CN108992669B - Composite yolk antibody composition for preventing and treating respiratory tract infection, aerosol inhalation solution, preparation process and application - Google Patents

Composite yolk antibody composition for preventing and treating respiratory tract infection, aerosol inhalation solution, preparation process and application Download PDF

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Publication number
CN108992669B
CN108992669B CN201810983399.8A CN201810983399A CN108992669B CN 108992669 B CN108992669 B CN 108992669B CN 201810983399 A CN201810983399 A CN 201810983399A CN 108992669 B CN108992669 B CN 108992669B
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respiratory tract
antibody composition
composite
tract infection
inhalation solution
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CN108992669A (en
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农定猛
蒙永祥
符美燕
叶梦婕
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Guangzhou Huigao Biotechnology Co ltd
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Guangzhou Huigao Biotechnology Co ltd
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/395—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum
    • A61K39/40—Antibodies; Immunoglobulins; Immune serum, e.g. antilymphocytic serum bacterial
    • 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)
    • A61K36/28—Asteraceae or Compositae (Aster or Sunflower family), e.g. chamomile, feverfew, yarrow or echinacea
    • 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)
    • A61K36/35—Caprifoliaceae (Honeysuckle family)
    • A61K36/355—Lonicera (honeysuckle)
    • 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)
    • A61K36/70—Polygonaceae (Buckwheat family), e.g. spineflower or dock
    • A61K36/704—Polygonum, e.g. knotweed
    • 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)
    • A61K36/80—Scrophulariaceae (Figwort family)
    • A61K36/808—Scrophularia (figwort)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/007—Pulmonary tract; Aromatherapy
    • A61K9/0073—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy
    • A61K9/0078—Sprays or powders for inhalation; Aerolised or nebulised preparations generated by other means than thermal energy for inhalation via a nebulizer such as a jet nebulizer, ultrasonic nebulizer, e.g. in the form of aqueous drug solutions or dispersions
    • 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
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/02—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies from eggs
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
    • C07K16/1214—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Pseudomonadaceae (F)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1203—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria
    • C07K16/1228—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia
    • C07K16/1232—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-negative bacteria from Enterobacteriaceae (F), e.g. Citrobacter, Serratia, Proteus, Providencia, Morganella, Yersinia from Escherichia (G)
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1271—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Micrococcaceae (F), e.g. Staphylococcus
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07K—PEPTIDES
    • C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
    • C07K16/12—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria
    • C07K16/1267—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria
    • C07K16/1275—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from bacteria from Gram-positive bacteria from Streptococcus (G)
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
    • Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
    • Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change

Abstract

A composite yolk antibody composition for preventing and treating respiratory tract infection, an aerosol inhalation solution, a preparation process and an application relate to the field of composite yolk antibodies. The composite yolk antibody composition is obtained by immunizing antigens of common pathogenic bacteria including respiratory tract infection, wherein the common pathogenic bacteria including staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa are safe and can prevent and treat the respiratory tract infection; the application of the composite yolk antibody composition of the embodiment of the invention is used for preparing preparations for preventing and treating respiratory tract infection; the atomized inhalation solution and the preparation process thereof adopt the composite yolk antibody composition to prepare the atomized inhalation solution for preventing and treating respiratory tract infection, and have the advantages of quick absorption and obvious effect.

Description

Composite yolk antibody composition for preventing and treating respiratory tract infection, aerosol inhalation solution, preparation process and application
Technical Field
The invention relates to the field of composite yolk antibodies, and in particular relates to a composite yolk antibody composition for preventing and treating respiratory tract infection, an aerosol inhalation solution, a preparation process and application.
Background
Respiratory tract infections are classified as upper respiratory tract infections, lower respiratory tract infections, bacterial pneumonia or viral pneumonia mixed with bacterial infections, and are the most common infectious diseases. At present, cephalosporins, quinolones and other synthetic antibacterial drugs are mainly used at home and abroad for treating respiratory tract infection. In order to control the disease development, the development of bacterial drug resistance is greatly accelerated by using a large dose of high-concentration antibiotics, a new antibiotic is used in the market for only two or three years, a drug-resistant strain appears, and the development of the new antibiotic needs about ten years. In addition, the toxic and side effects of antibiotics are also shocking. Based on various defects of various antibiotics, the requirement of the current clinical medicine for preventing and treating respiratory tract infection cannot be met.
The composite Yolk antibody (IgY) belongs to IgG Immunoglobulin, and is prepared through extracting, separating and purifying corresponding immune globulin produced by various pathogenic bacteria immunized healthy egg-laying fowl. The composite yolk immune antibody can be specifically combined with a corresponding antigen, so that the state and activity of the antigen are inhibited or changed, and phagocytosis of pathogenic bacteria by lobular nuclear cells or macrophages is promoted through opsonization. However, in many cases, due to the basic diseases of patients and the severity and duration of the disease, pathogenic bacteria are frequently diversified and often mainly mixed infection, so the selection of the pathogenic bacteria directly influences the efficacy of the obtained specific composite yolk antibody. At present, the specific composite yolk antibody prepared by immunizing a special breeding hen by using common pathogenic bacteria of respiratory tract infection as antigens has limitation on the treatment of respiratory tract infection, and does not have good treatment effect on all kinds of respiratory tract infection.
Therefore, there is a need to develop a specific formulation which is safe and can prevent and treat all respiratory infections.
Disclosure of Invention
The invention aims to provide a composite yolk antibody composition for preventing and treating respiratory tract infection and a preparation process thereof, and the product is safe and can prevent and treat all respiratory tract infections.
The invention aims to provide application of a composite yolk antibody composition for preventing and treating respiratory tract infection, which is used for preparing a preparation for preventing and treating respiratory tract infection.
The invention aims to provide an aerosol inhalation solution and a preparation process thereof, and the aerosol inhalation solution for preventing and treating respiratory tract infection is prepared by adopting a composite yolk antibody composition, and has the advantages of quick absorption and obvious effect.
The technical problem to be solved by the invention is realized by adopting the following technical scheme.
The invention provides a composite yolk antibody composition for preventing and treating respiratory tract infection, which is obtained by taking common pathogenic bacteria including respiratory tract infection as antigen for immunization, wherein the common pathogenic bacteria of the respiratory tract infection comprise staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa.
Further, in the preferred embodiment of the invention, the mass ratio of staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa is 4-8:4-8:3-5:4-8:4-8: 3-5.
Further, in the preferred embodiment of the invention, the pathogenic bacteria of respiratory tract infection also comprise staphylococcus epidermidis, and the mass ratio of staphylococcus aureus to staphylococcus epidermidis is 4-8: 3-5.
The invention provides a preparation process of the composite yolk antibody composition for preventing and treating respiratory tract infection, which comprises the following steps:
preparing a composite antigen containing staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa;
performing intensified immunity on the chicken by using the composite antigen to obtain an immune egg of the immunized chicken;
extracting yolk of the immune eggs to obtain crude extract dry powder;
and separating and purifying the crude extract dry powder by ion exchange chromatography and gel filtration chromatography to obtain the composite yolk antibody composition.
The invention provides application of the composite yolk antibody composition for preventing and treating respiratory tract infection, and the composite yolk antibody composition is used for preparing an atomized inhalation solution for preventing and treating respiratory tract infection.
The invention provides an aerosol inhalation solution, and each 100ml of the aerosol inhalation solution comprises the following components: 0.5-1.5g of the composite yolk antibody composition, a buffer pair and an isoosmotic adjusting agent, and the balance of a solvent.
Further, in a preferred embodiment of the present invention, the buffer pair is one selected from the group consisting of citric acid-sodium citrate, acetic acid-sodium acetate, citric acid-disodium hydrogen phosphate, sodium dihydrogen phosphate-disodium hydrogen phosphate, lactic acid-sodium lactate, and tartaric acid-sodium tartrate.
Further, in a preferred embodiment of the present invention, the isotonic adjusting agent is selected from one or more of sodium chloride, potassium chloride, magnesium chloride, calcium chloride, glucose, xylitol, and sorbitol.
The invention provides a preparation process of the atomization inhalation solution, which comprises the following steps:
adding the composite yolk antibody composition into a part of solvent, and uniformly stirring; adding buffer and isoosmotic adjusting agent, stirring to dissolve, filtering, adding solvent to full dose, and fine filtering.
Furthermore, in the preferred embodiment of the present invention, 0.3-1g of Chinese medicine extract can be added, and the specific preparation method of the Chinese medicine extract comprises:
extracting the cleaned groundsel, honeysuckle, figwort and giant knotweed with water at least twice, combining the extracting solutions, and centrifuging by a high-speed centrifuge to obtain a first centrifugal liquid;
reflux-extracting the residue with ethanol solution at least once, centrifuging the extractive solution with high speed centrifuge to obtain second centrifugate;
and combining the first centrifugate and the second centrifugate to obtain the traditional Chinese medicine extracting solution.
The composite yolk antibody composition for preventing and treating respiratory tract infection, the aerosol inhalation solution, the preparation process and the application of the composite yolk antibody composition have the beneficial effects that: the composite yolk antibody composition is obtained by immunizing antigens of common pathogenic bacteria including respiratory tract infection, wherein the common pathogenic bacteria of the respiratory tract infection include staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa, and is safe and capable of preventing and treating all respiratory tract infections; the application of the composite yolk antibody composition of the embodiment of the invention is used for preparing preparations for preventing and treating respiratory tract infection; the atomized inhalation solution and the preparation process thereof adopt the composite yolk antibody composition to prepare the atomized inhalation solution for preventing and treating respiratory tract infection, and have the advantages of convenient administration, quick absorption and obvious effect.
Detailed Description
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 composite yolk antibody composition for preventing and treating respiratory tract infection, the aerosol inhalation solution, the preparation process and the application of the composite yolk antibody composition are specifically described below.
The embodiment of the invention provides a composite yolk antibody composition for preventing and treating respiratory tract infection, which is obtained by immunizing a special breeding chicken with an antigen comprising common pathogenic bacteria strains of respiratory tract infection and separating and purifying the special breeding chicken, in particular to preparing a composite antigen by using the common pathogenic bacteria strains of respiratory tract infection, performing enhanced immunity on the special breeding chicken by using the composite antigen, and extracting the composite antigen from yolk of an obtained immune egg of the immune chicken. Common pathogenic bacteria of respiratory tract infection comprise staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa, wherein the mass ratio of the staphylococcus aureus, the hemolytic streptococcus, the streptococcus pneumoniae, the escherichia coli, the acinetobacter baumannii and the pseudomonas aeruginosa is 4-8:4-8:3-5:4-8:4-8: 3-5.
In some embodiments of the invention, the pathogenic bacteria of the respiratory tract infection further comprise staphylococcus epidermidis (accession number ATCC12228), and the mass ratio of staphylococcus aureus to staphylococcus epidermidis is 4-8: 3-5. The composite yolk antibody composition is a composite antibody extract for resisting the respiratory tract infection pathogenic bacteria, has a specific binding inhibition effect on various pathogenic microorganisms causing respiratory tract infection, can play an effective role even under the condition of extremely low concentration, only inhibits and kills pathogenic bacteria, does not generate drug-resistant strains, and does not find toxic and side effects on human bodies.
The embodiment of the invention provides a preparation process of a composite yolk antibody composition for preventing and treating respiratory tract infection, which comprises the following steps:
s1, preparing a composite antigen containing pathogenic bacteria of staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa for respiratory tract infection.
Specifically, respectively culturing staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa at a constant temperature of 34-36 ℃ for 20-24h, and then inactivating for later use; uniformly mixing inactivated staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa according to a mass ratio of 4-8:4-8:3-5:4-8:4-8:3-5 to obtain a strain mixture; dissolving the strain mixture in neutral 0.08-0.1mol/L PBS solution to obtain 1.2-2.2mg/mL strain mixture solution; adding Freund's adjuvant into the mixed solution of the strains in the same volume, and homogenizing at high speed to obtain the composite antigen.
S2, performing intensified immunization on the special breeding hens by using the composite antigen to obtain the immune eggs of the immune chickens.
Specifically, the compound antigen is injected into the breast muscle and thigh of 20-week-old chicken, 0.5-0.6ml is injected into each part, and then the compound antigen is injected into the chicken at intervals of 10 days in a boosting way for at least 3 times. The Freund adjuvant in the composite antigen used in the first injection is Freund incomplete adjuvant, the Freund adjuvant in the composite antigen used in the second and later injections is complete Freund adjuvant, and eggs laid by the chicken after the strengthened immunity are collected after the last injection.
In the embodiment, the chicken subjected to enhanced immunity is one of a blue brown chicken, a red chicken, an Isa white chicken and a white leghorn layer; in order to improve the quality of the prepared composite yolk antibody composition, the chicken for strengthening immunity is selected by the following method: marking the eggs laid by the chickens 7 months after the first injection, respectively extracting IgY in the eggs, and detecting the titer of the prepared IgY by an ELISA method; then comparing the titer, selecting out the chickens which can prepare the IgY solution with the titer more than or equal to 1:128, hatching out the chicken seeds by the eggs laid by the batch of chickens, and taking the chicken seeds as the chickens for strengthening immunity after the eggs grow up to 20 weeks.
S3, extracting the yolk of the immune eggs to obtain crude extract dry powder.
Specifically, breaking immune eggs by using an egg breaker, removing egg white, uniformly stirring yolk, adding distilled water for diluting and uniformly mixing according to 4-6 times of the volume of the yolk, and adjusting the pH value to 5.0-6.0; then cooling to 2-6 ℃, and standing for 12-24 h; then centrifugally separating for 20-30 minutes by a high-speed centrifugal separator; adding the separated supernatant into an ultrafilter for ultrafiltration and concentration by 10-20 times, adding a sodium sulfate solution with the mass concentration of 10% -13% into the concentrated slurry, and fully stirring; centrifuging by a high-speed centrifuge, taking the supernatant, and removing lipoprotein to obtain slurry; adding the slurry into an ultrafiltration machine, and filtering the slurry through an ultramicro membrane to remove bacteria; and (4) freeze-drying the filtered and sterilized slurry by using a freeze dryer to obtain crude extract dry powder.
S4, carrying out ion exchange chromatography on the crude extract dry powder through an ion exchange column and carrying out gel filtration chromatography on a gel exchange column to separate and purify to obtain the composite yolk antibody composition.
The embodiment of the invention provides application of the composite yolk antibody composition for preventing and treating respiratory tract infection, and the composite yolk antibody composition is used for preparing an aerosol inhalation solution for preventing and treating respiratory tract infection.
The embodiment of the invention provides an aerosol inhalation solution, and each 100ml of the aerosol inhalation solution comprises the following components: 0.5-1.5g of the composite yolk antibody composition, a buffer pair and an isoosmotic adjusting agent, and the balance of a solvent. Wherein the buffer pair is selected from one of citric acid-sodium citrate, acetic acid-sodium acetate, citric acid-disodium hydrogen phosphate, sodium dihydrogen phosphate-disodium hydrogen phosphate, lactic acid-sodium lactate, and tartaric acid-sodium tartrate. The isotonic regulator is selected from one or more of sodium chloride, potassium chloride, magnesium chloride, calcium chloride, glucose, xylitol, and sorbitol.
In some embodiments of the present invention, the composition may further comprise 0.3-1g of a Chinese herbal medicine extract, wherein the Chinese herbal medicine extract is extracted from Chinese herbal medicines comprising groundsel, honeysuckle, figwort and giant knotweed. Among the Chinese herbal medicines, groundsel has the function of clearing away heat and toxic materials and is mainly used for treating upper respiratory tract infection; the honeysuckle has stronger inhibitory power on various pathogenic bacteria, upper respiratory tract infection pathogenic viruses and the like; radix scrophulariae and rhizoma Polygoni Cuspidati can enhance body resistance. The traditional Chinese medicine extract is prepared by extracting groundsel, honeysuckle, figwort and giant knotweed, and has the functions of improving the antibacterial effect and enhancing the immunity of the product.
In some embodiments of the invention, the raw material further comprises 0.3-1g of levofloxacin, which is used for treating acute and chronic bronchitis, asthmatic bronchitis, bronchial asthma and chronic pulmonary inflammation with thick sputum and not easy to cough or without sputum.
The aerosol inhalation solution of the embodiment uses at least one of traditional Chinese medicine extract and levofloxacin (western medicine) to act synergistically with the composite yolk antibody composition, so that the antibacterial spectrum can be further expanded, and the purpose of treating respiratory tract infection is achieved.
The embodiment of the invention provides a preparation process of the atomization inhalation solution, which comprises the following steps:
(1) slowly adding the composite yolk antibody composition into a solvent with the prescription amount of 50-80%, and slowly stirring uniformly at room temperature for later use.
(2) Weighing appropriate amount of water for injection, cooling to 50-70 deg.C, slowly adding buffer pair, stirring to dissolve completely, and cooling to room temperature for use.
(3) Weighing appropriate amount of water for injection, cooling to 50-70 deg.C, slowly adding isotonic regulator, stirring to dissolve, and cooling to room temperature.
(4) Adding the above (2) and (3) into the solution (1), stirring, heating to 30-40 deg.C, adding 0.01% -0.1% (w/v) of active carbon for injection, stirring for 15-30min, filtering, and decarbonizing.
(5) Adding solvent to full volume, stirring, detecting pH and content, and adjusting pH to 5.0-8.0. In this embodiment, the pH is adjusted by using a pH adjuster, which includes at least one selected from citric acid, malic acid, tartaric acid, boric acid, sodium lactate, and sodium hydroxide.
(6) Filtering the medicinal liquid with 0.5-1.5 μm titanium filter core, detecting visible foreign matter and pH value of the intermediate, and adjusting and controlling pH to 5.0-8.0.
(7) Fine filtering the above medicinal liquid with 0.2-0.25 μm microporous membrane, filling into 2ml sterile ampoules under the protection of A-stage laminar flow, filling with nitrogen gas, and sealing.
(8) And after the lamp is detected to be qualified, detecting the visible foreign matters, the pH value, the aseptic condition and the antibody titer of the content in the ampoule bottle, wherein the visible foreign matters meet the specification, the pH value detection range is between 5.0 and 8.0, the visible foreign matters are aseptic, and the antibody titer is more than or equal to 1:128, thus obtaining the qualified aerosol inhalation solution.
In some embodiments of the invention, 0.3-1g of Chinese medicine extract can be added, and the specific preparation method of the Chinese medicine extract comprises the following steps:
extracting the cleaned groundsel, honeysuckle, figwort and giant knotweed with water at least twice, combining the extracting solutions, and centrifuging by a high-speed centrifuge to obtain a first centrifugal liquid;
reflux-extracting the residue with ethanol solution at least once, centrifuging the extractive solution with high speed centrifuge to obtain second centrifugate;
and combining the first centrifugate and the second centrifugate to obtain the traditional Chinese medicine extracting solution.
The features and properties of the present invention are described in further detail below with reference to examples.
Example 1
This example provides a complex yolk antibody composition, which is prepared according to the following processes:
respectively inoculating staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa into a Luria-Bertani culture medium, wherein the Luria-Bertani culture medium comprises 2% of tryptone, 1% of yeast extract, 1% of sodium chloride and 1.5% of agar in percentage by mass, culturing the Luria-Bertani culture medium in a three-gas incubator at the temperature of 35 ℃ for 22 hours, separating and inoculating the strain into a broth culture medium, wherein the broth culture medium comprises 1% of beef extract, 2% of tryptone, 0.5% of sodium chloride and 1.5% of agar in percentage by mass, culturing the Luria-Bertani culture medium in a constant-temperature shaking incubator at the temperature of 35 ℃ for 26 hours, and the rotation speed of the constant-temperature shaking incubator is 180rpm, and then inactivating the broth culture medium for later use; uniformly mixing inactivated staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii and pseudomonas aeruginosa according to a weight ratio of 6:6:4:6:6:4 to obtain a strain mixture; dissolving the strain mixture in neutral 0.09mol/L PBS solution to obtain strain mixture solution, and preparing strain mixture solution with the concentration of 1.8 mg/mL; adding Freund's adjuvant into the mixed solution of the strain in the same volume, and stirring to obtain milky whole-strain composite antigen; and (3) putting the whole-bacterium composite antigen into a high-speed homogenizer, and carrying out high-speed grinding and homogenization to obtain the composite antigen.
The prepared complex antigen is injected into the breast muscle and thigh of a chicken with 20 weeks old, 0.5ml is injected into each part, and then the injection is intensified once every 10 days for immunization four times. Freund's adjuvant used in the first injection is Freund's incomplete adjuvant, Freund's adjuvant used in the second to fourth injections is complete Freund's adjuvant, and eggs laid by the chicken after the last injection are collected.
Breaking the immune eggs by using an egg breaker, removing egg white, uniformly stirring the yolk, adding distilled water according to 5 times of the volume of the yolk, diluting and uniformly mixing, and adjusting the pH to 6.0; then cooling to 4 ℃, and standing for 20 h; then centrifugally separating for 25 minutes by a high-speed centrifugal separator; adding the separated supernatant into an ultrafilter for ultrafiltration and concentration by 15 times, adding a sodium sulfate solution with the mass concentration of 11% into the concentrated slurry, and fully stirring; centrifuging by a high-speed centrifuge, taking the supernatant, and removing lipoprotein to obtain slurry; adding the slurry into an ultrafiltration machine, and filtering the slurry through an ultramicro membrane to remove bacteria; and (4) freeze-drying the filtered and sterilized slurry by using a freeze dryer to obtain crude extract dry powder.
And (3) carrying out ion exchange chromatography on the crude extract dry powder through an ion exchange column and carrying out gel filtration chromatography on a gel exchange column to separate and purify to obtain the composite yolk antibody composition.
Example 2
This example provides a complex yolk antibody composition, which is prepared according to the following processes:
respectively inoculating staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii, pseudomonas aeruginosa and staphylococcus epidermidis into a Luria-Bertani culture medium, wherein the Luria-Bertani culture medium comprises 2% of tryptone, 1% of yeast extract, 1% of sodium chloride and 1.5% of agar in percentage by mass, culturing the Luria-Bertani culture medium in a three-gas incubator for 20 hours at 36 ℃, separating and inoculating the strain into a broth culture medium, and the broth culture medium comprises 1% of beef extract, 2% of tryptone, 0.5% of sodium chloride and 1.5% of agar in percentage by mass, culturing the strain in a constant-temperature shaking incubator for 30 hours at 34 ℃, wherein the rotating speed of the constant-temperature shaking incubator is 200rpm, and then inactivating the strain for later use; uniformly mixing inactivated staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii, pseudomonas aeruginosa and staphylococcus epidermidis according to the weight ratio of 8:8:3:4:4:3:4 to obtain a strain mixture; dissolving the strain mixture in neutral 0.1mol/L PBS solution to obtain strain mixture solution, and preparing strain mixture solution with the concentration of 2.2 mg/mL; adding Freund's adjuvant into the mixed solution of the strain in the same volume, and stirring to obtain milky whole-strain composite antigen; and (3) putting the whole-bacterium composite antigen into a high-speed homogenizer, and carrying out high-speed grinding and homogenization to obtain the composite antigen.
The prepared complex antigen is injected into the breast muscle and thigh of a 20-week-old chicken, 0.6ml of the complex antigen is injected into each breast muscle and thigh, and then the complex antigen is injected into the chicken at intervals of 10 days in a boosting manner for four times. Freund's adjuvant used in the first injection is Freund's incomplete adjuvant, Freund's adjuvant used in the second to fourth injections is complete Freund's adjuvant, and eggs laid by the chicken after the last injection are collected.
Breaking the immune eggs by using an egg breaker, removing egg white, uniformly stirring the yolk, adding distilled water according to 6 times of the volume of the yolk, diluting and uniformly mixing, and adjusting the pH to 5.0; then cooling to 6 ℃, and standing for 15 h; then centrifugally separating for 20 minutes by a high-speed centrifugal separator; adding the separated supernatant into an ultrafilter for ultrafiltration and concentration by 10 times, adding a sodium sulfate solution with the mass concentration of 10% into the concentrated slurry, and fully stirring; centrifuging by a high-speed centrifuge, taking the supernatant, and removing lipoprotein to obtain slurry; adding the slurry into an ultrafiltration machine, and filtering the slurry through an ultramicro membrane to remove bacteria; and (4) freeze-drying the filtered and sterilized slurry by using a freeze dryer to obtain crude extract dry powder.
And (3) carrying out ion exchange chromatography on the crude extract dry powder through an ion exchange column and carrying out gel filtration chromatography on a gel exchange column to separate and purify to obtain the composite yolk antibody composition.
Example 3
This example provides an aerosol inhalation solution, which is prepared according to the following preparation process:
(1) 1g of the complex yolk antibody composition of example 1 was slowly added to 80ml of water for injection cooled to room temperature, and the mixture was slowly stirred to be uniform for use.
(2) Weighing appropriate amount of water for injection, cooling to 60 deg.C, slowly adding citric acid-sodium citrate, stirring to dissolve completely, and cooling to room temperature.
(3) Weighing an appropriate amount of water for injection, cooling to 60 ℃, slowly adding 2g of sodium chloride, stirring to dissolve, and cooling to room temperature for later use.
(4) Adding the above (2) and (3) into the solution (1), stirring, heating to 35 deg.C, adding 0.05% of active carbon for injection, stirring for 20min, filtering, and decarbonizing.
(5) Adding water for injection to make the total volume 100ml, stirring well, detecting pH and content, and adjusting pH to 5.5.
(6) Filtering the medicinal liquid with 1.0 μm titanium filter core, detecting visible foreign matter and pH value of the intermediate, and adjusting pH to 5.5.
(7) Fine filtering the above medicinal liquid with 0.22 μm microporous membrane, filling into 2ml sterile ampoules under the protection of A-stage laminar flow, filling with nitrogen gas, and sealing.
(8) And after the lamp is detected to be qualified, detecting the visible foreign matters, the pH value, the aseptic condition and the antibody titer of the content in the ampoule bottle, wherein the visible foreign matters meet the regulation, the pH value meets the regulation, the aseptic condition is realized, and the antibody titer is more than or equal to 1:128, so that the qualified atomized inhalation solution is obtained.
Example 4
This example provides an aerosol inhalation solution, which is prepared according to the following preparation process:
(1) slowly adding 1g of the composite yolk antibody composition of example 1 and 0.5g of Chinese medicinal extractive solution (extracted from herba Senecionis Scandentis, flos Lonicerae, radix scrophulariae, and rhizoma Polygoni Cuspidati) into 50ml of water for injection cooled to room temperature, and slowly stirring well for use.
(2) Weighing an appropriate amount of water for injection, cooling to 70 ℃, slowly adding citric acid-disodium hydrogen phosphate, stirring to completely dissolve, and cooling to room temperature for later use.
(3) Weighing an appropriate amount of water for injection, cooling to 70 ℃, slowly adding 2g of magnesium chloride and glucose in total, stirring to dissolve, and cooling to room temperature for later use.
(4) Adding the above (2) and (3) into the solution (1), stirring, heating to 40 deg.C, adding 0.01% of active carbon for injection, stirring for 30min, filtering, and decarbonizing.
(5) Adding water for injection to make the total volume 100ml, stirring well, detecting pH and content, and adjusting pH to 6.0.
(6) Filtering the medicinal liquid with 1.0 μm titanium filter core, detecting visible foreign matter and pH value of the intermediate, and adjusting pH to 6.0.
(7) Fine filtering the above medicinal liquid with 0.22 μm microporous membrane, filling into 2ml sterile ampoules under the protection of A-stage laminar flow, filling with nitrogen gas, and sealing.
(8) And after the lamp is detected to be qualified, detecting the visible foreign matters, the pH value, the aseptic condition and the antibody titer of the content in the ampoule bottle, wherein the visible foreign matters meet the regulation, the pH value meets the regulation, the aseptic condition is realized, and the antibody titer is more than or equal to 1:128, so that the qualified atomized inhalation solution is obtained.
Example 5
This example provides an aerosol inhalation solution, which is prepared according to the following preparation process:
(1) 1g of the complex yolk antibody composition of example 2 and 0.5g of levofloxacin were slowly added to 70ml of water for injection cooled to room temperature, and the mixture was slowly stirred to be uniform for use.
(2) Weighing appropriate amount of water for injection, cooling to 60 deg.C, slowly adding sodium lactate, stirring to dissolve completely, and cooling to room temperature.
(3) Weighing an appropriate amount of water for injection, cooling to 60 ℃, slowly adding 2g of potassium chloride and sorbitol, stirring to dissolve, and cooling to room temperature for later use.
(4) Adding the above (2) and (3) into the solution (1), stirring, heating to 40 deg.C, adding 0.1% of active carbon for injection, stirring for 15min, filtering, and decarbonizing.
(5) Adding water for injection to make the total volume 100ml, stirring well, detecting pH and content, and adjusting pH to 5.0.
(6) Filtering the medicinal liquid with 1.0 μm titanium filter core, detecting visible foreign matter and pH value of the intermediate, and adjusting pH to 5.0.
(7) Fine filtering the above medicinal liquid with 0.22 μm microporous membrane, filling into 2ml sterile ampoules under the protection of A-stage laminar flow, filling with nitrogen gas, and sealing.
(8) And after the lamp is detected to be qualified, detecting the visible foreign matters, the pH value, the aseptic condition and the antibody titer of the content in the ampoule bottle, wherein the visible foreign matters meet the regulation, the pH value meets the regulation, the aseptic condition is realized, and the antibody titer is more than or equal to 1:128, so that the qualified atomized inhalation solution is obtained.
Example 6
This example provides an aerosol inhalation solution, which is prepared according to the following preparation process:
(1) slowly adding 1g of the composite yolk antibody composition of example 2, 0.3g of a traditional Chinese medicine extracting solution (obtained by extracting groundsel, honeysuckle, radix scrophulariae and polygonum cuspidatum) and 0.3g of levofloxacin into 50ml of water for injection cooled to room temperature, and slowly and uniformly stirring for later use.
(2) Weighing an appropriate amount of water for injection, cooling to 70 ℃, slowly adding citric acid-disodium hydrogen phosphate, stirring to completely dissolve, and cooling to room temperature for later use.
(3) Weighing an appropriate amount of water for injection, cooling to 70 ℃, slowly adding 2g of magnesium chloride and glucose in total, stirring to dissolve, and cooling to room temperature for later use.
(4) Adding the above (2) and (3) into the solution (1), stirring, heating to 40 deg.C, adding 0.01% of active carbon for injection, stirring for 30min, filtering, and decarbonizing.
(5) Adding water for injection to make the total volume 100ml, stirring well, detecting pH and content, and adjusting pH to 5.5.
(6) Filtering the medicinal liquid with 1.0 μm titanium filter core, detecting visible foreign matter and pH value of the intermediate, and adjusting pH to 5.5.
(7) Fine filtering the above medicinal liquid with 0.22 μm microporous membrane, filling into 2ml sterile ampoules under the protection of A-stage laminar flow, filling with nitrogen gas, and sealing.
(8) And after the lamp is detected to be qualified, detecting the visible foreign matters, the pH value, the aseptic condition and the antibody titer of the content in the ampoule bottle, wherein the visible foreign matters meet the regulation, the pH value meets the regulation, the aseptic condition is realized, and the antibody titer is more than or equal to 1:128, so that the qualified atomized inhalation solution is obtained.
The therapeutic effect of the aerosolized inhalation solution of the present embodiments was examined by the following clinical trials:
firstly, 50 volunteers with upper respiratory tract infection are selected, the atomized inhalation solution in the embodiment 3 is used for treatment, specifically, the atomized inhalation solution is atomized by an atomizer for inhalation treatment for the volunteers, and the volunteers are atomized for 2 times every day and 4mL each time, and various symptoms such as sneezing, nasal obstruction, watery nasal discharge and the like of the volunteers are observed.
After the volunteers took the medicine for 5-7 days, the symptoms of 45 volunteers basically disappeared, and the symptoms of the other 5 volunteers were relieved; symptoms disappeared in all volunteers 10 days after administration.
Therefore, the aerosol inhalation solution prepared from the composite yolk antibody composition of the embodiment of the invention has a remarkable treatment effect on the upper respiratory tract infection.
And secondly, selecting 50 volunteers with lower respiratory tract infection, carrying out atomization inhalation treatment on the volunteers by using the atomization inhalation solution in the embodiment 4, specifically carrying out atomization inhalation treatment on the volunteers by using an atomizer, atomizing for 2 times every day, and observing various symptoms of sneezing, rhinorrhea, pharyngalgia, hypodynamia, low fever and the like of the volunteers, wherein 4mL of the atomization inhalation solution is obtained every time.
After the volunteers took the medicine for 5-7 days, the symptoms of 46 volunteers basically disappeared, and the symptoms of the other 4 volunteers were relieved; symptoms disappeared in all volunteers 10 days after administration.
Therefore, the aerosol inhalation solution prepared from the composite yolk antibody composition of the embodiment of the invention has a remarkable treatment effect on the lower respiratory tract infection.
And thirdly, selecting 50 volunteers with bacterial pneumonia, using the atomized inhalation solution in the embodiment 5 for treatment, specifically, atomizing the atomized inhalation solution by using an atomizer for carrying out atomized inhalation treatment on the volunteers, wherein the atomized inhalation solution is atomized for 2 times every day, 4mL each time, and various symptoms of cough, expectoration (purulent sputum or bloody sputum), chest pain and the like of the volunteers are observed.
After the volunteers took the medicine for 5-7 days, the symptoms of 45 volunteers basically disappeared, and the symptoms of the other 5 volunteers were relieved; after 10 days of drug administration, symptoms disappeared in 49 volunteers, and in the remaining 1 volunteer, symptoms disappeared substantially.
Therefore, the aerosol inhalation solution prepared from the composite yolk antibody composition of the embodiment of the invention has a remarkable treatment effect on bacterial pneumonia.
And fourthly, selecting 50 volunteers with viral pneumonia infected by mixed bacteria, and using the atomized inhalation solution in the embodiment 6 for treatment besides using the same virus medicament, specifically, carrying out atomized inhalation treatment on the volunteers by using an atomizer, atomizing for 2 times every day, wherein 4mL of the atomized inhalation solution is used for each time, and observing various symptom changes of the volunteers, such as fever, headache, general aching pain, dry cough, lung infiltration and the like.
After the volunteers took the medicine for 5-7 days, the symptoms of 44 volunteers basically disappeared, and the symptoms of the other 6 volunteers were relieved; after 10 days of drug administration, symptoms disappeared in 48 volunteers, and in the remaining 2 volunteers, symptoms disappeared substantially.
Therefore, the aerosol inhalation solution prepared from the composite yolk antibody composition of the embodiment of the invention has remarkable treatment effect on viral pneumonia caused by mixed bacterial infection.
In addition, the comparative method of therapeutic efficacy for treating respiratory tract infections of examples 3-6 and the results are as follows:
80 patients with respiratory tract infection who have not been used with the medicine are selected, and the clinical symptoms are as follows: yellow sputum and cough were observed for 2 days after 2 days of fever, with no history of asthma, and patients ranged in age from 3-6 years, 40 men and 40 women. The therapeutic criteria are as follows:
and (3) curing: no cough, no yellow sputum and good spirit;
the method has the following advantages: the cough frequency is obviously reduced, yellow sputum is avoided, and the spirit is improved;
and (4) invalidation: cough frequency increases, yellow sputum increases, and mental retardation is poor.
80 patients with respiratory tract infection were divided into 4 test groups of 20 persons per test group and 10 persons for each male and female, and test groups 1-4 were treated by aerosol inhalation according to examples 3-6. The treatment method comprises the following steps: under the informed consent of the patients and their accompanying families, the patients were treated by aerosol inhalation with the aerosol inhalation of examples 3-6, 2 times per day, 4ml per time. The treatment effect of each group was counted after 5 days and 10 days of administration, as shown in table 1.
TABLE 1 comparison of therapeutic efficacy of examples 3-6 in treating respiratory infections
Figure BDA0001779146540000161
As can be seen from the table, the aerosol inhalation solution prepared from the composition for resisting various pathogenic bacteria in the embodiment of the invention has the effective rate of over 100 percent for treating the cough after fever, and has obvious curative effect.
In conclusion, the composite yolk antibody composition for preventing and treating respiratory tract infection and the preparation process thereof are safe, and can prevent and treat all respiratory tract infections; the application of the composite yolk antibody composition of the embodiment of the invention is used for preparing preparations for preventing and treating respiratory tract infection; the atomized inhalation solution and the preparation process thereof adopt the composite yolk antibody composition to prepare the atomized inhalation solution for preventing and treating respiratory tract infection, and have the advantages of convenient administration, quick absorption and obvious effect.
The embodiments described above are some, but not all embodiments of the invention. The detailed description of the embodiments of the present invention is not intended to limit the scope of the invention as claimed, but is merely representative of selected embodiments of the invention. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.

Claims (5)

1. An aerosolized inhalation solution comprising, per 100ml of aerosolized inhalation solution: 0.5-1.5g of compound yolk antibody composition, 0.3-1g of levofloxacin, a buffer pair and isoosmotic adjusting agent and the balance of solvent;
the composite yolk antibody composition is prepared by firstly preparing composite antigens of common pathogenic bacteria of respiratory tract infection; performing intensified immunity on the chicken by using the composite antigen to obtain an immune egg of the immune chicken; extracting the yolk of the immune egg to obtain crude extract dry powder; separating and purifying the crude extract dry powder by ion exchange chromatography and gel filtration chromatography to obtain the extract;
the composite antigen consists of staphylococcus aureus, hemolytic streptococcus, streptococcus pneumoniae, escherichia coli, acinetobacter baumannii, pseudomonas aeruginosa and staphylococcus epidermidis, and the mass ratio of the staphylococcus aureus, the hemolytic streptococcus, the streptococcus pneumoniae, the escherichia coli, the acinetobacter baumannii, the pseudomonas aeruginosa and the staphylococcus epidermidis is 4-8:4-8:3-5: 3-5;
crushing immune eggs, removing egg white, uniformly stirring egg yolks, adding distilled water according to 6 times of the volume of the egg yolks, diluting and uniformly mixing, and adjusting the pH value to 5.0; then cooling to 6 ℃, and standing for 15 h; then centrifugally separating for 20 minutes by a high-speed centrifugal separator; adding the separated supernatant into an ultrafilter for ultrafiltration and concentration by 10 times, adding a sodium sulfate solution with the mass concentration of 10% into the concentrated slurry, and fully stirring; centrifuging by a high-speed centrifuge, taking the supernatant, and removing lipoprotein to obtain slurry; adding the slurry into an ultrafiltration machine, and filtering the slurry through an ultramicro membrane to remove bacteria; and (4) freeze-drying the filtered and sterilized slurry by using a freeze dryer to obtain the product.
2. The aerosolized inhalation solution of claim 1, wherein the buffer pair is one selected from the group consisting of citric acid-sodium citrate, acetic acid-sodium acetate, citric acid-disodium hydrogen phosphate, sodium dihydrogen phosphate-disodium hydrogen phosphate, sodium lactate, and sodium tartrate-sodium tartrate.
3. The nebulizing inhalation solution of claim 1, wherein the isotonicity adjusting agent is selected from one or more of sodium chloride, potassium chloride, magnesium chloride, calcium chloride, glucose, xylitol, sorbitol.
4. A process for the preparation of an aerosolized inhalation solution according to claim 1, characterized in that it comprises the following steps:
adding the composite yolk antibody composition into a part of solvent, and uniformly stirring; adding buffer and isoosmotic adjusting agent, stirring to dissolve, filtering, adding solvent to full dose, and fine filtering.
5. The process for preparing an aerosol inhalation solution according to claim 4, wherein 0.3-1g of Chinese medicinal extract is further added, and the specific preparation method of the Chinese medicinal extract comprises:
extracting the cleaned groundsel, honeysuckle, figwort and giant knotweed with water at least twice, combining the extracting solutions, and centrifuging by a high-speed centrifuge to obtain a first centrifugal liquid;
reflux-extracting the residue with ethanol solution at least once, centrifuging the extractive solution with high speed centrifuge to obtain second centrifugate;
and combining the first centrifugate and the second centrifugate to obtain the traditional Chinese medicine extracting solution.
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