CN108310362A - Application of the carnosine in terms of hepatitis virus resisting - Google Patents
Application of the carnosine in terms of hepatitis virus resisting Download PDFInfo
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- CN108310362A CN108310362A CN201810114056.8A CN201810114056A CN108310362A CN 108310362 A CN108310362 A CN 108310362A CN 201810114056 A CN201810114056 A CN 201810114056A CN 108310362 A CN108310362 A CN 108310362A
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- Prior art keywords
- carnosine
- hepatitis virus
- hepatitis
- virus
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K38/00—Medicinal preparations containing peptides
- A61K38/04—Peptides having up to 20 amino acids in a fully defined sequence; Derivatives thereof
- A61K38/05—Dipeptides
-
- 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
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
Abstract
The application that the invention discloses carnosines in terms of hepatitis virus resisting.The present invention for the first time the study found that carnosine to hepatitis virus have significant antiviral activity, the duplication of hepatitis virus and its secreting, expressing of surface antigen can be inhibited, can be used for anti-hepatitis virus medicament, had great importance to the prevention of hepatitis virus.Simultaneously; carnosine is as the endogenic dipeptides of natural materials; with nontoxicity; molecular weight is small; widely distributed feature, on the one hand organismic internal environment stable state can also be improved, improve immunity while hepatitis virus resisting by taking it; on the other hand protection hepatic injury, the purpose for enhancing liver function are may also function as, it can be to avoid conventional synthesis drug etc. to the toxic side effect or drug resistance problems of human body.Therefore, carnosine has in terms of the exploitation of anti-hepatitis virus medicament and promotes and applies basis and foreground well, also has important practical significance to the expansion of the further application field of carnosine.
Description
Technical field
The invention belongs to biomedicine technical fields.More particularly, to application of the carnosine in terms of hepatitis virus resisting.
Background technology
Hepatitis virus refers to causing the pathogen of virus hepatitis, and human hepatitis virus has A type, B-mode, non-a, non-b type
With point of fourth type virus.Wherein virus B hepatitis(Abbreviation hepatitis B)It is popular one kind that is most extensive, endangering most serious
Hepatitis is infected, is by hepatitis type B virus(Abbreviation hepatitis B)Caused liver inflammatory damage, this disease extend over the entire globe, clinical table
Be now weak, anorexia, Nausea and vomiting, detest oil, diarrhea and abdominal distension, some cases have fever, jaundice, there are about half patients
Onset hide, found in inspection, after hepatitis B virus infection human body, be widely present in blood, saliva, vagina hepatitis secretion,
Milk, sperm etc., mainly by propagation such as blood, property contact, close contacts, so hepatitis B morbidity has familial.To second
Type virus hepatitis will be found as early as possible, early diagnosis, early isolation, early report, early treatment are handled early, to prevent fluid stopping row.
Antiviral therapy is the basic therapy of chronic hepatitis B, and the hepatitis B patient for meeting antiviral therapy uses second
Liver antiviral drugs is treated, and could realize the rehabilitation of disease.Domestic ten thousand people's findings are shown in the recent period:Oral
In antiviral, 63% patient is voluntarily discontinued, wherein 57% conditions of patients aggravates.Expert points out that hepatitis B virus antiviral drug therapy needs
It to take medicine for a long time, need 2 years or so time under normal conditions, be had to if be discontinued in the case where specialist instructs, it is not so sick
It is discontinued in the case of feelings are unsteady, does not have the inhibiting effect to hepatitis B not only, but also drug resistant generation may be accelerated,
The duplication rebound for even making virus, leads to aggravation.More safe and efficient newtype drug research and development, the control for hepatitis virus
System and treatment, have great importance.
Carnosine(Carnosine)The native endogenous water solubility dipeptides being made of Beta-alanine and L-Histidine, is deposited extensively
It is each tissue, especially with musculature and brain tissue content highest.Research shows that Carnosine has various biological work(
Can, such as:It is anti-oxidant, remove free radical, reduce inflammatory reaction, inhibiting carbonylation and couple metal ion etc.;It can lead to
Overprotection sertoli cell(Capsula glomeruli splanchnic cells)And mesangial cell, and then play the role of inhibiting diabetic nephropathy;It protects
Brain tissue is protected from injuries of organic solvents such as ethyl alcohol etc..But so far there has been no Carnosine it is antiviral especially
Research report in terms of hepatitis virus resisting effect.
Invention content
The technical problem to be solved by the present invention is to overcome the defects and deficiency of existing hepatitis virus protective agents, provide carnosine
(Carnosine)New opplication in terms of hepatitis virus resisting provides a kind of new medicament selection for hepatitis virus prevention, can be
The exploitation of Antihepatitis medicament provides new clinical treatment candidate targets.
The application that the object of the present invention is to provide carnosines in terms of preparing anti-hepatitis virus medicament.
Another object of the present invention is to provide a kind of anti-hepatitis virus medicament containing carnosine.
Above-mentioned purpose of the present invention is achieved through the following technical solutions:
Two angles have studied Carnosine in present invention hepatitis cell model in vitro and internal HBV transgenic mouse models
Hepatitis virus resisting effect, while tentatively find the mechanism involved by its antivirus action react.Chief discovery of the invention is simultaneously public
It has opened the hepatitis virus resisting DNA replication dna of Carnosine and has improved the effect of hepatitis mice liver function.
Therefore, applying below should all be within protection scope of the present invention:
Application of the carnosine in terms of preparing anti-hepatitis virus medicament.
Application of the carnosine in terms of preparing the drug for inhibiting hepatitis virus to replicate.
Application of the carnosine in terms of preparing the drug for inhibiting hepatitis virus surface antigen expression secretion.
Wherein it is preferred to which the hepatitis virus is hepatitis B(HBV), hepatitis C virus(HCV)Or hepatitis A virus(HAV).
In addition, a kind of drug of the hepatitis virus resisting containing carnosine, it also should be within protection scope of the present invention.
The invention has the advantages that:
The present invention for the first time the study found that carnosine to the hepatitis virus such as HBV, HAV, especially HBV have significant antiviral activity,
It can inhibit the duplication of hepatitis virus and its secreting, expressing of surface antigen, have great importance to the prevention of hepatitis virus.
Meanwhile carnosine is as the endogenic dipeptides of natural materials, is a kind of new food additive, has nontoxicity,
Molecular weight is small, widely distributed feature, on the one hand taking it is steady can also can to improve organismic internal environment while hepatitis virus resisting
State improves immunity;On the other hand protection hepatic injury is may also function as, enhances the purpose of liver function, it can be to avoid conventional synthesis medicine
The toxic side effect or drug resistance problems to human body such as object.
Therefore, carnosine has in terms of the exploitation of anti-hepatitis virus medicament and promotes and applies basis and foreground well.
Furthermore carnosine as it is a kind of field of medicaments be increasingly subject to researcher attention have effects that more dipeptides objects
Matter carries out it further application field expansion and has important practical significance.
Description of the drawings
Fig. 1 is that carnosine significantly inhibits effect to hepatitis B virus DNA copy number in external model.
Fig. 2 is that carnosine acts on the significant decrease that hepatitis B surface antigen is secreted in external model.
Fig. 3 to the inhibiting effect of hepatitis B virus duplication and is in dose dependent for carnosine in Hepatitis B Animal Model.
Specific implementation mode
It is further illustrated the present invention below in conjunction with Figure of description and specific embodiment, but embodiment is not to the present invention
It limits in any form.Unless stated otherwise, the present invention uses reagent, method and apparatus routinely try for the art
Agent, method and apparatus.
Unless stated otherwise, following embodiment agents useful for same and material are purchased in market.
1 Vitro hepatic inflammatory cell scale-model investigation of embodiment
1, hepatitis cell model is built
HepG2.2.15 cell lines are to commonly use hepatitis type B virus In vitro cell model in the world at present, and construction method is:Liver cancer
HepG2 cell line transfection HBV D type genomes, the steady of expression HBV viruses of stablizing then screened turn strain.
2, using constructed hepatitis cell model, carnosine is studied(Carnosine)To hepatitis B(HBV)It is antiviral
Effect.The structural formula of carnosine is as follows:
Specific research method is as follows:
1) plating cells:HepG2.2.15 cells are with 1.6x105Cell/ml concentration, per hole 0.5ml, plantation is cultivated in 24 holes
3 repetitions are arranged in plate.DMEM culture mediums, 10%FBS.
2) agent-feeding treatments:Next day replaces the carnosine containing gradient concentration(50 mM、25 mM、12.5 mM), positive right
According to drug:Entecavir(ETV, 10 uM)And Lamivudine(3-TC, uM).DMEM culture mediums, 5%FBS.
3) replaces culture solution:Dosing the 4th day, replaces fresh drug effect liquid.
4) collects supernatant:Drug effect the 7th day, collects cell conditioned medium culture solution, and detection HBV DNA and HBsAg contain
Amount.
5) data processings:Calculate the exposure level that carnosine inhibits HBV DNA and HBsAg.
3, result is as illustrated in fig. 1 and 2, and carnosine can inhibit the duplication of hepatitis virus, inhibits answering for hepatitis virus copy number
System;And the expression of external HBV DNA, hepatitis B surface antigen can be significantly inhibited.
2 Hepatitis B Animal Model of embodiment is studied
1, Hepatitis B Animal Model is built
Hydrodynamic force (HDI) mouse model evaluates the internal Anti-HBV activity activity of carnosine:
Six week old male BALB/c mouse tail vein injection pUC19-HBV1.3mer Plasmid DNA, 15mg/ n=5.
2, constructed Hepatitis B Animal Model, antivirus action of the research carnosine to HBV are utilized.
Specific research method is as follows:
1) modelings:0th day, HDI mouse models structure;
2) is administered:The 1-7 days, mouse solvent, ETV or carnosine, continuous processing 7 days, and blood was collected in blood sampling at the 1st, 3,5 day
Slurry is for HBV DNA detections.
3) sample collections:7th day, all mouse collected blood plasma and hepatic tissue after CO2 is euthanized, and are used for HBV
DNA is detected.
4) is detected:Mice plasma DNA is extracted, real-time fluorescence quantitative PCR is passed through(qPCR)Method detects the HBV in blood plasma
DNA level.
3, the results are shown in Figure 3, and carnosine can dose-dependently inhibit to reduce the duplication of hepatitis B, show that carnosine has
There is hepatitis virus resisting.
In addition studies have shown that carnosine is to hepatitis C virus(HCV)And hepatitis A virus(HAV)Also there is significant antiviral activity.
Claims (6)
1. application of the carnosine in terms of preparing anti-hepatitis virus medicament.
2. application of the carnosine in terms of preparing the drug for inhibiting hepatitis virus to replicate.
3. application of the carnosine in terms of preparing the drug for inhibiting hepatitis virus surface antigen expression secretion.
4. according to any application of claims 1 to 3, which is characterized in that the hepatitis virus is hepatitis B, hepatitis disease
Poison or hepatitis A virus.
5. a kind of drug of hepatitis virus resisting, which is characterized in that contain carnosine.
6. drug according to claim 5, which is characterized in that the hepatitis virus is hepatitis B or hepatitis A virus.
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CN109748875A (en) * | 2019-02-12 | 2019-05-14 | 南京纽邦生物科技有限公司 | A kind of preparation method of whale carnosine and its intermediate |
Citations (7)
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JPS61145118A (en) * | 1984-12-18 | 1986-07-02 | Kaneshiro Nagai | Immunomodulator |
EP0313654A4 (en) * | 1986-07-03 | 1990-01-11 | Zeria Pharm Co Ltd | Drug for prophylaxis and treatment of hepatopathy. |
CN1562344A (en) * | 2004-04-16 | 2005-01-12 | 北京大学 | Application of laevorotation carnosine in preparaing medication for assistant curing hepatitis and health foods |
US20050226947A1 (en) * | 2004-02-04 | 2005-10-13 | Dale Kern | Agents for sequestering serum aging factors and uses therefore |
CN1857715A (en) * | 2006-03-23 | 2006-11-08 | 恩泰柯数码科技(北京)有限公司 | Cirrhosis treating medicine |
JP2008195690A (en) * | 2007-02-15 | 2008-08-28 | Gunma Univ | INTERFERON alpha/beta RECEPTOR INDUCER |
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2018
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Patent Citations (7)
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JPS61145118A (en) * | 1984-12-18 | 1986-07-02 | Kaneshiro Nagai | Immunomodulator |
EP0313654A4 (en) * | 1986-07-03 | 1990-01-11 | Zeria Pharm Co Ltd | Drug for prophylaxis and treatment of hepatopathy. |
US20050226947A1 (en) * | 2004-02-04 | 2005-10-13 | Dale Kern | Agents for sequestering serum aging factors and uses therefore |
CN1562344A (en) * | 2004-04-16 | 2005-01-12 | 北京大学 | Application of laevorotation carnosine in preparaing medication for assistant curing hepatitis and health foods |
CN1857715A (en) * | 2006-03-23 | 2006-11-08 | 恩泰柯数码科技(北京)有限公司 | Cirrhosis treating medicine |
JP2008195690A (en) * | 2007-02-15 | 2008-08-28 | Gunma Univ | INTERFERON alpha/beta RECEPTOR INDUCER |
CN104610240A (en) * | 2015-01-28 | 2015-05-13 | 南京工业大学 | Bicyclol-carnosine conjugate, and preparation method and application thereof |
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包丽芹等: "肌肤在医药领域的应用及其研究概况", 《黑龙江医药》 * |
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Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
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CN109748875A (en) * | 2019-02-12 | 2019-05-14 | 南京纽邦生物科技有限公司 | A kind of preparation method of whale carnosine and its intermediate |
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