CN101744805A - Novel use of natural amentoflavone in curing viral diseases - Google Patents
Novel use of natural amentoflavone in curing viral diseases Download PDFInfo
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- CN101744805A CN101744805A CN200910248591A CN200910248591A CN101744805A CN 101744805 A CN101744805 A CN 101744805A CN 200910248591 A CN200910248591 A CN 200910248591A CN 200910248591 A CN200910248591 A CN 200910248591A CN 101744805 A CN101744805 A CN 101744805A
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Abstract
The invention discloses a novel use of natural amentoflavone compound in curing viral diseases. The natural amentoflavone compound is extracted from plants, Chinese medicinal materials or prepared herbal medicine in small pieces ready for decoction, which contain the components of amentoflavone. Through conventional methods, the compound is used as medicinal ingredients to prepare pharmaceutical preparations for curing viral diseases, and can be used separately or be combined with acceptable excipient in the pharmaceutical process to prepare oral preparations of troches, capsules, granules, sustained-release preparations, dropping pills and the like, to prepare gels, suppository and the like to be used in cavities such as the vagina, the anus, the nasal cavity and the like, and to prepare injections for use in muscles or veins. The content of amentoflavone is above 90 percent. The invention discloses the effective ingredient of the Chinese herbal Selaginella in the curing viral diseases, provides a scientific basis for clinical application of Selaginella and enables amentoflavone to be used as a natural antiviral agent, and the antiviral agent causes no addiction and is small in dosage.
Description
Technical field:
The present invention relates to medical technical field, relate to the new purposes of amentoflavone (amentoflavone), be specifically related to the new purposes of amentoflavone aspect the treatment viral disease at pharmaceutical field.
Background technology:
Various hepatitis viruss such as hepatitis B virus and the caused disease of viral infection of various Respirovirus are one group of commonly encountered diseases, and its sickness rate is progressively ascendant trend in the whole world, and new Causative virus constantly occurs.As being exactly by the caused a kind of serious viral infectious of the variant viral of coronavirus at the beginning of 2003 in the popular atypical pneumonias of China part provinces and cities (SARS).The H5N1 virus that also had occurred the year before last reaches the disease that the present H1N1 virus that occurs infects, and all belongs to disease of viral infection.
The harm of disease of viral infection not only is caused various infection, and main is its most secondary or merging bacterial infection, so cause clinical symptoms heavier, the course of disease is longer, and the performance variation is one of principal disease of harm humans health always.
The clinical treatment viral disease is based on chemosynthesis and semisynthetic medicine at present.But, because being extensive use of of chemosynthesis and semi-synthetic antibiotic, antiviral drugs since over half a century brought out pathogenic bacteria and produced endurance strain, and day by day increased the conditionality pathogenic bacterium.Shortcoming such as its toxic and side effects is bigger in addition is although cause such medicine to have many deficiencies as the first-line treatment medicine.Therefore, it is little and have broad application prospects that anti virus herb has side effect, the succeeding in developing generation important social benefit of this new drug.
Amentoflavone is a kind of by the chemical constituent with remarkable antivirus action that extracts in natural plants, Chinese crude drug or the prepared slices of Chinese crude drugs.The English of this natural product is by name: amentoflavone; Molecular formula is C
30H
18O
10Molecular weight is 538.47, chemical structure names is 4H-1-.alpha.-5:6-benzopyran-4-ketone, 8-[5-(5,7-dihydroxy-4-oxo-4H-1-.alpha.-5:6-benzopyran)-and the 2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)-, English chemical constitution name (4H-l-Benzopyran-4-one, 8-[5-(5,7-dihydroxy-4-oxo-4H-l-benzopyran-2-yl)-and 2-hydroxyphenyl]-5,7-dihydroxy-2-(4-hydroxyphenyl)-), structural formula is as follows:
The regulation Herba Selaginellae is the dry herb of Spikemoss plant Herba Selaginellae Selaginellatamariscina (Beauv.) Spring or cushion Herba Selaginellae Selaginella pulvinata (Hook.et Grev.) Maxim. in the Chinese Pharmacopoeia version in 2005.All can gather the whole year, removes fibrous root and silt, dries.Suffering, flat.Return liver, heart channel.Has promoting blood circulation to restore menstrual flow.Be used for amenorrhea dysmenorrhea ， mass in the abdomen mass in the abdomen, injury from falling down.The hemostasis of the Herba Selaginellae carbonization stasis of blood.Be used for spitting blood, metrorrhagia is had blood in stool, proctoptosis.Contain the number of chemical composition in the Herba Selaginellae, as flavonoid, have now found that and contain apigenin (apigenin), amentoflavone (amentoflavone), hinokiflavone (hinokiflavone), isocryptomerin (isocryptomerin) and Oman's holder yellow (amentoflavone) etc. in the Herba Selaginellae; Chemical compounds such as the plain class of phenylpropyl alcohol, alkaloids, phenols, organic acid.Pharmacological action shows to have: effects such as immunity and antitumor action, the effect to blood system, antiviral, antibacterial and antiinflammatory action, antalgic and sedative.And being used for the treatment of the effect of viral diseases such as hepatitis B virus, influenza virus, amentoflavone do not see relevant report.
Summary of the invention:
Technical problem to be solved by this invention provides the new purposes that a kind of native compound amentoflavone is used for the treatment of viral disease.Can be prepared into the pharmaceutical preparation that is used for the treatment of viral disease clinically.Described native compound amentoflavone, be from the plant, Chinese crude drug or the prepared slices of Chinese crude drugs that contain this composition, to extract, as Chinese medicine Herba Selaginellae or its prepared slices of Chinese crude drugs, preferred Chinese crude drug is: the dry herb of Spikemoss plant Herba Selaginellae Selaginella tamariscina (Beauv.) Spring or cushion Herba Selaginellae Selaginella pulvinata (Hook.etGrev.) Maxim..Prepare the pharmaceutical preparation that is used for the treatment of viral disease with this chemical compound as active ingredient, can combine separately or with acceptable excipient in the pharmaceutical technology, make the pharmaceutical dosage form of oral administration, cavity/canal drug administration, muscle or intravenously administrable according to conventional method.The content of described amentoflavone is more than 90%.The present invention has found the active ingredient of Chinese medicine Herba Selaginellae treatment viral disease, for its clinical practice provides scientific basis, makes the amentoflavone can be as a natural antiviral agent, has no addiction, characteristics that consumption is little.
Amentoflavone adopts the extracorporeal culture-ing screening experiment, the result shows: amentoflavone has inhibitory action to the HBsAg and the HBeAg of hepatitis B virus, and amentoflavone suppression ratio to HBsAg, HBeAg when the concentration of 12.5ug/ml is respectively 75.7%, 63.6%; Amentoflavone suppression ratio to HSV-I when the concentration of 25ug/ml is respectively 55.9%; Amentoflavone is respectively 61.1% to the suppression ratio of influenza virus A type (H1N1) when the concentration of 12.5ug/ml; Amentoflavone suppression ratio to CVB3 when the concentration of 25ug/ml is respectively 39.8%.
Therefore, amentoflavone is a kind of antiviral ingredients that obtains that separates from natural plants, and component content is a kind of anti virus herb new drug preparation with DEVELOPMENT PROSPECT more than 90%.
The clinical treatment viral disease is based on chemosynthesis and semisynthetic medicine at present.But, because being extensive use of of chemosynthesis and semi-synthetic antibiotic, antiviral drugs since over half a century brought out pathogenic bacteria and produced endurance strain, and day by day increased the conditionality pathogenic bacterium.Shortcoming such as its toxic and side effects is bigger in addition is although cause such medicine to have many deficiencies as the first-line treatment medicine.Therefore, it is little and have broad application prospects that anti virus herb has side effect, the succeeding in developing generation important social benefit of this new drug.
The specific embodiment:
Embodiment 1: amentoflavone (amentoflavone) is to the inhibitory action of hepatitis B virus.
Materials and methods
1. cell in vitro model: the HepG2 cell of hepatitis B virus (HBV) transfection, i.e. HepG2 2.215 cells.
2.MTT the toxicity of method test sample pair cell.
3. euzymelinked immunosorbent assay (ELISA) (EIA) test sample is to the inhibitory action of HBsAg and HBeAg.
Process of the test
1. the cytotoxicity of medicine detects
HepG2 2.2.15 cell was cultivated in 96 porocyte culture plates after 48 hours, added variable concentrations pastille culture fluid, continued to cultivate 9 days (changing liquid once in per 3 days), detected cell survival rate with mtt assay, determined the toxic concentration of medicine to HepG2 2.2.15 cell.
2. medicine detects HBV virus antigen inhibitory action
HepG2 2.2.15 cell is cultivated after 48 hours in 96 porocyte culture plates, the pastille culture fluid that adds the series concentration under the non-toxic concn, continue to cultivate 9 days (changing liquid once in per 3 days), collect supernatant, detect HBsAg and HBeAg with HBsAg and HBeAg diagnostic kit (ELISA method).
Experimental result:
Experimental result shows that antigenic secretion has inhibitory action to amentoflavone (amentoflavone) to HBsAg, HBeAg, is 12.5ug/ml, i.e. (TC to the non-toxic concn of 2215 cells
0=12.5ug/ml), amentoflavone suppression ratio to HBsAg, HBeAg when the concentration of 12.5ug/ml is respectively 75.7%, 63.6%.
Embodiment 2: amentoflavone (amentoflavone) is external to suppress active test material and method to herpesvirus
1. external host cell: Vero cell.
2. Strain: herpes simplex virus I-type (HSV-I).
3.CPE the toxicity of method detection of drugs pair cell.
4.CPE method (cytopathy) detection of drugs is to the inhibitory action of herpesvirus.
The antivirus test process
1. the cytotoxicity of medicine detects
After the Vero cell is cultivated and formed monolayer, add the medicinal liquid of variable concentrations in 96 porocyte culture plates, continue to cultivate 3 days, with the toxicity of CPE method detection of drugs the Vero cell.
2. the effect of medicine anti-herpesvirus detects
After the Vero cell is cultivated and formed monolayer,, add the pastille culture fluid of the series concentration under the non-toxic concn again in 96 porocyte culture plates, continue to cultivate 3 days, determine the inhibitory action of medicine herpesvirus through the CPE method with the HSV-I infection cell of 10TCID50.
Experimental result:
Experimental result shows that amentoflavone (amentoflavone) is 25ug/ml to the non-toxic concn of Vero cell, i.e. (TC0=25ug/ml), the amentoflavone suppression ratio to HSV-I when the concentration of 25ug/ml is respectively 55.9%.
Embodiment 3: amentoflavone (amentoflavone) is external to suppress active test material and method to influenza virus
1. external host cell: mdck cell.
2. Strain: influenza virus A type (H1N1) (A3/ capital section/30/95).
3.CPE the toxicity of method detection of drugs pair cell.
4.CPE method (cytopathy) detection of drugs is to the inhibitory action of influenza virus.
Process of the test
1. the cytotoxicity of medicine detects
After mdck cell is cultivated and formed monolayer, add the medicinal liquid of variable concentrations in 96 porocyte culture plates, continue to cultivate 3 days, with the toxicity of CPE method detection of drugs mdck cell.
2. the effect of medicine resisiting influenza virus detects
After mdck cell is cultivated and formed monolayer,, add the pastille culture fluid of the series concentration under the non-toxic concn again in 96 porocyte culture plates, continue to cultivate 3 days, determine the inhibitory action of medicine influenza virus through the CPE method with the influenza infection cell of 100TCID50.
Experimental result:
Experimental result shows that amentoflavone (amentoflavone) is 12.5ug/ml to the non-toxic concn of mdck cell, i.e. (TC0=12.5ug/ml), amentoflavone is respectively 61.1% to the suppression ratio of influenza virus A type (H1N1) when the concentration of 12.5ug/ml.
Embodiment 4: amentoflavone (amentoflavone) is external to suppress active detection, materials and methods to Coxsackie virus
1. external host cell: Vero cell.
2. Strain: anti-coxsackie B 3 viruses (CVB3) Nancy strain.
3.CPE the toxicity of method detection of drugs pair cell.
4.CPE method (cytopathy) detection of drugs is to the inhibitory action of coxsackie B 3 viruses.
Process of the test
1. the cytotoxicity of medicine detects
After the Vero cell is cultivated and formed monolayer, add the medicinal liquid of variable concentrations in 96 porocyte culture plates, continue to cultivate 3 days, with the toxicity of mtt assay detection of drugs the Vero cell.
2. anti-coxsackie B 3 virus functions of medicine detect
After the Vero cell is cultivated in 96 porocyte culture plates and is formed monolayer, coxsackie B 3 virus infected cells with 100TCID50, the pastille culture fluid that adds the series concentration under the non-toxic concn again continues to cultivate 3 days, determines the inhibitory action of medicine to coxsackie B 3 viruses through the CPE method.
Experimental result:
Experimental result shows that amentoflavone (amentoflavone) is 25ug/ml to the non-toxic concn of Vero cell, i.e. (TC0=25ug/ml), the amentoflavone suppression ratio to CVB3 when the concentration of 25ug/ml is respectively 39.8%.
Embodiment 5:
Get amentoflavone (amentoflavone) 25g, add starch dust 200g,, add Pulvis Talci 5g with equivalent incremental method mixing, magnesium stearate 2g, mixing is used 85% alcohol granulation, drying, granulate is pressed into 1000, every day 3 times, each 2.
Embodiment 6:
Get amentoflavone (amentoflavone) 25g, add starch dust 150g, Pulvis Talci 10g, magnesium stearate 5g, mixing is granulated, and drying incapsulates, and makes 1000, every day 3 times, each 2.
Embodiment 7:
Get amentoflavone (amentoflavone) 50g, add microcrystalline Cellulose 250g, crospolyvinylpyrrolidone 50g, mixing adds 90 alcohol granulations, drying, granulate adds carboxymethyl starch sodium 10g, magnesium stearate 5g, mixing is pressed into 1000, takes each 1 every day 3 times.
Embodiment 8:
Get amentoflavone (amentoflavone) 50g, mannitol 150g adds injection water 2000ml, stirs and makes dissolving, transfer pH to 9.60～10.0 with 1M NaOH solution, stir and make dissolving, filter, filtrate adds active carbon by 1% liquor capacity amount, heats 30 minutes the coarse filtration mistake down at 70～80 ℃, pipeline and container add water to 2500ml with the washing of 400mL water for injection, and medicinal liquid filters through 0.22 μ m sterilizing filter, fill, lyophilizing, tamponade, roll lid, make 1000 bottles, promptly.
Claims (8)
1. the application of amentoflavone in preparation treatment viral disease medicine.
2. application according to claim 1 is characterized in that: described viral disease comprises hepatitis B virus, herpesvirus, influenza virus, Coxsackie virus.
3. application according to claim 1 is characterized in that: the purity of described amentoflavone is: amentoflavone content is greater than 90%.
4. application according to claim 1 is characterized in that: described amentoflavone can be with pharmaceutically acceptable carrier or mixed with excipients prepare acceptable drug preparation clinically.
5. application according to claim 4 is characterized in that: described pharmaceutical preparation is oral Preparation; Vagina, anus, nasal cavity administrated preparation; Muscle or intravenous administration formulation.
6. application according to claim 5 is characterized in that: described oral formulations is tablet, capsule, granule, slow releasing preparation, drop pill.
7. according to any one described application among the claim 1-6, it is characterized in that: described amentoflavone is to extract from the plant, Chinese crude drug and the prepared slices of Chinese crude drugs that contain this composition.
8. application according to claim 7 is characterized in that described Chinese crude drug is: the dry herb of Spikemoss plant Herba Selaginellae Selaginella tamariscina (Beauv.) Spring or cushion Herba Selaginellae Selaginella pulvinata (Hook.etGrev.) Maxim..
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| Application Number | Priority Date | Filing Date | Title |
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| CN 200910248591 CN101744805B (en) | 2009-12-21 | 2009-12-21 | Use of amentoflavone biflavone as only active component in curing viral diseases |
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| CN 200910248591 CN101744805B (en) | 2009-12-21 | 2009-12-21 | Use of amentoflavone biflavone as only active component in curing viral diseases |
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Cited By (6)
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|---|---|---|---|---|
| CN103947854A (en) * | 2014-03-18 | 2014-07-30 | 李长林 | Disease-resistant pig forage and preparation method thereof |
| CN104510742A (en) * | 2014-11-11 | 2015-04-15 | 济南星懿医药技术有限公司 | Pharmaceutical composition for treating AIDS |
| CN104523728A (en) * | 2014-11-11 | 2015-04-22 | 济南星懿医药技术有限公司 | Pharmaceutical composition for treating phthisis |
| CN107137434A (en) * | 2017-06-22 | 2017-09-08 | 江苏红豆杉药业有限公司 | A kind of pharmaceutical composition and preparation method thereof and the application in anti-Coxsackie virus medicine is prepared |
| CN111995608A (en) * | 2020-08-31 | 2020-11-27 | 厦门一三九生物科技有限公司 | Antiviral compound containing luteolin and preparation method thereof |
| CN114394950A (en) * | 2022-01-19 | 2022-04-26 | 四川省中医药科学院 | Biflavonoid compound for resisting I-type simplex herpes virus as well as preparation method and application thereof |
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| CN101361765A (en) * | 2008-09-19 | 2009-02-11 | 湖北中医学院 | Anti-coxsackie and anti-herpesvirus extract of selaginella tamariscina and extraction technique and formulation thereof |
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| CN1454664A (en) * | 2003-05-29 | 2003-11-12 | 斯拉甫·艾白 | Liver-recovering capsule |
| CN101361765A (en) * | 2008-09-19 | 2009-02-11 | 湖北中医学院 | Anti-coxsackie and anti-herpesvirus extract of selaginella tamariscina and extraction technique and formulation thereof |
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Cited By (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103947854A (en) * | 2014-03-18 | 2014-07-30 | 李长林 | Disease-resistant pig forage and preparation method thereof |
| CN103947854B (en) * | 2014-03-18 | 2016-01-20 | 李长林 | A kind of disease-resistant pig feed and preparation method thereof |
| CN104510742A (en) * | 2014-11-11 | 2015-04-15 | 济南星懿医药技术有限公司 | Pharmaceutical composition for treating AIDS |
| CN104523728A (en) * | 2014-11-11 | 2015-04-22 | 济南星懿医药技术有限公司 | Pharmaceutical composition for treating phthisis |
| CN107137434A (en) * | 2017-06-22 | 2017-09-08 | 江苏红豆杉药业有限公司 | A kind of pharmaceutical composition and preparation method thereof and the application in anti-Coxsackie virus medicine is prepared |
| CN111995608A (en) * | 2020-08-31 | 2020-11-27 | 厦门一三九生物科技有限公司 | Antiviral compound containing luteolin and preparation method thereof |
| CN111995608B (en) * | 2020-08-31 | 2023-05-12 | 厦门一三九生物科技有限公司 | Antiviral compound and preparation method thereof |
| CN114394950A (en) * | 2022-01-19 | 2022-04-26 | 四川省中医药科学院 | Biflavonoid compound for resisting I-type simplex herpes virus as well as preparation method and application thereof |
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