CN101708182A - Application of troxerutin in preparing medicine resisting viral hepatitis - Google Patents
Application of troxerutin in preparing medicine resisting viral hepatitis Download PDFInfo
- Publication number
- CN101708182A CN101708182A CN200910198422A CN200910198422A CN101708182A CN 101708182 A CN101708182 A CN 101708182A CN 200910198422 A CN200910198422 A CN 200910198422A CN 200910198422 A CN200910198422 A CN 200910198422A CN 101708182 A CN101708182 A CN 101708182A
- Authority
- CN
- China
- Prior art keywords
- hepatitis
- troxerutin
- medicine
- virus
- viral hepatitis
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
Landscapes
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Medicinal Preparation (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
The invention relates to a novel application of troxerutin in a medicine. By carrying out in-vitro and in-vivo pharmacological experiments of resisting hepatitis B viruses and hepatitis C viruses on the troxerutin, a result proves that the troxerutin has an obvious function of suppressing the hepatitis B viruses and the hepatitis C viruses. Therefore, the troxerutin can be used for preparing a medicine resisting viral hepatitis, especially for preparing a medicine resisting viral hepatitis B and viral hepatitis C. Moreover, the price of the required raw materials is low, the raw materials are easy to obtain, and the use in a large range is convenient.
Description
Technical field
The present invention relates to the purposes of troxerutin (Troxerutin) in medicine; Relate in particular to the troxerutin new purposes in the preparation medicine resisting viral hepatitis, the particularly new purposes in preparation antiviral hepatitis B and viral hepatitis C medicine.
Background technology
Type B viral hepatitis is a kind of commonly encountered diseases of serious harm human health, and its control is a global public health problem, has caused the concern of countries in the world government.China is the district occurred frequently of viral hepatitis, and average attack rate is 120～1,40/,100,000.Be outstanding with hepatitis B especially wherein.Hepatitis B is a kind of worldwide disease that is caused by hepatitis B virus.Developing country's sickness rate height, according to statistics, the asymptomatic hepatitis B virus carriers in the whole world surpasses 2.8 hundred million, and China accounts for 9,300 ten thousand.Wherein 1/3 clinical manifestation that hepatic injury occurs, there is hepatitis B patient 3,000 ten thousand in China at present, and annual have 300,000 people to die from liver cirrhosis relevant with hepatitis B or hepatocarcinoma approximately." the popular present situation of Chinese hepatitis and relevant issues analysis report thereof " that China's hepatitis control foundation was announced in 2005 shows only have 19% people accepting this correct therapeutic modality of antiviral at present.The quantity of China's hepatitis virus carrier is just with the speed rapid growth about every year average 2,500,000 people.Hepatitis B is serious harm China people's health not only, but also bring the serious social economic burden to country.The treatment time of hepatitis B is long, and medical expense is higher, adds inappropriate Drug abuse again, has more increased the weight of extra financial burden.The direct medical treatment that China is used for the treatment of hepatitis B, liver cirrhosis, hepatocarcinoma every year expends and is about 30,000,000,000 yuans.Therefore, strengthening the prevention of viral hepatitis, seek effective Therapeutic Method of hepatitis B, is the current key subjects that need to be resolved hurrily.Chronic hepatitis B treatment key is an antiviral therapy.
The viral hepatitis C also is one of the infectious disease that involves the whole world, and the whole world has 1.7 hundred million people to infect hepatitis C virus, and China has 3700～4,000 ten thousand infection with hepatitis C virus persons, and its sickness rate has and increases trend year by year.The Center for Disease Control prediction from nineteen ninety to 2015 year, has among the population at risk of chronic hepatic diseases, and hepatitis C patients will increase by 4 times.In prediction on such basis, if the popular of the infection of China's hepatitis C virus and hepatitis C can not be well controlled, to 2015, the situation of the chronic hepatitis B that faced hepatitis C situation and today that we faced was the same severe.Therefore, the research of reinforcement hepatitis C has importance and urgency.And, owing to lack effective preventative vaccine, also will be secular to the control of hepatitis C.Infection with hepatitis C virus is the major reason of chronic hepatopathy, and the infected of about 50% can transfer chronic hepatitis to, and the hepatitis C of about 10%-20% developed into liver cirrhosis in 20 years, and close with being related of hepatocarcinoma (HCC).The pathomechanism of hepatitis C and drug research are one of research focuses, but also lack special pathology animal model at present, and also do not have ideal medicine to treat clinically.
Chinese invention patent (application number is 200810038858.1) discloses the application of rutin in the preparation anti-hepatic-B virus medicine, through hepatitis B surface antigen (HBsAg) and the experiment of hepatitis B virus core antigen (HBeAg) detectable, the result shows that rutin can significantly suppress hepatitis B surface antigen (HBsAg) and hepatitis B virus core antigen (HBeAg), has the effect of remarkable inhibition hepatitis B virus.
Troxerutin be Citrin belong to a kind of, be rutin through hydroxyethylated derivant, the known pharmacological action of troxerutin can suppress hematoblastic coagulation, prevents thrombotic effect; Simultaneously the blood vessel injury that can cause the gentle kassinin kinin of medmain increases capillary resistance, reduces capillary permeability, can prevent the edema that vascular permeability raises and causes; The acute ischemic brain injury there is significant protective effect.The safety of troxerutin and effectiveness have obtained abundant affirmation by clinical trial; So, State Food and Drug Administration has ratified troxerutin as drug use, dosage forms such as existing troxerutin tablet, capsule, oral liquid, injection, clinical hemiplegia, aphasia and premyocardial infarction syndrome, arteriosclerosis, central serous chorioretinopathy, thrombophlebitis, varicosis, vascular permeability due to cerebral thrombosis and the cerebral embolism edema that causes etc. that raises that is applicable to.
The chemical structural formula of troxerutin is as follows:
By retrieval, do not find the correlational study report of troxerutin, and the present invention can make application extension to a new field of troxerutin to anti-hepatitis virus and hepatitis C virus effect.
Summary of the invention
The invention provides the troxerutin new purposes in the preparation medicine resisting viral hepatitis, the particularly new purposes in preparation antiviral hepatitis B and viral hepatitis C medicine.The present invention has carried out new pharmacological evaluation to troxerutin:
The present invention has carried out external anti-hepatitis B surface antigen (HBeAg) and hepatitis B virus core antigen (HBsAg) experiment (referring to embodiment 1) to troxerutin, duck hepatitis b virus infection experiment (referring to embodiment 2) in the body, the result is (referring to table 1,2 and 3) prove that troxerutin has significant hepatitis B virus inhibitory action, and its great advantage does not see that after drug withdrawal tangible hepatitis B virus duplicates " knock-on " phenomenon again; Therefore troxerutin can be used to prepare the medicine of antiviral hepatitis B.
The present invention has carried out in the body experiment (referring to embodiment 3) to the liver protective effect of bacillus calmette-guerin vaccine (BCG) and lipopolysaccharide (LPS) induced mice immunologic liver injury model again to troxerutin, result's (referring to table 4) shows that troxerutin can suppress the rising of BCG and the inductive mice serum ALT of LPS, AST level to some extent, has protective effect to the mouse immune liver damage; Therefore troxerutin can be used to prepare the medicine of antiviral property hepatitis C.
According to above-mentioned The pharmacological results, troxerutin demonstrates good effect in anti-hepatitis B, hepatitis C virus activity test.Therefore troxerutin can be used for preparing antiviral hepatitis B or the hepatitis C medicine is used for animal, be preferred for mammal, particularly the people.
The medicine resisting viral hepatitis of troxerutin preparation contains the troxerutin of effective dose and pharmaceutically suitable carrier of routine in the medicine.This medicine can be used conventional process for preparing medicine, with troxerutin and one or more solids or liquid medicine excipient and (or) adjuvant combines, make the suitable administration form or the dosage shape that can be used as drug use, as the preparation of dosage forms such as tablet, pill, capsule, oral liquid, injection, also can make slow releasing preparation, controlled release preparation, targeting preparation and various microgranule drug-delivery preparation.The troxerutin that contains 0.1-90 weight % in the preparation.
The dosage of troxerutin of the present invention depends on all multifactor, for example will prevent or treat the character and the order of severity of disease, patient's sex, age, body weight and individual reaction, route of administration and administration number of times etc.The common about 75 kilograms of patients of body weight, the daily dose of the troxerutin of giving is 0.001mg/kg body weight-70mg/kg body weight, preferred 0.01mg/kg body weight-10mg/kg body weight.Dosage can the single dose form or be divided into several, for example two, three or four dosage form administrations.Concrete case can be by the doctor according to state of an illness adjustment.
Innovation part of the present invention is:
1. the invention provides the new purposes of troxerutin aspect the preparation antiviral hepatitis B medicine.
2. the invention provides the new purposes of troxerutin aspect preparation antiviral property hepatitis C medicine.
3. antiviral hepatitis B, the hepatitis C medicine of troxerutin preparation of the present invention can be made different dosage form, administration by different way, the selectivity of increase clinical practice.
4. cost of material required for the present invention is low, and raw material is easy to get, and is convenient to interior the use on a large scale.
The specific embodiment
The following examples only are used for further specifying the present invention, but this and do not mean that any limitation of the invention.
The external anti-hepatitis virus test of embodiment 1 troxerutin
1. material and method
1.1 cell culture and medicine
With HepG2 2.2.15 cell is model, with HepG2 2.2.15 cell inoculation to 25cm
2In the culture bottle, every bottle adds DMEM culture medium mixed-culture medium (containing 10%FBS and 380 μ g/mlG418) 5ml, puts 37 ℃, 5%CO
2In the constant incubator, went down to posterity in 3～4 days.Use 5%NaHCO
3Adjust pH to 7.2.(DMEM culture medium and hyclone are GIBCO company product; G418 is a Sigma company product).
Adefovir ester (Suzhou GlaxoSmithKline PLC pharmaceutical Co. Ltd product) with dmso solution, is made the solution of 1mg/ml, is diluted to 5 μ g/ml with culture fluid.
Troxerutin (Shaanxi Sen Fu Bioisystech Co., Ltd product) with dmso solution, is made the solution of 1mg/ml, is diluted to 1 μ g/ml respectively with culture fluid, 2.5 μ g/ml, the solution of 5 μ g/ml.
The cultured cell Digestive system is with 0.25% trypsin Costar company product) be digested to individual cells, behind the piping and druming mixing, (every porocyte number is 1 * 10 to be inoculated in 96 well culture plates respectively
4) and 24 well culture plates (every porocyte number is 1 * 10
5) on.Add culture fluid 200ul and 1ml respectively, 37 ℃ of 5%CO
2Incubator is cultivated 48h.After treating cell attachment, abandon culture supernatant, use the culture fluid that contains different pharmaceutical concentration instead, used the fresh medium that contains equal drug level in per 3 days instead.Experiment was carried out 9 days altogether, and culture supernatant ,-20 ℃ of preservations were collected in the end in the 9th day; Detect HBsAg, HBeAg content in the supernatant with batch test kit.
1.2 experiment grouping
Drug combination adopts the chessboard method design.Being divided into single is adefovir ester and the negative control group that does not add medicine with troxerutin, positive control medicine.Troxerutin concentration is got 1,2.5 and 5 μ g/ml, and positive control medicine adefovir ester concentration is got 5 μ g/ml.Every group of repeated experiments 3 times.
1.2.1 every hole adds specimen 50ul to be measured, establishes each 2 hole of positive and negative contrast, every hole adds each one of negative control (or positive control), and establishes blank one hole.
1.2.2 every hole adds 1 of enzyme conjugates (except the blank hole), abundant mixing, and shrouding is put 37 ℃ and was hatched 30 minutes;
1.2.3 discard liquid in the hole, cleaning mixture is filled with each hole, leaves standstill 5 seconds, dries, and pats dry after repeating five times;
1.2.4 every hole adds each 1 of developer A liquid, B liquid, abundant mixing, and shrouding is put 37 ℃ and was hatched 15 minutes;
1.2.5 every hole adds 1 of stop buffer, mixing;
1.2.6 use the microplate reader reading, get wavelength 450nm, reference wavelength 630nm reads each hole reading.
1.3 radioimmunology is adopted in the detection of supernatant HBsAg and HBeAg, the result represents with multiple hole meansigma methods.
Upright readable hepatitis B HBsAg, HBeAg diagnostic kit (Shanghai Kehua Bio-technology Co., Ltd's product) operational approach are undertaken by the test kit description.
Computational methods: suppression ratio (%)=(negative control group cpm-experimental group cpm)/negative control group cpm * 100%
2. result
Relatively use variance analysis between group, adopt SPSS1 1.0 to finish (seeing Table 1).
Table 1 troxerutin is to HBsAg and HBeAg inhibitory action
Above-mentioned experimental result shows that troxerutin has the hepatitis B virus inhibitory action; Therefore, troxerutin can be used to prepare the medicine of antiviral hepatitis B.
Anti-hepatitis virus test in the embodiment 2 troxerutin bodies
1. experiment material:
1.1 virus
DHB DNA (DHBV-DNA) strong positive serum picks up from the Shanghai sheldrake ,-70 ℃ of preservations.
1.2 animal
1 age in days Beijing duck (Beijing medical courses in general institute medicine is planted institute's animal feeding field product).
1.3 medicine
Adefovir ester (Chinese Suzhou GlaxoSmithKline PLC pharmaceutical Co. Ltd product); Troxerutin (Shaanxi Sen Fu Bioisystech Co., Ltd product).Above medicine is made the liposome of 1mg/ml respectively, with water for injection dilution back administration.
1.4 reagent α-32 P-dCTP (Beijing Fu Rui company product); Nick translation medicine box (Pu Luomaige company product); SephadexG-50, Ficoll PVP (Sweden Pharmacia company product); SDS (German Merck company product); Milt DNA, bovine serum albumin (Instite of Biophysics, Chinese Academy of Sciences's product); Nitrocellulose filter 0.45um (An Pu company product).
2. experimental technique
2.1 duplicate the duck hepatitis B virus infection model
Get 30 of 1 age in days Beijing ducks, be divided into 5 groups at random: model control group, positive controls, the basic, normal, high dosage group of troxerutin.Every group 6.Every clear through lower limb shin intravenous injection 0.2ml Shanghai sheldrake DHBV-DNA strong positive Sanguis Anas domestica.
2.2 Drug therapy
Get blood back 7 days of infection from duck lower limb shin vein, separation of serum, for treating preceding sample (T0) ,-70 ℃ of preservations are to be checked.DHBV infects duckling and carries out the Drug therapy test after 7 days, and the basic, normal, high dosage group of troxerutin gives troxerutin 10,25,50 μ g/kg respectively, and positive controls gives adefovir ester 50 μ g/kg, and model control group gives normal saline.Gastric infusion, every day 2 times, continuous 10 days, in medication the 5th day (T5), after the 10th day (T10) and the drug withdrawal the 3rd day (P3), get blood from duck lower limb shin vein, separation of serum ,-70 ℃ of preservations are to be checked.
2.3DHBV-DNA mensuration
Sanguis Anas domestica final proof product are used
32The P-DHBV dna probe is made dot blot hybridization, obtains radioautogram on the x-ray film, measures its OD value in the 490nm place with microplate reader, and dna level is calculated in sxemiquantitative.
3. result
DHBV-DNA total positives behind the duckling infection hepatitis B virus, troxerutin 25 μ g/kg, 50 μ g/kg have obvious inhibitory action (P＜0.05) to DHBV-DNA, and troxerutin is not seen " knock-on " phenomenon that tangible hepatitis B virus duplicates again after drug withdrawal.The positive control drug adefovir ester can significantly suppress duck DHBV-DNA (P＜0.05) during medication, but occurs " knock-on " phenomenon (P＜0.05) that hepatitis B virus duplicates again (see Table 2, table 3) after the drug withdrawal.
Table 2 troxerutin is to the influence (n=6) of the clear DHBV-DNA level of Sanguis Anas domestica
P＜0.05。
Table 3 troxerutin is to the influence (n=6) of the horizontal suppression ratio of the clear DHBV-DNA of Sanguis Anas domestica
P＜0.05。
Above-mentioned experimental result shows that troxerutin has significant hepatitis B virus inhibitory action; Therefore, troxerutin can be used to prepare the medicine of antiviral hepatitis B.
In the embodiment 3 troxerutin bodies to the experiment of the liver protective effect of bacillus calmette-guerin vaccine (BCG) and lipopolysaccharide (LPS) induced mice immunologic liver injury model
1. experiment material
1.1 laboratory animal
Kunming mouse, ♂, 18～22g (The 2nd Army Medical College Experimental Animal Center product).
1.2 medicine and reagent
Troxerutin (Shaanxi Sen Fu Bioisystech Co., Ltd product) is made the liposome of 1mg/ml, behind the dilute with water with drug administration by injection.
Ribavirin injection (Shanghai Xinyi Pharmaceutical Co., Ltd's product).
Bacillus calmette-guerin vaccine (BCG) (Shanghai biological product company product).
Lipopolysaccharide (LPS) (Sigma company product).
ALT, AST test kit (bio-engineering research institute product is built up in Nanjing)
2. experimental technique and result
The animal random packet, tail ivBCG2Sit/, the normal control group gives the equivalent normal saline, and the treatment group gives the medicine of various dose, and every day 1 time, positive controls gives ribavirin, 50ug/kg, every day 1 time.The normal raising 10 days, after the last administration once more tail ivLPS10ug/ only attack, 16h posterior orbit vein is got blood, carries out liver function and detects (Serum ALT, AST measure) (seeing Table 4).
Table 4 troxerutin is to the influence (n=6) of immunologic liver injury mice serum ALT, AST
P＜0.05
Above-mentioned experimental result shows, troxerutin can suppress the rising of BCG and the inductive mice serum ALT of LPS, AST level to some extent, and the mouse immune liver damage is had protective effect; Therefore, troxerutin can be used to prepare the medicine of antiviral property hepatitis C.
Claims (3)
1. troxerutin is in the purposes of preparation in the medicine resisting viral hepatitis.
2. the purposes of the described troxerutin of claim 1 in the preparation medicine resisting viral hepatitis is characterized in that the purposes of described troxerutin in the preparation antiviral hepatitis B medicine.
3. the purposes of the described troxerutin of claim 1 in the preparation medicine resisting viral hepatitis is characterized in that the purposes of described troxerutin in preparation antiviral property hepatitis C medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910198422A CN101708182A (en) | 2009-11-06 | 2009-11-06 | Application of troxerutin in preparing medicine resisting viral hepatitis |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN200910198422A CN101708182A (en) | 2009-11-06 | 2009-11-06 | Application of troxerutin in preparing medicine resisting viral hepatitis |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN101708182A true CN101708182A (en) | 2010-05-19 |
Family
ID=42401003
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN200910198422A Pending CN101708182A (en) | 2009-11-06 | 2009-11-06 | Application of troxerutin in preparing medicine resisting viral hepatitis |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN101708182A (en) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020053249A1 (en) * | 2018-09-14 | 2020-03-19 | F. Hoffmann-La Roche Ag | Flavone compounds for the treatment and prophylaxis of hepatitis b virus disease |
-
2009
- 2009-11-06 CN CN200910198422A patent/CN101708182A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2020053249A1 (en) * | 2018-09-14 | 2020-03-19 | F. Hoffmann-La Roche Ag | Flavone compounds for the treatment and prophylaxis of hepatitis b virus disease |
| WO2020052774A1 (en) * | 2018-09-14 | 2020-03-19 | F. Hoffmann-La Roche Ag | Flavone derivatives for the treatment and prophylaxis of hepatitis b virus disease |
| CN112601743A (en) * | 2018-09-14 | 2021-04-02 | 豪夫迈·罗氏有限公司 | Flavone compounds for treating and preventing hepatitis B virus diseases |
| CN112601743B (en) * | 2018-09-14 | 2023-12-19 | 豪夫迈·罗氏有限公司 | Flavone compounds for the treatment and prevention of hepatitis b virus diseases |
| US12012390B2 (en) | 2018-09-14 | 2024-06-18 | Hoffmann-La Roche Inc. | Flavone compounds for the treatment and prophylaxis of hepatitis B virus disease |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| KR102456294B1 (en) | Composition for preventing or treating coronavirus infection | |
| Singh et al. | Hepatitis B, C and human immunodeficiency virus infections in multiply-injected kala-azar patients in Delhi | |
| CN113082049B (en) | New application of potassium iodide or composition containing potassium iodide in preparation of drugs for treating African swine fever | |
| CN112791084B (en) | New application of ML-60218 in preparation of drugs for treating African swine fever | |
| Pang et al. | Antiviral effects of aqueous extract from Spatholobus suberectus Dunn. against coxsackievirus B3 in mice | |
| CN112675174A (en) | New use of poly ADP ribose polymerase inhibitor for treating hepatitis B virus related diseases | |
| CN101380318A (en) | Use of isochlorogenic acid compound and different combinations in hepatitis treatment | |
| CN101695511A (en) | Pomegranate rind extract and production method and application thereof | |
| CN102283838B (en) | Application of ethoxysanguinarine to pharmacy | |
| CN101708182A (en) | Application of troxerutin in preparing medicine resisting viral hepatitis | |
| CN102631384A (en) | Application of pomegranate in preparing medicament for treating or preventing hepatitis B virus infection | |
| CN102755316A (en) | Application of artemisinin and derivatives thereof in preparation of medicaments for treating hepatitis C viruses | |
| CN113304165B (en) | Application of monomeric compound Ciliaoside A in preparation of hepatitis B treatment drug | |
| CN102755355B (en) | Drug composition resisting influenza virus A or enterovirus | |
| CN105031613B (en) | A kind of human beta-defensin 1 is preparing the application in treating or preventing hepatitis B virus infective medicament | |
| CN111317752B (en) | Medicine for preventing or treating influenza virus infection and application | |
| CN1506092A (en) | Elsholizia extract capsule for treating diarrhea and its prepn | |
| CN101919840B (en) | Application of B/E ring substituted silybin for preparing medicament for treating virus hepatitis B | |
| CN110179785B (en) | Application of widmanone in preparation of medicine for treating or preventing hand-foot-and-mouth disease | |
| CN110840969B (en) | Traditional Chinese medicine composition for treating hepatitis C and application thereof | |
| CN106377537B (en) | Application of acetyl astragaloside | |
| CN106619591B (en) | The purposes and pharmaceutical composition of oxetacaine in medicine preparation | |
| CN110025612A (en) | Application of the Chrysin in preparation treatment methicillin-resistant staphylococcus aureus infectious pneumonia drug | |
| TWI803229B (en) | Compound tsyi-zac is used to inhibit dengue virus infection and its medicinal use | |
| CN111494388B (en) | Application of YM201636 and its pharmaceutically acceptable salt in preparation of medicine for resisting enterovirus infection |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C02 | Deemed withdrawal of patent application after publication (patent law 2001) | ||
| WD01 | Invention patent application deemed withdrawn after publication |
Open date: 20100519 |