Compound granules for treating and resisting viruses as well as preparation method and application of compound granules

Abstract

The invention provides compound granules for treating and resisting viruses as well as a preparation method and application of the compound granules. The compound granules comprise the following components in parts by weight: 15-45 parts of artemisia rupestris, 10-30 parts of adiantum, 15-45 parts of cordia dichotoma fruits, 15-45 parts of chicory seeds, 12-36 parts of viola tianshanensis, 10-30 parts of water lily flowers, 12-36 parts of humifuse euphorbia herb, 6-18 parts of rose petals and 5-15 parts of puffball. The compound granules containing the nine medicinal materials according to the ratio can improve the antiviral effect, are more effective in treatment of upper respiratory infection, have relatively weak toxicity and small side effects, particularly avoid the side effects of diarrhea, are convenient to take and carry, better in taste and relatively good in compliance, and are suitable for clinical application. Good application and popularization prospects are realized in the aspect of upper respiratory tract infection treatment.

Description

Technical Field

[0001] The present invention relates to the field of medical technology, and in particular to a compound granule for antiviral treatment, a preparation method thereof, and an application thereof. Background Art

[0002] Upper respiratory tract infection, abbreviated as "Upper respiratory infection", is a general term for acute inflammation of the nasal cavity, pharynx or throat, including a series of acute diseases that affect the antiviral system, such as acute rhinitis, acute pharyngitis, laryngitis, viral pharyngitis, herpes pharyngitis and "common cold" and so on. The main pathogens of upper respiratory tract infection are viruses, and a few are bacteria, including coronaviruses, rhinoviruses, adenoviruses, etc. The clinical incidence of this disease is extremely high and can occur throughout the year. It is more common in winter and spring and during periods of climate change. Children are susceptible to the disease and it can be transmitted through direct contact or droplets. The main clinical symptoms are dry throat, itchy throat, fever, cough, nasal congestion, runny nose, etc.

[0003] Currently, there is no specific treatment for upper respiratory tract infections. Western medicine primarily targets the typical symptoms of upper respiratory tract infections, using antiviral drugs for viral infections and antibiotics for bacterial infections, along with antipyretics, analgesics, antihistamines, and other medications. While these can effectively control clinical symptoms, the emergence of resistant strains and the emergence of viral strains have made long-term, repeated use of antiviral and antibiotic drugs in adults less effective, and they can also negatively impact the growth, development, and physical and mental health of children. Traditional Chinese Medicine classifies these conditions as "colds" or "febrile diseases." These conditions are caused by congenital or acquired internal organ weakness, weakened defenses, and vulnerable to external pathogens with the changing seasons. These pathogens enter the body through the mouth, nose, and skin, transforming into heat. This heat accumulates in the upper Jiao (burned-in-the-heart) and causes dry mouth and sore throat. Heat invades the clear orifices, causing headaches. The conflict between pathogenic and righteous forces causes fever. The lungs fail to descend, leading to nasal congestion and cough. Traditional Chinese Medicine categorizes pathogenic factors into three types: wind-cold, wind-heat, and summer-heat dampness. Treatments include dispersing wind and relieving exterior symptoms, relieving exterior symptoms with pungent and warm herbs, and clearing away summer heat. The most commonly used methods are dispersing wind-heat and clearing away heat and detoxifying. These methods offer the advantages of syndrome differentiation, integrated internal and external treatment, definite efficacy, minimal side effects, and resistance to drug resistance.

[0004] However, traditional Chinese medicine decoctions are inconvenient to consume and boil, and traditional extraction processes do not fully extract the active ingredients, resulting in toxic components that can cause adverse side effects (such as diarrhea) in patients. This makes the safety of traditional Chinese medicine decoctions unclear and their therapeutic effectiveness compromised. Therefore, developing an antiviral compound that is clinically convenient, effective, requires a small dosage, and has minimal side effects is of great significance for the effective and safe treatment of upper respiratory tract infections. Summary of the Invention

[0005] The main purpose of the present invention is to provide a compound granule for treating antiviral diseases and its preparation method and application, so as to solve the problem in the prior art of lack of compound granules specifically for treating diseases caused by viruses.

[0006] In order to achieve the above-mentioned object, according to the first aspect of the present invention, a compound granule for treating viruses is provided, which comprises: 15-45 parts of Artemisia annua, 10-30 parts of Adiantum officinale, 15-45 parts of Xanthocarpus tataricus, 15-45 parts of Chicory seeds, 12-36 parts of Viola tianshanica, 10-30 parts of Water Lily, 12-36 parts of Herba Lycopodii, 6-18 parts of Rose petals and 5-15 parts of Atractylodes macrocephala.

[0007] In order to achieve the above-mentioned purpose, according to the second aspect of the present invention, a preparation method of the above-mentioned compound granules for treating viruses is provided, and the preparation method comprises: S1, extracting and filtering a mixture of chicory seeds, violets of Tianshan Mountains and Artemisia annua using an alcohol solution to obtain an alcohol extraction solution and medicinal residues; S2, mixing the medicinal residues with water lilies, herba euphorbiae, ragwort fruit, rose petals, iris and adiantum to obtain a medicinal material mixture; decocting and filtering the medicinal material mixture with water to obtain a medicinal liquid; S3, mixing the alcohol extraction solution and the medicinal liquid to prepare the compound granules.

[0008] Furthermore, S1 includes: repeatedly refluxing and extracting the mixture of chicory seeds, violet herb and Artemisia striata with an alcohol solution; mixing and concentrating the filtrates of the repeated reflux extraction to obtain an alcohol extraction solution and medicinal residues.

[0009] Furthermore, the mass concentration of the alcohol solution is 55-60%; preferably, the mass ratio of the mixture of chicory seeds, violet tianshanica and artemisia striata to the alcohol solution is 1:8-10; preferably, the number of reflux extractions is 2-3 times; preferably, the reflux extraction time is 0.5-1 hour.

[0010] Furthermore, the concentration is reduced-pressure concentration; preferably, the pressure of the reduced-pressure concentration is -0.02 to -0.09 MPa; preferably, the temperature of the reduced-pressure concentration is 60 to 80° C. Preferably, the density of the concentrated alcohol extract solution is 1.1 to 1.2 times that of the unconcentrated solution.

[0011] Furthermore, S2 includes: repeatedly decocting and filtering the medicinal material mixture with water to obtain a medicinal liquid to be concentrated; concentrating the medicinal liquid to be concentrated to obtain a medicinal liquid; preferably, the mass ratio of the medicinal material mixture to water is 1:8-10; preferably, the particle size of the ragwort is 4-8mm; preferably, the particle size of the albifrons is 4-8mm; preferably, the number of decoctions is 2-3 times; preferably, the decoction time is 0.5-1 hour.

[0012] Furthermore, the concentration is reduced-pressure concentration; preferably, the pressure of the reduced-pressure concentration is -0.02 to -0.09 MPa; preferably, the temperature of the reduced-pressure concentration is 60 to 80° C. Preferably, the density of the concentrated medicinal solution is 1.0 to 1.1 times that of the unconcentrated solution.

[0013] Furthermore, S3 includes: mixing the alcohol extraction solution and the medicinal solution, and then centrifuging, filtering and concentrating in sequence to obtain a concentrated mixture; and mixing the concentrated mixture with excipients to obtain compound granules.

[0014] Furthermore, the centrifugal speed is 15000-20000 rpm / min; preferably, the concentration is reduced pressure concentration; preferably, the pressure of reduced pressure concentration is -0.02 to -0.09 MPa; preferably, the temperature of reduced pressure concentration is 60 to 80°C; preferably, the density of the concentrated mixture is 1.05 to 1.20 times that of the unconcentrated mixture; preferably, the mass ratio of the concentrated mixture to the auxiliary material is 1:0.30 to 0.45; preferably, the auxiliary material includes dextrin and lactose; preferably, the mass ratio of dextrin to lactose is 1:1 to 1.4.

[0015] In order to achieve the above object, according to the third aspect of the present invention, a compound granule for treating viruses obtained by the above preparation method is provided.

[0016] In order to achieve the above object, according to the fourth aspect of the present invention, there is provided a use of the compound particles for treating viruses obtained by the above preparation method in the preparation of drugs for treating viruses.

[0017] By applying the technical solution of the present invention, the compound granules containing the nine medicinal materials and their proportions can improve the antiviral effect, are more effective in treating upper respiratory tract infections, have weak toxicity and small side effects, especially avoid the side effect of diarrhea, are easy to take and carry, have a better taste, and have good compliance, and have good application and promotion prospects in the treatment of upper respiratory tract infections. DETAILED DESCRIPTION

[0018] It should be noted that, in the absence of conflict, the embodiments and features in the embodiments of the present application can be combined with each other. The present invention will be described in detail below with reference to the embodiments.

[0019] As mentioned in the background, existing Chinese herbal decoctions are difficult to decoct, and traditional extraction processes do not fully extract the active ingredients. This results in toxic components in these decoctions that can cause adverse side effects for patients, making their safety uncertain and their therapeutic effectiveness compromised. Therefore, this application aims to provide an antiviral compound that is clinically convenient, effective, and has minimal side effects.

[0020] To achieve the above object, according to a first aspect of the present invention, a compound granule for treating viruses is provided, comprising: 15-45 parts of Artemisia rupestris L., 10-30 parts of Adiantum venustum Don.var. venustum, 15-45 parts of Cordia dichotoma Forst., 15-45 parts of Cichorium glandulosum Boiss. Et Huet., 12-36 parts of Viola tianshanica Maxim, 10-30 parts of Nymphaea candida C. Presl, 12-36 parts of Euphorbia humifusa Willd or Euphorbia maculata L., 6-18 parts of Rose petals (Rosa damascena Mill. or Rosa rugosa Thunb.), and 5-15 parts of Cassia fistula L. The compound granules with the above composition have improved resistance to viruses compared with traditional Chinese medicine decoctions, and have removed some ingredients that may cause side effects of the drugs (such as diarrhea caused by senna leaves), thereby reducing the toxicity of the drugs and being more effective in treating upper respiratory tract infections.

[0021] Among them, existing studies have shown that chemical components such as sesquiterpenes and flavonoids are the main active ingredients for antiviral and anti-inflammatory effects.

[0022] Artemisia striata mainly contains sesquiterpenes, flavonoids, organic acids, alkaloids, glycosides, and polysaccharides, and has the effects of clearing heat and detoxifying, promoting digestion and strengthening the stomach, protecting the liver and promoting bile secretion. It is often clinically effective in treating influenza virus and hepatitis. Chicory seeds mainly contain flavonoids and polyphenols, and have the effects of regulating abnormal blood constitution, clearing heat and reducing inflammation. In terms of pharmacological effects, they can resist free radicals and have antioxidant effects. Tianshan Viola mainly contains flavonoids, glycosides, steroids, lactones, volatile oils, and tannins, and has the functions of dispelling wind and heat, detoxifying and reducing swelling. In terms of pharmacological effects, they can inhibit bacteria, fight influenza, have antioxidant effects, and have anti-inflammatory effects. The maidenhair fern primarily contains flavonoids, triterpenes, polysaccharides, volatile oils, alkaloids, phenols, and steroids. It also contains small amounts of tannins, various amino acids, and organic acids such as fatty acids. It has antibacterial, anti-tumor, anti-cardiovascular, anti-inflammatory, analgesic, immunomodulatory, hypoglycemic, antioxidant, and anti-aging properties. The fruit of the Chinese taro tree, containing mucilage, polysaccharides, flavonoid glycosides, and phenols, has been shown in modern pharmacological research to have antibacterial, analgesic, anti-tumor, anti-inflammatory, anti-ulcer, antioxidant, and wound-repairing properties.

[0023] On the basis of the original Chinese medicine prescription, senna leaves were reduced and the Psoralea corylifolia with the functions of promoting qi and relieving pain, resolving phlegm and relieving cough, relieving diarrhea, detoxifying and regulating the intestines and the maidenhair fern with the functions of clearing away heat and dampness, reducing swelling and detoxifying, relieving cough and relieving asthma, and promoting diuresis and promoting forestation were added. Together, they play the role of clearing heat, resolving phlegm and detoxifying, and can guide the heat-clearing and detoxifying drugs to the lung meridian. In addition, Artemisia selengensis with the functions of dispelling wind and relieving exterior symptoms, strengthening the stomach and eliminating accumulation, and promoting blood circulation and dispersing blood stasis was added. It can be combined with Tianshan Viola and Water Lotus to relieve exterior symptoms in a pungent and cool way, and can also be combined with Chicory Seed, Elaeagnus amurense and Psoralea corylifolia to strengthen the spleen and eliminate accumulation to strengthen the body, and relieve heat and promote bowel movements to eliminate evil.

[0024] In order to achieve the above-mentioned purpose, according to the second aspect of the present invention, a preparation method of the above-mentioned compound granules for treating viruses is provided, which comprises: S1, extracting and filtering a mixture of chicory seeds, violets of Tianshan Mountains and Artemisia annua using an alcohol solution to obtain an alcohol extract solution and medicinal residues; S2, mixing the medicinal residues with water lilies, herba euphorbiae, ragwort fruit, rose petals, iris and adiantum to obtain a medicinal material mixture; decocting and filtering the medicinal material mixture with water to obtain a medicinal liquid; S3, mixing the alcohol extract solution and the medicinal liquid to prepare the compound granules.

[0025] Among them, since components such as flavonoids, sesquiterpenes, and lactones are easily soluble in alcohol, and components such as polyphenols and glycosides are easily soluble in water, existing studies have shown that the above-mentioned water-soluble and alcohol-soluble components have the effect of treating antiviral infections. Therefore, it is necessary to use alcohol solution and water to extract the effective substances in different components respectively. The present application first extracts three medicinal materials, namely, chicory seeds, Tianshan violets, and Artemisia selengensis, with an alcohol solution to obtain alcohol-soluble components. The filtered medicinal residues are then mixed with six medicinal materials, namely, water lily, herba euphorbiae, ragwort, rose petals, euphorbia pulcherrima, and adiantum, and extracted with an aqueous solution to obtain water-soluble components, so that all potential medicinal ingredients are extracted as completely as possible.

[0026] In order to further fully extract the active ingredients from these three medicinal materials, in a preferred embodiment, S1 includes: repeatedly reflux extraction of a mixture of chicory seeds, violet herb and Artemisia argyi using an alcohol solution; mixing and concentrating the filtrates of the repeated reflux extraction to obtain an alcohol extraction solution and medicinal residues.

[0027] In order to more efficiently extract the active ingredients soluble in alcohol from the three medicinal materials, in a preferred embodiment, the mass concentration of the alcohol solution is 55-60%; the alcohol solution includes: ethanol solution; preferably, the mass ratio of the mixture of chicory seeds, violet tianshanica and Artemisia annua to the alcohol solution is 1:8-10; preferably, the number of reflux extractions is 2-3 times; preferably, the reflux extraction time is 0.5-1 hour.

[0028] To facilitate subsequent mixing with the aqueous extract, the alcohol extract is further concentrated. In a preferred embodiment, the concentration is performed under reduced pressure. Preferably, the pressure of the reduced pressure concentration is -0.02 to -0.09 MPa; preferably, the temperature of the reduced pressure concentration is 60 to 80°C. Preferably, the density of the concentrated alcohol extract solution is 1.1 to 1.2 times that of the unconcentrated solution.

[0029] In order to further fully extract the effective ingredients soluble in water from the remaining medicinal materials, in a preferred embodiment, S2 includes: repeatedly decocting and filtering the medicinal material mixture with water to obtain a medicinal liquid to be concentrated; concentrating the medicinal liquid to be concentrated to obtain a medicinal liquid; preferably, the mass ratio of the medicinal material mixture to water is 1:8-10; preferably, the particle size of the ragwort is 4-8mm; preferably, the particle size of the albifrons is 4-8mm; preferably, the number of decoctions is 2-3 times; preferably, the decoction time is 0.5-1 hour.

[0030] To facilitate mixing with the alcohol extract, the aqueous extract is further concentrated. In a preferred embodiment, the concentration is performed under reduced pressure; preferably, the pressure of the reduced pressure concentration is -0.02 to -0.09 MPa; preferably, the temperature of the reduced pressure concentration is 60 to 80°C. Preferably, the density of the concentrated medicinal solution is 1.0 to 1.1 times that of the unconcentrated solution.

[0031] In order to further obtain compound granules with high compliance, good taste and easy portability, in a preferred embodiment, S3 includes: mixing the alcohol extraction solution and the medicinal solution, and then centrifuging, filtering and concentrating in sequence to obtain a concentrated mixture; mixing the concentrated mixture with dextrin and lactose to obtain compound granules.

[0032] To prepare granules from the drug extract without losing the active ingredients of the drug, in a preferred embodiment, the centrifugal speed is 15,000-20,000 rpm / min; preferably, the concentration is concentrated under reduced pressure; preferably, the temperature for reduced pressure concentration is 60-80°C; preferably, the density of the concentrated mixture is 1.05-1.20 times that of the unconcentrated mixture; preferably, the mass ratio of the concentrated mixture to the excipient is 1:0.30-0.45; preferably, the excipient includes dextrin and lactose; preferably, the mass ratio of dextrin to lactose is 1:1-1.4. Using appropriate amounts of excipients, a compound granular drug that is easy to take and carry can be obtained.

[0033] To achieve the above objectives, according to a third aspect of the present invention, a compound granule for treating viruses, obtained by the above-described preparation method, is provided. The compound granule obtained by the above-described preparation method is easy to take and carry, has strong antiviral efficacy, few side effects, and a pleasant taste, and is particularly suitable for treating upper respiratory tract infections.

[0034] To achieve the above objectives, according to a fourth aspect of the present invention, there is provided a use of the compound granules for treating viruses obtained by the above-described preparation method in the preparation of a medicament for treating viruses. The compound granules obtained by the above-described preparation method are convenient to take and carry, have strong antiviral efficacy, minimal side effects, and a pleasant taste, and play a role in the treatment of upper respiratory tract infections.

[0035] The present application is further described in detail below with reference to specific embodiments. These embodiments should not be construed as limiting the scope of protection claimed in this application.

[0036] Example 1

[0037] Preparation of API:

[0038] 15 parts of chicory seeds, 12 parts of tianshanshan violets, 10 parts of water lilies, 12 parts of herba euphorbiae, 6 parts of rose petals, 5 parts of albifrons, 15 parts of wormwood, 10 parts of adiantum, 15 parts of ragweed fruit.

[0039] The preparation method comprises the following steps:

[0040] Step 1: Prepare the above nine raw medicinal materials according to the above proportions, among which the Ratna oleifera and the Atractylodes macrocephala are crushed and set aside.

[0041] Step 2: Chicory seeds, Viola tianshanica, and Artemisia striata are mixed in appropriate proportions, 420 parts of 60% ethanol is added, and reflux extraction is performed twice, each for 0.5 hours, to obtain the medicinal residue. The filtrates are combined and concentrated under reduced pressure (-0.09 MPa, 60°C) to recover the ethanol, and the filtrate is concentrated to an alcohol extract solution with a relative density of 1.012, which is then set aside.

[0042] Step 3: Combine the residues of chicory seeds, violets of Tianshanshan, and Artemisia scoparia obtained after the second step with water lilies, herba euphorbiae, tamarindus officinalis, rose petals, iris, and maidenhair fern. Add 800 parts of water and boil three times for 1.0 hour each time. Combine the filtrates. Concentrate the filtrates under reduced pressure (-0.09 MPa, 60°C) to a relative density of 1.002 and set aside. The particle size of the tamarind is 4-8 mm, and the particle size of the iris is 4-8 mm.

[0043] Step 4: The alcohol extraction solution obtained in the second and third steps and the medicinal solution are mixed, and high-speed centrifugation (15,000 rpm) is performed. The supernatant is taken and concentrated under reduced pressure (-0.09 MPa, 60° C.) to a concentrated mixture with a relative density of 1.125 for later use.

[0044] Step 5: The concentrated mixture is mixed with excipients (dextrin and lactose) at a dextrin:lactose ratio of 1:1 and a drug-excipient ratio of 1:0.30, and 21.89 portions of granules are prepared by a one-step granulation method, and the granules are granulated to obtain granules.

[0045] Example 2

[0046] Preparation of API:

[0047] 45 parts of chicory seeds, 36 parts of tianshanshan violets, 20 parts of water lilies, 24 parts of herba euphorbiae, 18 parts of rose petals, 10 parts of albifrons, 45 parts of wormwood, 30 parts of adiantum, 30 parts of ragweed fruit.

[0048] The preparation method comprises the following steps:

[0049] Step 1: Prepare the above nine raw medicinal materials according to the above proportions, among which the Ratna oleifera and the Atractylodes macrocephala are crushed and set aside.

[0050] Step 2: Chicory seeds, Viola tianshanica, and Artemisia striata are mixed in appropriate proportions, 1008 parts of 55% ethanol is added, and reflux extraction is performed three times, each for 0.8 hours, to obtain the medicinal residue. The filtrates are combined and concentrated under reduced pressure (-0.02 MPa, 80°C) to recover the ethanol, and the filtrate is concentrated to an alcohol extract solution with a relative density of 0.968, which is then set aside.

[0051] Step 3: Combine the residues of chicory seeds, violets of Tianshanshan, and Artemisia scoparia obtained after the second step with water lilies, herba euphorbiae, tamarindus officinalis, rose petals, iris, and maidenhair fern. Add 2580 parts of water and boil three times for 0.5 hours each time. Combine the filtrates and filter. Concentrate the filtrate under reduced pressure (-0.02 MPa, 80°C) to a relative density of 1.100 and set aside. The particle size of the iris is 4-8 mm, and the particle size of the iris is 4-8 mm.

[0052] Step 4: The alcohol extraction solution obtained in the second and third steps and the medicinal solution are mixed, and high-speed centrifugation (18,000 rpm) is performed. The supernatant is taken and concentrated under reduced pressure (-0.02 MPa, 80° C.) to a concentrated mixture with a relative density of 1.200 for later use.

[0053] Step 5: The concentrated mixture is mixed with excipients (dextrin and lactose) at a dextrin:lactose ratio of 1:1.4 and a drug-excipient ratio of 1:0.45, and 23.07 portions of granules are prepared by a one-step granulation method, and the granules are granulated to obtain granules.

[0054] Example 3

[0055] Preparation of API:

[0056] 30 parts of chicory seeds, 24 parts of tianshanshan violets, 30 parts of water lilies, 36 parts of herba euphorbiae, 12 parts of rose petals, 15 parts of albifrons, 30 parts of wormwood, 20 parts of adiantum, 45 parts of ragweed fruits.

[0057] The preparation method comprises the following steps:

[0058] Step 1: Prepare the above nine raw medicinal materials according to the above proportions, among which the Ratna oleifera and the Atractylodes macrocephala are crushed and set aside.

[0059] Step 2: Chicory seeds, Viola tianshanica, and Artemisia striata are mixed in appropriate proportions, and 756 parts of 58% ethanol are added. Reflux extraction is performed twice, each time for 1.0 hour, to obtain the medicinal residue. The filtrates are combined. The filtrates are concentrated under reduced pressure (-0.05 MPa, 70°C) to recover the ethanol, and the ethanol extract solution is concentrated to a relative density of 1.056, which is then set aside.

[0060] Step 3: Combine the residues of chicory seeds, violets of Tianshanshan, and Artemisia scoparia obtained after the second step with water lilies, herba euphorbiae, tamarindus officinalis, rose petals, iris, and maidenhair fern. Add 2178 parts of water and boil twice, each for 0.8 hours. Combine the filtrates. Concentrate the filtrates under reduced pressure (-0.05 MPa, 70°C) to a relative density of 1.006 and set aside. The particle size of the tamarind is 4-8 mm, and the particle size of the iris is 4-8 mm.

[0061] Step 4: The alcohol extraction solution obtained in the second and third steps and the medicinal solution are mixed, and high-speed centrifugation (20,000 rpm) is performed. The supernatant is taken and concentrated under reduced pressure (-0.05 MPa, 70° C.) to a concentrated mixture with a relative density of 1.051 for later use.

[0062] Step 5: The concentrated mixture is mixed with excipients (dextrin and lactose) at a dextrin:lactose ratio of 1:1.2 and a drug-excipient ratio of 1:0.37. 21.30 portions of granules are prepared by a one-step granulation method, and the granules are granulated to obtain granules.

[0063] Comparative Example 1

[0064] The preparation method is the same as that in Example 1, but the proportion of the raw materials is different. The therapeutic effect of this granule is worse than that of Examples 1-3, as follows:

[0065] 10 parts of chicory seeds, 10 parts of tianshanshan violets, 10 parts of water lilies, 12 parts of herba euphorbiae, 6 parts of rose petals, 5 parts of albifrons, 12 parts of wormwood, 10 parts of adiantum, 15 parts of ragweed fruits.

[0066] Comparative Example 2

[0067] The preparation method is the same as that in Example 2, but the proportion of the raw materials is different. The therapeutic effect of this granule is worse than that of Examples 1-3, as follows:

[0068] 12 parts of chicory seeds, 11 parts of tianshanshan violets, 20 parts of water lilies, 24 parts of herba euphorbiae, 18 parts of rose petals, 18 parts of albifrons, 10 parts of wormwood, 30 parts of adiantum, 30 parts of ragweed fruit.

[0069] Effect test 1

[0070] The compound granules of the present invention were used to treat 20 patients with upper respiratory tract infection. Clinical observation of the 20 outpatient respiratory tract infection patients showed that (runny nose, fever, cough, pharyngeal congestion, swollen tonsils, etc.), the total effective rate of the treatment group was better than that of the control group (oral azithromycin) when the compound granules of Example 1 of the present application were taken orally at a dosage of 8 g / time, 3 times a day.

[0071] Effect test 2

[0072] 23 patients (adults) were treated with the compound granules of Example 1 of the present application for upper respiratory tract infection. The observation results showed that the treatment group took the compound granules of the present application orally at a dosage of 8 g / time, 3 times a day. As shown in Table 1, the treatment group had a significant effect, and the overall therapeutic effect was better than that of the control group (oral azithromycin). After treatment, the serum TNF-α, IL-1β, and IL-4 levels were significantly decreased compared with those before treatment.

[0073] Table 1 Comparison of inflammatory index levels between the two groups

[0074]

[0075] Effect test 3: Effect of compound granules on the mouse pneumonia model induced by human coronavirus 229E

[0076] 1. Trial Grouping and Dosing

[0077] 190 ICR mice, SPF grade, 13-15 g, half male and half female, were randomly divided into 19 groups according to weight, namely a normal control group (administered with distilled water), a model control group (administered with distilled water), an azithromycin control group (administered with azithromycin), a high-dose group (administered with the compound granules in Examples 1-3 and Comparative Examples 1-2), a medium-dose group (administered with the compound granules in Examples 1-3 and Comparative Examples 1-2), a low-dose group (administered with the compound granules in Examples 1-3 and Comparative Examples 1-2), and an original prescription group, with 10 mice in each group. Among them, the high-dose group was administered with a dose of 18.52 g crude drug / kg / d, the medium-dose group was administered with a dose of 9.26 g crude drug / kg / d, and the low-dose group was administered with a dose of 4.63 g crude drug / kg / d. Generally speaking, the medium dose in animal experiments is equivalent to the normal human dose, and the high, medium, and low doses are equivalent to 2 times, the same multiple, and 1 / 2 times the human clinical dose, respectively. The prescription of the original prescription group is: 15 parts of chicory seeds, 12 parts of Tianshan Viola, 10 parts of water lily, 12 parts of ground ivy, 6 parts of rose petals, 2 parts of senna leaves, and 5 parts of Abrus precatorius.

[0078] Except for the normal control group, the other mice were lightly anesthetized with isoflurane and infected with human coronavirus 229E virus stock solution by nasal drops, 50μl / mouse. On the 3rd day, except for the normal control group, the other mice were reinfected once. On the first day of infection, the dose of azithromycin control group was 0.913mg / kg / d, the dose of the original prescription group was 11.33g crude drug / kg / d, and they were gavaged at 0.2ml / 10g body weight. The high-dose group was given a dose of 18.52g crude drug / kg / d, the medium-dose group was given a dose of 9.26g crude drug / kg / d, and the low-dose group was given a dose of 4.63g crude drug / kg / d. The three doses were gavaged at 0.2ml / 10g body weight once a day for 4 consecutive days; the normal control group and the model control group were given distilled water (0.2ml / 10g body weight) under the same conditions. After weighing on the 5th day, the animals were dissected and the following indicators were tested: observation of general physiological indicators, lung index and lung index inhibition rate, whole blood CD4 + T cells, CD8 + T cell percentage, viral load, inflammatory factors.

[0079] 2 Test results

[0080] 2.1 Observation of general physiological indicators

[0081] During the trial, the animals' behavior and physical appearance were normal. The feces of animals in the normal control group, model control group, azvudine control group, high-dose compound granule group, medium-dose compound granule group, and low-dose compound granule group were normal in color and shape, and no diarrhea occurred. Animals in the original prescription group experienced mild / moderate diarrhea, with light-colored, soft, and watery feces.

[0082] 2.2 Effects on mouse lung index

[0083] The Lung Index (LI) is an indicator of lung function in mice, reflecting the health of their lungs and the efficiency of their respiratory system. A high LI indicates lung infection, which can cause systemic symptoms such as high fever, chills, headache, and muscle aches. A drug that can suppress the LI indicates that the drug is effective in treating the infection. Therefore, a higher LI inhibition rate indicates a more effective drug.

[0084] The results in Table 2 show that after mice were infected with human coronavirus 229E, the lung index of mice in the model control group was significantly increased, which was significantly different from that in the normal control group (P<0.01); after 4 days of administration, the high-dose compound granule group and the azvudine group were able to significantly reduce the lung index of mice, which was significantly different from that in the model control group (P<0.05), and the average lung index inhibition rates were 65.53% and 93.13%, respectively.

[0085] Table 2 Effects of compound granules on the mouse pneumonia model induced by human coronavirus 229E

[0086] Group Dosage (g crude drug / kg / d) Number of animals Lung Index Inhibition rate (%) Normal control group - 10 0.72±0.06 - Model control group - 10 <![CDATA[0.82±0.07 ## ]]> - Azithromycin group 0.913 mg / kg / day 10 <![CDATA[0.73±0.09 * ]]> 93.13 Example 1 Low-dose group 4.63 10 0.80±0.05 14.68 Dose group in Example 1 9.26 10 0.80±0.06 14.62 Example 1 High-dose group 18.52 10 <![CDATA[0.76±0.05 * ]]> 63.03 Example 2 low dose group 4.63 10 0.80±0.04 14.29 Example 2 dose group 9.26 10 0.79±0.08 25.87 Example 2 High-dose group 18.52 10 <![CDATA[0.75±0.07 * ]]> 70.21 Example 3 Low-dose group 4.63 10 0.80±0.07 14.58 Example 3 dose group 9.26 10 0.80±0.05 14.01 Example 3 High-dose group 18.52 10 <![CDATA[0.76±0.02 * ]]> 63.36 Comparative Example 1 low dose group 4.63 10 0.81±0.03 13.95 Comparative Example 1: Middle dose group 9.26 10 0.80±0.05 14.63 Comparative Example 1 High-dose Group 18.52 10 0.80±0.01 14.70 Comparative Example 2 low dose group 4.63 10 0.82±0.00 5.33 Comparative Example 2 Middle Dose Group 9.26 10 0.81±0.03 13.56 Comparative Example 2 High-dose Group 18.52 10 0.80±0.06 14.66 Original prescription group 11.33 10 0.80±0.02 14.84

[0087] Note: Compared with the normal control group ## P<0.01; compared with the model control group * P<0.05.

[0088] 2.3 Effects on viral load in mouse lung tissue

[0089] The results in Table 3 show that after mice were infected with human coronavirus 229E, the nucleic acid expression in the lung tissue of mice in the model control group was obvious, which was significantly different from that in the normal control group (P<0.01); after 4 days of administration, the low, medium and high dose groups of the compound granules, as well as the azvudine group and the original prescription group, were able to significantly reduce the nucleic acid expression in the lung tissue of mice, which were significantly different from those in the model control group (P<0.01), and the reduction effect of the medium and high doses of the compound granules was better than that of the original prescription.

[0090] Table 3 Effects of compound granules on the mouse pneumonia model induced by human coronavirus 229E

[0091]

[0092]

[0093] Note: Compared with the normal control group ## P<0.01; compared with the model control group ** P<0.01.

[0094] 2.4 Effect on the percentage of peripheral blood lymphocytes in mice

[0095] The results in Table 4 show that after mice were infected with human coronavirus 229E, the CD4 + T cells, CD8 + The percentage of T cells in the two groups was significantly decreased, and there was a significant difference compared with the normal control group (P<0.01); after 4 days of administration, the medium and high dose groups of the compound granules, the original prescription group, and the azithromycin group were able to increase the CD4 + T cells and CD8 + T cell percentage, and increased CD4 / CD8, of which CD4 + The percentage of T cells increased significantly, and there was a significant difference compared with the model control group (P<0.05, P<0.01). The middle and high doses of compound granules had a significant effect on CD4 + T cells, CD8 + The increase in T cell and CD4 / CD8 percentages was more significant than that of the original prescription.

[0096] Table 4 Effects of compound granules on the mouse pneumonia model induced by human coronavirus 229E

[0097]

[0098]

[0099] Note: Compared with the normal control group # P<0.05; compared with the model control group * P<0.05, ** P<0.01.

[0100] 2.5 Effects on the levels of inflammatory factors in mouse lung tissue

[0101] Interleukin-6 (IL-6) is a cytokine produced by and acting on a variety of cells. Its biological effects are extremely broad, including regulating the growth and differentiation of B cells; enhancing the cytotoxicity of CTL and NK cells; stimulating the proliferation and differentiation of hematopoietic stem cells; and promoting the synthesis of acute phase proteins by hepatocytes. IL-6-secreting cells are found in various systems of the human body, and therefore, IL-6 plays a crucial role in maintaining physiological homeostasis. Illnesses such as colds, influenza, and bacterial pneumonia can compromise the body's immune system, and low interleukin-6 levels can occur following bacterial infection.

[0102] Tumor necrosis factor-α (TNF-α) is a proinflammatory cytokine produced primarily by macrophages and monocytes. It can kill and inhibit tumor cells, promote neutrophil phagocytosis, fight infection, cause fever, induce acute phase protein synthesis in hepatocytes, promote macrophage differentiation in myeloid leukemia cells, and promote cell proliferation and differentiation. It is a key inflammatory factor and is involved in the pathological damage of certain autoimmune diseases. This indicator decreased in the model group compared to the normal group, indicating that the disease causes a decrease in TNF-α, requiring medication to restore it to normal levels.

[0103] Vascular endothelial growth factor (VEGF), also known as vascular permeability factor (VPF), is a highly specific endothelial growth factor that promotes vascular endothelial cell growth. It promotes increased vascular permeability, extracellular matrix degeneration, endothelial cell migration and proliferation, and angiogenesis. This indicator decreased in the model group compared to the normal group, indicating that the disease causes a decrease in TNF-α, requiring medication to restore it to normal levels.

[0104] Interleukin-1β (IL-1β), also known as leukocyte pyogen, leukocyte endogenous mediator, monocytokine, and lymphocyte activation factor, is a typical proinflammatory cytokine that is crucial for the host's defense response to infection and injury. Following tissue damage, IL-1β concentrations may increase at the site of inflammation and at the spinal cord level, and it can also induce the gradual release of other proinflammatory factors, leading to inflammatory pain.

[0105] The results in Table 5 show that after mice were infected with human coronavirus 229E, the levels of IL-6, TNF-α, and VEGF in the lung tissues of mice in the model control group were significantly reduced, with significant differences compared to the normal control group (P<0.01). After 4 days of administration, the high-dose group of the compound granules significantly increased the levels of IL-6, TNF-α, and VEGF, while the medium-dose group significantly increased the levels of IL-6 and TNF-α, indicating that the compound granules of the present application can regulate body functions from multiple pathways and multiple targets. The azvudine group significantly increased the levels of IL-6, TNF-α, and VEGF, while the original prescription group had no significant effect on the levels of IL-6, TNF-α, and VEGF. The above changes were significantly different from those in the model control group (P<0.01).

[0106] The IL-1β content in the lung tissue of mice in the model control group was significantly increased, which was significantly different from that in the normal control group (P<0.01). After 4 days of administration, the compound granules in the low, medium and high dose groups, as well as the azithromycin group and the original prescription group, could significantly reduce the IL-1β content. The above changes were significantly different from those in the model control group (P<0.01).

[0107] Table 5 Effects of compound granules on the mouse pneumonia model induced by human coronavirus 229E

[0108]

[0109] Note: Compared with the normal control group ## P<0.01; compared with the model control group ** P<0.01.

[0110] From the above description, it can be seen that the above embodiments of the present invention achieve the following technical effects: the antiviral effect of the compound granules of the present application is comprehensively reflected by the rise and fall of lung index, viral load, CD4+ cell ratio, CD8+ cell ratio and inflammatory factors. The use of the compound granules containing the nine medicinal materials of the present application can improve the anti-coronavirus effect, which is specifically manifested in reducing the lung index of mice, reducing viral load, and increasing CD4+ cell ratio. + T cells and CD8 +It increases the percentage of T cells, increases the levels of inflammatory factors IL-6, TNF-α and VEGF, and reduces the level of inflammatory factor IL-1β, making it more effective in treating upper respiratory tract infections. It also has weaker toxicity and fewer side effects, especially avoiding the side effect of diarrhea. It is easy to take and carry, tastes better, and has better compliance. It has good application and promotion prospects in the treatment of upper respiratory tract infections.

[0111] The foregoing description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Those skilled in the art will readily appreciate that various modifications and variations of the present invention are possible. Any modifications, equivalent substitutions, or improvements made within the spirit and principles of the present invention are intended to be within the scope of protection of the present invention.

Claims

1. A compound granule for treating viruses, characterized in that: The compound granules include: 15-45 parts of Artemisia annua, 10-30 parts of Adiantum officinale, 15-45 parts of Rhapis tatarinowii, 15-45 parts of Chicory seeds, 12-36 parts of Viola tianshanica, 10-30 parts of Water Lily, 12-36 parts of Herba Lycopodii, 6-18 parts of Rose petals and 5-15 parts of Atractylodes macrocephala.

2. A method for preparing the compound granules for treating viruses according to claim 1, characterized in that: The preparation method comprises: S1, extracting and filtering a mixture of chicory seeds, violet herb, and Artemisia scoparia using an alcohol solution to obtain an alcohol extraction solution and medicinal residues; S2, mixing the medicinal residue with water lily, Herba Euphorbiae rutaecarpa, Rhizoma Cibotii, rose petals, Adiantum officinale, and Adiantum to obtain a medicinal material mixture; decocting and filtering the medicinal material mixture with water to obtain a medicinal liquid; S3, mixing the alcohol extraction solution and the medicinal solution to prepare the compound granules.

3. The preparation method according to claim 2, characterized in that Said S1 comprises: Repeatedly performing reflux extraction on the mixture of chicory seeds, violet herb and Artemisia striata using the alcohol solution; The filtrates of the repeated reflux extractions are mixed and then concentrated to obtain the alcohol extraction solution and the medicinal residue.

4. The preparation method according to claim 3, characterized in that The mass concentration of the alcohol solution is 55-60%; Preferably, the mass ratio of the mixture of chicory seeds, violet tianshanica and artemisia striata to the alcohol solution is 1:8-10; Preferably, the reflux extraction is performed 2-3 times; Preferably, the reflux extraction time is 0.5-1 hour.

5. The preparation method according to claim 3, characterized in that The concentration is concentration under reduced pressure; Preferably, the pressure of the reduced pressure concentration is -0.02 to -0.09 MPa; Preferably, the temperature of the reduced pressure concentration is 60-80°C Preferably, the density of the concentrated alcohol extraction solution is 1.1-1.2 times that of the unconcentrated solution.

6. The preparation method according to claim 2, characterized in that The S2 includes: Repeatedly boiling and filtering the medicinal material mixture with water to obtain a medicinal solution to be concentrated; Concentrating the to-be-concentrated medicinal liquid to obtain the medicinal liquid; Preferably, the mass ratio of the medicinal material mixture to the water is 1:8-10; Preferably, the particle size of the ragwort fruit is 4-8 mm; Preferably, the particle size of the Abel is 4-8 mm; Preferably, the decoction is performed 2-3 times; Preferably, the decocting time is 0.5-1 hour.

7. The preparation method according to claim 6, characterized in that The concentration is concentration under reduced pressure; Preferably, the pressure of the reduced pressure concentration is -0.02 to -0.09 MPa; Preferably, the temperature of the reduced pressure concentration is 60-80°C Preferably, the density of the concentrated medicinal solution is 1.0-1.1 times that of the unconcentrated medicinal solution.

8. The preparation method according to claim 2, characterized in that The S3 includes: After mixing the alcohol extraction solution and the medicinal solution, centrifugation, filtration and concentration are sequentially performed to obtain a concentrated mixture; The concentrated mixture is mixed with auxiliary materials to prepare the compound granules.

9. The preparation method according to claim 8, characterized in that The centrifugal speed is 15000-20000 rpm / min; Preferably, the concentration is concentrated under reduced pressure; Preferably, the pressure of the reduced pressure concentration is -0.02 to -0.09 MPa; Preferably, the temperature of the reduced pressure concentration is 60-80°C; Preferably, the density of the concentrated mixture is 1.05-1.20 times that of the unconcentrated mixture; Preferably, the mass ratio of the concentrated mixture to the auxiliary material is 1:0.30-0.45; Preferably, the excipients include dextrin and lactose; Preferably, the mass ratio of dextrin to lactose is 1:1-1.

4.

10. The compound granules for treating viruses obtained by the preparation method according to any one of claims 2 to 9.

11. Use of the compound granules for treating viruses obtained by the preparation method according to any one of claims 2 to 9 in preparing drugs for treating viruses.

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