CN104352549A - Dispersible tablets for preventing and controlling hemorrhagic fever viruses - Google Patents

Dispersible tablets for preventing and controlling hemorrhagic fever viruses Download PDF

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CN104352549A
CN104352549A CN201410571557.0A CN201410571557A CN104352549A CN 104352549 A CN104352549 A CN 104352549A CN 201410571557 A CN201410571557 A CN 201410571557A CN 104352549 A CN104352549 A CN 104352549A
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hemorrhagic fever
viruses
dispersible tablets
virus
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姜宝库
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/19—Acanthaceae (Acanthus family)
    • A61K36/195—Strobilanthes
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/31—Brassicaceae or Cruciferae (Mustard family), e.g. broccoli, cabbage or kohlrabi
    • A61K36/315—Isatis, e.g. Dyer's woad

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  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention discloses dispersible tablets for preventing and controlling hemorrhagic fever viruses. The dispersible tablets are named according to functions, are used for preventing and controlling the hemorrhagic fever viruses, and not only can be orally taken but also can be taken after being quickly dispersed in water. The dispersible tablets belong to the technical fields of epidemiology, molecular virology, molecular biology, cellular and molecular immunology and modern traditional Chinese medicine science, and various disciplines are mutually fused. The dispersible tablets are used for preventing and controlling Ebola hemorrhagic fever viruses which belong to segmental RNA (ribonucleic acid) viruses, and the segmental RNA viruses are easily mutated. High-risk easily infected persons are infected with the viruses due to low natural immunity and immunodeficiency. The dispersible tablets are proposed by developers and can be used for improving natural immunity, activating immune cells, inducing interferon and resisting the viruses in a broad-spectrum manner. The dispersible tablets are used for preventing the hemorrhagic fever viruses, protecting medical personnel, easily infected children, old people with vital energy deficiency and persons with low immunity, and treating people infected with the hemorrhagic fever viruses.

Description

Control hemorrhagic fever virus dispersible tablet
(1) technical field
Ebola hemorrhagic fever is cause the most fatal infectious disease by hemorrhagic fever virus.Now, accumulative 8399 examples in area, West Africa infect, dead 4644 people.Hemorrhagic fever virus is the one virus causing mankind's hemorrhagic fever illnesses, and viral hemorrhagic fever has 13 kinds, has harmless according to this sick kidney, is divided into and has kidney to undermine without kidney damage two large classes.Before pathogen is unresolved, China claims epidemic hemorrhagic fever (EHF), and Korea claims KHF (KHF), and Russia claims hemorrhagic nephroso-nephritis (HNN).Due to establishment and the etiologic solution of specific serological diagnosis, nineteen eighty-two World Health Organization's unification is named as hemorrhagic fever with renal syndrome, and existing China still continues to use the name of disease of epidemic hemorrhagic fever.The virus quoting hemorrhagic fever is mainly the Hantaan virus of bunyaviridae (Hantaanvirus), xinjiang hemorrhagic fever virus (Xinjiang hemorrhagiv fever virus) and dengue virus etc.Hemorrhagic fever virus, be segmented RNA viruses, this viroid is easily changed different, has caused more than 10 outbreak of epidemic.With regard to present U.S.-China Korea Spro towards four countries' vaccine, NAT is not high, and Conversion rate is below standard.Acquired vaccine development, also needs the long period.
Poor brother is in distress in Africa, and Chinese doctor ought to succour.Deep feeling and sagacity, develop traditional Chinese medical science new drug, " control hemorrhagic fever virus dispersible tablet ".There is the enhancing natural immunity, immune cell activated, inducement interferon, broad-spectrum antiviral; Prevention: hemorrhagic fever virus, protection medical worker, susceptible children, deficiency of vital energy old man and immunocompromised person; Treatment: hemorrhagic fever virus the infected.
Art: epidemiology, Molecular Virology, molecular biology, cellular elements immunology and modern Chinese medicine pharmacy, multiple subject merges mutually.
(2) background technology
1, the popular main cause of West Africa epidemic situation
1. HFRS vaccine is below standard, lacks and rushes out fever virus medicine.2. Virus latency is long long with the toxin expelling phase.Reach 21 days incubation period, in patient blood, viral level is high, and patient's vomitus, Excreta and conjunctival secretion etc., all have high risk, sustainable propagation.3. long-term continuing isolates, and food supply and medical services cannot meet, and prevention and control measure is not implemented.4. West Africa resident, for the deceased keeps vigil beside the coffin, cleans, embraces, kisses relatives' custom of passing away, causes viruses contact to be propagated.5. public health weak foundation, personnel's goods and materials lack.
2, hemorrhagic fever vaccine Development Status
Up to now, successfully develop three class HFRS vaccines both at home and abroad, i.e. purification suckling mouse brain inactivated vaccine, cell culture inactivated vaccine and genetic engineering restructuring (work) vaccine (table 15-1).
Table 15-1 HFRS Vaccines classes and type
Purification suckling mouse brain inactivated vaccine and cell culture inactivated vaccine all can stimulate generation specific antibody after inoculation human body, and preliminary large-scale inoculation is observed and also shown that it has better effects to prevention HFRS.But this two classes vaccine all also also exists some shortcomings part, and the Conversion rate mainly comprising neutralizing antibody does not also reach 100%, and NAT not high (being generally 1: 10 ~ 1: 40); Antibody is held time shorter, often needs supplementary immunization etc.
U.S. Schmal john CS etc. are carrier with vaccinia virus, high expression M and the S fragment of HTNV, develop restructuring HTNV vaccine.I phase clinical experiment shows, only has high-titer vaccine (7.5logPFU), 2 pin inoculation group create good Neutralizing antibody response.They are studying the recombiant vaccine carrying out Combined expression HTNV and PUUV with another kind of vaccinia virus vector at present, to improve safety and the immune effect of vaccine.
(3) summary of the invention
[name] medicine name: control hemorrhagic fever virus dispersible tablet.High-risk susceptible person, the natural immunity is low, and acquired immunity lacks, and susceptible virus, causes severe complication or death.Card belongs to, healthy energy interior-deficiency, and poison is evil to be invaded, and opposing is not enough, and virus is driven straight in, Fast-propagation.Name according to this product function: control hemorrhagic fever virus, strengthens the natural immunity, immune cell activated, inducement interferon, broad-spectrum antiviral; Prevention: protect high-risk susceptible person; Treatment: hemorrhagic fever virus the infected.Dispersible tablet can be oral, clothes after also can disperseing rapidly in water.
[prescription] Radix Astragali, Radix Isatidis, MCC301.
[pharmacology] ● the Radix Astragali strengthens the natural immunity, immune cell activated, inducement interferon, broad-spectrum antiviral.
Be 10 by dilution factor -5hemorrhagic fever virus (EHF.V) suspension, with 0.1ml/ dosage, be inoculated in neonatal rat intraperitoneal, continuous 7 days.Virus inoculation is after 6 days, and occur dehydration, hindlimb paralysis, towers or died, is all included in morbidity number.After virus inoculation, start to use astragalus injection abdominal cavity.Medication group neonatal rat sickness rate and EHF.V Positive rate are all starkly lower than matched group, and both have highly significant at difference.Experimental result: Radix Astragali injection can reduce the sickness rate of inoculation EHF.V neonatal rat, and reduces the positive rate that in do not fall ill suckling mouse brain, lung, EHF.V detects.Passage cell experiment display, Radix Astragali injection to the infection of EHF.V in VeioE6 cell, without obvious blocking effect.Think accordingly: Radix Astragali injection has certain blocking effect to the infection of EHF.V in neonatal rat body, its mechanism also non-immediate suppresses virus, but is played a role by the immunomodulating of host [1].
The Radix Astragali and Radix Isatidis are to the In-vitro Inhibitory Effect of pig parvoviral (PPV).[method] Radix Astragali, Radix Isatidis, as antiviral drugs, utilize cytopathy (CPE) inhibition test, measure the Radix Astragali and Radix Isatidis is used alone and equal-volume share, to the inhibitory action of pig parvoviral on PK-15 cell monolayer.When [result] Radix Isatidis is used alone, in vitro tests has obvious inhibitory action to PPV, is 0.63mg/mL to the minimum mass concentration of directly killing of PPV, minimum blocking-up mass concentration 0.31mg/mL; When the Radix Astragali is used alone to PPV without obvious inhibitory action; When Radix Isatidis and Radix Astragali equal-volume share, significantly strengthen the inhibitory action of PPV, minimum mass concentration of directly killing rises to 0.31mg/mL, and minimum blocking-up mass concentration rises to 0.038mg/mL.[conclusion] Radix Astragali and Radix Isatidis conbined usage anti-virus ability strengthen, and toxicity is more weak [2].
Only, intravenous injection, within 6 ~ 24 hours, effectively protect the Intravenous Infection of mice infected by influenza, the best protection time is 18 ~ 24 hours to Radix Astragali 0.4ml/, and protective rate is more than 50%.5% ~ 10% Radix Astragali, effectively Cell protection, suppress vesicular stomatitis virus cytopathogenic effect.Inducement interferon in body: the Radix Astragali quiet note mice, only, after 2 hours, serum interferon is 40U/ml to 0.4ml/, within 6 hours, can reach 160U/ml, within 24 hours, does not measure.Strengthen macrophage phagocytic function: astragalus injection mice, 18 ~ 24 hours, macrophage index significantly increased (P < 0.01), within 72 hours, be down to normal, and phagocytic function strengthened consistent with antiviral peak period.With macrophage inhibitors, block phagocytic function, do not affect Radix Astragali inducement interferon, but reduce and mice is protected.Show that Radix Astragali antiviral is relevant with activating macrophage.Strengthen antibodies against influenza virus to generate: astragalus injection mice (0.4ml/ only), between 2 ~ 3 weeks, in mice serum, antibodies against influenza virus titre is that 4 times (P < 0.05) the 4th week of matched group are equal [3].
Astragalus Injection in Treating viral myocarditis (34 example) treatment group: buchu Radix Astragali injection 20ml (being equivalent to crude drug 40g) is placed in 5% G/W or normal saline 250ml or 500ml medium-sized vein drop, every day 1 time, it within 2 weeks, was 1 course for the treatment of, change astragalus membranaceous 20g into later, every day 2 times, continuous 3 ~ 6 months; Vitamin C 0.3g, every day 3 times; Ubiquinone 1020mg, every day 3 times, 3 ~ 6 months courses for the treatment of.
Matched group: 5% glucose 500ml adds insulin 6U and 10% potassium chloride 10ml intravenous drip, 2 weeks is 1 course for the treatment of.Change ubiquinone into later 1020mg every day 3 times, vitamin C 0.3g, every day 3 times, take 3 ~ 6 months continuously, two groups of viewing durations, Primary Care is consistent, person adds with antiarrhythmic drug severe arrhythmia, if there is cardiac insufficiency, all use Di Gaoxin, enalapril, diuretic for two groups, drug withdrawal after cardiac insufficiency controls.
The negative conversion rate of result Astragalus in Treating group Number of Peripheral Blood Leucocyte EVs-RNA half a year is significantly higher than matched group, illustrates that the Radix Astragali may suppress EVs-RNA copying in vivo, makes virus in vivo can not Growth and reproduction.The Radix Astragali has many-sided immunomodulating and immunological enhancement simultaneously, it can the generation of enhancing antibody, macrophage phagocytic virus capable can be increased again, the activity of NK cell can also be strengthened, improve body opposing virus capable, alleviate the coup injury of virus to cardiac muscle, thus reach the effect of clinical treatment CMC [4].
10% Astragalus membranaceus, adopts interferon algoscopy.Table 1 is experimental result:
The table 1 variable concentrations Radix Astragali is inducement interferon in S wiss mouse boosting cell is cultivated
* interferon titre: (log 2unit/0.5ml):
Have obvious antiviral activity in supernatant, the latter is more obvious with the concentration rising of the Radix Astragali.When adding 0.4% Radix Astragali, antiviral activity is 4.42 ~ 5.17 (log 2), and only 2.8 ~ 3.85 (log during 0.05% Radix Astragali 2).
Adopt 3hTdRc participates in method and determines the Radix Astragali to LT effect, and table 3 illustrates, when Radix Astragali concentration is 0.025 ~ 0.2%, obvious conversion reaction occurs mouse spleen lymphocyte.During 0.2% Radix Astragali, transformation index is 7.55 ~ 8.55, is that 2.18 ~ 2.25. studies further and shows when being low to moderate 0.025%, and the height of interferon titre is parallel with the size of Lymphocyte transformation index haply.
The PRELIMINARY RESULTS of dynamic test also shows, mouse boosting cell stimulates at the Radix Astragali and namely starts inducement interferon in latter 2 hours, and within 6 hours, obviously increase, within 12 hours, namely arrive peak, what this and Con-A induced IFN-γ is dynamically similar.The Radix Astragali mouse boosting cell cultivate in, inducement interferon and stimulate lymphocyte transformation [5].
Radix Astragali endogenous inducement interferon, has extensive antiviral effect.Viral infection is early stage, interferon-induced host cell, produces antiviral protein (Mx), and suppress virus replication, wake up and close on cells against viral, activated macrophage, NK cell, cytotoxic cell, kill infection cell; In interferon born of the same parents, born of the same parents set up outward " antiviral united front ", and item during the natural immunity suppresses to copy, and prevent diffusion, remove virus, play decisive role, and strengthen MHC expression, promote acquired immunity.
● Radix Isatidis strengthens the natural immunity, immune cell activated, broad-spectrum antiviral.
Banlangen Polysaccharide (IIP) 50mg/kg lumbar injection has remarkable immunoenhancement result, mice spleen is heavily increased, immunocyte division growth, and IIP obviously can promote that macrophage system is engulfed carbon granules and clean up, and strengthens antagonist and forms cell function [6].IIP strengthens NK activity and the cell transformation of inductor endolymph of splenocyte [7].Radix Isatidis agglutinin can promote growth and the propagation of mouse thymus [8].
1: 100 Radix Isatidis injection has kill activity in vitro to hemorrhagic fever virus [9].Embryo Gallus domesticus is tested, and 50% Radix Isatidis injection has obvious inhibitory action to influenza A virus.6 hours, infected chicken proembryo, 24 hours preventive administrations, also have the effect of significant suppression influenza virus [10].Mtt assay detects, and 50% Radix Isatidis decoct has significant antitoxin effect to human cytomegalic inclusion disease virus when 1: 200 diluent [11].Radix Isatidis has moderate inhibitory action to hepatitis B virus DNA [12].
[side separate] medical worker, old germling are weak, immunocompromised person, and easy infection hemorrhage fever virus, causes serious complication or death.The traditional Chinese medical science is thought, healthy energy interior-deficiency, and the evil invasion of poison, drag is not enough, and virus is driven straight in, Fast-propagation.Molecular Virology and Immunology Today research: hemorrhagic fever virus is RNA viruses, easily changes different, acquired vaccine difficulty becomes.Merge multidisciplinary, development " control hemorrhagic fever virus dispersible tablet ", strengthens the natural immunity, immune cell activated, inducement interferon, broad-spectrum antiviral.Prevention: hemorrhagic fever virus, protects high-risk susceptible person; Treatment: hemorrhagic fever virus infected patient.
[toxicity] Radix Astragali toxicity, mouse peritoneal injection LD50 is 40 ± 5g crude drug/kg [14].The LD50 at least > 100g/kg of Radix Isatidis [15].
(4) detailed description of the invention
2490/gMCC301 is appropriate for [prescription] Radix Astragali 5478/g Radix Isatidis.
[method for making], with two tastes of going forward, decocts with water twice, 2 hours first times, second time 1 hour, collecting decoction, and filter, filtrate is concentrated into the clear paste that relative density is 1.15 ~ 1.20 (50 ~ 60 °), spraying dry; Add MCC301 appropriate, shake up, granulate, be pressed into 1000, obtain final product.
[function with cure mainly] QI invigorating righting, Gu Wei kills virus; Strengthen the natural immunity, immune cell activated, inducement interferon, broad-spectrum antiviral.Prevention: hemorrhagic fever virus, protection medical worker, susceptible children, deficiency of vital energy old man and immunocompromised person; Treatment: hemorrhagic fever virus infected patient.
[usage and consumption] prevents: one time 3,2 times on the one (two weeks).Treatment: one day, 9.Divide 3 clothes, each 3.Dispersible tablet can be oral, clothes after also can disperseing rapidly in water.
[specification] a slice is equivalent to crude drug 8g.
[storage] seals.
[list of references]
[1] Tang Xiaopeng, etc.The inhibitory action of Radix Astragali Epidemic Hemorrhagic Fever viral infection, Hunan Medical University's journal, 1990,15 (3): 250 ~ 252
[2] Zhong Hua, etc.The Radix Astragali and Radix Isatidis to the In-vitro Inhibitory Effect of pig parvoviral, Journal of Northwest Sci Tech University of Agriculture and Forestry, 2008,36 (10): 48 ~ 52
[3] Zhang Xingquan, etc.The effect of Radix Astragali resisiting influenza virus and inducement interferon, the research of Promote immunity function, Chinese microbiology and Journal of Immunology, 1984,4 (2): 94 ~ 97
[4] Zhang Hongxia, Astragalus Injection in Treating viral myocarditis 34 example, the Shaanxi traditional Chinese medical science, 2005,26 (11): 1148 ~ 1149
[5] Hou Yunde, etc.The Radix Astragali is inducement interferon and stimulation lymphocyte transformation in mouse boosting cell is cultivated, Chinese microbiology and Journal of Immunology, 1981,1 (2): 137 ~ 139
[6] Xu Yimin, etc.The experimentation of Banlangen Polysaccharide Promote immunity function, combination of Chinese and Western medicine magazine, 1991,11 (6): 357 ~ 359
[7] Lu Pingcheng, etc.Banlangen Polysaccharide to the immunoregulation effect of mice, Pharmacology and Clinics of Chinese Materia Medica, 1991,7 (2): 22 ~ 23
[8] Hu Xingchang, etc.The impact that Radix Isatidis agglutinin is grown mouse thymus, Chinese Journal of anatomy, 2003.23 (6): 559 ~ 561
[9] Li Wenwen, etc.Radix Isatidis, the experimentation of Fructus Camptothecae Acuminatae hf resi stant RSV and HSV-2 effect, Hunan Medical University's journal, 1994.19 (4): 309 ~ 311
[10] microbiology teaching and research group of Anhui Medical institute: the inhibitory action of 50% Radix Isatidis injection popularity cold virus, epidemic diseases study on prevention, 1974, (3): 176 ~ 179
[11] Sun Guanglian, etc.Mtt assay detects Radix Isatidis Against HFRSV giant cell toxic effect, Shandong Traditional Chinese Medicine University's journal, 2000,24 (2): 137 ~ 138
[12] Yang Jianying, etc.The experimentation of Traditional Chinese Medicine Anti hepatitis B virus, combination of Chinese and Western medicine magazine, 1989,9 (8): 494 ~ 495
[13] Huang Houpin, etc.The diuresis of the Radix Astragali and hypotensive effect, Acta Pharmaceutica Sinica, 1965,12 (5): 319 ~ 324
[14] the Cen Qinbo chief editor in building.Parts of generic medicinal plants kind arranges and quality research, first, combined publication society of China Concord Medical Science University of Beijing Medical University, 333 ~ 338

Claims (1)

1. " control hemorrhagic fever virus dispersible tablet ", hemorrhagic fever virus is RNA viruses, easily changes different.U.S.-China Korea Spro is towards four countries, and develop vaccine not up to standard, NAT is not high, and acquired immunity difficulty becomes.High-risk susceptible person, immunocompromised, susceptible virus; Card belongs to, and healthy energy interior-deficiency, failure of defensive QI to protect the body against pathogen, caused by drag deficiency.Combination of differentiation of syndrome and disease, development prescription: the Radix Astragali, Radix Isatidis, MCC301, have the enhancing natural immunity, immune cell activated, inducement interferon, broad-spectrum antiviral; Prevention: hemorrhagic fever virus, protection medical worker, susceptible children, deficiency of vital energy old man and immunocompromised person; Treatment: hemorrhagic fever virus the infected.
CN201410571557.0A 2014-10-24 2014-10-24 Dispersible tablets for preventing and controlling hemorrhagic fever viruses Pending CN104352549A (en)

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Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1629847A1 (en) * 2004-08-12 2006-03-01 Tian Shengxun Herbal AIDS treatment
CN101336957A (en) * 2008-03-11 2009-01-07 姜宝库 Strong Dikang oral liquid

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP1629847A1 (en) * 2004-08-12 2006-03-01 Tian Shengxun Herbal AIDS treatment
CN101336957A (en) * 2008-03-11 2009-01-07 姜宝库 Strong Dikang oral liquid

Non-Patent Citations (2)

* Cited by examiner, † Cited by third party
Title
唐晓鹏等: "黄芪对流行性出血热病毒感染的抑制作用", 《湖南医科大学学报》 *
李闻文: "板蓝根抗肾综合症出血热病毒的研究", 《实用预防医学》 *

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Application publication date: 20150218