A traditional Chinese medicine composition with efficacy of treating cold in children and application thereof

Abstract

The application relates to the technical field of traditional Chinese medicines, and particularly discloses a traditional Chinese medicine composition with the efficacy of treating children's cold and application thereof. The traditional Chinese medicine composition is composed of forsythia suspensa, honeysuckle and other medicines. The traditional Chinese medicine composition provided by the application coordinates external elimination of evil and internal clearing of lung heat, and combines clearing and tonifying, is safe and has no toxic side effects, can effectively treat children's cold, has the effects of antipyretic, anti-inflammatory, analgesic, cough relieving and sputum expelling, and can resist respiratory tract infection virus.

Description

TECHNICAL FIELD

[0001] The present application relates to the technical field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition with the efficacy of treating children's cold and application thereof. BACKGROUND

[0002] Influenza (hereinafter referred to as influenza) is one of the major public health problems faced by human beings, which is caused by influenza virus. Since 1889, there have been 6 detailed records of influenza pandemics. In the past 10 years, China has successively experienced outbreaks of influenza A H1N1, influenza B, and human avian influenza H7N9. Influenza virus is prone to recombination and variation, and spreads rapidly. It can cause seasonal epidemics every year, and some cases can develop into severe influenza due to complications such as pneumonia. A small number of severe cases progress rapidly, and can die of acute respiratory distress syndrome (ARDS) and / or multiple organ failure. Children are susceptible and high-risk groups of influenza, and outbreaks and epidemics can occur in places where children gather, such as schools and nurseries.

[0003] China's 0-15-year-old children have reached 247 million, accounting for 17.80% of the total population. Respiratory diseases rank first in the disease spectrum of children. A survey of 3576 children aged 0-14 in more than 100 cities shows that the top three diseases are cold (74.7%), fever (59.8%), and cough (56.0%). Children's cold ranks first in pediatric respiratory diseases. Children can have 6-8 colds a year, and 10%-15% of children have up to 12 colds a year, making it the most common respiratory disease. Common cold-related pathogens include rhinovirus, coronavirus, respiratory syncytial virus, parainfluenza virus, adenovirus, enterovirus, etc. Viruses are mediated by cough and sneezing and spread through respiratory droplets. First, they adhere to the M cells in the lymphoid epithelial area of the adenoid, and then move to the posterior nose through the nasal mucosa cilia. Respiratory mucosal edema and congestion lead to exudation. The disease often occurs during seasonal transition, especially in winter and spring. The onset is relatively acute, with symptoms such as fever, nasal congestion, sore throat, cough, sneezing, and runny nose. It is estimated that 10%-15% of children need to see a doctor due to influenza infection every year. During the influenza season, more than 40% of preschool children and 30% of school-age children may be affected by influenza. Due to passive immunization protection from the mother, children under 6 months are less likely to be infected with the disease. The 6-month to 3-year-old age group is at high risk for influenza, and is prone to severe influenza and a high incidence of complications. Children and adolescents aged 5 to 20 are at high risk for influenza, and the incidence of influenza in this age group can reach about 50% during the pandemic, which is 1.5-3 times higher than that of adults. Generally, infected individuals can expel viruses 24-48 hours before the onset of clinical symptoms, and the amount of virus expelled significantly increases 0.5-1.0 days after infection, reaching a peak within 24 hours of onset. Children with influenza have sudden onset, fever, and body temperature up to 39-40℃, accompanied by chills, rigor, headache, general muscle soreness, fatigue, loss of appetite, often cough, sore throat, runny nose or nasal congestion, and a small number of cases of nausea, vomiting, and diarrhea. Children's digestive symptoms are more common than adults, and infant influenza is atypical. Neonatal influenza is rare, but influenza is prone to pneumonia. Acute laryngitis, acute otitis media, tracheitis, bronchitis, bronchiolitis, and pneumonia caused by influenza virus in children are more common than in adults. Most influenza patients without complications recover in 3-7 days, but cough and physical recovery often last 1-2 weeks. Adults and older children generally expel viruses for 5 days (3-8 days), and the duration of virus shedding varies depending on the strain of the virus. Young children expel the same amount of virus as adults when they get sick, but the duration of virus shedding is longer than that of adults. Compared with adults, long-term virus shedding is common in infant cases (1-3 weeks). Therefore, children are actually the most important source of influenza transmission and the cause of repeated or acute exacerbations of illness in children. Timely treatment of children with influenza is of great significance to the health of children and the reduction of additional medical costs.

[0004] There is no specific antiviral drug for common cold in western medicine. Commonly used drugs for children's cold include antiviral drugs such as neuraminidase inhibitors (Oseltamivir, Zanamivir), M2 ion channel blockers (Amantadine and Rimantadine), but there are many adverse reactions and viral drug resistance problems in clinical application. At present, the proportion of children's drug market and market demand in China is rising, and the sales of pediatric drugs in Chinese public medical institutions in 2019 reached 8.905 billion yuan, with a year-on-year growth of 11.61%. However, there are few special dosage forms and specifications of children's drugs, and the market urgently needs a safe and effective drug for children's cold.

[0005] Viral respiratory infection is an acute respiratory infection caused by various viruses, which is divided into viral upper respiratory tract infection and viral lower respiratory tract infection. The former is manifested as acute rhinitis, pharyngitis and laryngitis, and the latter is manifested as acute tracheitis, bronchitis and pneumonia. This kind of disease has a high incidence, is generally susceptible to the population, and is more susceptible to children, the elderly, malnutrition and chronic diseases. It is worth noting that after the spread of the 2019 novel coronavirus disease (Corona Virus Disease 2019, COVID-19), viral respiratory infection has become prevalent worldwide.

[0006] Due to immature immunity, children may be more susceptible to infectious viruses than adults, and infants and young children are particularly susceptible to respiratory infections. In children, the mortality and morbidity of respiratory infections are still higher than those of any other disease. At present, viral respiratory infection is a frequently-occurring disease in pediatric clinics, ranking first in the number of pediatric outpatient and inpatient cases, and seriously threatening the health of children. Only for influenza, about 870,000 children under the age of 5 are hospitalized worldwide each year.

[0007] In addition, the incidence of viral lower respiratory tract infection has shown an increasing trend in recent years. According to the etiological study, viral pneumonia accounts for about 18% of community-acquired pneumonia and about 5% of hospital-acquired infection in the same period, and it has attracted more and more attention. Therefore, how to quickly and effectively cure respiratory viral infectious diseases is particularly important. SUMMARY

[0008] Children's physiological characteristics are characterized by delicate internal organs and underdeveloped physical constitution. The fact that children's internal organs are "developed but not fully formed" and "fully formed but not robust" determines their pathological characteristics of being "easily deficient or excessive" and "easily susceptible to cold or heat." Children's "qi and blood are not yet regulated, their internal organs are fragile, and their pores are open and loose." Being immature, they do not know how to protect themselves and cannot tell whether they are cold or hot, relying entirely on the care of their families. "Although their spirit is still strong, their temperament is not yet settled. They do not choose their clothing carefully; or they indulge in dressing as they please, are spoiled and unpredictable, indulge in raw and cold foods, or overeat cold or hot foods." All of these can cause children's pores to open and close improperly, their defenses against external pathogens to be weak, and they are susceptible to colds. The common cold in children is initially caused by the invasion of wind evil. The initial site of the infection is in the skin and muscles of the body. Heat is a yang evil, which is scorching and flaring upward. When wind-heat causes illness, the child may have a high fever, mild chills, and sweating or little sweating. When the heat evil disturbs the clear orifices, headache will occur. When wind-heat obstructs the throat and damages body fluids, redness, swelling and pain in the throat and dry mouth will occur. In clinical practice, headache, body aches and other head and face symptoms may be observed.

[0009] The lungs govern qi and respiration, and are responsible for the dispersing and descending of qi. They are externally connected to the skin and hair, and are responsible for protecting the body from external pathogens. The mouth, nose, skin, and hair are the channels through which external pathogens invade. When the lungs' defensive, protective, warming, and nourishing functions are normal, it is difficult for the six external pathogens to invade and harm the body. Children's skin is delicate and their defenses are thin, making it easy for pathogens to enter through the skin surface, thus easily damaging their lungs. When external wind-heat pathogens invade, the lungs are the first to be affected and become ill. Moreover, children's "lungs are often deficient," so the location of colds in children is in the "lungs."

[0010] Children are characterized by a "pure yang constitution," characterized by vigorous growth, rapid development, and abundant blood and qi. This internal and external heat easily transforms into internal heat, making them susceptible to external pathogenic factors that can manifest as internal heat. This can also occur when "heat in the heart and lungs is expelled by wind, thus allowing the wind to injure the skin and hair and enter the internal organs." The pathogenesis of wind-heat obstructing the lungs in children due to external pathogenic invasion stems from the combination of wind-heat pathogens and the child's pure yang constitution, resulting in internal heat accumulation and affecting both the lungs and the defensive qi.

[0011] The yang collaterals of the skin are where the lungs converge. The defensive qi relies on the lungs' qi-dispersing function to strengthen the skin surface and perform its protective function. If wind-heat attacks the surface, the yang collaterals become blocked, lung qi stagnates, and the defensive qi weakens. External pathogens like wind and heat can enter through the mouth, nose, or skin, causing lung qi to become congested and unable to circulate. Abnormal opening and closing of the airways leads to airway obstruction, and the turbid qi cannot escape. To expel the pathogens, the lung qi rises and impacts the glottis, causing coughing. The nose is an empty orifice, directly connected to the outside world, making it highly susceptible to external pathogens. When wind-yang rises and attacks the head and face, wind-heat obstructs the clear orifices, causing nasal congestion. When the orifices lose their clarity, the struggle between the body's resistance and pathogens occurs, leading to frequent sneezing as the pathogens are expelled. When external pathogens enter through the nose, nasal discharge cannot be contained, resulting in runny nose. In addition, the lungs and large intestine are internally and externally related. Lung heat can easily cause constipation by descending to the large intestine through the meridians. Timely bowel movement can help the lung heat to be released through the anus, thus clearing the lungs and relieving heat.

[0012] In summary, pediatric cold is caused by the invasion of pathogenic wind-heat from the skin, hair, mouth and nose. In addition, children's mental awareness has not fully developed, and they are unable to regulate their cold and warmth on their own. Once they are affected by pathogenic factors, the disease occurs. The pathological location is in the lung. The invasion of pathogenic wind-heat causes disharmony of the defensive aspect, and combined with the yang-exuberant constitution of children which is prone to transformation into heat, it affects the qi movement of the lung collaterals, leading to stagnation of qi collaterals, failure of the lung qi to disperse, congestion of pathogenic heat in the lung, blockage of the airway, and simultaneous disease of the lung and the defensive aspect.

[0013] Pediatric cold is characterized by the external invasion of wind-heat, disharmony of the defensive aspect, congestion of pathogenic heat in the lung, and blockage of the airway as its etiology and pathogenesis. The inventor proposed the treatment principle of "clearing the sense of discomfort and relieving the exterior, dispersing the lung qi and clearing heat", using pungent-cool herbs to relieve the exterior and clear away pathogenic factors, and dispersing the lung qi and clearing heat to eliminate internal fire, so that pathogenic factors are removed, the fire is dissipated, the lung resumes its dispersing function, and the airway is unobstructed, then the symptoms of the lung and the defensive aspect will naturally disappear.

[0014] Following the principle of "the visceral qi of children is pure and sensitive, and can respond promptly to treatment", the medication for children should be gentle and flexible. The physiological and pathological characteristics of children are that on the one hand, their viscera are delicate, their form and qi are not fully developed, they are prone to illness, and the disease transmission is rapid; on the other hand, they have vigorous vitality, rapid development, pure and sensitive visceral qi, and are prone to recovery. Therefore, the medication for children needs to be gentle and flexible, and heavy or strong medications should not be used. Pediatric cold is mostly caused by the invasion of pathogenic wind-heat into the lung and the defensive aspect, with a short course of disease and relatively mild symptoms. Therefore, during treatment, the medication should achieve the desired effect as soon as possible, and "the regulation should be balanced, and the tonifying and purging should not exceed the appropriate dosage".

[0015] The pharmaceutical composition of the present invention is modified based on the experience of Lianhua Qingwen in the treatment of pediatric cold and influenza. Based on the fact that the pathological location of this disease is in the lung and the defensive aspect, following the principle of "for diseases in the upper part, induce vomiting to expel them", the medications used should be light in quality, thin in flavor, cool in nature, and have the function of dispersing and penetrating, so as to exert the effect of clearing and dispersing, helping the pathogenic heat to disperse from the exterior, and also conforming to the fact that the lung is located at the highest position and is extremely clear in nature. Flos Lonicerae and Fructus Forsythiae in Yinqiao Powder are selected to disperse wind-heat and clear away heat and toxins, and Mentha haplocalyx is selected to disperse wind-heat and soothe the throat. The effect of relieving the pathogenic heat in the lung in Mahuang Xingshi Gancao Decoction in Treatise on Febrile Diseases by Zhang Zhongjing in the Han Dynasty is adopted. In the original formula of Mahuang Xingshi Gancao Decoction, there is 4 liang of Ephedrae Herba and half a jin of Gypsum Fibrosum, and the ratio of the two is 1:2. In the pharmaceutical composition of the present invention, honey-fried Ephedrae Herba is mainly used to relieve cough by dispersing the lung qi, and sweating and relieving the exterior is secondary, so the ratio of Ephedrae Herba to Gypsum Fibrosum is 1:3 to prevent excessive relieving of the exterior, following the treatment principle of Liu Wansu for pediatric cold that "it is advisable to prevent problems before they occur, adopt the method of patrolling guards, use medications for nourishing nature, and preserve their true nature".

[0016] The disease is characterized by wind-heat attacking from outside, loss of defensive qi, heat blocking the lung, and airway obstruction. The treatment should consider the lung-wei and coordinate the lung-qi. The disease is characterized by the child's failure to resolve the exterior syndrome, and the interior treatment of heat steaming. The disease is given a cool and refreshing medicine to resolve the exterior syndrome, open the pores, and give the exterior evil a way out. The heat in the interior can be resolved, and the heat can be cooled. The honeysuckle and forsythia are used to disperse and penetrate the heat in the lung-meridian. The gypsum is used to cool and disperse, resolve the exterior, and reduce fever. The mint disperses wind-heat and clears the throat. The isatis root clears heat and detoxifies, and relieves the throat and swelling. The child's cold is rapidly transmitted, so it should be actively intervened. The wind-heat is resolved to the outside, and the heat in the interior is cleared. The exterior evil and the interior heat are both resolved. The lung and the large intestine are related, so the purgation is used in the exterior treatment. The purpose is to clear the lung and purgation, and to clear the lung and purgation. The spleen and stomach are weak, so the red sage is used to clear the lung, remove blood stasis, and regulate immunity. The agastache is used to dispel dampness.

[0017] The pharmaceutical composition of the present application is derived from Lianhuaqingwen, which is composed of 13 drugs, i.e., forsythia, honeysuckle, fried ephedra, fried bitter apricot kernel, gypsum, isatis root, maima guanzhou, fishy grass, broadleaf, rhubarb, red sage, menthol, and licorice. The pharmaceutical composition of the present application is based on Lianhuaqingwen, which is composed of 11 drugs, i.e., forsythia, honeysuckle, mint, honey ephedra, gypsum, fried bitter apricot kernel, isatis root, broadleaf, red sage, rhubarb, and licorice. The maima guanzhou and fishy grass are removed, and the honeysuckle is replaced by the mint.

[0018] Maima guanzhou was first recorded in Shennong Bencao Jing and listed as inferior drug. It is bitter and slightly cold in nature, and has small toxicity. It is related to liver and stomach meridians, and has the effects of clearing heat and resolving toxicity, and cooling blood and stopping bleeding. The main effects and clinical research of maima guanzhou in respiratory system diseases are concentrated in anti-influenza virus and antibacterial aspects. Many children have liver and kidney dysfunction or weak spleen and stomach, and children are prone to vomiting after taking drugs. Therefore, maima guanzhou is removed from the prescription considering the above factors.

[0019] Fishy grass is a drug for treating phlegm-heat blocking the lung and lung abscess with pus and blood. The child's cold is in the lung-wei, and has not reached the stage of phlegm-heat blocking the lung and thick sputum. Fishy grass has a fishy smell and is not easy to correct, which causes poor compliance of children. Considering the child's immature yin and yang, and weak spleen and stomach, maima guanzhou and fishy grass are removed, so that the heat-clearing and toxicity-resolving effect is slow, and the spleen and stomach are prevented from being damaged.

[0020] Both *Lonicera japonica* (mountain honeysuckle) and *Lonicera macrantha* (golden honeysuckle) are included in the 2020 edition of the *Chinese Pharmacopoeia*. Their properties and meridian tropism (sweet, cold; entering the lung, heart, and stomach meridians), functions and indications (clearing heat and detoxifying, dispersing wind-heat; used for carbuncles, boils, sore throat, erysipelas, dysentery due to heat toxins, wind-heat colds, and febrile diseases), and dosage (6-15g) are exactly the same. However, *Lonicera japonica* is actually *Lonicera macrantha*, which has been shown in experiments to have a certain therapeutic effect on the common cold caused by influenza viruses. Flavonoids extracted and isolated from *Lonicera macrantha* have varying degrees of inhibitory effects on different types of bacteria, including *Staphylococcus aureus*, *Streptococcus pneumoniae*, *Corynebacterium diphtheriae*, and *Pseudomonas aeruginosa*. It also has strong antibacterial effects against common pathogens and opportunistic pathogens causing respiratory infections. Considering the comprehensive antibacterial effect, we used *Lonicera japonica* instead of *Lonicera macrantha* to achieve a better antibacterial effect.

[0021] Menthol can cause adverse reactions in the digestive system, mainly manifested as a cold feeling and discomfort in the stomach. Considering that children have incomplete gastrointestinal function, menthol was modified into peppermint medicinal material, and peppermint oil was extracted for medicinal use.

[0022] In this formula, the principal herbs are Forsythia suspensa and Lonicera japonica. Forsythia suspensa is slightly cold in nature and bitter in taste, and enters the lung and heart meridians. It clears heat and detoxifies, and disperses wind-heat. It soothes the exterior of the body and clears internal heat. On the one hand, it is used for its ascending and dispersing power to penetrate heat to the exterior, and is combined with Ephedra sinica to disperse wind-heat in the lungs, following the principle of "releasing stagnant fire." On the other hand, it targets the internal heat caused by external pathogens, and is aided by Gypsum fibrosum and Isatis indigotica to clear heat and detoxify. Its pungent and cool nature makes it the principal herb. Lonicera japonica: sweet and cold in nature, and enters the lung, heart, and stomach meridians. It disperses wind-heat, clears heat and detoxifies, and is used for wind-heat colds and febrile diseases. This product is sweet and cold in nature, which can effectively disperse heat evil in the lung meridian and allow heat to reach the exterior. When combined with forsythia, it helps to clear the stagnant heat in the lungs. Forsythia and honeysuckle complement each other. Both have a fragrant aroma. Forsythia has a strong ability to clear internal heat and detoxify, while honeysuckle tends to disperse exterior heat. Moreover, it is sweet and cold in nature and does not harm the spleen and stomach. It can gently promote the exterior and disperse wind-heat. While dispersing the exterior evil in the defensive qi, it also takes into account the characteristic of external wind-heat evil qi accumulating and transforming into heat.

[0023] The ingredients are peppermint, honey-processed ephedra, and gypsum.

[0024] The adjuvant herb is stir-fried bitter almond, which is bitter and pungent in taste, warm in nature, and enters the lung and large intestine meridians. Its function is to drain and moisten, moisten the lungs and stop cough, making it an essential medicine for treating cough and asthma. When almond is combined with ephedra, it can disperse and descend, lower qi and moisten dryness, and restore its descending function. One disperses and the other descends, so the cough is relieved and calmed. The combination of the two herbs disperses and stops cough, improving cough and shortness of breath in children with colds.

[0025] Isatis root: Bitter in taste, cold in nature, and enters the heart and stomach meridians. Its functions include clearing heat and detoxifying, cooling the blood and relieving sore throat. It is often used for external pathogenic factors causing fever and sore throat. It also has the effects of clearing heat and detoxifying, cooling the blood and relieving sore throat in children with colds that easily accumulate heat and cause sore throat.

[0026] Pogostemonis Herba: bitter, nature, spleen and stomach lung. Function of aromatic wet, wake up the stomach to help the stomach. Its nature is not sharp, Xidan, mild wet and not dry, good at wet and turbidity, wake up the stomach, and stop vomiting, children with weak intestines and stomach, susceptible to external pathogens, not fragrant, easy to wet and wet, so with Pogostemonis Herba aromatic wet, open the stomach and spleen, play the effect of "wake up the stomach and spleen, and the evil spirit will be no room and cure."

[0027] Rhodiola: sweet, bitter, nature, lungs, spleen, heart. Has the effect of clearing the lung and regulating immunity, the use of Rhodiola in this party, on the one hand, children are young Yin and Yang body, the development of five internal organs and six viscera is not complete, weak resistance, so use Rhodiola to improve the body's immunity, on the other hand, with gypsum to clear the lung and remove blood stasis.

[0028] Rhubarb: bitter, cold, spleen, stomach, large intestine, liver, pericardium. Clearing the lung and purging the lung. Based on the lung and large intestine, use rhubarb to clear the lung and purging the lung, and the lung heat is clear, considering the children can not bear the law, so the amount of drug in the prescription is small, to stop the disease.

[0029] Make medicine:

[0030] Licorice: sweet, nature, heart, lung, spleen and stomach. Effect of spleen and qi, lung moistening and coughing, regulating various drugs. The drug is sweet and flat, combined with the earth, into the spleen and stomach with Pogostemonis Herba to benefit the spleen and stomach and harmonize the center, and bitter apricot kernel to moisten the lungs and stop coughing, and harmonize various drugs, so the prescription is the medicine.

[0031] In summary, the pharmaceutical composition of the present application is formed according to the pathogenesis characteristics of pediatric cold and the physiological characteristics of the tender organs and viscera of children. The composition of the classical prescription combines the external and internal heat, and does not forget to protect the healthy qi, and the spleen and stomach, which embodies the treatment principle of lung and spleen, and the treatment principle of lung and spleen. The treatment principle of lung and spleen, and the treatment principle of lung and spleen. The composition is derived from the classical, and is applied in the clinic, combined with the physiological characteristics of pediatric disease, and is verified by experimental research. The theory of disease - pathogenesis - treatment principle - prescription and drug, reason, method, prescription and drug, and reason, method, prescription and drug, are connected, and the prescription is reasonable. Remove the mianma guanzhong, fishy grass, replace the honeysuckle with the mountain honeysuckle, and replace the mint with the mint. In the case of reducing the medicine, it is more suitable for children to take, and the curative effect is equivalent to the lianhuaqingwen. It provides a better choice for the most lacking professional children medicine.

[0032] In view of the above technical problems existing in the present viral respiratory tract infection, especially children's cold, the present application provides a traditional Chinese medicine composition with the effect of treating children's cold and its application.

[0033] In order to achieve the above-mentioned purpose of the application, the following technical scheme is adopted:

[0034] A traditional Chinese medicine composition with the efficacy of treating children's cold, which is composed of the following raw materials in parts by weight: 250-400 parts of forsythia, 250-400 parts of honeysuckle, 50-150 parts of ephedra, 50-150 parts of bitter apricot kernel, 250-400 parts of gypsum, 250-400 parts of radix isatidis, 50-150 parts of patchouli, 30-90 parts of rhubarb, 10-50 parts of rhodiola, 120-280 parts of mint and 50-150 parts of licorice.

[0035] Further, the traditional Chinese medicine composition with the efficacy of treating children's cold is composed of the following raw materials in parts by weight: 250 parts of forsythia, 400 parts of honeysuckle, 50 parts of ephedra, 150 parts of bitter apricot kernel, 250 parts of gypsum, 400 parts of radix isatidis, 50 parts of patchouli, 90 parts of rhubarb, 10 parts of rhodiola, 280 parts of mint and 50 parts of licorice.

[0036] Further, the traditional Chinese medicine composition with the efficacy of treating children's cold is composed of the following raw materials in parts by weight: 400 parts of forsythia, 250 parts of honeysuckle, 150 parts of ephedra, 50 parts of bitter apricot kernel, 400 parts of gypsum, 250 parts of radix isatidis, 150 parts of patchouli, 30 parts of rhubarb, 50 parts of rhodiola, 120 parts of mint and 150 parts of licorice.

[0037] Further, the traditional Chinese medicine composition with the efficacy of treating children's cold is composed of the following raw materials in parts by weight: 328 parts of forsythia, 328 parts of honeysuckle, 98 parts of ephedra, 98 parts of bitter apricot kernel, 328 parts of gypsum, 328 parts of radix isatidis, 98 parts of patchouli, 66 parts of rhubarb, 33 parts of rhodiola, 197 parts of mint and 98 parts of licorice.

[0038] Further, the traditional Chinese medicine composition with the efficacy of treating children's cold is composed of the following raw materials in parts by weight: 280 parts of forsythia, 360 parts of honeysuckle, 60 parts of ephedra, 120 parts of bitter apricot kernel, 280 parts of gypsum, 360 parts of radix isatidis, 60 parts of patchouli, 60 parts of rhubarb, 20 parts of rhodiola, 250 parts of mint and 60 parts of licorice.

[0039] Further, in the traditional Chinese medicine composition with the efficacy of treating children's cold, the ephedra is honey ephedra and the bitter apricot kernel is fried bitter apricot kernel.

[0040] Compared with the prior art, the traditional Chinese medicine composition provided by the present application has the effect of treating children's cold, and is obtained by the inventor on the basis of the prior art through a large amount of innovative labor, and is suitable for treating children's cold, specifically, the inventor adjusts the formula and the amount of Lianhuaqingwen according to the special physiological stage and physiological and pathological characteristics of children, improves the process, and adjusts the taste, and through multi-index evaluation of drug efficacy, the traditional Chinese medicine composition of the present application is invented, among 11 medicines, the monarch, minister, assistant and guide complement each other, that is, the traditional Chinese medicine composition for treating children's cold composed of specific medicinal ingredients and specific amount of proportioning. Compared with Lianhuaqingwen, the traditional Chinese medicine composition of the present application has the same effect on treating children's cold with less medicinal ingredients, and improves the taste of the product, and is more suitable for children's medication. It is proved by clinical trials that the clinical curative effect of the medicine prepared from the traditional Chinese medicine composition provided by the present application in treating children's influenza is much higher than that of the western medicine control group oseltamivir, and compared with the western medicine control group, it has good antipyretic effect, is safe and reliable, and has no adverse reactions and side effects.

[0041] Children's cold belongs to the category of new disease entering collaterals, based on the theory of collaterals disease and the space concept of collaterals disease, and the treatment law of lung collaterals disease, and combining the fact that the viscera of children are thin, the barriers are sparse, the pores are easy to open, and children are more susceptible to external pathogens than adults, the present application proposes that wind-heat invasion, loss of body surface defense, and heat obstruction in the lung and airway obstruction are the main pathogenesis of the disease, establishes the treatment method of clearing the common cold, relieving the exterior, and promoting the lung and discharging heat, follows the physiological characteristics of children that the viscera are clear and respond to the changes, uses light and agile medicine, and stops when the disease is treated; at the same time, the lung is considered as an internal and external adjustment, and active intervention is made to prevent transmission. The traditional Chinese medicine composition provided by the present application has the effect of treating children's cold, and the whole prescription coordinates external elimination of evil and internal clearing of lung heat, and combines clearing and tonifying, fully considers the physiological characteristics of children's disease, eliminates evil without damaging the normal, and conforms to the treatment strategy of lung collaterals disease that actively intervenes, the formula is derived from classics and applied in clinical practice, and embodies the research idea of integration of pathogenesis, treatment principle, prescription and medicine under the guidance of collaterals disease theory.

[0042] The present application also provides the use of the traditional Chinese medicine composition with the effect of treating children's cold in the preparation of a medicine for treating children's cold.

[0043] It is proved by pharmacological and clinical trials that the clinical curative effect of the medicine provided by the present application in treating children's influenza is much higher than that of the western medicine control group oseltamivir, and compared with the western medicine control group, it has good antipyretic effect, and has no adverse reactions and side effects such as nausea, diarrhea, vomiting, abdominal pain, abdominal distension, dry mouth, and skin rash, itching, dizziness and other gastrointestinal adverse reactions, and other side effects; compared with Lianhuaqingwen, the present application removes and replaces very medicinal materials, but has the same effect, which proves that the traditional Chinese medicine composition of the present application is very safe as children's medicine.

[0044] Further, the above-mentioned cold medicine for children is a fever-reducing medicine.

[0045] Further, the above-mentioned cold medicine for children is an anti-inflammatory and analgesic medicine.

[0046] Further, the above-mentioned cold medicine for children is a medicine for treating cough, expectoration, nasal congestion, and sore throat.

[0047] The application also provides use of the above-mentioned traditional Chinese medicine composition having the efficacy of treating cold for children in preparing an anti-respiratory infection virus medicine.

[0048] The traditional Chinese medicine composition provided by the application has in-vitro anti-virus effects on multiple strains of influenza A virus, influenza B virus, respiratory syncytial virus, and coronavirus, and acts on the early stage of virus replication. Meanwhile, the traditional Chinese medicine composition has obvious in-vivo anti-influenza A virus and respiratory syncytial virus effects. Common pathogens of viral respiratory infection include rhinovirus, influenza virus, parainfluenza virus, respiratory syncytial virus, and coronavirus. Therefore, the traditional Chinese medicine composition provided by the application can be applied to preparing an anti-respiratory infection virus medicine.

[0049] Further, the above-mentioned anti-respiratory infection virus medicine is a medicine for treating viral upper respiratory tract infection and / or viral lower respiratory tract infection.

[0050] Further, the above-mentioned anti-respiratory infection virus medicine is a medicine for treating acute rhinitis, acute pharyngitis, tonsillitis, and laryngitis.

[0051] Further, the above-mentioned anti-respiratory infection virus medicine is a medicine for treating acute tracheobronchitis or pneumonia.

[0052] Further, the active ingredients of the above-mentioned traditional Chinese medicine composition having the efficacy of treating cold for children are prepared by the following steps:

[0053] (1) The prescription amount of pachouli and mint is weighed and extracted by water vapor distillation to obtain volatile oil, which is collected and reserved; the water solution after distillation is filtered to obtain volatile oil extract, which is reserved;

[0054] (2) The prescription amount of other medicines except the medicines in step (1) is weighed and decocted with water, and the filtrate is combined with the volatile oil extract in step (1) to be concentrated, filtered, and obtained as extract, which is reserved;

[0055] The volatile oil obtained in step (1) and the extract obtained in step (2) jointly constitute the active ingredients of the traditional Chinese medicine composition.

[0056] Further, the active ingredients of the above-mentioned traditional Chinese medicine composition are prepared by the following steps:

[0057] (1) according to the prescription amount of broadleaf perilla, peppermint 10 times the amount of water, water vapor distillation extraction of volatile oil, extraction 8 hours, collection of volatile oil, ready for use; distilled water solution filter the volatile oil extract, ready for use;

[0058] (2) according to the prescription amount of other medicine except step (1) medicine, add 10 times the amount of water decoction two times, 2 hours each time, filter, filter and step (1) volatile oil extract combined, concentrated under reduced pressure to the relative density 1.15±0.05 (60℃) of the extract, filter, ready for use;

[0059] Step (1) the volatile oil obtained and step (2) the extract obtained together constitute the active ingredient of the traditional Chinese medicine composition.

[0060] The preparation method of the active ingredient of the traditional Chinese medicine composition provided by the present application is simple, convenient to operate, safe and environmentally friendly, can maximize the retention of active ingredients in traditional Chinese medicine, and ensures the efficacy of the drug.

[0061] Further, the dosage form of the above-mentioned traditional Chinese medicine composition is capsule, tablet, granule, injection, pill, powder or oral liquid.

[0062] In order to realize the above-mentioned dosage form, pharmaceutically acceptable excipients need to be added during the preparation of these dosage forms, such as: fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, flavoring agents, preservatives, bases, etc. Fillers include: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; disintegrants include: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, cross-linked sodium carboxymethyl cellulose, etc.; lubricants include: magnesium stearate, sodium dodecyl sulfate, talc, silicon dioxide, etc.; suspending agents include: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methyl cellulose, etc.; binders include: starch paste, polyvinylpyrrolidone, hydroxypropyl methyl cellulose, etc.; sweeteners include: sodium saccharin, aspartame, sucrose, cyclamate, glycyrrhetinic acid, etc.; flavoring agents include: sweeteners and various flavors; preservatives include: nipagin, benzoic acid, sodium benzoate, sorbic acid and its salts, benzalkonium bromide, chloroacetic acid, eucalyptus oil, etc.; bases include: PEG6000, PEG4000, insect wax, etc.

[0063] Further, the present application provides a preparation method of the above-mentioned granule, which is prepared by the following steps:

[0064] (1) according to the prescription amount of broadleaf perilla, peppermint using water vapor distillation method for extraction of volatile oil, collection of volatile oil, ready for use; distilled water solution filter the volatile oil extract, ready for use;

[0065] (2) Weigh other medicine tastes except the medicine tastes in step (1) according to the prescription amount, and boil with water, combine the filtrate with the volatile oil extraction liquid obtained in step (1), concentrate, filter, dry, and obtain dry extract powder, which is used for standby;

[0066] (3) The volatile oil obtained in step (1) is selected to be wrapped with betacyclodextrin to obtain volatile oil inclusion compound;

[0067] (4) The dry extract powder obtained in step (2) and the volatile oil inclusion compound obtained in step (3) are granulated with appropriate amount of excipient, and granules are prepared according to conventional method.

[0068] Further, the granules are prepared by the following steps:

[0069] (1) Distill volatile oil by steam distillation method with 10 times amount of water according to the prescription amount of pachouli and peppermint, and collect the volatile oil for standby; filter the water solution after distillation to obtain volatile oil extraction liquid for standby;

[0070] (2) Boil other medicine tastes except the medicine tastes in step (1) with water according to the prescription amount, filter, combine the filtrate with the volatile oil extraction liquid in step (1), and concentrate under reduced pressure to the extract with relative density of 1.15±0.05 (60℃), filter, and spray dry to obtain dry extract powder for standby;

[0071] (3) The volatile oil obtained in step (1) is selected to be wrapped with betacyclodextrin to obtain volatile oil inclusion compound;

[0072] (4) The dry extract powder obtained in step (2) and the volatile oil inclusion compound obtained in step (3) are granulated with appropriate amount of excipient, and granules are prepared according to conventional method.

[0073] Further, the granules are prepared by the following steps:

[0074] (1) Distill volatile oil by steam distillation method with 10 times amount of water according to the prescription amount of pachouli and peppermint, and collect the volatile oil for standby; filter the water solution after distillation to obtain volatile oil extraction liquid for standby;

[0075] (2) Boil other medicine tastes except the medicine tastes in step (1) with water according to the prescription amount, filter, combine the filtrate with the volatile oil extraction liquid in step (1), and concentrate, filter, dry, and obtain dry extract powder for standby;

[0076] (3) The volatile oil obtained in step (1) is selected to be wrapped with betacyclodextrin to obtain volatile oil inclusion compound;

[0077] (4) The dry extract powder obtained in step (2) and the volatile oil inclusion compound obtained in step (3) are granulated with appropriate amount of excipient, and granules are prepared according to conventional method.

[0078] Further, the present application provides a preparation method of the capsule, which is prepared by the following steps:

[0079] (1) The broadleaf sage and the peppermint are weighed according to the prescription amount, and the volatile oil is extracted by the water vapor distillation method, the volatile oil is collected, and the volatile oil extract is obtained by filtering the water solution after distillation;

[0080] (2) The other medicinal ingredients except the medicinal ingredients in step (1) are weighed according to the prescription amount, and are boiled with water, the filtrate is combined with the volatile oil extract obtained in step (1), and is concentrated, filtered and dried to obtain a dry extract powder, which is used for later steps;

[0081] (3) The volatile oil obtained in step (1) is combined with betacyclodextrin to obtain a volatile oil inclusion complex;

[0082] (4) The dry extract powder obtained in step (2) and the volatile oil inclusion complex obtained in step (3) are added with appropriate excipients, and are prepared into a capsule according to a conventional method. BRIEF DESCRIPTION OF DRAWINGS

[0083] Figure 1 Inhibition rate of LHQG on different cells (MTT method) in test example 5 of the present application;

[0084] Figure 2 Influence result of LHQG on expression of influenza virus NP protein in test example 5 of the present application;

[0085] Figure 3 LHQG influence result on lung tissue pathology in in vivo pharmacodynamic study of anti-influenza A virus in test example 7 of the present application (24h after infection);

[0086] Figure 4 LHQG influence result on lung tissue pathology in in vivo pharmacodynamic study of anti-influenza A virus in test example 7 of the present application (2h after the last administration);

[0087] Figure 5 LHQG influence result on CD4 + , CD8 + cell fluorescence intensity value in lung tissue in in vivo pharmacodynamic study of anti-influenza A virus in test example 7 of the present application (24h after infection);

[0088] Figure 6 LHQG influence result on CD4 + , CD8 + cell fluorescence intensity value in lung tissue in in vivo pharmacodynamic study of anti-influenza A virus in test example 7 of the present application (2h after the last administration);

[0089] Figure 7The result of the influence of LHQG on lung tissue pathology in the in vivo pharmacodynamic study of the respiratory syncytial virus of the present application (24h after infection);

[0090] Figure 8 The result of the influence of LHQG on lung tissue pathology in the in vivo pharmacodynamic study of the respiratory syncytial virus of the present application (2h after the last administration);

[0091] Figure 9 The result of the influence of LHQG on the fluorescence intensity value of CD4 + , CD8 + cells in lung tissue in the in vivo pharmacodynamic study of the respiratory syncytial virus of the present application (24h after infection);

[0092] Figure 10 The result of the influence of LHQG on the fluorescence intensity value of CD4 + , CD8 + cells in lung tissue in the in vivo pharmacodynamic study of the respiratory syncytial virus of the present application (2h after the last administration). DETAILED DESCRIPTION

[0093] In order to make the objectives, technical solutions and advantages of the present application clearer, the following further describes the present application with examples. It should be understood that the specific examples described herein are only used to explain the present application and do not limit the present application.

[0094] In order to better illustrate the Chinese medicinal composition with the efficacy of treating cold of children provided by the embodiments of the present application, the following further illustrates by examples.

[0095] Example 1

[0096] A Chinese medicinal composition with the efficacy of treating cold of children, which is composed of the following raw materials in weight parts, i.e. the prescription is: Forsythia 328g, Honeysuckle 328g, Honey Ephedra 98g, Fried Bitter Apricot Kernel 98g, Gypsum 328g, Indigo Root 328g, Patchouli 98g, Rhubarb 66g, Red Goutweed 33g, Mint 197g and Licorice 98g.

[0097] The above Chinese medicinal composition is prepared into granules, and the preparation method specifically includes the following steps:

[0098] (1) The Patchouli and the Mint are weighed according to the prescription amount and added with 10 times the amount of water, and the volatile oil is extracted by water vapor distillation method, and the extraction is performed for 8 hours, and the volatile oil is collected and reserved; the water solution after distillation is filtered to obtain the volatile oil extraction liquid and reserved;

[0099] (2) Weigh other medicine tastes except the medicine tastes in step (1) according to the prescription amount, add 10 times amount of water to decoct twice, each time for 2 hours, filter, combine the filtrate with the volatile oil extraction liquid in step (1), reduce pressure to concentrate to the extract with relative density of 1.15±0.05 (60℃), filter, spray dry to obtain dry extract powder, reserve for use;

[0100] (3) Use betacyclodextrin to package the volatile oil obtained in step (1) to obtain volatile oil inclusion compound;

[0101] (4) Mix the dry extract powder obtained in step (2), the volatile oil inclusion compound obtained in step (3), sucralose and maltodextrin, dry granulation to obtain granules, reserve for use.

[0102] Example 2

[0103] A traditional Chinese medicine composition with the efficacy of treating children's cold is composed of the following raw materials by weight, i.e. the prescription is: forsythia 350g, honeysuckle 350g, honey ephedra 100g, fried bitter apricot kernel 100g, gypsum 350g, isatis root 350g, patchouli 100g, rhubarb 70g, red ginseng 35g, peppermint 210g and licorice 100g.

[0104] The above traditional Chinese medicine composition is prepared into a capsule, and the preparation method specifically includes the following steps:

[0105] (1) Weigh patchouli and peppermint according to the prescription amount, add 12 times amount of water, extract volatile oil by water vapor distillation method, extract for 6 hours, collect volatile oil, reserve for use; filter the water solution after distillation to obtain volatile oil extraction liquid, reserve for use;

[0106] (2) Weigh other medicine tastes except the medicine tastes in step (1) according to the prescription amount, add 12 times amount of water to decoct twice, each time for 2 hours, filter, combine the filtrate with the volatile oil extraction liquid in step (1), reduce pressure to concentrate to the extract with relative density of 1.15±0.05 (60℃), filter, spray dry to obtain dry extract powder, reserve for use;

[0107] (3) Use betacyclodextrin to package the volatile oil obtained in step (1) to obtain volatile oil inclusion compound;

[0108] (4) Mix the dry extract powder obtained in step (2), the volatile oil inclusion compound obtained in step (3), sucralose and maltodextrin, dry granulation to obtain granules, reserve for use.

[0109] Example 3

[0110] A traditional Chinese medicine composition with the efficacy of treating children's cold is composed of the following raw materials by weight, i.e. the prescription is: forsythia 250g, honeysuckle 400g, ephedra 50g, bitter apricot kernel 150g, gypsum 250g, isatis root 400g, patchouli 50g, rhubarb 90g, red ginseng 10g, peppermint 280g and licorice 50g.

[0111] The above traditional Chinese medicine composition is prepared into tablets, and the preparation method specifically comprises the following steps:

[0112] (1) The amount of perilla and mint is weighed according to the prescription, and 8 times the amount of water is added. The volatile oil is extracted by water vapor distillation method, and the extraction is 12 hours. The volatile oil is collected and reserved. The water solution after distillation is filtered to obtain the volatile oil extract, which is reserved;

[0113] (2) The amount of other medicinal ingredients except the medicinal ingredients in step (1) is weighed according to the prescription, and 8 times the amount of water is added. It is boiled twice, each time for 1.5 hours. It is filtered, and the filtrate is combined with the volatile oil extract in step (1). It is concentrated under reduced pressure to a relative density of 1.15±0.05 (60°C) extract, filtered, and dried under reduced pressure to obtain dry powder, which is reserved;

[0114] (3) The volatile oil obtained in step (1) is selected to be wrapped with betacyclodextrin to obtain a volatile oil inclusion compound;

[0115] (4) The dry powder obtained in step (2) and the volatile oil inclusion compound obtained in step (3) are mixed with starch, granulated, dried, and tableted to obtain granules, which are reserved.

[0116] Example 4

[0117] A traditional Chinese medicine composition with the function of treating cold in children is composed of the following raw materials in weight parts, i.e. the prescription is: forsythia 350g, honeysuckle 350g, honey ephedra 100g, fried bitter apricot kernel 100g, gesso 350g, isatis root 350g, perilla 100g, rhubarb 70g, rhodiola 35g, mint 210g and licorice 100g.

[0118] The above traditional Chinese medicine composition is prepared into tablets, and the preparation method specifically comprises the following steps:

[0119] (1) The amount of perilla and mint is weighed according to the prescription, and 8 times the amount of water is added. The volatile oil is extracted by water vapor distillation method, and the extraction is 12 hours. The volatile oil is collected and reserved. The water solution after distillation is filtered to obtain the volatile oil extract, which is reserved;

[0120] (2) The amount of other medicinal ingredients except the medicinal ingredients in step (1) is weighed according to the prescription, and 8 times the amount of water is added. It is boiled twice, each time for 1.5 hours. It is filtered, and the filtrate is combined with the volatile oil extract in step (1). It is concentrated under reduced pressure to a relative density of 1.15±0.05 (60°C) extract, filtered, and dried under reduced pressure to obtain dry powder, which is reserved;

[0121] (3) The volatile oil obtained in step (1) is selected to be wrapped with betacyclodextrin to obtain a volatile oil inclusion compound;

[0122] (4) The dry powder obtained in step (2) and the volatile oil inclusion compound obtained in step (3) are mixed with starch, granulated, dried, and tableted to obtain granules, which are reserved.

[0123] Example 5

[0124] A traditional Chinese medicine composition with the efficacy of treating cold in children, which is composed of the following raw materials in weight parts, i.e. the prescription is: forsythia 280g, honeysuckle 360g, ephedra 60g, bitter almond 120g, gypsum 280g, isatis root 360g, patchouli 60g, rhubarb 60g, red ginseng 20g, mint 250g and licorice 60g.

[0125] The above traditional Chinese medicine composition is prepared into tablets, and the preparation method specifically includes the following steps:

[0126] (1) according to the prescription, patchouli and mint are weighed and 8 times the amount of water is added, and the volatile oil is extracted by water vapor distillation method, and the extraction is 12 hours, and the volatile oil is collected for standby; the water solution after distillation is filtered to obtain the volatile oil extract for standby;

[0127] (2) according to the prescription, other medicinal materials except those in step (1) are weighed and 8 times the amount of water is added, and boiled twice, each time for 1.5 hours, and filtered, and the filtrate is combined with the volatile oil extract in step (1), and concentrated under reduced pressure to the relative density of 1.15±0.05 (60℃) of the extract, and filtered, and dried under reduced pressure to obtain dry extract powder for standby;

[0128] (3) the volatile oil obtained in step (1) is selected to be wrapped with betacyclodextrin to obtain volatile oil inclusion complex;

[0129] (4) the dry extract powder obtained in step (2) and the volatile oil inclusion complex obtained in step (3) are mixed with starch, granulated, dried, and the granules are pressed into tablets for standby.

[0130] Example 6

[0131] A traditional Chinese medicine composition with the efficacy of treating cold in children, which is composed of the following raw materials in weight parts, i.e. the prescription is: forsythia 400g, honeysuckle 250g, ephedra 150g, bitter almond 50g, gypsum 400g, isatis root 250g, patchouli 150g, rhubarb 30g, red ginseng 50g, mint 120g and licorice 150g.

[0132] The above traditional Chinese medicine composition is prepared into granules, and the preparation method specifically includes the following steps:

[0133] (1) according to the prescription, patchouli and mint are weighed and 8 times the amount of water is added, and the volatile oil is extracted by water vapor distillation method, and the extraction is 12 hours, and the volatile oil is collected for standby; the water solution after distillation is filtered to obtain the volatile oil extract for standby;

[0134] (2) Weigh other medicinal ingredients except those in step (1) according to the prescription, add 10 times the amount of water, decoct twice, each for 2 hours, filter, combine the filtrate with the volatile oil extract in step (1), reduce pressure to concentrate to the extract with a relative density of 1.15±0.05 (60°C), filter, and spray dry to obtain dry extract powder for standby;

[0135] (3) Use betacyclodextrin to package the volatile oil obtained in step (1) to obtain volatile oil inclusion compound;

[0136] (4) Mix the dry extract powder obtained in step (2) and the volatile oil inclusion compound obtained in step (3) with sucralose and maltodextrin, dry granulate to obtain granules for standby.

[0137] Example 1

[0138] On the basis of Example 1, replace honeysuckle with wild chrysanthemum, and other drugs and their dosages remain unchanged, i.e. the prescription is: forsythia 328g, wild chrysanthemum 328g, honey ephedra 98g, fried bitter apricot kernel 98g, gypsum 328g, isatis root 328g, patchouli 98g, rhubarb 66g, rhodiola 33g, mint 197g, and licorice 98g.

[0139] The above traditional Chinese medicine composition is prepared into granules, and the preparation method specifically includes the following steps:

[0140] (1) Weigh patchouli and mint according to the prescription, add 10 times the amount of water, and extract volatile oil by water vapor distillation method for 8 hours, collect the volatile oil for standby; filter the water-soluble solution after distillation to obtain volatile oil extract for standby;

[0141] (2) Weigh other medicinal ingredients except those in step (1) according to the prescription, add 10 times the amount of water, decoct twice, each for 2 hours, filter, combine the filtrate with the volatile oil extract in step (1), reduce pressure to concentrate to the extract with a relative density of 1.15±0.05 (60°C), filter, and spray dry to obtain dry extract powder for standby;

[0142] (3) Use betacyclodextrin to package the volatile oil obtained in step (1) to obtain volatile oil inclusion compound;

[0143] (4) Mix the dry extract powder obtained in step (2) and the volatile oil inclusion compound obtained in step (3) with sucralose and maltodextrin, dry granulate to obtain granules for standby.

[0144] Example 1

[0145] On the basis of Embodiment 1, forsythia suspensa is used to replace forsythia, and other drugs and their dosages are not changed, i.e. the prescription is: forsythia suspensa 328 g, lonicera japonica 328 g, eupatorium fortunei 98 g, bitter apricot kernel 98 g, gypsum 328 g, isatidis radix 328 g, pachystachys juparana 98 g, rhubarb 66 g, rhodiola 33 g, mentha haplocalyx 197 g, and licorice 98 g.

[0146] The above traditional Chinese medicine composition is prepared into granules, and the preparation method specifically comprises the following steps:

[0147] (1) According to the prescription amount, eupatorium fortunei and mentha haplocalyx are weighed and added with 10 times the amount of water, and the volatile oil is extracted by water vapor distillation method, and the extraction is carried out for 8 hours. The volatile oil is collected and used. The water solution after distillation is filtered to obtain the volatile oil extraction liquid, which is used.

[0148] (2) According to the prescription amount, other drugs except the drugs in step (1) are weighed and added with 10 times the amount of water, and boiled twice, each for 2 hours. The filtrate is combined with the volatile oil extraction liquid in step (1), and concentrated under reduced pressure to a relative density of 1.15±0.05 (60℃) of the extract. The filtrate is filtered and spray dried to obtain a dry extract powder, which is used.

[0149] (3) The volatile oil obtained in step (1) is selected to be wrapped with betacyclodextrin to obtain a volatile oil inclusion compound.

[0150] (4) The dry extract powder obtained in step (2) and the volatile oil inclusion compound obtained in step (3) are mixed with sucralose and maltodextrin, and dry granulation is carried out to obtain granules, which are used.

[0151] In order to better illustrate the characteristics of the traditional Chinese medicine composition provided by the embodiments of the present application with the efficacy of treating children's cold, the granules prepared in Example 1 and Comparative Examples 1 and 2 are tested for prevention and treatment effect.

[0152] Test Example 1

[0153] In order to illustrate the safety of the traditional Chinese medicine composition, the granules prepared in Example 1 (hereinafter referred to as the traditional Chinese medicine composition or LHQG) are used for toxicity test.

[0154] The traditional Chinese medicine composition is repeatedly administered intragastrically to young SD rats for 6 weeks and recovery for 4 weeks for toxicity test.

[0155] The purpose of this test is to evaluate the possible toxic reactions (including developmental toxicity) of the traditional Chinese medicine composition of the present application after being repeatedly administered intragastrically to young SD rats for 6 weeks, target organs, and recovery of toxicity reactions after 4 weeks of drug withdrawal, to provide animal test data for clinical research of the test product.

[0156] Test selected young SD rats (21 days after birth, PND21) 200, half male and female, according to the gender section randomly divided into 8 groups, 1~4 groups for toxicology research group, 30 in each group (male and female half), respectively, solvent control group (sterile water for injection), low-dose group (6g crude drug / kg / day), middle-dose group (12g crude drug / kg / day) and high-dose group (24g crude drug / kg / day); 5~8 groups for behavior function and estrus cycle inspection, respectively, solvent control group, low-dose group, middle-dose group and high-dose group, each group of 20 (male and female half), the same as the dose of toxicology research group. Gavage administration, animals on the 21st day after birth (PND21) start to give medicine, once a day, continuous administration for 6 weeks, to 63 days of age (adult), a total of 42 times of administration. During the test period, the animals were observed, body weight, food intake, physical development, behavior development, blood cell count, coagulation function, blood biochemistry, urine, ophthalmic examination, and male sperm count and activity, sperm morphology and female estrus cycle were checked. The next day after the last administration, some animals were euthanized, and the remaining animals were euthanized after a 4-week recovery period. After euthanasia, gross autopsy was performed, the main organs were weighed, the organ-to-body ratio and organ-to-brain ratio were calculated, and more than 40 kinds of tissue organs were subjected to histopathological examination.

[0157] During the test period, the body weight, food intake, ophthalmic examination, urine analysis, blood cell count, coagulation index, and blood biochemistry index of animals in each dose group showed no abnormal changes related to the test product; the growth and development indicators, including unit time growth rate, physical development indicators (the age of reaching the standard of vaginal opening, testicular descent and prepuce separation, body length, tail length and tibia length), behavior development indicators (total distance and activity frequency of animals in spontaneous activity test, spontaneous alternation rate of animals in Y maze test), and reproductive related indicators (sperm count and activity of male mice, sperm morphology, irregular rate of female estrus cycle) showed no obvious abnormal changes related to the test product.

[0158] Under the conditions of this test, the traditional Chinese medicine composition in the present application was repeatedly gavaged to young SD rats at a dose of 6, 12, and 24g of crude drug / kg / day, once a day, for 6 weeks of continuous administration and 4 weeks of recovery. No growth and development toxicity and systemic toxicity related to the test product were observed at doses of 6, 12 and 24g of crude drug / kg / day, indicating that the traditional Chinese medicine composition in the present application is safe when administered to young SD rats.

[0159] Test Example 2

[0160] To illustrate the activity of the traditional Chinese medicine composition in the present application in treating cold, the granules prepared in Example 1 (hereinafter referred to as the traditional Chinese medicine composition in the present application) and the granules prepared in Comparative Examples 1 and 2 were subjected to the following efficacy tests.

[0161] 1. Experimental purpose

[0162] The experiment adopts a mouse ammonia water spray induced cough model (antitussive), a mouse tracheal segment phenol red excretion model (expectorant), a rat intraperitoneal injection of lipopolysaccharide (LPS) induced fever model (antipyretic), and a mouse dimethylbenzene induced ear swelling model (anti-inflammatory) to evaluate the efficacy of the traditional Chinese medicine composition (LHQG) in the application.

[0163] 2 Test method

[0164] 2.1 Antitussive test

[0165] Half of the KM mice are female and half are male, and are randomly divided into 6 groups according to body weight, namely the model group, dextromethorphan group, Lianhuaqingwen group, the traditional Chinese medicine composition (LHQG) group, the comparative example 1 (LHQG-A) group, and the comparative example 2 (LHQG-B) group. The tentative clinical dose is 0.4g of crude drug / kg of body weight, and the mouse dose is 4.0g of crude drug / kg, which is 10 times the tentative clinical dose, and this is the clinical equivalent dose. Continuous administration for 3d, 1 time / d, about 0.5h after the last administration, induce cough, and record the cough latency period and the number of coughs within 3min.

[0166] 2.2 Expectorant test

[0167] Half of the KM mice are female and half are male, and are randomly divided into 6 groups according to body weight, namely the model group, ambroxol group, Lianhuaqingwen group, the traditional Chinese medicine composition (LHQG) group, the comparative example 1 (LHQG-A) group, and the comparative example 2 (LHQG-B) group. The tentative clinical dose is 0.4g of crude drug / kg of body weight, and the mouse dose is 4.0g of crude drug / kg, which is 10 times the tentative clinical dose, and this is the clinical equivalent dose. Continuous administration for 3d, 1 time / d, about 0.5h after the last administration, the mice are intraperitoneally injected with 2.5% phenol red solution, 0.5h later, the animals are sacrificed by cervical dislocation, and the same tracheal segment is cut and placed in a test tube containing 2ml of normal saline, 0.1ml of 1mol / l NaOH solution is added, the absorbance value is measured at a wavelength of 546nm, and the phenol red concentration is calculated.

[0168] 2.3 Antipyretic test

[0169] Male SD rats are randomly divided into 6 groups according to the basal body temperature, namely the model group, ibuprofen group, Lianhuaqingwen group, the traditional Chinese medicine composition (LHQG) group, the comparative example 1 (LHQG-A) group, and the comparative example 2 (LHQG-B) group. The tentative clinical dose is 0.4g of crude drug / kg of body weight, and the mouse dose is 3.2g of crude drug / kg, which is 8 times the tentative clinical dose, and this is the clinical equivalent dose. Before the test, the basal body temperature is measured once and recorded as T0, the basal body temperature is screened and grouped, the grouping is completed, and then the drug is administered, 30min after the administration, the rats are intraperitoneally injected with 20μg / kg LPS, and the anal temperature is measured every 1h after modeling and recorded as T xCalculate the body temperature difference ΔT over 5 consecutive hours, where ΔT = T x -T0.

[0170] 2.4 Anti-inflammatory experiment

[0171] KM mice, with equal numbers of males and females, were randomly divided into 6 groups according to body weight: the model group, the aspirin group, the Lianhua Qingwen group, the traditional Chinese medicine composition of this invention (LHQG) group, the comparative example 1 (LHQG-A) group, and the comparative example 2 (LHQG-B) group. The proposed clinical dose was 0.4 g crude drug / kg body weight, and the mouse dose was set at 4.0 g crude drug / kg, which was 10 times the proposed clinical dose; this was the clinically equivalent dose. The mice were administered the drug once daily for 3 consecutive days. Approximately 0.5 hours after the last administration, xylene was applied to the middle of the right ear, 15 μl on each side. The left ear was left untreated. Forty minutes later, the mice were euthanized by cervical dislocation. Ear flaps were punched out symmetrically from both ears, weighed using a precision analytical balance, and the weight was recorded. The degree of swelling and the swelling inhibition rate were calculated. The degree of swelling was calculated as: weight of the right ear flap - weight of the left ear flap. Swelling inhibition rate = (average swelling degree of model group - average swelling degree of drug treatment group) / average swelling degree of model group × 100%.

[0172] 3 Statistical Methods

[0173] Experimental data are expressed as mean ± standard deviation ( The significance levels were set at 0.05 and 0.01. Statistical analysis was performed using SPSS software. One-way ANOVA was used to compare means. First, a test for homogeneity of variance was performed. If the variances were homogeneous, the least significant difference (LSD) test was used. If the variances were not homogeneous, Dunnett's T3 test was used.

[0174] 4 Results

[0175] 4.1 Antitussive test

[0176] Compared with the model group, the cough latency period of mice in the Lianhua Qingwen group and the traditional Chinese medicine composition (LHQG) group of this invention was significantly prolonged (P<0.05), and the number of coughs was significantly reduced (P<0.05). There were no significant differences in the cough latency period and the number of coughs in the comparative example 1 (LHQG-A) group and the comparative example 2 (LHQG-B) group (P>0.05). Compared with the model group, the cough latency period of mice in the dextromethorphan group was significantly prolonged (P<0.05), and the number of coughs was significantly reduced (P<0.05).

[0177]

[0178] 4.2 Expectorant test

[0179] Compared with the model group, the concentration of phenol red in the Lianhuaqingwen group and the LHQG group was significantly increased (P<0.05), and the concentration of phenol red in the LHQG-A group and the LHQG-B group was not significantly different (P>0.05); the concentration of phenol red in the ambroxol group was significantly increased compared with the model group (P<0.05).

[0180]

[0181] 4.3 Antipyretic test

[0182] Compared with the model group, the temperature difference of the rats in the Lianhuaqingwen group and the LHQG group was significantly reduced 3h and 4h after modeling (P<0.05), and the temperature difference of the rats in the LHQG-A group and the LHQG-B group was not significantly different (P>0.05); the temperature difference of the rats in the ibuprofen group was significantly reduced 2h, 3h and 4h after modeling (P<0.01 or P<0.05).

[0183]

[0184] 4.4 Anti-inflammatory experiment

[0185] Compared with the model group, the ear swelling degree of the mice in the Lianhuaqingwen group and the LHQG group was significantly reduced (P<0.05), and the swelling inhibition rates were 30.29% and 30.85%, respectively. The ear swelling degree of the mice in the LHQG-A group and the LHQG-B group was not significantly different (P>0.05); the ear swelling degree of the mice in the aspirin group was significantly reduced (P<0.01), and the swelling inhibition rate was 37.70%.

[0186]

[0187] 5. Conclusion

[0188] Under the conditions of the present experiment, the LHQG significantly inhibited the cough caused by ammonia water in mice, significantly increased the phenol red excretion of the tracheal segment of the mice, significantly inhibited the fever caused by LPS in rats, and significantly reduced the ear swelling degree of the mice caused by dimethylbenzene. The drug efficacy of the LHQG-A and the LHQG-B is not obvious. It is proved that the traditional Chinese medicine composition provided by the present application can effectively treat cold and can be applied to the preparation of a medicine for treating cold in children. Specifically, the medicine can be an antipyretic, anti-inflammatory, cough-relieving and expectorant medicine.

[0189] Test Example 3

[0190] In order to clarify the analgesic effect of the traditional Chinese medicine composition of the present application, the granules prepared in Example 1 (hereinafter referred to as the traditional Chinese medicine composition (LHQG) of the present application) were used to perform the following efficacy tests.

[0191] 1. Test purpose

[0192] In this experiment, mice were induced to writhe by intraperitoneal injection of 0.7% acetic acid to observe the effect of the herbal composition of this invention on pain.

[0193] 2. Test Methods

[0194] 1) Dosage and grouping

[0195] Sixty KM mice were randomly divided into five groups according to their body weight, including the model group; the indomethacin group; and the high, medium, and low dose groups of LHQG, with dosages of 2.00, 1.00, and 0.50 g / kg, respectively. The dosage of indomethacin in mice was set at 5.00 mg / kg.

[0196] 2) Administration method

[0197] The drug was administered via gavage, following the same route of administration as in clinical practice. A disposable syringe was used, with a dosage of 10 ml / kg. Animals in the model group received the corresponding volume of solvent, and administration continued for 5 days.

[0198] 3) Observation indicators, time, and content

[0199] Newly received experimental animals were numbered, acclimatized for 5 days, and grouped as described above. All animals were fasted for at least 15 hours before the last administration. One hour after the last administration, 10 ml / kg of 0.7% acetic acid was injected into the peritoneal cavity of the mice to stimulate the visceral and parietal peritoneum, causing a deep, large-area, and prolonged pain response. This resulted in writhing behaviors in the mice, such as abdominal retraction, trunk and hind limb extension, and raised buttocks. The latency period of the writhing response and the number of writhing movements within 15 minutes were recorded as quantitative indicators of pain.

[0200] 4) Statistical methods

[0201] Experimental data were analyzed using SPSS 18.0 statistical software, with significance levels of 0.05 and 0.01. Results are expressed as mean ± standard deviation. The method involves first performing a normality test. For data that conforms to a normal distribution, one-way ANOVA is used to compare the means. If the variances are homogeneous, the least significant difference (LSD) method is used for pairwise comparisons. If the variances are not homogeneous, Dunnett's T3 test is used for pairwise comparisons. If the data does not conform to a normal distribution, nonparametric tests are used.

[0202] 3. Results

[0203] As shown in Table 5, compared with the model group, the number of writhing movements in the indomethacin group was significantly reduced (P<0.05), and the writhing latency in the LHQG medium-dose group was significantly prolonged (P<0.05), while the number of writhing movements was significantly reduced (P<0.05). The writhing latency in the indomethacin group and the LHQG high-dose group was slightly prolonged compared with the model group, but the difference was not significant (P>0.05). The number of writhing movements in the LHQG high- and low-dose groups was slightly reduced compared with the model group, but the difference was not significant (P>0.05).

[0204]

[0205] 4. Conclusion

[0206] Under the conditions of this experiment, LHQG significantly inhibited the pain response induced by acetic acid stimulation of the mouse peritoneum. This indicates that the herbal composition of this invention has analgesic effects and can be used in the preparation of analgesic drugs.

[0207] Test Example 4

[0208] To further illustrate the clinical efficacy of the traditional Chinese medicine composition of the present invention, a clinical study was conducted using the granules prepared in Example 1 (hereinafter referred to as the traditional Chinese medicine composition of the present invention).

[0209] 1. General Information

[0210] Patients diagnosed with influenza in children who visited the respiratory or pediatric departments of Hebei Yiling Hospital were selected. 101 patients who met the inclusion criteria were randomly assigned to the drug group or the western medicine control group of this invention and used the drug for 5 consecutive days.

[0211] 2. Selection of research subjects

[0212] 2.1 Western Medicine Diagnostic Criteria

[0213] Referencing the "Guidelines for the Diagnosis and Treatment of Influenza (2011 Edition)" formulated by the Ministry of Health.

[0214] I. Clinical Circumstances Requiring Consideration for Influenza: (I) During an influenza epidemic, the following situations should prompt consideration of influenza: 1. Fever accompanied by acute respiratory symptoms such as cough and / or sore throat. 2. Fever accompanied by acute exacerbation of pre-existing chronic lung disease. 3. Fever in infants and children without other symptoms and signs. 4. New respiratory symptoms or worsening of pre-existing respiratory symptoms in the elderly (≥65 years of age), with or without fever. 5. Fever or hypothermia in severely ill patients. (II) At any time, the presence of fever accompanied by acute respiratory symptoms such as cough and / or sore throat, and the traceability of an influenza-related epidemiological history—such as the patient having visited a workplace or community with an influenza outbreak within 7 days prior to the onset of illness; living with or having close contact with suspected influenza cases; returning from travel to countries or regions with influenza epidemics, etc.

[0215] II. Cases requiring pathogenic examination: If conditions permit, cases with the above conditions can be arranged for pathogenic examination to obtain a clear diagnosis. For cases where a clear diagnosis will affect clinical treatment, pathogenic examination should be actively arranged. These cases generally include: high-risk cases requiring a decision on whether to promptly initiate antiviral treatment; cases requiring a diagnosis to arrange other diagnostic tests; cases requiring a decision on whether to use antibiotic treatment; cases waiting for a diagnosis to arrange appropriate infection control measures; cases for epidemiological sampling investigation, etc.

[0216] III. Diagnostic criteria: A person with clinical symptoms and one or more of the following positive pathogenic test results can be diagnosed with influenza: (1) positive influenza virus nucleic acid test (real-time RT-PCR and RT-PCR methods can be used); (2) positive influenza virus rapid antigen test (immunofluorescence and colloidal gold methods can be used), which requires comprehensive judgment in combination with epidemiological history; (3) positive influenza virus isolation culture; (4) a 4-fold or greater increase in influenza virus-specific IgG antibody levels in acute and convalescent phase serum.

[0217] 2.2 Diagnosis criteria for TCM syndromes

[0218] TCM compound preparation diagnosis and treatment should comply with the basic principle of "correspondence between prescription and syndrome", and recognized diagnostic criteria for syndromes should be selected. The "Guiding Principles for Clinical Trials of New Drugs for Treating Influenza" states that the main TCM syndromes of influenza are wind-heat invading the defensive aspect, wind-cold binding the exterior, interior heat with exterior cold, and damp-heat stagnation, etc. The drug of the present application is mainly suitable for the heat-toxin invading the lung syndrome (Influenza Diagnosis and Treatment Scheme (2018 Edition)), and the symptoms are: fever or high fever, aversion to cold, muscle soreness, nasal congestion and runny nose, cough, headache, dry throat, sore throat, tongue redness, yellow or yellowish greasy fur, and slippery and rapid pulse, etc.

[0219] 2.3 Inclusion criteria

[0220] 1. Meet the diagnostic criteria for influenza, have clinical symptoms of influenza, and have at least one respiratory symptom (cough, runny nose / nasal congestion, sore throat, etc.) caused by influenza virus infection. The onset time of influenza symptoms is within 48 hours before the study. 2. Age 3-14 years old, male and female. 3. Within the influenza season, body temperature ≥ 37.3℃ or fever history of body temperature ≥ 37.3℃ within 48 hours before baseline. 4. No use of any antiviral / anti-influenza drugs after onset. 5. Positive nasal or throat swab influenza virus rapid antigen test. 6. The legal guardian voluntarily signs a written informed consent form before the study begins (children ≥ 10 years old also need to voluntarily sign an informed consent form).

[0221] 2.4 Exclusion criteria

[0222] 1. Severe influenza and influenza patients with complications. 2. Fever temperature ≥ 39.5℃. 2. Subjects with the following conditions: non-influenza virus-induced lower respiratory tract infection, asthma requiring daily treatment, any other chronic respiratory disease, respiratory bacterial infection such as suppurative tonsillitis, acute tracheobronchitis, sinusitis, otitis and other respiratory diseases affecting the evaluation of clinical trials. 3. The subject was inoculated with influenza vaccine within 1 month; is receiving systemic hormone or other immunosuppressive therapy, or taking traditional Chinese medicine or other antiviral drugs. 4. Patients with severe liver, kidney, heart, lung, vascular, neurological, endocrine, immune function diseases, cancer. 5. Participated in other clinical trials within 1 month. 6. Allergic or known history of allergy to test drug ingredients. 7. Any other related diseases or conditions that the investigator believes may limit or interfere with study participation or affect study results.

[0223] 2.5 Subject withdrawal criteria

[0224] 2.5.1 Decided by the investigator: 1. The investigator believes that the complications or physiological abnormalities make the subject no longer eligible to participate in this clinical trial. 2. The subject has taken less than 80% or more than 120% of the test drug. 3. The subject has a serious adverse event and / or laboratory test abnormality, and the investigator believes that and / or for safety reasons, the subject is required to withdraw from the trial. 4. The subject has taken drugs prohibited by the trial protocol.

[0225] 2.5.2 Decided by the subject: The subject can withdraw from the study at any time with or without reason, and if the subject stops taking the drug or refuses to undergo examination, it is considered to terminate the trial. The study records of all subjects who withdraw from the trial or terminate the trial should be recorded in full, and the last observed data should also be used for efficacy and safety analysis.

[0226] 3 Treatment method

[0227] (1) Grouping: divided into the drug group of the application and the western medicine control group (oral oseltamivir granules), patients meeting the inclusion and exclusion criteria are randomly allocated to the above two groups.

[0228] Drug group of the application: granules prepared in Example 1, taken for 5 days.

[0229] Western medicine control group: oral oseltamivir granules, 25mg / bag, taken for 5 days, taken with warm water. The dosage recommended for children according to the following body weight-dosage table (Table 6) is taken.

[0230] Table 6 Body weight-dosage table

[0231]

[0232] (2) Combination medication: During the trial, the protocol prohibits the use of any other medication for the treatment of influenza and its related symptoms, including but not limited to antiviral drugs, antipyretic analgesics, and any traditional Chinese medicine antiviral drugs. Any other medication that the investigator believes may affect the trial is also not allowed. In addition, during the trial, the following practical situations are allowed: (1) If the subject's body temperature is ≥ 38.5℃, or the body pain (headache, sore throat, muscle soreness) is unbearable, ibuprofen or paracetamol can be given for treatment. (2) If the subject's cough is severe, expectorant can be given. (3) If the subject has bacterial infection indications, antibacterial drugs can be given for treatment, and all medications used should be recorded.

[0233] 4 Observation items and indicators

[0234] 4.1 Demographic data

[0235] Including age, gender, height, weight, medical history, current illness history, and allergy history.

[0236] 4.2 Safety observation

[0237] General physical examination, blood routine (white blood cell count, neutrophil, lymphocyte, red blood cell count, hemoglobin, platelet), urine routine (urine protein, red blood cells (high power microscopy), white blood cells (high power microscopy)), liver and kidney function (glutamic-pyruvic transaminase, glutamic-oxalacetic transaminase, total bilirubin, gamma-glutamyl transpeptidase, alkaline phosphatase, urea nitrogen, creatinine), electrocardiogram examination.

[0238] 4.3 Efficacy observation

[0239] Primary indicator: fever relief efficiency.

[0240] Secondary indicator: clinical efficiency.

[0241] Efficacy record: (1) Record the course of the disease: All subject parents were trained by a dedicated person, and the parents filled out the symptom diary card every day from the first day of enrollment, recording the symptom score related to influenza, body temperature, adverse reactions, secondary diseases, and the use of combined drugs, etc.

[0242] 4.4 Efficacy determination criteria

[0243] 4.4.1 Fever efficacy determination criteria Cure: The child's body temperature returned to normal within 24 hours after taking the medicine, and there was no recurrence; Marked effect: The child's body temperature decreased by ≥ 1.0℃ within 24 hours after taking the medicine, but the body temperature did not completely return to normal; Effective: The child's body temperature decreased by 0.5-<1.0℃ after taking the medicine for 24 hours, and the body temperature did not completely return to normal; Ineffective: The child's body temperature decreased by <0.5℃ after taking the medicine for 24 hours. Total effective rate = (number of cured cases + number of markedly effective cases) / total number of cases x 100%.

[0244] 4.4.2 Criteria for Clinical Efficacy Judgment Referring to the Guiding Principles for Clinical Research of New Drugs of Traditional Chinese Medicine, the efficacy was judged in combination with the influenza symptom score. Recovery: the clinical symptoms and signs disappeared or basically disappeared after treatment, and the influenza symptom score was reduced by ≥ 95%; marked effect: the influenza symptom score was reduced by < 95% and ≥ 70% after treatment; effect: the influenza symptom score was reduced by < 70% and ≥ 30% after treatment; no effect: the influenza symptom score was reduced by < 30% after treatment. The total effective rate = (the number of recovery cases + the number of marked effect cases) / the total number of cases x 100%. The symptom score table is shown in Table 7.

[0245] Table 7 Symptom Score Table

[0246]

[0247] 5 Statistics

[0248] After the end of the test, a professional statistician performed statistical processing. Those who did not meet the inclusion criteria, did not take the prescribed medication, and had serious incomplete data were excluded as cases not meeting the requirements and were not statistically processed. The statistical method used t-test method. Finally, according to the statistical results, the efficacy of the agreement party in treating children's influenza was objectively evaluated, and a summary report was written.

[0249] 6 Results

[0250] 6.1 Fever Efficacy Results

[0251] The total effective rate of the drug of the present application in treating children's influenza reached 96.1%, which was much higher than 74.0% of the western medicine control group; and the fever efficacy of the drug of the present application was only ineffective in 2 patients, while the number of ineffective cases in the western medicine control group reached 13; at the same time, the number of cured and markedly effective patients in the fever effect of the drug of the present application reached 38, while that of the western medicine control group was only 23. From the above test results, it can be known that the drug of the present application has better fever efficacy compared with the western medicine control group, and the specific results are shown in the following Table 8.

[0252] Table 8 Fever Test Results

[0253]

[0254] 6.2 Clinical Efficacy Results

[0255] The total effective rate of the clinical efficacy of the drug of the present application in treating children's influenza reached 98%, which was much higher than 84% of the western medicine control group; and the clinical efficacy of the drug of the present application in treating children's influenza was only ineffective in 1 patient, while the number of ineffective cases in the western medicine control group reached 8; at the same time, the number of cured and markedly effective patients in the fever effect of the drug of the present application reached 43, while that of the western medicine control group was only 22. From the above test results, it can be known that the drug of the present application has very good efficacy compared with the western medicine control group, and the specific results are shown in the following Table 9.

[0256] Table 9 Clinical test results

[0257]

[0258] 6.3 Safety evaluation results

[0259] During the test period, 2 cases of adverse events occurred, of which 2 cases occurred in the western medicine control group and were related to the test drug, and did not cause health damage to the subjects. The patients in the traditional Chinese medicine composition group of the present application did not have adverse reactions such as nausea, diarrhea, vomiting, abdominal pain, abdominal distension, dry mouth, and rash, itching, dizziness, etc. No other adverse events occurred, in addition, no laboratory abnormalities related to the drug of the present application were found and there were no clinically significant adverse events, indicating that the traditional Chinese medicine composition of the present application has good safety.

[0260] Test Example 5

[0261] To clarify the in vitro antiviral activity of the traditional Chinese medicine composition of the present application, the granules prepared in Example 1 (hereinafter referred to as the traditional Chinese medicine composition (LHQG) of the present application) were used to perform the following tests.

[0262] 1. Experimental purpose

[0263] By screening the efficacy of the traditional Chinese medicine composition of the present application on different respiratory tract infection viruses, the broad spectrum of its antiviral activity was determined, as well as the efficacy mechanism of the traditional Chinese medicine composition of the present application in inhibiting the replication of influenza A virus in vitro.

[0264] 2. Experimental materials

[0265] ① Strain and cell source:

[0266]

[0267] ② Drug source

[0268] 1) Source of test drug and dissolution method

[0269] Take 1225 mg of granules prepared in Example 1 and add 20 ml of DMSO for dissolution, and use ultrasonic heating to assist dissolution (20000 Hz, 50℃ water bath ultrasonic for 1 h); after ultrasonic, 2000 RPM, room temperature centrifugation for 15 min, discard the precipitate and take the supernatant to divide 500 μl / tube, freeze-20℃ for standby, and the drug storage concentration is 61.25 mg / ml.

[0270] 2) Positive drug source

[0271]

[0272] 3. Experimental method

[0273] ① Determination of virus semi-tissue infectious dose (TCID50)

[0274] The host cells were inoculated into 96-well plates, and after the cells grew into a monolayer, the culture solution was discarded, and the cell surface was washed twice with PBS. Different concentrations of virus diluent were added, and incubated in a CO2 incubator for 48-72 hours. The cell growth condition was observed every day, and when the cells showed signs of atrophy, rounding, shedding and other pathological phenomena (CPE), the occurrence of CPE was recorded.

[0275] ② In vitro toxicity determination of LHQG (MTT method)

[0276] The cells were inoculated in 96-well plates, and blank groups (without cells, only culture medium), normal cell control groups (containing drug dissolution medium) were set up. Incubate for 48 hours, continue to culture for 4 hours, terminate the culture, add 100 uL DMSO to each well, and shake on a shaker for 10 minutes. Measure the OD value of each well at 490 nm wavelength on a full-wavelength scanner. Calculate the TC50 of the drug.

[0277] ③ In vitro anti-influenza virus spectrum activity screening

[0278] The cell lesion inhibition method was used to detect the antiviral activity of the test drug. The test drug was diluted by eight times with 1 ug / mL TPCK (trypsin) containing medium, and the positive drug (ribavirin) was diluted by eight times. MDCK cells were inoculated into 96-well plates, and after the cells grew into a monolayer, the culture solution was discarded, and the cell surface was washed twice with PBS. Normal cell control group, virus control group, drug control group were set up, and after incubation in the incubator for 2 hours, the virus solution was discarded, and the medium containing the test drug and the positive drug was added, and incubated in the incubator for 48 hours. Observe and record the cell lesions every day. The degree of cell lesion was recorded according to the following Table 12 6-level standard.

[0279]

[0280] ④ In vitro anti-other virus activity screening

[0281] The antiviral activity of the test drug is detected by cytopathic inhibition method. The test drug is diluted by eight concentrations with culture medium, and the positive drugs (ribavirin and arbidol) are also diluted by eight concentrations. The host cells are inoculated into a 96-well plate, and after the cells grow into a monolayer (about 24 h), the culture solution is discarded, and the cell surface is washed twice with PBS. Virus diluent 100 uL / well is added, four replicates for each concentration, and normal cell control group, virus control group and drug control group are set at the same time, and incubated in an incubator, and after 2 hours, the virus solution is discarded, and the culture medium containing the test drug and the positive drug is added, and incubated in an incubator for 48-72 hours, and the cytopathic effect is observed and recorded every day. The degree of cytopathic effect is recorded according to the 6-level standard (see Table 12).

[0282] 5. Inhibition of influenza virus (A / PR / 8 / 34, H1N1) and lipopolysaccharide (LPS) induced host inflammatory factor expression in vitro

[0283] A549 cells with moderate growth density are inoculated into a 6-well cell culture plate, and after 48 h, the supernatant culture medium is discarded, and the cells are washed twice, 1 ml of influenza A virus culture solution is added, and is adsorbed in an incubator for 2 hours, and then the supernatant is discarded, and the culture medium containing the test drug is added, and after 24 h, the supernatant is aspirated and discarded, and the cells are washed twice, and the reagent is added to lyse the cells, and the sample is used for subsequent RNA extraction, and a virus infection control group, different dose test drug intervention groups and non-infected drug control groups are set.

[0284] Macrophages with moderate growth density are inoculated into a cell culture plate, and after 48 h, the supernatant culture medium is discarded, and the cells are washed, and the serum-free culture medium is changed to starve for 24 h; on the third day, lipopolysaccharide and culture medium with different drug doses are added for treatment; 24 h later, the cells are lysed, and the sample is used for subsequent RNA extraction, and the experimental groups include: model group, drug intervention group and drug control group.

[0285] RT-PCR is used to detect the influence of the traditional Chinese medicine composition on the expression level of the mRNA of the host cell infection related inflammatory factor.

[0286] 6. LHQG action phase experiment

[0287] MDCK cells are inoculated into a 12-well plate, and grow into a monolayer, and the culture supernatant is removed, and the cells are washed twice with PBS, and then influenza A virus A / PR / 34 strain is added at 4℃ for adsorption for 2 hours. Remove the virus that has not been adsorbed to the host cells. Then add the culture medium and incubate in the incubator. Add the drug at the post-infection and designated time points. After 10 h, the 12-well plate is repeatedly frozen and thawed 3 times, and the samples at each time point are collected for progeny virus titer determination (TCID 50 ).

[0288] 7. Indirect immunofluorescence experiment (influenza virus NP protein expression)

[0289] MDCK cells were inoculated into 8-Well Glass, and the cells were grown to about 40%, the culture medium was discarded, and the cells were washed with PBS. After virus incubation, the cell nucleus was stained with DAPI glycerol sealing dye solution, and the results were observed under a fluorescence microscope.

[0290] 4. Statistical methods

[0291] The experimental results in the report were statistically analyzed by SPSS 20.0 software, and the graph was drawn by GraphPad Prism 5 software. All data were calculated by mean standard deviation. Two sample comparisons were tested by t test, multiple sample comparisons were analyzed by One-Way ANOVA, pairwise comparisons assumed homogeneity of variance using LSD method, assumed heterogeneity of variance using Tamhane, s T2 or Dunnett, s T3. If the multiple groups of measurement data do not conform to the normal distribution and the homogeneity of variance, then the Kruskal-Wallis rank sum test is used. P<0.05 indicates statistical significance.

[0292] 5. Results

[0293] ① The median infectious dose (TCID 50 Results:

[0294] After 48-72h of virus inoculation in the corresponding host cells, CPE was observed under a microscope, and the TCID 50 was calculated according to the Reed-Muench method, as shown in Table 13.

[0295]

[0296] ② In vitro toxicity determination of LHQG (MTT method)

[0297] MTT method was used to test the in vitro cell (MDCK, Hep-2, Huh-7, MRC-5, Vero) toxicity of LHQG, and the TC 50 was calculated according to the Reed-Muench method, as shown in Figure 1 .

[0298] ③ In vitro antiviral spectrum screening of LHQG (CPE method)

[0299] The cytopathic effect method was used to test the in vitro antiviral activity of LHQG, and the IC 50 was calculated according to the Reed-Muench method, and the results are shown in Tables 14 and 15.

[0300]

[0301] (4) Effect of LHQG on mRNA expression levels of cytokines induced by influenza virus and lipopolysaccharide

[0302] The results of RT-PCR experiments showed that, compared with the virus infection model group, LHQG can significantly reduce the mRNA expression levels of host cell inflammatory factors MIP-1β, IFN-β, IP-10, IL-6, CCL5, MCP-1, TNF-α, RIG-I, MIG and CXCL1 induced by influenza virus, as shown in Table 16 below (Note: *P < 0.05, **P < 0.01, ***P < 0.001).

[0303]

[0304] Meanwhile, LHQG can reduce the expression of host cell inflammatory factors IL-6, TNF-α, IP-10, MCP-1 and IL-1β stimulated by lipopolysaccharide in a dose-dependent manner, as shown in Table 17 below (Note: *P < 0.05, **P < 0.01).

[0305]

[0306] (5) Time phase of anti-influenza virus effect of LHQG

[0307] At the time points (0h, 2h, 4h, 6h, 8h) of a single replication cycle of influenza virus, after adding LHQG for intervention, the samples after intervention at each time point and the virus infection control samples were collected, and the results showed that, after adding LHQG at the time points of 0~4h (early stage of virus replication), the virus titer was significantly reduced (P < 0.01 or P < 0.001). It is indicated that LHQG has an anti-virus effect, and mainly acts on the early stage of virus replication, as shown in Table 18 (Note: ** indicates P < 0.01, *** indicates P < 0.001).

[0308]

[0309] (6) Indirect immunofluorescence experiment (influenza virus NP protein expression experiment)

[0310] After host cells were infected with virus (0h, 2h, 4h, 6h, 8h), LHQG was added for intervention, and the cells were taken for immunofluorescence experiment, and observed under a fluorescence microscope, and the results showed that, after virus infection (0h), LHQG intervention can significantly reduce the expression of NP protein of influenza virus, as shown in Table 19 below. Figure 2 .

[0311] 6. Conclusion

[0312] The traditional Chinese medicine composition (LHQG) in the present application has in vitro antiviral effects on multiple strains of influenza A virus, influenza B virus, respiratory syncytial virus and coronavirus, that is, the LHQG has broad-spectrum antiviral effects in vitro and acts on the early stage of virus replication. In addition, the traditional Chinese medicine composition in the present application can significantly reduce the expression of host cell inflammatory factors induced by influenza virus and LPS, and has clear in vitro anti-inflammatory effects.

[0313] Test Example 6

[0314] To clarify the in vivo antiviral activity of the traditional Chinese medicine composition in the present application, the following tests were performed on the granules prepared in Example 1 (hereinafter referred to as the traditional Chinese medicine composition in the present application) and the granules prepared in Comparative Examples 1 and 2.

[0315] 1. Purpose of the experiment

[0316] In this study, BALB / c mice were infected with influenza A virus (H3N2) and respiratory syncytial virus, respectively, to establish animal models of influenza A virus and respiratory syncytial virus. The effects of the traditional Chinese medicine composition in the present application on the clinical symptoms (body weight, lung index, cytokines) and pathogen-related indicators (viral load) of infected mice were observed to evaluate the efficacy of the traditional Chinese medicine composition (LHQG) in the present application.

[0317] 2. Experimental method

[0318] 2.1 In vivo pharmacodynamic study against influenza A virus

[0319] SPF BALB / c mice, half male and half female, weighing 17.0-20.0 g, were randomly divided into 7 groups according to gender and body weight, namely, normal control group, model control group, oseltamivir phosphate capsule group, Lianhuaqingwen group, LHQG group, LHQG-A group (Comparative Example 1), and LHQG-B group (Comparative Example 2). The LHQG, LHQG-A, and LHQG-B were at a tentative clinical dose of 0.4 g of crude drug per kg of body weight, and the mouse dose was 4.0 g of crude drug per kg, which was 10 times the tentative clinical dose, which was the clinical equivalent dose. Each administration group was given the corresponding concentration of drug solution at 10 mL / kg by oral gavage, the normal control group and the model control group were given the same volume of pure water, 1 time / day, for 7 consecutive days. On D4 of administration (before administration), the mice in each group were slightly anesthetized with diethyl ether, and 80 μL of H3N2 influenza A virus stock solution (the hemagglutination titer of the virus was 6log2, and the virus was pre-cooled at 4℃ before nasal instillation) was instilled into the nose, and the normal control group was instilled with the same volume of blank medium. The lungs were dissected and weighed 2 h after the last administration, and the lung index was calculated; the content of IL-1β and TNF-α in lung homogenate was detected by ELISA; and the influenza virus load in the lung was determined by fluorescent quantitative PCR.

[0320] 2.2 In vivo pharmacodynamic studies against respiratory syncytial virus

[0321] SPF-grade BALB / c mice, half male and half female, weighing 17.0–20.0 g, were randomly divided into 7 groups according to sex and weight: normal control group, model control group, ribavirin tablet group, Lianhua Qingwen group, LHQG group, LHQG-A formula group, and LHQG-B formula group. The proposed clinical dose for LHQG, LHQG-A, and LHQG-B was 0.4 g crude drug / kg body weight, and the mouse dose was set at 4.0 g crude drug / kg, which is 10 times the proposed clinical dose; this is the clinically equivalent dose. Each treatment group was administered the corresponding concentration of drug solution orally at a dose of 10 mL / kg, while the normal control group and model control group were given an equal volume of pure water. Administration was once daily for 7 consecutive days. On day 4 (before administration), mice were lightly anesthetized with ether. Each group of mice received 80 μL of RSV virus solution (100 TCID, pre-cooled to 4°C before administration) via nasal instillation. The normal control group received an equal volume of blank culture medium via nasal instillation. Two hours after the last administration, lungs were dissected, weighed, and lung index was calculated. The levels of IL-1β and TNF-α in lung homogenates were detected using ELISA. The viral load in the lungs was determined using quantitative real-time PCR.

[0322] 3 Statistical Methods

[0323] Experimental data are expressed as mean ± standard deviation ( The significance levels were set at 0.05 and 0.01. Statistical analysis was performed using SPSS software. One-way ANOVA was used to compare means. First, a test for homogeneity of variance was performed. If the variances were homogeneous, the least significant difference (LSD) test was used. If the variances were not homogeneous, Dunnett's T3 test was used.

[0324] 4 Results

[0325] 4.1 In vivo pharmacodynamic studies against influenza A virus

[0326] As shown in Tables 19, 20, and 21, compared with the normal control group, the lung index of the model control group was significantly increased after viral infection (P<0.01), and the content of inflammatory factors (IL-1β, TNF-α) and viral load in lung tissue homogenate were significantly increased (P<0.01). Compared with the model control group, the lung index, pulmonary inflammatory factors, and viral load of the Lianhua Qingwen group and LHQG group were significantly decreased (P<0.01 or P<0.05), while no significant differences were found in the above indicators in the LHQG-A group and LHQG-B group (P>0.05). The lung index, pulmonary inflammatory factor content, and viral load of the oseltamivir phosphate capsule group were significantly decreased (P<0.01 or P<0.05).

[0327]

[0328] 4.2 Anti-respiratory syncytial virus in vivo pharmacodynamic study

[0329] As shown in Tables 22, 23 and 24, compared with the normal control group, the lung index of the model control group was significantly increased after viral infection (P<0.01), and the contents of inflammatory factors (IL-1β, TNF-α) and viral load in lung homogenate were significantly increased (P<0.01). Compared with the model control group, the lung index, lung inflammatory factors and viral load of the Lianhuaqingwen group and the LHQG group were significantly reduced (P<0.01 or P<0.05), and there was no significant difference in the above indexes of the LHQG-A group and the LHQG-B group (P>0.05), and the lung index, lung inflammatory factor content and viral load of the oseltamivir phosphate capsule group were significantly reduced (P<0.01 or P<0.05).

[0330]

[0331] 5. CONCLUSION

[0332] Under the experimental conditions, the LHQG (the traditional Chinese medicine composition of the present application) significantly reduced the lung index, lung inflammatory factor content and viral load after influenza A virus and respiratory syncytial virus infection, and the efficacy was equivalent to that of Lianhuaqingwen. The LHQG-A group and the LHQG-B group did not show significant antiviral efficacy.

[0333] Test Example 7

[0334] To further illustrate the in vivo antiviral activity of the traditional Chinese medicine composition of the present application, the granules prepared in Example 1 (hereinafter referred to as the traditional Chinese medicine composition of the present application) were used to perform the following tests.

[0335] 1. Purpose of the experiment

[0336] In this study, BALB / c mice were infected by nasal instillation of influenza A virus (H3N2) and respiratory syncytial virus, respectively, to establish animal models of influenza A virus and respiratory syncytial virus. The efficacy of the traditional Chinese medicine composition of the present application (LHQG) was evaluated by observing the effects of the traditional Chinese medicine composition of the present application on the clinical symptoms and pathogen-related indexes of infected mice.

[0337] 2. Experimental method

[0338] 2.1 Anti-influenza A virus in vivo pharmacodynamic study

[0339] BALB / c mice 140, SPF, half male and female, body weight 15.6-20.0 g, according to gender and weight were randomly divided into 7 groups, respectively, normal control group, model control group, oseltamivir phosphate capsules group (20 mg / kg), Lianhuaqingwen capsule group (0.5 g / kg) and LHQG low, medium and high dose groups, 20 in each group. Each day using 0.5% sodium carboxymethyl cellulose (CMC-Na) to prepare LHQG into a concentration of 0.05, 0.10, 0.20 g powder / mL drug solution (dose in subsequent test table is crude drug amount), oseltamivir phosphate capsules using pure water to prepare into a concentration of 2 mg / mL drug solution, Lianhuaqingwen capsule using pure water to prepare into a concentration of 0.05 g / mL drug solution, LHQG low, medium and high dose groups, oseltamivir phosphate capsules group, Lianhuaqingwen capsule group mice were given 10 mL / kg oral gavage corresponding concentration of drug solution, normal control group and virus model group were given the same volume of pure water, 1 day / time, continuous administration for 7 days. On D4 (before administration), the mice in each group were slightly anesthetized with ether, except for the normal control group, each group of mice were dropped into H3N2 influenza A virus liquid (pre-cooled at 4℃ before nasal infection) through the nose, 80 μL / one, the normal control group was dropped into the same volume of blank medium through the nose.

[0340] On D5 (24 h after infection) and D7 (2 h after the last administration), animals were randomly selected from each group, and the content of IL-1β, TNF-α, INF-γ and IL-10 in lung homogenate was detected by ELISA kit; hemagglutination inhibition test was used to detect the hemagglutination inhibition titer of lung suspension (the maximum dilution multiple that completely inhibited the agglutination of red blood cells was the hemagglutination inhibition titer), expressed as log2 (maximum dilution multiple), reflecting the virus titer in the lung; HE staining, light microscope observation of pathological changes, and comprehensive evaluation of lung pathological changes according to alveolar structure, alveolar septum, lung interstitium, bronchiolar mucosa pathological changes and inflammatory cell infiltration (scoring according to the degree of lesion, the scoring criteria are as follows: 0 points: normal; 1 point: very mild (lesion less than 10%); 2 points: mild (lesion 10%-30%); 3 points: moderate (lesion 30%-50%); 4 points: severe (lesion more than 50%)); immunohistochemical staining of CD4 + + lymphocytes in animal lung, and Image J software was used to analyze the fluorescence signal, in which CD4 + cells were red fluorescence signal and CD8 + cells were green fluorescence signal, the fluorescence value reflected the number of CD4+ and CD8+ cells, and the CD4 + / CD8 + ratio was calculated.

[0341] 2.2 Anti-syncytial virus in vivo pharmacodynamic study ​

[0342] BALB / c mice 224, SPF level, half male and female, body weight 14.4-20.3 g, randomly divided into 7 groups according to gender and body weight, respectively, normal control group, model control group, ribavirin tablet group (60 mg / kg), Lianhuaqingwen capsule group (0.5 g / kg) and LHQG low, medium and high dose groups, 32 in each group. Each day, 0.5% sodium carboxymethylcellulose (CMC-Na) was used to prepare LHQG into a concentration of 0.05, 0.10, 0.20 g powder / mL of drug solution (dose in subsequent test table is crude drug amount), ribavirin tablets were prepared into a concentration of 6.0 mg / mL of drug solution with pure water, and Lianhuaqingwen capsules were prepared into a concentration of 0.05 g / mL of drug solution with pure water. The above groups of mice were given corresponding concentrations of drug solution by oral gavage at 10 mL / kg, and the normal control group and virus model group were given the same volume of pure water, 1 day / time, for 7 consecutive days. On D4 (before administration), the mice in each group were slightly anesthetized with ether, and except for the normal control group, each group of mice was given RSV virus stock solution by nasal instillation (pre-cooled at 4°C before nasal instillation), 80 μL per mouse. The normal control group was given the same volume of blank culture medium by nasal instillation.

[0343] On D5 (24 h after infection) and D7 (2 h after the last administration), animals were randomly selected from each group, and the content of IL-1β, TNF-α, INF-γ and IL-10 in lung homogenate was detected by ELISA kit; flow cytometry was used to detect CD4 + , CD8 + cells in whole blood, and the ratio of CD4 + , CD8 + cells was calculated; flow cytometry was used to detect CD4 + , CD8 + cells and macrophages (M1, M2) in lung homogenate, and the ratio of CD4 + / CD8 + , M1 / M2 was calculated; flow cytometry was used to detect NK cells in spleen; HE staining was used to observe pathological changes under light microscope, and the pathological changes of lung were comprehensively evaluated according to alveolar structure, alveolar septum, lung interstitium, bronchiolar mucosa pathological changes and inflammatory cell infiltration (scoring according to the degree of lesion, scoring criteria as follows: 0 points: normal; 1 point: very mild (lesion less than 10%); 2 points: mild (lesion 10%-30%); 3 points: moderate (lesion 30%-50%); 4 points: severe (lesion more than 50%)); immunohistochemical staining was used to stain CD4 + , CD8 + lymphocytes in animal lung, and Image J software was used to analyze the fluorescence signal, in which CD4 + cells were red fluorescence signal and CD8 +The cells were green fluorescent signal, and the CD4 + + cells were reflected by the fluorescence value, and the number of CD4 + / CD8 + ratio was calculated.

[0344] 3 Statistical Methods

[0345] The statistical software used was SPSS. The measurement data was expressed as mean ± standard deviation (x±s), and the normality and homogeneity of variance were tested by Leven's test method. If there was no statistical significance (P>0.05), single factor analysis of variance (ANOVA) was used for statistical analysis. If ANOVA had statistical significance (P≤0.05), LSD test (parametric method) was used for comparative analysis. If the variance was not homogeneous (P≤0.05), Kruskal-Wallis test was used. If Kruskal-Wallis test had statistical significance (P≤0.05), Dunnett's Test (non-parametric method) was used for comparative analysis. The statistical results were tested with α=0.05 as the test limit, wherein P≤0.05 indicated statistical significance, and P≤0.01 indicated that the difference tested had very significant significance.

[0346] 4 Results

[0347] 4.1 Results of in vivo pharmacodynamic study of anti-influenza A virus

[0348] 1) Effect on IL-1β, TNF-α, IL-10, INF-γ content in lung tissue

[0349] ​As shown in Table 25, compared with the normal control group, the IL-1β, TNF-α, IL-10 and INF-γ contents of the model control group were significantly increased (P ≤ 0.05 or P ≤ 0.01) at 24 h after infection. Compared with the model control group, the IL-1β contents of the LHQG low, medium and high dose groups, the oseltamivir phosphate capsule group and the Lianhuaqingwen capsule group were significantly decreased (P ≤ 0.05 or P ≤ 0.01); the TNF-α contents of the LHQG medium and high dose groups, the oseltamivir phosphate capsule group and the Lianhuaqingwen capsule group were significantly decreased (P ≤ 0.05 or P ≤ 0.01), and the TNF-α content of the LHQG low dose group showed a downward trend but had no statistical difference; the INF-γ content of the LHQG high dose group was significantly decreased (P ≤ 0.05 or P ≤ 0.01), and the IL-10 and INF-γ contents of the LHQG low, medium and high dose groups, the oseltamivir phosphate capsule group and the Lianhuaqingwen capsule group showed a downward trend but had no statistical difference. At 2 h after the last administration, compared with the normal control group, the IL-1β and TNF-α contents of the model control group were significantly increased (P ≤ 0.05 or P ≤ 0.01), and the IL-10 and INF-γ contents showed an upward trend but had no statistical difference. Compared with the model control group, the IL-1β contents of the LHQG high dose group and the Lianhuaqingwen capsule group were significantly decreased (P ≤ 0.01), and the IL-1β content of the LHQG low and medium dose groups and the oseltamivir phosphate capsule group showed a downward trend but had no statistical difference; the TNF-α contents of the LHQG medium and high dose groups, the oseltamivir phosphate capsule group and the Lianhuaqingwen capsule group were significantly decreased (P ≤ 0.05 or P ≤ 0.01), and the TNF-α content of the LHQG low dose group showed a downward trend but had no statistical difference; the IL-10 and INF-γ contents of the LHQG low, medium and high dose groups, the oseltamivir phosphate capsule group and the Lianhuaqingwen capsule group showed a downward trend but had no statistical difference.

[0350]

[0351] 2) Effect on the hemagglutination titer of H3N2 influenza A virus in lung tissue

[0352] As shown in Table 26, the normal control group was not infected with influenza virus, and there was no virus titer in the lung. Compared with the model control group, the virus hemagglutination titer in the lung of the LHQG low, medium and high dose groups, the oseltamivir phosphate capsule group and the Lianhuaqingwen capsule group was significantly decreased (P ≤ 0.01) at 24 h after infection and at 2 h after the last administration.

[0353]

[0354] 3) Effect on the pathological changes of lung tissue

[0355] As shown in Table 27 and Figure 3 , 4 , wherein, Figure 3 is the result of the influence on lung tissue pathology 24h after exposure: A, normal control group; B, model control group; C, oseltamivir phosphate capsule group; D, Lianhuaqingwen capsule group; E, LHQG low-dose group; F, LHQG medium-dose group; G, LHQG high-dose group; black arrow indicates alveoli (B, D); blue arrow indicates lung interstitium (B, C, D); red arrow indicates bronchiole (B, F), Figure 4 is the result of the influence on lung tissue pathology 2h after the last administration: A, normal control group; B, model control group; C, oseltamivir phosphate capsule group; D, Lianhuaqingwen capsule group; E, LHQG low-dose group; F, LHQG medium-dose group; G, LHQG high-dose group; black arrow indicates alveoli (B, E); blue arrow indicates lung interstitium (B, D, E); red arrow indicates bronchiole (B, C).

[0356] 24h after exposure, the bronchial and alveolar structure of the normal control group was clear, and the cells were arranged in order; the model control group showed obvious swelling of the alveolar wall, partial collapse and rupture, thickening of the bronchiole wall and partial shedding of the mucosal cells, accompanied by a large number of inflammatory cell infiltration. Compared with the model control group, the LHQG low-, medium- and high-dose groups, the oseltamivir phosphate capsule group and the Lianhuaqingwen capsule group showed significantly reduced pathological changes and significantly reduced pathological scores (P ≤ 0.05 or P ≤ 0.01). 2h after the last administration, the bronchial and alveolar structure of the normal control group was clear, and the cells were arranged in order; the model control group showed partial collapse and rupture of the alveolar wall, thickening of the lung interstitium, and accompanied by inflammatory cell infiltration. Compared with the model control group, the LHQG low-, medium- and high-dose groups, the oseltamivir phosphate capsule group and the Lianhuaqingwen capsule group showed significantly reduced pathological changes and significantly reduced pathological scores (P ≤ 0.05 or P ≤ 0.01).

[0357]

[0358] 4) Influence on CD4 + , CD8 + lymphocytes in lung tissue

[0359] As shown in Table 28 and Figure 5 , 6 , wherein, Figure 5 is the result of the influence on CD4 + , CD8 + cell fluorescence intensity values in lung tissue 24h after exposure: CD4 + , CD8 +Signal merge plots: A, normal control group; B, model control group; C, oseltamivir phosphate capsule group; D, Lianhua Qingwen capsule group; E, low-dose LHQG group; F, medium-dose LHQG group; G, high-dose LHQG group. Figure 6 The effect of CD4 concentration in lung tissue 2 hours after the last dose + CD8 + The effect of CD4 on cell fluorescence intensity values: + CD8 + Signal merge diagram: A, normal control group; B, model control group; C, oseltamivir phosphate capsule group; D, Lianhua Qingwen capsule group; E, low-dose LHQG group; F, medium-dose LHQG group; G, high-dose LHQG group.

[0360] 24 hours after exposure and 2 hours after the last administration, compared with the normal control group, CD4 in the lungs + / CD8 + All significantly reduced ( P ≤0.01), indicating that H3N2 influenza A virus infection can cause CD4+ in the lungs of mice. + CD8 + Imbalanced proportions. Compared with the model control, at 24 hours post-exposure and 2 hours post-last administration, the CD4 counts in the low, medium, and high dose LHQG groups, the oseltamivir phosphate capsule group, and the Lianhua Qingwen capsule group were significantly lower. + / CD8 + All significantly increased ( P ≤ 0.01), indicating that oral administration of LHQG can improve CD4 levels in the lungs of infected mice. + CD8 + Lymphocyte ratio imbalance.

[0361]

[0362] The above experimental results indicate that LHQG can reduce the lung index and decrease the viral load of H3N2 influenza A virus in the lungs. Furthermore, low, medium, and high doses of LHQG can reduce the accumulation of inflammatory factors in the lungs, improve virus-induced pathological changes in lung tissue, and significantly increase CD4 levels in lung tissue. + / CD8 + The ratio of these components regulates lymphocyte activity. In summary, LHQG exhibits significant in vivo antiviral efficacy against influenza A virus, which may be related to its ability to regulate local lung tissue immune cells and inhibit inflammatory responses in lung tissue.

[0363] 4.2 Results of in vivo pharmacodynamic studies against respiratory syncytial virus

[0364] 1) Effects on the levels of IL-1β, TNF-α, IL-10, and INF-γ in lung tissue

[0365] As shown in Table 29, 24 hours after exposure, compared with the normal control group, the levels of IL-1β, TNF-α, IL-10, and INF-γ in the model control group were significantly increased (P ≤ 0.01). Compared with the model control group, the levels of IL-1β in the medium- and high-dose LHQG groups, ribavirin tablets, and Lianhua Qingwen capsules were significantly decreased (P ≤ 0.01), while the IL-1β level in the low-dose LHQG group showed a decreasing trend, but there was no statistical difference. Compared with the model control group, the levels of TNF-α, IL-10, and INF-γ in the low-, medium-, and high-dose LHQG groups, ribavirin tablets, and Lianhua Qingwen capsules were significantly decreased (P ≤ 0.05 or P ≤ 0.01). Two hours after the last administration, compared with the normal control group, the levels of IL-1β, TNF-α, and IL-10 in the model control group were significantly increased (P ≤ 0.01), and the level of INF-γ showed an increasing trend, but there was no statistical difference. Compared with the model control group, the levels of TNF-α and IL-10 in the low-, medium-, and high-dose LHQG groups, the ribavirin tablet group, and the Lianhua Qingwen capsule group were significantly decreased (P ≤ 0.01). The levels of IL-1β in the low-, medium-, and high-dose LHQG groups, the ribavirin tablet group, and the Lianhua Qingwen capsule group were significantly decreased (P ≤ 0.01), and the level of IL-1β in the high-dose LHQG group showed a decreasing trend, but there was no statistical difference. Compared with the model control group, the levels of INF-γ in the low-, medium-, and high-dose LHQG groups, the ribavirin tablet group, and the Lianhua Qingwen capsule group all showed a decreasing trend, but there was no statistical difference.

[0366]

[0367] 2) CD4 in peripheral blood and lung tissue + / CD8 + Effect of lymphocyte ratio

[0368] As shown in Table 30, compared with the normal control group, 24 hours after exposure and 2 hours after the last administration, the CD4+ levels in peripheral blood and lung tissue of the model control group were significantly higher. + / CD8 + The ratios all decreased significantly ( P ≤ 0.05 or P ≤ 0.01). 24 hours after exposure, compared with the model control group, the peripheral blood CD4 levels in the high-dose LHQG group were significantly lower. + / CD8 + The ratio increased significantly ( P ≤ 0.05), CD4+ in peripheral blood of low- and medium-dose LHQG groups, ribavirin tablet group, and Lianhua Qingwen capsule group + / CD8 +The ratio showed an increasing trend, but there was no statistical difference; compared with the model control group, the CD4 + / CD8 + ratio in the lung tissue of the LHQG medium-dose group, ribavirin tablet group, and Lianhuaqingwen capsule group increased significantly (P ≤ 0.05) 24 h after exposure. P The CD4 + / CD8 + ratio in the lung tissue of the LHQG low-dose and high-dose groups showed an increasing trend, but there was no statistical difference. Compared with the model control group, the CD4 + / CD8 + ratio in the peripheral blood of the LHQG high-dose group increased significantly (P ≤ 0.05) 2 h after the last administration. P The CD4 + / CD8 + ratio in the peripheral blood of the LHQG low-dose and medium-dose groups, ribavirin tablet group, and Lianhuaqingwen capsule group showed an increasing trend, but there was no statistical difference; 2 h after the last administration, the CD4 + / CD8 + ratio in the lung tissue of the LHQG high-dose group increased significantly (P ≤ 0.05). P The CD4 + / CD8 + ratio in the lung tissue of the ribavirin tablet group and Lianhuaqingwen capsule group showed an increasing trend, but there was no statistical difference. The CD4 + / CD8 + ratio in the lung tissue of the LHQG low-dose and medium-dose groups showed no significant difference compared with the model control group.

[0369]

[0370] 3) Effects on lung macrophages and spleen NK cells

[0371] As shown in Table 31, compared with the normal control group, the M1 / M2 ratio of macrophages in the lung tissue of the model control group increased significantly (P ≤ 0.01) 24 h after exposure and 2 h after the last administration, and the number of NK cells in the spleen decreased significantly (P ≤ 0.05) 24 h after exposure. 2 h after the last administration, the number of NK cells in the spleen showed a decreasing trend, but there was no statistical difference. Compared with the model control group, the M1 / M2 ratio in the lung of the LHQG low-dose, medium-dose, and high-dose groups and the ribavirin tablet group decreased significantly (P ≤ 0.05) 24 h after exposure, and the M1 / M2 ratio in the lung of the LHQG low-dose, medium-dose, and high-dose groups, ribavirin tablet group, and Lianhuaqingwen capsule group decreased significantly (P ≤ 0.05 or P ≤ 0.01) 2 h after the last administration; compared with the model control group, the number of NK cells in the spleen of the LHQG low-dose, medium-dose, and high-dose groups, ribavirin tablet group, and Lianhuaqingwen capsule group showed an increasing trend, but there was no statistical difference 24 h after exposure and 2 h after the last administration.

[0372]

[0373] 4)Effects on lung tissue pathological changes

[0374] As shown in Table 32 and Figure 7 , 8 , wherein, Figure 7 is the result of the effect of lung tissue pathology 24h after exposure: A, normal control group; B, model control group; C, ribavirin tablet group; D, Lianhuaqingwen capsule group; E, LHQG low dose group; F, LHQG medium dose group; G, LHQG high dose group; black arrow indicates alveoli; blue arrow indicates lung interstitium; red arrow indicates bronchiole, Figure 8 is the result of the effect of lung tissue pathology 2h after the last administration: A, normal control group; B, model control group; C, ribavirin tablet group; D, Lianhuaqingwen capsule group; E, LHQG low dose group; F, LHQG medium dose group; G, LHQG high dose group; black arrow indicates alveoli; blue arrow indicates lung interstitium; red arrow indicates bronchiole.

[0375] 24h after exposure, the bronchial and alveolar structure of the normal control group was clear, and the cells were arranged in order; in the model control group, the alveolar wall was obviously collapsed and broken, the bronchiolar wall was thickened and part of the mucosal cells were shed, accompanied by a large number of inflammatory cell infiltration, and the pathological score was significantly increased (P ≤ 0.01). The pathological scores of the LHQG medium and high dose groups, the ribavirin tablet group, and the Lianhuaqingwen capsule group were significantly reduced (P ≤ 0.05 or P ≤ 0.01) compared with the model control group, and the lung tissue lesions of the LHQG low dose group were reduced, but the pathological score had no statistical difference. 2h after the last administration, the bronchial and alveolar structure of the normal control group was clear, and the cells were arranged in order; in the model control group, the alveolar wall was partially collapsed and broken, the lung interstitium was thickened, the bronchial wall was thickened, and was accompanied by inflammatory cell infiltration, and the pathological score was significantly increased (P ≤ 0.01). Compared with the model control group, the pathological scores of the LHQG medium and high dose groups, the ribavirin tablet group, and the Lianhuaqingwen capsule group were significantly reduced (P ≤ 0.05 or P ≤ 0.01), and the lung tissue lesions of the LHQG low dose group were reduced, but the pathological score had no statistical difference.

[0376]

[0377] 5)Effects on CD4 + , CD8 + lymphocytes in lung tissue

[0378] As shown in Table 33 and Figure 9 , 10Shown in the figure, wherein, Figure 9 The effect of CD4 + , CD8 + cell fluorescence intensity value in lung tissue after 24h of exposure: CD4 + , CD8 + signal merge chart, A, normal control group; B, model control group; C, ribavirin tablet group; D, Lianhuaqingwen capsule group; E, LHQG low dose group; F, LHQG medium dose group; G, LHQG high dose group, Figure 10 The effect of CD4 + , CD8 + cell fluorescence intensity value in lung tissue after 2h of last administration: CD4 + , CD8 + signal merge chart, A, normal control group; B, model control group; C, ribavirin tablet group; D, Lianhuaqingwen capsule group; E, LHQG low dose group; F, LHQG medium dose group; G, LHQG high dose group.

[0379] Compared with the normal control group, CD4 + / CD8 + in the lung was significantly reduced (P ≤0.01) at 24h after exposure and 2h after last administration, indicating that the proportion of CD4 + , CD8 + in the lung was imbalanced in mice infected with respiratory syncytial virus. Compared with the model control group, CD4 + / CD8 + was significantly increased (P ≤0.05 or P ≤0.01) in the LHQG medium and high dose groups, ribavirin tablet group, and Lianhuaqingwen capsule group at 24h after exposure, and the LHQG low dose group showed an increasing trend, but there was no statistical difference. Compared with the model control group, CD4 + / CD8 + was significantly increased (P ≤0.01) in the LHQG low, medium, and high dose groups, ribavirin tablet group, and Lianhuaqingwen capsule group at 2h after last administration, indicating that oral administration of LHQG could inhibit the imbalance of CD4 + , CD8 + lymphocyte proportion in the lung of infected mice.

[0380]

[0381] The above test results show that LHQG can reduce the lung index, inhibit the replication of respiratory syncytial virus in the lung, reduce the accumulation of inflammatory factors in the lung, improve the pathological changes in the lung of the infected model mice, and LHQG can increase the CD4 + / CD8 +The ratio, inhibition of M1 polarization of macrophages, indicates that LHQG has the effect of regulating immune cells and maintaining immune balance. It is shown that the traditional Chinese medicine composition has obvious in vivo anti-respiratory syncytial virus effect, which may be related to its ability to regulate the balance of immune cells in the whole body and local lung tissue, and inhibit local inflammation in lung tissue.

[0382] Pharmacodynamic studies have confirmed that the traditional Chinese medicine composition provided in the present application has the effects of eliminating pathogenic factors, supporting healthy qi, overall regulation, simultaneous treatment of lung and defensive qi, and active intervention.

[0383] Eliminating pathogenic factors and supporting healthy qi, overall regulation: research has confirmed that LHQG can not only effectively eliminate pathogens, but also mobilize immune function. In vitro anti-viral pharmacodynamic studies have confirmed that LHQG has in vitro anti-viral effects on multiple strains of influenza A virus, influenza B virus, respiratory syncytial virus, and coronavirus, and acts on the early stage of viral replication. In vivo pharmacodynamic studies have further confirmed that LHQG has obvious in vivo anti-influenza A virus and anti-respiratory syncytial virus effects, and can increase the CD4 + / CD8 + ratio in peripheral blood and lung tissue, reduce the M1 / M2 ratio of lung macrophages, enhance the body's resistance to external viral infection, mobilize the anti-disease immune function, and prevent the occurrence of repeated upper respiratory tract infections. LHQG not only effectively resists cold viruses, but also targets cold-related clinical symptoms, and plays a comprehensive therapeutic role in relieving fever, relieving pain, reducing phlegm, and relieving cough.

[0384] Simultaneous treatment of lung and defensive qi, active intervention: LHQG can significantly reduce the expression of host cell inflammatory factors induced by influenza virus and LPS, and has a clear in vitro anti-inflammatory effect. In in vivo experiments, it effectively reduces the levels of IL-1β, TNF-α, IL-10, and INF-γ in the lungs of respiratory syncytial virus-infected mice, protects the alveolar wall structure, reduces the degree of inflammatory cell infiltration, reduces the thickness of lung interstitium, and improves lung pathological damage. At the same time, it effectively inhibits the lung inflammation caused by cold, reduces the level of inflammatory factors, improves lung pathological damage, treats cold, and prevents the development to pneumonia.

[0385] From the above data, it can be seen that the traditional Chinese medicine composition provided in the embodiments of the present application has the effect of treating children's cold, 11 kinds of medicines, the monarch, minister, and assistant complement each other, the whole prescription coordinates external relieving exterior and internal clearing lung heat, and combines clearing and tonifying. It is safe and reliable, has no toxic and side effects, can not only effectively treat pediatric cold, has the effects of relieving fever, anti-inflammatory, analgesic, relieving cough and expectorant, but also can resist respiratory infection viruses, can be used for preventing and treating viral respiratory infection (viral upper respiratory tract infection and viral lower respiratory tract infection), and has significant effect.

[0386] The above merely provides the preferred embodiment of the present application, and is not used to limit the present application, and any modification, equivalent replacement or improvement made in the spirit and principle of the present application should be included in the protection scope of the present application.

Claims

1. A traditional Chinese medicine composition for treating colds in children, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 250-400 parts of Forsythia suspensa, 250-400 parts of Lonicera japonica, 50-150 parts of Ephedra sinica, 50-150 parts of Prunus armeniaca, 250-400 parts of Gypsum fibrosum, 250-400 parts of Isatis indigotica, 50-150 parts of Pogostemon cablin, 30-90 parts of Rheum palmatum, 10-50 parts of Rhodiola rosea, 120-280 parts of Mentha haplocalyx, and 50-150 parts of Glycyrrhiza uralensis.

2. The traditional Chinese medicine composition for treating colds in children as described in claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 250 parts forsythia, 400 parts honeysuckle, 50 parts ephedra, 150 parts bitter almond, 250 parts gypsum, 400 parts isatis root, 50 parts patchouli, 90 parts rhubarb, 10 parts rhodiola rosea, 280 parts peppermint, and 50 parts licorice.

3. The traditional Chinese medicine composition for treating colds in children as described in claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 400 parts forsythia, 250 parts honeysuckle, 150 parts ephedra, 50 parts bitter almond, 400 parts gypsum, 250 parts isatis root, 150 parts patchouli, 30 parts rhubarb, 50 parts rhodiola rosea, 120 parts peppermint, and 150 parts licorice.

4. The traditional Chinese medicine composition for treating colds in children as described in claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 328 parts of Forsythia suspensa, 328 parts of Lonicera japonica, 98 parts of Ephedra sinica, 98 parts of Prunus armeniaca, 328 parts of Gypsum fibrosum, 328 parts of Isatis indigotica, 98 parts of Pogostemon cablin, 66 parts of Rheum palmatum, 33 parts of Rhodiola rosea, 197 parts of Mentha haplocalyx and 98 parts of Glycyrrhiza uralensis.

5. The traditional Chinese medicine composition for treating colds in children as described in claim 1, characterized in that, The traditional Chinese medicine composition is made from the following raw materials in parts by weight: 280 parts of Forsythia suspensa, 360 parts of Lonicera japonica, 60 parts of Ephedra sinica, 120 parts of Prunus armeniaca, 280 parts of Gypsum fibrosum, 360 parts of Isatis indigotica, 60 parts of Pogostemon cablin, 60 parts of Rheum palmatum, 20 parts of Rhodiola rosea, 250 parts of Mentha haplocalyx and 60 parts of Glycyrrhiza uralensis.

6. The traditional Chinese medicine composition according to any one of claims 1-5, characterized in that, The ephedra is honey-processed ephedra, and the bitter almond is roasted bitter almond.

7. The traditional Chinese medicine composition according to any one of claims 1-5, characterized in that... The cold mentioned refers to either influenza or the common cold.

8. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a drug for resisting H1N1, H3N2, H9N2, H6N2, H7N3, FluB, RSV or hCoV-229E virus.

9. The use of the traditional Chinese medicine composition as described in any one of claims 1-5 in the preparation of a drug for inhibiting MDCK, Hep-2, Huh-7, MRC-5 or Vero cells.

10. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a drug that reduces the mRNA expression levels of inflammatory factors MIP-1β, IFN-β, IP-10, IL-6, CCL5, MCP-1, TNF-α, RIG-I, MIG or CXCL1.

11. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a drug for reducing the expression of influenza virus NP protein.

12. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a drug that inhibits the increase of the lung index and reduces the content of IL-1β, TNF-α, IL-10 or INF-γ in lung tissue.

13. The use of the traditional Chinese medicine composition as described in any one of claims 1-5 in the preparation of drugs that improve the imbalance of CD4+ and CD8+ lymphocyte ratio in lung tissue, improve the imbalance of macrophage M1 and M2 ratio in lung tissue, and inhibit macrophage M1 polarization.

14. The use of the traditional Chinese medicine composition as described in claim 7 in the preparation of antipyretic drugs.

15. The use of the traditional Chinese medicine composition as described in claim 7 in the preparation of anti-inflammatory and analgesic drugs.

16. The use of the traditional Chinese medicine composition as described in claim 7 in the preparation of a medicine for treating cough, phlegm, nasal congestion, and sore throat.

17. The use of the traditional Chinese medicine composition according to any one of claims 1-5 in the preparation of a drug for treating respiratory tract infections caused by viruses.

18. The application as described in claim 17, characterized in that, The antiviral drug for respiratory tract infection is a drug for treating viral upper respiratory tract infection and / or viral lower respiratory tract infection.

19. The application as described in claim 18, characterized in that, The antiviral drugs for respiratory tract infections are used to treat acute rhinitis, acute pharyngitis, tonsillitis, and laryngitis.

20. The application as described in claim 17, characterized in that, The antiviral drug for respiratory tract infection is a drug for treating acute tracheobronchitis or pneumonia.

21. The traditional Chinese medicine composition according to any one of claims 1-5, characterized in that, The active ingredients of the traditional Chinese medicine composition are prepared by the following steps: (1) Weigh out the amount of patchouli and peppermint according to the prescription and extract the volatile oil by steam distillation. Collect the volatile oil and set aside. Filter the aqueous solution after distillation to obtain the volatile oil extract and set aside. (2) Weigh out the other medicinal ingredients except for the Chinese medicine ingredients in step (1) according to the prescription amount, add water and decoct, combine the filtrate with the volatile oil extract in step (1), concentrate, filter, and obtain the extract for later use; The volatile oil obtained in step (1) and the extract obtained in step (2) together constitute the active ingredients of the traditional Chinese medicine composition.

22. The traditional Chinese medicine composition according to claim 21, characterized in that, The active ingredients of the traditional Chinese medicine composition are prepared by the following steps: (1) Weigh out the amount of patchouli and peppermint according to the prescription, add 10 times the amount of water, and extract the volatile oil by steam distillation for 8 hours. Collect the volatile oil for later use; filter the aqueous solution after distillation to obtain the volatile oil extract for later use. (2) Weigh out the other medicinal ingredients except for the Chinese medicine ingredients in step (1) according to the prescription amount, add 10 times the amount of water and decoct twice, 2 hours each time. Filter, combine the filtrate with the volatile oil extract in step (1), concentrate under reduced pressure at 60℃ to a relative density of 1.15±0.05, filter, and set aside. The volatile oil obtained in step (1) and the extract obtained in step (2) together constitute the active ingredients of the traditional Chinese medicine composition.

23. The traditional Chinese medicine composition according to any one of claims 1-5, characterized in that, The dosage form of the traditional Chinese medicine composition is capsule, tablet, granule, pill, powder, or oral liquid.

24. The traditional Chinese medicine composition according to claim 23, characterized in that, The granules are prepared by the following steps: (1) Weigh out the amount of patchouli and peppermint according to the prescription and extract the volatile oil by steam distillation. Collect the volatile oil and set aside. Filter the aqueous solution after distillation to obtain the volatile oil extract and set aside. (2) Weigh out the other medicinal ingredients except those in step (1) according to the prescription, add water and decoct, combine the filtrate with the volatile oil extract obtained in step (1), concentrate, filter, dry to obtain dry powder, and set aside; (3) The volatile oil obtained in step (1) is encapsulated with beta-cyclodextrin to obtain a volatile oil inclusion complex; (4) The dry powder obtained in step (2) and the volatile oil inclusion complex obtained in step (3) are granulated with an appropriate amount of excipients and made into granules according to conventional methods.

25. The traditional Chinese medicine composition according to claim 23, characterized in that, The granules are prepared by the following steps: (1) Weigh out the amount of patchouli and peppermint according to the prescription, add 10 times the amount of water, and extract the volatile oil by steam distillation for 8 hours. Collect the volatile oil for later use; filter the aqueous solution after distillation to obtain the volatile oil extract for later use. (2) Weigh out the other medicinal ingredients except for the Chinese medicine ingredients in step (1) according to the prescription amount, add 10 times the amount of water and decoct twice, 2 hours each time. Filter, combine the filtrate with the volatile oil extract in step (1), concentrate under reduced pressure at 60℃ to a relative density of 1.15±0.05, filter, spray dry to obtain dry powder, and set aside. (3) The volatile oil obtained in step (1) is encapsulated with beta-cyclodextrin to obtain a volatile oil inclusion complex; (4) The dry powder obtained in step (2) and the volatile oil inclusion complex obtained in step (3) are combined with an appropriate amount of excipients and granulated by dry granulation according to conventional methods.

26. The traditional Chinese medicine composition according to claim 23, characterized in that, The tablet is made by the following steps: (1) Weigh out the amount of patchouli and peppermint according to the prescription and extract the volatile oil by steam distillation. Collect the volatile oil and set aside. Filter the aqueous solution after distillation to obtain the volatile oil extract and set aside. (2) Weigh out the other medicinal ingredients except those in step (1) according to the prescription, add water and decoct, combine the filtrate with the volatile oil extract obtained in step (1), concentrate, filter, dry to obtain dry powder, and set aside; (3) The volatile oil obtained in step (1) is encapsulated with beta-cyclodextrin to obtain a volatile oil inclusion complex; (4) Add appropriate excipients to the dry powder obtained in step (2) and the volatile oil inclusion complex obtained in step (3) and make tablets according to conventional methods.

27. The traditional Chinese medicine composition according to claim 23, characterized in that, The capsules are prepared by the following steps: (1) Weigh out the amount of patchouli and peppermint according to the prescription and extract the volatile oil by steam distillation. Collect the volatile oil and set aside. Filter the aqueous solution after distillation to obtain the volatile oil extract and set aside. (2) Weigh out the other medicinal ingredients except those in step (1) according to the prescription, add water and decoct, combine the filtrate with the volatile oil extract obtained in step (1), concentrate, filter, dry to obtain dry powder, and set aside; (3) The volatile oil obtained in step (1) is encapsulated with beta-cyclodextrin to obtain a volatile oil inclusion complex; (4) The dry powder obtained in step (2) and the volatile oil inclusion complex obtained in step (3) are combined with an appropriate amount of excipients and made into capsules according to conventional methods.

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