CN115770236A - Application of turmeric in preparing anti-respiratory virus medicine - Google Patents
Application of turmeric in preparing anti-respiratory virus medicine Download PDFInfo
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Abstract
The invention provides application of at least one of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin or in-vivo metabolite thereof as an active ingredient in preparing a medicament for resisting respiratory viruses. The invention also discloses a medicament taking the curcumin or the analogues thereof as active ingredients, which can inhibit and/or treat respiratory virus infections such as coronavirus, human metapneumovirus, influenza virus, parainfluenza virus, respiratory syncytial virus, measles virus, mumps virus, rubella virus, adenovirus, cytomegalovirus, coxsackie virus, echovirus, herpes simplex virus, varicella-zoster virus or rhinovirus, and provides a new choice for clinic.
Description
Technical Field
The invention belongs to the field of biological medicine, and particularly relates to application of turmeric in preparation of a respiratory virus resistant medicine.
Background
Respiratory tract virus is a virus which takes a respiratory tract as an invasion portal and proliferates in epithelial cells of a mucosal membrane of the respiratory tract to cause local infection of the respiratory tract or lesion of tissues and organs except the respiratory tract, wherein the invasion of the respiratory tract virus can cause diseases such as pharyngolaryngitis, nasosinusitis and the like, and the invasion of the respiratory tract virus can cause lung infectious diseases, such as respiratory tract virus pneumonia. Common respiratory viruses include influenza virus, parainfluenza virus, cytomegalovirus, adenovirus, rhinovirus, coronavirus, and enterovirus such as coxsackie, echovirus, etc., and viruses such as herpes simplex, varicella-zoster, rubella, measles, etc., and pneumonia is also commonly produced by respiratory syncytial virus infection in infants. In addition, some enteroviruses such as coxsackie virus and echovirus can cause pneumonia symptoms through respiratory tract infection.
Pneumonia caused by various respiratory virus infections seriously threatens human health, so that the search for new anti-respiratory virus medicines is very necessary.
The traditional Chinese medicine turmeric was recorded in Tang Ben Cao (herbal medicine of Tang Dynasty) at first, and it is pungent, bitter and warm in nature, enters liver and spleen meridians, and has the effects of breaking blood, promoting qi, restoring menstrual flow and relieving pain. Curcumin (curcumin) is a fat-soluble polyphenol compound extracted from rhizome of Curcuma longa, is a main active ingredient of Curcuma longa playing pharmacological action, is orange yellow crystalline powder, has slightly bitter taste, poor light and heat resistance and extremely low toxicity. Curcumin also has a plurality of analogues, and common analogues (demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin) have the following structures, and researches find that curcumin and analogues of curcumin play a wide role in treating infection, trauma and tumor. However, the action and mechanism of turmeric or its active ingredient against respiratory viruses have not been reported so far.
Disclosure of Invention
The invention provides application of at least one of curcumin, tetrahydrocurcumin, demethoxycurcumin and bisdemethoxycurcumin or metabolites thereof in vivo as an active ingredient in preparation of a medicament for resisting respiratory viruses.
Further, the above-mentioned medicament is a medicament for treating and/or preventing respiratory tract infection caused by respiratory tract virus, the respiratory tract infection being upper respiratory tract infection and/or lower respiratory tract infection.
Furthermore, the above-mentioned medicament for treating and/or preventing upper respiratory tract infection includes medicament for treating and/or preventing rhinitis, pharyngitis, sinusitis, otitis media, laryngitis and/or epiglottitis;
the medicament for treating and/or preventing the lower respiratory tract infection comprises a medicament for treating and/or preventing tracheitis, bronchitis and/or pneumonia.
Further, the above-mentioned drug is a drug which decreases the activity of respiratory viruses.
Further, the above-mentioned respiratory virus is coronavirus, human metapneumovirus, influenza virus, parainfluenza virus, respiratory syncytial virus, measles virus, mumps virus, rubella virus, adenovirus, cytomegalovirus, enterovirus, herpes simplex virus, varicella-zoster virus or rhinovirus; the enterovirus includes Coxsackie virus and echovirus.
Further, the active ingredient is at least one of curcumin, demethoxycurcumin and bisdemethoxycurcumin or a metabolite thereof in vivo, and the respiratory virus is human metapneumovirus;
or, the active ingredient is tetrahydrocurcumin or a metabolite thereof in vivo, and the respiratory virus is a coronavirus or an influenza virus.
Further, the above-mentioned coronavirus is SARS-Cov-2 virus, and said influenza virus is influenza A virus.
The invention also provides a medicament for resisting respiratory viruses, which is a preparation prepared by taking at least one of curcumin, tetrahydrocurcumin, demethoxycurcumin and bisdemethoxycurcumin or a metabolite thereof in vivo as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
Further, the above-mentioned respiratory virus is coronavirus, human metapneumovirus, influenza virus, parainfluenza virus, respiratory syncytial virus, measles virus, mumps virus, rubella virus, adenovirus, cytomegalovirus, enterovirus, herpes simplex virus, varicella-zoster virus or rhinovirus; the enterovirus includes Coxsackie virus and echovirus.
Further, the content of the active ingredient in the above preparation is not less than 1. Mu.M, preferably not less than 5. Mu.M.
It will be apparent that various other modifications, substitutions and alterations can be made in the present invention without departing from the basic technical concept of the invention as described above, according to the common technical knowledge and common practice in the field.
The present invention will be described in further detail with reference to the following examples. This should not be understood as limiting the scope of the above-described subject matter of the present invention to the following examples. All the technologies realized based on the above contents of the present invention belong to the scope of the present invention.
Drawings
FIG. 1 shows the results of the cell activity test of bisdemethoxycurcumin on the action of 16 HBE.
FIG. 2 shows the results of the cell viability assay of the effect of demethoxycurcumin on 16 HBE.
Fig. 3 shows the results of the cell activity test of curcumin on 16 HBE.
FIG. 4 shows the results of a HMPV virus titer assay in cells with bisdemethoxycurcumin.
FIG. 5 shows the results of tests of HMPV virus titer in cells with demethoxycurcumin.
Fig. 6 shows the results of curcumin assay on HMPV virus titer in cells.
FIG. 7 shows the results of the HMPV virus titer test of bisdemethoxycurcumin on infected cells.
FIG. 8 is the results of the HMPV virus titer test on infected cells with demethoxycurcumin.
Fig. 9 shows the results of HMPV virus titer test of curcumin on infected cells.
FIG. 10 shows the body weight change of mice.
FIG. 11 shows the results of the measurement of the pulmonary viral titer of mice.
FIG. 12 shows a PCR amplification standard curve for SARS-Cov-2 virus.
Figure 13 is the toxicity of tetrahydrocurcumin (sample a) on Vero E6 cells.
FIG. 14 is a graph of the antiviral activity of tetrahydrocurcumin (sample A) against SARS-CoV-2WIV04 strain.
FIG. 15 is a graph of the antiviral activity of tetrahydrocurcumin (sample A) against the SARS-CoV-2Omicron strain.
Fig. 16 is a graph of the toxicity of tetrahydrocurcumin (sample a) to MDCK cells.
FIG. 17 is a graph of the antiviral activity of tetrahydrocurcumin (sample A) against influenza A virus H1N 1.
Detailed Description
The starting materials used in the present invention are, unless otherwise stated, known products, obtained by purchasing commercially available products.
The invention utilizes Vero-E6 cells to culture Human Metapneumovirus (HMPV) live virus, and virus liquid (MOI = 10) is obtained by separation and is used for experimental examples 1-3.
The MDCK cell line used for detection was stored in the laboratory of the Wuhan virus institute of Chinese academy of sciences.
Example 1 preparation of curcumin-containing drug of the invention
Curcumin was diluted with a culture medium for cell culture to 5. Mu.M, 10. Mu.M, 20. Mu.M, 30. Mu.M, or 40. Mu.M, to prepare a mother liquor by adding DMSO to the mother liquor.
Example 2 preparation of a drug containing demethoxycurcumin according to the present invention
The mother liquor was prepared by adding DMSO to demethoxycurcumin, and then diluted with a medium for cell culture to give solutions having concentrations of 5. Mu.M, 10. Mu.M, 20. Mu.M, 30. Mu.M and 40. Mu.M.
Example 3 preparation of a bis-demethoxycurcumin-containing drug of the present invention
Didemethoxycurcumin was added with DMSO to prepare a mother liquor, and then diluted with a medium for cell culture to give solutions having concentrations of 5. Mu.M, 10. Mu.M, 20. Mu.M, 30. Mu.M and 40. Mu.M.
Example 4 preparation of a Tetrahydrocurcumin-containing drug of the invention
The mother liquor was prepared by adding DMSO to tetrahydrocurcumin, and then diluted with a medium for cell culture to give solutions having concentrations of 0.09. Mu.M, 0.27. Mu.M, 0.82. Mu.M, 2.47. Mu.M, 7.41. Mu.M, 22.22. Mu.M, 66.67. Mu.M and 200. Mu.M.
Experimental example 1 cytotoxicity experiments on curcumin, demethoxycurcumin and bisdemethoxycurcumin
Cell recovery: and (3) taking out the frozen 16HBE cells from the liquid nitrogen tank, quickly placing the cells into a 37 ℃ water bath kettle to shake and dissolve, adding the dissolved cells into a 15ml BD tube which has absorbed 3ml of culture solution, centrifuging at 800rpm for 4min, removing supernatant, adding 1ml of culture solution for resuspension, adding the resuspended cells into a T25 culture bottle, and placing the bottle into an incubator for culture.
Cell plating: when 16HBE cells were cultured to approximately 80%, they were digested, resuspended and counted, diluted to a cell concentration of 1 x 10 5 Per mL; add 100. Mu.L per well to 96-well plate; adding curcumin, demethoxycurcumin and bisdemethoxycurcumin solutions with different concentrations into cells; setting a control hole and a blank hole; putting into an incubator to culture for 24h overnight. Sucking out the culture solution containing the medicine, washing with PBS for three times, adding new culture solution, and adding 10 μ L of CCK-8 reagent; after 1-4h of action, the absorbance value at 450nm is measured by using an enzyme-labeling instrument, and the cell survival rate is calculated according to the following formula.
A＝A C -A 0 /A b -A 0
A c Is a medicine adding hole;
A b is an unadministered well containing cells;
A 0 non-dosed wells containing no cells;
the obtained results are shown in fig. 1 to 3, and the results show that the experimental results show that when the concentration of the drug solution is higher (higher than 50 μ M), the cell viability of the 16HBE cells can be influenced, and the virus infection and the virus titer can be influenced, so that the concentration which has no influence on the cell viability is selected in the subsequent experiments.
Experimental example 2 experiments on HMPV viral activity inhibition by curcumin, demethoxycurcumin and bisdemethoxycurcumin
1. After the logarithmic growth phase of cells were digested and resuspended the day before the experiment, 2 x 10 cells were added 5 16HBE cells/well were seeded in 24-well plates and grown overnight. The next day, the cell confluence reached 70-80%, 200 μ L HMPV virus solution (MOI = 10) was added, and the incubator was infected for 2h; suction deviceThe virus was washed with PBS for three times to prepare drug-containing solutions (curcumin, demethoxycurcumin, bisdemethoxycurcumin solutions of curcumin, demethoxycurcumin, etc. of examples 1-3, 0. Mu.M, 5. Mu.M, 10. Mu.M, 20. Mu.M, 30. Mu.M, 40. Mu.M), and the drug-containing solutions were added to each well of each experimental group. After 24h of action, the supernatant was discarded, and RNA was extracted using the total RNA extraction kit according to the instructions. Carrying out reverse transcription on the extracted RNA by using a reverse transcription kit (AG 11706-S); a TaqMan fluorescence probe method and a fluorescence quantitative PCR (Q-PCR) method are used for investigating the intracellular viral load after adding curcumin, demethoxycurcumin and bisdemethoxycurcumin with different concentrations according to Cq values of different groups in a Q-PCR experiment.
The results are shown in fig. 4-6, and experimental results show that the drug-containing solution added with curcumin and bisdemethoxycurcumin can effectively reduce the intracellular virus titer, which indicates that curcumin and bisdemethoxycurcumin can effectively inhibit the virus activity in cells.
2. One day before the experiment, after the cells in the logarithmic growth phase were digested and resuspended, 2 x 10 cells were added 5 The 16 HBE/well cells were seeded in 24-well plates and grown overnight. The next day, after adding maximum drug concentration (40 μ M) corresponding to curcumin, demethoxycurcumin and bisdemethoxycurcumin into the culture solution for 24h, adding HMPV virus solution 200 μ L (MOI = 10), and infecting at 37 deg.C for 2h; then, 3% FBS-containing DMEM virus-maintained medium was added. After infection for 24h, RNA was extracted using the total RNA extraction kit, and RNA was extracted according to the instructions. For reverse transcription and fluorescent quantitative PCR experiments, reference is made to the above method.
The results are shown in fig. 7-9, and experimental results show that under the action of the drug, the titer of virus-infected cells is reduced, and the titer is significantly different from that of a control group, which indicates that curcumin and analogues thereof can effectively inhibit the virus activity in the cells and have the potential of preventing HMPV virus infection.
Experimental example 3 curcumin, demethoxycurcumin and bisdemethoxycurcumin treatment experiment for inhibiting mouse HMPV viral infection
5-6weeks of BALB/c mice, 17-20g, were purchased; a female; adaptation for one week.
Experimental grouping: (total of 3 groups, 3 per group):
1. virus infection group (hMPV); 2. drug group (example 3) administered at a dose of 100mg/kg; 3. the ribavirin group is administered at a dose of 50mg/kg;
the experimental steps are as follows:
1. preparing before experiment, randomly grouping mice and marking;
a. virus preparation: before the experiment, the virus is taken out from a refrigerator at the temperature of-80 ℃ and placed on ice;
b. anesthesia: after weighing the mice, carrying out intraperitoneal injection on 1% pentobarbital (the dose is 50mg/kg body weight), placing the mice in a feeding cage, and waiting for about 5-10 min;
2. viral instillation
The anesthetized mice were fixed and treated with purified hMPV virus by nasal drip (virus titer 10) 7 ) Fully opening the air passage, and dripping 10 mu L of virus liquid into two nostrils alternately, wherein the dripping amount is 60 mu L; the condition of the mouse is observed until the mouse is awake, and appropriate warming measures can be taken.
3. The virome is orally administrated with 0.4ml of bisdemethoxycurcumin solution every day; the ribavirin group is administered with 100 mu L of ribavirin solution every day;
4. continuously administering for 4 days, and weighing the body weight of the mice; observing the state of the mouse; after 5 days, picking up eyeballs and taking blood; lung tissues of mice were each placed in EP tubes frozen in a-80 ℃ freezer to examine the lung virus titer.
A. Blood is taken from eyeballs:
the mouse picks up eyeballs and takes blood, 1500rpm,4 ℃; centrifuge for 10min and carefully aspirate the supernatant. For virus titer detection (Q-PCR), inflammatory factor levels (ELISA), immune cell species detection (lymphocytes; T cells; macrophages).
B. Lymph node lymphocyte suspension preparation
1) After the mice pick eyeballs and blood, the cervical vertebrae are dislocated to kill the mice, and then the lymph nodes of the mice are taken out. Adding 1ml of PBS into a clean bacterial culture dish, then paving a stainless steel net with 100 meshes (the steel net is larger than the dish as much as possible) on the opening of the dish, and then putting the picked lymph node tissue on the steel net;
2) The lymph nodes were ground with the end of a 10ml syringe handle until there was no tissue mass. In the process, the lymph node tissue is ensured to be always soaked in PBS;
3) Transferring the cell suspension obtained by grinding into a 15ml centrifuge tube through a 100-mesh filter screen, flushing the plate with PBS (phosphate buffer solution), and collecting more cells as much as possible to reduce cell loss;
4) Centrifuging at the temperature of 4 ℃ and the rpm of 500 for 1min;
5) Centrifuging lymph node filtered liquid, removing supernatant, centrifuging at 4 ℃ at 500Xg for 4 minutes, and removing supernatant; 1ml of PBS was added for cell counting, then centrifuged and frozen at-80 ℃ for subsequent analysis of immune cells.
The results are shown in fig. 10 to 11, and it can be seen that the weight of the mice is reduced after the mice are infected with the HMPV virus, and the weight reduction of the mice can be improved by the ribavirin and bisdemethoxycurcumin administration group. The virus titer of the lung of the mice in the bisdemethoxycurcumin administration group is lower than that of the HMPV group, so that the bisdemethoxycurcumin can obviously reduce the virus titer in the mice and has a treatment effect on preventing respiratory virus pneumonia caused by HMPV infection.
Experimental example 4 Tetrahydrocurcumin resistant to novel coronavirus
The SARS-CoV-2 virus used for detection was WIV04 strain and Omicron variant strain (CSTR: 16533.06.IVCAS 6.7600), which was deposited by the institute of Wuhan Virus, national academy of sciences. Viral infection experiments were all performed in the BSL-3 laboratory.
The cell line used for detection is monkey kidney cell line Vero E6, and is subcultured in the laboratory. Cell culture conditions: culturing in DMEM medium supplemented with 10% fetal bovine serum, 100U/mL penicillin and 100. Mu.g/mL streptomycin at 37 ℃ and 5% 2 Culturing in an incubator.
1. Experimental methods
Cytotoxicity test: after 24h of cell culture, cellTiter-Glo reagent was added and incubated at room temperature for 10min. And then transferring all cell lysates into a totally black 96-well plate, and detecting Lum luminescent signals on a Synergy LX multifunctional microplate detector. The toxicity of the compound to cells was calculated from the luminescence values.
Compound antiviral assay: after the cells are cultured for 24 hours, the culture supernatant is taken and added into AVL lysine buffer solution in the virus nucleic acid extraction kit, the incubation is carried out for 10min at room temperature, and then absolute ethyl alcohol is added for inactivation and virus Lysis. Viral RNA was extracted according to the kit instructions. Then configuring an RT-PCR reaction system, and detecting the S gene of the virus by fluorescent quantitative PCR reaction; meanwhile, a plasmid with the S gene is used as a standard curve.
The antiviral activity and cytotoxicity of the compound are represented by the inhibition rate (%) and cell viability (%) of the compound against viral replication. The calculation formula is as follows:
cell viability (%) =100 × sample reading/average value of cell control group
Inhibition (%) =100 × (1-sample RNA copy number/virus control RNA copy number)
And (3) data analysis: EC of the Compound 50 Value sum CC 50 Values were calculated for fit using GraphPad Prism software.
The cytotoxicity effect of the detected sample is obtained by detecting the activity of the Vero E6 cell after the compound treatment; and detecting the replication level of the Vero E6 cell infected by the virus after the compound treatment by a qRT-PCR method to obtain the inhibition effect of the detected sample on virus replication. The results are shown in FIGS. 12 to 15 and Table 1.
TABLE 1 Tetrahydrocurcumin anti-neocoronavirus results
This experimental example evaluated the effect of tetrahydrocurcumin on the replication of SARS-CoV-2 virus on Vero E6 cells. The experimental result shows that the concentration CC of the toxicity of the tetrahydrocurcumin on the half number of Vero E6 cells 50 It was 140.1. Mu.M. Half effective concentration EC of tetrahydrocurcumin for inhibiting replication of SARS-CoV-2WIV04 strain in Vero E6 cells 50 25.49 μ M; half effective concentration EC for SARS-CoV-2Omicron BA.1 strain 50 17.61. Mu.M.
That is, tetrahydrocurcumin has an effect of inhibiting the replication of SARS-CoV-2.
Experimental example 5 tetrahydrocurcumin anti-influenza Virus
The influenza A virus used (H1N 1, A/puerto Rico/8/1934) was tested and stored in the laboratory.
The cell line used for detection is MDCK cell, and is preserved in laboratories of Wuhan virus institute of Chinese academy of sciences. Cell culture conditions: culturing in DMEM medium supplemented with 10% fetal calf serum, 100U/ml penicillin and 100. Mu.g/ml streptomycin at 37 ℃ and 5% 2 Culturing in an incubator.
1. Experimental methods
Cytotoxicity experiments: after 24h of cell culture, cellTiter-Glo reagent was added and incubated at room temperature for 10min. And then transferring all cell lysates into a totally black 96-well plate, and detecting Lum luminescent signals on a Synergy LX multifunctional microplate detector. The toxicity of the compound to cells was calculated from the luminescence values.
Compound antiviral assay: after the cells are cultured for 24h, the culture supernatant is taken and added with MUNANA substrate, incubated for 45min at 37 ℃, and then the fluorescence luminescence (excitation light 360 nm/emission light 485 nm) is detected on a Synergy LX multifunctional microplate detector.
The antiviral activity and cytotoxicity of the compound are represented by the inhibition rate (%) and cell viability (%) of the compound against viral replication. The calculation formula is as follows:
cell viability (%) =100 × sample reading/average value of cell control group
Inhibition (%) =100-100 × (sample fluorescence-cell control fluorescence)/(virus control fluorescence-cell control fluorescence)
And (3) data analysis: EC of the Compound 50 Value sum CC 50 Values were calculated for fit using GraphPad Prism software.
2. Results of the experiment
The cytotoxicity effect of the detected sample is obtained by detecting the activity of the MDCK cells treated by the tetrahydrocurcumin; the inhibition effect of the detected sample on virus replication is obtained by detecting the protein expression level of virus infected MDCK cells treated by tetrahydrocurcumin. The results are shown in FIGS. 16 to 17 and Table 2.
TABLE 2 tetrahydrocurcumin anti-influenza virus data
| Compound (I) | EC 50 (μM) | CC 50 (μM) |
| Tetrahydrocurcumin | ＞200 | 95.48 |
This experimental example evaluated the effect of tetrahydrocurcumin on the replication of influenza a virus H1N1 on MDCK cells. The experimental result shows that the half cytotoxicity concentration CC of the tetrahydrocurcumin on MDCK cells 50 95.48. Mu.M. Half-effective concentration EC of tetrahydrocurcumin on inhibiting replication of influenza A virus H1N1 strain in MDCK cells 50 Is > 200. Mu.M.
That is, tetrahydrocurcumin has an effect of inhibiting the replication of influenza a virus H1N 1.
In conclusion, the invention proves the effects of curcumin, demethoxycurcumin and bisdemethoxycurcumin on resisting human metapneumovirus and the effects of tetrahydrocurcumin on resisting novel coronavirus and influenza A virus, can be used for treating respiratory tract virus infection, and has good clinical application prospect.
Claims (10)
1. The application of at least one of curcumin, demethoxycurcumin, bisdemethoxycurcumin and tetrahydrocurcumin or in vivo metabolite thereof as active ingredient in preparing medicine for resisting respiratory viruses is provided.
2. Use according to claim 1, wherein the medicament is a medicament for the treatment and/or prophylaxis of respiratory infections caused by respiratory viruses, said respiratory infections being upper respiratory infections and/or lower respiratory infections.
3. The use of claim 2, wherein the medicament for the treatment and/or prevention of an upper respiratory infection comprises a medicament for the treatment and/or prevention of rhinitis, pharyngitis, sinusitis, otitis media, laryngitis and/or epiglottitis;
the medicament for treating and/or preventing the lower respiratory tract infection comprises a medicament for treating and/or preventing tracheitis, bronchitis and/or pneumonia.
4. The use according to any one of claims 1 to 3, wherein the medicament is a medicament for reducing the activity of a respiratory virus.
5. The use according to any one of claims 1 to 3, wherein the respiratory virus is a coronavirus, human metapneumovirus, influenza virus, parainfluenza virus, respiratory syncytial virus, measles virus, mumps virus, rubella virus, adenovirus, cytomegalovirus, enterovirus, herpes simplex virus, varicella-zoster virus or rhinovirus; the enterovirus includes Coxsackie virus and echovirus.
6. The use according to claim 5, wherein the active ingredient is at least one of curcumin, demethoxycurcumin, bisdemethoxycurcumin, or a metabolite thereof in vivo, and the respiratory virus is human metapneumovirus;
or, the active ingredient is tetrahydrocurcumin or a metabolite thereof in vivo, and the respiratory virus is a coronavirus or an influenza virus.
7. The use of claim 6, wherein the coronavirus is a SARS-Cov-2 virus and the influenza virus is an influenza A virus.
8. The medicine for resisting respiratory viruses is characterized by being a preparation prepared by taking at least one of curcumin, tetrahydrocurcumin, demethoxycurcumin and bisdemethoxycurcumin or a metabolite thereof in vivo as an active ingredient and adding pharmaceutically acceptable auxiliary materials or auxiliary ingredients.
9. The medicament of claim 8, wherein the respiratory virus is a coronavirus, human metapneumovirus, influenza virus, parainfluenza virus, respiratory syncytial virus, measles virus, mumps virus, rubella virus, adenovirus, cytomegalovirus, enterovirus, herpes simplex virus, varicella-zoster virus or rhinovirus; the enterovirus includes Coxsackie virus and echovirus.
10. Pharmaceutical according to claim 8 or 9, wherein the active ingredient content of the formulation is not less than 1 μ M, preferably not less than 5 μ M.
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| CN110891557A (en) * | 2018-06-06 | 2020-03-17 | 黄志清 | Curcumin carbon quantum dot and application thereof |
| WO2021173020A1 (en) * | 2020-02-24 | 2021-09-02 | Nomi Biotech Corporation Sp. Z O.O. | Formulation of a turmeric extract comprising curcuminoids, method of production thereof, the use of the formulation and products comprising thereof |
| WO2021256547A1 (en) * | 2020-06-19 | 2021-12-23 | 株式会社セラバイオファーマ | Composition for treating, preventing, or alleviating sars-cov-2 infectious disease |
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| WO2011049348A2 (en) * | 2009-10-19 | 2011-04-28 | 주식회사 중앙백신연구소 | Antiviral agents obtained from curcuma longa, having inhibitory activities against avian influenza, swine influenza, and novel influenza |
| CN102462674A (en) * | 2010-11-04 | 2012-05-23 | 刘丽宏 | Application of curcumin and curcumin derivatives in preparation of drug and/or health care product for treating and preventing diseases related to human cytomegalovirus infection |
| CN110891557A (en) * | 2018-06-06 | 2020-03-17 | 黄志清 | Curcumin carbon quantum dot and application thereof |
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