue, etc., which brings many inconveniences to patients' work and life, and even induces anxiety, depression, insomnia and other physical and mental diseases. Traditional decoctions require patients to register for treatment and wait for medicine to be picked and boiled. The intermediate links are cumbersome and the waiting time is long. At the same time, it also increases the risk of infection and the workload of medical workers. In view of the similar symptoms and the same pathogenesis after the epidemic, we specially selected granules to develop preparations for the treatment of disharmony between the Ying and Wei systems and damage to both Qi and Yin in the late stage of COVID-19, in order to reduce the transformation of mild cases to severe cases, reduce the mortality rate, intervene and treat early, and alleviate the pain for the majority of patients to the greatest extent.

[0004] According to the pathogenesis of "disharmony between Ying and Wei, and injury of Qi and Yin" in the late stage of fever, Chinese medicine is used to treat respiratory viral diseases, with definite efficacy and minimal side effects. Chinese medicine decoctions are often bitter and inconvenient to carry, while Chinese medicine mixtures are small in quantity, good in taste, and easy to carry and take. There are very few Chinese patent medicines on the market that truly treat this pathogenesis. This invention fills this gap. Summary of the invention

[0005] The present invention relates to a Chinese medicine for treating the late stage of respiratory virus infection, which has the effects of invigorating qi and nourishing yin, clearing away heat and resolving phlegm. The main functions are: in the late stage of new coronavirus infection, influenza, common cold, etc., the disharmony between Ying and Wei, the consumption of qi and the damage to yin, the body is weak and susceptible, the body is tired and weak, spontaneous sweating and fear of wind, coughing and expectoration, dry throat and sore throat, loss of appetite, pale red tongue, thin white or yellow fur, and floating and weak pulse. The Chinese medicine is easy to take, has significant clinical efficacy, and is simple in preparation process, and has a good market application prospect.

[0006] The Chinese medicine prescription for treating the late stage of respiratory virus infection such as novel coronavirus infection of the present invention is guided by the basic theory of traditional Chinese medicine, and is combined with the classic prescriptions of traditional Chinese medicine such as "Guizhi Decoction", "Sijunzi Decoction" and "Jigen Decoction" and is optimized, and is combined with the clinical practice and treatment experience of the inventor of the present application, Chief Physician Xu Jianqin, for many years, based on the feedback of clinical efficacy, and repeatedly explored and summarized. It has a good effect on epidemics, influenza, common colds, etc. with disharmony between Ying and Wei, and consumption of Qi and damage to Yin.

[0007] The etiology and pathogenesis of the diseases treated by the Chinese medicine of the present invention are as follows:

[0008] Cold and dampness, along with the evil spirit, invade the human body through the three surfaces (skin, respiratory tract, and digestive tract). The human body's positive energy fights with the evil cold and dampness, causing fever. The evil invades the lungs, causing the lungs to lose their ability to clear and purify, resulting in cough. After the fever subsides, the positive energy is depleted, especially the lung and spleen energy, resulting in nasal congestion, runny nose, fatigue, sweating, shortness of breath, and laziness to speak. Spleen energy deficiency produces phlegm, resulting in cough and lots of phlegm. Spleen deficiency is not functioning, resulting in loss of appetite and poor appetite. Phlegm and dampness block the middle part of the body, which turns into heat over time and blocks the throat, resulting in dry throat and sore throat. Heat evil consumes body fluids, decocting body fluids, and damaging yin fluids, resulting in fever in the five hearts. The main symptoms are all signs of lung and spleen energy depletion, disharmony between the Ying and Wei, and deficiency of both Qi and Yin.

[0009] The therapeutic principles of the diseases treated by the Chinese medicine of the present invention are as follows:

[0010] This pathological feature is exactly the characteristics of the two plagues in the late Eastern Han Dynasty and the late Ming and early Qing dynasties: internal heat and toxicity are not resolved, and external wind and cold bind the surface. These characteristics determine its treatment principles: ① "Harmony method", using cinnamon twig and white peony to harmonize the Ying and Wei, taking into account both the evil and the righteous, and complementing each other; dispersing with astringent, sweating with tonic, opposites complement each other; ② "Taking care of the stomach qi", this prescription uses Shenqu, which can slightly relieve the surface and reduce fever, especially for those with food stagnation and external symptoms; Poria cocos and Atractylodes macrocephala strengthen the spleen and eliminate dampness; ③ "Preserve body fluids", Pseudostellaria baicalensis is the main medicine, which can replenish qi and strengthen the spleen, produce body fluids and moisten the lungs, and provide a continuous energy for expelling evil and clearing heat. In order to ensure that the source of sweat is abundant and the body fluids are continuously produced to expel evil and clear heat.

[0011] Aiming at this basic pathogenesis, on the basis of traditional classical theory, we developed the Chinese medicine in-hospital preparation product of the present invention: Shenbeining Lung Granules.

[0012] The inventive concept and prescription of the Chinese medicine of the present invention are as follows:

[0013] In the late stage of COVID-19, the struggle between the positive and negative forces leads to deficiency of the lung and spleen qi, obstruction of cold and dampness, depression and heat, and phlegm, which hinder the spleen's transportation and transformation. Because "the spleen is the source of phlegm and the lung is the container of phlegm", the spleen and lung qi are bound to be blocked, and the rise and fall of qi is stagnant, so there are symptoms such as cough, sputum, sore throat, poor appetite, fatigue, etc. This prescription is based on the idea of ​​"balance of yin and yang" and "emphasis on acquired stomach qi" in traditional Chinese medicine. The whole prescription uses Pseudostellariae Radix as the main drug, which can invigorate the Qi and strengthen the spleen, promote the production of body fluids and moisten the lungs, and clear and nourish the lungs and spleen; cinnamon, peony, Poria, Atractylodes, and Qu are combined as the assistant drugs, cinnamon twig and white peony harmonize the Ying and Wei, Poria and Atractylodes strengthen the spleen and transport dampness; Shenqu helps digestion and harmonizes the stomach; mulberry leaves, trichosanthes, Fritillaria thunbergii, Houttuynia cordata, and Platycodon grandiflorum are adjuvant drugs; mulberry leaves are sweet, cold, and moisturize the dry lungs, Houttuynia cordata clears the excess heat of the lungs, trichosanthes clears heat and removes phlegm, relieves chest congestion, and Fritillaria thunbergii clears heat and resolves phlegm; Platycodon grandiflorum is the guiding drug of the hand Taiyin lung meridian, like a boat carrying all the drugs into the lung meridian, opening and dispersing the lung Qi, removing phlegm and pus, and adding licorice to the meaning of Platycodon grandiflorum decoction, dispersing the lungs and relieving throat, clearing heat and detoxifying. Licorice is the guiding drug, harmonizing all the drugs. Strengthening the body and eliminating evil, when the evil is gone, the body is at peace. The whole prescription focuses on supporting the body's Qi, and also clears heat and resolves phlegm, playing the effect of "invigorating Qi and nourishing Yin, clearing heat and resolving phlegm". The components and dosage ratios of the Chinese medicine of the present invention are also obtained through a large amount of clinical practice exploration and summary by the inventor of the present application to obtain an effective treatment prescription. The dosage of each component has a good clinical effect within the following weight range.

[0014] Clinical applications in recent years have shown that all medicines that meet this pathogenesis have obvious antipyretic effects and can effectively relieve symptoms, overcoming to a certain extent the shortcomings of Western medicine antipyretics that fever is prone to recurrence.

[0015] The technical solution of this patent application is:

[0016] A traditional Chinese medicine for treating late respiratory viral infection, comprising the following raw materials in proportions by weight: 280-350 parts of Pseudostellariae Radix, 100-140 parts of Cassia Twig, 130-170 parts of White Peony Root, 130-170 parts of Poria, 130-170 parts of Atractylodes Macrocephala, 280-340 parts of Shenqu, 100-140 parts of Morus Album, 100-140 parts of Trichosanthes, 130-170 parts of Houttuynia Cordata, 100-140 parts of Platycodon, 100-140 parts of Fritillariae Thunbergii, and 50-70 parts of Licorice.

[0017] As a preferred embodiment of the present invention, the traditional Chinese medicine includes the following raw materials in the following weight ratio: 330 parts of Pseudostellariae Radix, 135 parts of Cinnamon Twig, 165 parts of White Peony Root, 165 parts of Poria, 165 parts of Atractylodes Macrocephala, 330 parts of Shenqu, 135 parts of Morus Album, 135 parts of Trichosanthes, 165 parts of Houttuynia Cordata, 135 parts of Platycodon, 135 parts of Fritillariae Thunbergii, and 66 parts of Licorice.

[0018] As a further preferred embodiment of the present invention, the traditional Chinese medicine comprises raw materials in the following weight proportions: 300 parts of Pseudostellariae Radix, 120 parts of cinnamon twig, 150 parts of white peony root, 150 parts of Poria cocos, 150 parts of Atractylodes macrocephala, 300 parts of Shenqu, 120 parts of mulberry leaves, 120 parts of Trichosanthes kirilowii, 150 parts of Houttuynia cordata, 120 parts of Platycodon grandiflorum, 120 parts of Fritillaria thunbergii, and 60 parts of Licorice.

[0019] The present invention provides a method for preparing a traditional Chinese medicine for treating late-stage respiratory virus infections such as novel coronavirus infection, the preparation method comprising the following steps:

[0020] Take Radix Pseudostellariae Radix, Cinnamon Twig, White Peony Root, Poria, Atractylodes Macrocephala, Shenqu, Folium Mori, Fructus Trichosanthis, Houttuynia Cordata, Platycodon Grandiflorum, Fritillaria Thunbergii, and Licorice, add 8-11 times of the weight of the above medicinal materials in water, decoct for 1-3 times, decoct for 0.6-1.5 hours, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry under reduced pressure to form a clear paste with a relative density of 1.30-1.35, and then add pharmaceutical excipients to prepare a Chinese medicine oral preparation.

[0021] Preferably, in the preparation method, water 10 times the weight of the medicinal material is added, and the mixture is decocted twice for 1 hour.

[0022] Preferably, in the preparation method, the ratio of the clear paste to the auxiliary materials is 1:2-3, preferably 1:1.5.

[0023] Preferably, the auxiliary material in the preparation method is: dextrin.

[0024] Preferably, the dosage form of the oral Chinese medicine preparation can be: granules, oral liquid, capsules, tablets, and pills.

[0025] Preferably, the traditional Chinese medicine is used in the preparation of medicines for treating common colds, winter and spring influenza, viral pneumonia, new coronavirus pneumonia, and respiratory viral infections.

[0026] The quality detection method of the traditional Chinese medicine of the present invention comprises the following steps: thin layer identification of medicinal materials such as Trichosanthes kirilowii, Licorice and White Peony Root. The thin layer identification method can be used as an internal control standard for the production quality inspection of the traditional Chinese medicine.

[0027] Beneficial effects of the Chinese medicine of the present invention

[0028] ⑴. The prescription of the present invention is the clinical practice experience of the inventor of the present application for many years, and it is continuously optimized, revised, summarized and sorted out based on the feedback of clinical efficacy. The prescription is composed of twelve medicines such as Pseudostellariae Radix, Cinnamon Twig, White Peony Root, Poria, Stir-fried Atractylodes Macrocephala, Shenqu, Morus Alba, Trichosanthes, Houttuynia Cordata, Platycodon, Fritillaria Thunbergii, and Licorice. The whole prescription is reasonably compatible with the monarch, minister, assistant and envoy, and plays the effect of invigorating qi and nourishing yin, clearing heat and resolving phlegm. It is clinically used to treat respiratory viral diseases such as the common cold, influenza, and even the new crown infection. It is safe and effective for relieving cough and phlegm and alleviating various discomforts.

[0029] The present invention treats the Chinese medicine of respiratory viral infection, and its corresponding in-hospital preparation product is Shenbei Ningfei Shenbei Ningfei granules. Mainly treat viral cold symptoms: cough and expectoration, loss of appetite, dry throat and sore throat, fatigue, easy sweating, nasal congestion and runny nose, shortness of breath and laziness, five heart irritability, pale red tongue with white or yellow fur, floating and weak pulse. This prescription was originally used in the form of decoction, but the decoction needs to be newly made, and it is easy to mold after being placed for a long time, which is inconvenient to carry, and the oral dosage is also large, which is difficult to meet the requirements of modern preparations such as definite efficacy, controllable quality, convenient production, and convenient clinical medication, and such patients need to take medicine for a long time, so it is more suitable to make oral preparations. Commonly used oral agents are tablets, granules, capsules, mixtures, etc. The most preferred dosage form of the Chinese medicine of the present invention is granules, which are developed and improved on the basis of decoctions and maintain the characteristics of decoctions. The dosage is smaller than that of decoctions and can be produced in batches, eliminating the trouble of temporary formulation and decoction. The quality is relatively stable, and it is easy to take, carry and store, and is suitable for industrial production.

[0030] (2) The preparation process of the present invention is scientific and reasonable, and can extract the effective substance components contained in the traditional Chinese medicine of the present invention to the maximum extent. In order to achieve the best extraction efficiency, the optimal process of the present invention is: add 10 times the amount of water, decoct twice, each time for 1.0 hour, filter, combine the filtrate, concentrate to an extract with a relative density of 1.3 (60°C), add an appropriate amount of dextrin and mix well, use sucralose as a flavoring agent, granulate with ethanol, dry, and granulate to obtain.

[0031] ⑶. The Chinese medicine of the present invention has been repeatedly used in the clinic for many years and has been verified. In particular, the total clinical efficacy during the current novel coronavirus infection period reached nearly 95%. The Chinese medicine of the present invention has significant clinical efficacy in treating epidemics, influenza, and the common cold, and has the advantages of safety and convenience, and is worthy of promotion and application in clinical practice.

[0032] The sources, efficacy, and chemical components of the raw materials contained in the traditional Chinese medicine for treating the late stages of respiratory viral infections such as new coronavirus infection are summarized as follows so that those skilled in the art can more clearly understand and implement the technical solution of the present invention.

[0033] Pseudostellaria heterophylla (Miq.) Pax ex Paxet Hoffm. is a dried root tuber of the Caryophyllaceae plant. Efficacy: replenishing qi and strengthening the spleen, promoting fluid production and moistening the lungs. It is used for spleen deficiency, fatigue, loss of appetite, weakness after illness, insufficient qi and yin, spontaneous sweating and thirst, dry cough due to lung dryness. Pseudostellaria heterophylla mainly contains amino acids, polysaccharides, saponins, flavonoids, tannins, coumarins, sterols, triterpenes and various trace elements.

[0034] Cinnamon twig is the dried young branch of Cinnamomum cassia Presl, a plant of Lauraceae. Efficacy: sweating and relieving muscles, warming and unblocking meridians, promoting yang and transforming qi, calming the qi and relieving adverse reactions. It is used for colds, cold pain in the abdomen, amenorrhea, dysmenorrhea, joint pain and other pain syndromes caused by cold blood stagnation, phlegm and fluid retention, edema, palpitations, and running pig. Cinnamon twig mainly contains volatile oils: cinnamaldehyde, camphene, benzaldehyde, β-elemene, β-cuberene, etc. It also contains phenols, organic acids, polysaccharides, glycosides, coumarins and tannins.

[0035] White peony root, this product is the dried root of Paeonia lactiflora Pall, a plant of the Ranunculaceae family. Efficacy: nourishing blood and regulating menstruation, consolidating yin and stopping sweating, softening the liver and relieving pain, and calming liver yang. It is used for blood deficiency and chlorosis, irregular menstruation, metrorrhagia, spontaneous sweating, night sweats, pain in the ribs and abdomen, cramps and pain in the limbs, hyperactivity of liver yang, headache and dizziness. It mainly contains monoterpenoid components: paeoniflorin, oxidized paeoniflorin, benzoyl paeoniflorin, white paeoniflorin, and paeoniflorin ketone. Its main chemical components are galloyl paeoniflorin, paeoniflorin A, B, and C; sterol components: β-sitosterol; tannin components: 1,2,3,6-tetragalloyl glucose, gallic acid, and dextrorotatory catechin; phenolic components: paeonol.

[0036] Poria cocos, this product is the dried sclerotium of the fungus Poria cocos (Schw.) Wolf of the Polyporaceae family. Efficacy: diuresis and dampness elimination, spleen strengthening, tranquilizing the mind and calming the nerves. It is used for edema, oliguria, phlegm and fluid retention, palpitations, spleen deficiency, poor appetite, loose stools, restlessness, palpitations and insomnia. Its main chemical components: mainly polysaccharides, with the highest content of β-poria polysaccharide; triterpenoid components: pachymic acid, pyrimethicone, stoloniferous acid, etc.; sterol components: ergosterol, etc. It also contains protein, fat, lecithin, adenine, etc.

[0037] Atractylodes macrocephala, this product is the dried rhizome of Atractylodes macrocephala Koidz. of the Asteraceae family. Efficacy: replenishing qi and strengthening the spleen, drying dampness and promoting diuresis, stopping sweating, and calming the fetus. It is used for spleen deficiency, poor appetite and fatigue, abdominal distension and diarrhea, phlegm and fluid, palpitations, edema, leucorrhea, spontaneous sweating due to qi deficiency, and restless fetal movement due to spleen deficiency. Its chemical composition: mainly contains volatile oils such as atractylodesone, atractylodes alcohol, atractylodes ether, juniper brain, atractylodes lactone, lactone compounds such as atractylodes lactone I~IV, and double atractylodes lactone, and contains fructose, inulin, atractylodes polysaccharide, various amino acids, atractylodes triol and vitamin A and other ingredients.

[0038] Shenqu, this product is a fermented mixture of Polygonum hydropiper, Artemisia annua, and Apricot kernels, etc., mixed with flour. Efficacy: helps digestion and soothes the stomach. Used for food stagnation. Its main chemical components: Liu Shenqu is a yeast preparation, containing yeast, amylase, vitamin B complex, ergosterol, protein, fat, volatile oil, etc.

[0039] Mulberry leaf, this product is the dried leaves of Morus alba L., a plant of the Moraceae family. Efficacy: evacuate wind-heat, clear the lungs and moisten dryness, calm the liver yang, clear the liver and improve eyesight. Used for wind-heat cold, early stage of febrile disease, wind-heat cold, early stage of febrile disease, wind-heat cold, early stage of febrile disease, red and swollen eyes, and blurred vision. Its chemical composition: mainly contains flavonoids: rutin, quercetin, isoquercetin, mulberry glycosides, etc.; steroids: cynanchum acetosterone, hydroxyecdysterone, rapesterone, stigmasterone, etc.; coumarin components: umbelliferone, scopoletin, scopolamine, etc. It also contains volatile oils, alkaloids, terpenes, etc.

[0040] Trichosanthes kirilowii Maxim. or Trichosanthes rosthornii Harms, a plant of the Cucurbitaceae family, is a dried mature fruit. Efficacy: clearing away heat and removing phlegm, widening the chest and dispersing stagnation, moistening and lubricating the intestines. It is used for cough due to lung heat, turbid yellow and thick phlegm, chest pain, chest congestion, lung abscess, intestinal abscess, breast abscess, and constipation. Trichosanthes kirilowii mainly contains organic acid components: n-triacontanoic acid, fumaric acid, succinic acid; terpenoid components: trichosanthes diol; it also contains serine proteases A and B and sterol components.

[0041] Houttuynia cordata Thunb. is the fresh whole herb or dried aerial part of Houttuynia cordata Thunb. of the Saururaceae family. Efficacy: clearing away heat and detoxifying, eliminating carbuncle and draining pus, promoting diuresis and relieving stranguria. It is used for lung carbuncle vomiting pus, phlegm-heat cough, carbuncle swelling and toxicity, stranguria due to heat, and dysentery due to heat. The chemical components of Houttuynia cordata mainly include volatile oil, flavonoids, polysaccharides, alkaloids, phenolic compounds, organic acids, proteins, amino acids, etc.

[0042] Platycodon grandiflorum, this product is the dried root of Platycodon grandiflorum (Jacq.) A.DC. of the Campanulaceae family. Efficacy: clearing the lungs, removing phlegm, relieving sore throat, and draining pus. It is used for coughing with a lot of phlegm, uncomfortable expectoration, chest tightness, sore throat, hoarseness, and pulmonary abscess with vomiting pus. The chemical components of Platycodon grandiflorum mainly include triterpenoid saponins: Platycodon saponins A, D, Polygala tenuifolia saponins, etc. It also contains Platycodon polysaccharides composed of fructose.

[0043] Fritillaria thunbergii Miq., this product is the dried bulb of Fritillaria thunbergii Miq., a plant of the Liliaceae family. Efficacy: clearing away heat, resolving phlegm and relieving cough, detoxifying, dispersing knots and eliminating carbuncle. It is used for wind-heat cough, phlegm-fire cough, scrofula, goiter, sores, lung carbuncle and breast carbuncle. Fritillaria thunbergii mainly contains alkaloids: Fritillaria A (Fritillaria A), Fritillaria B (Fritillaria B), Fritillaria ketone, Fritillaria cin, isofritillarine, Fritillaria glycoside, Fritillaria C and so on.

[0044] Licorice, this product is the dried root and rhizome of Glycyrrhizauralensis Fisch. Glycyrrhizainflate Bat. or Glycyrrhiza glabra L. of the Leguminosae family. Efficacy: tonifying the spleen and replenishing qi, clearing away heat and detoxifying, removing phlegm and relieving cough, relieving pain, and harmonizing various medicines. It is used for spleen and stomach weakness, fatigue, insufficient heart qi, palpitations and shortness of breath, pulse knot, carbuncle, sore throat, cough with sputum, abdominal and limb cramps and pain, and relieving drug toxicity and potency. Licorice chemical components mainly include triterpenes such as glycyrrhizin, glycyrrhizic acid, and glycyrrhetinic acid, flavonoids such as glycyrrhizin, isoliquiritigenin, glycyrrhizin, and isoliquiritigenin, as well as alkaloids, polysaccharides, coumarins, amino acids, and a small amount of volatile components.

[0045] In order to further illustrate the innovativeness of the Chinese medicine preparation process of the present invention, we provide some experimental data for screening process optimization, in order to further illustrate the scientificity and rationality of the process technology of the present invention.

[0046] Screening of process conditions for preparing the Chinese medicine of the present invention

[0047] 1. Materials and Instruments

[0048] Instruments Agilent 1260 high performance liquid chromatograph (Agilent Technologies); electronic temperature control electric heating mantle (Tianjin Test Instrument Co., Ltd., model: 98-1-B); ultrasonic cleaner (Panda Group Nanjing Electronic Metrology Co., Ltd., model: UP3200H); electric blast drying oven (Chongqing Sida Testing Equipment Co., Ltd., model: CS101-3EB); electronic balance (Beijing Sartorius Balance Co., Ltd., model: BT125D, d = 0.01 mg; BS210S, d = 0 .1mg); electronic balance (Yuyao Jiming Weighing and Calibration Equipment Co., Ltd., model: JM-B20001); electronic constant temperature stainless steel water bath (Shanghai Yichang Instrument Screen Factory, model: XMTD-b000); digital constant temperature water bath (Jiangsu Jintan Jincheng Tongsheng Experimental Instrument Factory, model: HH-δ); high-speed refrigerated centrifuge (Changsha Yingtai Instrument Co., Ltd., model: TGL18); 200g portable high-speed crusher (Wenling Linda Machinery Co., Ltd., DFT-200A). Reagents: methanol and acetonitrile are chromatographically pure; the rest of the reagents are analytically pure; water is distilled water.

[0049] The reference substance, paeoniflorin (batch number: 110736-202145), was purchased from China Food and Drug Inspection Institutes.

[0050] 2. Extraction process screening

[0051] Experimental design

[0052] From the data analysis, we know that decocting twelve herbs including Pseudostellariae Radix, Cinnamon Twig, White Peony Root, Poria, Stir-fried Atractylodes Macrocephala, Shenqu, Morus Album, Trichosanthes, Houttuynia Cordata, Platycodon, Fritillaria Thunbergii, and Licorice is beneficial to the dissolution of active ingredients without increasing production costs, and meets the preparation requirements of granule dosage forms. Therefore, we designed it as a water decoction. Through orthogonal experiments, we took the paeoniflorin content in white peony root as the investigation index, and conducted a comprehensive analysis in combination with the amount of dry extract, focusing on the number of extractions, the amount of water added and the extraction time to determine the optimal water extraction process conditions.

[0053] 2.2 Examination of water absorption rate of medicinal materials

[0054] According to the half decoction prescription, weigh 15g of Radix Pseudostellariae Radix, 6g of Cinnamon Twig, 7.5g of White Peony Root, 7.5g of Poria, 7.5g of Stir-fried Atractylodes Macrocephala, 15g of Shenqu, 6g of Morus Album, 6g of Trichosanthes, 7.5g of Houttuynia Cordata, 6g of Platycodon Grandiflorum, 6g of Fritillaria Thunbergii and 3g of Licorice, a total of 93g, add 8 times of water, let it stand, observe the water absorption of the medicinal materials, and calculate the water absorption rate of the medicinal materials (%). The results show that the wet medicinal materials weigh 241.5g, and the water absorption rate of the medicinal materials is 159.7%. Because the water absorption rate is greater than 100%, the subsequent orthogonal test water addition amount is selected to be 8 times, 10 times and 12 times.

[0055] 2.3 Determination of factor levels and selection of orthogonal arrays

[0056] In order to determine the optimal extraction conditions, orthogonal experiments were used to optimize the conditions involved in the water extraction process. Generally, extraction time, water addition, and extraction times have a greater impact on the extraction results. Therefore, water addition (A), extraction time (B), and extraction times (C) were selected as influencing factors, and three levels were selected for each. The L9 (34) table was used to arrange the experiment and screen the optimal extraction process conditions. The factor level table is shown in Table 1.

[0057] Table 1 Factor level table

[0058]

[0059] 2.3 Test methods

[0060] According to the prescription of a decoction, 30g of Radix Pseudostellariae Radix, 12g of Cinnamon Twig, 15g of White Peony Root, 15g of Poria, 15g of Stir-fried Atractylodes Macrocephala, 30g of Shenqu, 12g of Morus Albizia Folium, 12g of Trichosanthes Fructus, 15g of Houttuynia Cordata, 12g of Platycodon Grandiflorum, 12g of Fritillaria Thunbergii and 6g of Licorice were weighed, totaling 186g, and 9 parallel portions were randomly sampled and numbered as 1 to 9 test numbers. The test was carried out according to the requirements of each test number in the orthogonal table L9 (34), and the extracts were combined and filtered. The filtrate was used for the following test (dry extract yield, determination of paeoniflorin content). The results of the L9 (34) orthogonal design experiment are shown in Table 2, and the results of variance analysis are shown in Table 3.

[0061] 2.4 Preparation of dry extract

[0062] Accurately measure 50 mL of each of the above extracts, place them in evaporating dishes at constant weight, evaporate them to dryness in a water bath, dry the residue at 105°C for 3 hours, take it out, place it in a desiccator for 30 minutes, weigh and calculate, the results are shown in Table 2.

[0063] 2.5 Determination of paeoniflorin content

[0064] The chromatographic conditions and system suitability test used octadecylsilane bonded silica gel as the filler; chromatographic column: Kromasil C18 (4.6×250mm, 5μm); mobile phase: acetonitrile-0.1% phosphoric acid solution (14:86); column temperature: 25°C; detection wavelength: 230nm; flow rate: 1.0ml / min; the theoretical plate number calculated based on the berberine hydrochloride peak should be no less than 2000.

[0065] Preparation of reference solution: Take an appropriate amount of paeoniflorin reference substance, weigh it accurately, and add methanol to make a solution containing 60 μg per 1 ml.

[0066] Determination method: Accurately pipette 10 μl of reference solution and test solution respectively, inject into liquid chromatograph, record the chromatogram, and calculate the content by peak area according to the external standard method. The results are shown in Table 2.

[0067] Table 2 Orthogonal test table of water extraction L9 (34)

[0068]

[0069]

[0070] *Comprehensive value = (amount of peony glycosides / maximum amount of peony glycosides)*70+(amount of dry paste / maximum amount of dry paste)*30

[0071] 2.6 Analysis of variance

[0072] Based on the data in the orthogonal experiment arrangement and data analysis in Table 2, variance analysis was performed and the results are shown in Table 3 below.

[0073] Table 3 Analysis of variance table

[0074]

[0075]

[0076] Note: F0.1(2.2)=9.00F0.05(2.2)=19.00F0.01(2.2)=99.00

[0077] From the K and R values ​​in Table 2, we can see that A2>A1>A3, B2>B3>B1, C3>C1>C2, and the influence of each factor on the extraction process is C>B>A. The best process is A2B2C3 according to intuitive analysis. From the variance analysis results in Table 4, we can see that factors A, B, and C have no significant effect. After comprehensive consideration, the best process combination is determined to be A2B1C2. That is, add 10 times the amount of water, decoct twice, each time for 1.0 hour.

[0078] 2.7 Verification test

[0079] The medicinal materials were weighed according to the prescription ratio, and three verification tests were carried out according to the preferred process conditions. The results are shown in Table 4.

[0080] Table 4 Verification test results

[0081]

[0082] From the verification results in Table 4, it can be seen that the content of paeoniflorin and the amount of dry paste are relatively stable, indicating that the optimal process conditions are basically feasible.

[0083] 3. Molding process screening

[0084] 3.1 Formulation Process Framework Design

[0085] (1) Selection of granulation method

[0086] At present, there are granulation methods such as dry granulation, wet granulation, and direct granulation. Among them, wet granulation is the most commonly used. There are two methods in wet granulation. One is to concentrate the extract, dry and crush it, mix it with an appropriate amount of auxiliary materials, and then add a wetting agent to granulate; the other is to concentrate the extract to a clear paste of a certain concentration, add an appropriate amount of auxiliary materials and mix it evenly, and then granulate. The former is easy to control the amount of auxiliary materials and powder, which is convenient for calculation. However, since drying is a long process, the long-term high temperature during the period causes a lot of loss of active ingredients, thus affecting the efficacy; although the latter does not have a relatively accurate ratio in the amount of clear paste and auxiliary materials, its concentration time is shorter than the former, thereby ensuring the retention of more active ingredients. In summary, the latter has the following advantages over the former: First, from the research process, extracting and retaining as many active ingredients as possible is a very important part of any new drug research, and the latter is superior to the former in this respect; secondly, from the perspective of resources, choosing the latter can save resources. Through comprehensive analysis, a method of concentrating the extract to a certain concentration of clear paste and then mixing it with appropriate amount of auxiliary materials for granulation was selected for research.

[0087] (2) Selection of auxiliary materials

[0088] Granules are water-soluble granules. Common auxiliary materials for water-soluble granules include dextrin, sucrose powder, lactose, mannitol, etc. Usually, during use, cheap and easily available sucrose powder is selected and mixed with dextrin in a certain proportion. Sucrose powder and dextrin mixed in a certain proportion as auxiliary materials can both correct the taste and reduce hygroscopicity. Since this preparation is a sugar-free water-soluble granule, dextrin is selected as the diluent.

[0089] Commonly used sugar-free flavoring agents include cyclamate, stevia, high fructose, protein sugar, xylitol, sucralose, etc. Cyclamate is low in cost, but not safe, and has a metallic aftertaste; high fructose and xylitol are used in large quantities due to their low sweetness; sucralose is the only functional sweetener made from sucrose, and its sweetness can be up to 600 times that of sucrose. This experiment intends to choose sucralose as a flavoring agent.

[0090] (3) Selection of dextrin dosage for granulation

[0091] The drug solution was concentrated to a clear paste with a relative density of 1.30-1.35 (60℃~65℃). A certain amount of the clear paste was weighed and added with dextrin in the ratios of 1:1, 1:1.5, 1:2, and 1:3 respectively. Granulation was carried out and the soft material condition, sieving difficulty, and particle appearance were investigated. The results are shown in Table 5.

[0092] Table 5 Effect of dextrin dosage on granulation

[0093]

[0094] It can be seen from Table 5 that the granules prepared by selecting 1.5 times the amount of dextrin as the clear paste have better quality.

[0095] (4) Selection of ethanol concentration for granulation

[0096] The ratio of clear paste to dextrin was 1:1.5, and 75%, 80%, 85%, and 90% ethanol were used as wetting agents, respectively, for granulation. The soft material condition and the difficulty of sieving were investigated. The results are shown in Table 6.

[0097] Table 6 Effect of ethanol concentration on granulation

[0098]

[0099]

[0100] It can be seen from Table 6 that the quality of the particles prepared when the ethanol concentration is 85% is better.

[0101] (5) Screening of sucralose dosage

[0102] The ratio of clear paste to dextrin was 1:1.5, and the amount of sucralose was according to the ratio in the following table. The mixture was dissolved in 85% ethanol to prepare a soft material, and the granules were granulated. After the granules were dried, their taste was tasted. The results are shown in Table 7.

[0103] Table 7 Taste comparison results of different amounts of sucralose

[0104]

[0105] From the results in Table 7, it can be seen that the soft material prepared with the ratio of (clear paste + dextrin) total amount: sucralose = 100:0.08 has appropriate sweetness and good taste.

[0106] 3.2 Granulation and packaging

[0107] Chinese medicine granules are generally easy to absorb moisture, so they should be sealed. This granule is packaged in a composite aluminum-plastic bag that is not breathable or moisture-permeable to prevent moisture absorption during storage and affect the quality of the finished product. BRIEF DESCRIPTION OF THE DRAWINGS

[0108] The drawings described herein are used to provide further understanding of the present invention and constitute a part of the present invention. The exemplary embodiments of the present invention and their descriptions are used to explain the present invention and do not constitute improper limitations on the present invention.

[0109] Figure 1 This is a thin layer identification chromatogram of Trichosanthes kirilowii (from left to right: samples 1 to 3, batch numbers: 20230101, 20230102, 20230103, 4-Trichosanthes kirilowii control medicinal material, 5-negative control sample lacking Trichosanthes kirilowii);

[0110] Figure 2This is a thin layer identification chromatogram of licorice (from left to right: samples 1 to 3, batch numbers: 20230101, 20230102, 20230103, 4-licorice control medicinal material, 5-negative control sample lacking licorice);

[0111] Figure 3 This is the thin layer identification chromatogram of white peony root (from left to right: samples 1 to 3, batch numbers: 20230101, 20230102, 20230103, 4-paeoniflorin reference substance, 5-peony root-deficient negative control sample). DETAILED DESCRIPTION

[0112] In order to more fully understand the implementation of the present invention, one or more experimental examples are listed below, and the present invention is further described below through typical embodiments.

[0113] Example 1 Preparation of Chinese medicine granules of the present invention

[0114] Weigh the following raw materials in proportion by weight: 330g of Pseudostellariae Radix, 135g of Cinnamon Twig, 165g of White Peony Root, 165g of Poria, 165g of Atractylodes Macrocephala, 330g of Shenqu, 135g of Morus Album, 135g of Trichosanthes, 165g of Houttuynia Cordata, 135g of Platycodon, 135g of Fritillariae Thunbergii, and 66g of Licorice, add 10 times the weight of the above medicinal materials in water, decoct twice for 1 hour, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry under reduced pressure to form a clear paste with a relative density of 1.30-1.35, add dextrin 1.5 times the amount of the clear paste, add ethanol concentration of 85% for granulation, and then add sucralose for flavor correction, and prepare soft materials in a ratio of (clear paste + dextrin): sucralose = 100:0.08 to prepare Chinese medicine granules.

[0115] Example 2 Preparation of Chinese medicine granules of the present invention

[0116] Weigh the following raw materials in proportion by weight: 330g of Pseudostellariae Radix, 135g of Cinnamon Twig, 165g of White Peony Root, 165g of Poria, 165g of Atractylodes Macrocephala, 330g of Shenqu, 135g of Morus Album, 135g of Trichosanthes, 165g of Houttuynia Cordata, 135g of Platycodon, 135g of Fritillariae Thunbergii, and 66g of Licorice, add 10 times the weight of the above medicinal materials in water, decoct twice for 1 hour, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry under reduced pressure to form a clear paste with a relative density of 1.30-1.35, add dextrin 1.5 times the amount of the clear paste, add ethanol concentration of 85% for granulation, and then add sucralose for flavor correction, and prepare soft materials in a ratio of (clear paste + dextrin): sucralose = 100:0.08 to prepare Chinese medicine granules.

[0117] Example 3 Preparation of Chinese medicine granules of the present invention

[0118] Weigh the following raw materials in proportion by weight: 300g of Radix Pseudostellariae, 120g of Cinnamon Twig, 150g of White Peony Root, 150g of Poria, 150g of Atractylodes Macrocephala, 300g of Shenqu, 120g of Morus Album, 120g of Trichosanthes, 150g of Houttuynia Cordata, 120g of Platycodon Grandiflorum, 120g of Fritillaria Thunbergii, and 60g of Licorice, add 10 times the weight of the above medicinal materials in water, decoct twice for 1 hour, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry under reduced pressure to form a clear paste with a relative density of 1.30-1.35, add dextrin in an amount of 1.5 times that of the clear paste, add ethanol concentration of 85% for granulation, and then add sucralose for flavor correction, and prepare a soft material in a ratio of (clear paste + dextrin) to sucralose = 100:0.08 to prepare a Chinese medicine granule.

[0119] Example 4 Preparation of Chinese medicine oral liquid of the present invention

[0120] Weigh the following raw materials in the weight ratio: 300g of Pseudostellariae Radix, 120g of Cinnamon Twig, 150g of White Peony Root, 150g of Poria, 150g of Atractylodes Macrocephala, 300g of Shenqu, 120g of Morus Album, 120g of Trichosanthes, 150g of Houttuynia Cordata, 120g of Platycodon, 120g of Fritillaria Thunbergii, and 60g of Licorice, add 8 times the weight of the above medicinal materials in water, decoct for 3 times, the decoction time is 0.6 hour, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry under reduced pressure to form a clear paste with a relative density of 1.30-1.35, add sucrose and sodium benzoate, mix and stir evenly, and dilute with water to make a Chinese medicine oral liquid preparation.

[0121] Example 5 Preparation of Chinese medicine capsules of the present invention

[0122] Weigh the following raw materials in proportion by weight: 350g of Pseudostellariae Radix, 140g of Cinnamon Twig, 130g of White Peony Root, 170g of Poria, 130g of Atractylodes Macrocephala, 340g of Shenqu, 100g of Morus Album, 100g of Trichosanthes, 170g of Houttuynia Cordata, 100g of Platycodon, 140g of Fritillariae Thunbergii, and 70g of Licorice, add 11 times the weight of the above medicinal materials in water, decoct once for 1.5 hours, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry under reduced pressure to form a clear paste with a relative density of 1.30-1.35, add starch and dextrin for granulation, add magnesium stearate and mix evenly, and fill into capsules.

[0123] Example 6 Preparation of Chinese medicine pills of the present invention

[0124] Weigh the following raw materials in the weight ratio: 280g of Pseudostellariae Radix, 100g of cinnamon twig, 170g of white peony root, 130g of Poria, 170g of Atractylodes macrocephala, 280g of Shenqu, 140g of mulberry leaf, 140g of Trichosanthes, 130g of Houttuynia cordata, 140g of Platycodon grandiflorum, 100g of Fritillaria thunbergii, and 50g of Licorice, add 9 times the weight of the above medicinal materials in water, decoct twice for 1.1 hours, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry them under reduced pressure to form a clear paste with a relative density of 1.30-1.35, add pharmaceutical excipients such as PEG4000, PEG6000, stearic acid, and drip them into Chinese medicine dripping pills.

[0125] Example 7 Preparation of Chinese medicine tablets of the present invention

[0126] Weigh the following raw materials in proportion by weight: 310g of Pseudostellariae Radix, 120g of Cinnamon Twig, 140g of White Peony Root, 140g of Poria, 150g of Atractylodes Macrocephala, 310g of Shenqu, 110g of Morus Album, 130g of Trichosanthes, 150g of Houttuynia Cordata, 120g of Platycodon, 110g of Fritillariae Thunbergii, and 63g of Licorice, add 10 times the weight of the above medicinal materials in water, decoct twice for 0.9 hour, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry under reduced pressure to form a clear paste with a relative density of 1.30-1.35, add hydroxypropyl methylcellulose and starch, granulate, add magnesium stearate to mix evenly, and press into Chinese medicine tablets.

[0127] Example 8 Preparation of Chinese medicine pills of the present invention

[0128] Weigh the following raw materials in proportion by weight: 290g of Pseudostellariae Radix, 130g of Cinnamon Twig, 130g of White Peony Root, 140g of Poria, 150g of Atractylodes Macrocephala, 290g of Shenqu, 120g of Morus Album, 110g of Trichosanthes, 160g of Houttuynia Cordata, 120g of Platycodon, 130g of Fritillaria Thunbergii, and 65g of Licorice, add 8 times the weight of the above medicinal materials in water, decoct twice for 0.8 hour, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry under reduced pressure to form a clear paste with a relative density of 1.30-1.35, then add an appropriate amount of honey to prepare a soft material, cut into pills, and roll into Chinese medicine pills.

[0129] Example 9 Internal Control Quality Standards of Chinese Medicine of the Present Invention

[0130] 9.1 Instruments, reagents and test drugs:

[0131] Ultrasonic cleaning machine (H66025T), BP211D analytical balance (Sartorius, Germany), WS70-1 infrared rapid drying oven (manufactured by Shanghai Wusong Hardware Factory), FW135 crusher (Tianjin Test Instrument Co., Ltd.), four-hole water bath (Beijing Kewei Yongxing Instrument Co., Ltd.), three-purpose UV analyzer (Shanghai Jingke Industrial Co., Ltd., WFH-201B UV transmission and reflection instrument). 101 electric heating blast drying oven (Beijing Yongguangming Medical Instrument Factory), double-slot chromatography cylinder (specifications 200mm×200mm).

[0132] Silica gel G (Qingdao Ocean Chemical Co., Ltd., batch number: 20210220). The samples used in this item were homemade, batch numbers (20230101, 20230102, 20230103).

[0133] 9.2 Identification results:

[0134] Properties: This product is brown-yellow granules and powder, with a slight odor, sweet and slightly bitter taste.

[0135] (1) Thin layer identification of Trichosanthes kirilowii: Take 40g of the granules of this product, grind them into powder, add 100mL of methanol, sonicate for 30min, filter, evaporate the filtrate to dryness, add 30mL of water to dissolve the residue, shake and extract with water-saturated n-butanol 3 times, 30mL each time, combine the n-butanol solution, evaporate to dryness, add 2mL of methanol to dissolve the residue, and use it as the test solution. Take another 2g of Trichosanthes kirilowii control medicinal material, add 30mL of methanol, sonicate for 30min, and prepare the control medicinal material solution in the same way. According to the thin layer chromatography method (Chinese Pharmacopoeia 2020 Edition Part IV General Rules 0502), 10-15 μL of the test solution and 5 μL of the control medicinal material solution were respectively spotted on the same silica gel G thin layer plate, and n-hexane-ethyl acetate-formic acid (20:10:0.2) was used as the developing agent. The plate was placed in a developing cylinder pre-saturated with the developing agent for 15 minutes, developed, taken out, dried, sprayed with 10% sulfuric acid ethanol solution, and examined under ultraviolet light (365nm). In the chromatogram of the test sample, 1 to 2 spots of the same color appeared at the corresponding position of the chromatogram of the control medicinal material, see the attached instructions. Figure 1 .

[0136] ⑵、Thin layer identification of licorice: Take 40g of this product, grind it, add 100mL of methanol, ultrasonically treat it for 30 minutes, filter it, evaporate the filtrate to dryness, dissolve the residue in 40mL of water, shake and extract it 3 times with n-butanol saturated with water, 30mL each time, combine the n-butanol solution, wash it 3 times with water saturated with n-butanol, 25mL each time, discard the water solution, evaporate the n-butanol solution, dissolve the residue in 0.5mL of methanol, and use it as the test solution. Take another 1g of licorice control medicinal material, and prepare 5mL of control medicinal material solution in the same way. According to the thin layer chromatography method (General Rule 0502), 5 μl of each of the above two solutions were taken and spotted on the same silica gel G thin layer plate prepared with 1% sodium hydroxide solution, and ethyl acetate-formic acid-glacial acetic acid-water (15:1:1:2) was used as the developing agent. After development, the plate was taken out, dried, sprayed with 10% sulfuric acid ethanol solution, heated at 105°C until the spots were clearly colored, and examined under ultraviolet light (365nm). In the chromatogram of the test sample, 2-3 fluorescent spots of the same color appeared at the corresponding position of the chromatogram of the control medicinal material, see the attached instructions. Figure 2 .

[0137] ⑶. Thin layer identification of white peony root: Take 40g of the powder of this product, grind it into powder, add 100ml of ethanol, shake for 5 minutes, filter, evaporate the filtrate to dryness, add 1ml of ethanol to the residue to dissolve it, and use it as the test solution. Take another reference substance of paeoniflorin, add ethanol to make a solution containing 1mg per 1ml, and use it as the reference solution. According to the thin layer chromatography method (General Rule 0502), take 20μl of the test solution and 10μl of the reference solution, and spot them on the same silica gel G thin layer plate, respectively, with chloroform-ethyl acetate-methanol-formic acid (40:5:10:0.2) as the developing agent, develop, take out, dry, spray with 5% vanillin sulfuric acid solution, and heat until the spots are clearly colored. In the chromatogram of the test sample, the same blue-purple spots appear at the corresponding position of the chromatogram of the reference substance, see the attached instructions. Figure 3 .

[0138] In order to further illustrate the safety and effectiveness of the Chinese medicine of the present invention in clinical practice, we have summarized some clinical trial results of the Chinese medicine of the present invention as follows.

[0139] 1. Clinical observation of the Chinese medicine of the present invention in treating novel coronavirus pneumonia

[0140] 1.1 General Information

[0141] A total of 124 epidemic patients with disharmony between Ying and Wei and injury of Qi and Yin syndrome who met the clinical standard requirements were collected from the outpatient department of Shaanxi Provincial Hospital of Traditional Chinese Medicine. The general data of the patients, such as age, course of disease, and severity of the disease, were compared, and there was no statistically significant difference (P>0.05), indicating that the patients were comparable.

[0142] 1.2 Diagnostic criteria

[0143] 1.2.1 Western medicine diagnostic criteria

[0144] 1.2.1.1 Refer to the diagnostic criteria of the Diagnosis and Treatment Plan for Novel Coronavirus Pneumonia (Trial Version 10):

[0145] (1) Have clinical manifestations related to COVID-19 infection;

[0146] (2) Having one or more of the following etiological and serological test results:

[0147] ① The nucleic acid test for the new coronavirus is positive; ② The antigen test for the new coronavirus is positive; ③ The isolation and culture of the new coronavirus are positive; ④ The level of IgG antibodies specific to the new coronavirus in the recovery period is 4 times or more higher than that in the acute period.

[0148] (3) Patients whose COVID-19 nucleic acid and antigen test results have turned negative;

[0149] 1.2.2 Standards for TCM Syndrome Differentiation

[0150] TCM Syndrome Diagnostic Criteria (formulated with reference to the Syndrome Section of TCM Clinical Diagnosis and Treatment Terminology GB / T16751.2-1997 and the Guiding Principles for Clinical Research of New Chinese Medicines in 2002)

[0151] Main symptoms: cough and sputum, loss of appetite, dry and sore throat, fatigue, pale red tongue with white or yellow fur, floating and weak pulse. Secondary symptoms: easy sweating, nasal congestion and runny nose, shortness of breath and laziness to speak, fever in the five parts of the body, etc. Combined with clinical practice, we summarized the syndrome of the patients we treated as "disharmony between Ying and Wei, and damage to both Qi and Yin".

[0152] 1.3 Inclusion criteria

[0153] Meet the above-mentioned Western medicine and Chinese medicine diagnostic standards.

[0154] 1.4 Exclusion criteria

[0155] ①. Patients with fever caused by infection of digestive, urinary, or blood system diseases are excluded; ②. Patients with allergic constitution or allergic to multiple drugs, or those with a history of allergy to the components of the trial drugs; ③. Patients who have used other drugs to treat the disease after the onset of the disease; ④. Patients who did not take the medicine as prescribed and whose efficacy cannot be determined, or whose data are incomplete and whose efficacy cannot be determined; ⑤. Patients with severe primary cardiovascular disease, liver disease, kidney disease, hematological disease, lung disease, or serious diseases that affect their survival, such as tumors or AIDS.

[0156] 1.5 Treatment

[0157] Preparation of the experimental drug of the present invention: 30g of Radix Pseudostellariae, 12g of Cinnamon Twig, 15g of White Peony Root, 15g of Poria, 15g of Stir-fried Atractylodes Macrocephala, 30g of Shenqu, 12g of Morus Album, 12g of Trichosanthes, 15g of Houttuynia Cordata, 12g of Platycodon Grandiflorum, 12g of Fritillaria Thunbergii, and 6g of Licorice. The above is a Chinese medicine decoction, and the method of taking is: add 400ml of water to each dose, boil over high heat, simmer for 30 minutes, take 200ml of juice, add 400ml of water to the second decoction, take 200ml of juice, mix the two decoctions, and the Chinese medicine water decoction of the present invention is obtained.

[0158] Dosage and administration: Patients take the Chinese medicine decoction of the present invention, one dose per day, twice a day, morning and evening. Pregnant women can take the medicine normally, and children can take half the dosage. During the medication period, avoid spicy and stimulating food, drink plenty of water, and pay attention to rest.

[0159] Note:

[0160] ①. People with allergic constitutions should use with caution. ②. Do not use this product when its properties change. ③. This product is suitable for epidemics, influenza, and common colds caused by disharmony between the Ying and Wei, and damage to both the Qi and Yin. It can be used by people with no sweating, aversion to cold, muscle and joint pain, fever or those who have not yet developed a fever. The earlier it is used, the better the effect. ④. If the symptoms persist and cannot be relieved, please take other medicines or go to the hospital for treatment. ⑤. People with cold gastrointestinal diseases can take it with ginger soup. ⑥. Please keep this product out of reach of children. ⑦. If you are using other medicines, please consult a doctor or pharmacist before using this product.

[0161] 1.6 Efficacy evaluation criteria

[0162] Efficacy index (nimodipine method) = (score before treatment - score after treatment) / score before treatment × 100%

[0163] Recovery: Clinical symptoms disappear or almost disappear, and syndrome score decreases by ≥95%.

[0164] Markedly effective: Clinical symptoms were significantly improved, with syndrome scores reduced by ≥70%.

[0165] Effective: Clinical symptoms are partially improved, and the syndrome score is reduced by ≥30%.

[0166] Ineffective: There is no significant improvement in clinical symptoms or they may even worsen, and the syndrome score decreases by less than 30%.

[0167] 1.7 Treatment Outcomes

[0168] All cases had a history of contact with the epidemic, cough and (or) upper respiratory tract symptoms. This study focused on cough and clinical discomfort of patients. The clinical efficacy of 124 patients with respiratory virus infection, including four main symptoms of cough and sputum, loss of appetite, dry throat and sore throat, fatigue and weakness, and four secondary symptoms of sweating, nasal congestion and runny nose, shortness of breath and laziness, and fever in the five hearts, was observed 3 days and 7 days after treatment. The results are as follows:

[0169] Table 8 Clinical efficacy observation of cough and sputum

[0170]

[0171] Table 9 Clinical efficacy observation of loss of appetite

[0172]

[0173] Table 10 Clinical efficacy observation of dry throat and sore throat

[0174]

[0175] Table 11 Observation on clinical efficacy of fatigue

[0176]

[0177] Table 12 Clinical efficacy observation on easy sweating, nasal congestion, runny nose, shortness of breath, lazy speech, and five-heart fever

[0178]

[0179] From the clinical observation results in Table 8, it can be seen that the total effective rate of the Chinese medicine of the present invention in treating cough and sputum symptoms caused by respiratory viral infection is 94.6%, and the fever symptoms of most patients can be relieved within 3 days.

[0180] From the clinical observation results in Table 9, it can be seen that the total effective rate of the Chinese medicine of the present invention in treating the loss of appetite symptoms caused by respiratory viral infection is 96.5%, and the loss of appetite symptoms of most patients can be alleviated within 3 days.

[0181] From the clinical observation results in Table 10, it can be seen that the total effective rate of the Chinese medicine of the present invention in treating dry throat and sore throat symptoms caused by respiratory viral infection is 91.2%, and the dry throat and sore throat symptoms of most patients can be relieved within 3 days.

[0182] From the clinical observation results in Table 11, it can be seen that the total effective rate of the Chinese medicine of the present invention in treating symptoms of fatigue and tiredness caused by respiratory viral infection is 90.6%, and the symptoms of fatigue and tiredness of most patients can be relieved within 3 days.

[0183] From the clinical observation results in Table 12, it can be seen that the total effective rate of the Chinese medicine of the present invention in treating the symptoms of easy sweating, nasal congestion and runny nose, shortness of breath and lazy speech, and five-heart upset heat caused by respiratory virus infection is 94.54%, and the clinical symptoms of the patients are significantly improved, with an effective rate of more than 90%. The improvement rate for five-heart upset heat is 98%.

[0184] 1.8 Safety and adverse reactions

[0185] The Chinese medicine of the present invention has no adverse reactions found in the clinical treatment observation process. The above clinical statistical results show that the Chinese medicine of the present invention has significant clinical efficacy in treating epidemics, influenza, and common colds caused by respiratory viral infections, and is safe and convenient to take, and has broad market application prospects.

[0186] Typical cases:

[0187] Case 1: Wang, male, 64 years old, chief complaint: cough, sputum and fatigue for 10 days. Current medical history: After the patient came into contact with a confirmed case of novel coronavirus infection 10 days ago, he developed fever and fatigue, with the highest body temperature of 37.8℃. After taking antipyretics and drinking a lot of water, the body temperature returned to normal. Later, he developed cough, sputum, a small amount of yellow sticky sputum, which was difficult to cough up, fatigue, dry throat, sore throat, and poor appetite. The tongue was pale red, with a thin yellow coating, tortuous sublingual collaterals, and a thin and smooth pulse.

[0188] Prescription: Pseudostellariae Radix 30g, Cinnamon Twig 12g, White Peony 15g, Poria 15g, Stir-fried Atractylodes 15g, Shenqu 30g, Mulberry Leaf 12g, Trichosanthes 12g, Houttuynia Cordata 15g, Platycodon 12g, Fritillaria thunbergii 12g, Licorice 6g. 7 sets of the above, Chinese medicine decoction, one dose per day. How to take: Add 400ml of water to each dose, boil over high heat, simmer for 30 minutes, take 200ml of juice, add 400ml of water to the second decoction, take 200ml of juice, and mix the two decoctions. One dose per day, take warm twice a day, morning and evening.

[0189] After taking the medicine, the patient covered himself with a blanket and sweated, and fatigue was relieved. After taking 3 doses, his appetite improved, and he ate food with a sweet aroma. There was no obvious dry throat or sore throat. Coughing and expectoration were relieved, and the sputum turned white, clear, and easy to cough up. The patient was in good condition.

[0190] Case 2: Gu, female, 25 years old, chief complaint: dry throat, sore throat and sweating for 9 days. Current medical history: The patient developed fever at work 9 days ago, with the highest temperature of 39.0℃, accompanied by dry throat and sore throat. Rapid new coronavirus nucleic acid test was positive. The body temperature dropped to normal after oral ibuprofen tablets. The remaining symptoms persisted, with obvious sweating. The symptoms did not improve after taking amoxicillin capsules. Expectorant, yellow, sticky and difficult to cough up, poor appetite. Red tongue with little coating, small sublingual collaterals, and thin pulse.

[0191] Prescription: Pseudostellariae Radix 30g, Cinnamon Twig 12g, White Peony 15g, Poria 15g, Stir-fried Atractylodes 15g, Shenqu 30g, Mulberry Leaf 12g, Trichosanthes 12g, Houttuynia Cordata 15g, Platycodon 12g, Fritillaria thunbergii 12g, Licorice 6g. 7 sets of the above, Chinese medicine decoction, one dose per day. How to take: Add 400ml of water to each dose, boil over high heat, simmer for 30 minutes, take 200ml of juice, add 400ml of water to the second decoction, take 200ml of juice, and mix the two decoctions. One dose per day, take warm twice a day, morning and evening.

[0192] After taking the medicine, the patient's dry throat and sore throat were relieved, sweating decreased, only slight sweating, no obvious cough, less sputum frequency, less sputum volume, white sputum, thin texture and easy to cough up, appetite improved, and food intake increased.

[0193] Case 3: Zhang, female, 23 years old, main complaint: sore throat, fatigue, shortness of breath for 1 week. Current medical history: The patient developed fever and sore throat after being infected with the new coronavirus 1 week ago. After taking ibuprofen tablets and compound paracetamol tablets, the fever symptoms were relieved, but the sore throat persisted, affecting eating and swallowing. After that, fatigue, shortness of breath, sweating, sticky sputum that is difficult to cough up, and poor appetite appeared. The tongue is pale red with a greasy white coating, the sublingual collaterals are thin, and the pulse is deep and fine.

[0194] Prescription: Pseudostellariae Radix 30g, Cinnamon Twig 12g, White Peony 15g, Poria 15g, Stir-fried Atractylodes 15g, Shenqu 30g, Mulberry Leaf 12g, Trichosanthes 12g, Houttuynia Cordata 15g, Platycodon 12g, Fritillaria thunbergii 12g, Licorice 6g. 7 sets of the above, Chinese medicine decoction, one dose per day. How to take: Add 400ml of water to each dose, boil over high heat, simmer for 30 minutes, take 200ml of juice, add 400ml of water to the second decoction, take 200ml of juice, and mix the two decoctions. One dose per day, take warm twice a day, morning and evening.

[0195] After taking the medicine, the patient felt that shortness of breath and sweating were significantly relieved, his appetite improved, and he had no abdominal distension or diarrhea. After taking the above medicine for 5 doses, the sticky phlegm became thinner and easier to cough up, fatigue and sore throat were relieved, and he could eat and swallow.

[0196] Case 4: Jia, male, 24 years old, chief complaint: cough and expectoration for 10 days. Current medical history: The patient developed fever after being infected with the new coronavirus 10 days ago, with the highest body temperature of 38.9℃. After taking loxofenadine sodium tablets, the body temperature returned to normal. After that, cough and expectoration occurred, and the sputum was white, sticky, and large in quantity. After taking ambroxol hydrochloride tablets, he still had a cough, coughed up a small amount of yellow sticky sputum, which was not easy to cough up, fatigue, sweating of hands and feet, and poor appetite. The tongue was pale red, with a thin white greasy coating, small sublingual collaterals, and a deep and fine pulse.

[0197] Prescription: Pseudostellariae Radix 30g, Cinnamon Twig 12g, White Peony 15g, Poria 15g, Stir-fried Atractylodes 15g, Shenqu 30g, Mulberry Leaf 12g, Trichosanthes 12g, Houttuynia Cordata 15g, Platycodon 12g, Fritillaria thunbergii 12g, Licorice 6g. 7 sets of the above, Chinese medicine decoction, one dose per day. How to take: Add 400ml of water to each dose, boil over high heat, simmer for 30 minutes, take 200ml of juice, add 400ml of water to the second decoction, take 200ml of juice, and mix the two decoctions. One dose per day, take warm twice a day, morning and evening.

[0198] After taking the medicine, the patient ate hot porridge, sweated a little, and his body temperature was normal. The number of coughs decreased, and the sputum was clearer and easier to cough up, and the amount was reduced. After taking 4 doses of the medicine, fatigue and sweating were significantly improved, appetite improved, and there was no wheezing or chest tightness.

[0199] Case 5: Du, female, 77 years old, chief complaint: cough with fatigue for 20 days, aggravated for 3 days. Current medical history: After being infected with the new coronavirus 20 days ago, the patient developed fever, cough, and fatigue, with the highest body temperature of 38.0℃. The self-test antigen was "positive". After taking ibuprofen tablets, the body temperature gradually returned to normal after sweating, but there was still cough and fatigue. Chest CT showed: 1. Infectious lesions in both lungs, considering the possibility of viral pneumonia, 2. Fiber foci and local inflammatory changes in the posterior basal segment of the right lower lobe and the lower lingual segment of the left upper lobe, 3. Calcification of the aorta and coronary arteries. Symptomatic treatment such as anti-infection, cough and asthma was given, and the symptoms improved slightly. 3 days ago, due to cold, cough and fatigue worsened, coughing frequently, coughing a small amount of white sticky sputum, fatigue, dry mouth, sweating, poor appetite, and less food intake than before. The tongue is dark red, the tongue coating is white and greasy, the sublingual veins are tortuous, and the pulse is stringy and thin.

[0200] Prescription: Pseudostellariae Radix 30g, Cinnamon Twig 12g, White Peony 15g, Poria 15g, Stir-fried Atractylodes 15g, Shenqu 30g, Mulberry Leaf 12g, Trichosanthes 12g, Houttuynia Cordata 15g, Platycodon 12g, Fritillaria thunbergii 12g, Licorice 6g. 7 sets of the above, Chinese medicine decoction, one dose per day. How to take: Add 400ml of water to each dose, boil over high heat, simmer for 30 minutes, take 200ml of juice, add 400ml of water to the second decoction, take 200ml of juice, and mix the two decoctions. One dose per day, take warm twice a day, morning and evening.

[0201] After taking the above medicine, the patient's cough frequency was significantly reduced, and a small amount of white sputum was coughed up easily. Fatigue improved, and spirits improved. There was no obvious dry mouth, and sweating decreased. Diet improved, and there was no abdominal distension or diarrhea.

[0202] Case 6: Wu, female, 53 years old, chief complaint: intermittent cough and expectoration for 2 weeks. Current medical history: The patient developed cough and expectoration after being infected with the new coronavirus 2 weeks ago. The sputum was white, large in quantity and thin in texture, accompanied by fever, with the highest temperature of 38.0℃, muscle aches, fatigue, sweating, chest tightness, poor appetite, and sticky and unformed stools. Chest CT: scattered ground-glass lesions in both lungs, consistent with the symptoms of new coronavirus infection. The tongue is pale and dark, with a white and greasy coating, tortuous sublingual collaterals, and a thin pulse.

[0203] Prescription: Pseudostellariae Radix 30g, Cinnamon Twig 12g, White Peony 15g, Poria 15g, Stir-fried Atractylodes 15g, Shenqu 30g, Mulberry Leaf 12g, Trichosanthes 12g, Houttuynia Cordata 15g, Platycodon 12g, Fritillaria thunbergii 12g, Licorice 6g. 7 sets of the above, Chinese medicine decoction, one dose per day. How to take: Add 400ml of water to each dose, boil over high heat, simmer for 30 minutes, take 200ml of juice, add 400ml of water to the second decoction, take 200ml of juice, and mix the two decoctions. One dose per day, take warm twice a day, morning and evening.

[0204] After taking the medicine, the patient sweated slightly, the body temperature dropped to normal, the muscle soreness was relieved, and he was able to sleep peacefully. The next day, the cough and chest tightness gradually eased. After taking the medicine for 6 days, there was no fever, the frequency of coughing decreased, the amount of sputum decreased and was easier to cough up, there was no obvious muscle soreness, the appetite improved, and the stool was soft and formed.

[0205] Case 7: Xue, female, 87 years old, main complaint: fever, cough, fatigue for 7 days. Current medical history: The patient developed fever 7 days ago after contact with a confirmed case of novel coronavirus infection, with the highest body temperature of 37.7℃, accompanied by cough, white sticky sputum, fatigue, decreased appetite, body temperature fluctuated around 37.0℃ after self-medication, dry throat, itchy throat, pain after eating or drinking, dry mouth. The tongue is pale and dark, with white fur, tortuous sublingual collaterals, and deep and stringy pulse.

[0206] Prescription: Pseudostellariae Radix 30g, Cinnamon Twig 12g, White Peony 15g, Poria 15g, Stir-fried Atractylodes 15g, Shenqu 30g, Mulberry Leaf 12g, Trichosanthes 12g, Houttuynia Cordata 15g, Platycodon 12g, Fritillaria thunbergii 12g, Licorice 6g. The above is a Chinese medicine decoction. How to take it: Add 400ml of water to each dose, boil over high heat, simmer for 30 minutes, take 200ml of juice, add 400ml of water to the second decoction, take 200ml of juice, and mix the two decoctions. Take one dose daily, twice a day, morning and evening.

[0207] After taking the first dose of the medicine, the patient began to sweat and his body temperature was 36.8℃. After intermittent monitoring, his temperature dropped to normal. After taking 3 doses, his dry throat, itchy throat, dry mouth and sputum were relieved, and he could eat and drink normally. After taking 5 doses, his cough, sputum, fatigue and poor appetite were all improved.

[0208] Case 8: Huang, male, 77 years old, main complaint: intermittent fatigue, cough for 10 days. Current medical history: The patient developed fatigue, cough, a small amount of white sticky sputum, sweating, palpitations, chest tightness, poor appetite, and dry mouth after being infected with the new coronavirus 10 days ago. The tongue is dark red, with a thin yellow coating, tortuous sublingual collaterals, and a deep, stringy, and thin pulse.

[0209] Prescription: Pseudostellariae Radix 30g, Cinnamon Twig 12g, White Peony 15g, Poria 15g, Stir-fried Atractylodes 15g, Shenqu 30g, Mulberry Leaf 12g, Trichosanthes 12g, Houttuynia Cordata 15g, Platycodon 12g, Fritillaria thunbergii 12g, Licorice 6g. The above is a Chinese medicine decoction. How to take it: Add 400ml of water to each dose, boil over high heat, simmer for 30 minutes, take 200ml of juice, add 400ml of water to the second decoction, take 200ml of juice, and mix the two decoctions. Take one dose daily, twice a day, morning and evening.

[0210] After taking the above prescription, the patient's fatigue was significantly relieved and his mental state was good. The number of coughs decreased, the sputum was less, the dry mouth and sweating were relieved. After taking 5 doses of the above prescription, the patient's appetite improved, the food intake was more, and the symptoms of palpitation and chest tightness disappeared.

Claims

1. A Chinese medicine for treating late respiratory viral infection, characterized in that: The traditional Chinese medicine is prepared from the following raw materials in proportion by weight: 280-350 parts of Pseudostellariae Radix, 100-140 parts of cinnamon twig, 130-170 parts of white peony root, 130-170 parts of Poria cocos, 130-170 parts of Atractylodes macrocephala, 280-340 parts of Shenqu, 100-140 parts of mulberry leaves, 100-140 parts of Trichosanthes kirilowii, 130-170 parts of Houttuynia cordata, 100-140 parts of Platycodon grandiflorum, 100-140 parts of Fritillaria thunbergii and 50-70 parts of liquorice.

2. The Chinese medicine for treating late respiratory viral infection as claimed in claim 1, characterized in that: The traditional Chinese medicine is made of raw materials with the following weight ratio: 330 parts of Pseudostellariae Radix, 135 parts of cinnamon twig, 165 parts of white peony root, 165 parts of Poria cocos, 165 parts of Atractylodes macrocephala, 330 parts of Shenqu, 135 parts of mulberry leaves, 135 parts of Trichosanthes kirilowii, 165 parts of Houttuynia cordata, 135 parts of Platycodon grandiflorum, 135 parts of Fritillaria thunbergii, and 66 parts of Licorice.

3. The Chinese medicine for treating late respiratory viral infection as claimed in claim 1, characterized in that: The traditional Chinese medicine is prepared from raw materials in the following weight proportions: 300 parts of Pseudostellariae Radix, 120 parts of cinnamon twig, 150 parts of white peony root, 150 parts of Poria cocos, 150 parts of Atractylodes macrocephala, 300 parts of Shenqu, 120 parts of mulberry leaves, 120 parts of Trichosanthes kirilowii, 150 parts of Houttuynia cordata, 120 parts of Platycodon grandiflorum, 120 parts of Fritillaria thunbergii, and 60 parts of Licorice.

4. The method for preparing the Chinese medicine according to any one of claims 1 to 3, characterized in that: The preparation method comprises the following steps: Take Radix Pseudostellariae Radix, Cinnamon Twig, White Peony Root, Poria, Atractylodes Macrocephala, Shenqu, Folium Mori, Fructus Trichosanthis, Houttuynia Cordata, Platycodon Grandiflorum, Fritillaria Thunbergii, and Licorice, add 8-11 times of the weight of the above medicinal materials in water, decoct for 1-3 times, decoct for 0.6-1.5 hours, filter, and combine the above decoction filtrates; take the combined decoction filtrates, concentrate and dry under reduced pressure to form a clear paste with a relative density of 1.30-1.35, and then add pharmaceutical excipients to prepare a Chinese medicine oral preparation.

5. The method for preparing the oral Chinese medicine preparation according to claim 4, characterized in that: In the preparation method, water 10 times the weight of the medicinal material is added and boiled twice for 1 hour.

6. The method for preparing the Chinese medicine according to claim 4, characterized in that: The ratio of the clear paste to auxiliary materials in the preparation method is 1:2-3.

7. The method for preparing the Chinese medicine according to claim 4, characterized in that: The auxiliary material in the preparation method is: dextrin.

8. The method for preparing the Chinese medicine according to claim 4, characterized in that: The dosage forms of the oral Chinese medicine preparation are: granules, oral liquid, capsules, tablets, and pills.

9. Use of the traditional Chinese medicine according to any one of claims 1 to 3 in the preparation of medicines for treating common cold, winter and spring influenza, and viral pneumonia.

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