WO2021238836A1 - Cantharidin antiviral and antibacterial preparation, preparation method therefor, and use thereof for preventing and treating novel coronavirus infection - Google Patents

Cantharidin antiviral and antibacterial preparation, preparation method therefor, and use thereof for preventing and treating novel coronavirus infection Download PDF

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Publication number
WO2021238836A1
WO2021238836A1 PCT/CN2021/095429 CN2021095429W WO2021238836A1 WO 2021238836 A1 WO2021238836 A1 WO 2021238836A1 CN 2021095429 W CN2021095429 W CN 2021095429W WO 2021238836 A1 WO2021238836 A1 WO 2021238836A1
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cantharidin
oil
solution
mutual
water
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PCT/CN2021/095429
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French (fr)
Chinese (zh)
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王卫
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甘肃芫美药业有限公司
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Priority claimed from CN202010446540.8A external-priority patent/CN111568897A/en
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Publication of WO2021238836A1 publication Critical patent/WO2021238836A1/en

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    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
    • A61K31/365—Lactones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K35/00—Medicinal preparations containing materials or reaction products thereof with undetermined constitution
    • A61K35/56—Materials from animals other than mammals
    • A61K35/63—Arthropods
    • A61K35/64—Insects, e.g. bees, wasps or fleas
    • A61K35/644—Beeswax; Propolis; Royal jelly; Honey
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/48—Fabaceae or Leguminosae (Pea or Legume family); Caesalpiniaceae; Mimosaceae; Papilionaceae
    • A61K36/481—Astragalus (milkvetch)
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K39/00—Medicinal preparations containing antigens or antibodies
    • A61K39/02—Bacterial antigens
    • 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
    • A61K39/12—Viral antigens
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/22—Heterocyclic compounds, e.g. ascorbic acid, tocopherol or pyrrolidones
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/44—Oils, fats or waxes according to two or more groups of A61K47/02-A61K47/42; Natural or modified natural oils, fats or waxes, e.g. castor oil, polyethoxylated castor oil, montan wax, lignite, shellac, rosin, beeswax or lanolin
    • 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
    • A61K9/08—Solutions
    • 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
    • A61K9/10—Dispersions; Emulsions
    • A61K9/12—Aerosols; Foams
    • 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
    • A61K9/20—Pills, tablets, discs, rods
    • 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
    • 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
    • A61P31/02—Local antiseptics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/16—Antivirals for RNA viruses for influenza or rhinoviruses
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV

Definitions

  • the invention relates to the field of biopharmaceuticals, in particular to provide a cantharidin antiviral and antibacterial preparation and a preparation method thereof.
  • the preparation provided by the invention can be used as antiviral and antibacterial preventive and therapeutic drugs. In particular, it will also have an important preventive and therapeutic effect on the infection of pathogens such as the new coronavirus, influenza virus, Ebola virus, and HIV.
  • Cantharidin is an animal's defensive substance. It is a high-efficiency, low-toxicity, broad-spectrum antiviral and antibacterial bioactive raw material drug, which has been recorded in Chinese medicine for a long time.
  • Cantharidin is also a kind of raw material of modern western medicine. A hundred years ago, Western medical scientists have purified cantharidin and studied its physical properties and chemical structure. Clinically, this defensive substance of the genus Lycane insects was classified as a "skin irritant, blistering drug".
  • cantharidin cream has significant antipyretic, antiemetic and antidiarrheal effects in the treatment of children's autumn diarrhea.
  • the effective rate was 97% within 48 hours, the average improvement time was 23.4 hours, the antiemetic time was 19.7 hours, and the antipyretic time was 18.75 hours, which significantly shortened the course of the disease.
  • External treatment can also avoid the difficulty of taking medicine caused by vomiting in children. During the treatment, no local adverse skin reactions and other side effects were found.
  • “Cantharidin Cream” is a safe and effective medicine for treating infantile diarrhea.
  • cantharidin antiviral and antibacterial series preparations In the development of cantharidin antiviral and antibacterial series preparations and the search for solvent carriers of cantharidin, the inventors studied the application of fats and essential oils to prepare cantharidin antiviral and antibacterial series preparations, and obtained ZL90106365.7 and 01140066.8 patents. However, the development of cantharidin antiviral and antibacterial series preparations, the search for the solvent carrier of cantharidin, until the application of essential oils, is far from obtaining an ideal cantharidin solvent carrier.
  • the maximum solubility of cantharidin in water is 33.33ppm; after more than 50 years of research in this medical research project, pure water is used as the solvent carrier of cantharidin to prepare a formulation of cantharidin human in vitro target efficacy. When its water evaporates, its highest The drug concentration can reach 33.33ppm. Compared with the long-term large number of cantharidin toxicology studies in this subject, compared with the data of the target drug concentration of cantharidin in the human body ⁇ 5.6ppm, it is obvious that the drug concentration is too high. Therefore, cantharidin preparations that are simply dissolved in water become "blistering agents" with toxic and side effects when applied to targets outside the body, and cannot produce the therapeutic effects that cantharidin should have.
  • the present invention selects oil-oil mutual soluble and oil-water mutual solubles as the solvent carrier of cantharidin, and obtains significant advantages in cantharidin pharmacy, toxicology, and pharmacodynamics than the oils and essential oils used in the ZL90106365.7 and 01140066.8 invention patents. improve.
  • the first aspect of the present invention is to provide an antiviral and antibacterial cantharidin preparation containing cantharidin as an effective drug Ingredients, the cantharidin is dissolved in an oil-water mutual soluble or an oil-oil mutual soluble to obtain a cantharidin solvent carrier, and the cantharidin solvent carrier is formulated with a pharmaceutically acceptable carrier or excipient into a variety of dosage forms for the prevention and treatment of new crowns Viral drugs.
  • the oil-water mutual solution or the oil-oil mutual solution contains essential oils of ketones and/or lactones.
  • the second aspect of the present invention is to provide a cantharidin skin absorption lotion for the prevention and treatment of new coronavirus, which contains cantharidin as an effective pharmaceutical ingredient, and the solvent carrier of cantharidin is an oil-water mutual solution, including:
  • Ketone essential oil 40.0-60.0g
  • a transdermal absorption lotion containing 0.16-0.2mg of cantharidin per gram is prepared.
  • the third aspect of the present invention is to provide an intravenous injection for the treatment of neocoronavirus with an oil-water mutual solution as a solvent carrier of cantharidin, which contains cantharidin as an effective pharmaceutical ingredient, according to the following ingredients:
  • the rest is physiological water for injection: total 16000.00g.
  • the fourth aspect of the present invention is to provide a cantharidin tablet with a cantharidin solvent carrier as a cantharidin solvent for the treatment of new coronaviruses, containing cantharidin as an effective drug ingredient, including:
  • Cocoa butter 80.0-120.0g
  • the fifth aspect of the present invention is to provide a cantharidin capsule for the treatment of the new coronavirus, with an oil-oil mutual soluble as a cantharidin solvent carrier, which contains cantharidin as an effective pharmaceutical ingredient, including:
  • the sixth aspect of the present invention is to provide a cantharidin nasal and eye spray which is used as the prevention of new coronavirus, and the oil-water mutual soluble solvent is the solvent carrier of cantharidin, which contains cantharidin as an effective drug ingredient, which includes:
  • the balance is distilled water: a total of 10000.0g cantharidin nose and eye spray.
  • the seventh aspect of the present invention is to provide a cantharidin nasal and ophthalmic oil for the prevention of new coronaviruses, the oil-oil mutual soluble as the solvent carrier of cantharidin, which contains cantharidin as an effective pharmaceutical ingredient, and includes:
  • the rest is olive oil: a total of 1000.0g cantharidin nose and eye oil is made.
  • the eighth aspect of the present invention is to provide a cantharidin solution disinfectant cloth used as a prevention of new coronavirus, oil-water mutual soluble as cantharidin solvent carrier, containing cantharidin as an effective drug ingredient, including:
  • the remainder is distilled water, making 10000.0g.
  • the obtained solvent is sprayed on the carrier to prepare a cantharidin solution disinfection cloth towel.
  • the ninth aspect of the present invention is to provide a combined oral pill of cantharidin Chinese and Western medicine for the treatment of new coronavirus, which contains cantharidin as an effective drug ingredient, and the solvent carrier of cantharidin is an oil-oil mutual soluble substance, according to the following ingredients:
  • Cocoa butter 10.0g
  • Cantharidin lysate (containing cantharidin 330.0mg): 126.0g
  • Astragalus extract 100.0g
  • the tenth aspect of the present invention is to provide a cleaning agent prepared by families and soldiers who are mutually soluble in oil and water to prevent traumatic infections, characterized in that the solution is a cantharidin oil-water mutual soluble body, and has the following components:
  • the eleventh aspect of the present invention is to provide a cantharidin antiviral and antibacterial invisible condom for preventing HIV sexual transmission. It is characterized in that the solution is a cantharidin oil-water mutual solution, and has the following ingredients:
  • Lactic acid 1000.0g
  • Hyaluronic acid 30.0-120.0g
  • the remainder is distilled water to make: a total of 10000.0g cantharidin invisible condom for preventing HIV sexual transmission.
  • the twelfth aspect of the present invention is to provide a cantharidin antibiotic solution for preparing an anti-new coronavirus inactivated vaccine, which contains cantharidin as an effective drug ingredient, and is a solution containing 1.6 ppm ⁇ cantharidin ⁇ 3.6 ppm.
  • the solution containing 1.6 ppm ⁇ cantharidin ⁇ 3.6ppm is a cantharidin oil-oil mutual soluble or a cantharidin oil-water mutual soluble.
  • the oil-oil mutual solution is a cantharidin solvent carrier, including: 2-butanone and olive oil, the cantharidin content is 1.6-3.6 ppm, the 2-butanone content is 8-12% by weight, and the rest is The olive oil.
  • the oil-water mutual solution is a cantharidin solvent carrier, including: cantharidin, the content is 1.6-3.6ppm; ethanol, the content is 3.75-5.2% by weight; 2-butanone, the content is: 0.8-1.2% by weight; propylene glycol , The content is: 4.95-7.2 5 wt%; benzyl alcohol, the content is: 0.06-0.12 wt%; 2-phenylethanol, the content is: 0.06-0.12 wt%; the raspberry ketone, the content is: 0.03.-0.06% by weight ; The rest is distilled water.
  • cantharidin solvent carrier including: cantharidin, the content is 1.6-3.6ppm; ethanol, the content is 3.75-5.2% by weight; 2-butanone, the content is: 0.8-1.2% by weight; propylene glycol , The content is: 4.95-7.2 5 wt%; benzyl alcohol, the content is: 0.06-0.12 wt%; 2-phenylethanol,
  • the thirteenth aspect of the present invention is to provide a method for preparing a cantharidin antibiotic solution for preparing an anti-new coronavirus inactivated vaccine, which is to dissolve a certain amount of cantharidin and 2-butanone in olive oil, and then add the olive oil Until the cantharidin content is 1.6-3.6 ppm, the 2-butanone content is 8-12% by weight, and the rest is the cantharidin antibiotic solution of the olive oil.
  • the fourteenth aspect of the present invention is to provide a preparation method for preparing cantharidin antibiotic solution for inactivated vaccine against new coronavirus, which is to combine a certain amount of cantharidin with a content of 1.6-3.6 ppm; ethanol with a content of: 3.75-5.25 Weight%; 2-butanone, content: 0.8-1.2% by weight; Propylene glycol, content: 4.95-7.25% by weight; Benzyl alcohol, content: 0.06-0.12% by weight; 2-Phenylethanol, content: 0.06- 0.12% by weight; raspberry ketone, the content is: 0.03.-0.06% by weight; after being dissolved in distilled water, distilled water is added to obtain a cantharidin antibiotic solution.
  • the cantharidin solvent ⁇ 5.6 ppm of the present invention is used as a solution and can be used to manufacture antibiotic "ecological" inactivated vaccines.
  • the use of this solution does not use physical methods or chemical methods, but uses the ecological biological activity of the cantharidin solution to inactivate pathogens to make virus or bacterial inactivated vaccines.
  • the antigenicity of the present invention will be more ideal, and it is a new technical route for manufacturing inactivated vaccines that is highly worth testing.
  • Cantharidin is a refined cantharidin obtained according to the prior art (ZL patent number 90106365.7 or 01140066.8).
  • Ketone essential oil 40.0-60.0g
  • a skin absorption lotion containing 0.16-0.2mg of cantharidin per gram is prepared.
  • the skin absorption lotion contains 0.32-0.4 mg cantharidin.
  • the preparation enters the blood circulation through the lymphatic system, exerts a medicinal effect on the internal organs of cantharidin, and treats respiratory infections such as influenza with remarkable curative effect. It can be preferentially used to treat infections of viruses and bacteria such as new coronaviruses and influenza viruses.
  • the rest is physiological water for injection, made into a total of 16000.00ml.
  • cantharidin anti-infective preparations of the present invention For patients with lung virus and germ infection, it is suitable for alternate application or combination with other cantharidin anti-infective preparations of the present invention during rescue.
  • Daily intravenous injection of 100.0-160.0ml (based on the amount of cantharidin is 0.1-0.3mg per day). It can be used to treat infections of viruses and bacteria such as new coronaviruses and influenza viruses.
  • 60kg adults treat respiratory virus and bacterial infections, 2-3 times a day, 8-16 tablets each time, equivalent to 0.32-1.44mg pure cantharidin. It can be used to treat infections of viruses and bacteria such as new coronaviruses and influenza viruses.
  • the total amount produced 10,000 grains, each grain weighs 0.392-0.588g.
  • 60kg adults treat respiratory virus and bacterial infections, 2-3 times a day, 8-16 capsules each time, which is equivalent to 0.32-1.44mg pure cantharidin. It can be used to treat infections of viruses and bacteria such as new coronaviruses and influenza viruses.
  • distilled water made: a total of 10000.0g of cantharidin is a common trauma cleaning agent for families and soldiers to prevent infection.
  • the preparation can be used to clean wounds and prevent trauma infections, and has been proved to be very effective through long-term clinical practice. It can also be sprayed on the nose and eyes to prevent and treat infections of viruses and bacteria such as new coronaviruses and influenza viruses. It is the sanitary cleaning supplies for households and soldiers.
  • the remaining olive oil is made into: a total of 1000.0g cantharidin nose and eye oil.
  • the preparation can be used to bandage trauma. It has been used in hospital surgical treatment rooms and rural primary medical institutions for a long time. It has been used in medical institutions for a long time. In tens of thousands of clinical practice, there is no case of wound infection treated with this preparation, indicating that the preparation is used for trauma. , Can completely kill viruses and bacteria that can infect humans. It can be preferentially used to prevent infections of viruses and germs such as new coronaviruses and influenza viruses.
  • cantharidin solution disinfection cloth towel cantharidin is 1.0-2.6ppm
  • preparation method of oil-water miscible solution is as follows:
  • the remainder is distilled water to make a solution with a total amount of 10000.0g and a cantharidin content of 1.0-2.6ppm.
  • the cotton fabric is soaked with the above solution to obtain a cantharidin solution disinfection cloth towel.
  • the cloth towel can be used as the lining of personnel masks, etc., and is a disposable disinfection and protection product for protecting against new coronary pneumonia and other viruses. It can be preferentially used to prevent infections of viruses and germs such as new coronaviruses and influenza viruses.
  • Cocoa butter 10.0g
  • cantharidin oil-oil mixed solution which is used as the traditional Chinese and Western medicine Combines the main effective ingredients of pills.
  • Cantharidin lysate (containing cantharidin 330.0mg): 126.0g
  • Astragalus extract 100.0g
  • cantharidin oral pills combined with Chinese and Western medicine were prepared. Each pill contains 0.33mg cantharidin. 60kg adults 2-3 times a day, 1 pill each time, equivalent to a daily dose of 0.66-1.0mg cantharidin. It can be preferentially used to prevent infections of viruses and germs such as new coronaviruses and influenza viruses.
  • the pathogens can be put into the solution separately and in groups according to conventional techniques, protected from light, at a constant temperature of 34-36°C, and continue to carry out various methods of cantharidin antibiotics. Research and experiment on ecological inactivated vaccines.
  • Example 1 For 2 suspected persons with obvious symptoms of the new coronavirus, use the cantharidin skin absorption lotion prepared in Example 1 to apply 2.0g on the chest, back, and limbs of a 60kg adult three times a day, after applying it for 12 hours. , The body temperature dropped to 37.6 °C, after 24 hours, the body temperature dropped to normal. On the 2nd day of medication, symptoms of chest tightness and anorexia began to be significantly reduced. After 4 days of continuous medication, the suspected person's symptoms disappeared and returned to normal.
  • Example 2 To 8 suspected persons with mild chest tightness and dry cough symptoms, use the cantharidin skin absorption lotion prepared in Example 1 to apply 2.0g on the skin of the chest, back and limbs three times a day for a 60kg adult. After 1 day, the symptoms of fatigue and dry cough alleviated. After 3 days of application, the suspected person’s symptoms disappeared completely and returned to normal.

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Abstract

Disclosed is a cantharidin antiviral and antibacterial preparation, containing cantharidin as an effective drug ingredient. The cantharidin is dissolved in an oil-water miscible substance or an oil-oil miscible substance to obtain a cantharidin solvent carrier, and the cantharidin solvent carrier is formulated with a pharmaceutically acceptable carrier or excipient into various dosage forms of antiviral and antibacterial drugs. The drugs can be used to prevent and treat a novel coronavirus infection, and the cantharidin solvent carrier can also be used as a solution for preparing an ecological antibiotic inactivated vaccine against novel coronavirus.

Description

一种斑蝥素抗病毒、抗菌制剂、其制备方法及用作预防和治疗新冠病毒感染Cantharidin antiviral and antibacterial preparation, its preparation method and its use for preventing and treating new coronavirus infection 技术领域Technical field
本发明涉及生物制药领域，具体的说是提供一种斑蝥素抗病毒、抗菌制剂及其制备方法。本发明提供的制剂可用于作为抗病毒、抗菌的预防和治疗的药物。特别是，在对新冠病毒、流感病毒、埃博拉病毒、艾滋病毒等病原体感染方面，也会具有重要的预防和治疗作用。The invention relates to the field of biopharmaceuticals, in particular to provide a cantharidin antiviral and antibacterial preparation and a preparation method thereof. The preparation provided by the invention can be used as antiviral and antibacterial preventive and therapeutic drugs. In particular, it will also have an important preventive and therapeutic effect on the infection of pathogens such as the new coronavirus, influenza virus, Ebola virus, and HIV.
背景技术Background technique
斑蝥素是一种动物的防御物质，它是一种高效、低毒、广谱的抗病毒、抗菌生物活性原料药，在我国医学上很早就有记载。Cantharidin is an animal's defensive substance. It is a high-efficiency, low-toxicity, broad-spectrum antiviral and antibacterial bioactive raw material drug, which has been recorded in Chinese medicine for a long time.
《神农本草经》、《本草纲目》记载：“斑蝥、芫菁、地胆……，解疔毒；猘犬毒……”。"Shen Nong's Materia Medica" and "Compendium of Materia Medica" record: "Cantharidin, Coriander, Earth gall... detoxify boil; Pygmy poison...".
斑蝥素也是一种现代西药原料药。百年前，西方医药学家已经将斑蝥素提纯，并研究了其物理性质、化学结构，在临床上将这种芫菁科昆虫的防御物质，定性为“皮肤刺激药、发疱药”。Cantharidin is also a kind of raw material of modern western medicine. A hundred years ago, Western medical scientists have purified cantharidin and studied its physical properties and chemical structure. Clinically, this defensive substance of the genus Lycane insects was classified as a "skin irritant, blistering drug".
制造防御物质，以抵抗各种微生物之能力，不独存在于动物体；即属下等植物，甚至细菌(1877年Pasteur与Joubert氏)有时亦能产生物质，以抑制或妨碍他种微生物之生长。此类物质被总称为抗生素(Antibiotics)。The ability to manufacture defensive substances to resist various microorganisms does not exist exclusively in animals; that is, subordinate plants and even bacteria (Pasteur and Joubert in 1877) can sometimes produce substances to inhibit or hinder the growth of other kinds of microorganisms. Such substances are collectively referred to as antibiotics (Antibiotics).
受上述古、今医药学成就的启发，本发明人1959年，设立了“斑蝥素是一种抗生素”的医药学研究课题。1963年，开始在农村做斑蝥素实验研究的动物抗病毒实验。1971年开始在农村基层医疗机构，用斑蝥素脂溶性“医疗院所制剂”，进行抗病毒、抗菌的临床实践和科研相结合的研究。Inspired by the above-mentioned ancient and modern medical achievements, the inventor set up the medical research project "Cantharidin is an antibiotic" in 1959. In 1963, began to do animal antiviral experiments on cantharidin experimental research in rural areas. Beginning in 1971, in rural primary medical institutions, using cantharidin fat-soluble "medical hospital preparations" to conduct research on the combination of antiviral and antibacterial clinical practice and scientific research.
上海1974年，批产了水溶性剂的《斑蝥素片》、《斑蝥素注射液》的药品 标准。用于治疗肿瘤的应用，其60kg体重的患者，每日剂量为4.0mg。In Shanghai, in 1974, water-soluble drug standards for "Cantharidin Tablets" and "Cantharidin Injection" were approved. For the application of the treatment of tumors, the daily dose is 4.0 mg for patients with a body weight of 60 kg.
本发明人在1980年6期《自然杂志》发表了《斑蝥素—抗病毒抗生素》。The inventor published "Cantharidin-Antiviral Antibiotic" in the 6th issue of "Nature Magazine" in 1980.
1991年12月5日，卫生部批产“四类新药”抗病毒药《斑蝥素乳膏》。On December 5, 1991, the Ministry of Health produced the "four new drugs" antiviral drug "Cantharidin Cream".
大量临床验证表明，斑蝥素乳膏治疗小儿秋季腹泻，有显著的退热、止吐、止泻效果。治疗后，48小时内有效率为97％，平均好转时间23.4小时，止吐时间19.7小时，退热时间为18.75小时，显著缩短了病程。外治法又可避免患儿呕吐带来的服药困难。治疗期间未发现皮肤局部不良反应和其他毒副作用。《斑蝥素乳膏》治疗婴泻是一种安全有效的药物。A large number of clinical verifications have shown that cantharidin cream has significant antipyretic, antiemetic and antidiarrheal effects in the treatment of children's autumn diarrhea. After treatment, the effective rate was 97% within 48 hours, the average improvement time was 23.4 hours, the antiemetic time was 19.7 hours, and the antipyretic time was 18.75 hours, which significantly shortened the course of the disease. External treatment can also avoid the difficulty of taking medicine caused by vomiting in children. During the treatment, no local adverse skin reactions and other side effects were found. "Cantharidin Cream" is a safe and effective medicine for treating infantile diarrhea.
本发明人在研制斑蝥素抗病毒、抗菌系列制剂，寻找斑蝥素的溶剂载体工作中，对应用油脂、精油制备斑蝥素抗病毒、抗菌系列制剂进行研究，并获得了ZL90106365.7和01140066.8专利。但是，研制斑蝥素抗病毒、抗菌系列制剂，寻找斑蝥素的溶剂载体工作，直至应用精油，远远没有取得理想的斑蝥素溶剂载体。In the development of cantharidin antiviral and antibacterial series preparations and the search for solvent carriers of cantharidin, the inventors studied the application of fats and essential oils to prepare cantharidin antiviral and antibacterial series preparations, and obtained ZL90106365.7 and 01140066.8 patents. However, the development of cantharidin antiviral and antibacterial series preparations, the search for the solvent carrier of cantharidin, until the application of essential oils, is far from obtaining an ideal cantharidin solvent carrier.
斑蝥素在水中的最大溶解度是33.33ppm；经过本医药学研究课题50余年的研究，单纯用水做斑蝥素溶剂载体，制成斑蝥素人体外靶点药效的制剂，当其水分挥发后,其最高药物浓度可达33.33ppm，与本课题长期大量斑蝥素毒理学研究结论，斑蝥素在人体靶点药物浓度为≤5.6ppm的数据相比，显而易见的药物浓度太高。因而单纯溶解于水中的斑蝥素制剂，在人体外靶点应用，就变成有毒副作用的“发疱剂”了，无法产生其斑蝥素应有的治疗作用。The maximum solubility of cantharidin in water is 33.33ppm; after more than 50 years of research in this medical research project, pure water is used as the solvent carrier of cantharidin to prepare a formulation of cantharidin human in vitro target efficacy. When its water evaporates, its highest The drug concentration can reach 33.33ppm. Compared with the long-term large number of cantharidin toxicology studies in this subject, compared with the data of the target drug concentration of cantharidin in the human body ≤5.6ppm, it is obvious that the drug concentration is too high. Therefore, cantharidin preparations that are simply dissolved in water become "blistering agents" with toxic and side effects when applied to targets outside the body, and cannot produce the therapeutic effects that cantharidin should have.
目前，新冠病毒已经肆虐全球，虽然有证据显示瑞德西韦、氯喹及某些中药对抑制新冠病毒有一定疗效，但是远不能遏止病毒的大规模传播。因此人们把控制新冠病毒的希望寄托在尽快研制疫苗上。在制备疫苗中，有一类是灭活疫苗，也是最传统的疫苗，病原体已经失去活性，因此在临床应用，安全性好且简便。研制抗新冠病毒疫苗的关键步骤之一是寻找一种能够抑制或杀灭对人体侵染的新冠病毒病原体，同时不伤害人体的正常生理功能的载体。At present, the new crown virus has ravaged the world. Although there is evidence that remdesivir, chloroquine and certain Chinese medicines have a certain effect on suppressing the new crown virus, they are far from stopping the large-scale spread of the virus. Therefore, people pin their hopes of controlling the new coronavirus on the development of a vaccine as soon as possible. In the preparation of vaccines, there is a type of inactivated vaccines, which is also the most traditional vaccine. The pathogen has lost its activity. Therefore, it is safe and simple in clinical application. One of the key steps in the development of an anti-coronavirus vaccine is to find a carrier that can inhibit or kill the neocoronavirus pathogen that infects the human body without harming the normal physiological functions of the human body.
至今，还没有见到“斑蝥素用作预防和治疗新冠病毒等病原体感染的药物及斑蝥素用作制备抗新冠病毒疫苗用的生态抗生素溶体”的报道。So far, there has been no report of "cantharidin used as a drug for preventing and treating infections by pathogens such as the new coronavirus and cantharidin used as an ecological antibiotic solution for the preparation of vaccines against the new coronavirus".
发明内容Summary of the invention
为了解决上述斑蝥素药剂学、毒理学难点，本发明人课题经长期研究发现，选用油油互溶体，或选用油水互溶体做斑蝥素的溶剂载体，制成的制剂，克服了斑蝥素制剂的药剂学、毒理学难点，能使斑蝥素的高效抗病毒、抗菌药效得以安全、理想发挥。In order to solve the above-mentioned difficulties in cantharidin pharmacology and toxicology, the inventor of the present invention has discovered through long-term research that the use of oil-oil mutual solubles or oil-water mutual solubles as the solvent carrier of cantharidin has been made to overcome the problems of cantharidin preparations. Difficulties in pharmacy and toxicology can make cantharidin's high-efficiency antiviral and antibacterial efficacy safe and ideal.
在选用油剂时，单纯应用一种油剂，尚达不到斑蝥素药剂学、药理学、毒理学的要求，必须从多种油剂中选择顺应斑蝥素理化性质的油剂，以达到斑蝥素药理作用显著提高的目的。When selecting an oil agent, simply using one oil agent cannot meet the requirements of cantharidin pharmacology, pharmacology, and toxicology. It is necessary to choose an oil agent that conforms to the physical and chemical properties of cantharidin from a variety of oil agents to achieve cantharidin. The purpose of significantly improving the pharmacological effect of the element.
《合成实用香料手册》记载，目前，国外已经认定能安全食用的香料有1700多种。包括：烃类及其衍生物、醇类、醚类、酚类及其衍生物、醛类、缩醛类、酮类、内酯类、酸类、酯类、含硫含氮化合物……。本发明经过多年的实验研究，发现只有酮类和内酯类的精油适合做斑蝥素的溶剂载体，具有一定的实用性。According to the "Handbook of Synthetic Practical Flavors", there are currently more than 1,700 flavors recognized as safe for consumption abroad. Including: hydrocarbons and their derivatives, alcohols, ethers, phenols and their derivatives, aldehydes, acetals, ketones, lactones, acids, esters, sulfur-containing and nitrogen-containing compounds... After years of experimental research, the present invention has found that only essential oils of ketones and lactones are suitable as solvent carriers of cantharidin and have certain practicability.
本发明选用油油互溶体、油水互溶体做斑蝥素的溶剂载体，取得在斑蝥素药剂学、毒理学，药效学方面比ZL90106365.7和01140066.8发明专利中所应用的油脂、精油，有显著提高。The present invention selects oil-oil mutual soluble and oil-water mutual solubles as the solvent carrier of cantharidin, and obtains significant advantages in cantharidin pharmacy, toxicology, and pharmacodynamics than the oils and essential oils used in the ZL90106365.7 and 01140066.8 invention patents. improve.
为了提供用作预防和治疗新冠病毒的药物及用于制备抗新冠病毒疫苗用的生态抗生素溶体，本发明的第一方面是，提供一种斑蝥素抗病毒、抗菌制剂，含有斑蝥素作为有效药物成分，所述斑蝥素溶解于油水互溶体或油油互溶体得到斑蝥素溶剂载体，将所述斑蝥素溶剂载体与可药用载体或赋形剂配制而成多种剂型用作预防和治疗新冠病毒的药物。In order to provide drugs for the prevention and treatment of new coronaviruses and ecological antibiotic solutions for preparing vaccines against new coronaviruses, the first aspect of the present invention is to provide an antiviral and antibacterial cantharidin preparation containing cantharidin as an effective drug Ingredients, the cantharidin is dissolved in an oil-water mutual soluble or an oil-oil mutual soluble to obtain a cantharidin solvent carrier, and the cantharidin solvent carrier is formulated with a pharmaceutically acceptable carrier or excipient into a variety of dosage forms for the prevention and treatment of new crowns Viral drugs.
优选的，所述油水互溶体或油油互溶体含有酮类和/或内酯类的精油。Preferably, the oil-water mutual solution or the oil-oil mutual solution contains essential oils of ketones and/or lactones.
本发明的第二方面是，提供一种用作预防和治疗新冠病毒的斑蝥素皮肤吸收涂剂，含有斑蝥素作为有效药物成分，斑蝥素溶剂载体为油水互溶体，包括：The second aspect of the present invention is to provide a cantharidin skin absorption lotion for the prevention and treatment of new coronavirus, which contains cantharidin as an effective pharmaceutical ingredient, and the solvent carrier of cantharidin is an oil-water mutual solution, including:
斑蝥素：160-200mgCantharidin: 160-200mg
植物油：8.0-12.0gVegetable oil: 8.0-12.0g
动物油：8.0-12.0gAnimal oil: 8.0-12.0g
酮类精油：40.0-60.0gKetone essential oil: 40.0-60.0g
十八醇：20.0-40.0gStearyl alcohol: 20.0-40.0g
硬脂酸：20.0-40.0gStearic acid: 20.0-40.0g
乳化剂(吐温-80)40-60.0gEmulsifier (Tween-80) 40-60.0g
其余蒸馏水：总量1000.0gThe rest of distilled water: total 1000.0g
制成每克含斑蝥素0.16-0.2mg的透皮吸收涂剂。A transdermal absorption lotion containing 0.16-0.2mg of cantharidin per gram is prepared.
本发明的第三方面是，提供一种用作治疗新冠病毒的、油水互溶体为斑蝥素溶剂载体的静脉注射剂，含有斑蝥素作为有效药物成分，按下列成份：The third aspect of the present invention is to provide an intravenous injection for the treatment of neocoronavirus with an oil-water mutual solution as a solvent carrier of cantharidin, which contains cantharidin as an effective pharmaceutical ingredient, according to the following ingredients:
斑蝥素：15.0-30.0mgCantharidin: 15.0-30.0mg
2-丁酮：30.0-60.0g2-Butanone: 30.0-60.0g
3-庚酮：0.3-0.6g3-Heptanone: 0.3-0.6g
2-仲丁基环已酮：0.3-0.6g2-sec-butyl cyclohexanone: 0.3-0.6g
其余为生理注射用水：总量16000.00g。The rest is physiological water for injection: total 16000.00g.
本发明的第四方面是，提供一种用作治疗新冠病毒的、油油互溶体为斑蝥素溶剂载体的斑蝥素片，含有斑蝥素作为有效药物成分，包括：The fourth aspect of the present invention is to provide a cantharidin tablet with a cantharidin solvent carrier as a cantharidin solvent for the treatment of new coronaviruses, containing cantharidin as an effective drug ingredient, including:
斑蝥素：200.0-300.0mgCantharidin: 200.0-300.0mg
可可脂：80.0-120.0gCocoa butter: 80.0-120.0g
橄榄油：60.0-90.0gOlive oil: 60.0-90.0g
2-丁酮：60.0-90.0g2-Butanone: 60.0-90.0g
2-仲丁基环已酮：200.0-300.0g2-sec-butyl cyclohexanone: 200.0-300.0g
淀粉：3200.0-4800.0gStarch: 3200.0-4800.0g
谷朊粉：320.0-480.0gGluten: 320.0-480.0g
制成总量：10000片；每片片重0.392-0.588g的斑蝥素片。Total produced: 10,000 tablets; cantharidin tablets each weighing 0.392-0.588g.
本发明的第五方面是，提供一种用作治疗新冠病毒的、油油互溶体为斑蝥素溶剂载体的斑蝥素胶囊，含有斑蝥素作为有效药物成分，包括：The fifth aspect of the present invention is to provide a cantharidin capsule for the treatment of the new coronavirus, with an oil-oil mutual soluble as a cantharidin solvent carrier, which contains cantharidin as an effective pharmaceutical ingredient, including:
斑蝥素：200.0-300.0mgCantharidin: 200.0-300.0mg
脱臭牛脂：80.0-120.0gDeodorized tallow: 80.0-120.0g
橄榄油：60.0-90.0gOlive oil: 60.0-90.0g
2-丁酮：60.0-90.0g2-Butanone: 60.0-90.0g
6-羟基-3，7-二甲基辛酸内酯：200.0-300.0g6-hydroxy-3,7-dimethylcaprylic acid lactone: 200.0-300.0g
淀粉：3200.0-4800.0gStarch: 3200.0-4800.0g
谷朊粉：320.0-480.0gGluten: 320.0-480.0g
制成总量：10000粒，每粒粒重0.392-0.588g的斑蝥素胶囊。A total of 10,000 cantharidin capsules with a weight of 0.392-0.588g each are made.
本发明的第六方面是，提供一种用作预防新冠病毒的、油水互溶体为斑蝥素溶剂载体的斑蝥素鼻眼喷剂，含有斑蝥素作为有效药物成分，包括：The sixth aspect of the present invention is to provide a cantharidin nasal and eye spray which is used as the prevention of new coronavirus, and the oil-water mutual soluble solvent is the solvent carrier of cantharidin, which contains cantharidin as an effective drug ingredient, which includes:
斑蝥素：1.6-3.2mgCantharidin: 1.6-3.2mg
95％乙醇:375.0-525.0g95% ethanol: 375.0-525.0g
2-丁酮：80.0-120.0g2-Butanone: 80.0-120.0g
丙二醇：495.0-725.0gPropylene glycol: 495.0-725.0g
苯甲醇：6.0-12.0gBenzyl alcohol: 6.0-12.0g
2-苯乙醇：6.0-12.0g2-Phenylethanol: 6.0-12.0g
覆盆子酮：3.0-6.0gRaspberry ketone: 3.0-6.0g
余量为蒸馏水：总量为10000.0g的斑蝥素鼻眼喷剂。The balance is distilled water: a total of 10000.0g cantharidin nose and eye spray.
本发明的第七方面是，提供一种用作预防新冠病毒的、油油互溶体为斑蝥素溶剂载体的斑蝥素鼻眼药油，含有斑蝥素作为有效药物成分，包括：The seventh aspect of the present invention is to provide a cantharidin nasal and ophthalmic oil for the prevention of new coronaviruses, the oil-oil mutual soluble as the solvent carrier of cantharidin, which contains cantharidin as an effective pharmaceutical ingredient, and includes:
斑蝥素：2.2-3.6mgCantharidin: 2.2-3.6mg
2-丁酮：80.0-120.0g2-Butanone: 80.0-120.0g
覆盆子酮：3.0-6.0g，Raspberry ketone: 3.0-6.0g,
其余为橄榄油：制成总量为1000.0g的斑蝥素鼻眼药油。The rest is olive oil: a total of 1000.0g cantharidin nose and eye oil is made.
本发明的第八方面是，提供一种用作预防新冠病毒的、油水互溶体为斑蝥素溶剂载体的斑蝥素溶液消毒布巾，含有斑蝥素作为有效药物成分，包括：The eighth aspect of the present invention is to provide a cantharidin solution disinfectant cloth used as a prevention of new coronavirus, oil-water mutual soluble as cantharidin solvent carrier, containing cantharidin as an effective drug ingredient, including:
斑蝥素：1.0-2.6mgCantharidin: 1.0-2.6mg
95％乙醇:500.0-600.0g95% ethanol: 500.0-600.0g
2-丁酮：40.0-60.0g2-Butanone: 40.0-60.0g
丙二醇：425.0-525.0gPropylene glycol: 425.0-525.0g
苯甲醇：8.0-10.0gBenzyl alcohol: 8.0-10.0g
2-苯乙醇：8.0-10.0g2-Phenylethanol: 8.0-10.0g
覆盆子酮：2.0-4.0gRaspberry Ketone: 2.0-4.0g
余量为蒸馏水，制得10000.0g。将所得溶剂喷涂在载体上，制成斑蝥素溶液消毒布巾。The remainder is distilled water, making 10000.0g. The obtained solvent is sprayed on the carrier to prepare a cantharidin solution disinfection cloth towel.
本发明的第九方面是，提供一种用作治疗新冠病毒的斑蝥素中西药结合口服丸剂，含有斑蝥素作为有效药物成分，斑蝥素溶剂载体为油油互溶体，按下列成份：The ninth aspect of the present invention is to provide a combined oral pill of cantharidin Chinese and Western medicine for the treatment of new coronavirus, which contains cantharidin as an effective drug ingredient, and the solvent carrier of cantharidin is an oil-oil mutual soluble substance, according to the following ingredients:
斑蝥素溶体，按下列成份：Cantharidin solution, according to the following ingredients:
斑蝥素：330.0mgCantharidin: 330.0mg
橄榄油：20.0gOlive oil: 20.0g
可可脂：10.0gCocoa butter: 10.0g
γ-任内酯：6.0gγ-Rhinolactone: 6.0g
2-丁酮：30.0g2-Butanone: 30.0g
2-仲丁基环已酮：60.0g2-sec-butyl cyclohexanone: 60.0g
斑蝥素中西药结合口服丸剂，按下列成份：Cantharidin combined with Chinese and Western medicine oral pills, according to the following ingredients:
斑蝥素溶体(含斑蝥素330.0mg):126.0gCantharidin lysate (containing cantharidin 330.0mg): 126.0g
淀粉：2000.0gStarch: 2000.0g
谷朊粉：274.0gGluten: 274.0g
黄芪提取物：100.0gAstragalus extract: 100.0g
中蜂蜂蜜：2500.0gChina Bee Honey: 2500.0g
制成斑蝥素中西药结合口服丸剂1000丸，每丸含斑蝥素0.33mg。1000 cantharidin oral pills combined with Chinese and Western medicine were prepared, each of which contained 0.33mg cantharidin.
本发明的第十方面是，提供一种油水互溶预防外伤感染的家庭、士兵常备的清洗剂，其特征在于，所述溶体为斑蝥素油水互溶体，按下述成分：The tenth aspect of the present invention is to provide a cleaning agent prepared by families and soldiers who are mutually soluble in oil and water to prevent traumatic infections, characterized in that the solution is a cantharidin oil-water mutual soluble body, and has the following components:
斑蝥素：1.6-3.2mgCantharidin: 1.6-3.2mg
95％乙醇:375.0-525.0g95% ethanol: 375.0-525.0g
2-丁酮：80.0-120.0g2-Butanone: 80.0-120.0g
丙二醇：495.0-725.0gPropylene glycol: 495.0-725.0g
苯甲醇：6.0-12.0gBenzyl alcohol: 6.0-12.0g
2-苯乙醇：6.0-12.0g2-Phenylethanol: 6.0-12.0g
覆盆子酮：3.0-6.0gRaspberry ketone: 3.0-6.0g
余量为蒸馏水。制成：总量为10000.0g的斑蝥素预防外伤感染的家庭、士兵常备的清洗剂。The balance is distilled water. Preparation: 10000.0g of cantharidin is a cleaning agent for families and soldiers who prevent traumatic infections.
本发明的第十一方面是，提供一种预防HIV性行为传染的斑蝥素抗病毒、抗菌无形避孕套，其特征在于，所述溶体为斑蝥素油水互溶体，按下列成份：The eleventh aspect of the present invention is to provide a cantharidin antiviral and antibacterial invisible condom for preventing HIV sexual transmission. It is characterized in that the solution is a cantharidin oil-water mutual solution, and has the following ingredients:
斑蝥素：16.0—36.0mgCantharidin: 16.0-36.0mg
95％乙醇:100.0-300.0g95% ethanol: 100.0-300.0g
丙二醇：495.0-725.0gPropylene glycol: 495.0-725.0g
丙三醇：495.0-725.0gGlycerol: 495.0-725.0g
乳酸：1000.0gLactic acid: 1000.0g
乳酸钠：2000.0gSodium lactate: 2000.0g
苯甲醇：16.0-21.0gBenzyl alcohol: 16.0-21.0g
2-苯乙醇：6.0-12.0g2-Phenylethanol: 6.0-12.0g
透明质酸：30.0—120.0gHyaluronic acid: 30.0-120.0g
瓜尔豆胶：10.0—40.0gGuar Gum: 10.0-40.0g
余量为蒸馏水，制成：总量为10000.0g的预防HIV性行为传染的斑蝥素无形避孕套。The remainder is distilled water to make: a total of 10000.0g cantharidin invisible condom for preventing HIV sexual transmission.
本发明的第十二方面是，提供一种制备抗新冠病毒灭活疫苗用的斑蝥素抗生素溶体，含有斑蝥素作为有效药物成分，为含有1.6ppm≤斑蝥素≤3.6ppm的溶体。The twelfth aspect of the present invention is to provide a cantharidin antibiotic solution for preparing an anti-new coronavirus inactivated vaccine, which contains cantharidin as an effective drug ingredient, and is a solution containing 1.6 ppm ≤ cantharidin ≤ 3.6 ppm.
优选的，所述含有1.6ppm≤斑蝥素≤3.6ppm的溶体为斑蝥素油油互溶体或斑蝥素油水互溶体。Preferably, the solution containing 1.6 ppm≤cantharidin≤3.6ppm is a cantharidin oil-oil mutual soluble or a cantharidin oil-water mutual soluble.
优选的，油油互溶体为斑蝥素溶剂载体，包括：2-丁酮和橄榄油，所述斑蝥素含量为1.6-3.6ppm，所述2-丁酮含量为8-12重量％，其余为所述橄榄油。Preferably, the oil-oil mutual solution is a cantharidin solvent carrier, including: 2-butanone and olive oil, the cantharidin content is 1.6-3.6 ppm, the 2-butanone content is 8-12% by weight, and the rest is The olive oil.
优选的，油水互溶体为斑蝥素溶剂载体，包括：斑蝥素，含量为1.6-3.6ppm；乙醇，含量为:3.75-5.2重量％；2-丁酮，含量为：0.8-1.2重量％；丙二醇，含量为：4.95-7.2 5重量％；苯甲醇，含量为：0.06-0.12重量％；2-苯乙醇，含量为：0.06-0.12重量％；覆盆子酮，含量为：0.03.-0.06重量％；其余为蒸馏水。Preferably, the oil-water mutual solution is a cantharidin solvent carrier, including: cantharidin, the content is 1.6-3.6ppm; ethanol, the content is 3.75-5.2% by weight; 2-butanone, the content is: 0.8-1.2% by weight; propylene glycol , The content is: 4.95-7.2 5 wt%; benzyl alcohol, the content is: 0.06-0.12 wt%; 2-phenylethanol, the content is: 0.06-0.12 wt%; the raspberry ketone, the content is: 0.03.-0.06% by weight ; The rest is distilled water.
本发明的第十三方面是，提供一种制备抗新冠病毒灭活疫苗用斑蝥素抗生素溶体的配制方法，是将一定量斑蝥素及2-丁酮溶解在橄榄油中后，再加入橄榄油到所述斑蝥素含量为1.6-3.6ppm，所述2-丁酮含量为8-12重量％，其余为所述橄榄油的斑蝥素抗生素溶体。The thirteenth aspect of the present invention is to provide a method for preparing a cantharidin antibiotic solution for preparing an anti-new coronavirus inactivated vaccine, which is to dissolve a certain amount of cantharidin and 2-butanone in olive oil, and then add the olive oil Until the cantharidin content is 1.6-3.6 ppm, the 2-butanone content is 8-12% by weight, and the rest is the cantharidin antibiotic solution of the olive oil.
本发明的第十四方面是，提供一种制备抗新冠病毒灭活疫苗用斑蝥素抗生素溶体的配制方法，是将一定量斑蝥素，含量为1.6-3.6ppm；乙醇，含量为:3.75-5.25重量％；2-丁酮，含量为：0.8-1.2重量％；丙二醇，含量为：4.95-7.25重量％；苯甲醇，含量为：0.06-0.12重量％；2-苯乙醇，含量为：0.06-0.12重量％；覆盆子酮，含量为：0.03.-0.06重量％；溶解在蒸馏水后，再加入蒸馏水得到斑蝥素抗生素溶体。The fourteenth aspect of the present invention is to provide a preparation method for preparing cantharidin antibiotic solution for inactivated vaccine against new coronavirus, which is to combine a certain amount of cantharidin with a content of 1.6-3.6 ppm; ethanol with a content of: 3.75-5.25 Weight%; 2-butanone, content: 0.8-1.2% by weight; Propylene glycol, content: 4.95-7.25% by weight; Benzyl alcohol, content: 0.06-0.12% by weight; 2-Phenylethanol, content: 0.06- 0.12% by weight; raspberry ketone, the content is: 0.03.-0.06% by weight; after being dissolved in distilled water, distilled water is added to obtain a cantharidin antibiotic solution.
本发明的≤5.6ppm的斑蝥素溶剂作为溶体，可用于制造抗生素“生态”灭活疫苗。使用这种溶体，不使用物理方法，化学方法，而是用斑蝥素溶液的生态生物活性，灭活病原体制成病毒或细菌灭活疫苗。在生态理论上，较之用高温或化学方法灭活疫苗，本发明其抗原性将更加理想，是高度值得试验的制造灭活疫苗的一条新的技术路线。The cantharidin solvent ≤5.6 ppm of the present invention is used as a solution and can be used to manufacture antibiotic "ecological" inactivated vaccines. The use of this solution does not use physical methods or chemical methods, but uses the ecological biological activity of the cantharidin solution to inactivate pathogens to make virus or bacterial inactivated vaccines. In ecological theory, compared with inactivating vaccines by high temperature or chemical methods, the antigenicity of the present invention will be more ideal, and it is a new technical route for manufacturing inactivated vaccines that is highly worth testing.
下面，通过实施例对本发明的技术方案给予进一步的说明。Hereinafter, the technical solution of the present invention will be further explained through examples.
具体实施方式Detailed ways
这里将详细地对示例性实施例进行说明，以下示例性实施例中所描述的实施方式并不代表与本发明相一致的所有实施方式。它们仅是进一步所详述地说明本发明一些方面相一致的斑蝥素抗生素溶体及其配制方法的例子。The exemplary embodiments will be described in detail here, and the implementation manners described in the exemplary embodiments below do not represent all implementation manners consistent with the present invention. They are only examples of cantharidin antibiotic solutions and their formulation methods that further illustrate some aspects of the present invention in detail.
在下面实施例中使用的原料：Raw materials used in the following examples:
1、斑蝥素为按现有技术(ZL专利号90106365.7或01140066.8)得到的精制斑蝥素。1. Cantharidin is a refined cantharidin obtained according to the prior art (ZL patent number 90106365.7 or 01140066.8).
2、其它原料为精制工业品。2. Other raw materials are refined industrial products.
实施例1Example 1
制备油油互溶体的斑蝥素皮肤吸收涂剂，按下列成份：Prepare the cantharidin skin absorption lotion of oil-oil mutual soluble body, according to the following ingredients:
斑蝥素：160.0-200.0mgCantharidin: 160.0-200.0mg
植物油：8.0-12.0gVegetable oil: 8.0-12.0g
动物油：8.0-12.0gAnimal oil: 8.0-12.0g
酮类精油：40.0-60.0gKetone essential oil: 40.0-60.0g
十八醇：20.0-40.0gStearyl alcohol: 20.0-40.0g
硬脂酸：20.0-40.0gStearic acid: 20.0-40.0g
乳化剂(吐温-80)40-60.0gEmulsifier (Tween-80) 40-60.0g
其余蒸馏水：总量1000.0gThe rest of distilled water: total 1000.0g
制成每克含斑蝥素0.16-0.2mg的皮肤吸收涂剂。A skin absorption lotion containing 0.16-0.2mg of cantharidin per gram is prepared.
60kg成人每天在胸、背、四肢皮肤涂抹三次，每次应用2.0g该皮肤吸收 涂剂，该皮肤吸收涂剂中含斑蝥素0.32-0.4mg。该制剂通过淋巴系统进入血液循环，在斑蝥素人体内脏靶点发挥药效，治疗流感等呼吸系统感染，疗效显著。可优先选用于治疗新冠病毒、流感病毒等病毒、病菌的感染。An adult of 60 kg should apply the skin absorption lotion three times a day on the skin of the chest, back, and extremities, each time applying 2.0 g of the skin absorption lotion. The skin absorption lotion contains 0.32-0.4 mg cantharidin. The preparation enters the blood circulation through the lymphatic system, exerts a medicinal effect on the internal organs of cantharidin, and treats respiratory infections such as influenza with remarkable curative effect. It can be preferentially used to treat infections of viruses and bacteria such as new coronaviruses and influenza viruses.
实施例2Example 2
制备油水互溶体为斑蝥素溶剂载体的静脉注射剂，按下述成份：To prepare an intravenous injection in which the oil-water mutual solution is the solvent carrier of cantharidin, the following ingredients are used:
斑蝥素：15.0-30.0mgCantharidin: 15.0-30.0mg
2-丁酮：30.0-60.0g2-Butanone: 30.0-60.0g
3-庚酮：0.3-0.6g3-Heptanone: 0.3-0.6g
2-仲丁基环已酮：0.3-0.6g2-sec-butyl cyclohexanone: 0.3-0.6g
其余为生理注射用水，制成总量16000.00ml。The rest is physiological water for injection, made into a total of 16000.00ml.
对肺部病毒、病菌感染患者，适合抢救时和其他本发明斑蝥素抗感染制剂交替应用或合用。每日静脉注射100.0-160.0ml(以斑蝥素量计为每日0.1-0.3mg)。可选用于治疗新冠病毒、流感病毒等病毒、病菌的感染。For patients with lung virus and germ infection, it is suitable for alternate application or combination with other cantharidin anti-infective preparations of the present invention during rescue. Daily intravenous injection of 100.0-160.0ml (based on the amount of cantharidin is 0.1-0.3mg per day). It can be used to treat infections of viruses and bacteria such as new coronaviruses and influenza viruses.
实施例3Example 3
制备油油互溶体为斑蝥素溶剂载体的斑蝥素片，按下述成分：The preparation of cantharidin tablets with the oil-oil mutual soluble substance as the solvent carrier of cantharidin is as follows:
斑蝥素：200.0-300.0mgCantharidin: 200.0-300.0mg
橄榄油：60.0-90.0gOlive oil: 60.0-90.0g
2-丁酮：60.0-90.0g2-Butanone: 60.0-90.0g
2-仲丁基环已酮：200.0-300.0g2-sec-butyl cyclohexanone: 200.0-300.0g
淀粉：3200.0-4800.0gStarch: 3200.0-4800.0g
谷朊粉：320.0-480.0gGluten: 320.0-480.0g
制成总量：10000片；每片片重0.384-0.58g。Total produced: 10,000 pieces; each piece weighs 0.384-0.58g.
60kg成人治疗呼吸系统病毒、细菌感染，一日2-3次，一次8-16片，相当于含纯斑蝥素0.32-1.44mg。可选用于治疗新冠病毒、流感病毒等病毒、病菌的感染。60kg adults treat respiratory virus and bacterial infections, 2-3 times a day, 8-16 tablets each time, equivalent to 0.32-1.44mg pure cantharidin. It can be used to treat infections of viruses and bacteria such as new coronaviruses and influenza viruses.
实施例4Example 4
制备油油互溶体为斑蝥素溶剂载体的斑蝥素胶囊，按下述成分：To prepare the cantharidin capsules with the oil-oil mutual soluble substance as the solvent carrier of cantharidin, according to the following ingredients:
斑蝥素：200.0-300.0mgCantharidin: 200.0-300.0mg
脱臭牛脂：80.0-120.0gDeodorized tallow: 80.0-120.0g
橄榄油：60.0-90.0gOlive oil: 60.0-90.0g
2-丁酮：60.0-90.0g2-Butanone: 60.0-90.0g
6-羟基-3，7-二甲基辛酸内酯：200.0-300.0g6-hydroxy-3,7-dimethylcaprylic acid lactone: 200.0-300.0g
淀粉：3200.0-4800.0gStarch: 3200.0-4800.0g
谷朊粉：320.0-480.0gGluten: 320.0-480.0g
制成总量：10000粒，每粒粒重0.392-0.588g。The total amount produced: 10,000 grains, each grain weighs 0.392-0.588g.
60kg成人治疗呼吸系统病毒、细菌感染，一日2-3次，一次8-16粒，相当于含纯斑蝥素0.32-1.44mg。可选用于治疗新冠病毒、流感病毒等病毒、病菌的感染。60kg adults treat respiratory virus and bacterial infections, 2-3 times a day, 8-16 capsules each time, which is equivalent to 0.32-1.44mg pure cantharidin. It can be used to treat infections of viruses and bacteria such as new coronaviruses and influenza viruses.
实施例5Example 5
制备油水互溶的杜绝感染的家庭、士兵常备的外伤清洗剂，按下述成分：Prepare oil-water-miscible trauma cleaning agent for households and soldiers to prevent infection, according to the following ingredients:
斑蝥素：1.6-3.2mgCantharidin: 1.6-3.2mg
95％乙醇:375.0-525.0g95% ethanol: 375.0-525.0g
2-丁酮：80.0-120.0g2-Butanone: 80.0-120.0g
丙二醇：495.0-725.0gPropylene glycol: 495.0-725.0g
苯甲醇：6.0-12.0gBenzyl alcohol: 6.0-12.0g
2-苯乙醇：6.0-12.0g2-Phenylethanol: 6.0-12.0g
覆盆子酮：3.0-6.0gRaspberry ketone: 3.0-6.0g
余量为蒸馏水，制成：总量为10000.0g的斑蝥素杜绝感染的家庭、士兵常备的外伤清洗剂。The remainder is distilled water, made: a total of 10000.0g of cantharidin is a common trauma cleaning agent for families and soldiers to prevent infection.
该制剂可用于清洗伤口，预防外伤感染，经长期临床实践，证明十分有效。也可选用喷于鼻、眼，预防和治疗新冠病毒、流感病毒等病毒、病菌的感染。是家庭、士兵常备卫生清洗用品。The preparation can be used to clean wounds and prevent trauma infections, and has been proved to be very effective through long-term clinical practice. It can also be sprayed on the nose and eyes to prevent and treat infections of viruses and bacteria such as new coronaviruses and influenza viruses. It is the sanitary cleaning supplies for households and soldiers.
实施例6Example 6
制备油油互溶的斑蝥素鼻眼药油，按下述成分：Prepare the oil-oil-soluble cantharidin nose and eye oil according to the following ingredients:
斑蝥素：2.2-3.6mgCantharidin: 2.2-3.6mg
2-丁酮：80.0-120.0g2-Butanone: 80.0-120.0g
覆盆子酮：3.0-6.0g，Raspberry ketone: 3.0-6.0g,
余量橄榄油，制成：总量为1000.0g斑蝥素鼻眼药油。The remaining olive oil is made into: a total of 1000.0g cantharidin nose and eye oil.
该制剂可用于包扎外伤，在医院外科处置室、农村基层医疗机构，长期以医疗院所制剂加以应用，数万例临床实践，未见一例用该制剂处置的创伤感染，说明该制剂用于外伤，能够完全杀灭可感染人的病毒、细菌。可优先选用于预防新冠病毒、流感病毒等病毒、病菌的感染。The preparation can be used to bandage trauma. It has been used in hospital surgical treatment rooms and rural primary medical institutions for a long time. It has been used in medical institutions for a long time. In tens of thousands of clinical practice, there is no case of wound infection treated with this preparation, indicating that the preparation is used for trauma. , Can completely kill viruses and bacteria that can infect humans. It can be preferentially used to prevent infections of viruses and germs such as new coronaviruses and influenza viruses.
实施例7Example 7
制备斑蝥素溶液消毒布巾，斑蝥素为1.0-2.6ppm，油水互溶溶液的配制方法如下：Prepare cantharidin solution disinfection cloth towel, cantharidin is 1.0-2.6ppm, the preparation method of oil-water miscible solution is as follows:
斑蝥素：1.0-2.6mgCantharidin: 1.0-2.6mg
95％乙醇:500.0-600.0g95% ethanol: 500.0-600.0g
2-丁酮：40.0-60.0g2-Butanone: 40.0-60.0g
丙二醇：425.0-525.0gPropylene glycol: 425.0-525.0g
苯甲醇：8.0-10.0gBenzyl alcohol: 8.0-10.0g
2-苯乙醇：8.0-10.0g2-Phenylethanol: 8.0-10.0g
覆盆子酮：2.0-4.0gRaspberry Ketone: 2.0-4.0g
余量为蒸馏水，制成：总量为10000.0g，斑蝥素为1.0-2.6ppm的溶液。The remainder is distilled water to make a solution with a total amount of 10000.0g and a cantharidin content of 1.0-2.6ppm.
将棉质织布用上述溶液浸透，得到斑蝥素溶液消毒布巾。该布巾可用于人员口罩内衬等，是防护新冠肺炎等病毒的一次性消毒防护用品。可优先选用于预防新冠病毒、流感病毒等病毒、病菌的感染。The cotton fabric is soaked with the above solution to obtain a cantharidin solution disinfection cloth towel. The cloth towel can be used as the lining of personnel masks, etc., and is a disposable disinfection and protection product for protecting against new coronary pneumonia and other viruses. It can be preferentially used to prevent infections of viruses and germs such as new coronaviruses and influenza viruses.
实施例8Example 8
制备斑蝥素中西药结合口服丸剂Preparation of oral pills of cantharidin combined with traditional Chinese and western medicine
油油互溶的斑蝥素溶体的制备：Preparation of cantharidin lysate that is miscible with oil and oil:
斑蝥素：330.0mgCantharidin: 330.0mg
橄榄油：20.0gOlive oil: 20.0g
可可脂：10.0gCocoa butter: 10.0g
γ-任内酯：6.0gγ-Rhinolactone: 6.0g
2-丁酮：30.0g2-Butanone: 30.0g
2-仲丁基环已酮：60.0g2-sec-butyl cyclohexanone: 60.0g
斑蝥素中西药结合口服丸剂的制备：Preparation of oral pills of cantharidin combined with Chinese and Western medicine:
将330.0mg斑蝥素投入到组合油中，加热至60-70℃，持续保持30分钟左右，直至斑蝥素全部溶解，室温环境自然冷却，即制成斑蝥素的油油混合溶液，作为本中西药结合丸剂的主要有效成份。Put 330.0mg of cantharidin into the combined oil, heat it to 60-70°C and keep it for about 30 minutes until the cantharidin is completely dissolved, and the room temperature environment is naturally cooled to make a cantharidin oil-oil mixed solution, which is used as the traditional Chinese and Western medicine Combines the main effective ingredients of pills.
斑蝥素溶体(含斑蝥素330.0mg):126.0gCantharidin lysate (containing cantharidin 330.0mg): 126.0g
淀粉：2000.0gStarch: 2000.0g
谷朊粉：274.0gGluten: 274.0g
黄芪提取物：100.0gAstragalus extract: 100.0g
中蜂蜂蜜：2500.0gChina Bee Honey: 2500.0g
制成斑蝥素中西药结合口服丸剂1000丸。每丸含斑蝥素0.33mg。60kg成人一日2-3次，一次1丸，相当于一日剂量含斑蝥素0.66-1.0mg。可优先选用于预防新冠病毒、流感病毒等病毒、病菌的感染。1000 cantharidin oral pills combined with Chinese and Western medicine were prepared. Each pill contains 0.33mg cantharidin. 60kg adults 2-3 times a day, 1 pill each time, equivalent to a daily dose of 0.66-1.0mg cantharidin. It can be preferentially used to prevent infections of viruses and germs such as new coronaviruses and influenza viruses.
实施例9Example 9
生态抗生素灭活疫苗用斑蝥素抗生素溶体的配制：Preparation of cantharidin antibiotic solution for ecological antibiotic inactivated vaccine:
将斑蝥素1.6-3.6mg，2-丁酮溶解80.0-120.0g加入到橄榄油200g中，搅拌溶解后，再加入橄榄油制成总量为1000.0g油油互溶的斑蝥素溶体。Dissolve 1.6-3.6 mg of cantharidin and 80.0-120.0 g of 2-butanone into 200 g of olive oil. After stirring and dissolving, add olive oil to make a total of 1000.0 g of oil-oil-soluble cantharidin solution.
实施例10Example 10
生态抗生素灭活疫苗用斑蝥素抗生素溶体的配制：Preparation of cantharidin antibiotic solution for ecological antibiotic inactivated vaccine:
将斑蝥素16.0-36.0mg,95％乙醇375.0-525.0g,2-丁酮80.0-120.0g,丙二醇495.0-725.0g,苯甲醇6.0-12.0g,2-苯乙醇6.0-12.0g,覆盆子酮3.0-6.0g,加入蒸馏水1000g中，搅拌溶解后，再加入蒸馏水制成总量为10000.0g油水互溶的斑蝥素溶体。Cantharidin 16.0-36.0mg, 95% ethanol 375.0-525.0g, 2-butanone 80.0-120.0g, propylene glycol 495.0-725.0g, benzyl alcohol 6.0-12.0g, 2-phenylethanol 6.0-12.0g, raspberry ketone 3.0-6.0g, add to 1000g of distilled water, stir to dissolve, then add distilled water to make a total of 10000.0g cantharidin solution which is mutually soluble in oil and water.
利用实施例9及10得到的斑蝥素溶体作为制备疫苗母体，可依据常规技术将病原体分别、分组投入到该溶体当中，避光、恒温34-36℃，继续进行多种方式的斑蝥素抗生素“生态”灭活疫苗的研究实验。Using the cantharidin lysates obtained in Examples 9 and 10 as the vaccine matrix, the pathogens can be put into the solution separately and in groups according to conventional techniques, protected from light, at a constant temperature of 34-36°C, and continue to carry out various methods of cantharidin antibiotics. Research and experiment on ecological inactivated vaccines.
临床应用实例Clinical application examples
自2020年1-5月，本课题组对10位新冠病毒疑似人员，利用本发明制备的斑蝥素制剂进行临床使用，收到明显效果。From January to May 2020, this research group has used the cantharidin preparations prepared by the present invention on 10 persons suspected of new coronaviruses in clinical use, and achieved significant results.
1、对2位新冠病毒症状明显的疑似人员，利用实施例1制备的斑蝥素皮肤吸收涂剂，按60kg成人每天在胸、背、四肢皮肤涂抹三次，每次应用2.0g，涂抹12小时后，体温降至37.6℃，24小时后，体温降至正常。用药2日，开始胸闷、厌食症状明显减轻。连续用药4日后，疑似人员自感症状消失，恢复正常。1. For 2 suspected persons with obvious symptoms of the new coronavirus, use the cantharidin skin absorption lotion prepared in Example 1 to apply 2.0g on the chest, back, and limbs of a 60kg adult three times a day, after applying it for 12 hours. , The body temperature dropped to 37.6 ℃, after 24 hours, the body temperature dropped to normal. On the 2nd day of medication, symptoms of chest tightness and anorexia began to be significantly reduced. After 4 days of continuous medication, the suspected person's symptoms disappeared and returned to normal.
2、对8名感到轻微胸闷，有干咳症状的疑似人员，利用实施例1制备的斑蝥素皮肤吸收涂剂，按60kg成人每天在胸、背、四肢皮肤涂抹三次，每次应用2.0g，涂抹1日后，乏力、干咳症状减轻，涂抹3日后，疑似人员自感症状完全消失，恢复正常。2. To 8 suspected persons with mild chest tightness and dry cough symptoms, use the cantharidin skin absorption lotion prepared in Example 1 to apply 2.0g on the skin of the chest, back and limbs three times a day for a 60kg adult. After 1 day, the symptoms of fatigue and dry cough alleviated. After 3 days of application, the suspected person’s symptoms disappeared completely and returned to normal.
3、对20多名申请人公司的工作人员，利用实施例7制备的斑蝥素溶液消毒布巾，进行消毒，或用斑蝥素溶液涂覆口罩。这些人员均保持健康。3. More than 20 employees of the applicant company used the cantharidin solution disinfection cloth prepared in Example 7 for disinfection, or coated the mask with the cantharidin solution. All these personnel remain healthy.
本课题组临床应用结果认为，本发明对新冠病毒、流感病毒等病毒、病菌的感染方面，会具有重要的预防和治疗效果。The clinical application results of this research group believe that the present invention will have important preventive and therapeutic effects on the infection of new coronaviruses, influenza viruses and other viruses and bacteria.
本领域技术人员在考虑说明书所公开的内容后，将容易想到本发明的其它实施方案。本申请旨在涵盖本发明的任何变型、用途或者适应性变化，这些变型、用途或者适应性变化遵循本发明的一般性原理并包括本发明未公开的本技术领域中的公知常识或惯用技术手段。Those skilled in the art will easily think of other embodiments of the present invention after considering the content disclosed in the specification. This application is intended to cover any variations, uses, or adaptive changes of the present invention. These variations, uses, or adaptive changes follow the general principles of the present invention and include common knowledge or conventional technical means in the technical field that are not disclosed by the present invention. .

Claims (12)

  1. 一种斑蝥素抗病毒、抗菌制剂，含有斑蝥素作为有效药物成分，其特征在于，所述斑蝥素溶解于油水互溶体或油油互溶体得到斑蝥素溶剂载体，将所述斑蝥素溶剂载体与可药用载体或赋形剂配制而成多种剂型用作预防和治疗新冠病毒的药物。A cantharidin antiviral and antibacterial preparation containing cantharidin as an effective drug component, characterized in that the cantharidin is dissolved in an oil-water mutual soluble or an oil-oil mutual soluble to obtain a cantharidin solvent carrier, and the cantharidin solvent carrier is combined with Pharmaceutical carriers or excipients are formulated into a variety of dosage forms to be used as drugs for the prevention and treatment of new coronavirus.
  2. 根据权利要求1所述的斑蝥素抗病毒、抗菌制剂，其特征在于，所述油水互溶体或油油互溶体，含有酮类和/或内酯类的精油。The cantharidin antiviral and antibacterial preparation according to claim 1, wherein the oil-water mutual soluble or oil-oil mutual soluble contains essential oils of ketones and/or lactones.
  3. 一种斑蝥素皮肤吸收涂剂，含有斑蝥素作为有效药物成分，其特征在于，斑蝥素溶剂载体为油油互溶体，按下列成份：A cantharidin skin absorption lotion contains cantharidin as an effective drug ingredient, and is characterized in that the solvent carrier of cantharidin is an oil-oil mutual solution and has the following ingredients:
    斑蝥素：160.0-200.0mgCantharidin: 160.0-200.0mg
    植物油：8.0-12.0gVegetable oil: 8.0-12.0g
    动物油：8.0-12.0gAnimal oil: 8.0-12.0g
    酮类精油：40.0-60.0gKetone essential oil: 40.0-60.0g
    十八醇：20.0-40.0gStearyl alcohol: 20.0-40.0g
    硬脂酸：20.0-40.0gStearic acid: 20.0-40.0g
    乳化剂(吐温-80)40-60.0gEmulsifier (Tween-80) 40-60.0g
    其余蒸馏水：总量1000.0gThe rest of distilled water: total 1000.0g
    制成每克含斑蝥素0.16-0.2mg的皮肤吸收涂剂。A skin absorption lotion containing 0.16-0.2mg of cantharidin per gram is prepared.
  4. 一种斑蝥素静脉注射剂，含有斑蝥素作为有效药物成分，其特征在于，斑蝥素溶剂载体为油水互溶体，按下列成份：A cantharidin intravenous injection containing cantharidin as an effective drug ingredient, characterized in that the solvent carrier of cantharidin is an oil-water mutual solution, and has the following ingredients:
    斑蝥素：15.0-30.0mgCantharidin: 15.0-30.0mg
    2-丁酮：30.0-60.0g2-Butanone: 30.0-60.0g
    3-庚酮：0.3-0.6g3-Heptanone: 0.3-0.6g
    2-仲丁基环已酮：0.3-0.6g2-sec-butyl cyclohexanone: 0.3-0.6g
    其余为生理注射用水：总量16000.00g，制成斑蝥素静脉注射剂。The rest is physiological water for injection: the total amount is 16000.00g, which is made into cantharidin intravenous injection.
  5. 一种斑蝥素片，含有斑蝥素作为有效药物成分，其特征在于，斑蝥素溶剂载体为油水互溶体，按下列成份：A cantharidin tablet containing cantharidin as an effective pharmaceutical ingredient, characterized in that the solvent carrier of cantharidin is an oil-water mutual solution, and has the following ingredients:
    斑蝥素：200.0-300.0mgCantharidin: 200.0-300.0mg
    可可脂：80.0-120.0gCocoa butter: 80.0-120.0g
    橄榄油：60.0-90.0gOlive oil: 60.0-90.0g
    2-丁酮：60.0-90.0g2-Butanone: 60.0-90.0g
    2-仲丁基环已酮：200.0-300.0g2-sec-butyl cyclohexanone: 200.0-300.0g
    淀粉：3200.0-4800.0gStarch: 3200.0-4800.0g
    谷朊粉：320.0-480.0gGluten: 320.0-480.0g
    制成总量：10000片；每片片重0.392--0.588g的斑蝥素片。Total production: 10,000 tablets; cantharidin tablets each weighing 0.392-0.588g.
  6. 一种斑蝥素胶囊，含有斑蝥素作为有效药物成分，其特征在于，斑蝥素溶剂载体为油水互溶体，按下列成份：A cantharidin capsule containing cantharidin as an effective drug component, characterized in that the solvent carrier of cantharidin is an oil-water mutual solution, and has the following ingredients:
    斑蝥素：200.0-300.0mgCantharidin: 200.0-300.0mg
    脱臭牛脂：80.0-120.0gDeodorized tallow: 80.0-120.0g
    橄榄油：60.0-90.0gOlive oil: 60.0-90.0g
    2-丁酮：60.0-90.0g2-Butanone: 60.0-90.0g
    6-羟基-3，7-二甲基辛酸内酯：200.0-300.0g6-hydroxy-3,7-dimethylcaprylic acid lactone: 200.0-300.0g
    淀粉：3200.0-4800.0gStarch: 3200.0-4800.0g
    谷朊粉：320.0-480.0gGluten: 320.0-480.0g
    制成总量：10000粒，每粒粒重0.392-0.588g的斑蝥素胶囊。A total of 10,000 cantharidin capsules with a weight of 0.392-0.588g each are made.
  7. 一种斑蝥素鼻眼药油，含有斑蝥素作为有效药物成分，其特征在于，斑蝥素溶剂载体为油油互溶体，按下列成份：A cantharidin nasal and eye medicinal oil, containing cantharidin as an effective drug ingredient, characterized in that the solvent carrier of cantharidin is an oil-oil mutual solution, and has the following ingredients:
    斑蝥素：2.2-3.6mgCantharidin: 2.2-3.6mg
    2-丁酮：80.0-120.0g2-Butanone: 80.0-120.0g
    覆盆子酮：3.0-6.0gRaspberry ketone: 3.0-6.0g
    其余为橄榄油：总量为1000.0g的斑蝥素鼻眼药油。The rest is olive oil: a total of 1000.0g cantharidin nose and eye oil.
  8. 一种斑蝥素溶液消毒布巾，含有斑蝥素作为有效药物成分，其特征在于，斑蝥素溶剂载体为油水互溶体，按下列成份：A cantharidin solution disinfection cloth towel contains cantharidin as an effective drug ingredient, and is characterized in that the solvent carrier of cantharidin is an oil-water mutual solution, and has the following ingredients:
    斑蝥素：1.0-2.6mgCantharidin: 1.0-2.6mg
    95％乙醇:500.0-600.0g95% ethanol: 500.0-600.0g
    2-丁酮：40.0-60.0g2-Butanone: 40.0-60.0g
    丙二醇：425.0-525.0gPropylene glycol: 425.0-525.0g
    苯甲醇：8.0-10.0gBenzyl alcohol: 8.0-10.0g
    2-苯乙醇：8.0-10.0g2-Phenylethanol: 8.0-10.0g
    覆盆子酮：2.0-4.0gRaspberry Ketone: 2.0-4.0g
    余量为蒸馏水：总量10000.0g。将所得溶剂喷涂在载体上，制成斑蝥素溶液消毒布巾。The remainder is distilled water: the total amount is 10000.0g. The obtained solvent is sprayed on the carrier to prepare a cantharidin solution disinfection cloth towel.
  9. 一种斑蝥素中西药结合口服丸剂，含有斑蝥素作为有效药物成分，其特征在于，斑蝥素溶剂载体为油油互溶体，按下列成份：A combined oral pill of cantharidin with Chinese and Western medicine, containing cantharidin as an effective drug ingredient, characterized in that the solvent carrier of cantharidin is an oil-oil mutual solution, and has the following ingredients:
    斑蝥素溶体，按下列成份：Cantharidin solution, according to the following ingredients:
    斑蝥素：330.0mgCantharidin: 330.0mg
    橄榄油：20.0gOlive oil: 20.0g
    可可脂：10.0gCocoa butter: 10.0g
    γ-任内酯：6.0gγ-Rhinolactone: 6.0g
    2-丁酮：30.0g2-Butanone: 30.0g
    2-仲丁基环已酮：60.0g2-sec-butyl cyclohexanone: 60.0g
    斑蝥素中西药结合口服丸剂，按下列成份：Cantharidin combined with Chinese and Western medicine oral pills, according to the following ingredients:
    斑蝥素溶体(含斑蝥素330.0mg):126.0gCantharidin lysate (containing cantharidin 330.0mg): 126.0g
    淀粉：2000.0gStarch: 2000.0g
    谷朊粉：274.0gGluten: 274.0g
    黄芪提取物：100.0gAstragalus extract: 100.0g
    中蜂蜂蜜：2500.0gChina Bee Honey: 2500.0g
    制成斑蝥素中西药结合口服丸剂1000丸，每丸含斑蝥素0.33mg。1000 cantharidin oral pills combined with Chinese and Western medicine were prepared, each of which contained 0.33mg cantharidin.
  10. 一种油水互溶预防外伤感染的家庭、士兵常备的清洗剂，其特征在于，所述溶体为斑蝥素油水互溶体，按下述成分：An oil-water mutual soluble cleaning agent for households and soldiers to prevent traumatic infection, characterized in that the solution is a cantharidin oil-water mutual soluble, and has the following components:
    斑蝥素：1.6-3.2mgCantharidin: 1.6-3.2mg
    95％乙醇:375.0-525.0g95% ethanol: 375.0-525.0g
    2-丁酮：80.0-120.0g2-Butanone: 80.0-120.0g
    丙二醇：495.0-725.0gPropylene glycol: 495.0-725.0g
    苯甲醇：6.0-12.0gBenzyl alcohol: 6.0-12.0g
    2-苯乙醇：6.0-12.0g2-Phenylethanol: 6.0-12.0g
    覆盆子酮：3.0-6.0gRaspberry ketone: 3.0-6.0g
    余量为蒸馏水。制成：总量为10000.0g的斑蝥素预防外伤感染的家庭、士兵常备的清洗剂。The balance is distilled water. Preparation: 10000.0g of cantharidin is a cleaning agent for families and soldiers who prevent traumatic infections.
  11. 一种预防HIV性行为传染的斑蝥素抗病毒、抗菌无形避孕套，其特征在于，所述溶体为斑蝥素油水互溶体，按下列成份：A cantharidin antiviral and antibacterial invisible condom for preventing HIV sexual transmission, characterized in that the solution is a cantharidin oil-water mutual solution, and has the following ingredients:
    斑蝥素：16.0—36.0mgCantharidin: 16.0-36.0mg
    95％乙醇:100.0-300.0g95% ethanol: 100.0-300.0g
    丙二醇：495.0-725.0gPropylene glycol: 495.0-725.0g
    丙三醇：495.0-725.0gGlycerol: 495.0-725.0g
    乳酸：1000.0gLactic acid: 1000.0g
    乳酸钠：2000.0gSodium lactate: 2000.0g
    苯甲醇：16.0-21.0gBenzyl alcohol: 16.0-21.0g
    2-苯乙醇：6.0-12.0g2-Phenylethanol: 6.0-12.0g
    透明质酸：30.0—120.0gHyaluronic acid: 30.0-120.0g
    瓜尔豆胶：10.0—40.0gGuar Gum: 10.0-40.0g
    余量为蒸馏水，制成：总量为10000.0g的预防HIV性行为传染的斑蝥素无形避孕套。The remainder is distilled water to make: a total of 10000.0g cantharidin invisible condom for preventing HIV sexual transmission.
  12. 一种制备抗新冠病毒生态抗生素灭活疫苗用的斑蝥素抗生素溶体，其特征在于，所述溶体为斑蝥素油油互溶体或斑蝥素油水互溶体，含有1.6ppm≤斑蝥素≤3.6ppm。A cantharidin antibiotic solution for preparing an ecological antibiotic inactivated vaccine against neocorona virus, characterized in that the solution is a cantharidin oil-oil mutual soluble or a cantharidin oil-water mutual soluble, and contains 1.6ppm≤cantharidin≤3.6ppm.
PCT/CN2021/095429 2020-05-25 2021-05-24 Cantharidin antiviral and antibacterial preparation, preparation method therefor, and use thereof for preventing and treating novel coronavirus infection WO2021238836A1 (en)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1421202A (en) * 2001-11-23 2003-06-04 王卫 Antiviral and antibacterial cantharidinic anhydride medicine composition and its prepn process
CN1449752A (en) * 2003-05-09 2003-10-22 王卫 Cantharidin total anhydride pharmaceutics for treating and preventing SARS and preparation thereof
CN111568897A (en) * 2020-05-25 2020-08-25 甘肃芫美药业有限公司 An antiviral and antibacterial cantharidin preparation, its preparation method, and its application in preventing and treating new coronavirus infection

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN1421202A (en) * 2001-11-23 2003-06-04 王卫 Antiviral and antibacterial cantharidinic anhydride medicine composition and its prepn process
CN1449752A (en) * 2003-05-09 2003-10-22 王卫 Cantharidin total anhydride pharmaceutics for treating and preventing SARS and preparation thereof
CN111568897A (en) * 2020-05-25 2020-08-25 甘肃芫美药业有限公司 An antiviral and antibacterial cantharidin preparation, its preparation method, and its application in preventing and treating new coronavirus infection

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