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WO2022170845A1 - Utilisation d'un nanomatériau d'or pour inhiber le coronavirus - Google Patents

Utilisation d'un nanomatériau d'or pour inhiber le coronavirus Download PDF

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Publication number
WO2022170845A1
WO2022170845A1 PCT/CN2021/137753 CN2021137753W WO2022170845A1 WO 2022170845 A1 WO2022170845 A1 WO 2022170845A1 CN 2021137753 W CN2021137753 W CN 2021137753W WO 2022170845 A1 WO2022170845 A1 WO 2022170845A1
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Prior art keywords
coronavirus
hcov
nanomaterials
sars
gold nanomaterials
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Ceased
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PCT/CN2021/137753
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English (en)
Chinese (zh)
Inventor
李洋
张国芳
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Shenzhen Institute of Advanced Technology of CAS
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Shenzhen Institute of Advanced Technology of CAS
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Publication of WO2022170845A1 publication Critical patent/WO2022170845A1/fr
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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K33/00—Medicinal preparations containing inorganic active ingredients
    • A61K33/24—Heavy metals; Compounds thereof
    • A61K33/242—Gold; Compounds thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N59/00—Biocides, pest repellants or attractants, or plant growth regulators containing elements or inorganic compounds
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P1/00—Disinfectants; Antimicrobial compounds or mixtures thereof
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01P—BIOCIDAL, PEST REPELLANT, PEST ATTRACTANT OR PLANT GROWTH REGULATORY ACTIVITY OF CHEMICAL COMPOUNDS OR PREPARATIONS
    • A01P3/00—Fungicides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
    • A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/19—Cosmetics or similar toiletry preparations characterised by the composition containing inorganic ingredients
    • 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
    • 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
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • 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
    • A61K9/0019—Injectable compositions; Intramuscular, intravenous, arterial, subcutaneous administration; Compositions to be administered through the skin in an invasive manner
    • 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
    • A61K9/0043—Nose
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • 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
    • A61K9/0053—Mouth and digestive tract, i.e. intraoral and peroral administration
    • A61K9/006—Oral mucosa, e.g. mucoadhesive forms, sublingual droplets; Buccal patches or films; Buccal sprays
    • 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
    • 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
    • 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
    • A61K9/48—Preparations in capsules, e.g. of gelatin, of chocolate
    • A61K9/50—Microcapsules having a gas, liquid or semi-solid filling; Solid microparticles or pellets surrounded by a distinct coating layer, e.g. coated microspheres, coated drug crystals
    • A61K9/51—Nanocapsules; Nanoparticles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2/00—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor
    • A61L2/16—Methods or apparatus for disinfecting or sterilising materials or objects other than foodstuffs or contact lenses; Accessories therefor using chemical substances
    • A61L2/23—Solid substances, e.g. granules, powders, blocks, tablets
    • A61L2/232—Solid substances, e.g. granules, powders, blocks, tablets layered or coated
    • 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
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q17/00—Barrier preparations; Preparations brought into direct contact with the skin for affording protection against external influences, e.g. sunlight, X-rays or other harmful rays, corrosive materials, bacteria or insect stings
    • A61Q17/005—Antimicrobial preparations
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q19/00—Preparations for care of the skin
    • A61Q19/10—Washing or bathing preparations
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B82—NANOTECHNOLOGY
    • B82Y—SPECIFIC USES OR APPLICATIONS OF NANOSTRUCTURES; MEASUREMENT OR ANALYSIS OF NANOSTRUCTURES; MANUFACTURE OR TREATMENT OF NANOSTRUCTURES
    • B82Y5/00—Nanobiotechnology or nanomedicine, e.g. protein engineering or drug delivery
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61L—METHODS OR APPARATUS FOR STERILISING MATERIALS OR OBJECTS IN GENERAL; DISINFECTION, STERILISATION OR DEODORISATION OF AIR; CHEMICAL ASPECTS OF BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES; MATERIALS FOR BANDAGES, DRESSINGS, ABSORBENT PADS OR SURGICAL ARTICLES
    • A61L2101/00—Chemical composition of materials used in disinfecting, sterilising or deodorising

Definitions

  • the invention belongs to the technical field of antivirus, and particularly relates to the application of a gold nanomaterial in inhibiting coronavirus.
  • Coronaviruses are a large family of viruses known to cause colds and more serious diseases such as Middle East Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome (SARS).
  • MERS Middle East Respiratory Syndrome
  • SARS Severe Acute Respiratory Syndrome
  • the 2019 novel coronavirus (SASR-CoV-2, which causes novel coronavirus pneumonia COVID-19) is the seventh known type, the first six are HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, For SARS-CoV (which causes severe acute respiratory syndrome) and MERS-CoV (which causes Middle East respiratory syndrome), no effective drugs have emerged so far.
  • one aspect of the present invention proposes the application of gold nanomaterials in the preparation of medicines for treating or preventing diseases caused by coronaviruses.
  • the medicament further comprises a pharmaceutically acceptable carrier or excipient.
  • the medicine further includes the administration of a therapeutically effective amount of at least one other therapeutic agent or its composition
  • the other therapeutic agent or its composition is selected from corticosteroids, anti-inflammatory drugs Inflammatory signaling modulators, beta2-adrenoceptor agonist bronchodilators, anticholinergics, mucolytics, hypertonic saline, and other drugs used in the treatment of coronavirus infections; or mixtures thereof.
  • a second aspect of the present invention provides a pharmaceutical composition for treating or preventing diseases caused by coronavirus, wherein gold nanomaterials are used as active ingredients in the pharmaceutical composition.
  • the pharmaceutical composition further comprises a pharmaceutically acceptable carrier or excipient.
  • the pharmaceutical composition further includes a second active ingredient selected from the group consisting of corticosteroids, anti-inflammatory signal transduction regulators, ⁇ 2 -Adrenoreceptor agonists bronchodilators, anticholinergics, mucolytics, hypertonic saline, and other drugs used to treat coronavirus infections; or mixtures thereof.
  • a second active ingredient selected from the group consisting of corticosteroids, anti-inflammatory signal transduction regulators, ⁇ 2 -Adrenoreceptor agonists bronchodilators, anticholinergics, mucolytics, hypertonic saline, and other drugs used to treat coronavirus infections; or mixtures thereof.
  • the formulation form of the pharmaceutical composition is selected from oral preparations, injection preparations, mucosal administration preparations, inhalation preparations, and external preparations.
  • a third aspect of the present invention provides a method of treating or preventing coronavirus infection, comprising administering to a subject a therapeutically effective amount of gold nanomaterials.
  • the therapeutically effective amount of gold nanomaterials is administered in the form of a preparation, and the preparation further comprises a pharmaceutically acceptable carrier or excipient.
  • the method further comprises the step of administering to the subject a therapeutically effective amount of a second active ingredient selected from the group consisting of corticosteroids, anti-inflammatory signal transduction Modulators, beta2-adrenoceptor agonist bronchodilators, anticholinergics, mucolytics, hypertonic saline, and other drugs used to treat coronavirus infections; or mixtures thereof.
  • a second active ingredient selected from the group consisting of corticosteroids, anti-inflammatory signal transduction Modulators, beta2-adrenoceptor agonist bronchodilators, anticholinergics, mucolytics, hypertonic saline, and other drugs used to treat coronavirus infections; or mixtures thereof.
  • the fourth aspect of the present invention provides the use of gold nanomaterials in the preparation of a preparation that inhibits coronavirus and reduces the binding of SARS-CoV-2 virus Spike protein to its host cell receptor ACE2;
  • the viral Spike protein inhibits its binding to its host cell receptor ACE2.
  • the fifth aspect of the present invention provides the use of gold nanomaterials in the preparation of materials for inhibiting coronavirus infection or reducing and killing coronavirus materials.
  • a sixth aspect of the present invention provides a material for inhibiting coronavirus infection, the material comprising gold nanomaterials and a matrix.
  • the material is a material for preparing protective equipment, preferably the protective equipment is a mask, protective clothing, protective face shield, and protective cap.
  • the material is a kind of paint.
  • the material is a disinfectant or a personal care product.
  • the material is a packaging material.
  • the material is a filter material.
  • a seventh aspect of the present invention provides an article, which comprises gold nanomaterials
  • the article is selected from protective articles, coatings, disinfectants, personal care articles, packaging materials or filtration devices;
  • the coating is a suspension containing gold nanomaterials, whether the coating can impart a coating with gold nanomaterials on the surface of the attached object;
  • the disinfectant is an environmental disinfectant, hand sanitizer, hand sanitizer, and detergent; more preferably, the disinfectant is used for surface disinfection of packaging materials, medical instruments, oral appliances, and beauty appliances;
  • the packaging material has a coating containing gold nanomaterials, or the packaging material is a composite material containing gold nanomaterials; more preferably, the packaging material is a packaging material for medicine or food, especially is a drug or food intended for cold chain transportation;
  • the filter device is a device for air filtration, a device for water body filtration, and a device for mask filtration; more preferably, the filter device is an air filter, and the surface of the air filter has Gold nanomaterials; more preferably, the filtering device is air filter cotton, and gold nanomaterials are attached to the air filter cotton fibers.
  • the coronavirus is selected from one of HCoV-229E, HCoV-OC43, HCoV-NL63, HCoV-HKU1, SARS-CoV, SARS-CoV2 or MERS-CoV.
  • the coronavirus is preferably selected from SARS-CoV or SARS-CoV-2.
  • the disease caused by coronavirus is a disease caused by coronavirus infection.
  • the present invention achieves the following beneficial effects:
  • gold nanomaterials can inhibit the cell infection of coronaviruses, and on the other hand, they can specifically act on the infection targets of coronaviruses, reduce the infection efficiency of the virus, and reduce the number of coronaviruses, and can be used as therapeutic drugs for coronaviruses .
  • the nanomaterial of the present invention inhibits the infection of host cells by the SARS-CoV-2 virus, the specific adsorption and immobilization of the virus is realized. Therefore, in addition to being used to prepare medicines, it can also be used for meltblown cloth, cold storage coating and outer packaging coating or spray that can be applied to masks, which can absorb the new coronavirus and play a role in preventing new coronary pneumonia.
  • the gold nanomaterials of the present invention can be stored at room temperature to 4°C for a long time, which is convenient for storage.
  • the gold nanomaterial of the present invention has high stability, and can be mixed or compounded with any material to form a composite material, and is not affected by factors such as temperature and pH.
  • the present invention adopts inorganic nanomaterials, and the source of materials is not limited, and is suitable for large-scale mass production, with low cost and less consumption.
  • Figure 1 shows the detection results of the physical and chemical properties of gold nanomaterials, in which the left is the transmission electron microscope (TEM) picture, and the right is the particle size distribution.
  • TEM transmission electron microscope
  • Figure 2 shows the inhibitory effect of gold nanomaterials in Example 1 on pseudovirus SC2-P infecting ACE2/293T cells.
  • Figure 3 shows the inhibitory effect of gold nanomaterials in Example 1 on the infection of Vero-E6 cells by the true virus SARS-CoV-2.
  • gold nanomaterials are effective in inhibiting the infection of coronaviruses, especially the cell infection of the SARS virus SARS-CoV and the new coronavirus pneumonia virus SARS-CoV-2.
  • the invention confirms that the gold nanomaterial has high biological safety and low toxicity, and can be used in the fields of medicine, disinfection preparation, food and material.
  • gold has the same meaning as Au.
  • nanomaterials and “nanoparticles” have similar meanings, and both refer to materials with a dimension in space that is nanoscale, such as a particle size of 1-300 nm or a particle size of 1-100 nm of nanoparticles.
  • the particle size is 1 nm, 5 nm, 10 nm, 15 nm, 20 nm, 30 nm, 40 nm, 50 nm, 60 nm, 70 nm, 80 nm, 90 nm.
  • ACE2 protein and angiotensin converting enzyme 2 have the same meaning. Studies have shown that the key to the infection of human cells by the new coronavirus is the combination of the Spike protein of the coronavirus and the ACE2 protein on the surface of human cells to enter the host cell.
  • Spike glycoproteins are glycoproteins that protrude from the surface of the viral envelope, allowing the virus to bind to and enter cells.
  • “Pharmaceutically acceptable carrier or excipient” includes, but is not limited to, any adjuvant, carrier, excipient, glidant, sweetener, diluent, preservative, dye/colorant, flavor enhancer, surface active agent agents, wetting agents, dispersing agents, suspending agents, stabilizers, isotonic agents, solvents or emulsifying agents that have been approved by the Food and Drug Administration as acceptable for use in humans or livestock.
  • “Pharmaceutical composition” refers to a formulation of a compound of the present invention and a vehicle generally accepted in the art for delivering a biologically active compound to a mammal (eg, a human). Such vehicles include all pharmaceutically acceptable excipients for this purpose.
  • an “effective amount” or “therapeutically effective amount” refers to an amount of a compound according to the present invention which, when administered to a patient in need thereof, is sufficient to effect the treatment of a disease state, condition or disorder for which gold nanomaterials have utility. Such an amount will be sufficient to elicit the biological or medical response of the tissue system or patient sought by the researcher or clinician.
  • the amount of a compound according to the invention that constitutes a therapeutically effective amount will vary depending on factors such as the compound and its biological activity, the composition used for administration, the time of administration, the route of administration, the rate of excretion of the compound, the duration of treatment, the treatment duration the type and severity of the disease state or disorder, the drugs used in combination or in consonance with the compounds of the present invention, and the patient's age, weight, general health, sex, and diet.
  • Such therapeutically effective amounts can be routinely determined by those of ordinary skill in the art based on their own knowledge, prior art, and this disclosure.
  • treating refers to reversing, alleviating, inhibiting the progression of, or preventing the disorder or condition to which the term applies, or one or more of such disorders or conditions symptom.
  • treatment refers to the act of treating, as “treatment” is as immediately described above.
  • treatment is intended to mean the administration of gold nanomaterials or compositions thereof according to the present invention to reduce or eliminate symptoms of coronavirus infection and/or reduce viral load in a patient.
  • Prevention refers to any treatment of a disease or disorder that results in the absence of clinical symptoms of the disease or disorder.
  • the term “prophylaxis” also includes the administration of a therapeutically effective amount of a compound or composition according to the invention (eg, pre-exposure prophylaxis) prior to exposure of the individual to the virus to prevent the development of symptoms of disease and/or to prevent the virus from becoming detectable in the blood Level.
  • subject refers to an animal, such as a mammal (including a human), that has been or will be the subject of treatment, observation, or experimentation.
  • the methods described herein can be used in human therapy and/or veterinary applications.
  • the subject is a mammal (or patient).
  • subjects (or patients) are humans, livestock (eg, dogs and cats), farm animals (eg, cattle, horses, sheep, goats, and pigs) and/or laboratory animals (eg, mice) , rats, hamsters, guinea pigs, pigs, rabbits, cats, dogs and monkeys).
  • the subject (or patient) is a human.
  • erson (or patient) in need refers to a person who may have or is suspected of having a disease or disorder that would benefit from certain treatments; Treatment with a pharmaceutical composition comprising the above ingredients.
  • the gold nanomaterials of the present invention are formulated with conventional carriers and excipients, which will be selected according to conventional practice. Tablets will contain excipients, glidants, fillers, binders and the like. Aqueous formulations are prepared in sterile form and are expected to be generally isotonic for delivery other than by oral administration.
  • the active ingredient gold nanomaterials can be administered alone, it may be preferable to present them as a pharmaceutical formulation.
  • the formulations for veterinary and human use of the present invention comprise at least one active ingredient as defined above (the active ingredient is gold nanomaterials, the same below) together with one or more acceptable carriers and optionally other Therapeutic ingredients such as corticosteroids, anti-inflammatory signaling modulators, beta2-adrenoceptor agonist bronchodilators, anticholinergics, mucolytics, hypertonic saline, and other drugs used in the treatment of coronavirus infections drug; or a mixture thereof.
  • Formulations of the invention suitable for oral administration may be presented in discrete unit form such as capsules, cachets or tablets, each containing a predetermined amount of the active ingredient; as powders or granules; as solutions in aqueous or non-aqueous liquids or suspension; or as an oil-in-water liquid emulsion or a water-in-oil liquid emulsion. Or prepared into oral administration formulations by other known techniques.
  • a tablet is made by compression or molding, optionally with one or more accessory ingredients.
  • Compressed tablets may be prepared by compressing in a suitable machine the active ingredient in a free-flowing form such as powder or granules, optionally mixed with a binder, lubricant, inert diluent, preservative, surface active or dispersing agent.
  • Molded tablets may be made by molding in a suitable machine a mixture of the powdered active ingredient moistened with an inert liquid diluent. Tablets may optionally be coated or scored and optionally formulated to provide slow or controlled release of the active ingredient therefrom.
  • the pharmaceutical composition of the present invention may be an external preparation such as an ointment for topical administration.
  • the formulation is preferably as a topical ointment or cream containing the active ingredient.
  • the active ingredient can be used with a paraffin or water-miscible ointment base.
  • the active ingredient may be formulated in a cream with an oil-in-water cream base.
  • topical formulations may include compounds that enhance the absorption or penetration of the active ingredient through the skin or other affected area. Examples of such skin penetration enhancers include dimethyl sulfoxide and related analogs.
  • the oily phase of the emulsions of the present invention may be constituted in a known manner from known ingredients.
  • the oily phase may contain only emulsifiers, but it may also contain at least one emulsifier in admixture with fat or oil or both.
  • a hydrophilic emulsifier is included together with a lipophilic emulsifier which acts as a stabilizer.
  • Oils and fats are also preferably included.
  • compositions of the present invention may be in the form of sterile injectable preparations, such as sterile injectable aqueous or oily suspensions.
  • compositions of the present invention may be formulations suitable for topical administration to the eye and also include eye drops wherein the active ingredient is dissolved or suspended in a suitable carrier, especially an aqueous solvent for the active ingredient.
  • compositions of the present invention may be in formulations suitable for oral topical administration including lozenges containing the active ingredients in a flavored base, usually sucrose and acacia or tragacanth; in an inert base such as gelatin and glycerol or sucrose and A lozenge containing the active ingredient in acacia; and a mouthwash containing the active ingredient in a suitable liquid carrier.
  • compositions of the present invention may be formulated for rectal administration, which may be presented as a suppository with a suitable base containing, for example, cocoa butter or salicylates.
  • compositions of the present invention may be formulations suitable for intrapulmonary or intranasal administration, such formulations typically have particle sizes in the range of 0.1-500 microns, such as 0.5, 1, 30, 35 microns, etc., which pass through the nasal passages Administer by rapid inhalation or by oral inhalation to reach the alveoli.
  • the active ingredients of the present invention have dimensions that can be used for intrapulmonary or intranasal administration, such as inhalation.
  • compositions of the present invention may be in formulations suitable for parenteral administration including aqueous and non-aqueous sterile injectable solutions, which may contain antioxidants, buffers, bacteriostatic agents and are isotonic with the blood of the intended recipient. solutes; and aqueous and non-aqueous sterile suspensions which may contain suspending and thickening agents.
  • Formulations of the pharmaceutical compositions of the present invention are presented in unit-dose or multi-dose containers (eg, sealed ampoules and vials) and can be stored in a freeze-dried (lyophilized) condition requiring only the addition of a sterile liquid carrier immediately before use (eg water for injection). Extemporaneous injection solutions and suspensions are prepared from sterile powders, granules and tablets of the kind previously described.
  • Preferred unit dosage formulations are those containing a daily dose or unit daily sub-dose, as recited above, or an appropriate fraction thereof, of the active ingredient.
  • the pharmaceutical composition of the present invention may be a veterinary composition comprising at least one active ingredient as defined above together with a veterinary carrier.
  • the compounds of the present invention are useful in providing controlled release pharmaceutical formulations containing one or more active ingredients of the present invention as active ingredients, wherein the release of the active ingredients is controlled and regulated to allow less frequent dosing or to improve the pharmacokinetics of a given active ingredient Kinetic or toxicity profile.
  • the medicament, pharmaceutical composition or active ingredient of the present invention can also be used in combination with other active ingredients.
  • other active ingredients are active against coronavirus infections, especially SARS or SARS-CoV-2 infections.
  • Non-limiting examples of these other active therapeutic agents are corticosteroids, anti-inflammatory signaling modulators, beta2-adrenoceptor agonist bronchodilators, anticholinergics, mucolytics, hypertonic saline and others for Drugs for the treatment of coronavirus infections; or mixtures thereof.
  • the medicaments, pharmaceutical compositions, or active ingredients of the present invention may also be administered to a patient simultaneously or sequentially in combination with one or more other active ingredients in unit dosage form.
  • Combination therapy can be administered as a simultaneous or sequential regimen.
  • the combination may be administered in two or more administrations.
  • Co-administration of a medicament, pharmaceutical composition, or active ingredient of the present invention with one or more other active ingredients generally refers to the simultaneous or sequential administration of a compound of the present invention and one or more other active therapeutic agents such that a therapeutically effective amount of the present invention is administered
  • the drug, pharmaceutical composition, or active ingredient and one or more other active ingredients are present in the patient.
  • Combination therapy can provide "synergistic effect” and “synergistic effect”, that is, the effect obtained when used together is greater than the sum of the effects produced by the compounds used alone. Synergistic effects can be achieved when the active ingredients are: (1) co-formulated and administered or delivered simultaneously in a combined formulation; (2) delivered alternately or in parallel as separate formulations; or (3) by other regimens.
  • An application scheme of the present invention provides the use of gold nanomaterials in the preparation of materials for inhibiting coronavirus infection.
  • An application solution of the present invention is to provide a material for inhibiting coronavirus infection, the material comprising gold nanomaterials and a matrix.
  • the material is a material for preparing protective equipment, preferably the protective equipment is a mask, protective clothing, protective face shield, and protective cap.
  • the material is a kind of paint.
  • the material is a disinfectant.
  • the material is a packaging material.
  • the material is a filter material.
  • the material for inhibiting coronavirus infection is a material for preparing a mask, and the material is a fabric, and the surface or interior of the fabric contains the gold nanomaterial of the present invention.
  • the material for inhibiting coronavirus infection is a material for preparing masks, and the material is a non-woven fabric, preferably a spunbond non-woven fabric or a melt-blown non-woven fabric cloth; the surface or interior of the non-woven fabric contains the gold nanomaterials of the present invention.
  • the gold nanomaterials and the matrix materials can be composited by conventional methods in the art.
  • the meltblown material can be compounded with gold nanomaterials before meltblown spinning, and then meltblown, or the obtained meltblown cloth can be compounded with gold nanomaterials.
  • the material for inhibiting coronavirus infection is a packaging material
  • the packaging material is used for cold chain transportation or storage of medicines or foods.
  • the surface of the packaging material has a coating comprising gold nanomaterials, or the packaging material is a composite material comprising gold nanomaterials.
  • the material for inhibiting coronavirus infection is a filter material
  • the filter material is a material for air filtration, a material for water filtration, and a material for mask filtration.
  • the filter material is an air filter
  • the surface of the air filter has gold nanomaterials.
  • the filter material is air filter cotton, and gold nanomaterials are attached to the air filter cotton fibers.
  • the filter material can be used for air conditioner filtration, air purifier filtration, fresh air system filtration and any other device or equipment that needs to filter air. The scenarios used are not limited to homes, offices, laboratories, factories, etc.
  • the liquid material is a coating containing gold nanomaterials, a disinfectant containing gold nanomaterials, and personal care products containing gold nanomaterials.
  • the solid material is a device or a packaging material containing gold nanomaterials on the surface.
  • the semi-solid material is a gel containing gold nanomaterials.
  • ACE2/293T and Vero-E6 cells pseudovirus SC2-P.
  • the materials, reagents, vectors, strains, etc. used in the following examples can be purchased through commercial channels unless otherwise specified.
  • HEK-293T cell a derivative of human embryonic kidney cell 293, is a cell line derived from human embryonic kidney cells. It has the characteristics of high transfection efficiency and easy culture. Cell lines have become a powerful tool for researchers to study gene function.
  • ACE2/293T refers to the expression of ACE2 in HEK-293T cells.
  • ACE2 also known as ACEH
  • angiotensin-converting enzyme 2 is called angiotensin-converting enzyme 2.
  • the protein encoded by this gene belongs to the angiotensin-converting enzyme family of dipeptidyl carboxydipeptidase, and has considerable homology with human angiotensin-converting enzyme 1.
  • the protein encoded by this gene is a functional receptor for the Spike glycoprotein of SARS, SARS-CoV-2, and HCoV-NL63 human coronaviruses.
  • Vero-E6 cell is an African green monkey kidney cell line, one of the verified cells that can be infected by the new coronavirus, and can be used as a cell host for culturing the new coronavirus. For example: to determine the effect of a drug on the replication rate of the new coronavirus, to test for the presence of the new coronavirus, or to cultivate the new coronavirus for research purposes.
  • Pseudovirus SC2-P is a pseudovirus particle of SARS-CoV-2, which wraps marker genes such as Luciferase/GFP with Spike protein, simulates virus infection of cells, and detects the expression of marker genes.
  • SC2-P used in the following examples can be obtained from Ordered by Goldwisdom.com.
  • SARS-P is a pseudovirus of SARS, and it is also a commercial product, so I won't repeat it here.
  • the gold nanomaterials (Au) used in the examples are nanoparticles with a particle size of less than 100 nm.
  • the particle size of Au nanoparticles was detected by DLS and observed by transmission electron microscope. The experimental results are shown in Figure 1, and the particle size is about 5 nm.
  • ACE2/293T cells were seeded into 96-well plates at a density of 1 ⁇ 10 4 cell/wall, and cultured overnight at 37°C in 5% CO 2 .
  • ACE2/293T cells were infected with SC2-P of ⁇ g/mL Au nanomaterials for 2 h, washed once in DMEM, and then cultured with DMED medium for 40-48 The infection efficiency was detected after h.
  • Vero-E6 cells were seeded into 24-well plates at a density of 5 ⁇ 10 4 cells/wall, and cultured overnight at 37°C in 5% CO 2 .
  • Vero-E6 cells were infected with the true virus SARS-CoV-2 of Au nanomaterials at ⁇ g/mL for 2 h, washed once with DMEM, and then cultured with DMED medium for 40-48 The infection efficiency was detected after h. After harvesting the infected Vero-E6 cells, their RNA was extracted, and quantitative PCR was used to detect the mRNA levels of non-structural protein (NSP2) and spike protein (S protein, spike) in host cells, respectively.
  • NSP2 non-structural protein
  • S protein, spike spike
  • the experimental results show that adding Au nanomaterials can effectively reduce the mRNA levels of non-structural protein (NSP2) and spike protein (S protein, spike) in host cells, indicating that Au nanomaterials can reduce the infection efficiency of SARS-CoV-2 ( image 3). This indicates that Au nanomaterials can not only effectively inhibit the infection of host cells by SC2-P, but also inhibit the infection of the virus SARS-CoV-2. Since SC2-P is a simulation of the surface S protein of SARS-CoV-2 virus, according to the experimental results, it can be expected that gold nanomaterials can competitively act on the surface S protein of ARS-CoV-2 virus and inhibit its interaction with the host cell receptor ACE2. combine.

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Abstract

L'invention concerne l'utilisation de nanomatériau d'or pour inhiber le coronavirus, et l'utilisation de nanomatériau d'or dans la préparation de médicaments pour le traitement ou la prévention de maladies provoquées par un coronavirus ou de matériaux pour faire adhérer ou inhiber le coronavirus. Le coronavirus est choisi parmi le HCoV-229E, le HCoV-OC43, le HCoV-NL63, le HCoV-HKU1, le SARS-CoV, le SARS-CoV2 ou le MERS-CoV. La maladie provoquée par le coronavirus est une maladie provoquée par une infection à coronavirus. Le matériau présente les avantages d'une préparation simple, d'une sécurité biologique élevée, ainsi que d'excellents effets.
PCT/CN2021/137753 2021-02-10 2021-12-14 Utilisation d'un nanomatériau d'or pour inhiber le coronavirus Ceased WO2022170845A1 (fr)

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