CN1965853A - Application of gentiopicroside in preparation of antiviral medicament - Google Patents
Application of gentiopicroside in preparation of antiviral medicament Download PDFInfo
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- CN1965853A CN1965853A CN 200610104855 CN200610104855A CN1965853A CN 1965853 A CN1965853 A CN 1965853A CN 200610104855 CN200610104855 CN 200610104855 CN 200610104855 A CN200610104855 A CN 200610104855A CN 1965853 A CN1965853 A CN 1965853A
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- gentiopicrin
- radix gentianae
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Abstract
The invention relates to the application of gentian in antiviral drug, while its gentian content is more than 50%, wherein the test has proved that gentian has activity resistant to CVB3 and HFRS. Therefore, the gentian can treat viral myocarditis and nephrotic syndrome. And it can be made into tablet, capsule, etc.
Description
Technical field
The present invention relates to gentiopicrin or contain the new purposes of the Radix Gentianae total glucosides of gentiopicrin more than 50% in antiviral drugs, belong to field of medicaments.
Background technology
(viralmyocarditis VMC) is the heart disease that is caused by viral infection to viral myocarditis, has become a major reason of child and teenager sudden death.Show according to The World Health Organization's whole world virosis study on monitoring report: the sickness rate of VMC in neonate, child is 3,60/,100,000, and mortality rate is 8%.Show about 45%~60% myocarditis and Coxsackie virus (CVB recent or recurrence according to Epidemiological study
3) infect relevant.CVB
3Can cause slight upper respiratory tract infection and aseptic encephalitis; In children's, also can cause lower respiratory infection, but symptom is slighter.CVB
3Can stick myocardial cell, with receptors bind, permeates cell membranes, in time multiplexed cell system, coup injury cell or indirect immunoreation cause VMC.As seen VMC is a kind of serious harm people ' s health and the disease that is difficult for treatment.Modern medicine does not have specific anti-CVB to the treatment of primary disease at present
3Medicine, preparations such as Chinese medicine such as the Radix Astragali and Radix Sophorae Flavescentis prove that through clinical practice though VMC is had certain therapeutical effect, cost is higher, and composition is complicated, and curative effect is also unsatisfactory.Therefore, the medicine of seeking effective antiviral therapy VMC becomes pressing for of contemporary medicine and pharmacology.
Hantaan virus infects and can cause hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS) the acute viral infectious disease of etc.ing, is popular in the world much countries and regions.HFRS is a class with heating, hemorrhage and kidney damage is the disease of main clinical characteristics, the HFRS case of the whole world more than 90% occurs in China, epidemic situation is very serious, annual morbidity surpasses 100,000 people, and it is in the majority with person between twenty and fifty, the about 5-10% of mortality rate has become one of maximum acute viral infectious disease of the present death toll of China.Hantaan virus (HTNV) is under the jurisdiction of the bunyaviridae Hanta virases, and the HFRS that takes place in China is mainly caused by this virus; In addition, HTNV also can be used as potential biological warfare agent, is listed in Biological Weapons Convention by international community, and therefore the research to HTNV has crucial meaning.To the treatment of HFRS, also there is not special, effective medicine so far, mainly be to take methods such as hemodialysis to carry out anti symptom treatment clinically, and the expense costliness.
Gentiopicrin is the secoiridoid chemical compound that extracts from the Chinese medicine Radix Gentianae Macrophyllae, studies show that, Radix Gentianae total glucosides (containing gentiopicrin more than 50%) can be used for preparation and promotes digestive functions medicine (Chinese patent 97108434.3), gentiopicrin also can be used for preparation and suppresses hepatitis B virus medicaments (Chinese patent 200410073488.7), is used to prepare hepatic cholagogic anti-inflammatory drug (Chinese patent 03114558.2).Present known gentiopicrin has the pharmacotoxicological effect of anti-hepatitis virus, but its anti-CVB
3Do not see the research report with the HTNV virus function.
Summary of the invention
The purpose of this invention is to provide gentiopicrin or contain the new purposes of the Radix Gentianae total glucosides of gentiopicrin more than 50% in antiviral drugs, i.e. new application in pharmacy.
The present invention relates to gentiopicrin or contain the application of the Radix Gentianae total glucosides of gentiopicrin more than 50% in antiviral property myocarditis medicine.
The present invention relates to gentiopicrin or contain the Radix Gentianae total glucosides of gentiopicrin more than 50% anti-hantavirus infect cause application in hemorrhagic fever with renal syndrome (HFRS) and Hantavirus pulmonary syndrome (HPS) medicine.
For achieving the above object, technical scheme of the present invention is: prepare Radix Gentianae total glucosides (containing gentiopicrin more than 50%) from Radix Gentianae Macrophyllae, re-refine into gentiopicrin, utilize its antiviral activity, can be applicable to prepare the medicine that treatment VMC and Hantaan virus infect caused HFRS and HPS.
The preparation technology of gentiopicrin is as follows:
Get Radix Gentianae Macrophyllae, decoct three times, each 15 minutes, merge decoction liquor centrifuging and taking supernatant with 5-20 times of water gaging; D101 macroporous resin column on the decocting liquid, the water elution of 2~6 times of amounts of 0.8mL medicinal liquid discards water lotion on every gram resin, the ethanol elution that the macroporous resin reuse is 3~10 times 30%, reclaim the ethanol in the eluent, decompressing and extracting gets residue, i.e. Radix Gentianae total glucosides (containing gentiopicrin more than 50%), macroporous resin will be gone up after the Radix Gentianae total glucosides hydrolysis more as stated above, 30% ethanol elution, the residue behind the recovery eluent is dissolved in 95% ethanol of 2~5 times of amounts, filters, recovery ethanol is also drained, reuse 95% dissolve with ethanol is drained again, is dissolved at last in the dense ethanol, place, separate out crystallization, filter, get the pure product of gentiopicrin.
Effective ingredient prepares antiviral drugs with gentiopicrin to be used with the form of conventional pharmaceutical formulation; Described conventional medicine with preparation contain as active component in preparation with pharmaceutically acceptable carrier as being suitable in the intestines and stomach and the solid or the liquid excipient of the organic or inorganic of parenteral mix, this pharmaceutical formulation can be solid form such as tablet, capsule, powder, pill, granule, also can be liquid form such as injection, Emulsion etc.
Can contain auxiliary substance, stabilizing agent, wetting agent and other additive commonly used in the above-mentioned preparation, as lactose, citric acid, tartaric acid, magnesium stearate, Gypsum Fibrosum powder, sucrose, corn starch, Pulvis Talci, gelatin, agar, pectin, Oleum Arachidis hypogaeae semen, olive oil, cocoa butter, ethylene glycol, ascorbic acid, mannitol etc.
Above-mentioned preparation can be made according to the preparation technology of various preparation routines.
Extracorporeal antivirus effect experiment confirm gentiopicrin has anti-CVB
3With the activity of HFRS, therefore, gentiopicrin will can be used for preparing the medicine of viral diseases such as viral myocarditis that treatment causes by these two kinds of viruses and hemorrhagic fever with renal syndrome.
For understanding essence of the present invention better, pharmacological testing and the result with gentiopicrin illustrates its new purposes in pharmaceutical field below.
Gentiopicrin extracorporeal antivirus effect experiment:
Experiment one, investigation gentiopicrin are to CVB
3Direct deactivation on 24 orifice plates, add 0.5 * 10
424h is cultivated in the myocardial cell 1mL/ hole of/mL concentration, removes the CVB that the every hole of normal group adds 100TCID
31mL, hatch 1h after, abandoning supernatant, PBS flushing 3 times adds gentiopicrin, the medicine final concentration is 1,0.1,0.01mmoL/mL, positive controls adds virazole 1mmoL/mL, every group four hole adds cell maintenance medium, 5%CO
2Incubator is cultivated 72h, observation of cell pathological changes effect (CPE) day by day.Detect cell survival rate with mtt assay at last.
Experimental result: behind the infective virus, the CPE due to the virus group is characterized as cell shrinkage, become justify, come off, cracked (shown in Figure 1).Virazole group cell shrinkage, come off arhythmicity beat (shown in Figure 5); Gentiopicrin treatment group cell still can be rhythmic pulsation, and the part cell shrinkage is to CVB
3Suppression ratio and its concentration be proportionate (shown in Fig. 2-4).The result shows: gentiopicrin is to CVB
3Has direct deactivation.Dose-effect relationship sees Table 1.
Table 1 gentiopicrin is to CVB
3Inhibitory action
Drug dose (mmoL/mL) | Cytopathic effect (CPE) | Virus suppression ratio (%) |
1 0.1 0.01 virus groups | + ++ +++ +++++ | 67 43 11 0 |
Experiment two, investigate gentiopicrin to the direct deactivation of HTNV on 24 orifice plates, add 0.5 * 10
4The Vero cell 1mL/ hole of/mL concentration, cultivate 24h, remove the HTNV1mL that the every hole of normal group adds 100TCID, hatch 1h after, abandoning supernatant, PBS flushing 3 times adds gentiopicrin, and the medicine final concentration is 1,0.1,0.01mmoL/mL, positive controls adds virazole 1mmoL/mL, every group four hole adds cell maintenance medium, 5%CO
2Incubator is cultivated 72h, observation of cell pathological changes effect (CPE) day by day.Detect virus titer with the ElASA method at last.
Experimental result: behind the infective virus, the CPE due to virus is organized is characterized as the part cell and begins to wear out and have the distortion of crispaturaing, and part comes off then.Virazole group cell shrinkage, come off; Gentiopicrin treatment group cell part cell shrinkage does not come off but have.Suppression ratio and its concentration to HTNV are proportionate.The result shows: gentiopicrin has direct deactivation to HTNV.
The beneficial effect of the invention: gentiopicrin or contain the Radix Gentianae total glucosides of gentiopicrin more than 50% and have anti-CVB
3With the pharmacologically active of HTNV virus, be that medicinal raw material is made tablet, capsule, granule, injection, syrup with the gentiopicrin, can be used for treating diseases such as viral myocarditis and hemorrhagic fever with renal syndrome.
The specific embodiment
Embodiment 1
The pharmaceutical formulation gentiopicrin is prepared into tablet, is that example is raw materials used as follows with adjuvant and weight proportion thereof to produce 1000 of tablet products:
Gentiopicrin 200g
Starch 100g
Or
Radix Gentianae total glucosides (containing gentiopicrin about 70%) 285g
Starch 100g
Its preparation technology is undertaken by the common process of galenic pharmacy tablet, every heavy 0.3g, and every contains gentiopicrin 200mg.Usage and dosage: oral, each 1,1 time on the one, children's is cut down according to the circumstance, and 30 days is a course of treatment.
Embodiment 2
The pharmaceutical formulation gentiopicrin is prepared into capsule, is that example is raw materials used as follows with adjuvant and weight proportion thereof to produce 1000 of capsule products:
Gentiopicrin 200g
Starch 100g
Or
Radix Gentianae total glucosides (containing gentiopicrin about 70%) 285g
Starch 100g
Its preparation technology is undertaken by the common process of galenic pharmacy capsule, every heavy 0.3g, and every contains gentiopicrin 200mg.Usage and dosage: oral, each 1,1 time on the one, children's is cut down according to the circumstance, and 30 days is a course of treatment.
Embodiment 3
The pharmaceutical formulation gentiopicrin is prepared into granule, is that example is raw materials used as follows with adjuvant and weight proportion thereof to produce granule product 1000g:
Gentiopicrin 200g
Sucrose 400g
Dextrin 400g
Or
Radix Gentianae total glucosides (containing gentiopicrin about 70%) 285g
Sucrose 400g
Dextrin 400g
Its preparation technology is undertaken by the common process of galenic pharmacy granule, every bag heavy 1g, and every bag contains gentiopicrin 200mg.Usage and dosage: oral, each 1 bag, 1 time on the one, children's is cut down according to the circumstance, and 30 days is a course of treatment.
Embodiment 4
The pharmaceutical formulation gentiopicrin is prepared into syrup, is that example is raw materials used as follows with adjuvant and weight proportion thereof to produce syrup product 1000mL:
Gentiopicrin 200g
Sucrose 600g
Distilled water adds to 1000mL
Or
Radix Gentianae total glucosides (containing gentiopicrin about 70%) 285g
Sucrose 600g
Distilled water adds to 1000mL
Its preparation technology is undertaken by the common process of galenic pharmacy granule, and every bottle of 10mL, 1mL contain gentiopicrin 20mg.Usage and dosage: oral, each 1 bottle, 1 time on the one, children's is cut down according to the circumstance, and 30 days is a course of treatment.
The pharmaceutical formulation gentiopicrin is prepared into injection, is that example is raw materials used as follows with adjuvant and weight proportion thereof to produce 1000 of injection products:
Gentiopicrin 200g
Injection mannitol 20g
Or
Radix Gentianae total glucosides (containing gentiopicrin about 70%) 285g
Injection mannitol 20g
Its preparation technology is undertaken by the common process of galenic pharmacy injection, every heavy 0.22g, and every contains gentiopicrin 200mg.Usage and dosage: be dissolved in the 250mL glucose injection, 1 time on the one, children's is cut down according to the circumstance, and 30 days is a course of treatment.
Claims (6)
1, gentiopicrin or contain the purposes of the Radix Gentianae total glucosides of gentiopicrin more than 50% in the anti-Coxsackie virus medicine of preparation treatment.
2, gentiopicrin or contain the purposes of the Radix Gentianae total glucosides of gentiopicrin more than 50% in preparation treatment anti-hantavirus medicament.
3, gentiopicrin or contain the purposes of the Radix Gentianae total glucosides of gentiopicrin more than 50% in preparation treatment viral myocarditis medicine.
4, gentiopicrin or contain the purposes of the Radix Gentianae total glucosides of gentiopicrin more than 50% in preparation treatment hemorrhagic fever with renal syndrome medicine.
5, gentiopicrin or contain the purposes of the Radix Gentianae total glucosides of gentiopicrin more than 50% in preparation treatment Hantavirus pulmonary syndrome medicine.
6,, it is characterized in that the medicine for preparing adopts tablet, capsule, powder, pill, granule, injection or Emulsion according to one of any described purposes of claim 1-5.
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CNB2006101048554A CN100479825C (en) | 2006-11-06 | 2006-11-06 | Application of gentiopicroside in preparation of antiviral medicament |
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Cited By (6)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102018756A (en) * | 2010-12-02 | 2011-04-20 | 董承贵 | Application of gentian serving as antiviral drug |
CN102696638A (en) * | 2012-04-19 | 2012-10-03 | 云南省农业科学院生物技术与种质资源研究所 | Sweroside pharmaceutical preparation and application thereof in prevention of tobacco mosaic virus |
CN102696637A (en) * | 2012-04-19 | 2012-10-03 | 云南省农业科学院生物技术与种质资源研究所 | Gentiopicroside pharmaceutical preparation and application thereof to prevention and treatment tobacco mosaic virus (TMV) disease |
CN103830260A (en) * | 2014-02-21 | 2014-06-04 | 李君印 | Broad spectrum virus-killing medicine and preparation method thereof |
CN105641035A (en) * | 2016-03-10 | 2016-06-08 | 广西大学 | Radix gentianae total-glycosides thin film coating and preparation method thereof |
CN107669625A (en) * | 2017-09-29 | 2018-02-09 | 昆明医科大学 | Anti-fibrosis drug, preparation method, application and animal model constructing method |
-
2006
- 2006-11-06 CN CNB2006101048554A patent/CN100479825C/en not_active Expired - Fee Related
Cited By (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN102018756A (en) * | 2010-12-02 | 2011-04-20 | 董承贵 | Application of gentian serving as antiviral drug |
CN102696638A (en) * | 2012-04-19 | 2012-10-03 | 云南省农业科学院生物技术与种质资源研究所 | Sweroside pharmaceutical preparation and application thereof in prevention of tobacco mosaic virus |
CN102696637A (en) * | 2012-04-19 | 2012-10-03 | 云南省农业科学院生物技术与种质资源研究所 | Gentiopicroside pharmaceutical preparation and application thereof to prevention and treatment tobacco mosaic virus (TMV) disease |
CN102696638B (en) * | 2012-04-19 | 2013-10-16 | 云南省农业科学院生物技术与种质资源研究所 | Sweroside pharmaceutical preparation and application thereof in prevention of tobacco mosaic virus |
CN103830260A (en) * | 2014-02-21 | 2014-06-04 | 李君印 | Broad spectrum virus-killing medicine and preparation method thereof |
CN105641035A (en) * | 2016-03-10 | 2016-06-08 | 广西大学 | Radix gentianae total-glycosides thin film coating and preparation method thereof |
CN107669625A (en) * | 2017-09-29 | 2018-02-09 | 昆明医科大学 | Anti-fibrosis drug, preparation method, application and animal model constructing method |
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