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WO2021179950A1 - Utilisation d'une composition pharmaceutique dans la préparation d'un médicament antiviral - Google Patents

Utilisation d'une composition pharmaceutique dans la préparation d'un médicament antiviral Download PDF

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Publication number
WO2021179950A1
WO2021179950A1 PCT/CN2021/078623 CN2021078623W WO2021179950A1 WO 2021179950 A1 WO2021179950 A1 WO 2021179950A1 CN 2021078623 W CN2021078623 W CN 2021078623W WO 2021179950 A1 WO2021179950 A1 WO 2021179950A1
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pharmaceutical composition
time
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pinellia
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Chinese (zh)
Inventor
贾振华
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Shijiazhuang Yiling Pharmaceutical Co Ltd
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Shijiazhuang Yiling Pharmaceutical Co Ltd
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Priority to CA3167240A priority Critical patent/CA3167240A1/fr
Priority to PH1/2022/552280A priority patent/PH12022552280A1/en
Priority to MYPI2022004285A priority patent/MY201855A/en
Publication of WO2021179950A1 publication Critical patent/WO2021179950A1/fr
Priority to ZA2022/08676A priority patent/ZA202208676B/en
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    • A—HUMAN NECESSITIES
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    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/331—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using water, e.g. cold water, infusion, tea, steam distillation or decoction
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    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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    • A61K2236/30—Extraction of the material
    • A61K2236/33—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones
    • A61K2236/333—Extraction of the material involving extraction with hydrophilic solvents, e.g. lower alcohols, esters or ketones using mixed solvents, e.g. 70% EtOH
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    • A61K2236/30—Extraction of the material
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    • A—HUMAN NECESSITIES
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    • A61K2236/50—Methods involving additional extraction steps
    • A61K2236/51—Concentration or drying of the extract, e.g. Lyophilisation, freeze-drying or spray-drying
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
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Definitions

  • the invention relates to the application of a pharmaceutical composition in the preparation of antiviral drugs, and belongs to the field of medicine.
  • Viruses are the smallest kind of pathogenic microorganisms. They multiply in cells. The core is ribonucleic acid (RNA) or deoxyribonucleic acid (DNA), and the outer shell is protein, which does not have a cell structure. Most viruses lack an enzyme system and cannot live independently. They must rely on the host's enzyme system to reproduce (replicate) themselves. Viral nucleic acids are sometimes integrated in cells and are difficult to eliminate. Therefore, the development of antiviral drugs has been slow.
  • Viral infection refers to the process by which viruses invade the body through multiple channels and multiply in susceptible host cells.
  • Human viruses refer to viruses that can infect humans or have disease-causing effects on humans. The essence of virus infection is the process of interaction between virus and body, virus and susceptible cells. Viral infections often cause varying degrees of damage or viral diseases due to different types of viruses and body conditions. Virus pathogenicity begins by invading the host and infecting cells, and the pathogenic effect is manifested in both the human body and the cells.
  • Viral diseases are a class of highly contagious diseases.
  • the antiviral chemical drugs currently on the market are divided into the following categories:
  • Penetration and shelling inhibitors amantadine, rimantadine, enfuvirtide, maraviro
  • DNA polymerase inhibitors acyclovir, ganciclovir, valacyclovir, famciclovir, foscarnet sodium
  • Nucleosides lamivudine, zidovudine, emtricitabine, tenofovir, adefovir dipivoxil
  • Non-nucleoside efavirenz, nevirapine
  • the existing antiviral drugs are not yet satisfactory in terms of effectiveness and/or safety.
  • ribavirin a commonly used antiviral chemical drug in clinical practice, can cause heart damage when used in large doses, and can also cause a decrease in white blood cells and lead to reversible anemia. .
  • the toxicity and side effects of chemical drugs limit their application to a certain extent.
  • the present invention is an improved invention based on the pharmaceutical composition disclosed in the patent of CN101549060A, and the content recorded in the patent document is quoted here in full.
  • the aforementioned patent does not disclose that the pharmaceutical composition has an antiviral effect.
  • the pharmaceutical composition of the present invention has an excellent antiviral effect
  • the pharmaceutical composition is made of the following raw materials in parts by weight:
  • the weight ratio of the bulk drug of the pharmaceutical composition of the present invention is preferably:
  • the weight ratio of the bulk drug of the pharmaceutical composition of the present invention is also preferably:
  • the weight ratio of the bulk drug of the pharmaceutical composition of the present invention is also preferably:
  • Ephedra 69 Gypsum 259; Forsythia 259; Scutellaria baicalensis 104; Mulberry bark 259; Bitter almond 104; Qianhu 104; Pinellia 104; Licorice 52.
  • the weight ratio of the bulk drug of the pharmaceutical composition of the present invention is also preferably:
  • the bitter almonds are fried bitter almonds
  • the fritillary is Fritillaria fritillary
  • the honeysuckle is the Lonicera japonica
  • the Pinellia ternata is the Qing Pinellia.
  • the pharmaceutical composition of the present invention has been confirmed by in vitro studies and clinical experiments to effectively kill a variety of viruses, and the effect is significant.
  • the active ingredient of the pharmaceutical composition of the present invention is made by the following steps:
  • step D Mix the fine powder obtained in step A and the clear ointment mixture obtained in step C to obtain the active ingredient of the pharmaceutical composition.
  • the dosage form of the medicine of the present invention can be capsules, tablets, powders, granules, oral liquids, soft capsules, pills, tinctures, syrups, suppositories, gels, sprays or injections.
  • compositions such as fillers, disintegrants, lubricants, suspending agents, binders, sweeteners, correctives, and preservatives. , Substrate, etc.
  • Fillers include: starch, pregelatinized starch, lactose, mannitol, chitin, microcrystalline cellulose, sucrose, etc.; disintegrants include: starch, pregelatinized starch, microcrystalline cellulose, sodium carboxymethyl starch, Cross-linked polyvinylpyrrolidone, low-substituted hydroxypropyl cellulose, croscarmellose sodium, etc.; lubricants include: magnesium stearate, sodium lauryl sulfate, talc, silicon dioxide, etc.; suspending agent Including: polyvinylpyrrolidone, microcrystalline cellulose, sucrose, agar, hydroxypropyl methylcellulose, etc.; binders include starch slurry, polyvinylpyrrolidone, hydroxypropyl methylcellulose, etc.; sweeteners include: Saccharin sodium, aspartame, sucrose, cyclamate, glycyrrhetinic acid, etc.; correctives include:
  • the tablet can be made by a method including the following steps:
  • step D Spray drying the cleansing paste mixture obtained in step C, and collect the spray powder for later use;
  • step E The spray powder obtained in step D and the fine powder obtained in step A are prepared by using ethanol as a binder to prepare a soft material, and then sieved to granulate; it is obtained by pressing according to the conventional method of pharmacy.
  • the preferred preparation method of the tablet may be a method including the following steps:
  • step D Spray drying the cleansing paste mixture obtained in step C, and collect the spray powder for later use;
  • step E The spray powder obtained in step D and the fine powder obtained in step A are used to prepare a soft material with ethanol as a binder, sieved, granulated, dried, and then sieved, and then mixed with sodium starch glycolate, microcrystalline cellulose, and magnesium stearate. Evenly, press the tablet and get it.
  • the raw materials can be weighed in proportion and prepared by conventional preparation methods, for example, according to the preparation described in Fan Biting's "Chinese Medicine Pharmacy” (Shanghai Science Press, December 1997, 1st edition) Process, made into a pharmacologically acceptable conventional dosage form.
  • the pharmaceutical composition of the present invention can inhibit influenza virus, especially influenza A virus; the pharmaceutical composition of the present invention can inhibit the new coronavirus.
  • Figure 1 shows the protective effect of the pharmaceutical composition of the present invention on mice infected with influenza virus.
  • step D Spray drying the cleansing paste mixture obtained in step C, and collect the spray powder for later use;
  • step E Prepare a soft material with the spray powder obtained in step D and the fine powder obtained in step A using 80% ethanol as a binder, sieving and granulating, drying at 60 degrees, and sizing. Add sodium carboxymethyl starch, microcrystalline cellulose, and magnesium stearate, mix well, and prepare tablets according to the conventional preparation method to obtain.
  • step D Spray drying the cleansing paste mixture obtained in step C, and collect the spray powder for later use;
  • step E Prepare a soft material with the spray powder obtained in step D and the fine powder obtained in step A using 80% ethanol as a binder, sieving and granulating, drying at 60 degrees, and sizing. Add sodium carboxymethyl starch, microcrystalline cellulose, and magnesium stearate, mix well, and prepare tablets according to the conventional preparation method to obtain.
  • step D Spray drying the cleansing paste mixture obtained in step C, and collect the spray powder for later use;
  • step E The spray powder obtained in step D and the fine powder obtained in step A are prepared using 80% ethanol as a binder to prepare a soft material, sieved and granulated, dried at 60 degrees, and then granulated. Add sodium carboxymethyl starch, microcrystalline cellulose, and magnesium stearate, mix well, and prepare tablets according to the conventional preparation method to obtain.
  • the API formula is:
  • step D Spray drying the cleansing paste mixture obtained in step C, and collect the spray powder for later use;
  • step E Prepare a soft material with the spray powder obtained in step D and the fine powder obtained in step A using 80% ethanol as a binder, sieving and granulating, drying at 60 degrees, and sizing. Add sodium carboxymethyl starch, microcrystalline cellulose, and magnesium stearate, mix well, and prepare tablets according to the conventional preparation method to obtain.
  • Ephedra 62g Plaster 220g Forsythia 256g Radix Scutellaria 90g Mulberry Bark 300g Bitter Almond 90g Qian Hu 90g Pinellia 90g Tangerine Peel 100g Fritillaria 100g Burdock Seed 100g Honeysuckle 100g Rhubarb 50g Platycodon 66g Licorice 50g
  • the above medicinal materials can be obtained as capsules according to conventional methods.
  • Ephedra 68g Plaster 215g Forsythia 215g Radix Scutellariae 100g Mulberry Bark 220g Bitter Almond 90g Qian Hu 90g Pinellia 90g Tangerine Peel 90g Fritillaria 90g Burdock Seed 90g Honeysuckle 90g Rhubarb 50g Platycodon 50g Licorice 50g
  • the above medicinal materials are prepared into granules according to conventional methods.
  • Ephedra 50g Plaster 200g Forsythia 300g Radix Scutellaria 100g Mulberry Bark 250g Bitter Almond 100g Qianhu 100g Pinellia 100g Tangerine Peel 100g Fritillaria 100g Burdock Seed 100g Honeysuckle 100g Rhubarb 50g Platycodon 50g Licorice 50g
  • the above medicinal materials can be obtained as injections according to conventional methods.
  • the above medicinal materials can be obtained as pills according to conventional methods.
  • the pharmaceutical composition of the present invention prepared in Example 3 that is, the granules (hereinafter referred to as the drug of the present invention) after the granulation in step E of Example 3 and before the tableting are performed.
  • the drug of the present invention after the granulation in step E of Example 3 and before the tableting are performed.
  • the test drug is the pharmaceutical composition of the present invention (prepared in Example 3): the pharmaceutical composition is brown-yellow particles, and each gram of particles is equivalent to 4.095 grams of crude drug.
  • the daily dosage is 22g crude drug/person, orally, the human weight is 60kg, which is equivalent to 0.367g pharmaceutical composition/kg body weight.
  • the positive control drug is Shuanghuanglian Oral Liquid, produced by Harbin Pharmaceutical Group Sanjing Pharmaceutical Co., Ltd.
  • Virus strain Influenza virus subtype murine lung-adapted strain (FM1), provided by the Institute of Chinese Medicine, China Academy of Chinese Medical Sciences. After the 9-day-old chicken embryo allantoic cavity was successively passaged twice, the virus liquid was taken to measure the hemagglutination titer of 1:512, and the aliquots were frozen and stored at -76°C for later use.
  • FM1 Influenza virus subtype murine lung-adapted strain
  • Cell line Canine kidney cell line (MDCK) was purchased from the cell room of the Academy of Military Medical Sciences, and used in this room after routine freezing, resuscitation, and passage.
  • DMEM medium product of GBICO company.
  • the DMEM growth medium is a DMEM culture medium containing 10% newborn calf serum; the DMEM maintenance medium is a serum-free DMEM medium containing 0.002 mg/ml trypsin.
  • the inverted microscope is a product of Olympus, Japan, and the CalaxyS CO 2 incubator is a product of RSBiotech.
  • Cell preparation subculture the MDCK cells for 3-5 days, make them into slices, when the boundary is clear, the three-dimensional sense and the refractive index are strong, digest with trypsin, wait until the needle-like holes appear on the cell surface, suck up the digestion solution, and take a count Disperse the cells with ml of culture medium, count them, and dilute with culture medium to about 3 ⁇ 10 8 /L, then inoculate them in a 96-well culture plate, and wait for the cells to grow into a single layer.
  • Preparation of the pharmaceutical composition of the present invention Weigh 4.88 g of the extract powder of the pharmaceutical composition of the present invention and dissolve it in 40 ml of physiological saline, which is equivalent to 500 mg crude drug/ml. After autoclaving and storing in a refrigerator at 4°C for 5 days, centrifuged at 5000 rpm for 20 minutes, and the supernatant was taken for in vitro experiments.
  • TCID50 of influenza virus Use serum-free DMEM medium to dilute influenza virus FM1 mouse lung-adapted strain continuously by 10 times, and inoculate the virus of each dilution into 3 ⁇ 10 8 /L MDCK cells, each Make 6 replicate wells in parallel with each dilution, and set a normal cell control at the same time. After adsorbing at 37°C for 2 hours, aspirate the virus solution and replace it with a maintenance solution to continue the culture. Observe the cytopathic effect (CPE) under an inverted microscope every day, and record the degree of disease and the number of holes. The cell control has no obvious degeneration, and the virus infected cytopathic disease.
  • CPE cytopathic effect
  • TCID50 median tissue culture infective dosage
  • the MDCK cells grow in the best state, digest the cells with 0.02% EDTA and 0.5% trypsin, adjust the cells to the required concentration with the growth medium, and add the cell liquid to a 96-well cell culture plate, 100 ⁇ L/well, at 37°C , Cultivate to a dense cell monolayer in a 5% CO 2 incubator.
  • Dilute the pharmaceutical composition of the present invention to different concentrations with the maintenance solution respectively 500mg/ml, 250mg/ml, 125mg/ml, 62.5mg/ml, 31.3mg/ml, 15.6mg/ml, 7.8mg/ml, 3.9mg /ml; add to the cell culture plate, 100 ⁇ L/well, the final concentration of the drug in the culture well is 250mg/ml, 125mg/ml, 62.5mg/ml, 31.3mg/ml, 15.6mg/ml, 7.8mg/ml , 3.9mg/ml, 1.9mg/ml; Shuanghuanglian takes the original solution as the original concentration, dilutes them in sequence and adds them to the culture wells.
  • CPE cytopathic condition
  • the experiment also set up a cell control group, a Shuanghuanglian control group and a virus control group.
  • CPE was observed at the same time as the experimental group.
  • the degree of CPE is expressed by the proportion of CPE cells, which is judged according to the following 6-level criteria: (-) Cells grow normally without lesions; ( ⁇ ) Cytopathies are less than 10% of the entire cell monolayer; (+) Cytopathies are less than 25% of the entire cell monolayer; (++) 25%-50% of cells produce lesions; (+++) 50%-75% of cells produce lesions; (++++) 75%-100% of cells produce lesions.
  • the Reed-Muench method is used to calculate the half effective concentration (IC 50 ) of the drug.
  • IC 50 half effective concentration of the drug.
  • the IC 50 of Shuanghuanglian Oral Liquid is about 1:8 dilution. See Table 1.
  • Table 1 Protective effect of the pharmaceutical composition of the present invention on virus-induced cytopathic changes
  • the TCID50 of the mouse influenza virus is 5 ⁇ 10 -4 .
  • the concentration of the positive control drug Shuanghuanglian oral liquid is in the range of 1:8 dilution to 1:1 dilution, all have the effect of inhibiting the pathological changes caused by influenza virus on cells, and its IC 50 is about 1:8 dilution.
  • the 31-125 mg/ml concentration of the drug of the present invention has a protective effect on cytopathic changes caused by influenza virus, and its IC 50 is 65.4 mg/ml.
  • mice ICR mice, half male and half male, weighing 13-15g, purchased from Beijing Weitong Lihua Experimental Animal Technology Co., Ltd., license number SCXK (Beijing 2005-2006).
  • test drug is a pharmaceutical composition of the present invention, which is the same as in vitro anti-mouse influenza A virus test study I. Use 0.5% CMC-Na to make the required concentration before using this product.
  • Virus strain The same in vitro anti-mouse influenza A virus test study I.
  • the 400R high-speed refrigerated centrifuge is a product of Heraeus, Germany, and the AE100 analytical balance is a product of METTLER, Switzerland.
  • virulence assay Mice were lightly anesthetized with ether, nasal infection, each nostril was added 50 ⁇ l of different dilutions of virus, Percent mortality was recorded, and to calculate the minimum lethal dose LD 50. The results showed that the LD 50 of the virus used in this experiment was 2.5 ⁇ 10 -5 .
  • mice were randomly divided into 5 groups, namely the influenza model control group (gavage equal volume 0.5% CMC-Na); Shuanghuanglian group (gavage 10ml/kg, equivalent to 10 times the daily dosage per person); the pharmaceutical composition group of the present invention is administered intragastrically, and the dosages are respectively 1.9g/kg (equivalent to 5 times the daily dosage of a person) and 3.7g/kg (equivalent to 10 times the daily dosage of a person). Times), 7.4g/kg (equivalent to 20 times the human consumption).
  • the mice in each group were administered continuously for 5 days, and the administration volume was 0.4ml/20g body weight.
  • mice in each group were given intragastric administration the day before infection for 5 consecutive days, and the viral pneumonia model group was given an equal volume of solvent. 2 days after administration, the mice were anesthetized with ether shallow intranasally infected with influenza virus strain rat lung adaptation FM1, virus inoculation amount of 10 times LD 50, mice were observed daily after the infection, death of the mice were recorded The test was terminated 2 weeks after infection, and the survival time of mice that did not die was calculated as 14 days. For statistical processing, SPSS software was used for chi-square test and t-test. The results show that both large and medium doses of the pharmaceutical composition of the present invention can significantly reduce the mortality of mice infected with influenza virus, and can significantly prolong the survival time of mice infected with the virus. The results are shown in Tables 2, 3 and Figure 1.
  • Table 2 Protective effect of the pharmaceutical composition of the present invention on death of mice infected with influenza virus
  • Table 3 Protective effect of the pharmaceutical composition of the present invention on death of mice infected with influenza virus
  • mice 70 ICR mice were randomly divided into 6 groups, namely the normal control group (gavage equal volume 0.5% CMC-Na); Viral pneumonia model group (gavage equal volume 0.5% CMC) -Na), Shuanghuanglian group (gave 10ml/kg, equivalent to 10 times the daily dosage of human); the pharmaceutical composition group of the present invention, administered by gavage, the dosage is 1.9g/kg (equivalent to daily dosage per person) 5 times the amount), 3.7g/kg (equivalent to 10 times the daily dosage of a person), 7.4g/kg (equivalent to 20 times the daily dosage of a person). Except for the normal control group, the other groups were all nasally inhaled influenza virus to prepare a virus-infectious pneumonia model.
  • mice in each group were given intragastric administration on the day before infection for 5 consecutive days.
  • the normal control group and the viral pneumonia model group were given an equal volume of solvent .
  • Day 2 after administration in addition to the normal control group, the mice were anesthetized with ether shallow intranasally infected with influenza virus strain rat lung adaptation FM1, virus inoculation amount of 10 times LD 50, dissected 5 days after infection, lung Weigh, and calculate the lung index according to the following formula.
  • the results showed that the lung index of the virus model group was significantly increased compared with the normal control group, and the large and medium doses of the pharmaceutical composition of the present invention could significantly reduce the lung index of the model mice.
  • Statistical analysis was performed with SPSS software for t test. The results are shown in Table 4.
  • Table 4 Effect of the pharmaceutical composition of the present invention on the lung index of mice with viral pneumonia
  • the virus model group is compared with the normal control group, ⁇ p ⁇ 0.01, and each administration group is compared with the model group, **p ⁇ 0.01.
  • the end point is when red blood cells agglutinate (++), and the reciprocal of the suspension dilution is used to indicate the virus titer in the mouse lung.
  • the results show that the virus content in the mouse lungs in the large and medium dose groups of the pharmaceutical composition of the present invention is significantly lower than that in the model group.
  • Statistical analysis was performed with SPSS software for t test. The results are shown in Table 5.
  • Table 5 The effect of the pharmaceutical composition of the present invention on the virus titer in the lungs of mice with viral pneumonia
  • virus model group is compared with the normal control group, ⁇ p ⁇ 0.01, and each administration group is compared with the model group, *p ⁇ 0.05, **p ⁇ 0.01.
  • the 7.4g/kg and 3.7g/kg doses of the pharmaceutical composition of the present invention can reduce the mortality of mice infected with influenza virus by 50% and 63%, respectively, p ⁇ 0.01 compared with the model group.
  • the three doses of 7.4g/kg, 3.7g/kg and 1.9g/kg of the pharmaceutical composition of the present invention can significantly prolong the survival time of virus-infected mice, and compared with the model group, p ⁇ 0.01.
  • the lung index of influenza virus infection model mice was significantly higher than that of normal control mice, p ⁇ 0.01.
  • the virus titer in the lungs of model mice reached 34.7 ⁇ 9.2, and no influenza virus was detected in the lungs of normal control mice.
  • the 7.4g/kg and 3.7g/kg doses of the pharmaceutical composition of the present invention can significantly inhibit the lung index and the virus titer in the lungs of virus-infected mice. Compared with the model group, p ⁇ 0.01.
  • the in vivo anti-influenza virus of the drug combination of the present invention shows that the dosage of 7.4g/kg and 3.7g/kg can reduce the mortality of mice infected with influenza virus by 50% and 63%, respectively, which is p ⁇ 0.05 compared with the model group.
  • the 7.4g/kg, 3.7g/kg and 1.9g/kg doses of the pharmaceutical composition of the present invention can significantly prolong the survival time of virus-infected mice, and compared with the model group, p ⁇ 0.01.
  • the 7.4g/kg and 3.7g/kg doses of the pharmaceutical composition of the present invention can significantly inhibit the lung index and the virus titer in the lungs of virus-infected mice. Compared with the model group, p ⁇ 0.01 and p ⁇ 0.05.
  • the pharmaceutical composition of the present invention has an in vitro antiviral effect; the pharmaceutical composition of the present invention has significant resistance to mice when administered in large doses (7.4g/kg) and medium doses (3.7g/kg) in vivo.
  • the role of golden influenza virus infection is reflected in reducing the mortality of mice, prolonging survival time, alleviating lung lesions and reducing the virus content in the lungs.
  • VeroE6 cells preserved by the Virus Room of the State Key Laboratory of Respiratory Diseases, Guangzhou Institute of Respiratory Health.
  • the virus titer used is 100TCID50.
  • DMSO dimethyl sulfoxide
  • VeroE6 cells in a 96-well plate, add 100 ⁇ L of VeroE6 cells at a concentration of 2 ⁇ 10 5 cells/mL to each well, set up 4 multiple wells, and culture at 37°C with 5% CO 2.
  • the cells grow into a monolayer, the cells are divided into blanks. Group (without cells, only medium), solvent control group (DMSO group), and pharmaceutical composition group of the present invention.
  • the cells were incubated with 5% CO 2 and 37°C for 48 hours. 4 hours before the end of the experiment, 100uL of 1mg/mL MTT solution was added, and the culture was continued for 4 hours. Then, the culture was terminated. Measure the absorbance value of each well at 490nm wavelength on a full-wavelength scanner, and calculate the TC 50 value of the drug with GraphPad Prism 6.0.
  • the antiviral activity of the drug was tested by the cytopathic inhibition method. Inoculate VeroE6 cells in a 96-well plate, add 100 ⁇ L of VeroE6 cells at a concentration of 2 ⁇ 10 5 cells/mL to each well, set up 4 multiple wells, culture with 5% CO 2 at 37°C, and discard the culture solution when the cells grow into a monolayer. Wash the cell surface twice with PBS. The cells are divided into a blank group, a solvent control group, a virus control (negative control) group and a pharmaceutical composition group of the present invention.
  • the degree of cell lesions is recorded according to the following 6-level standards: "-" no lesions; “ ⁇ ” means cytopathic less than 10%; “+” means cytopathic greater than or equal to 10% but less than 25%; “++” means Cell lesions are greater than or equal to 25% but less than 50%; “+++” means that cells have lesions greater than or equal to 50% but less than 75%; “++++” means that more than 75% of cells have lesions.
  • GraphPad Prism 6.0 was used to calculate the half inhibitory concentration (IC 50 ).
  • the TC 50 of the pharmaceutical composition of the present invention on VeroE6 cells is 3383 ⁇ g/ml. See Table 6.
  • the pharmaceutical composition of the present invention has the effect of anti-SARS-CoV-2 virus, and its selection index SI is 5.8.

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Abstract

L'invention concerne l'utilisation d'une composition pharmaceutique dans la préparation d'un médicament antiviral, la composition pharmaceutique étant faite de : Ephedra sinica, gypse, Forsythia, Scutellaria baicalensis, écorce de racines de mûrier blanc, noyaux d'abricot amer, racine de Peucedanum, rhizome de Pinellia, écorce de mandarine séchée, bulbe de fritillaire, fruit de la grande bardane, chèvrefeuille du Japon, rhubarbe chinoise, campanule à grandes fleurs et réglisse chinoise.
PCT/CN2021/078623 2020-03-07 2021-03-02 Utilisation d'une composition pharmaceutique dans la préparation d'un médicament antiviral Ceased WO2021179950A1 (fr)

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MYPI2022004285A MY201855A (en) 2020-03-07 2021-03-02 Use of pharmaceutical composition in preparing anti-viral drug
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CN113995816A (zh) * 2021-11-17 2022-02-01 福州市丰宇中医药研发有限公司 一种治疗流感的中药组合物及其制备方法
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