CN114668805B - Use of a composition in the preparation of a medicament - Google Patents

Use of a composition in the preparation of a medicament Download PDF

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CN114668805B
CN114668805B CN202011565157.0A CN202011565157A CN114668805B CN 114668805 B CN114668805 B CN 114668805B CN 202011565157 A CN202011565157 A CN 202011565157A CN 114668805 B CN114668805 B CN 114668805B
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coronavirus
medicament
infection
cells
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CN114668805A (en
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苗彦
孙瑞鸿
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Xi'an Beilin Pharmaceutical Co ltd
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Xi'an Beilin Pharmaceutical Co ltd
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    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • A61K36/35Caprifoliaceae (Honeysuckle family)
    • A61K36/355Lonicera (honeysuckle)
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
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    • A61K35/56Materials from animals other than mammals
    • A61K35/63Arthropods
    • A61K35/64Insects, e.g. bees, wasps or fleas
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
    • AHUMAN NECESSITIES
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    • A61KPREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
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    • A61K36/00Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18Magnoliophyta (angiosperms)
    • A61K36/185Magnoliopsida (dicotyledons)
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    • A61K36/18Magnoliophyta (angiosperms)
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    • A61K36/53Lamiaceae or Labiatae (Mint family), e.g. thyme, rosemary or lavender
    • A61K36/539Scutellaria (skullcap)
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    • A61K36/60Moraceae (Mulberry family), e.g. breadfruit or fig
    • A61K36/605Morus (mulberry)
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Abstract

The present invention proposes the use of a composition for the preparation of a medicament for combating coronaviruses, said composition comprising: honeysuckle, weeping forsythiae capsule, figwort root, radix isatidis, red paeony root, baical skullcap root, mulberry leaf, chrysanthemum, peucedanum root, bitter apricot seed, great burdock achene, oriental waterplantain rhizome, boat-fruited scaphium seed, stiff silkworm, cicada slough and oroxylum indicum. The medicine of the invention has better anti-coronavirus effect, lays a foundation for the research and treatment of coronavirus infection diseases, and has wide application prospect.

Description

Use of a composition in the preparation of a medicament
Technical Field
The invention relates to the field of medicine. In particular, the invention relates to the use of the composition in the preparation of antiviral drugs.
Background
Coronaviruses are pathogens mainly causing respiratory and intestinal diseases, the surfaces of single-strand positive-strand RNA virus particles are provided with a plurality of protrusions which are regularly arranged, and the whole virus particle is like a imperial crown, so the name "coronaviruses", which are a large virus family, and are widely existing in nature. There are 7 coronaviruses known to infect humans, four of which are more common in the human population (HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU 1), and the other three are middle east respiratory syndrome-associated coronavirus (MERSr-CoV) and severe acute respiratory syndrome-associated coronavirus (SARSr-CoV) and 2019 novel coronavirus (2019-nCoV). Symptoms after coronavirus infection vary from one species to another, and common signs are respiratory symptoms, fever, cough, shortness of breath, dyspnea, and the like. In more severe cases, the infection can lead to pneumonia, severe acute respiratory syndrome, renal failure, and even death.
Human coronavirus (HCoV-229E) is a pathogen causing upper respiratory tract infection in humans, is one of the main epidemic strains of coronavirus, clinically presents symptoms such as fever, runny nose, sore throat and the like, and clinically causes acute gastroenteritis of low-age groups, particularly children, besides respiratory tract infection.
Current drug therapies for coronaviruses are mainly: antiviral drug treatment, antibacterial drug treatment and traditional Chinese medicine treatment. The pneumonia infected by coronavirus belongs to the traditional Chinese medicine epidemic disease category, the basic pathogenesis is characterized by dampness, heat, toxin and blood stasis, and the effect of the traditional Chinese medicine for preventing and treating the coronavirus pneumonia at present has been proved clinically.
However, current antiviral drugs remain to be studied.
Disclosure of Invention
The present invention aims to solve at least one of the technical problems existing in the prior art to at least some extent. Therefore, the invention provides the application of the composition in preparing medicines, the medicines have better anti-coronavirus effect, and lay a foundation for researching and treating coronavirus infection diseases, and have wide application prospects.
The invention provides application of a composition in preparing medicines. According to an embodiment of the invention, the medicament is for use against coronavirus, the composition comprising: honeysuckle, weeping forsythiae capsule, figwort root, radix isatidis, red paeony root, baical skullcap root, mulberry leaf, chrysanthemum, peucedanum root, bitter apricot seed, great burdock achene, oriental waterplantain rhizome, boat-fruited scaphium seed, stiff silkworm, cicada slough and oroxylum indicum. The inventor discovers that the composition has better anti-coronavirus effect, thereby laying a foundation for researching and treating coronavirus infection diseases and having wide application prospect.
According to an embodiment of the present invention, the use of the above composition for the preparation of a medicament may also have the following additional technical features:
according to an embodiment of the invention, the coronavirus is selected from HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, MERSr-CoV, SARSr-CoV or 2019-nCoV.
According to an embodiment of the invention, infection with coronavirus increases the lung index and the drug is used to decrease the lung index. The inventors have found that the above composition is effective in reducing the lung index and thereby treating lung injury caused by infection with a virus.
According to an embodiment of the invention, infection with coronavirus increases the expression of IL-1 beta, IL-6 in lung tissue, and the medicament is used to reduce the expression of IL-1 beta, IL-6 in lung tissue. The inventors have found that the above composition is effective in inhibiting the above inflammatory cytokines of lung tissue, thereby acting as an antiviral agent.
According to an embodiment of the invention, infection with coronavirus causes CD4 in peripheral blood + T cells, B cells and CD8 + Elevated T cell content, and the medicament is used forIncrease CD4 in peripheral blood + T cells, B cells and CD8 + T cell content. The inventor finds that the composition can effectively improve the content of immune cells in peripheral blood, thereby playing an antiviral role.
According to an embodiment of the invention, the medicament is for the treatment of respiratory diseases caused by infection with coronaviruses.
According to an embodiment of the invention, the medicament is in a single dosage form and comprises 1g/60kg/d to 5g/60kg/d of the composition. The medicine with the composition content is taken once a day, so that a better treatment purpose can be achieved. Correspondingly, the mice can be administrated once a day by adopting the medicine with the content of the composition of 0.2 g/kg/d-0.9 g/kg/d, thereby achieving better treatment purpose.
According to an embodiment of the present invention, the pharmaceutical is in the form of a pill, tablet, capsule or granule.
According to an embodiment of the invention, the composition is selected from: 115-135 parts of honeysuckle; 115-135 parts of fructus forsythiae; 115-135 parts of radix scrophulariae; 115-135 parts of radix isatidis; 40-60 parts of red paeony root; 65-85 parts of baical skullcap root; 40-60 parts of mulberry leaves; 40-60 parts of chrysanthemum; 40-60 parts of radix peucedani; 40-60 parts of bitter apricot kernel; 40-60 parts of burdock; 40-60 parts of rhizoma alismatis; 40-60 parts of boat-fruited scaphium seed; 40-60 parts of stiff silkworm; 40-60 parts of periostracum cicadae and 40-60 parts of oroxylum indicum. Therefore, the composition has better anti-coronavirus effect.
Additional aspects and advantages of the invention will be set forth in part in the description which follows, and in part will be obvious from the description, or may be learned by practice of the invention.
Detailed Description
The scheme of the present invention will be explained below with reference to examples. It will be appreciated by those skilled in the art that the following examples are illustrative of the present invention and should not be construed as limiting the scope of the invention. The examples are not to be construed as limiting the specific techniques or conditions described in the literature in this field or as per the specifications of the product. The reagents or apparatus used were conventional products commercially available without the manufacturer's attention.
Example 1
In this example, an anti-coronavirus drug (pill) was prepared as follows:
1. the formula of the raw materials is as follows:
2. the preparation method of the process for producing the pill comprises the following steps:
(1) Parching Bombyx Batryticatus bran, and peeling semen Armeniacae amarum.
(2) Pulverizing sixteen Chinese medicinal materials into fine powder, sieving with 100-120 mesh sieve, and mixing well for use.
(3) Mixing 100 parts of fine powder with 35-50 parts of refined honey and a proper amount of purified water, uniformly mixing, refining, discharging, rubbing pills, drying, selecting pills and the like, and preparing into pills with the weight of 1 gram per 10 pills.
Example 2
In this example, an anti-coronavirus drug (tablet) was prepared according to the following method:
1. the formula of the raw materials is as follows:
2. the preparation method of the process for producing the tablet comprises the following steps:
(1) Parching Bombyx Batryticatus bran, and peeling semen Armeniacae amarum.
(2) Pulverizing radix Isatidis and Bombyx Batryticatus into fine powder, sieving with 100-120 mesh sieve, and mixing.
(3) Pulverizing flos Lonicerae, fructus forsythiae, radix Paeoniae Rubra, and semen Armeniacae amarum into 60 coarse powder, reflux-extracting with 80% ethanol twice for 2 hr each time, mixing extractive solutions, filtering, and collecting filtrate.
(4) Decocting the residue in the step (3) and the rest ten traditional Chinese medicines such as radix scrophulariae, radix Scutellariae and the like with water twice, each time for 2 hours, merging decoction, filtering, concentrating the filtrate to obtain fluid extract with the relative density of 1.28-1.30 at the temperature of 25 ℃, adding ethanol to ensure that the alcohol content reaches 70%, stirring uniformly, standing, filtering, merging the filtrate with the alcohol extract in the step (3), recovering ethanol, concentrating to obtain fluid extract with the relative density of 1.38-1.40 at the temperature of 60 ℃, adding the fine powder prepared in the step (2) and auxiliary materials for granulating, wherein the auxiliary materials can be dextrin, starch, maltose, magnesium stearate and the like, drying at the temperature of 70-80 ℃ by using a normal-temperature oven, and tabletting, and coating to obtain the film.
Example 3
In this example, an anti-coronavirus drug (capsule) was prepared as follows:
1. the formula of the raw materials is as follows:
2. the preparation method of the capsule preparation process comprises the following steps:
(1) Parching Bombyx Batryticatus bran, and peeling semen Armeniacae amarum.
(2) Pulverizing radix Isatidis and Bombyx Batryticatus into fine powder, sieving with 100-120 mesh sieve, and mixing.
(3) Pulverizing flos Lonicerae, fructus forsythiae, radix Paeoniae Rubra, and semen Armeniacae amarum into 60 coarse powder, reflux-extracting with 80% ethanol twice for 2 hr each time, mixing extractive solutions, filtering, and collecting filtrate.
(4) Decocting the residue in the step (3) and the rest ten traditional Chinese medicines such as radix scrophulariae, radix scutellariae and the like with water twice, each time for 2 hours, merging decoction, filtering, concentrating filtrate to fluid extract with the relative density of 1.28-1.30 at the temperature of 25 ℃, adding ethanol to ensure that the alcohol content reaches 70%, stirring uniformly, standing, filtering, merging filtrate with the alcohol extract in the step (3), recovering ethanol, concentrating to fluid extract with the relative density of 1.38-1.40 at the temperature of 60 ℃, adding the fine powder prepared in the step (2), stirring uniformly, drying at the temperature of 70-80 ℃, granulating, and filling into 1000 capsules to obtain the capsule.
Example 4
In this example, an anti-coronavirus drug (granule) was prepared as follows:
1. the formula of the raw materials is as follows:
2. the preparation method of the process for producing the granules comprises the following steps:
(1) Parching Bombyx Batryticatus bran, and peeling semen Armeniacae amarum.
(2) Pulverizing radix Isatidis and Bombyx Batryticatus into fine powder, sieving with 100-120 mesh sieve, and mixing.
(3) Pulverizing flos Lonicerae, fructus forsythiae, radix Paeoniae Rubra, and semen Armeniacae amarum into 40-60 coarse powder, reflux-extracting with 80% ethanol twice for 2 hr each time, mixing extractive solutions, filtering, and collecting filtrate.
(4) Decocting the residue in the step (3) and the rest ten traditional Chinese medicines such as radix scrophulariae, radix scutellariae and the like with water twice, each time for 2 hours, merging decoction, filtering, concentrating filtrate to fluid extract with the relative density of 1.18-1.20 at the temperature of 50 ℃, adding ethanol to ensure that the alcohol content reaches 70%, uniformly stirring, standing, filtering, merging filtrate with the alcohol extract in the step (3), recovering ethanol, concentrating to fluid extract with the relative density of 1.38-1.40 at the temperature of 60 ℃, and adding the fine powder prepared in the step (2).
(5) Then 400g of sucrose and 200g of starch are added, and the granules are obtained.
Example 5
In this example, an anti-coronavirus drug (soft capsule) was prepared as follows:
1. the formula of the raw materials is as follows:
2. the preparation method of the process for producing the soft capsule comprises the following steps:
(1) Parching Bombyx Batryticatus bran, and peeling semen Armeniacae amarum.
(2) Pulverizing radix Isatidis and Bombyx Batryticatus into fine powder, sieving with 100-120 mesh sieve, and mixing.
(3) Pulverizing flos Lonicerae, fructus forsythiae, radix Paeoniae Rubra, and semen Armeniacae amarum into 40-60 coarse powder, reflux-extracting with 80% ethanol twice for 2 hr each time, mixing extractive solutions, filtering, and collecting filtrate.
(4) Decocting the residue in the step (3) and the rest ten traditional Chinese medicines such as radix scrophulariae, radix Scutellariae and the like with water twice, each time for 2 hours, mixing decoctions, filtering, concentrating the filtrate to obtain fluid extract with the relative density of 1.18-1.20 at 50 ℃, adding ethanol to ensure that the ethanol content reaches 85%, stirring uniformly, standing, filtering, mixing the filtrate with the ethanol extract in the step (3), recovering ethanol, and concentrating to obtain fluid extract with the relative density of 1.38-1.40 at 60 ℃.
(5) Adding the fine powder prepared in the step (2), drying, pulverizing, adding salad oil, mixing to obtain 45-50% suspension, and making into soft capsule.
Comparative example 1
In this example, an anti-coronavirus drug (capsule) was prepared as follows:
1. the formula of the raw materials is as follows:
fructus forsythiae: 255g, 255g of honeysuckle, 85g of roasted ephedra herb, 85g of fried bitter apricot seed, 255g of gypsum, 255g of radix isatidis, 255g of rhizoma dryopteris crassirhizomae, 255g of cordate houttuynia, 85g of patchouli, 51g of rheum officinale, 85g of rhodiola rosea, 7.5g of menthol and 85g of liquorice.
2. Preparation method
Same as in example 3.
Example 6
The anti-coronavirus drugs obtained in examples 1 to 5 were tested for their properties and found to have good antiviral effects. The antiviral agent obtained in example 3 is described in detail below.
1 test materials
1.1 laboratory animals
Species of type Level of Weight of body Sex (sex)
ICR mice SPF stage 14±1g Female
ICR mice SPF stage 14±1g Male male
1.2 strains and cells
1.2.1 viral strains: human coronavirus 229E (HCoV-229E) is supplied by the institute of medical biotechnology of the national academy of medical sciences, passaged in the laboratory and stored in a refrigerator at-80℃for further use.
1.2.2 cell lines: mouse mononuclear macrophage RAW264.7 purchased from Beijing North Innovative biological technology institute, passaged in this laboratory and stored in liquid nitrogen for later use.
1.3 test reagents
2 test method
2.1 drug dosage design and formulation
(1) The medicine of the invention
2.2 passage of virus
25cm of RAW264.7 cells grown as a monolayer were taken 2 The flask was then emptied, the cell surface was rinsed 3 times with cell maintenance solution, 200. Mu.l of HCoV-229E virus solution was added, and the flask was incubated at 37℃with 5% CO 2 Culturing in an incubator, observing cytopathic condition under an inverted microscope every day for 48-72 h until 80% of cells have obvious lesions (CPE), and freezing and storing the cell culture flask in a low-temperature refrigerator at-80 ℃ for 3 times, and repeatedly freezing and thawing virus liquid for detecting virus virulence.
2.3 Virus titre assay
Taking a culture plate of single-layer RAW264.7 cells, pouring out the culture solution, flushing the cell surface with a cell maintenance solution for 3 times, and diluting with 10 times of HCoV-229E virus solution with different titers, wherein the culture solution is prepared by -1 ~10 -8 A total of 8 dilutions, 100. Mu.l/well, 4 multiplex wells per concentration, were used with normal cell controls. Placing at 37deg.C 5% CO 2 Culturing in an incubator, observing cytopathic conditions under a daily inverted microscope, and recording cytopathic conditions of each hole for 48-72 hours. 50% cytopathic concentration (TCID) was calculated as Reed-Muench 50 )。
2.4 Model modeling and administration of HCOV-229E infected mice pneumonia
ICR mice were randomly divided into a normal control group, a model control group, a comparative example 1 group, and a drug group of the present invention, 10 animals per group, and male and female halves according to body weight. The mice of each group, except the normal control group, were lightly anesthetized with diethyl ether, 100TCID 50 HCoV-229E nasal drip infection. The administration was started on the day of infection, and each administration group was lavaged at 20ml/kg/d, 1 time per day for 4 consecutive days. The normal control group was given 20ml/kg/d distilled water for gastric lavage under the same conditions. The dissections were examined after weighing on day 5 of infection.
2.5 calculation of Lung index and inhibition Rate
The mice were weighed one day after the last dose, dissected and weighed for lung and lung index inhibition were calculated.
2.6 detection of viral load in pulmonary tissue (Real-time RT-PCR method)
Nucleic acid cleavage treatment:
dissecting the mice, and then sub-packaging the lung tissues in a low-temperature refrigerator at-80 ℃ for preservation; taking out the lung tissue of the mice from a low-temperature refrigerator at the temperature of minus 80 ℃, placing the mice in a clean mortar, pouring a small amount of liquid nitrogen into the mortar, grinding the small amount of liquid nitrogen into powder by using a pestle, collecting the powder into a 1.5ml centrifuge tube, immediately adding 1ml TRIzol Reagent, flicking the bottom of the tube, and mixing the sample as soon as possible until the sample is resuspended; horizontally placing a centrifuge tube at room temperature, and incubating for 20min; centrifuging at 12000rpm at 4deg.C for 10min; the clarified supernatant was transferred to a new 1.5ml centrifuge tube; adding 0.2ml chloroform, covering the tube cover, shaking the centrifuge tube for 15s with force, and incubating at room temperature for 2-3min until the liquid is layered; centrifuging at 12000rpm at 4deg.C for 15min; carefully transferring the transparent supernatant into a new 1.5ml centrifuge tube, adding 0.5ml isopropanol, uniformly mixing, and incubating for 30min at room temperature; centrifuging at 12000rpm at 4deg.C for 10min; the supernatant was discarded, and the pellet was gently washed with 1ml of 75% ethanol (the white pellet was gently buoyed); centrifuging at 4 ℃ and 7500rpm for 5min; sucking out the supernatant, and briefly drying the RNA precipitate for 5-10min; m) dissolving the precipitate with 20 μl DEPC water, and storing in a low temperature refrigerator at-80deg.C.
Nucleic acid determination:
control nucleic acid treatment: DEPC-H 2 O served as a negative control. The positive control was diluted 10, 100, 1000-fold gradient.
And (3) preparation of a reagent: n.times.18. Mu.l of HCoV-229E nucleic acid fluorescence PCR detection mixture, n.times.1. Mu.l of internal control, and n.times.1. Mu.l of RT-PCR enzyme (n is the number of reaction tubes) were mixed by shaking for several seconds and centrifuged at 3000rpm for several seconds.
And (3) PCR amplification: real-time RT-PCR of human coronavirus using Shanghai river Biotechnology Co., ltdThe kit is carried out. Specifically, 20. Mu.l of the above mixture was placed in a PCR tube, and then the sample nucleic acid extract and DEPC-H were put into a PCR tube 2 And adding 5 mu l of each of the O and positive control substances into a PCR tube, covering a tube cover, centrifuging for several seconds to ensure that all liquid is placed at the bottom, and immediately performing PCR amplification reaction. The cycle parameters are set as follows: 45 ℃ for 10min;95 ℃ for 15min; then circulating for 40 times according to the temperature of 95 ℃ multiplied by 15sec to 60 ℃ multiplied by 60 sec; single-point fluorescence detection was carried out at 60℃with a reaction system of 25. Mu.l.
Fluorescence channel detection selection: FAM and HEX/VIC/JOE channels are selected.
2.7 detection of IL-1 beta and IL-6 in mouse lung tissue (Elisa method)
Lung tissue homogenate sample: after the lung tissue of the mice is weighed, the lung tissue of the mice is collected and stored at-4 ℃. After weighing 50mg of lung tissue and adding 500. Mu.L of physiological saline, the tissue was homogenized by using an ultrasonic cytoclasis apparatus, and centrifuged at 1000rpm at-4℃for 10 minutes by using a low-temperature high-speed centrifuge. Sucking supernatant, packaging, and storing in refrigerator at-80deg.C. Avoiding repeated freezing and thawing. IL-1 beta and IL-6 to be detected.
The detection is carried out according to the instruction of the kit, and the absorbance at 450nm is detected by an enzyme-labeled instrument.
2.8 mouse peripheral blood T lymphocyte subpopulation and B lymphocyte proportional flow assay
And (5) precooling at 4 ℃ by a centrifugal machine. Mice were bled from the eyeballs, 3 drops (approximately 150. Mu.l) were added to a 15ml centrifuge tube containing 10ml of 1 XPBS, spun at 160 rpm for 15min at room temperature; the supernatant was carefully discarded by pipette, 1ml of red blood cell lysate was added to each tube to resuspend the cell pellet, lysis was performed at room temperature for about 5-10min until the liquid became clear from cloudy, lysis was stopped by adding 10ml of PBS, centrifugation was performed at 2000rpm,5min at 4℃and the supernatant was discarded. The cell pellet was resuspended in 10ml PBS, centrifuged at 2000rpm for 5min at 4℃and the supernatant discarded, resuspended in 1ml blocking solution (PBS with 5% FBS), centrifuged at 2000rpm for 5min at 4℃and the supernatant discarded. The flow antibody was formulated in a blocking solution protected from light as follows: PE-labeled anti-mouse B220, perCP-Cy5.5-labeled anti-mouse CD4, APC-labeled anti-mouse CD8a, the preparation volume is: antibody 0.8. Mu.l/sample each, blocking solution 50. Mu.l/sample. Adding flow antibody, 50 μl each tube, staining at 4deg.C for 30min in dark, adding 1ml PBS,2000rpm,5min,4 deg.C, centrifuging, and discarding supernatant. 100 μl of PBS containing 2% FBS and 100 μl of 4% paraformaldehyde were added to resuspend the cells, stored at 4deg.C and checked as soon as possible.
2.9 statistical analysis
Statistical analysis was performed using SPSS17.0 software, the differences between groups were analyzed using one-way variance analysis, and P <0.05 was statistically significant.
3 results of experiments
3.1 Effect of the drug of the present invention on pulmonary index and inhibition ratio of mice infected with HCOV-229E in the pneumonia model
TABLE 1 therapeutic effect of the inventive drug on model of pneumonia in HCOV-229E infected mice
Note that: comparison with the Normal control group ## P<0.01, compared with the model control group ** P<0.01; in comparison with the group of comparative example 1, P<0.05。
table 1 the results show that: the lung index of the mice in the model control group was significantly increased (P < 0.01) compared to the normal control group; the lung index of the drug mice is obviously reduced, and compared with a model control group, the drug mice have obvious differences (P < 0.01); compared to the comparative example 1 group, the inventive drug group had a lower lung index than the comparative example 1 group (P < 0.05); the inhibition rate of the lung index reaches 141.95 percent.
3.2 Effect of the drug of the present invention on pulmonary tissue viral load in mice infected with HCOV-229E in a model of pneumonia
TABLE 2 therapeutic effect of the drug of the present invention on the model of pneumonia in HCOV-229E infected mice
Note that: in comparison with the normal group, ## P<0.01; in comparison with the set of models, ** P<0.01;
table 2 the results show that: normal control mice had no HCOV-229E nucleic acid expression in lung tissue; after mice are infected by HCOV-229E, obvious nucleic acid expression exists in lung tissues of the mice, the virus load of lung tissues of mice in a model control group is obviously increased, and compared with a normal control group, the virus load of the mice in the model control group is obviously different (P < 0.01); the drug groups of the invention can obviously reduce the expression level of virus nucleic acid in lung tissues, and compared with the model groups, the drug groups have obvious differences (P < 0.01).
3.3 effects of the drug of the present invention on inflammatory cytokines in lung tissue of mice infected with HCOV-229E in a model of pneumonia
TABLE 3 therapeutic effect of the inventive drug on model of pneumonia in HCOV-229E infected mice
Note that: comparison with the Normal control group ## P<0.01, compared with the model control group ** P<0.01。
Table 3 the results show that: after HCOV-229E infection, the expression of IL-1 beta and IL-6 in the lung tissues of mice in the model control group is obviously increased, and compared with the normal control group, the expression of IL-1 beta and IL-6 in the lung tissues of mice in the model control group is obviously different (P < 0.01); the drug groups of the invention can obviously reduce the expression of IL-1 beta and IL-6 in lung tissues, and compared with a model control group, the drug groups have obvious differences (P is less than 0.01).
3.4 Effect of the drug of the present invention on the lymphocyte proportion in the peripheral blood of HCOV-229E-infected mice
TABLE 4 therapeutic effect of the inventive drug on the model of pneumonia in HCOV-229E infected mice
Note that: comparison with the Normal control group ## P<0.01, compared with the model control group ** P<0.01. In comparison with the group of comparative example 1, P<0.05, ☆☆ P<0.01。
table 4 the results show that: immune cell CD4 in peripheral blood of mice of model control group after HCOV-229E infection + Percentage of T cells, CD8 + The percentage of T cells and the percentage of B cells are obviously reduced, and compared with the normal group, the T cells and the B cells have obvious difference (P<0.01,P<0.05 A) is provided; the medicine of the invention can obviously raise CD4 + T cells, CD8 + The percentages of T cells and B cells were significantly different from the model control group (P<0.05,P<0.01 Compared with the comparative example 1 group, the CD4+ T cell percentage of the inventive drug group was significantly higher than that of the comparative example 1 group (P<0.05,P<0.01)。
4 knots
The experiment adopts human coronavirus 229E (HCoV-229E) nasal drop infection to prepare a coronavirus pneumonia mouse model, evaluates the treatment effect of the medicine of the invention on the HCOV-229E infection mouse pneumonia model, and results show that: the invention obviously reduces the lung index after HCOV-229E infection, obviously reduces the virus load of lung tissues, obviously reduces the inflammatory cytokines IL-1 beta and IL-6 expression of the lung tissues, and obviously increases the immune cell CD4 in peripheral blood + Percentage of T cells, CD8 + T cell percentage, B cell percentage. In conclusion, the medicine has a therapeutic effect on human coronavirus HCOV-229E infectious pneumonia.
In the description of the present specification, a description referring to terms "one embodiment," "some embodiments," "examples," "specific examples," or "some examples," etc., means that a particular feature, structure, material, or characteristic described in connection with the embodiment or example is included in at least one embodiment or example of the present invention. In this specification, schematic representations of the above terms are not necessarily directed to the same embodiment or example. Furthermore, the particular features, structures, materials, or characteristics described may be combined in any suitable manner in any one or more embodiments or examples. Furthermore, the different embodiments or examples described in this specification and the features of the different embodiments or examples may be combined and combined by those skilled in the art without contradiction.
While embodiments of the present invention have been shown and described above, it will be understood that the above embodiments are illustrative and not to be construed as limiting the invention, and that variations, modifications, alternatives and variations may be made to the above embodiments by one of ordinary skill in the art within the scope of the invention.

Claims (7)

1. Use of a composition in the manufacture of a medicament for combating a coronavirus, said coronavirus being HCoV-229E;
the composition comprises 135 parts of honeysuckle, 135 parts of weeping forsythia, 135 parts of figwort, 135 parts of radix isatidis, 60 parts of red paeony root, 85 parts of baical skullcap root, 60 parts of mulberry leaf, 60 parts of chrysanthemum, 60 parts of common hogfennel root, 60 parts of bitter apricot seed, 60 parts of great burdock achene, 60 parts of oriental waterplantain rhizome, 60 parts of boat-fruited sterculia seed, 60 parts of stiff silkworm, 60 parts of cicada slough and 60 parts of oroxylum indicum.
2. The use according to claim 1, wherein infection with coronavirus increases the lung index and the medicament is for decreasing the lung index.
3. The use according to claim 1, wherein infection with coronavirus increases the expression of IL-1 β, IL-6 in lung tissue, and the medicament is for reducing the expression of IL-1 β, IL-6 in lung tissue.
4. The use according to claim 1, wherein infection with coronavirus causes CD4 in peripheral blood + T cells, B cells and CD8 + Elevated T cell content, and the medicament is used for increasing CD4 in peripheral blood + T cells, B cells and CD8 + T cell content.
5. The use according to claim 1, wherein the medicament is for the treatment of respiratory diseases caused by infection with coronavirus.
6. The use according to claim 1, wherein the medicament is in a single dosage form comprising 1g/60kg/d to 5g/60kg/d of the composition.
7. The use according to claim 1, wherein the medicament is in the form of a pill, tablet or capsule.
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Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1544069A (en) * 2003-05-21 2004-11-10 西安碑林药业股份有限公司 Chinese traditional medicine for treating acute laryngopharyngitis and its preparing process
CN102973746A (en) * 2012-12-18 2013-03-20 西安碑林药业股份有限公司 Compound Chinese herbal extract for dispelling wind, clearing heat and relieving sore-throat to restore voice, and preparations thereof
CN108837045A (en) * 2018-09-27 2018-11-20 西安碑林药业股份有限公司 A kind of preparation method for paediatric acute tonsillitis, the Chinese medicine composition of acpuei pharyngitis
CN111297969A (en) * 2020-03-25 2020-06-19 鲁南制药集团股份有限公司 Application of Chaihingzhi preparation in preparing anti-coronavirus medicine and its preparation method

Patent Citations (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1544069A (en) * 2003-05-21 2004-11-10 西安碑林药业股份有限公司 Chinese traditional medicine for treating acute laryngopharyngitis and its preparing process
CN102973746A (en) * 2012-12-18 2013-03-20 西安碑林药业股份有限公司 Compound Chinese herbal extract for dispelling wind, clearing heat and relieving sore-throat to restore voice, and preparations thereof
CN108837045A (en) * 2018-09-27 2018-11-20 西安碑林药业股份有限公司 A kind of preparation method for paediatric acute tonsillitis, the Chinese medicine composition of acpuei pharyngitis
CN111297969A (en) * 2020-03-25 2020-06-19 鲁南制药集团股份有限公司 Application of Chaihingzhi preparation in preparing anti-coronavirus medicine and its preparation method

Non-Patent Citations (1)

* Cited by examiner, † Cited by third party
Title
徐世军等.金嗓开音丸.《实用临床药物学•中成药卷》.中国医药科技出版社,2019,(第1版),第666页. *

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