Application of composition in preparation of medicine for preventing and / or treating influenza A

Abstract

The invention provides application of a composition in preparation of a medicine. The medicine is used for preventing and / or treating influenza A; the composition comprises honeysuckle, fructus forsythiae, radix isatidis, scutellaria baicalensis, folium mori, chrysanthemum, scaphium scaphigerum, burdock, cicada slough, radix peucedani, stiff silkworm and semen armeniacae amarae. The composition has the effects of preventing and treating influenza A, and is high in safety, free of toxic and side effects and high in application value.

Description

Technical Field

[0001] The present invention relates to the field of medicine, and in particular to the use of a composition in preparing a drug for preventing and / or treating influenza A. Background Art

[0002] Influenza A is an acute respiratory infectious disease caused by influenza A virus. Its early clinical manifestations are similar to other influenza symptoms, including high fever, cough, runny nose, myalgia, etc. Most cases are accompanied by severe pneumonia. In severe cases, multiple organ failure such as heart and kidney failure leads to death, and the mortality rate is very high.

[0003] Antiviral drugs are the main choice for preventing and controlling the pandemic of influenza A. Among the drugs available on the market, there are few varieties of special anti-influenza A drugs, such as oseltamivir, zanamivir, and arbidol hydrochloride, but they have certain adverse reactions, are expensive, and the number of drug-resistant strains is gradually increasing. In recent years, Chinese patent medicine preparations have been effective in treating influenza A, which can effectively inhibit viral replication, enhance the body's immunity, and significantly reduce adverse reactions. There are currently a variety of Chinese patent medicines with antiviral effects on the market, but no drug has been found to be effective in treating influenza A. Chinese medicine compositions for the treatment of influenza A remain to be studied. Summary of the invention

[0004] The present invention aims to solve the technical problems existing in the prior art at least to a certain extent. To this end, the present invention provides the use of a composition in the preparation of a medicine, the composition has the efficacy of preventing and / or treating influenza A, has high safety, no toxic side effects, and high application value.

[0005] The present invention provides use of a composition in preparing a medicine, wherein the medicine is used for preventing and / or treating influenza A; the composition comprises: honeysuckle, forsythia, isatis root, scutellaria baicalensis, mulberry leaf, chrysanthemum, sterculia lychnophora, burdock fruit, cicada shell, peucedanum peucedanum, bombyx batryticatus, and bitter almond.

[0006] The composition of the present invention has a preventive and / or therapeutic effect on influenza A, significantly reduces pulmonary inflammatory pathological damage, reduces the expression of inflammatory factors IL-6, IL-10 and / or TNF-α caused by infection, and can significantly reduce the influenza A virus load, thus having important application value.

[0007] According to an embodiment of the present invention, the use of the above composition in preparing a drug may also have the following additional technical features:

[0008] Specifically, the composition of the present invention includes honeysuckle, forsythia, isatis root, scutellaria baicalensis, mulberry leaf, chrysanthemum, sterculia lychnophora, burdock fruit, cicada shell, peucedanum, bombyx batryticatus and bitter almond as active ingredients; in other words, in the composition of the present invention, the active ingredients include honeysuckle, forsythia, isatis root, scutellaria baicalensis, mulberry leaf, chrysanthemum, sterculia lychnophora, burdock fruit, cicada shell, peucedanum, bombyx batryticatus and bitter almond.

[0009] According to an embodiment of the present invention, the composition includes: 115-135 parts by weight of honeysuckle, 115-135 parts by weight of forsythia, 115-135 parts by weight of isatis root, 65-85 parts by weight of scutellaria, 40-60 parts by weight of mulberry leaves, 40-60 parts by weight of chrysanthemum, 40-60 parts by weight of sterculia lychnophora, 40-60 parts by weight of burdock seeds, 40-60 parts by weight of cicada shells, 40-60 parts by weight of peucedanum peucedanum, 40-60 parts by weight of bombyx batryticatus, and 40-60 parts by weight of bitter almonds.

[0010] Specifically, the composition of the present invention comprises 115-135 parts by weight of honeysuckle, 115-135 parts by weight of forsythia, 115-135 parts by weight of isatis root, 65-85 parts by weight of scutellaria, 40-60 parts by weight of mulberry leaves, 40-60 parts by weight of chrysanthemum, 40-60 parts by weight of sterculia lychnophora, 40-60 parts by weight of burdock fruit, 40-60 parts by weight of cicada shell, 40-60 parts by weight of peucedanum peucedanum, 40-60 parts by weight of bombyx batryticatus, and 40-60 parts by weight of bitter almond as active ingredients; In other words, in the composition of the present invention, the active ingredients include 115-135 parts by weight of honeysuckle, 115-135 parts by weight of forsythia, 115-135 parts by weight of isatis root, 65-85 parts by weight of scutellaria, 40-60 parts by weight of mulberry leaves, 40-60 parts by weight of chrysanthemum, 40-60 parts by weight of sterculia lychnophora, 40-60 parts by weight of burdock seeds, 40-60 parts by weight of cicada shells, 40-60 parts by weight of peucedanum peucedanum, 40-60 parts by weight of bombyx batryticatus, and 40-60 parts by weight of bitter almonds.

[0011] According to an embodiment of the present invention, the composition includes: honeysuckle, forsythia, isatis root, scutellaria, mulberry leaf, chrysanthemum, peucedanum, bitter almond, burdock fruit, sterculia lychnophora, bombyx batryticatus, cicada shell, scrophularia, red peony root, oriental water plantain and oroxylum butterfly.

[0012] Specifically, the composition of the present invention comprises honeysuckle, forsythia, isatis root, scutellaria, mulberry leaf, chrysanthemum, peucedanum, bitter almond, burdock fruit, sterculia lychnophora, bombyx batryticatus, cicada shell, Scrophularia ningpoensis, red peony root, orientalism and orientalism as active ingredients; in other words, in the composition of the present invention, the active ingredients comprise honeysuckle, forsythia, isatis root, scutellaria, mulberry leaf, chrysanthemum, peucedanum, bitter almond, burdock fruit, sterculia lychnophora, bombyx batryticatus, cicada shell, Scrophularia ningpoensis, red peony root, orientalism and orientalism; preferably, the active ingredients consist of honeysuckle, forsythia, isatis root, scutellaria, mulberry leaf, chrysanthemum, peucedanum, bitter almond, burdock fruit, sterculia lychnophora, bombyx batryticatus, cicada shell, Scrophularia ningpoensis, red peony root, orientalism and orientalism.

[0013] According to an embodiment of the present invention, the composition includes: 115-135 parts by weight of honeysuckle, 115-135 parts by weight of forsythia, 115-135 parts by weight of isatis root, 65-85 parts by weight of scutellaria, 40-60 parts by weight of mulberry leaves, 40-60 parts by weight of chrysanthemum, 40-60 parts by weight of sterculia lychnophora, 40-60 parts by weight of burdock seeds, 40-60 parts by weight of cicada shells, 40-60 parts by weight of peucedanum, 40-60 parts by weight of bombyx batryticatus, 40-60 parts by weight of bitter almond, 115-135 parts by weight of Scrophularia, 40-60 parts by weight of red peony root, 40-60 parts by weight of orientalis, and 40-60 parts by weight of oroxylum bungeana.

[0014] Specifically, the composition of the present invention comprises 115-135 parts by weight of honeysuckle, 115-135 parts by weight of forsythia, 115-135 parts by weight of isatis root, 65-85 parts by weight of scutellaria, 40-60 parts by weight of mulberry leaves, 40-60 parts by weight of chrysanthemum, 40-60 parts by weight of sterculia lychnophora, 40-60 parts by weight of burdock fruit, 40-60 parts by weight of cicada shell, 40-60 parts by weight of peucedanum peucedanum, 40-60 parts by weight of bombyx batryticatus, and 40-60 parts by weight of bitter almond. , 115-135 parts by weight of Scrophularia, 40-60 parts by weight of Red Peony Root, 40-60 parts by weight of Alisma Oroxylum, and 40-60 parts by weight of Oroxylum butterflyium as active ingredients; in other words, in the composition of the present invention, the active ingredients include 115-135 parts by weight of Honeysuckle, 115-135 parts by weight of Forsythia, 115-135 parts by weight of Isatis, 65-85 parts by weight of Scutellaria, 40-60 parts by weight of Morus alba, 40-60 parts by weight of Chrysanthemum, 40-60 parts by weight of Sterculia lychnophora. 0 weight parts, 40-60 weight parts of burdock seeds, 40-60 weight parts of cicada shells, 40-60 weight parts of peucedanum, 40-60 weight parts of bombyx batryticatus, 40-60 weight parts of bitter almonds, 115-135 weight parts of Scrophularia, 40-60 weight parts of red peony root, 40-60 weight parts of orientalis, 40-60 weight parts of oroxylum butterfly, preferably, the active ingredients are 115-135 weight parts of honeysuckle, 115-135 weight parts of forsythia, 115-135 weight parts of isatis root, 115-135 weight parts of The invention discloses a novel nanostructured carbon foam, which is composed of 65-85 weight parts of scutellaria baicalensis, 40-60 weight parts of mulberry leaves, 40-60 weight parts of chrysanthemums, 40-60 weight parts of Sterculia lychnophora, 40-60 weight parts of burdock seeds, 40-60 weight parts of cicada shells, 40-60 weight parts of peucedanum, 40-60 weight parts of bombyx batryticatus, 40-60 weight parts of bitter almonds, 115-135 weight parts of Scrophularia ningpoensis, 40-60 weight parts of red peony root, 40-60 weight parts of orientalis, and 40-60 weight parts of oroxylum bungeana.

[0015] According to an embodiment of the present invention, the composition further comprises a pharmaceutically acceptable excipient.

[0016] According to an embodiment of the present invention, the medicament is used to reduce the content of inflammatory factors IL-6, IL-10 and / or TNF-α in lung tissue.

[0017] IL-6 and TNF-α are important factors that cause cytokine storms in patients with severe pneumonia caused by influenza. IL-6 is an important factor in regulating immune and inflammatory responses, and its increased levels are associated with the severity of influenza virus infection. Studies have shown that increased IL-6 levels indicate an increased inflammatory response during the acute phase of influenza A (such as H1N1, etc.) virus infection. Animal studies have shown that inhibition of TNF-α can prevent fatal diseases in mice infected with influenza A (such as H1N1, etc.). Plasma IL-10 levels are elevated during the acute phase of infection. The immunosuppressive effects of IL-10 and IL-6 synergistically may support viral persistence or secondary infection, leading to more severe clinical outcomes of influenza A (such as H1N1, etc.) viruses. Clinical trials have shown that in subjects infected with influenza A (such as H1N1, etc.), TNF-α and IL10snp as well as IL-6 and IL-10 levels are associated with the severity of the disease. In addition, IL-6 levels may serve as a biomarker for predicting fatal outcomes in subjects infected with influenza A (such as H1N1, etc.). The inventors have proved through a large number of experiments that the composition can be used to effectively prevent and / or treat influenza A, significantly reduce inflammatory pathological damage to the lungs, and reduce the expression of inflammatory factors IL-6, IL-10 and / or TNF-α caused by infection. It is particularly suitable for influenza A (such as H1N1, etc.) and the lung damage (such as inflammatory pathological damage to the lungs) caused by it, and can significantly reduce the influenza A virus load.

[0018] According to an embodiment of the present invention, the drug is in the form of pills, tablets, capsules, oral liquid or syrup.

[0019] According to an embodiment of the present invention, the influenza A is selected from one or more of influenza A (H1N1), influenza A (H2H2), influenza A (H3N2), influenza A (H5N1), influenza A (H7N1), influenza A (H7N2), influenza A (H7N3), influenza A (H7N7), influenza A (H7N9), influenza A (H9N2), and influenza A (H10N8), preferably selected from one or more of influenza A (H1N1), influenza A (H5N1), and influenza A (H7N9).

[0020] According to an embodiment of the present invention, the drug is used to prevent and / or treat lung injury caused by influenza A. Preferably, the lung injury is selected from inflammatory pathological lung injury.

[0021] According to an embodiment of the present invention, the medicament is used to reduce influenza A viral load.

[0022] Additional aspects and advantages of the present invention will be given in part in the following description and in part will be obvious from the following description, or will be learned through practice of the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] The above and / or additional aspects and advantages of the present invention will become apparent and easily understood from the description of the embodiments in conjunction with the following drawings, in which:

[0024] Figure 1 The lung tissue pathological changes of the mouse pneumonia model induced by the H1N1 influenza virus PR8 strain in Example 7 of the present invention (HE staining × 400), a is the normal control group, b is the model control group, c is the Example 1 group, d is the Comparative Example 1 group, e is the Example 2 group, and f is the Example 3 group;

[0025] Figure 2 The following are the pathological changes of pulmonary bronchioles in the mouse pneumonia model induced by the H1N1 influenza virus PR8 strain in Example 7 of the present invention (HE staining × 400), where a is the normal control group, b is the model control group, c is the Example 1 group, d is the Comparative Example 1 group, e is the Example 2 group, and f is the Example 3 group. DETAILED DESCRIPTION

[0026] The embodiments of the present invention are described in detail below. The embodiments described below are exemplary and are only used to explain the present invention, and should not be understood as limiting the present invention.

[0027] The endpoints and any values ​​of the ranges disclosed in this article are not limited to the precise ranges or values, and these ranges or values ​​should be understood to include values ​​close to these ranges or values. For numerical ranges, the endpoint values ​​of each range, the endpoint values ​​of each range and the individual point values, and the individual point values ​​can be combined with each other to obtain one or more new numerical ranges, which should be considered as specifically disclosed in this article.

[0028] As used herein, the term "treatment" or "prevention" refers to both therapeutic treatment measures and preventive or prophylactic measures, and its purpose is to refer to obtaining the desired pharmacological and / or physiological effect. The effect may be preventive in terms of completely or partially preventing a disease or its symptoms, and / or may be therapeutic in terms of partially or completely curing a disease and / or the adverse effects caused by the disease. "Treatment" or "prevention" as used herein covers diseases in mammals, especially humans, and includes: (a) preventing the occurrence of a disease or condition in an individual who is susceptible to the disease but has not yet been diagnosed with the disease; (b) inhibiting the disease, such as blocking the development of the disease; or (c) alleviating the disease, such as alleviating the symptoms associated with the disease. "Treatment" or "prevention" as used herein covers any medication that administers a drug to an individual to treat, cure, alleviate, improve, reduce or inhibit the individual's disease, including but not limited to administering a drug described herein to an individual in need.

[0029] In this article, the term "influenza A" refers to an acute respiratory infectious disease caused by influenza A virus (including H1, H2, H3, H5, H7, H9 and H10 subtypes). Specifically, influenza A includes one or more of influenza A H1N1, influenza A H2H2, influenza A H3N2, influenza A H5N1, influenza A H7N1, influenza A H7N2, influenza A H7N3, influenza A H7N7, influenza A H7N9, influenza A H9N2, influenza A H10N8. Preferably, influenza A includes one or more of influenza A H1N1, influenza A H5N1, influenza A H7N9. Most preferably, influenza A is influenza A H1N1.

[0030] In this article, "pharmaceutically acceptable excipients" are pharmaceutically acceptable carriers, solvents, suspending agents or excipients for delivering the compositions of the present invention to animals or humans. Exemplary excipients can be liquid or solid, including but not limited to: pH regulators, surfactants, adjuvants, antioxidants, chelating agents, ionic strength enhancers, preservatives, carriers, glidants, sweeteners, dyes / colorants, flavor enhancers, wetting agents, dispersants, suspending agents, stabilizers, isotonic agents, solvents, emulsifiers, sprays, or other suitable inactive ingredients used in combination with active ingredients.

[0031] The scheme of the present invention will be explained below in conjunction with the embodiments. It will be appreciated by those skilled in the art that the following embodiments are only used to illustrate the present invention and should not be considered as limiting the scope of the present invention. Where specific techniques or conditions are not indicated in the embodiments, the techniques or conditions described in the literature in this area or the product specifications are used. The reagents or instruments used are not indicated by the manufacturer and are all conventional products that can be obtained commercially.

[0032] Example 1

[0033] 1. Recipe:

[0034] 125 parts of Flos Lonicerae, 125 parts of Fructus Forsythiae, 125 parts of Radix Isatidis, 75 parts of Radix Scutellariae, 50 parts of Folium Mori, 50 parts of Flos Chrysanthemi, 50 parts of Sterculia Lycopodiellae, 50 parts of Fructus Arcti, 50 parts of Periostracum Cicadae, 50 parts of Peucedanum, 50 parts of Bombyx Batryticatus, 50 parts of Apricot Kernel.

[0035] 2. Preparation method

[0036] (1) Fry the silkworm bran and peel the bitter almonds. Set aside.

[0037] (2) Grind the Radix Isatidis and Bombyx Batryticatus into fine powder, pass through a 100-120 mesh sieve, mix well, and set aside.

[0038] (3) Grind honeysuckle, forsythia suspensa and bitter almond into 60% coarse powder, extract twice with 80% ethanol under heating and reflux, each time for 2 hours, combine the extracts, filter and collect the filtrate.

[0039] (4) The residue from step (3) and the remaining seven Chinese medicinal herbs are decocted twice with water, each time for 2 hours, the decoctions are combined, filtered, and the filtrate is concentrated to a clear paste with a relative density of 1.28-1.30 at a temperature of 25° C., ethanol is added to make the alcohol content reach 70%, stirred evenly, allowed to stand, filtered, and the filtrate is combined with the alcohol extract from the above step (3), the ethanol is recovered and concentrated to a clear paste with a relative density of 1.38-1.40 at a temperature of 60° C., and the fine powder prepared in step (2) is added, stirred evenly, dried, granulated, and filled into capsules to obtain the product.

[0040] Comparative Example 1

[0041] 1. Formulation

[0042] 125 parts of Flos Lonicerae, 125 parts of Fructus Forsythiae, 125 parts of Radix Isatidis, 75 parts of Rhizoma Coptidis, 50 parts of Folium Mori, 50 parts of Flos Chrysanthemi, 50 parts of Sterculia Lycopodiellae, 50 parts of Fructus Arcti, 50 parts of Periostracum Cicadae, 50 parts of Peucedanum, 50 parts of Bombyx Batryticatus, and 50 parts of Apricot Kernel.

[0043] 2. Preparation method

[0044] (1) Fry the silkworm bran and peel the bitter almonds. Set aside.

[0045] (2) Grind the Radix Isatidis and Bombyx Batryticatus into fine powder, pass through a 100-120 mesh sieve, mix well, and set aside.

[0046] (3) Grind honeysuckle, forsythia suspensa and bitter almond into 60% coarse powder, extract twice with 80% ethanol under heating and reflux, each time for 2 hours, combine the extracts, filter and collect the filtrate.

[0047] (4) The residue from step (3) and the remaining seven Chinese medicinal herbs are decocted twice with water, each time for 2 hours, the decoctions are combined, filtered, and the filtrate is concentrated to a clear paste with a relative density of 1.28-1.30 at a temperature of 25° C., ethanol is added to make the alcohol content reach 70%, stirred evenly, allowed to stand, filtered, and the filtrate is combined with the alcohol extract from the above step (3), the ethanol is recovered and concentrated to a clear paste with a relative density of 1.38-1.40 at a temperature of 60° C., and the fine powder prepared in step (2) is added, stirred evenly, dried, granulated, and filled into capsules to obtain the product.

[0048] Example 2

[0049] 1. Recipe:

[0050] 125 parts of Flos Lonicerae, 125 parts of Fructus Forsythiae, 125 parts of Scrophulariae, 125 parts of Radix Isatidis, 50 parts of Red Peony Roots, 75 parts of Radix Scutellariae, 50 parts of Folium Mori, 50 parts of Flos Chrysanthemi, 50 parts of Peucedanum, 50 parts of Amaranthus Bitter, 50 parts of Fructus Arcti, 50 parts of Rhizoma Alismatis, 50 parts of Sterculia Lycopodiellae, 50 parts of Bombyx Batryticatus, 50 parts of Periostracum Cicadae, and 50 parts of Oroxylum Indici.

[0051] 2. Preparation method

[0052] (1) Fry the silkworm bran and peel the bitter almonds. Set aside.

[0053] (2) Grind the Radix Isatidis and Bombyx Batryticatus into fine powder, pass through a 100-120 mesh sieve, mix well, and set aside.

[0054] (3) Grind honeysuckle, forsythia, red peony root and bitter almond into 60% coarse powder, extract twice with 80% ethanol under heating and reflux, each time for 2 hours, combine the extracts, filter and collect the filtrate.

[0055] (4) The residue from step (3) and the remaining ten kinds of Chinese medicine such as Scrophularia ningpoensis and Scutellaria baicalensis are decocted twice with water, each time for 2 hours, the decoctions are combined, filtered, and the filtrate is concentrated to a clear paste with a relative density of 1.28-1.30 at a temperature of 25°C, ethanol is added to make the alcohol content reach 70%, stirred evenly, allowed to stand, filtered, and the filtrate is combined with the alcohol extract from the above step (3), the ethanol is recovered and concentrated to a clear paste with a relative density of 1.38-1.40 at a temperature of 60°C, and the fine powder prepared in step (2) is added, stirred evenly, dried in a room temperature oven at 70-80°C, granulated, and filled into 1000 capsules to obtain the product.

[0056] Comparative Example 2

[0057] 1. Formulation

[0058] 110 parts of Flos Lonicerae, 110 parts of Fructus Forsythiae, 140 parts of Scrophulariae, 140 parts of Radix Isatidis, 70 parts of Red Peony Root, 90 parts of Radix Scutellariae, 30 parts of Folium Mori, 30 parts of Flos Chrysanthemi, 30 parts of Peucedanum, 30 parts of Apricot Kernel, 30 parts of Fructus Arcti, 30 parts of Rhizoma Alismatis, 30 parts of Sterculia Lycopodiellae, 30 parts of Bombyx Batryticatus, 30 parts of Periostracum Cicadae, and 30 parts of Oroxylum Indici.

[0059] 2. Preparation method

[0060] Same as Example 2.

[0061] Example 3

[0062] 1. Formulation

[0063] 115 parts of Flos Lonicerae, 115 parts of Fructus Forsythiae, 115 parts of Scrophulariae, 115 parts of Radix Isatidis, 40 parts of Red Peony Roots, 65 parts of Radix Scutellariae, 40 parts of Folium Mori, 40 parts of Flos Chrysanthemi, 40 parts of Peucedanum, 40 parts of Amaranthus Bitter, 40 parts of Fructus Arcti, 40 parts of Rhizoma Alismatis, 40 parts of Sterculia Lycopodiellae, 40 parts of Bombyx Batryticatus, 40 parts of Periostracum Cicadae, and 40 parts of Oroxylum Indici.

[0064] 2. Preparation method

[0065] Same as Example 2.

[0066] Example 4

[0067] 1. Formulation

[0068] 135 parts of Flos Lonicerae, 135 parts of Fructus Forsythiae, 135 parts of Scrophulariae, 135 parts of Radix Isatidis, 60 parts of Red Peony Roots, 85 parts of Radix Scutellariae, 60 parts of Folium Mori, 60 parts of Flos Chrysanthemi, 60 parts of Peucedanum, 60 parts of Amarum Bitter, 60 parts of Fructus Arcti, 60 parts of Rhizoma Alismatis, 60 parts of Sterculia Lycopodiellae, 60 parts of Bombyx Batryticatus, 60 parts of Periostracum Cicadae, and 60 parts of Oroxylum Indici.

[0069] 2. Preparation method

[0070] Same as Example 2.

[0071] Example 5

[0072] 1. Recipe:

[0073] 115 parts of Flos Lonicerae, 115 parts of Fructus Forsythiae, 115 parts of Scrophulariae, 115 parts of Radix Isatidis, 40 parts of Red Peony Roots, 65 parts of Radix Scutellariae, 40 parts of Folium Mori, 40 parts of Flos Chrysanthemi, 40 parts of Peucedanum, 40 parts of Amaranthus Bitter, 40 parts of Fructus Arcti, 40 parts of Rhizoma Alismatis, 40 parts of Sterculia Lycopodiellae, 40 parts of Bombyx Batryticatus, 40 parts of Periostracum Cicadae, and 40 parts of Oroxylum Indici.

[0074] 2. Preparation method

[0075] (1) Fry the silkworm bran and peel the bitter almonds. Set aside.

[0076] (2) Grind all 16 Chinese medicinal herbs into fine powder, pass through a 100-120 mesh sieve, mix well, and set aside.

[0077] (3) Mix 100 parts of fine powder with 35-50 parts of refined honey and an appropriate amount of purified water, and then make 10 pellets weighing 1 gram each through the process of refining, making strips, rolling pills, drying, and selecting pills.

[0078] Example 6

[0079] 1. Formulation

[0080] 135 parts of Flos Lonicerae, 135 parts of Fructus Forsythiae, 135 parts of Scrophulariae, 135 parts of Radix Isatidis, 60 parts of Red Peony Roots, 85 parts of Radix Scutellariae, 60 parts of Folium Mori, 60 parts of Flos Chrysanthemi, 60 parts of Peucedanum, 60 parts of Amarum Bitter, 60 parts of Fructus Arcti, 60 parts of Rhizoma Alismatis, 60 parts of Sterculia Lycopodiellae, 60 parts of Bombyx Batryticatus, 60 parts of Periostracum Cicadae, and 60 parts of Oroxylum Indici.

[0081] 2. Preparation method

[0082] (1) Fry the silkworm bran and peel the bitter almonds. Set aside.

[0083] (2) Grind the Radix Isatidis and Bombyx Batryticatus into fine powder, pass through a 100-120 mesh sieve, mix well, and set aside.

[0084] (3) Grind honeysuckle, forsythia, red peony root and bitter almond into 60% coarse powder, extract twice with 80% ethanol under heating and reflux, each time for 2 hours, combine the extracts, filter and collect the filtrate.

[0085] (4) The residue from step (3) and the remaining ten kinds of Chinese medicine such as Scrophularia ningpoensis and Scutellaria baicalensis are decocted twice with water, each time for 2 hours, the decoctions are combined, filtered, and the filtrate is concentrated to a clear paste with a relative density of 1.28-1.30 at a temperature of 25°C, ethanol is added to make the alcohol content reach 70%, stirred evenly, allowed to stand, filtered, and the filtrate is combined with the alcohol extract from the above step (3), the ethanol is recovered and concentrated to a clear paste with a relative density of 1.38-1.40 at a temperature of 60°C, and then the fine powder prepared in step (2) and auxiliary materials are added to granulate. The auxiliary materials can be dextrin, starch, maltose, magnesium stearate, etc., and then dried in a room temperature oven at 70-80°C, pressed into tablets, and film-coated to obtain the product.

[0086] Example 7

[0087] 1 Experimental Materials

[0088] 1.1 Drugs under investigation

[0089] The Chinese medicine compositions prepared in Example 1, Example 2, Example 3, Example 4 and Comparative Examples 1-2.

[0090] 1.2 Experimental animals

[0091]

[0092] 1.3 Virus strains

[0093] Virus strain name source H1N1 influenza virus FM1 strain ATCC H1N1 influenza virus PR8 strain ATCC

[0094] 1.4 Test reagents

[0095] Reagent name batch number Manufacturer Isoflurane S200106 Shanghai Yuyan Scientific Instrument Co., Ltd. Mouse IL-6 ELISA KIT 11 / 2021 Shanghai ELISA Biotechnology Co., Ltd. <![CDATA[Mouse IL-10valukine TM ELISA KIT]]> 600205 NOVUSBIO Biotechnology Co., Ltd. <![CDATA[Mouse TNF-αvalukine TM ELISA KIT]]> 600309 NOVUSBIO Biotechnology Co., Ltd. Trizol Reagent 257403 Life Technologies USA Influenza Virus A Real Time RT-PCR kit P20210901 Shanghai Zhijiang Biotechnology Co., Ltd. 4% tissue cell fixative DE0094-500ml Beijing Biodi Biotechnology Co., Ltd.

[0096] 1.5 Test equipment

[0097] Instrument Name model Manufacturer Type A2 Biological Safety Cabinet Thermo MSC1.8 Thermo Corporation Electronic balance YP1002 Shanghai Yueping Scientific Instrument Co., Ltd. Electronic balance AL204 Mettler-Toledo Instruments (Shanghai) Co., Ltd. IVC mouse cage ZJ-4 Suzhou Fengshi Co., Ltd. Type A2 Biological Safety Cabinet Thermo MSC1.2 Thermo Corporation Oscillating pyrolysis instrument <![CDATA[Fastprep TM -24]]> MP Biomedicals Real-Time PCR Instrument QuantStudio 5 Applied biosystems Eight-row tube mini centrifuge LX-300 Kylin-Bell Lab Instruments Mini Vortex Mixer OL-901 Haimen Qilin Bell Instrument Manufacturing Co., Ltd. Multifunctional ELISA reader Enspire type PerkinElmer, Germany Centrifuge Eppendorf-5180R Eppendorf, Germany

[0098] 2 Experimental methods and results 2.1 Drug dosage design and preparation

[0099] Clinical dose 2.4g / 60kg / d, orally. Mouse Dosage Clinical dose converted to mouse dose: 2.4g÷60kg×11=0.44g / kg / d Dosage for mice 20ml / kg / d, intragastric administration Preparation concentration 440mg / kg / d÷20ml / kg / d=22mg / ml Preparation method 0.88g, distilled water to 40ml, stored at 4℃

[0100] 2.2 Therapeutic effects of different tested drugs on the pneumonia model of mice induced by H1N1 influenza virus FM1 / PR8 strain

[0101] 2.2.1 Effects of different tested drugs on lung index in the mouse pneumonia model induced by H1N1 influenza virus FM1 / PR8 strain

[0102] 80 ICR mice (SPF grade, 13-15 g) were randomly divided into 8 groups according to body weight: normal control group, model control group, Example 1 group, comparative example 1 group, Example 2 group, comparative example 2 group, Example 3 group, Example 4 group, 10 mice in each group, half male and half female. Except for the normal control group, the mice in other groups were lightly anesthetized with isoflurane and infected with 15 LD 50 H1N1 influenza virus FM1 strain or PR8 strain virus liquid, 35μl per mouse. Each group of mice was given the corresponding drug after infection, and the normal control group and model control group were given distilled water under the same conditions for 4 consecutive days. On the 5th day, the mice were weighed and dissected to weigh the lung wet weight, and the lung index and lung index inhibition rate were calculated. The lung index of each group was expressed as The differences among the groups were analyzed using T test, and P < 0.05 was considered statistically significant.

[0103] The lung tissues of experimental mice infected with influenza virus PR8 strain were fixed with 4% tissue cell fixative and then subjected to histopathological examination. The lung tissues of experimental mice infected with influenza virus FM1 strain were stored at -80°C for testing of inflammatory factors and viral load.

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[0106] The results in Table 1 show that compared with the normal control group, the lung index of the FM1 and PR8 strain infection model control groups were significantly increased (P<0.01); compared with the model control group, the lung index of Examples 1, 2, 3, and 4 were significantly reduced (P<0.05, P<0.01); among them, after FM1 and PR8 strain infection in Example 2, the lung index inhibition rates were 74.40% and 55.58%, respectively, which were slightly higher than those of Example 1, Example 3, and Example 4. Compared with Examples 1, 2, 3, and 4, the lung index of Comparative Examples 1 and 2 was higher and the inhibition rate was lower.

[0107] Table 1 Effects of different tested drugs on H1N1 influenza virus-induced pneumonia model in mice (lung index and inhibition rate)

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[0110] Note: Compared with the normal control group ## P<0.01; compared with the model control group ** P<0.01, * P<0.05.

[0111] 2.2.2 Effects of different tested drugs on the viral load in lung tissue of the mouse pneumonia model induced by H1N1 influenza virus FM1 strain

[0112] Sample extraction: Take the lung tissue out of the -80℃ freezer and add 1mL TRIzol Reagent. Place it on a tissue homogenizer and shake for 20 seconds. Incubate at room temperature for 10-15 minutes and then heat at 4℃, 12000r / min. -1 Centrifuge for 10 min, carefully pipette the supernatant into a new 1.5 mL EP tube (be careful not to suck up the precipitate at the bottom of the tube), add 0.2 mL chloroform, shake vigorously for 15 s, incubate at room temperature for 2-3 min until the liquid separates, and incubate at 4 °C, 12000 r / min -1 Centrifuge for 15 min, carefully pipette the clear supernatant into a new 1.5 mL EP tube, add 0.5 mL isopropanol, mix by inversion, and let stand at room temperature for 30 min, 4 °C, 12000 r / min -1 Centrifuge for 10 min, wash the precipitate with 1 mL of 75% ethanol (make the white precipitate float lightly), 4°C, 7500 r·min -1 Centrifuge for 5 minutes, aspirate and discard the supernatant, briefly dry the RNA precipitate for 5 minutes, dissolve it in 45 μL DEPC water, and store it in a -80°C refrigerator.

[0113] Nucleic acid detection: prepare the reaction system mixture according to the instructions of the kit, load 20μL of the mixture + 5μL of the test product (the test product includes the sample, blank control and a 10-fold gradient dilution standard curve), and perform PCR amplification reaction. Reaction parameters: 45℃10min, 95℃15min; 95℃15s, 60℃60s, 40 cycles; single-point fluorescence detection at 60℃. Fluorescence channel detection selection: Use FAM and HEX / VIC / JOE channels (when using this laboratory model PCR instrument, select "none" for passivereference and quencher). Calculate the viral load based on the standard curve. The viral load of each group is expressed as The differences among the groups were analyzed using T test, and P < 0.05 was considered statistically significant.

[0114] The results in Table 2 show that: there is no viral nucleic acid expression in the lung tissue of mice in the normal control group, and influenza virus nucleic acid is significantly expressed in the lung tissue of mice in the model control group (P<0.01); compared with the model control group, the expression of viral nucleic acid in the lung tissue of groups 1, 2, 3, and 4 was significantly reduced (P<0.01), and Example 2 was the most obvious. Compared with groups 1, 2, 3, and 4, the expression of viral nucleic acid in the lung tissue of groups 1 and 2 of the comparative examples was higher.

[0115] Table 2 Effects of different tested drugs on the pneumonia model of mice induced by H1N1 influenza virus FM1 strain (viral load)

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[0118] Note: Compared with the normal control group ## P<0.01; compared with the model group ** P<0.01.

[0119] 2.2.3 Effects of different tested drugs on inflammatory factors in lung tissue of mice pneumonia model induced by H1N1 influenza virus FM1 strain

[0120] Weigh 50 mg of lung tissue, add 500 μl of saline, use an ultrasonic cell disruptor to homogenize the tissue, use a low-temperature high-speed centrifuge to centrifuge at 4°C, 10,000 rpm for 10 minutes, and aspirate the supernatant. Detect IL-6, IL-10, and TNF-α according to the ELISA test kit operating procedures. The differences among the groups were analyzed using T test, and P < 0.05 was considered statistically significant.

[0121] The results in Table 3 show that compared with the normal control group, the content of inflammatory factors IL-6, IL-10, and TNF-α in the lung tissue of the model control group was significantly increased (P<0.01); compared with the model control group, the content of inflammatory factors IL-6, IL-10, and TNF-α in the lung tissue of Example 1, 2, 3, and 4 groups was significantly reduced (P<0.01), among which the inflammatory factors IL-6 and IL-10 in the lung tissue of Example 2 were most significantly reduced. Compared with Example 1, 2, 3, and 4 groups, the content of inflammatory factors IL-6, IL-10, and TNF-α in the lung tissue of Comparative Example 1 and 2 groups was higher.

[0122] Table 3 Effects of different tested drugs on the pneumonia model of mice induced by H1N1 influenza virus FM1 strain (inflammatory factors in lung tissue)

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[0124] Note: Compared with the normal control group ## P<0.01; compared with the model control group ** P<0.01.

[0125] 2.2.4 Effects of different tested drugs on pathological changes in lung tissue of the mouse pneumonia model induced by H1N1 influenza virus PR8 strain

[0126] The lung tissues fixed in tissue cell fixative were taken out after 48 hours, rinsed with running water, dehydrated with gradient ethanol, transparentized with xylene, embedded in wax, and sliced; the slices were stained with HE, observed under a microscope, and photographed. The rank sum test was used to analyze the pathological changes between the groups, and P<0.05 was considered statistically significant.

[0127] Microscopic observation standards:

[0128] “-”: No exudation was observed in the alveoli of the mouse lung tissue, no inflammation was observed in the interstitium, no alveolar fusion was observed, no inflammation was observed around the bronchioles in the lung, and the tissue structure was normal.

[0129] “+”: There was mild red blood cell infiltration and a small amount of lymphocyte infiltration in the alveolar interstitium of the mouse lung tissue, no obvious proliferation and enlargement of B cells, and no obvious inflammation around the bronchioles in the lungs.

[0130] “++”: There is mild congestion in the alveolar interstitium of the mouse lung tissue, with a small amount of mucus and inflammatory exudate, mainly lymphocytes, mild edema in the lung tissue, and mild inflammatory exudate around the bronchioles in the lung.

[0131] “+++”: There is a large area of ​​inflammatory exudate in the alveolar interstitium of the mouse lung tissue, mainly composed of lymphocytes, and there is a large area of ​​interstitial congestion; the tissue is edematous, and there are a small number of eosinophils; pink mucus exudates in the lung interstitium, and there are no cellular components in the mucus.

[0132] "++++": There is a large area of ​​congestion in the alveolar interstitium of the mouse lung tissue, tissue edema, and a large amount of inflammatory exudate, mainly lymphocytes, with some eosinophils. There is a large area of ​​pink mucus exudation in the lung interstitium, the mucus has no cellular components, the blood vessels are hyalinized, and the lesions are diffuse.

[0133] Table 4 Figure 1 , Figure 2The results showed that the alveoli of the lung tissue of the mice in the normal control group did not show significant enlargement, interstitial thickening, and interstitial cells did not increase; there was no obvious inflammation around the bronchioles in the lungs, and the lung tissue structure was normal. The mice in the model control group had large-area inflammatory exudation in the interstitial tissue of the lung tissue, mainly lymphocytes, and granulocyte lobed nuclear exudation, obvious proliferation of tissue cells, and uneven size of the proliferated cells. There was a large area of ​​ground-glass degeneration in the lung tissue, and there was congestion exudation, tissue edema, and thick mucus exudation. The inflammation around the bronchioles in the lungs was more severe, and there was inflammatory endothelial shedding in the bronchiolar cavity, and apoptotic cells were common. Compared with the model control group, the exudative inflammation of the lung tissue, increased inflammatory cells, tissue edema, mucus exudation, inflammation around the bronchioles in the lungs, endothelial thickening and other lesions in the mice in Example 1, 2, 3, and 4 groups were alleviated to varying degrees. Compared with the normal control group, the lung tissue and bronchiolar lesions in the model control group were significantly aggravated (P<0.01); compared with the model control group, the lung tissue and bronchiolar lesions in Example 1, 2, 3, and 4 groups were significantly improved (P<0.01), and Example 2 was the most obvious; compared with Example 1, 2, 3, and 4 groups, the lung tissue and bronchiolar lesions in Comparative Examples 1 and 2 groups were more serious (the number of "++" and "+++" was larger). This shows that the use of the Chinese medicine composition of the present invention can effectively reduce pulmonary inflammatory pathological damage.

[0134] Table 4 Effects of different tested drugs on the pneumonia model of mice induced by H1N1 influenza virus PR8 strain (pathology)

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[0137] Note: P values ​​are compared with the model control group

[0138] In summary, the Chinese medicine composition of the present invention has a preventive and / or therapeutic effect on influenza A and the lung damage caused by it, and can significantly reduce the influenza virus load and reduce the expression of inflammatory factors IL-6, IL-10 and / or TNF-α caused by infection.

[0139] Although the embodiments of the present invention have been shown and described above, it is to be understood that the above embodiments are exemplary and are not to be construed as limitations of the present invention. A person skilled in the art may change, modify, replace and vary the above embodiments within the scope of the present invention.

Claims

1. Use of the composition in preparing a medicine, characterized in that: The medicine is used for preventing and / or treating influenza A; The composition comprises: honeysuckle, forsythia, isatis root, scutellaria, mulberry leaf, chrysanthemum, Sterculia lychnophora, burdock fruit, cicada shell, peucedanum peucedanum, bombyx batryticatus and bitter almond.

2. The use according to claim 1, characterized in that The composition comprises: 115-135 parts by weight of honeysuckle, 115-135 parts by weight of forsythia, 115-135 parts by weight of isatis root, 65-85 parts by weight of scutellaria, 40-60 parts by weight of mulberry leaves, 40-60 parts by weight of chrysanthemum, 40-60 parts by weight of sterculia lychnophora, 40-60 parts by weight of burdock seeds, 40-60 parts by weight of cicada shells, 40-60 parts by weight of peucedanum peucedanum, 40-60 parts by weight of bombyx batryticatus, and 40-60 parts by weight of bitter almonds.

3. The use according to claim 1, characterized in that The composition comprises: honeysuckle, forsythia, isatis root, scutellaria, mulberry leaf, chrysanthemum, peucedanum, bitter almond, burdock fruit, Sterculia lychnophora, bombyx batryticatus, cicada shell, Scrophularia ningpoensis, red peony root, oriental water plantain and oroxylum butterfly.

4. The use according to claim 3, characterized in that The composition comprises: 115-135 parts by weight of honeysuckle, 115-135 parts by weight of forsythia, 115-135 parts by weight of isatis root, 65-85 parts by weight of scutellaria, 40-60 parts by weight of mulberry leaves, 40-60 parts by weight of chrysanthemum, 40-60 parts by weight of sterculia lychnophora, 40-60 parts by weight of burdock seeds, 40-60 parts by weight of cicada shells, 40-60 parts by weight of peucedanum peucedanum, 40-60 parts by weight of bombyx batryticatus, 40-60 parts by weight of bitter almonds, 115-135 parts by weight of scrophularia, 40-60 parts by weight of red peony root, 40-60 parts by weight of orientalis, and 40-60 parts by weight of oroxylum butterfly.

5. The use according to claim 1, characterized in that: The composition further includes a pharmaceutically acceptable excipient.

6. The use according to any one of claims 1 to 5, characterized in that: The medicine is used for reducing the content of inflammatory factors IL-6, IL-10 and / or TNF-α in lung tissue.

7. The use according to any one of claims 1 to 5, characterized in that: The medicine is in the form of pills, tablets, capsules, oral liquid or syrup.

8. The use according to any one of claims 1 to 5, characterized in that: The influenza A is selected from one or more of influenza A H1N1, H2H2, H3N2, H5N1, H7N1, H7N2, H7N3, H7N7, H7N9, H9N2, and H10N8, preferably selected from one or more of influenza A H1N1, H5N1, and H7N9.

9. The use according to any one of claims 1 to 5, characterized in that: The drug is used for preventing and / or treating lung damage caused by influenza A. Preferably, the lung damage is selected from inflammatory pathological damage of the lung.

10. The use according to any one of claims 1 to 5, characterized in that: The drug is used to reduce influenza A viral load.

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