Traditional Chinese medicine composition for treating common cold or influenza and preparation method thereof

Abstract

The invention relates to a traditional Chinese medicine composition for treating common cold or influenza and a preparation method thereof, the traditional Chinese medicine composition is prepared from 5-30 parts by weight of honeysuckle, 5-30 parts by weight of fructus forsythiae, 1-20 parts by weight of radix bupleuri, 1-20 parts by weight of radix puerariae, 1-15 parts by weight of mint, 1-10 parts by weight of honey-fried ephedra and 1-5 parts by weight of licorice. The traditional Chinese medicine composition has a good effect of treating viral pneumonia caused by influenza viruses, and the preparation method of the traditional Chinese medicine composition is simple and suitable for large-scale production and popularization.

Description

Technical Field

[0001] The invention belongs to the field of traditional Chinese medicine, and particularly relates to a traditional Chinese medicine composition for treating common cold or influenza and a preparation method thereof. Background Art

[0002] Influenza (flu) is an infectious disease caused by influenza virus. Influenza virus is prone to mutation and highly contagious. It is divided into four types according to its core protein: type A (A), type B (B), type C (C) and type D (D). There are three types of influenza virus that can infect humans: type A, type B and type C. There is no report of human infection with type D virus. Influenza is mainly transmitted through droplets in the air, contact between people or contact with contaminated objects. Clinically, it is characterized by high fever, fatigue, headache, body aches, etc. Influenza has an acute onset. Although most of them are self-limiting, some patients develop into severe cases due to complications such as pneumonia or aggravation of underlying diseases. A few cases progress rapidly and may die due to complications such as acute respiratory distress syndrome (ARDS), acute necrotizing encephalopathy or multiple organ dysfunction. Severe influenza mainly occurs in high-risk groups such as the elderly, young children, obese people, pregnant women and those with chronic underlying diseases, and can also occur in the general population. Since influenza is still a major disease that endangers human health, it is of great significance to explore better influenza prevention and treatment solutions.

[0003] Among the drugs currently used to treat influenza, chemical drugs are prone to drug resistance and have large side effects. Although some traditional Chinese medicines have anti-influenza virus efficacy and generally do not produce drug resistance, the effect is relatively single and will be affected by individual differences. Different groups of people may have different responses to traditional Chinese medicine. Syndrome differentiation and treatment is the basic principle of TCM in understanding and treating diseases. The influenza diagnosis and treatment plan released in 2020 divides influenza into mild and severe cases. Mild cases are divided into wind-heat invading the Wei syndrome, wind-cold binding the exterior syndrome, exterior cold and interior heat syndrome, and heat toxicity attacking the lung syndrome; severe cases are divided into toxic heat blocking the lung syndrome and toxic heat sinking, internal closure and external release syndrome. This syndrome is mostly caused by the six evil pathogens headed by wind or seasonal evil viruses, which enter from the mouth and nose or from the skin and fur and invade the upper-jiao lung defense. The lung is a delicate organ that cannot tolerate evil invasion. When it is affected by evil, it will malfunction, resulting in disharmony between the Wei and the exterior, and the lungs fail to clear and purify. Disharmony between the Wei and the surface leads to aversion to cold, fever, headache, and body pain, while failure of the lung to clear and purify leads to nasal congestion, runny nose, sneezing, etc. Influenza viruses are prone to mutation. If the condition changes, it is necessary to carry out syndrome differentiation and treatment according to the actual situation. Therefore, although there are many Chinese medicine compositions or Chinese medicine preparations for preventing and / or treating influenza in the prior art, there is still a great demand for Chinese medicine compositions with better effects in treating influenza. Summary of the invention

[0004] In view of the above problems and shortcomings, the present invention provides a Chinese medicine composition. The Chinese medicine composition of the present invention is composed of honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra, and liquorice, and has a good effect of treating viral pneumonia caused by influenza virus.

[0005] The invention also aims at a reasonable prescription: the prescription uses honeysuckle and forsythia as the main medicine, bupleurum and kudzu root as the ministerial medicine, mint and honey ephedra as the adjuvant medicine, and liquorice as the guiding medicine. Honeysuckle and forsythia are pungent and cool flat drugs with cold nature and light quality, aromatic and penetrating, pungent and cool clearing, and can penetrate heat toxins, especially suitable for wind-heat attacking the surface and the symptoms of intense heat toxins; bupleurum is pungent and dispersing, bitter and purgative, belongs to the Shaoyang meridian, is located in the pivot of the three yang meridians, can mediate yin and yang, dredge the triple burner, and reach the inside and outside; kudzu root is clear and ascending, enters the Taiyang and Yangming meridians, and can relieve muscle and penetrate heat. If the wind evil is trapped inside, kudzu root combined with bupleurum can lead the evil to penetrate outside, and all kinds of exogenous infections caused by the evil entering the three yang meridians can be resolved. Honey ephedra is pungent and warm, but less dry and intense. It specifically enters the Taiyang meridian to dispel wind and can help the suppressed Wei Yang and disperse the cold evil. When the wind and cold are completely dispersed, the symptoms on the surface can be relieved. Honey-processed ephedra is better at relieving cough and asthma than raw ephedra, and is especially suitable for cough and asthma caused by exogenous infection. Peppermint is pungent and cool in nature. Pungent can disperse, and cool can penetrate heat. It has a particularly strong power to promote qi and relieve depression. On the surface, it can help other medicines to disperse, penetrate evil and relieve the surface. On the inside, it can be aromatic to avoid filth, transform dampness and harmonize the middle, promote the internal and external qi, relieve exogenous wind evil, and eliminate internal injury and dampness. Honey ephedra and peppermint are used together, and the combination of cold and warm can disperse the wind-cold and wind-heat evils that invade the surface, and take the meaning of balancing cold and heat. Licorice as a guiding drug can not only reconcile other medicines, but also replenish deficiency and benefit qi because of its sweet, moist and peaceful nature, so that this prescription can penetrate evil without dispersing qi and relieve the surface without hurting the body. The core of this prescription is to clear and relieve the symptoms, operate the key organs, so that the external evil, no matter whether it is cold or hot and the location of the disease, can be turned out of the body surface, and then dispersed by the antipyretic herbs. At the same time, it focuses on protecting the positive energy, so that the evil can be eliminated and the positive energy can be restored and the disease can be cured.

[0006] The present invention provides a traditional Chinese medicine composition, which is prepared from the following traditional Chinese medicine raw materials in parts by weight:

[0007] 5-30 parts of honeysuckle, 5-30 parts of forsythia, 1-20 parts of bupleurum, 1-20 parts of kudzu root, 1-15 parts of mint, 1-10 parts of honey ephedra, and 1-5 parts of liquorice.

[0008] In one embodiment, the traditional Chinese medicine composition of the present invention is made of the following traditional Chinese medicine raw materials in parts by weight: 5-25 parts of honeysuckle, 5-25 parts of forsythia, 5-20 parts of bupleurum, 5-20 parts of kudzu root, 5-15 parts of mint, 1-8 parts of honey ephedra, and 1-5 parts of liquorice.

[0009] In one embodiment, the traditional Chinese medicine composition of the present invention is made of the following traditional Chinese medicine raw materials in parts by weight: 10-25 parts of honeysuckle, 10-25 parts of forsythia, 5-15 parts of bupleurum, 5-15 parts of kudzu root, 5-10 parts of mint, 1-5 parts of honey ephedra, and 1-3 parts of licorice.

[0010] In one embodiment, the traditional Chinese medicine composition of the present invention is made of the following traditional Chinese medicine raw materials in parts by weight: 12-20 parts of honeysuckle, 12-20 parts of forsythia, 8-12 parts of bupleurum, 8-12 parts of kudzu root, 5-8 parts of mint, 3-5 parts of honey ephedra, and 1-3 parts of licorice.

[0011] In one embodiment, the Chinese medicine composition of the present invention is made of the following Chinese medicinal raw materials in parts by weight: 15 parts of honeysuckle, 15 parts of forsythia, 10 parts of bupleurum, 10 parts of kudzu root, 6 parts of mint, 4 parts of honey ephedra, and 2 parts of liquorice.

[0012] The Chinese medicine composition of the present invention is in the form of a pharmaceutical preparation, and the pharmaceutical preparation may further include pharmaceutical excipients as required. The pharmaceutical preparation is selected from the group consisting of tablets, capsules, lozenges, granules, pills, powders, pastes, pills, suspensions, solutions, injections, suppositories, pastes, sprays, drops, pills or patches.

[0013] The present invention further provides a method for preparing the traditional Chinese medicine composition, which comprises the following steps: taking seven traditional Chinese medicines, namely honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra, and licorice, respectively, adding 2-16 times the amount of water and boiling for 1-3 times, each time for 0.5-4 hours, combining the extracts, filtering, and concentrating the filtrate to obtain the composition.

[0014] Preferably, the method comprises the following steps: taking 7 kinds of Chinese medicinal materials including honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and licorice respectively, adding 10 times of water and boiling twice, each time for 1 hour, combining the extracts, filtering through 300 mesh, and concentrating the filtrate to a density of 1.20-1.30 (60°C).

[0015] The present invention further provides use of the traditional Chinese medicine composition in preparing medicines for common cold and / or influenza.

[0016] In one embodiment, a Chinese medicine composition is prepared from the following Chinese medicine raw materials in parts by weight: 5-30 parts of honeysuckle, 5-30 parts of forsythia, 1-20 parts of bupleurum, 1-20 parts of kudzu root, 1-15 parts of mint, 1-10 parts of honey ephedra, and 1-5 parts of liquorice;

[0017] The preparation method is as follows: take the above 7 Chinese medicinal materials respectively, add 2-16 times amount of water and boil for 1-3 times, each time for 0.5-4 hours, combine the extracts, filter, and concentrate the filtrate to obtain the product.

[0018] Further preferably, the Chinese medicine composition of the present invention is made of the following Chinese medicinal raw materials in parts by weight: 5-25 parts of honeysuckle, 5-25 parts of forsythia, 5-20 parts of bupleurum, 5-20 parts of kudzu root, 5-15 parts of mint, 1-8 parts of honey ephedra, and 1-5 parts of licorice; it is prepared by the following method: take the above 7 Chinese medicinal materials respectively, add 2-16 times the amount of water, decoct 1-3 times, each time for 0.5-4 hours, combine the extracts, filter, and concentrate the filtrate to obtain.

[0019] More preferably, the Chinese medicine composition of the present invention is made of the following Chinese medicine raw materials in parts by weight: 15 parts of honeysuckle, 15 parts of forsythia, 10 parts of bupleurum, 10 parts of kudzu root, 6 parts of mint, 4 parts of honey ephedra, and 2 parts of liquorice;

[0020] The preparation method is as follows: take the above 7 Chinese medicinal materials respectively, add 2-16 times amount of water and boil for 1-3 times, each time for 0.5-4 hours, combine the extracts, filter, and concentrate the filtrate to obtain the product.

[0021] Most preferably, the Chinese medicine composition of the present invention is made of the following Chinese medicinal raw materials in parts by weight: 15 parts of honeysuckle, 15 parts of forsythia, 10 parts of bupleurum, 10 parts of kudzu root, 6 parts of mint, 4 parts of honey ephedra, and 2 parts of licorice; it is prepared by the following method: take 7 Chinese medicinal materials of honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra, and licorice, add 10 times water and boil twice, each time for 1 hour, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60°C).

[0022] The preparation method of the active ingredient of the present invention is obtained through a large number of screenings, and the specific process is as follows:

[0023] 1. The Chinese medicine composition of the present invention is prepared from the following raw materials:

[0024] 750g of honeysuckle, 750g of forsythia, 500g of bupleurum, 500g of kudzu root, 300g of mint, 200g of honey ephedra, and 100g of liquorice (screening sample 1).

[0025] 600g of honeysuckle, 600g of forsythia, 400g of bupleurum, 400g of kudzu root, 240g of mint, 160g of honey ephedra, and 80g of liquorice (screening sample 2).

[0026] 4500g of honeysuckle, 4500g of forsythia, 3000g of bupleurum, 3000g of kudzu root, 1800g of mint, 1200g of honey ephedra, and 600g of liquorice (screening sample 3).

[0027] 2. Preparation method

[0028] Take 7 Chinese medicinal materials of honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra, and liquorice according to the above weight. Add 10 times water and boil twice, each time for 1 hour, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60°C) to obtain the Chinese medicine composition of the present invention. The extraction and preparation parameter conditions are shown in Table 1 below:

[0029] Table 1 Parameters and conditions for sample preparation of the Chinese medicine composition of the present invention

[0030]

[0031] It can be seen that the optimal extraction preparation parameter conditions of the Chinese medicine composition of the present invention have been determined through screening.

[0032] The following is an explanation and description of the terms of the present invention. The raw materials involved in the Chinese medicine composition for treating influenza and / or common cold in the present invention are as follows:

[0033] Honeysuckle is the dried buds or flowers of Lonicera japonica Thunb. of the Caprifoliaceae family. It is harvested before the flowers open in early summer and dried. It is sweet and cold in nature. It enters the lung, heart, and stomach meridians. It clears away heat and detoxifies, and evacuates wind-heat. It is used for carbuncle, furuncle, throat paralysis, erysipelas, heat-toxic bloody dysentery, wind-heat cold, and fever caused by febrile diseases.

[0034] Forsythia suspensa (Thunb.) Vahl is a dried fruit of the Oleaceae plant Forsythia suspensa (Thunb.) Vahl. The fruit is harvested in autumn when it is just beginning to ripen and still green, and then impurities are removed, steamed, and dried in the sun. It is commonly known as "green forsythia"; the fruit is harvested when it is fully ripe, dried in the sun, and impurities are removed. It is commonly known as "old forsythia". It is bitter and slightly cold in nature. It enters the lung, heart, and small intestine meridians. It clears away heat and detoxifies, reduces swelling and resolves stagnation, and evacuates wind-heat. It is used for carbuncle, scrofula, breast carbuncle, erysipelas, wind-heat cold, the initial stage of febrile disease, warm and heat entering the camp, high fever and thirst, coma and rash, and hot stranguria and astringent pain.

[0035] Bupleurum is the dried root of Bupleurum chinense DC. or Bupleurumscorzonerifolium Willd. of the Umbelliferae family. According to different properties, they are commonly known as "Northern Bupleurum" and "Southern Bupleurum". It is dug in spring and autumn, the stems, leaves and mud are removed, and dried. It is pungent and bitter in nature, slightly cold. It enters the liver, gallbladder, and lung meridians. It can dissipate heat, relieve liver depression, and raise Yang Qi. It is used for colds and fever, alternating cold and heat, chest and flank pain, irregular menstruation, uterine prolapse, and rectal prolapse.

[0036] Pueraria root is the dried root of Pueraria lobata (Willd.) Ohwi, a plant of the Leguminosae family. It is commonly known as wild kudzu. It is dug in autumn and winter, cut into thick slices or small pieces while fresh, and dried. It is sweet, spicy, and cool in nature. It enters the spleen, stomach, and lung meridians. It relieves muscle and reduces fever, promotes the production of body fluids and quenches thirst, clears rashes, raises yang and stops diarrhea, promotes blood circulation and activates collaterals, and clears alcohol poisoning. It is used for exogenous fever and headache, stiff neck and back pain, thirst, thirst, measles that does not clear up, heat dysentery, diarrhea, dizziness and headache, hemiplegia caused by stroke, chest pain, and alcohol poisoning.

[0037] Mint is the dried aerial part of Mentha haplocalyx Briq., a plant of the Lamiaceae family. In summer and autumn, when the stems and leaves are lush or the flowers are in full bloom, it is harvested in several batches on sunny days and dried in the sun or in the shade. It is pungent and cool in nature. It enters the lung and liver meridians. It can dispel wind-heat, clear the head and eyes, relieve sore throat, clear rashes, and soothe the liver and promote qi. It is used for wind-heat colds, the initial onset of wind-heat, headaches, red eyes, throat paralysis, mouth sores, rubella, measles, and chest and flank distension.

[0038] Honey ephedra is the dried herbaceous stem of Ephedra sinica Stapf or Ephedra intermedia Schrenk et CAmey. or Ephedra equisetina Bge. of the Ephedraceae family. The green herbaceous stems are harvested in autumn and dried in the sun. Take the ephedra segments and stir-fry them according to the honey roasting method until they are not sticky. For every 100kg of ephedra, use 20kg of refined honey. It is pungent, slightly bitter and warm in nature. It enters the lung and bladder meridians. It can induce sweating and dispel cold, clear the lungs and relieve asthma, and promote diuresis and reduce swelling. It is used for colds caused by wind and cold, chest tightness, asthma and cough, and edema caused by wind and water. Honey ephedra moistens the lungs and relieves cough. It is often used for asthma and cough when the exterior symptoms have been resolved.

[0039] Licorice is the dried root and rhizome of Glycyrrhiza uralensis Fisch., Glycyrrhiza inflata Bat. or Glycyrrhiza glabra L. of the Leguminosae family. It is harvested in spring and autumn, the fibrous roots are removed and dried in the sun. It is sweet and neutral in nature. It enters the heart, lung, spleen and stomach meridians. It can nourish the spleen and replenish qi, clear away heat and detoxify, eliminate phlegm and relieve cough, relieve pain and harmonize various medicines. It is used for spleen and stomach weakness, fatigue, palpitations and shortness of breath, cough with sputum, acute pain in the abdomen and limbs, carbuncle, sore and ulcer, and relieve drug toxicity and potency.

[0040] The Chinese medicine composition / Chinese medicine preparation of the present invention is preferably in the form of a unit dose pharmaceutical preparation. The oral preparation is selected from one of capsules, tablets, dripping pills, granules, concentrated pills, oral liquids and mixtures. The injection is selected from one of injection liquids, freeze-dried powder injections and water injections.

[0041] The pharmaceutical composition of the present invention, its oral administration preparation may contain common excipients, such as binders, fillers, diluents, tableting agents, lubricants, disintegrants, colorants, flavoring agents and wetting agents, and the tablets may be coated if necessary.

[0042] Suitable fillers include cellulose, mannitol, lactose and other similar fillers. Suitable disintegrants include starch, polyvinyl pyrrolidone and starch derivatives, such as sodium starch glycolate. Suitable lubricants include, for example, magnesium stearate. Suitable pharmaceutically acceptable wetting agents include sodium lauryl sulfate.

[0043] The pharmaceutical composition of the present invention can be prepared into a solid oral composition by conventional methods such as mixing, filling, tableting, etc. Repeated mixing can distribute the active substance throughout those compositions using a large amount of fillers.

[0044] Oral liquid preparations may be in the form of aqueous or oily suspensions, solutions, emulsions, syrups or elixirs, or may be a dry product that can be reconstituted with water or other suitable carriers before use. Such liquid preparations may contain conventional additives, such as suspending agents, for example sorbitol, syrup, methylcellulose, gelatin, hydroxyethylcellulose, carboxymethylcellulose, aluminum stearate gel or hydrogenated edible fats, emulsifiers, for example lecithin, sorbitan monooleate or gum arabic; non-aqueous carriers (which may include edible oils), for example almond oil, fractionated coconut oil, oily esters such as glycerol esters, propylene glycol or ethanol; preservatives, for example methylparaben or propylparaben or sorbic acid, and, if desired, conventional flavoring or coloring agents.

[0045] For injection, a liquid unit dosage form is prepared containing the active substance of the invention and a sterile carrier. Depending on the carrier and concentration, the compound can be suspended or dissolved. Solutions are usually prepared by dissolving the active substance in a carrier, filtering and sterilizing it before filling it into a suitable vial or ampoule, and then sealing it. Excipients such as a local anesthetic, preservatives and buffers can also be dissolved in this carrier. In order to improve its stability, the composition can be frozen after filling into the vial and the water removed under vacuum.

[0046] The pharmaceutical composition of the present invention can be selectively added with a suitable pharmaceutically acceptable carrier when it is prepared into a medicament. The pharmaceutically acceptable carrier is selected from the group consisting of mannitol, sorbitol, sodium pyrosulfite, sodium bisulfite, sodium thiosulfate, cysteine ​​hydrochloride, thioglycolic acid, methionine, vitamin C, disodium EDTA, sodium calcium EDTA, carbonates, acetates, phosphates of monovalent alkali metals or their aqueous solutions, hydrochloric acid, acetic acid, sulfuric acid, phosphoric acid, amino acids, sodium chloride, potassium chloride, sodium lactate, xylitol, maltose, glucose, fructose, dextran, glycine, starch, sucrose, lactose, mannitol, silicon derivatives, cellulose and its derivatives, alginate, gelatin, polyvinyl pyrrolidone, glycerol, soil temperature 80, agar, calcium carbonate, calcium bicarbonate, surfactants, polyethylene glycol, cyclodextrin, β-cyclodextrin, phospholipid materials, kaolin, talc, calcium stearate, magnesium stearate, etc.

[0047] Obviously, according to the above contents of the present invention, in accordance with common technical knowledge and customary means in the art, without departing from the above basic technical ideas of the present invention, other various forms of modification, replacement or change may be made.

[0048] Beneficial technical effects of the present invention:

[0049] 1. The Chinese medicine composition for treating influenza, antipyretic and anti-inflammatory of the present application has obvious anti-influenza virus effect, and has excellent antipyretic and anti-inflammatory effect at the same time. The main medicines of honeysuckle and forsythia are used to take their pungent, cool and dispersing properties to clear away heat and toxicity. Honey ephedra is pungent and warm to dispel wind and dispel cold, and the combination can disperse the cold and heat evils that violate the surface; Bupleurum is pungent and dispersing, bitter and purgative, and controls the opening and closing of the pivot of the three yang meridians. Pueraria enters the Taiyang and Yangming meridians, which can relieve muscle and penetrate heat, lead evil to penetrate outside, and ephedra enters the Taiyang meridian to dispel cold and relieve the surface. The three medicines can solve various difficulties inside and outside the three yang meridians. In addition to relieving the surface, peppermint can also promote qi and relieve depression, transform dampness and harmonize the middle, and eliminate chest tightness and abdominal distension caused by external wind evil and internal injury and dampness stagnation. Licorice harmonizes various medicines, replenishes deficiency and replenishes qi, and can prevent the dispersing of evil and relieving the surface from being incomplete and the subsequent lack of source, so that this side can penetrate the evil without dispersing qi, relieving the surface without hurting the body, and can make the evil removal work complete and can also consolidate the foundation and strengthen the body.

[0050] 2. The Chinese medicine composition of the present invention has good preventive and therapeutic effects on viral pneumonia caused by influenza virus, and the preparation method of the Chinese medicine composition of the present invention is simple and suitable for large-scale production and promotion. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 : Effect of the Chinese medicine composition in Example 1 of the present invention on lung lesions in mice infected with influenza virus PR / 8 / 34 strain. DETAILED DESCRIPTION

[0052] The present invention is further illustrated by the following examples, but are not intended to limit the present invention.

[0053] Example 1

[0054] Honeysuckle 750g, Forsythia suspensa 750g, Bupleurum 500g, Pueraria lobata 500g, Mint 300g, Honey Ephedra 200g, Licorice 100g

[0055] Take 7 kinds of Chinese medicinal materials, including honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and licorice, according to the above weight, add 10 times water respectively and boil twice, each time for 1 hour, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60℃).

[0056] Example 2

[0057] Honeysuckle 600g, Forsythia suspensa 600g, Bupleurum 400g, Pueraria lobata 400g, Mint 240g, Honey Ephedra 160g, Licorice 80g

[0058] Take 7 kinds of Chinese medicinal materials, including honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and liquorice, according to the above weight. Add 10 times water and boil twice, each time for 1 hour, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60℃).

[0059] Example 3

[0060] Honeysuckle 4500g, Forsythia suspensa 4500g, Bupleurum 3000g, Pueraria lobata 3000g, Mint 1800g, Honey Ephedra 1200g, Licorice 600g

[0061] Take 7 kinds of Chinese medicinal materials, including honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and liquorice, according to the above weight. Add 10 times water and boil twice, each time for 1 hour, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60℃).

[0062] Example 4

[0063] Honeysuckle 750g, Forsythia suspensa 750g, Bupleurum 500g, Pueraria lobata 500g, Mint 300g, Honey Ephedra 200g, Licorice 100g

[0064] Take 7 kinds of Chinese medicinal materials including honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and licorice according to the above weight, add 16 times of water respectively and boil twice, each time for 4 hours, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60℃).

[0065] Example 5

[0066] Honeysuckle 250g, Forsythia suspensa 250g, Bupleurum 50g, Pueraria lobata 50g, Mint 50g, Honey Ephedra 50g, Licorice 50g

[0067] Take 7 kinds of Chinese medicinal materials, including honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and licorice, according to the above weight, add 10 times water respectively and boil twice, each time for 1 hour, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60℃).

[0068] Example 6

[0069] Honeysuckle 1500g, Forsythia suspensa 1500g, Bupleurum 1000g, Pueraria lobata 1000g, Mint 750g, Honey Ephedra 500g, Licorice 250g

[0070] Take 7 kinds of Chinese medicinal materials, including honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and licorice, according to the above weight, add 10 times water respectively and boil twice, each time for 1 hour, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60℃).

[0071] Example 7

[0072] Honeysuckle 500g, Forsythia suspensa 500g, Bupleurum 400g, Pueraria lobata 400g, Mint 300g, Honey Ephedra 160g, Licorice 100g

[0073] Take 7 kinds of Chinese medicinal materials, including honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and licorice, according to the above weight, add 10 times water respectively and boil twice, each time for 1 hour, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60℃).

[0074] Example 8

[0075] The Chinese medicine extract prepared in any one of Examples 1-7 is used as a Chinese medicine raw material to prepare granules, centrifuge and filter, vacuum dry the filtrate, spray dry and crush, add sucralose and dextrin, mix well, and obtain granules.

[0076] Example 9

[0077] The capsules are prepared by using the Chinese medicine extract prepared in any one of Examples 1-7 as the Chinese medicine raw material, and are prepared by conventional pharmaceutics techniques. Starch and ethanol can be added as wetting agents, granulated, and encapsulated to obtain the capsules.

[0078] Example 10

[0079] Take 0.5 g of the traditional Chinese medicine composition obtained in any one of Examples 1 to 7 and 10.5 g of PEG-6000, mix them evenly, heat to melt, and transfer the materials to the dripping pill drip irrigation, drip the medicine liquid into 6-8° C. liquid paraffin, remove oil, and prepare 400 dripping pills.

[0080] Embodiment 11

[0081] Take 0.5 g of the traditional Chinese medicine composition obtained in any one of Examples 1 to 7, 4.5 g of glucose, 0.9 g of sodium thiosulfate and 1 ml of distilled water, mix the above components evenly, freeze-dry, and pack into 500 vials.

[0082] Example 12

[0083] The Chinese medicine composition obtained in any one of Examples 1 to 7 is diluted with water, and then volatile oil is added, mixed, packaged in single doses, and sterilized to prepare an oral solution.

[0084] Embodiment 13

[0085] Take the traditional Chinese medicine composition obtained in any one of Examples 1-7, centrifuge and filter, vacuum dry the filtrate, spray dry, and add microcrystalline cellulose and other auxiliary materials to obtain extract powder to make tablets.

[0086] Effect Example 1 Anti-inflammatory and immunomodulatory experiments

[0087] An acute lung injury model and an acute inflammation model were established in mice by intraperitoneal injection of different concentrations of lipopolysaccharide (LPS), and the effect of the Chinese medicine composition of the present invention on the survival rate of mice in the acute lung injury model, and the anti-inflammatory and immunomodulatory effects in the acute inflammation model were evaluated.

[0088] 1. Experimental equipment

[0089] Balance, model: T-1000, manufacturer: Changshu Shuangjie Testing Instrument Factory; electronic balance, model: MS204S, ML204, manufacturer: Mettler Toledo Instrument Shanghai Co., Ltd.; centrifuge, model: Centrifuge5418, manufacturer: Eppendorf; microplate reader, model: InfiniteM200, manufacturer: TECAN; flow cytometer, model: FACSCalibur, manufacturer: BD.

[0090] 2. Experimental Animals

[0091] 90 BALB / c male mice, SPF grade, weighing 18-20g (Beijing Weitonglihua Laboratory Animal Technology Co., Ltd., certificate number: 110011220101340045, production license number: SCXK (Beijing) 2021-0006). The animal breeding environment conditions meet the relevant standards of the Chinese national standard "Experimental Animal Environment and Facilities" (GB14925-2001) for barrier animal experimental facilities. Animal breeding management and animal experimental operations meet the requirements of the "Tianjin Laboratory Animal Management Regulations" and other regulations. Temperature: 20-26℃, humidity: 40%-70%, light: 12 hours of light and 12 hours of dark, ventilation: more than 15 times / hour of fresh air, and animals drink sterile water prepared by a multiple microporous membrane filtration system (four-stage filtration and ultraviolet sterilization).

[0092] 3. Experimental reagents

[0093] Experimental group: the Chinese medicine composition (Chinese medicine water extract) of the present invention prepared in Example 1 of the present invention, with a clinical intended dosage of 62 g of crude drug / person / day, and a clinical equivalent dose of 6.7 g of extract / kg for mice.

[0094] Positive control group: dexamethasone sodium phosphate injection (No. YLS-2022-FTCM2111-001, Tianjin Jinyao Pharmaceutical Co., Ltd., batch number: 2006082)

[0095] Other reagents: lipopolysaccharide (batch number 039M4004V, Sigma), mouse tumor necrosis factor α (INF-α) ELISA detection kit (batch number: 2021.12, Shanghai ELISA Biotechnology Co., Ltd.), FITC anti-mouse CD3 antibody (batch number: 2109081, Biolegend), PE anti-mouse CD4 antibody (batch number: 2187200, Biolegend), PE anti-mouse CD8a antibody (batch number: 2183599, Biolegend).

[0096] 4. Experimental methods

[0097] 4.1 Effect of the Chinese medicine composition of the present invention on the survival rate of mice with lipopolysaccharide-induced acute lung injury model

[0098] 30 BALB / c mice were randomly divided into 3 groups, namely, a model control group, a high-dose group of the Chinese medicine composition of Example 1 of the present invention, and a dexamethasone group, with 10 mice in each group. Each group of mice was intraperitoneally injected with 35 mg / kg lipopolysaccharide to simulate an acute lung injury model, as shown in Table 2, and each administration group was immediately given the drug and a positive control drug (dexamethasone) after the modeling was completed. The death of each group of mice within 72 hours was observed and recorded, and the survival rate was calculated.

[0099] Table 2 Animal grouping and drug administration

[0100]

[0101] 4.2 Protective effect of the Chinese medicine composition of the present invention on the low-dose lipopolysaccharide-induced mouse inflammation model

[0102] Dosage design: The proposed clinical dosage of the Chinese medicine composition in Example 1 of the present invention is 62g crude drug / person / day, which is converted into a clinical equivalent dose of 62g crude drug / 60kg (adult body weight)*12.3 (conversion factor)=12.7g crude drug / kg for mice. In this experiment, the clinical equivalent dose of 12.7g crude drug / kg for mice was used as a low dose, and each gram of extract was equivalent to 1.90g crude drug. The clinical equivalent dose of mice was converted into an extract amount of 6.7g extract / kg, and 2 times (13.4g extract / kg) and 4 times (26.8g extract / kg) clinical equivalent doses were used as medium and high doses, respectively. The positive control dexamethasone injection, the clinical human dose is 2-20mg per intravenous injection, and the clinical equivalent dose converted into mice is 20mg / 60kg*12.3=4.1mg / kg. In this experiment, 2 times the clinical equivalent dose of 8.2mg / kg was used as the positive control drug dose.

[0103] 60 BALB / c mice were randomly divided into 6 groups, 10 mice in each group, namely normal control group, model control group, low, medium and high dose groups of the Chinese medicine composition of Example 1 of the present invention and dexamethasone group. Each group of mice was treated as shown in Table 3. After 30 minutes of drug treatment in each group on the 7th day, except for the normal control group, the remaining groups were intraperitoneally injected with 20 mg / kg of lipopolysaccharide at one time to establish an acute inflammation model in mice. They were fasted overnight before modeling, but water was not allowed. Mice were killed after 6 hours, and mice were killed by cervical dislocation after blood collection. Thymus, spleen, and lung tissues were weighed and quickly frozen in liquid nitrogen for subsequent index detection.

[0104] Table 3 Animal grouping and drug administration

[0105]

[0106] 4.3 The detection indicators are as follows:

[0107] 1) Lung index, thymus index, spleen index

[0108] The mice were weighed and recorded, and the lungs, thymus and spleen were dissected and weighed after being killed by cervical dislocation. The lung index, thymus index and spleen index were calculated.

[0109] Calculation formula: lung index / thymus / spleen index = (lung / thymus / spleen) mass (mg) / body weight (g).

[0110] 2) Determination of inflammatory factor tumor necrosis factor-α (TNF-α) content (serum)

[0111] Lipopolysaccharide is a direct inducer of TNF-α, and the change of TNF-α content is also one of the indicators for evaluating inflammation. After blood was collected from the mouse orbit, it was centrifuged at 3000r / min for 10 minutes, and then the serum was collected to detect the TNF-α content according to the operating steps in the ELISA kit manual.

[0112] 3) CD4+T lymphocyte count and CD4+ / CD8+ ratio

[0113] The spleen is an important immune organ of mice. The content and relative proportion of Th cells (CD4+ lymphocytes) and Tc cells (CD8+ lymphocytes) in the spleen of mice are important indicators of the immune status of mice. Fresh spleen tissue was taken, ground and passed through a cell sieve, incubated with FITC-CD3 monoclonal antibody, FITC-CD4 monoclonal antibody and FITC-CD8a monoclonal antibody respectively, and the number of CD4+ and CD8+ cells was detected by flow cytometry, and the CD4+ / CD8+ ratio was calculated.

[0114] Statistical methods: Data were expressed as mean ± standard deviation (Mean ± SD). One-way analysis of variance (ANOVA) or non-parametric test was used to analyze data differences, and P < 0.05 was used to judge the differences between groups. The chi-square test was used to compare the survival rate, and P < 0.05 was used to judge the differences between groups.

[0115] 5. Experimental results

[0116] 5.1 Effect of the Chinese medicine composition in Example 1 of the present invention on the survival rate of mice in the acute lung injury model induced by high doses of lipopolysaccharide

[0117] As shown in Table 4, after lipopolysaccharide modeling, all mice in the model group died within 72 hours after modeling, with a survival rate of 0%. In the high-dose group of the Chinese medicine composition in Example 1 of the present invention, 2 mice survived within 72 hours after modeling, with a survival rate of 20%, which was improved to a certain extent compared with the model control group, but there was no significant difference. In the dexamethasone group, 8 mice survived within 72 hours, with a survival rate of 80%, which was significantly improved compared with the model control group (P<0.05).

[0118] Table 4 Effect of the Chinese medicine composition of the present invention on the survival rate of model mice

[0119]

[0120] 5.2 Protective effect of the Chinese medicine composition of the present invention on the low-dose lipopolysaccharide-induced mouse inflammation model

[0121] 5.2.1 Effects on lung index, thymus index, and spleen index

[0122] As shown in Table 5, after lipopolysaccharide modeling, the lung index and spleen index of the model group increased significantly (P<0.05 or P<0.01), and the thymus index did not change significantly. Administration of low, medium and high doses of the Chinese medicine composition of Example 1 of the present invention and dexamethasone can significantly improve the spleen index of the model mice, but has no significant effect on the lung index and thymus index.

[0123] Table 5 Effect of the Chinese medicine composition of Example 1 of the present invention on the lung index, thymus index and spleen index of model mice

[0124]

[0125] Note: Compared with the blank control group, #p<0.05, ##p<0.01; compared with the model control group, *p<0.05, **p<0.01.

[0126] 5.2.2 Effects on inflammatory factors (TNF-α) in serum and lung tissue

[0127] As shown in Table 6, after lipopolysaccharide modeling, the TNF-α content in the serum of the model group was significantly increased (P < 0.01). Administration of low, medium and high doses of the Chinese medicine composition of the present invention and dexamethasone could reduce the TNF-α content in the serum and lung tissue of the model mice to a certain extent, but did not reach a statistical difference.

[0128] Table 6 Effect of the Chinese medicine composition of the present invention on the TNF-α content in the serum of model mice

[0129] Group Clinical dose multiples Serum TNF-α concentration (pg / ml) Normal control / 3.36±4.20 Model comparison / 16.27±7.58## Chinese medicine composition of Example 1 of the present invention 6.7g extract / kg 1 14.73±6.31 Chinese medicine composition of Example 1 of the present invention 13.4g extract / kg 2 12.87±7.99 Chinese medicine composition of Example 1 of the present invention 26.8g extract / kg 4 11.61±6.97 Dexamethasone 8.2 mg / kg 2 9.99±8.31

[0130] Note: Compared with the normal control group##p<0.01.

[0131] 5.2.3 Effects on the number of CD4+ T lymphocytes and CD4+ / CD8+ ratio in the spleen

[0132] As shown in Table 7, after lipopolysaccharide modeling, CD4+ and CD4+ / CD8+ in T cells of the model group were significantly reduced, indicating that lipopolysaccharide infection caused low immunity in the model mice. Each administration group can increase CD4+ and CD4+ / CD8+ to a certain extent, among which the high-dose group of the Chinese medicine composition in Example 1 of the present invention and the dexamethasone group can significantly improve the immune function of the model mice (P<0.05).

[0133] Table 7 Effect of the Chinese medicine composition of the present invention on CD4+, CD8+, CD4+ / CD8+ in spleen tissue of model mice

[0134]

[0135] Note: #p<0.05 compared with the normal control group; *p<0.05 compared with the model control group.

[0136] 6. Experimental conclusion

[0137] An acute lung injury model and an acute inflammation model induced by intraperitoneal injection of lipopolysaccharide were used to observe the survival rate and explore the anti-inflammatory and immunomodulatory effects in vivo. The results showed that the Chinese medicine composition in Example 1 of the present invention has a certain effect of prolonging the survival rate of infected mice, and has a significant immunomodulatory effect and a certain anti-inflammatory effect.

[0138] Effect Example 2 In vitro antiviral experiment of the Chinese medicine composition of the present invention

[0139] Using MDCK (dog kidney) cells as virus hosts, the antiviral effect of the Chinese medicine composition of Example 1 of the present invention was detected in vitro.

[0140] 1. Experimental materials and reagents

[0141] Influenza virus A / PR / 8 / 34 (H1N1) was cultured and passaged in the allantoic cavity of chicken embryos and stored at -80°C; the Chinese medicine composition of Example 1 of the present invention (Modern Chinese Medicine Development Center of Tasly Research Institute); ribavirin (RBV, Hubei Tianyao Pharmaceutical Co., Ltd., batch number: 31712252, positive control drug); oseltamivir phosphate (Shanghai Roche Pharmaceuticals Co., Ltd., batch number: SH0071, positive control drug).

[0142] 2. Experimental methods

[0143] Test method: MDCK cells were inoculated into 96-well culture plates and cultured at 5% CO2 and 37°C. After 24 hours, they were infected with 1 / 210 of the influenza virus. -4 , adsorb for 2 hours, discard the virus solution, add the maintenance solution containing the Chinese medicine composition of Example 1 of the present invention and the positive control drug of different dilutions, set up cell control wells and virus control wells at the same time, 5% CO2, 37°C culture. When the lesion degree (CPE) of the virus control group reaches 4+ ((cell death ratio 75% to 100%), observe the cytopathic degree (CPE) of each group, and use the cumulative method of the median lethal dose (Reed-Muench method) to calculate the half toxic concentration (TC50) of the Chinese medicine composition of the present invention, oseltamivir phosphate, and ribavirin to cells and the half inhibitory concentration (IC50) to viruses. The selection index (SI) is the safe range for judging the effect of the drug, and the selection index (SI) is TC50 / IC50. The selection index is greater than 1 for effectiveness, and the larger the index, the larger the safety range.

[0144] 3. Experimental results and conclusions

[0145] As shown in Table 8 below, the experimental results show that the selectivity index of the Chinese medicine composition of Example 1 of the present invention is 2.5, indicating that it has anti-influenza virus activity when used at the maximum non-toxic dose in vitro.

[0146] Table 8 Effect of the Chinese medicine composition of the present invention on in vitro antiviral test

[0147]

[0148] The Chinese medicine composition of Example 1 of the present invention has an inhibitory effect on the activity of influenza virus A / PR / 8 / 34, indicating that the Chinese medicine composition of the present invention has an antiviral effect in vitro.

[0149] Effect Example 3 Study on the efficacy of the Chinese medicine composition of Example 1 of the present invention against influenza virus in mice

[0150] The therapeutic effect of the Chinese medicine composition of the present invention on influenza A virus infection in mice was observed.

[0151] 1. Experimental materials and reagents

[0152] 192 female Kunming mice (SPF grade), weighing 14-16 grams (purchased from Beijing Huafukang Biotechnology Co., Ltd., certificate number: NO.11032222110002368 and NO.110322221102596035). The influenza infection experiment of mice was carried out in the second-level animal biosafety laboratory (ABSL-2), and all operations were carried out in accordance with the standard operating procedures of the International Animal Ethics Committee and the Animal Ethics Committee of the Institute of Medical Biotechnology, Chinese Academy of Medical Sciences. The mice were raised at a temperature of 22±1℃ for 2 days, with 12h of light alternating day and night, and sufficient water and food. After 2 days of adaptive feeding, the mice were randomly divided into groups.

[0153] Virus: Influenza virus type A mouse lung-adapted strain A / PR / 8 / 34 (PR8, H1N1), cultured and preserved at the Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences.

[0154] Chinese medicine composition according to Example 1 of the present invention; pentobarbital (Germany), distilled water (product of Watsons Food and Beverage Co., Ltd.). Experimental equipment: single-channel pipette (Eppendorf), electronic balance (Ohaus Instrument Shanghai Co., Ltd.), 1 mL disposable syringe (Shandong Weigao Group Medical Polymer Products Co., Ltd.), Precellys homogenizer (Bertin), A2 type biological safety cabinet (LABCONCO), carbon dioxide incubator (Thermo Scientific), SorvallST16R low-temperature centrifuge (Thermo Scientific), -80°C refrigerator (Haier), inverted microscope (OLYMPUS).

[0155] 2. Experimental methods

[0156] 2.1 Determination of the median infectious dose (LD50) of influenza A virus (PR / 8) in mice via intranasal infection

[0157] Kunming mice, female, 14-16 g, 6 mice per group. Mice were lightly anesthetized with pentobarbital, and the freshly harvested PR / 8 chicken embryo allantoic fluid was diluted 10 times into 7 dilutions: 10 -2 -10 -8 40 μL of virus solution was evenly dripped into both nostrils of each mouse to infect the mice. The mice were observed for two weeks after infection and the median infectious dose (LD50) of the mice was calculated.

[0158] 2.2 Experimental study on the treatment of influenza virus-infected mouse model using the Chinese medicine composition of Example 1 of the present invention

[0159] The experimental mice were anesthetized with 50 mg / kg pentobarbital intraperitoneally and injected intranasally for 10 -5 The diluted virus was administered at 40 μL / mouse, 10 mice per group, twice daily for 7 days, and the death rate within 14 days was recorded. A virus infection control group and a normal mouse control group were set up at the same time. The average survival day, survival rate, death protection rate and life extension rate of each group were calculated.

[0160] 2.3 Lung index and lung lesion inhibition experiment

[0161] The experimental mice were anesthetized with 50 mg / kg pentobarbital intraperitoneally and injected intranasally for 10 -5 The diluted virus was administered at 40 μL / mouse, 10 mice per group, twice a day. The mice were killed on the 4th day after virus infection, and the whole lungs were removed after weighing, and the lung index and lung index inhibition rate were calculated. At the same time, lung lesions were judged by naked eye, with no lesions as (-), <25% lesions as (+), 25-50% lesions as (++), 50-75% lesions as (+++), and 75-100% lesions as (++++), and photos were taken.

[0162] 2.4 Experiment on determination of virus titer in mouse lung tissue

[0163] The right lung was taken from the lungs after the evaluation of lung lesions, weighed, and frozen in a -80°C refrigerator. Tissue culture medium was added to the lung tissue and fully ground into lung tissue homogenate using a Precellys homogenizer. Centrifuged at 4°C, 8000rpm for 10 minutes, and the supernatant was collected. The lung homogenate supernatant was used to infect MDCK cells, and the degree of cytopathic effect (CPE) was observed and the TCID50 of the lung was determined.

[0164] 2.5 Result calculation method

[0165] 1) Death protection rate (%): The death protection rate of animals after administration was calculated by comparing with the virus control group.

[0166] Death protection rate = (mortality rate of virus control group - mortality rate of experimental group) / mortality rate of virus control group * 100%

[0167] 2) Life extension rate (%): The life extension rate of animals after administration was calculated by comparing with the virus control group.

[0168] Extended life rate = (average life days of experimental group - average life days of virus control group) / average life days of virus control group * 100%

[0169] 3) Lung index (%) = lung wet weight (g) / body weight (g) * 100

[0170] Lung index inhibition rate (%) = [lung weight of model control group (g) - lung weight of drug administration group (g)] / [lung weight of model control group (g) - lung weight of normal control group] * 100.

[0171] 3. Statistical processing

[0172] SPSS 27.0 statistical software was used to compare mortality and Kaplan-Meier method to compare mean survival days, and Ridit t-test was used to analyze lung lesions. Lung tissue virus titer and lung index were analyzed.

[0173] 4. Experimental results

[0174] 4.1 The median infectious dose of mice infected with the mouse lung-adapted influenza virus strain by intranasal drip

[0175] The chicken embryo allantoic fluid virus of influenza virus mouse lung adapted strain A / PR / 8 / 34 (PR8, H1N1) was diluted 10 times to form 7 dilutions (10 -2 -10 -8 ), 6 animals in each group, pentobarbital anesthesia, 40 μL / animal, intranasal infection. After two weeks of observation, the LD50 was calculated by the Reed-Muench method, and the LD50 was 10 -5.5 The virus infection dose for mice is: dilution 10 -5 , 40μL / mouse. See Table 9 for details.

[0176] Table 9 The median infection dose of mice infected by intranasal drip of influenza virus mouse lung adapted strains

[0177]

[0178] 4.2 Antiviral effect of the Chinese medicine composition of Example 1 of the present invention administered 2 hours after infection

[0179] After anesthesia, mice were infected with the virus by intranasal drip. Two hours after infection, the three dose groups of 26.8 g / kg, 13.4 g / kg, and 6.7 g / kg were administered twice a day for a total of 7 days. Deaths were recorded daily for a total of 14 days. The protective effect of the Chinese medicine composition of Example 1 of the present invention on mice infected with influenza virus is shown in Table 10.

[0180] Table 10 Antiviral efficacy of the Chinese medicine composition of the present invention administered 2 hours after infection

[0181]

[0182] Note: The survival rate was compared with the virus control group *p<0.05, **p<0.01, and the average life days were compared with the virus control group #p<0.05, ##p<0.01.

[0183] The antiviral effects of the drug-administered group 2 hours after infection were as follows:

[0184] The average life span of mice in the group of mice treated with 6.7 g / kg of the Chinese medicine composition of Example 1 of the present invention was 10.0±3.5 days, which was 3.2 days longer than that of the virus control group, with a life span extension rate of 20.5% and a survival rate of 40%. The survival rate was significantly different from that of the virus control group.

[0185] The average life span of mice in the group of mice treated with 13.4 g / kg of the Chinese medicine composition of Example 1 of the present invention was 11.1±3.2 days, which was 4 days longer than the average life span of the virus control group, with a life span extension rate of 33.7% and a survival rate of 50%. Compared with the virus control group, the survival rate and the average life span were significantly different.

[0186] The average life span of mice in the group of mice treated with 26.8 g / kg of the Chinese medicine composition of Example 1 of the present invention was 12.0±2.6 days, which was 4.3 days longer than the average life span of the virus control group, with a life span extension rate of 44.6% and a survival rate of 60%. There were significant differences in survival rate and average life span compared with the virus control group.

[0187] 4.3 Antiviral effect of the Chinese medicine composition of Example 1 of the present invention when administered 24 hours after infection

[0188] After anesthesia, mice were infected with the virus by intranasal drip. 24 hours after infection, three dose groups of 26.8 g / kg, 13.4 g / kg, and 6.7 g / kg were administered twice a day for a total of 7 days. Deaths were recorded daily for a total of 14 days. The protective effect of the Chinese medicine composition of Example 1 of the present invention on mice infected with influenza virus is shown in Table 11.

[0189] Table 11 Antiviral efficacy of the Chinese medicine composition of the present invention administered 24 hours after infection

[0190]

[0191] Note: The survival rate was compared with the virus control group *p<0.05, **p<0.01, and the average life days were compared with the virus control group #p<0.05, ##p<0.01.

[0192] The antiviral effects of the drug-administered group 24 hours after infection were as follows:

[0193] The average life span of mice in the group of mice treated with 6.7 g / kg of the Chinese medicine composition of Example 1 of the present invention was 11.5±3.0 days, which was 4.2 days longer than the average life span of the virus control group, with a life span extension rate of 38.6% and a death protection rate of 50%. The survival rate and average life span were significantly different from those of the virus control group.

[0194] The average life span of mice in the group of mice treated with 13.4 g / kg of the Chinese medicine composition of Example 1 of the present invention was 10.4±3.3 days, which was 3.4 days longer than that of the virus control group, with a life span extension rate of 25.3% and a death protection rate of 40%. The survival rate was significantly different from that of the virus control group.

[0195] The average life span of mice in the group of mice treated with 26.8 g / kg of the Chinese medicine composition of Example 1 of the present invention was 9.3±4.5 days, which was 3.5 days longer than that of the virus control group, with a life span extension rate of 12.4% and a death protection rate of 33.3%. The survival rate was significantly different from that of the virus control group.

[0196] 4.4 Determination of lung index and lung lesions in mice infected with influenza virus PR / 8 by administration of the Chinese medicine composition of Example 1 of the present invention starting 2 hours after infection

[0197] Mice were anesthetized and intranasally infected with the virus for 10 -5 , administration started 2 hours after infection. The three dosage groups of the Chinese medicine composition of Example 1 of the present invention (6.7g / kg, 13.4g / kg and 26.8g / kg) were administered twice a day. The mice were killed on the 4th day after viral infection, and the whole lungs were removed after weighing, and the lung index and lung index inhibition rate were calculated; at the same time, the lung lesions were judged by naked eye and photographed. No lesions are (-), <25% lesions are (+), 25-50% lesions are (++), 50-75% lesions are (+++), and 75-100% lesions are (++++). The protective effect of the Chinese medicine composition of the present invention on the lung index of mice infected with influenza virus is shown in Table 12 and the attached figure of the specification. Figure 1 .

[0198] Table 12 Effect of the Chinese medicine composition of the present invention on lung lesions, lung index and virus titer of mice infected with influenza virus PR / 8 / 34 strain

[0199]

[0200] Note: Lung lesion score and virus control were analyzed by Ridit analysis, **p<0.01 compared with the virus control group. Lung index and virus control were analyzed by t test, #p<0.05, ##p<0.01 compared with the virus control group. Lung virus titer and virus control were analyzed by t test. Compared with the virus control group ★ p<0.05, ★★ p<0.01.

[0201] From the above results, it can be seen that the lung lesions in the 26.8 g / kg group of the Chinese medicine composition of Example 1 of the present invention are significantly different from those in the virus control group, and there are no statistically significant differences in the lung lesions in the other drug-administered groups compared with the virus control group.

[0202] The lung index of the 13.4 g / kg group of the Chinese medicine composition of Example 1 of the present invention was significantly different from that of the virus control group, while the lung index of the other drug administration groups was not statistically significantly different from that of the virus control group.

[0203] The lung tissue virus titer of the 6.7 g / kg Chinese medicine composition group in Example 1 of the present invention was significantly different from that of the virus control group, and there was no statistically significant difference in the lung tissue virus titer of the other drug-administered groups compared with the virus control group.

[0204] 5. Experimental conclusion

[0205] Under the conditions of this experiment, mice were gavaged with the medicine 26.8 g / kg and 13.4 g / kg of the Chinese medicine composition of Example 1 of the present invention had certain anti-influenza virus effects 24 hours after being infected with the influenza virus. Mice were gavaged with the medicine 26.8 g / kg, 13.4 g / kg, and 6.7 g / kg of the Chinese medicine composition of Example 1 of the present invention had certain anti-influenza virus effects.

[0206] Effect Example 4 Toxicity test of single intragastric administration of the Chinese medicine composition of the present invention to rats

[0207] After the Chinese medicine composition of the present invention is administered to rats by oral gavage, the toxic reactions of the rats are observed to obtain the maximum tolerated dose and / or the minimum lethal dose, thereby providing a reference for the safety of the Chinese medicine composition of the present invention.

[0208] 1. Experimental Materials and Methods

[0209] This experiment is to detect the toxic effect of a single oral administration of the Chinese medicine composition in Example 1 of the present invention. According to the requirements of the "Technical Guidelines for Single-dose Toxicity Studies of Drugs" of the State Food and Drug Administration, CD (SD) rats, a conventional rodent species, were selected for this experiment. 70 SD rats, SPF grade, male weight 177-216g, female 162-200g. After the adaptation period, abnormal animals were eliminated, and 60 normal animals in good condition and moderate weight were selected for formal experiments, half male and half female (Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., License No.: SCXK (Beijing) 2021-0011).

[0210] Animals were kept in a barrier environment with a temperature of 20-26°C, a relative humidity of 40%-70%, a 12-hour light-dark cycle, and ventilation ≥15 times / hour of fresh air. Except for 17 hours before administration and on the day of administration, when animals were fasted but not watered, sufficient feed and drinking water were provided at other times. Cages were changed weekly, and bedding was changed as needed.

[0211] The Chinese medicine composition of Example 1 of the present invention, the extract concentration of the Chinese medicine composition of Example 1 of the present invention is: 1.2388g extract / mL. The amount of crude drug contained in the Chinese medicine composition of Example 1 of the present invention is: 1.87g crude drug / g, and the extract storage conditions are: refrigerated.

[0212] The preparation method of the Chinese medicine composition of the present invention:

[0213] 1) Low concentration solution: Accurately weigh 278.73 g of the Chinese medicine composition of the present invention, place it in a volume-corrected container, add a small amount of ultrapure water, vortex mix, and dilute to 300 mL with ultrapure water. The solution concentration is 0.9291 g extract / mL. The solution is prepared on the spot and used for administration to the low-dose group animals.

[0214] 2) High concentration solution: The extract is used for administration. No preparation is required and it can be taken immediately for administration to high-dose group animals.

[0215] 2. Experimental methods

[0216] 2.1 Grouping and Dosing

[0217] There are 3 groups in this experiment, namely control group, low-dose group and high-dose group, each group has 20 mice, half of them are male and half are female. The specific administration method is as follows: 1) Control group: equal volume of ultrapure water.

[0218] 2) Low-dose group: 104.2 g crude drug / kg, which is 117.7 times the intended clinical dosage for humans.

[0219] 3) High-dose group: 139.0 g crude drug / kg, 156.9 times the intended clinical dosage for humans. The administration volume for each of the above groups was 20 mL / kg / time.

[0220] According to the requirements of the "Technical Guidelines for Toxicity Studies of Single-Dose Drugs", the route of administration should be consistent with the intended clinical route of administration. Therefore, this experiment used gavage to administer the drug to animals. This experiment was divided into three doses within 24 hours, with an interval of 4 hours. According to the requirements of the "Technical Guidelines for Toxicity Studies of Single-Dose Drugs", continuous observation for 14 days after administration. 17 hours before administration and during the three doses, the animals were fasted but not watered. On the day of administration, the fasting body weight of the animals was weighed, and the dosing volume was calculated based on the body weight. Each group of rats was administered the drug by gavage. During the administration process, the operation was gentle to avoid damaging the animal's esophagus or causing accidental death.

[0221] 2.2 Observation indicators

[0222] 1) General observation: physical appearance, behavioral activities, mental state, excretion, etc.

[0223] 2) Body weight examination: The body weight of rats was examined before administration and on days 1, 3, 7, and 14 after administration.

[0224] 3) Anatomical examination: body surface, head, chest cavity and chest organs, abdominal cavity and abdominal organs, pelvic cavity and pelvic organs, etc.

[0225] 4) Histopathological examination: Based on the results of the anatomical examination, if any animal's tissues and organs show changes in volume, color, texture, etc., a histopathological examination should be conducted on the abnormal tissues and organs of the animal and the corresponding tissues and organs of the control group animals at the same time.

[0226] 2.3 Statistics

[0227] Statistical analysis was performed using SPSS software. All indicators were analyzed by gender. The t-test was used to compare the drug-treated groups with the control group, and P ≤ 0.05 was considered statistically significant to determine the safety of the Chinese medicine composition of the present invention.

[0228] 3. Experimental results

[0229] In this experiment, CD rats were gavaged with the Chinese medicine composition of Example 1 of the present invention three times at intervals of 4 hours within 24 hours. Within 24 hours after administration, 1 / 10 female animals in the high-dose group died, and the remaining rats and rats in the low-dose group showed varying degrees of hair contamination and loose stools; by the third day of drug withdrawal, the surviving rats in each experimental group could basically recover, see Table 13. By the end of the recovery period, the weight of the surviving rats in each experimental group increased steadily, and no visible abnormalities were found in the autopsy, see Table 14.

[0230] Table 13 Overview of toxic reactions in rats

[0231]

[0232] Table 14 Statistical analysis results of rat body weight (g) before and after administration (mean ± SD)

[0233]

[0234]

[0235] 4. Experimental conclusion

[0236] Under the experimental conditions, the maximum tolerated dose (MTD) of the Chinese medicine composition of the present invention for rats by single oral administration was 104.2 g crude drug / kg, and the minimum lethal dose (MLD) was 139.0 g crude drug / kg, which were 117.7 and 156.9 times the intended clinical dose for humans, respectively. The Chinese medicine composition of Example 1 of the present invention did not cause obvious acute toxic reactions.

[0237] The above is only a preferred specific embodiment of the present invention, but the protection scope of the present invention is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed by the present invention should be included in the protection scope of the present invention. Therefore, the protection scope of the present invention shall be subject to the protection scope of the claims.

Claims

1. A Chinese medicine composition, characterized in that: The invention is prepared from the following Chinese medicinal raw materials in parts by weight: 5-30 parts of honeysuckle, 5-30 parts of forsythia, 1-20 parts of bupleurum, 1-20 parts of kudzu root, 1-15 parts of mint, 1-10 parts of honey ephedra and 1-5 parts of liquorice.

2. The Chinese medicine composition according to claim 1, characterized in that: The invention is prepared from the following Chinese medicinal raw materials in parts by weight: 5-25 parts of honeysuckle, 5-25 parts of forsythia, 5-20 parts of bupleurum, 5-20 parts of kudzu root, 5-15 parts of mint, 1-8 parts of honey ephedra and 1-5 parts of liquorice.

3. The Chinese medicine composition according to claim 2, characterized in that: The invention is prepared from the following Chinese medicinal raw materials in parts by weight: 10-25 parts of honeysuckle, 10-25 parts of forsythia, 5-15 parts of bupleurum, 5-15 parts of kudzu root, 5-10 parts of mint, 1-5 parts of honey ephedra and 1-3 parts of liquorice.

4. The Chinese medicine composition according to claim 3, characterized in that: The invention is prepared from the following Chinese medicinal raw materials in parts by weight: 12-20 parts of honeysuckle, 12-20 parts of forsythia, 8-12 parts of bupleurum, 8-12 parts of kudzu root, 5-8 parts of mint, 3-5 parts of honey ephedra and 1-3 parts of liquorice.

5. The Chinese medicine composition according to any one of 1-3, characterized in that: The invention is prepared from the following Chinese medicinal raw materials in parts by weight: 15 parts of honeysuckle, 15 parts of forsythia, 10 parts of bupleurum, 10 parts of kudzu root, 6 parts of mint, 4 parts of honey ephedra, and 2 parts of liquorice.

6. The Chinese medicine composition according to any one of claims 1 to 3, characterized in that: The composition is in the form of a pharmaceutical preparation, and the pharmaceutical preparation may further include pharmaceutical excipients as required.

7. The Chinese medicine composition according to claim 6, characterized in that: The pharmaceutical preparation is selected from the group consisting of tablets, capsules, lozenges, granules, pills, powders, ointments, pills, suspensions, solutions, injections, suppositories, ointments, sprays, drops, pills or patches.

8. The method for preparing the Chinese medicine composition according to any one of claims 1 to 5, characterized in that: According to any one of claims 1 to 5, take 7 Chinese medicinal materials, namely, honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and licorice, add 2-16 times the amount of water and boil them 1-3 times, each time for 0.5-4 hours, combine the extracts, filter, and concentrate the filtrate to obtain the product.

9. The preparation method according to claim 8, characterized in that: According to any one of claims 1 to 5, take 7 Chinese medicinal materials, namely, honeysuckle, forsythia, bupleurum, kudzu root, mint, honey ephedra and licorice, add 10 times of water and boil twice, each time for 1 hour, combine the extracts, filter through 300 mesh, and concentrate the filtrate to a density of 1.20-1.30 (60° C.) to obtain the product.

10. Use of the Chinese medicine composition according to any one of claims 1 to 5 in the preparation of medicines for common cold and / or influenza.

11. A Chinese medicine composition, characterized in that: The invention is prepared from the following Chinese medicinal raw materials in parts by weight: 5-30 parts of honeysuckle, 5-30 parts of forsythia, 1-20 parts of bupleurum, 1-20 parts of kudzu root, 1-15 parts of mint, 1-10 parts of honey ephedra, and 1-5 parts of liquorice; The preparation method is as follows: take the above 7 Chinese medicinal materials respectively, add 2-16 times amount of water and boil for 1-3 times, each time for 0.5-4 hours, combine the extracts, filter, and concentrate the filtrate to obtain the product.

Images