CN114796189A - Pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof - Google Patents

Pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof Download PDF

Info

Publication number
CN114796189A
CN114796189A CN202210223547.2A CN202210223547A CN114796189A CN 114796189 A CN114796189 A CN 114796189A CN 202210223547 A CN202210223547 A CN 202210223547A CN 114796189 A CN114796189 A CN 114796189A
Authority
CN
China
Prior art keywords
rotenone
human
pharmaceutical composition
virus
respiratory
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.)
Granted
Application number
CN202210223547.2A
Other languages
Chinese (zh)
Other versions
CN114796189B (en
Inventor
张科
罗语思
杨筱萌
沈祥春
张晗溪
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Guizhou Medical University
Original Assignee
Guizhou Medical University
Priority date (The priority date 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 date listed.)
Filing date
Publication date
Application filed by Guizhou Medical University filed Critical Guizhou Medical University
Priority to CN202210223547.2A priority Critical patent/CN114796189B/en
Publication of CN114796189A publication Critical patent/CN114796189A/en
Application granted granted Critical
Publication of CN114796189B publication Critical patent/CN114796189B/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
    • A61K31/352—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom condensed with carbocyclic rings, e.g. methantheline 
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Virology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Pulmonology (AREA)
  • Engineering & Computer Science (AREA)
  • Epidemiology (AREA)
  • Molecular Biology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Medical Informatics (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)

Abstract

The invention discloses a pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof, and relates to the technical field of respiratory tract diseases. The inventors have found a new use of rotenone. In vitro and in vivo experiments prove that the rotenone can reduce the virus titer of human laryngeal cancer epithelial cells infected by Human Respiratory Syncytial Virus (HRSV), improve the survival rate of animals and promote the weight of the infected animals to gradually rise from a low level. The rotenone has good effect of resisting respiratory pathogens (particularly respiratory infection resisting viruses), is used for treating and/or preventing respiratory pathogen infection, has good application prospect, and can be used for developing corresponding respiratory pathogen infection treating or preventing medicines. Brings good news to patients with pneumonia such as viral pneumonia.

Description

Pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof
Technical Field
The invention relates to the technical field of respiratory diseases, in particular to a pharmaceutical composition for treating and preventing respiratory pathogen infection and application thereof.
Background
Rotenone (Rotenone) is a natural compound derived from the roots and stems of derris, turfgrass, agave and mungbean species. Since the discovery of rotenone at the end of the 19 th century, it has been widely used as an insecticide for controlling insects, ticks and lice, and as a fish insecticide for managing fish in lakes and reservoirs. Betarbet et al reproduced most of the behavioral, biochemical and pathological features of Parkinson's disease in rotenone-treated rats in 2000. Since then, rotenone has received much attention as an environmental neurotoxin involved in the pathogenesis of parkinson's disease. In addition, researchers are currently available to construct a common experimental model of rotenone-treated rats for studying the underlying mechanisms responsible for parkinson's disease and for evaluating new potential treatments for this disease.
The existing research shows that: mitochondria produce ATP via oxidative phosphorylation complexes present in their inner membranes, which are known as NADH ubiquinone oxidoreductase (complex I), succinate dehydrogenase (complex II), ubiquinone cytochrome c oxidoreductase (complex III), cytochrome c oxidase (complex IV), and ATP synthase (complex V). The oxidative phosphorylation process begins with the oxidation of NADH by the complex I enzyme. It is now known that rotenone can lead to a significant decrease in cellular mitochondrial ATP production by oxidative phosphorylation of the complex I by inhibiting complex I, while electrons leaking at complex I can reduce unreduced oxygen at complex IV to Reactive Oxygen Species (ROS), leading to ROS elevation.
At present, rotenone is reported to resist human virus infection: in 2020, deguelin inhibition of autophagy could be studied as a new anti-Hepatitis C Virus (HCV) compound (Liao W, X Liu, Yang Q, et al. deguelin inhibition of HCV replication method of Beclin1 expression in human hepatoma cells. antiviral Research,2020,174: 104704); in 2018, it was possible that derris-hydrone could be used to study human cytomegalovirus (HMCV) infection through its inhibition of viral Replication (Nukui M, O' Connor, Christine, Murphy e.the Natural viral Compound Deguelin inhibition of HCMV Lytic Replication with human fibers, viruses,2018,10 (11)).
Human Respiratory Syncytial Virus (HRSV) is the most important pathogen causing viral pneumonia in children, and is also one of the important pathogens for lower respiratory tract infection of long people, severe pneumonia caused by the virus infection can cause hundreds of thousands of children or long people to die every year, and no vaccine is available on the market so far.
In view of this, the invention is particularly proposed.
Disclosure of Invention
The invention aims to provide a pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof, and aims to provide a pharmaceutical scheme for treating and preventing respiratory tract pathogen infection.
The invention is realized by the following steps:
the invention provides application of rotenone in preparation of a medicament for treating and/or preventing respiratory pathogen infection.
The inventors have found a new use of rotenone. In vitro and in vivo experiments prove that rotenone can reduce the virus titer of animal cells infected by Human Respiratory Syncytial Virus (HRSV), improve the survival rate of animals and promote the weight of the infected animals to gradually rise from a low level. The rotenone has good effect of resisting respiratory pathogens (particularly respiratory infection resisting viruses), is used for treating and/or preventing respiratory pathogen infection, has good application prospect, and can be used for developing corresponding respiratory pathogen infection treating or preventing medicines. Brings good news to patients with pneumonia such as viral pneumonia.
Such treatments include, but are not limited to: compared with the prior art, the traditional Chinese medicine composition provided by the invention has the advantages that the respiratory tract of a patient obviously breathes more smoothly, or cough symptoms are relieved, or swelling and pain of the throat/lung are relieved or eliminated, or inflammation of the respiratory tract is eliminated. It is within the scope of the present invention that the respiratory tract can achieve a certain therapeutic effect after the drug provided by the present invention is used.
Rotenone, CAS registry No. 83-79-4, also named derris essence, derris cyanide, Derris trifoliata.
In preferred embodiments of the invention, the respiratory pathogens include, but are not limited to: human respiratory syncytial virus, influenza a virus, influenza b virus, influenza a virus H1N1, influenza a virus H5N1, human parainfluenza virus, human metapneumovirus (metapneumovirus), human adenovirus, human enterovirus, human rhinovirus, Bordetella pertussis (Bordetella pertussis), chlamydia pneumoniae (Chlamydophila pneumoniae), Mycoplasma pneumoniae (Mycoplasma pneumoniae) and other microorganisms from the genera: streptococcus (Streptococcus), Haemophilus (Haemophilus), Moraxella (Moraxella), Pseudomonas (Pseudomonas), Klebsiella (Klebsiella), Pleurospora (Stenotrophoromonas), Acinetobacter (Acinetobacter), Staphylococcus (Staphylococcus), Mycoplasma (Mycoplasma), Legionella (Legionella), Chlamydophila (Chlamydophila), Mycobacterium (Mycobacterium), Coxiella (Coxiella), Nocardia (Nocardia), Pneumocystis (Pneumocystis), Nocardia (Nocardia) and Aspergillus (Aspergillus).
The antiviral effect of rotenone comes from the induction of apoptosis of the endogenous pathway of the cell, i.e. of the mitochondrial pathway. Theoretically, any virus or bacterium that inhibits apoptosis of host cells at an early stage of infection can be treated with rotenone.
In a preferred embodiment of the present invention, the human respiratory syncytial virus is selected from the group consisting of human respiratory syncytial virus subtype A and human respiratory syncytial virus subtype B.
In a preferred embodiment to which the present invention is applied, the human parainfluenza virus is selected from the group consisting of human parainfluenza virus type 1, human parainfluenza virus type 2, human parainfluenza virus type 3 and human parainfluenza virus type 4.
In a preferred embodiment of the present invention, the human adenovirus is selected from the group consisting of human adenovirus subtype B, human adenovirus subtype C and human adenovirus subtype E.
The present invention also provides a pharmaceutical composition for the treatment and/or prevention of infection by a respiratory pathogen, the pharmaceutical composition comprising:
a plant-derived rotenone or an extract containing rotenone, or a pharmaceutical composition containing a synthetic compound of rotenone or a synthetic derivative thereof, or a pharmaceutical composition containing a rotenone compound selected from a dehydro compound or a crystalline compound of rotenone.
The rotenone extract comprises all or part of the components obtained by extraction.
In a preferred embodiment of the present invention, the dehydro-compound of rotenone is dehydrorotenone, and the crystalline compound is rotedione.
In a preferred embodiment of the present invention, the plant is selected from the group consisting of leguminous plants;
in an alternative embodiment, the leguminous plant is selected from the group consisting of plants of the Papilionaceae family, the genus Cyperus, the genus Pimenta, the genus Derricellia, the genus Ipomoea, and the genus Millettia.
In an alternative embodiment, the byttva genus is selected from the group consisting of leatherleaf milletia.
Ipomoea is selected from sweet potato seed;
the Papilionaceae family is selected from Pterocarpus indicus.
Plants of the genus derris include, but are not limited to: derris crenulata, Derris japonica lancifolia, Derris heteroptera pallalis lancifolia, Derris elliptica, Derris obustifolia, Derris palmifolia, Derris crenulata robusta, Derris crassifolia, Derris scabra, Derris crenulata, Derris scabrosifera, Derris japonica thunbergiana, Derris trifoliata, Derris crassifolia, Derris yunnanensis, Derris albi, Derris crenulata thunbergiana, Derris trifoliata, Derris yunnanensis, Derris crenulata terrestris, Derris alumina, Derris crenulata Derris japonica, Derris calaris japonica, Derris calamus grandiflora hemsleyana, Derris calamus grandis, Derris calamus grandiflora.
In a preferred embodiment of the application of the invention, the pharmaceutical composition contains rotenone or a rotenone compound as an active ingredient in a mass percentage concentration of 10-90%.
In a preferred embodiment of the present invention, the pharmaceutical composition is in the form of tablet, pill, powder, suspension, gel, emulsion, cream, granule, nanoparticle, capsule, suppository, injection, spray or injection.
Optionally, the pharmaceutical composition further comprises a pharmaceutically acceptable salt, and the "pharmaceutically acceptable salt" includes a pharmaceutically acceptable inorganic acid salt or organic acid salt.
Alternatively, the inorganic acid salt may be a sulfate, sulfite, hydrochloride, hydrobromide, nitrate, phosphate or dihydrogen phosphate salt.
Alternatively, the organic acid salt may be acetate, maleate, fumarate, succinate, citrate, p-toluenesulfonate, tartrate, formate, propionate, heptanoate, oxalate, benzoate, malonate, succinate, maleate, hydroxybutyrate, citrate, methanesulfonate, benzenesulfonate, lactate or mandelate.
Alternatively, the organic acid salt may be an organic acid salt compound having a functional group such as a carboxyl group, a sulfonic group, a sulfinic acid, or a thiocarboxylic acid.
In other alternative embodiments, the inorganic acid salt and the organic acid salt are not limited to the scope defined in the present invention.
The modes of use of the above pharmaceutical compositions include, but are not limited to: injection, oral administration, nasal inhalation (aerosol).
The invention has the following beneficial effects:
the inventors have found a new use of rotenone. In vitro and in vivo experiments prove that the rotenone can reduce the virus titer of human laryngeal cancer epithelial cells infected by Human Respiratory Syncytial Virus (HRSV) and the virus load of animal lungs, improve the pathological changes of the lungs, improve the survival rate of animals and promote the weight of infected animals to gradually rise from a low level. The rotenone has good effect of resisting respiratory pathogens (particularly respiratory infection resisting viruses), is used for treating and/or preventing respiratory pathogen infection, has good application prospect, and can be used for developing corresponding respiratory pathogen infection treating or preventing medicines. Brings good news to patients with pneumonia such as viral pneumonia.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the embodiments will be briefly described below, it should be understood that the following drawings only illustrate some embodiments of the present invention and therefore should not be considered as limiting the scope, and for those skilled in the art, other related drawings can be obtained according to the drawings without inventive efforts.
FIG. 1 is a statistical plot of the viral titer and viral gene copy number of rotenone-treated groups at different concentrations in the cell pellet and in the cell supernatant, respectively, 48 hours after infection;
FIG. 2 is a statistical plot of the viral titer and viral gene copy number of rotenone-treated groups at different concentrations in the cell pellet and in the cell supernatant, respectively, 72 hours post-infection;
FIG. 3 is a graph comparing body weight (A) and survival rate (B) of mice in a normal saline-treated group after HRSV infection, mice in a rotenone-treated group at different concentrations after HRSV infection, and mice in a rotenone-treated group at different concentrations;
FIG. 4 is a graph showing the survival rate statistics of mice in the normal saline treated group after HRSV infection, mice in the rotenone treated group with different concentrations after HRSV infection, and mice in the rotenone treated group with different concentrations;
FIG. 5 is a graph showing the measurement results of the pulmonary virus titer of mice in the HRSV-treated group after HRSV infection at 4, 5 and 6 days after HRSV infection and mice in the rotenone-treated group at 1.0mg/kg after HRSV infection;
FIG. 6 is a graph showing the H & E staining results of lung pathological sections of HRSV-infected mice in a normal saline-treated group, HRSV-infected mice in a rotenone-treated group at 1.0mg/kg, rotenone-treated mice at 1.0mg/kg, and blank control mice at day 5 after HRSV infection.
Detailed Description
Reference will now be made in detail to embodiments of the invention, one or more examples of which are described below. Each example is provided by way of explanation, not limitation, of the invention. In fact, it will be apparent to those skilled in the art that various modifications and variations can be made in the present invention without departing from the scope or spirit of the invention. For instance, features illustrated or described as part of one embodiment, can be used on another embodiment to yield a still further embodiment.
Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure belongs. Although any methods and materials similar or equivalent to those described herein can be used in the practice or testing of the formulations or unit dosages herein, some are now described. Unless otherwise indicated, the techniques employed or contemplated herein are standard methods. The materials, methods, and examples are illustrative only and not intended to be limiting.
The practice of the present invention will employ, unless otherwise indicated, conventional techniques of cell biology, molecular biology (including recombinant techniques), microbiology, biochemistry and immunology, which are within the skill of the art. Such techniques are well explained in the literature, e.g. "molecular cloning: a Laboratory Manual, second edition (Sambrook et al, 1989); oligonucleotide Synthesis (oligo Synthesis) (eds. m.j. goal, 1984); animal Cell Culture (Animal Cell Culture) (edited by r.i. freshney, 1987); methods in Enzymology (Methods in Enzymology), Academic Press, Handbook of Experimental Immunology, eds (D.M.Weir and C.C.Blackwell, Methods in Gene Transfer Vectors for Mammalian Cells, eds (J.M.Miller and M.P.Calos, 1987), Methods in Current Protocols in Molecular Biology, eds (F.M.Ausubel et al, 1987), PCR, eds (PCR: Polymerase Chain Reaction, resins in Molecular Biology, Mullis et al, catalog J.2017, Methods in Current Protocols, catalog J.J.J.1993, Methods in vitro, catalog J.D.J.M.J.M.J.D.D.A.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.A.D.D.D.A.A. and Methods in Enzymology, catalog J.D.D.D.D.A.D.D.D.D.A.D.D.A. (environmental) and Methods in vitro, catalog J.D.D.D.D.D.D.D.D.D.D.D.D.A.D.D.A.A.D.D. (Methods in Enzymology, catalog J.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D. (Methods, catalog J.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.D.A.D.D.A.D.D.D.D.D.D.D.D.A. (Methods, catalog, 2016) (ii) a Clinical Virology Manual (Michael Loeffellholz et al, 2016), each of which is expressly incorporated herein by reference.
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. The examples, in which specific conditions are not specified, were conducted under conventional conditions or conditions recommended by the manufacturer. The reagents or instruments used are not indicated by the manufacturer, and are all conventional products available commercially.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
This example provides an in vitro antiviral validation experiment for rotenone.
The HRSV low strain HRSV-A-GZ08-0 and the high strain HRSV-A-GZ08-18 used were referred to Zhang K, Li C, Luo Y S, et al.expression of a simple gene mouse model of human respiratory syndrome infection. antibiotic Research,2019,161: 125-.
In vitro antiviral experiments: we infected HEp-2 cells with low strain HRSV-A-GZ08-0 and high strain HRSV-A-GZ08-18 for 1 hr, and changed the medium with cell culture medium (DMEM-F12) containing rotenone at concentrations of 1. mu.M, 0.75. mu.M, 0.5. mu.M, 0.25. mu.M and 0.125. mu.M, respectively(GlutaMax-I, 10565, Gibco; 2% FBS; 1% P/S) followed by TCID at 48 and 72 hours post-infection, respectively 50 And measuring and comparing virus titer in the cell sediment and the cell supernatant by a real-time fluorescent quantitative PCR method.
As shown in FIGS. 1 and 2, it can be seen that the virus titers in the cell pellet at 48 hours after infection (FIG. 1) were lower in the rotenone-treated groups than in the virus control group at 1. mu.M, 0.75. mu.M, 0.5. mu.M and 0.25. mu.M, most of which had statistical significance; in the cell supernatant, the virus titers of the rotenone-treated groups were lower than those of the virus control group at 1. mu.M, 0.75. mu.M, 0.5. mu.M and 0.25. mu.M, most of which were statistically significant.
The real-time fluorescent quantitative PCR result shows that the virus copy number of the rotenone treatment groups of 1 mu M, 0.75 mu M, 0.5 mu M and 0.25 mu M in the cell sediment is lower than that of the virus control group; in the cell supernatant, the virus copy numbers of the rotenone-treated groups were lower than those of the virus control group at 1. mu.M, 0.75. mu.M, 0.5. mu.M and 0.25. mu.M, most of which were statistically significant.
At 72 hours post-infection (FIG. 2), the viral titers of the rotenone-treated groups at 1. mu.M, 0.75. mu.M, 0.5. mu.M, 0.25. mu.M and 0.125. mu.M were all lower than those of the virus control group, most of which were statistically significant; in the cell supernatant, the virus titers of the rotenone-treated groups were lower than those of the virus control group at 1. mu.M, 0.75. mu.M, 0.5. mu.M, 0.25. mu.M and 0.125. mu.M, most of which had statistical significance.
The real-time fluorescent quantitative PCR result shows that the virus copy numbers of 1 mu M, 0.75 mu M, 0.5 mu M, 0.25 mu M and 0.125 mu M rotenone treatment groups are all lower than those of a virus control group in cell precipitation; in the cell supernatant, the virus copy numbers of the rotenone-treated groups were lower than those of the virus control group at 1. mu.M, 0.75. mu.M, 0.5. mu.M, 0.25. mu.M and 0.125. mu.M, most of which were statistically significant.
***：p<0.001。
Example 2
This example was performed in vivo antiviral validation experiments with rotenone.
After infecting BALB/c mice with HRSV highly virulent strain HRSV-A-GZ08-18 (from the same source as in example 1), rotenone was dissolved in physiological saline at different concentrations and injected subcutaneously into the mice at 1.5mg/kg, 1.0mg/kg and 0.5mg/kg for 3 days, while HRSV-A-GZ08-18 virus control groups and rotenone injection control groups at 1.5mg/kg, 1.0mg/kg and 0.5mg/kg were set.
FIG. 5 is a graph showing the results of measurement of pulmonary virus titer of HRSV-infected mice in the normal saline-treated group at 4, 5 and 6 days after HRSV infection and mice in the rotenone-treated group at 1.0mg/kg after HRSV infection in TCID 50 The method is carried out. The results show that the lung viral load of mice in the normal saline treatment groups at 4 th day and 5 th day after HRSV infection is obviously higher than the lung viral load (p) of mice in the rotenone treatment group of 1.0mg/kg after HRSV infection<0.05)。
FIG. 6 is a graph showing H & E staining results of lung pathological sections of HRSV-infected mice in a normal saline-treated group, HRSV-infected mice in a rotenone-treated group at 1.0mg/kg, rotenone-treated mice at 1.0mg/kg and blank control mice on day 5 after HRSV infection. As can be seen from fig. 6, on day 5 after HRSV infection, acute interstitial pneumonia in mice treated with saline after HRSV infection was marked, mainly manifested as interstitial edema and looseness around bronchioles and small blood vessels, increased aggregation of inflammatory cells at alveolar septum, thickening of alveolar wall, and presence of inflammatory cells mainly including neutrophils, erythrocytes, and a large amount of pink protein exudate and edema fluid in alveolar cavity. The alveolar walls of mice in a rotenone treatment group at 1.0mg/kg after HRSV infection are thickened, a small amount of inflammatory cells mainly including neutrophils and erythrocytes are exuded in the alveolar cavities, a small amount of inflammatory cells at alveolar intervals are aggregated, the overall acute interstitial pneumonia is not obvious in expression, and no obvious interstitial edema and inflammatory cell aggregation around bronchioles and small blood vessels are seen. The mice of the 1.0mg/kg rotenone treated group and the mice of the blank control group have clear lung bronchioles, small blood vessels and alveolar space structures and have no inflammatory cell infiltration. The results show that lung lesions of mice treated by physiological saline after HRSV infection are more obvious than that of mice treated by 1.0mg/kg rotenone after HRSV infection.
Mice were then observed for mortality to day 21 post-infection and mice body weight and survival were counted.
As a result, 1.5mg/kg, 1.0mg/kg and 0.5mg/kg of rotenone of the mice in the control group were not dead; the survival rates of 1.5mg/kg, 1.0mg/kg and 0.5mg/kg rotenone treated groups after HRSV-A-GZ08-18 infection were 44.44%, 41.67% and 33.33%, respectively, and the body weight decreased to about 70% on day 6 after infection, followed by slow rebound; the survival rate of the HRSV-A-GZ08-18 virus control group is 16.67%, and the body weight is continuously reduced. The results are shown in FIGS. 3 and 4.
The experimental result shows that the rotenone can effectively improve the survival rate of infected mice and recover the weight loss caused by virus infection.
The safety evaluation of rotenone was carried out by reference to the LD of rotenone orally administered to rats as described in http:// extoxnet 50 LD of rotenone in white mouse at 132mg/kg to 1500mg/kg 50 It was 350 mg/kg. References Kidd, H.and James, D.R., eds. the electrochemistry Handbook, Third edition. Royal Society of Chemistry Information Services, Cambridge, UK,1991(as updated). 2-13.
In conclusion, the rotenone has good effect of resisting respiratory pathogens (particularly resisting viruses of respiratory infection), is used for treating and/or preventing respiratory pathogen infection, has good application prospect, and can be used for developing corresponding medicaments for treating or preventing respiratory pathogen infection. Brings good news to patients with pneumonia such as viral pneumonia.
The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.

Claims (10)

1. Use of rotenone for the preparation of a medicament for the treatment and/or prevention of infection by a respiratory pathogen.
2. Use according to claim 1, characterized in that the respiratory pathogens are selected from the group consisting of human respiratory syncytial virus, influenza a virus, influenza b virus, influenza a virus H1N1, influenza a virus H5N1, human parainfluenza virus, human metapneumovirus (metapneumovirus), human adenovirus, human enterovirus, human rhinovirus, Bordetella pertussis (Bordetella pertussis), chlamydia pneumoniae (chlamydia pneumoniae), Mycoplasma pneumoniae (myco pneumoniae) and other microorganisms from the genera: streptococcus (Streptococcus), Haemophilus (Haemophilus), Moraxella (Moraxella), Pseudomonas (Pseudomonas), Klebsiella (Klebsiella), Pleurospora (Stenotrophoromonas), Acinetobacter (Acinetobacter), Staphylococcus (Staphylococcus), Mycoplasma (Mycoplasma), Legionella (Legionella), Chlamydophila (Chlamydophila), Mycobacterium (Mycobacterium), Coxiella (Coxiella), Nocardia (Nocardia), Pneumocystis (Pneumocystis), Nocardia (Nocardia) or Aspergillus (Aspergillus).
3. The use according to claim 2, wherein the human respiratory syncytial virus is selected from the group consisting of human respiratory syncytial virus subtype A and human respiratory syncytial virus subtype B.
4. The use of claim 2, wherein said human parainfluenza virus is selected from the group consisting of human parainfluenza virus type 1, human parainfluenza virus type 2, human parainfluenza virus type 3 and human parainfluenza virus type 4.
5. The use according to claim 2, wherein the human adenovirus is selected from the group consisting of human adenovirus subtype B, human adenovirus subtype C and human adenovirus subtype E.
6. A pharmaceutical composition for the treatment and/or prevention of infection by a respiratory pathogen, said pharmaceutical composition comprising:
rotenone derived from a plant or an extract containing said rotenone, or said pharmaceutical composition comprises a synthetic compound of rotenone or a synthetic derivative thereof, or said pharmaceutical composition comprises a rotenone compound selected from the group consisting of dehydro compounds or crystalline compounds of rotenone.
7. The pharmaceutical composition of claim 6, wherein said dehydrogenized compound of rotenone is dehydrorotenone and said crystalline compound is rotedione.
8. The pharmaceutical composition according to claim 6, wherein the plant is selected from the group consisting of leguminous plants;
preferably, the leguminous plant is selected from the plants of the families Papilionaceae, the genus Cyperus, the genus Pistis, the genus Yucca, the genus Ipomoea or the genus Millettia;
preferably, the Millettia genus is selected from the group consisting of Millettia reticulata;
said genus ipomoea is selected from sweet potato seeds;
the Papilionaceae is selected from Pterocarpus indicus.
9. The pharmaceutical composition according to claim 6, wherein the pharmaceutical composition comprises rotenone or a rotenone compound as an active ingredient in a concentration of 10 to 90% by mass.
10. The pharmaceutical composition of claim 6, wherein the pharmaceutical composition is in the form of tablet, pill, powder, suspension, gel, emulsion, cream, granule, nanoparticle, capsule, suppository, injection, spray or injection.
CN202210223547.2A 2022-03-09 2022-03-09 Pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof Active CN114796189B (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
CN202210223547.2A CN114796189B (en) 2022-03-09 2022-03-09 Pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
CN202210223547.2A CN114796189B (en) 2022-03-09 2022-03-09 Pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof

Publications (2)

Publication Number Publication Date
CN114796189A true CN114796189A (en) 2022-07-29
CN114796189B CN114796189B (en) 2024-02-06

Family

ID=82528603

Family Applications (1)

Application Number Title Priority Date Filing Date
CN202210223547.2A Active CN114796189B (en) 2022-03-09 2022-03-09 Pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof

Country Status (1)

Country Link
CN (1) CN114796189B (en)

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000027423A2 (en) * 1998-11-12 2000-05-18 Musc Foundation For Research Development Methods and compositions for treating common cold symptoms
US20090163449A1 (en) * 2007-12-20 2009-06-25 Eastman Chemical Company Sulfo-polymer powder and sulfo-polymer powder blends with carriers and/or additives
CN111265538A (en) * 2020-03-14 2020-06-12 中国水产科学研究院长江水产研究所 Application of periplocin in preparing medicine for killing fish ectoparasite

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2000027423A2 (en) * 1998-11-12 2000-05-18 Musc Foundation For Research Development Methods and compositions for treating common cold symptoms
US20090163449A1 (en) * 2007-12-20 2009-06-25 Eastman Chemical Company Sulfo-polymer powder and sulfo-polymer powder blends with carriers and/or additives
CN111265538A (en) * 2020-03-14 2020-06-12 中国水产科学研究院长江水产研究所 Application of periplocin in preparing medicine for killing fish ectoparasite

Non-Patent Citations (4)

* Cited by examiner, † Cited by third party
Title
KATHERINE E. NOLAN ET AL.: "Metabolic Shifts Modulate Lung Injury Caused by Infection with H1N1 Influenza A Virus", 《VIROLOGY》, vol. 559, pages 2 *
SVETLANA REZINCIUC ET AL.: ""Respiratory syncytial virus induces hypermetabolism in pediatric airways", 《BIORXIV PREPRINT》, pages 7 *
富杭育: "中草药和天然药物中的抗病毒活性物质及其作用原理", 《中国药学杂志》, vol. 23, no. 4, pages 195 - 199 *
胡丹;张兆辉;: "N-乙酰半胱氨酸对PC12细胞的保护作用研究", 卒中与神经疾病, no. 06, pages 328 - 330 *

Also Published As

Publication number Publication date
CN114796189B (en) 2024-02-06

Similar Documents

Publication Publication Date Title
CN112451517A (en) Application of epigallocatechin 3-O- (3-O-methyl) gallate in preparing anti-coronavirus medicine
CN102000156A (en) Traditional Chinese medicine compound preparation for treating cold, influenza and upper respiratory tract infection
Singh et al. Shikimic acid as intermediary model for the production of drugs effective against influenza virus
CN112546038A (en) Application of myricetin in preparation of medicine for preventing or treating coronavirus and influenza virus
CN109419786B (en) Application of cannabidiol in preparation of anti-influenza drugs
CN114796189A (en) Pharmaceutical composition for treating and preventing respiratory tract pathogen infection and application thereof
US20230090982A1 (en) Drug for treating coronaviral and retroviral infections and hepatitis c
WO2022143710A1 (en) Use of pyrroloquinoline quinone, derivative and/or salt thereof as novel antiviral drug and pharmaceutical composition thereof
CA3073576C (en) Use of cannabidiol in preparation of drugs for resisting against influenza
CN110812357B (en) Application of biapenem in preparation of medicine for preventing and treating bovine enterovirus infection
CN109908127B (en) Application of compounds in preparation of anti-small RNA virus drugs
CN105943540B (en) A kind of purposes of simiarenol
CN108245586B (en) Application of children cold-relieving granules in resisting virus
CN109078051B (en) Application of pharmaceutical composition in preparation of antiviral drugs
CN115317468B (en) Application of terpin-4-ol in preparing anti-inflammatory medicine or anti-respiratory syncytial virus medicine
US20220401472A1 (en) Compositions for prevention and treatment of rsv and coronavirus infection
CN107198728A (en) Chinese medicine preparation for treating children&#39;s upper respiratory tract infection and preparation method thereof
CN107540631A (en) Application of the amino carboxylic acid esters compound in terms of zika virus infection is treated
CN117510409A (en) Broad-spectrum antiviral traditional Chinese medicine monomer bat Ge Sulin alkali, and pharmaceutical composition and application thereof
CN113440545A (en) Application of asafetida sesquiterpene lactone in preparation of anti-schistosomiasis drugs
CN117510408A (en) Antiviral traditional Chinese medicine monomer dauricine, pharmaceutical composition and application thereof
US7282599B2 (en) Dithiocarbamate antiviral agents and methods of using same
CN116687912A (en) Use of gomisin N and derivatives thereof in the treatment of liver injury related diseases
CN116270647A (en) Application of rilpivirine in preparation of anti-H1N 1 subtype swine influenza virus drugs
CN117323361A (en) Pharmaceutical composition for treating brain glioma and application thereof

Legal Events

Date Code Title Description
PB01 Publication
PB01 Publication
SE01 Entry into force of request for substantive examination
SE01 Entry into force of request for substantive examination
GR01 Patent grant
GR01 Patent grant