CN1535724B - New application of recombinant human interferon for preventing serious acute respiratory tract syndrome - Google Patents
New application of recombinant human interferon for preventing serious acute respiratory tract syndrome Download PDFInfo
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- CN1535724B CN1535724B CN 03122221 CN03122221A CN1535724B CN 1535724 B CN1535724 B CN 1535724B CN 03122221 CN03122221 CN 03122221 CN 03122221 A CN03122221 A CN 03122221A CN 1535724 B CN1535724 B CN 1535724B
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Abstract
The present invention relates to a new application of antiviral cytokine-recombinant human interferon for preventing serious acute syndrome of respiratory tract. The invention finds that recombinant human interferon alpha 1b and alpha 2b and beta interferon can inhibit the reproduction of SARS virus in vitro so as to prompt that said recombinant human interferon alpha 1b, alpha 2b and beta interferon can be used for preventing SARS due to corona virus and its mutant. Therefore, the invention effectively guarantees the health of human beings.
Description
The cytokine that the present invention relates to recombinate: recombinant human interferon alpha 2 is used to prevent seriousness acute respiratory syndrome (recombinant human interferon, new treatment indication rhIFN).The cytopathy that rhIFN can cause the vitro inhibition SARS virus is significantly found in experiment, and this prompting rhIFN can be used as the new drug that is used to prevent SARS.
According to interferon (interferons; IFNs) definition; Interferon is one type to be had broad-spectrum antiviral, anti-cell division, immunoregulatory activity and on different approaches, is influencing the protein of metabolism, growth and the differentiation of cell at least on the allogenic cell, its active performance needs new synthetic RNA and protein.It is one type of important cytokines.Through nearly more than 30 years clinical research and application, explain that it is a kind of important broad-spectrum antiviral, antineoplaston medicine.
Know that so far there are a plurality of types in human interferon: interferon-' alpha ', β, δ, γ, ε, K, λ, types such as τ and ω, table 1. is seen in their main feature and possible clinical practice
The main feature of 9 kinds of type interferon of table 1 and its clinical practice or possible clinical application catalog
At present, study more and be used for the α that has of clinical treatment, beta, gamma; Whether other type interferon has clinical value still among research.
Know that so far mammiferous interferon such as people, mice, cattle, horse has three types such as α, β, γ at least.IFN-α and IFN-β are called I type interferon; IFN-ω and IFN-τ etc. also belong to the I type; IFN-γ is an II type interferon.Once there was a kind of IFN-β 2 to name and is not belong to interferon by IL-6.Titles such as LeIF, fiblaferon, immune interferon were once arranged in history, do not adopt at present.
U.S. FDA in 1986 ratifies genetic engineering interferon-α 2a (Roche company) at first simultaneously and interferon-' alpha ' 2b (Schering company) puts on market; Genetic engineering interferon-β, γ also get permission to put on market in nineteen ninety, 1993 in succession.More than 60 about more than the 40 kinds of diseases of state approval interferon therapy are arranged at present.
Domestic human, α 2a type by common development of units such as Virology Inst., Chinese Academy of Preventive Medical Science, Shanghai Biological Products Inst., Ministry of Public Health, Changchun Biological Products Institute, Ministry of Public Health and Nat'l Pharmaceutical & Biological Products Control Institute and exploitation; α 2b type; China Drug Administration approval of γ type genetic engineering interferon is put on market; It is China's first genetic engineering high-tech medicine through national official approval; Wherein people's gene engineering interferon-' alpha ' 1b is China's initiative, compares with external like product, has the low advantage of side effect.But many indications of interferon are to use the interferon alpha 2 b type to obtain in the world.
From in November, 2002 in China Guangdong Province popular a kind of " severe acute respiratory syndrome "; In short several months, popular in the whole world, be referred to as seriousness acute respiratory syndrome (severe acute respiratory syndrome; SARS), receive the concern of countries in the world.Its original cause of disease mainly is human coronary virus's a new variant.Therefore, coronavirus receives numerous medical workers and virologist's attention.
The circulation way of SARS virus thought by cough originally and to play the droplet transmission that tears cause be main, still, and according to its regularty of epidemic; And find that the virus quantity that exists in patient's feces is higher than blood, therefore, possibly infect the same with ani mal coronavirus; Except that breathing; But fecal-oral transmission also, through the excremental pollution of patient, directly the touching etc. of hands.WHO estimates that the mortality rate of SARS is about 4%, and death is often with other state of an illness, and like diabetes or heart disease, or body's immunological function descends.Case recovery in 1 week after infection of 90% is arranged approximately.This and West Nile Virus infection are similar.Still do not have special effect medicine therapeutic at present, do not have vaccine yet and can prevent..
Interferon spray individual protection prevention is present first-selected attainable method, and its scientific evidence is following:
1, SARS virus belongs to novel coronavirus; It is (+) strand rna virus; Many (+) strand rna virus member is all very responsive to interferon; Like rhinovirus, this laboratory once carried out the research work of interferon therapy rhinovirus 14 types and 39 types in a large number on cell culture, had proved that interferon is to the rhinoviral sensitivity of this (+) chain RNA.
2, on the webpage of Britain cat peritonitis coronavirus, suggestion once is with interferon therapy and control FCV.And the antibody of FCV can suppress the growth of SARS virus on cell culture.
http://www.dr-addie.com/
3, Pei et al. (2001) report: the infection that can suppress and treat the chicken bronchitis coronavirus and cause with chicken interferon I type.And the antiserum of chicken bronchitis coronavirus also can suppress the growth of SARS virus on cell culture.
Pei?et?al.(2001)Chicken?interferon?type?I?inhibits?infectious?bronchitis?virusreplication?and?associated?respiratory?illness.J?Interferon?Cytokine?Res.21(12)：1071-1077。
4, virazole (Ribavirin) is limited to new isolating coronavirus effect: wherein the MMWR of CDC point out virazole in vitro tests to new isolating coronavirus unrestraint effect.Lancet finds the report of coronavirus also to point out virazole poor effect in the considerable part critically ill patient about Hong Kong University.
5, Aurisicchio et al. (2000) report: have a liking for the infection that liver property 2 type interferon can be protected murine hepatitis virus (a kind of coronavirus).
Aurisicchio?et?al.(2000)Liver-specific?alpha?2?interferon?gene?expression?resultsin?protection?from?induced?hepatitis.
J?Virol.74(10)：4816-4823。
6, can suppress pig toxigenicity respiratory syndrome virus (a kind of coronavirus) with body internal interference element in vitro infects.Buddaert?et?al.(1998)In?vivo?and?in?vitro?interferon(IFN)studies?with?the?porcinereproductive?and?respiratory?syndrome?virus(PRRSV).Adv?Exp?Med?Biol.440：461-467。
7, the cell line Vero E6 (and FRhk-4) that is separated to novel coronavirus produce have aspect the interferon damaged, so be easy to separate and produce pathological changes.
Emeny?JM，Morgan?MJ.(1979)Regulation?of?the?interferon?system：evidence?thatVero?cells?have?a?genetic?defect?in?interferon?production.J?Gen?Virol43(1)：247-252。
Other to the old people, the immune level descender will carry out immune strengthening treatment (interferon itself also has this effect).Because can destroy the immune system of body during coronavirus infection.The immune strengthening agent has multiple, comprises the vitamin A that the crown poison of prevention animal uses when infecting, E, C etc., thymosin, interleukin-2 etc.
The present invention has proved that the interferon of recombinant human interferon alpha 2 b that Beijing plan far away pharmaceutcal corporation, Ltd produces and other type can suppress the breeding of SARS virus on cell culture.
The present invention adopts classical interferon activity assay method, adopts SARS virus-RDa cell (people's rhabdomyoma cell strain) system.With the RDa cell of the RPMI-1640 culture medium that is grown in 10%FCS by 1 * 10
5/ ml inoculates 96 porocyte culture plates; Every pore volume 100 μ l; The interferon a2b (recombinant human interferon alpha 2 b that plan far away pharmaceutcal corporation, Ltd in Beijing produces), a1b (Beijing Jindike Biological Technology Inst.'s development), β (Beijing Jindike Biological Technology Inst.'s development), the ω (Beijing Jindike Biological Technology Inst.'s development) (each three parallel hole) that add 100 μ l serial dilutions after the incubated overnight; Act on and abandon culture fluid after 12 hours; Again add SARS virus 150 μ l (what Chinese Disease Control and Prevention Center virosis separated and cultivated) with 50 * TCID50 of the RPMI-1640 culture medium dilution that contains 2%FCS; Observe pathological changes after 24 hours; After treating the complete pathological changes of virus control, the range estimation record suppresses the minimum of the interferon of 50% cytopathy (CPE), and the result confirms that recombinant human interferon alpha 2 a2b, a1b, β have comparatively obvious suppression effect, recombinant human interferon omega inhibitory action less (result sees Figure of description 1) to SARS virus (being preced with 9 strains) on the RDa cell culture.
The explanation of Figure of description 1 drawing: to the inhibition test of SARS virus (being preced with 9 strains), recombinant human interferon alpha 2 a2b, a1b, β, ω suppress SARS virus and cause that the cytopathic consumption of 50%RDa is respectively every milliliter 0.28 nanogram, 7 nanograms, 9 nanograms and 39 nanograms on the RDa cell culture for recombinant human interferon alpha 2 a2b, a1b, β, ω.
Embodiment 1: the recombinant human interferon alpha 2 b of variable concentrations, a1b, β spray are used for nasal cavity and nasopharynx part medication control SARS virus or its mutant; The Main Ingredients and Appearance of these article: recombinant human interferon alpha 2, human albumin; Mannitol, its effective ingredient are recombinant human interferon alpha 2.
Embodiment 2: the recombinant human interferon alpha 2 b of variable concentrations, a1b, β nasal drop are used for nasal cavity and nasopharynx part medication control SARS virus or its mutant; The Main Ingredients and Appearance of these article: recombinant human interferon alpha 2, human albumin; Mannitol, its effective ingredient are recombinant human interferon alpha 2.
Embodiment 3: the recombinant human interferon alpha 2 b of variable concentrations, a1b, β suppository are used for vagina, rectal application control SARS virus or its mutant; The Main Ingredients and Appearance of these article: recombinant human interferon alpha 2, human albumin; Mannitol, its effective ingredient are recombinant human interferon alpha 2.
Embodiment 4: the recombinant human interferon alpha 2 b of variable concentrations, a1b, β peroral dosage form (comprising buccal dosage forms) are used for digestive tract medication control SARS virus or its mutant; The Main Ingredients and Appearance of these article: recombinant human interferon alpha 2, human albumin; Mannitol, its effective ingredient are recombinant human interferon alpha 2.
Embodiment 5: the recombinant human interferon alpha 2 b of variable concentrations, a1b, β injection type (comprising aqueous injection and injectable powder) are used for vein, abdominal cavity, muscle drug administration preventing and controlling SARS virus or its mutant; The Main Ingredients and Appearance of these article: recombinant human interferon alpha 2, human albumin; Mannitol, its effective ingredient are recombinant human interferon alpha 2.
Claims (2)
1. the application aspect the severe acute respiratory syndrome medicine that caused by coronavirus and mutant thereof in preparation prevention of recombined human I type interferon is characterized in that described recombined human I type interferon is recombinant human interferon alpha 1 b, α 2b and IFN-.
2. application according to claim 1 is characterized in that, the dosage form of said medicine is spray, nasal drop, suppository, oral agents, injection.
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| CN1535724B true CN1535724B (en) | 2012-09-05 |
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| CN106784341A (en) * | 2017-01-20 | 2017-05-31 | 电子科技大学中山学院 | Microwave annealing treatment method for perovskite solar cell photoactive layer |
| CN111346219B (en) * | 2020-02-21 | 2021-05-14 | 上海甘翼生物医药科技有限公司 | Use of interferon in preparing medicine for preventing coronavirus infection or preventing diseases caused by coronavirus infection |
| CN111671886B (en) * | 2020-03-05 | 2022-11-15 | 上海甘翼生物医药科技有限公司 | Pharmaceutical composition for preventing high-risk susceptible people from infecting coronavirus or generating coronavirus infection disease and application of pharmaceutical composition |
| CN113425832A (en) * | 2020-03-23 | 2021-09-24 | 杭州先为达生物科技有限公司 | Use of interferon lambda in the treatment of infections with novel coronaviruses (2019-nCoV) |
| KR20230041097A (en) | 2020-07-20 | 2023-03-23 | 시네어젠 리서치 리미티드 | Inhaled interferon-beta to improve outcomes in patients with SARS-CoV-2 infection |
Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997039127A1 (en) * | 1996-04-12 | 1997-10-23 | University Of Florida | Hybrid interferon compositions and methods of use |
| EP0888122A1 (en) * | 1995-12-28 | 1999-01-07 | Tanox Biosystems, Inc. | HYBRID WITH INTERFERON-alpha AND AN IMMUNOGLOBULIN Fc LINKED THROUGH A NON-IMMUNOGENIC PEPTIDE |
| EP1082132A1 (en) * | 1998-05-29 | 2001-03-14 | Biogen, Inc. | Recombinant human interferon beta-1a (ifn-beta-1a) formulation |
| WO2002081519A2 (en) * | 2001-03-21 | 2002-10-17 | Genemedix Plc | Ifn-thy fusion protein,dna coding therefore,its preparation and application |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0888122A1 (en) * | 1995-12-28 | 1999-01-07 | Tanox Biosystems, Inc. | HYBRID WITH INTERFERON-alpha AND AN IMMUNOGLOBULIN Fc LINKED THROUGH A NON-IMMUNOGENIC PEPTIDE |
| WO1997039127A1 (en) * | 1996-04-12 | 1997-10-23 | University Of Florida | Hybrid interferon compositions and methods of use |
| EP1082132A1 (en) * | 1998-05-29 | 2001-03-14 | Biogen, Inc. | Recombinant human interferon beta-1a (ifn-beta-1a) formulation |
| WO2002081519A2 (en) * | 2001-03-21 | 2002-10-17 | Genemedix Plc | Ifn-thy fusion protein,dna coding therefore,its preparation and application |
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