CN100404030C - Application of leflunomide in the preparation process of anti SARS virus medicine - Google Patents
Application of leflunomide in the preparation process of anti SARS virus medicine Download PDFInfo
- Publication number
- CN100404030C CN100404030C CNB031514812A CN03151481A CN100404030C CN 100404030 C CN100404030 C CN 100404030C CN B031514812 A CNB031514812 A CN B031514812A CN 03151481 A CN03151481 A CN 03151481A CN 100404030 C CN100404030 C CN 100404030C
- Authority
- CN
- China
- Prior art keywords
- leflunomide
- sars
- virus
- sars virus
- medicine
- 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.)
- Expired - Lifetime
Links
Landscapes
- Measuring Or Testing Involving Enzymes Or Micro-Organisms (AREA)
- Investigating Or Analysing Biological Materials (AREA)
Abstract
The present invention provides an application of leflunomide to prepare anti-SARS virus medicine. The anti-SARS virus screening test of the national medicine screening center proves that fusaimi of active metabolite of leflunomide has the effects for resisting SARS viruses and protecting infected cells, so leflunomide and fusaimi of active metabolite of leflunomide can be used for preparing anti-SARS viruse medicine.
Description
Technical field
The present invention relates to SARS resisting medicine, be specifically related to the application of leflunomide on the preparation SARS resisting medicine.
Background technology
Although the research of antiviral therapy medicine has obtained very big progress in recent years, and the extensive use clinically of these antiviral drugs,, the incidence rate of the various diseases that is caused by virus and mortality rate are still high.The atypical pneumonia that spring in 2003 took place with ground such as Hong Kong, Taiwan in China promptly is a typical example, this atypical pneumonia is that the mutation by coronavirus causes, invalid to nearly all antiviral drugs, still there is not effective specific treatment medication clinically.At present, normally used antiviral drugs all is to play a role by suppressing the synthetic of viral DNA, RNA or transcribe on the market, therefore these antiviral drugs are a large amount of use in, the generation of drug resistance virus strains is also just not at all surprising.
Leflunomide is a kind of synthetic isoxazole compounds, has immunosuppressant and antiproliferative effect.Since the nineties in 20th century, leflunomide has been carried out in the process of various bases and clinical research, unexpected discovery leflunomide has anti-cytomegalovirus (ID concurrently
50=40～60 μ M) and herpes simplex virus (IC
5015 μ M) and the characteristic of other multiple viruses, and this mechanism of action has the significantly different (new mechanisms of W.J.Waldman et al. experiment immunization inhibitor leflunomide inhibition cytomegalovirus with other antiviral drugs, Transplantation, 68 (6): 814-825,1999; D.A.Knight et al. experiment immunization inhibitor leflunomide is to the inhibitory action of herpes simplex virus, Transplantation, 71:170-174,2001).Leflunomide can not suppress duplicating, transcribing of viral DNA, RNA, but leflunomide can suppress the kinase whose activity of butyric acid, to the peplos building-up process generation inhibitory action of part virus, thus the performance antivirus action.Have not yet to see the correlational study report of clinicing aspect, but Hardinger etc. are in the research process of the anti-organ rejection of medicine, the patient who observes cytomegalovirus infection is using the phenomenon (generation that K.L.Hardinger et al. leflunomide replacement therapy can slow down the transplanted kidney function obstacle that leflunomide immunologic rejection treatment back viral infection also disappears, meeting, 2002 are transplanted by the U.S.).Can leflunomide produce inhibitory action by similar mechanism to SARS virus is worth research.
Summary of the invention
The purpose of this invention is to provide the application of leflunomide on the preparation SARS resisting medicine.
The applicant entrusts national drug screening center to carry out the anti-SARS virus screening test in July, 2003, adopts the active metabolite Fusaimi (A771726) of leflunomide, and sample is dissolved in culture fluid or DMSO, is made into suitable initial concentration, and dilution.The Vero-E6 cell inoculation in 96 well culture plates, is put 37 ℃, 5%CO
2Cultivate, behind the SARS virus infection cell, add the sample of different diluted concentrations respectively, establish virus control, cell contrast and sample contrast.Observed result under the every day mirror, record CPE, and measure OD value with dimethyl diaminophenazine chloride dyeing, carries out the calculating and the evaluation of sample anti-SARS virus active function with reference to contrasting.Experimental result shows: the active metabolite Fusaimi of leflunomide has the effect of anti-SARS virus, the infected cell of protection.
The specific embodiment
The anti-SARS virus effect of embodiment 1 leflunomide active metabolite Fusaimi
TestDate: 2003-7-17
Test event; Medicine anti-SARS virus screening active ingredients (virus-cellular level model)
Test philosophy: as virus host cell (permissive cell), specimen is resisted the effect of virus infected cell with the Vero-E6 cell, and detecting index is cytopathy reaction (CPE) and infection cell protective rate.
Test material and method:
1. specimen: Fusaimi (A771726)
2. The National Center for Drug Screening's sample number: S01160
3. Strain: BJ-01 (deriving from microorganism epidemic research institute of Beijing Academy of Military Sciences)
4. experiment place: Shanghai disease prevention and the P3 of control centre laboratory
5. the specimen unit of providing: Xinkai Co Ltd of Medicinal and Chemical Intermediates (Shanghai)
6. sample treatment: sample is dissolved in culture fluid or DMSO, is made into suitable initial concentration, 5 times of dilutions, 3 dilution factors.
7. method of testing: the Vero-E6 cell inoculation in 96 well culture plates, is put 37 ℃, 5%CO
2Cultivate, behind the SARS virus infection cell, add the sample of different diluted concentrations respectively, if observed result under contrast of virus control, cell and sample contrast, the every day mirror, record CPE, and, carries out sample anti-SARS virus active function and calculating and evaluation with reference to contrast with dimethyl diaminophenazine chloride dyeing mensuration OD value.
Test result: sample S01160
Cytopathy political reform (CPE):, do not see tangible disengaging, but cell quantity what do not compare with "-" expression cell attachment complete form; With "+" expression cytopathy degree,＜25%+, 25%～50%++, 50%～75%+++,＞75%++++.
Infected cytoprotective rate; By comparing the OD value of virus control, cell contrast and sample contrast, calculation sample is to the protection activity of virus infected cell, protective rate＞EC
20Tentatively be considered to sample to being had the certain protection effect, antiviral activity is arranged by the cell of viral infection.
*Sample cell toxicity: if the cytotoxicity of sample and cell contrast ratio are greater than 50 (＞CC
50) time, do not estimate and protective rate calculating to CPE.
The experiment preliminary conclusion: the sample product S01160 of institute sees anti-SARS virus, the infected cell activity effect of protection a little less than having when 100 μ g/ml concentration in in-vitro screening model.
Claims (1)
1. the application of leflunomide on the preparation SARS resisting medicine.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031514812A CN100404030C (en) | 2003-09-29 | 2003-09-29 | Application of leflunomide in the preparation process of anti SARS virus medicine |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CNB031514812A CN100404030C (en) | 2003-09-29 | 2003-09-29 | Application of leflunomide in the preparation process of anti SARS virus medicine |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN1602862A CN1602862A (en) | 2005-04-06 |
| CN100404030C true CN100404030C (en) | 2008-07-23 |
Family
ID=34659964
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CNB031514812A Expired - Lifetime CN100404030C (en) | 2003-09-29 | 2003-09-29 | Application of leflunomide in the preparation process of anti SARS virus medicine |
Country Status (1)
| Country | Link |
|---|---|
| CN (1) | CN100404030C (en) |
Families Citing this family (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN113456632B (en) * | 2020-02-18 | 2023-09-26 | 华东理工大学 | anti-RNA virus medicine and its application |
Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1286086A (en) * | 2000-09-08 | 2001-03-07 | 欣凯医药化工中间体（上海）有限公司 | Application of leflunomide |
| CN1286085A (en) * | 2000-09-08 | 2001-03-07 | 欣凯医药化工中间体（上海）有限公司 | Application of leflunomide |
| CN1337230A (en) * | 2001-08-03 | 2002-02-27 | 欣凯医药化工中间体（上海）有限公司 | Application of Lavermit in preparing medicine for tetanic rachitis |
| CN1342458A (en) * | 2001-08-31 | 2002-04-03 | 欣凯医药化工中间体（上海）有限公司 | Application of leflunomide in preparing medicines to treat lupoid nephritis and nephrotic syndrome |
| CN1387845A (en) * | 2002-04-30 | 2003-01-01 | 上海欣凯医药发展有限公司 | Medicinal composition for treating autoimmune disease |
-
2003
- 2003-09-29 CN CNB031514812A patent/CN100404030C/en not_active Expired - Lifetime
Patent Citations (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1286086A (en) * | 2000-09-08 | 2001-03-07 | 欣凯医药化工中间体（上海）有限公司 | Application of leflunomide |
| CN1286085A (en) * | 2000-09-08 | 2001-03-07 | 欣凯医药化工中间体（上海）有限公司 | Application of leflunomide |
| CN1337230A (en) * | 2001-08-03 | 2002-02-27 | 欣凯医药化工中间体（上海）有限公司 | Application of Lavermit in preparing medicine for tetanic rachitis |
| CN1342458A (en) * | 2001-08-31 | 2002-04-03 | 欣凯医药化工中间体（上海）有限公司 | Application of leflunomide in preparing medicines to treat lupoid nephritis and nephrotic syndrome |
| CN1387845A (en) * | 2002-04-30 | 2003-01-01 | 上海欣凯医药发展有限公司 | Medicinal composition for treating autoimmune disease |
Non-Patent Citations (2)
| Title |
|---|
| "非典"的诊断标准与防治方案. 医药卫生报. 2003 |
| "非典"的诊断标准与防治方案. 医药卫生报. 2003 * |
Also Published As
| Publication number | Publication date |
|---|---|
| CN1602862A (en) | 2005-04-06 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| Velavan et al. | Monkeypox 2022 outbreak: an update | |
| Martín-Delgado et al. | Monkeypox in humans: a new outbreak | |
| Kern et al. | Oral activity of a methylenecyclopropane analog, cyclopropavir, in animal models for cytomegalovirus infections | |
| Berhanu et al. | ST-246 inhibits in vivo poxvirus dissemination, virus shedding, and systemic disease manifestation | |
| CN113289018B (en) | Application of old medicines such as auranofin and the like and compositions thereof in resisting single positive strand RNA viruses | |
| CN105535012A (en) | Broad-spectrum virus infection inhibitor | |
| Lu et al. | Mpox (formerly monkeypox): pathogenesis, prevention, and treatment | |
| Hobden et al. | In vitro synergism of trifluorothymidine and ganciclovir against HSV-1 | |
| CN100404030C (en) | Application of leflunomide in the preparation process of anti SARS virus medicine | |
| Stanberry et al. | Genital reinfection after recovery from initial genital infection with herpes simplex virus type 2 in guinea pigs | |
| Sall et al. | Successful treatment of progressive acyclovir-resistant herpes simplex virus using intravenous foscarnet in a patient with the acquired immunodeficiency syndrome | |
| CN114762694B (en) | Use of oligosaccharide transferase inhibitors for the prevention and/or treatment of novel coronavirus infections | |
| CN114377027A (en) | Application of pulsatilla saponin B4 in preparation of medicine for treating or preventing SARS-CoV-2 | |
| Basit et al. | Genesis of monkeypox | |
| CN110279693B (en) | Application of composition in preparation of medicine for preventing and/or treating fever with thrombocytopenia syndrome virus | |
| Silvera et al. | Effect of PMPA and PMEA on the kinetics of viral load in simian immunodeficiency virus-infected macaques | |
| CN105560351A (en) | Preparation for restraining adenovirus infection | |
| CN113440527A (en) | Application of naphthoquine or naphthoquine-containing combined preparation in resisting coronavirus | |
| JP2001072597A (en) | Anti-herpes viral agent | |
| CN105582015B (en) | The application of Fusidic Acid or its pharmaceutical salts in anti-hand-foot-and-mouth-disease medicine is prepared | |
| CN105560268A (en) | Preparation for restraining influenza virus infection | |
| Carp | Studies on the guanidine character of poliovirus | |
| CN113546076B (en) | Application of verteporfin in preparing medicine for resisting novel coronavirus SARS-CoV-2 | |
| CN111214472B (en) | Application of enoxacin in preparing medicament for preventing and/or treating flavivirus infection | |
| CN115381828B (en) | Application of pilalaisib in preparation of anti-enterovirus 71 type medicine |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant | ||
| EE01 | Entry into force of recordation of patent licensing contract |
Application publication date: 20050406 Assignee: SUZHOU CHANGZHENG-XINKAI PHARMACEUTICAL CO.,LTD. Assignor: CINKATE PHARMACEUTICAL INTERMEDIATES Co.,Ltd. Contract record no.: 2014310000070 Denomination of invention: Application of leflunomide in the preparation process of anti SARS virus medicine Granted publication date: 20080723 License type: Exclusive License Record date: 20140422 |
|
| LICC | Enforcement, change and cancellation of record of contracts on the licence for exploitation of a patent or utility model | ||
| CX01 | Expiry of patent term | ||
| CX01 | Expiry of patent term |
Granted publication date: 20080723 |